bluuebunny/crossref_metadata_2025 huggingface dataset:
A mutation in monoamine oxidase (MAO) affects the evolution of stress behavior in the blind cavefishAstyanax mexicanus
Authors: Pierre Constance , Pradère Naomie , Froc Cynthia , Ornelas-García Patricia , Callebert Jacques , Rétaux Sylvie
Published: April 2020

The neurotransmitter serotonin controls a great variety of physiological and behavioral processes. In humans, mutations affecting the monoamine oxidase or MAO, the serotonin-degrading enzyme, are highly deleterious. Yet, blind cavefish of the speciesA. mexicanuscarry a partial loss-of-function mutation in MAO (P106L) and seem to thrive in their subterranean environment. Here, we established 4 fish lines, corresponding to the blind cave-dwelling and the sighted river-dwelling morphs of this species, with or without the mutation, in order to decipher the exact contribution ofmaoP106L in the evolution of cavefish neuro-behavioral traits. Unexpectedly, althoughmaoP106L appeared as an excellent candidate for the genetic determinism of the loss of aggressive and schooling behaviors in cavefish, we demonstrated that it was not the case. Similarly, the anatomical variations in monoaminergic systems observed between cavefish and surface fish brains were independent frommaoP106L, and rather due other, morph-dependent developmental processes. On the other hand, we found thatmaoP106L strongly affected anxiety-like behaviors. Cortisol measurements showed lower basal levels and an increased amplitude of stress response after a change of environment in fish carrying the mutation. Finally, we studied the distribution of the P106Lmaoallele in wild populations of cave and riverA. mexicanus, and discovered that the mutant allele was present - and sometimes fixed - in all populations inhabiting caves of the Sierra de El Abra. The possibility that this partial loss-of-functionmaoallele evolves under a selective or a genetic drift regime in the particular cave environment is discussed.
Crystal structure of the NS3-like helicase from Alongshan virus
Authors: Gao Xiaopan , Zhu Kaixiang , Wojdyla Justyna Aleksandra , Chen Pu , Qin Bo , Li Ziheng , Wang Meitian , Cui Sheng
Published: April 2020

Alongshan virus (ALSV) is an emerging human pathogen that was identified in China and rapidly spread to the European continent in 2019, raising concerns about public health. ALSV belongs to the distinct Jingmenvirus group within the Flaviviridae family with segmented RNA genomes. While segments 2 and 4 of the ALSV genome encode the VP1–VP3 proteins of unknown origin, segments 1 and 3 encode the NS2b–NS3 and NS5 proteins, which are related to Flavivirus nonstructural proteins, suggesting an evolutionary link between segmented and unsegmented viruses within the Flaviviridae family. Here, the enzymatic activity of the ALSV NS3-like helicase (NS3-Hel) was characterized and its crystal structure was determined to 2.9 Å resolution. ALSV NS3-Hel exhibits an ATPase activity that is comparable to those measured for Flavivirus NS3 helicases. The structure of ALSV NS3-Hel exhibits an overall fold similar to those of Flavivirus NS3 helicases. Despite the limited amino-acid sequence identity between ALSV NS3-Hel and Flavivirus NS3 helicases, structural features at the ATPase active site and the RNA-binding groove remain conserved in ALSV NS3-Hel. These findings provide a structural framework for drug design and suggest the possibility of developing a broad-spectrum antiviral drug against both Flavivirus and Jingmenvirus.
Crystal structure and Hirshfeld surface analysis of hexyl 1-hexyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
Authors: Bouzian Younos , Kansiz Sevgi , Mahi Lhassane , Ahabchane Noureddine Hamou , Mague Joel T. , Dege Necmi , Karrouchi Khalid , Essassi El Mokhtar
Published: April 2020

The asymmetric unit of the title compound, C22H31NO3, comprises of one molecule. The molecule is not planar, with the carboxylate ester group inclined by 33.47 (4)° to the heterocyclic ring. Individual molecules are linked by aromaticC—H...Ocarbonyl hydrogen bonds into chains running parallel to [001]. Slipped π–π stacking interactions between quinoline moieties link these chains into layers extending parallel to (100). Hirshfeld surface analysis, two-dimensional fingerprint plots and molecular electrostatic potential surfaces were used to quantify the intermolecular interactions present in the crystal, indicating that the most important contributions for the crystal packing are from H...H (72%), O...H/H...O (14.5%) and C...H/H...C (5.6%) interactions.
Crystal structure of trans-dichlorido(1,4,8,11-tetraazacyclotetradecane-κ4
N)chromium(III) bis(formamide-κO)(1,4,8,11-tetraazacyclotetradecane-κ4
N)chromium(III) bis[tetrachloridozincate(II)]
Authors: Moon Dohyun , Choi Jong-Ha
Published: April 2020

The structure of the title compound, [CrCl2(C10H24N4)][Cr(HCONH2)2(C10H24N4)][ZnCl4]2 (C10H24N4 = 1,4,8,11-tetraazacyclotetradecane, cyclam; HCONH2 = formamide, fa), has been determined from synchrotron X-ray data. The asymmetric unit contains two independent halves of the [CrCl2(cyclam)]+ and [Cr(fa)(cyclam)]3+ cations, and one tetrachloridozincate anion. In each complex cation, the CrIII ion is coordinated by the four N atoms of the cyclam ligand in the equatorial plane and two Cl ligands or two O-bonded formamide molecules in a trans axial arrangement, displaying a distorted octahedral geometry with crystallographic inversion symmetry. The Cr—N(cyclam) bond lengths are in the range 2.061 (2) to 2.074 (2) Å, while the Cr—Cl and Cr—O(fa) bond distances are 2.3194 (7) and 1.9953 (19) Å, respectively. The macrocyclic cyclam moieties adopt the centrosymmetric trans-III conformation with six- and five-membered chelate rings in chair and gauche conformations. The crystal structure is stabilized by intermolecular hydrogen bonds involving the NH or CH groups of cyclam and the NH2 group of coordinated formamide as donors, and Cl atoms of the ZnCl4
2− anion as acceptors.
Redetermination of diammonium trivanadate, (NH4)2V3O8
Authors: Pérez-Benítez Aarón , Bernès Sylvain
Published: April 2020

The crystal structure of (NH4)2V3O8 has been reported twice using single-crystal X-ray data [Theobald et al. (1984). J. Phys. Chem. Solids, 45, 581–587; Range et al. (1988). Z. Naturforsch. Teil B, 43, 309–317]. In both cases, the orientation of the ammonium cation in the asymmetric unit was poorly defined: in Theobald's study, the shape and dimensions were constrained for NH4
+, while in Range's study, H atoms were not included. In the present study, we collected a highly redundant data set for this ternary oxide, at 0.61 Å resolution, using Ag Kα radiation. These accurate data reveal that the NH4
+ cation is disordered by rotation around a non-crystallographic axis. The rotation axis coincides with one N—H bond lying in the mirror m symmetry element of space-group type P4bm, and the remaining H sites were modelled over two disordered positions, with equal occupancy. It therefore follows that the NH4
+ cations filling the space available in the (001) layered structure formed by (V3O8)2– ions do not form strong N—H...O hydrogen bonds with the mixed-valent oxidovanadate(IV,V) anions. This feature could have consequences for the Li-ion intercalation properties of this material, which is used as a cathode for supercapacitors.
Investigating the consequences of theme park experience through the lenses of self-congruity and flow
Authors: Fu Xiaoxiao , Kang Juhee , Hahm Jeeyeon Jeannie , Wiitala Jessica
Published: April 2020

Purpose

This paper aims to propose and test a conceptual model of theme park experiences by investigating the relationships among brand experience, self-congruity, flow and brand-related outcomes.

Design/methodology/approach

Data were collected from guests who had visited a theme park in the past 12 months. Confirmatory factor analysis, consisting of second-order factor analysis and structural equation modeling with the incorporation of alternative model testing, was employed.

Findings

The findings revealed that theme park customers’ internalization of brand experience influenced their attitudinal and behavioral tendency with regard to the brand through self-congruity and flow.

Practical implications

This study provides strategies for theme park designers and marketers under pressure to create a desired experiential setting that motivates visitors to engage in activities through various brand stimuli. Well-designed theme parks can create an optimal state of focus and attention, immersing visitors to the extent that they lose their sense of time and place, affecting their attitude and behavior toward the theme park brand.

Originality/value

Theme parks provide a highly experiential, immersive and personally relevant experience with brand elements. Very few studies have attempted to investigate the consequences of theme park experience from the theoretical perspective of customers’ connection with the brand. This study proposed and validated a conceptual model to capture how theme park experience influenced visitors’ commitment to and active engagement with theme park brands through the mechanisms of self-congruity and flow.
Authentic leadership’s effect on customer orientation and turnover intention among Portuguese hospitality employees
Authors: Ribeiro Neuza , Duarte Patrícia , Fidalgo Jessica
Published: April 2020

Purpose

Hospitality employees’ attitudes and behaviors play a crucial role in enhancing customer satisfaction and service quality and ultimately firms’ success; therefore, organizations must have skilled, customer-oriented staff. More research is required to help hospitality managers gain insights into the best strategies to promote and retain customer-oriented employees. This study specifically sought to provide a more comprehensive understanding of the ways that authentic leadership (AL) can affect employees’ customer orientation and turnover intention, including exploring affective commitment’s (AC) potential mediating role.

Design/methodology/approach

The sample included 350 employees from different hospitality organizations in Portugal. Data were collected using anonymously completed structured questionnaires available online or in a paper-and-pencil format.

Findings

The results demonstrate that AL has a positive effect on customer orientation and a negative effect on turnover intention. Moreover, they indicate that AC mediates the relationships between AL and both customer orientation and turnover intention. All hypotheses received empirical support.

Practical implications

Hotel managers can increase employees’ AC and customer orientation by engaging in AL behaviors. Similarly, management can avoid having employees voluntarily leave their jobs using more AL styles and strengthening employees’ affective bonds to their organization.

Originality/value

Prior hospitality studies have rarely focused on AL. This study is the first to analyze AL’s effect on customer orientation and AC’s role as a mediator variable in the relationships between AL and customer orientation and turnover intention, thus integrating all these variables into a single research model.
Star(tup) wars: decoupling task from relationship conflict
Authors: Kozusznik Malgorzata W. , Aaldering Hillie , Euwema Martin C.
Published: April 2020

Purpose

A strong relation between task and relationship conflict has toxic impact on teams and poses a high-risk factor in startup organizations. The purpose of this study is to investigate the moderating role of conflict behavior and related coping strategies on the relationship between task and relationship conflict in startup teams.

Design/methodology/approach

The authors conducted surveys among 100 Dutch and German startup members (Study 1) and 75 Belgium startup members (Study 2). In Study 3, 75 startup members completed weekly surveys in 11 consecutive weeks.

Findings

Both Study 1 and 2 show that the positive association between task and relationship conflict is buffered by problem-solving conflict behavior while this relationship is amplified by the use of avoiding strategies in startup teams. Similarly, the results of Study 3 show that individual and team-level problem-focused coping over a period of 11 weeks buffers the association between task and relationship conflict during this period, while individual disengagement coping potentiates it.

Originality/value

This study adds to the literature on conflict management and entrepreneurship by studying conflict behavior as a moderator in the association between task and relationship conflict in startup teams. Moreover, it takes a comprehensive perspective by including coping strategies conceptually related to conflict behaviors at both individual and teamlevel, as moderators in this relationship. The results of this study provide practical recommendations for entrepreneurs on how to prevent conflict escalation via conflict-oriented behaviors and more general coping strategies.
Financial integration and bank profitability in five regional economic communities in Africa
Authors: Banyen Kannyiri , Biekpe Nicholas
Published: April 2020

Purpose

This paper examines the effect of both de jure and de facto measures of financial integration on bank profitability in five regional economic communities of Africa.

Design/methodology/approach

Using panel data from 405 banks operating in 47 African countries across five regional economic communities over 2007–2014, the study constructs a composite measure of bank profitability. The study then employs the dynamic two-step system GMM estimation technique to test the effect of both de jure and de facto measures of financial integration on bank profitability in Africa and across five sub-regional markets.

Findings

Overall, the results support a positive relationship between financial integration and overall bank profitability in Africa, except for the Arab Maghreb Union and Southern Africa Development Community.

Practical implications

The findings of this study suggest that increased financial integration in Africa directly improves bank’s overall profitability and the variations among the sub-regional markets inform tailored policy initiatives.

Originality/value

To the best of the authors' knowledge, this is the first study on Africa to employ a composite measure of bank profitability to assess its determinants. It is also the first to include both de facto and de jure financial integration measures in a single study. This is also the first largest comparative study on bank profitability in Africa.
Strong species differences in life history do not predict oxidative stress physiology or sensitivity to an environmental oxidant
Authors: Tüzün Nedim , Debecker Sara , Stoks Robby
Published: April 2020

Species typically align along a fast–slow life‐history continuum, yet it is not clear to what extent oxidative stress physiology can be integrated with this continuum to form a ‘pace‐of‐life syndrome’, especially so in invertebrates. This is important, given the assumed role of oxidative stress in mediating life‐history trade‐offs, and the prediction that species with a faster pace should be more vulnerable to oxidative stress.

We tested whether a species' life‐history pace, here represented by its growth rate, can predict species‐level differentiation in physiology and sensitivity to oxidative stress. Therefore, we exposed four species of Ischnura damselflies that strongly align along a fast–slow life‐history continuum to different levels of ultraviolet (UV) radiation. We measured an extended set of physiological traits linked to the pace‐of‐life: standard metabolic rate, oxidative stress physiology (antioxidant enzymes and oxidative damage) and defence/condition traits (investment in immune function, energy storage and structural defence).

Despite strong species differences in growth rate and physiology, growth rate did not predict species‐level differentiation in physiology. Hence there was no support for the integration of metabolic rate, oxidative stress physiology or defence/condition traits into a species‐level syndrome.

Ultraviolet exposure affected nearly all traits: it reduced growth rate and increased metabolic rate, affected all oxidative stress physiology traits and increased the two defence traits (immune function, and melanin content). Nevertheless, the pace‐of‐life based on growth rate did not predict sensitivity to UV. Instead, the observed pattern of investment in structural UV defence (melanin) might have reduced the need for enzymatic antioxidant defence, this way potentially decoupling the covariation between the life‐history pace and oxidative stress physiology.

The absence of an integrated axis of life‐history and physiological variation indicates no major constraints for the evolution of these traits among the studied damselfly species. Our study highlights that ecological differences between species may decouple covariation between species' life‐history pace and their physiology, as well as their sensitivity to environmental stressors.
Temperate deciduous forests embedded across developed landscapes: Younger forests harbour invasive plants and urban forests maintain native plants
Authors: Trammell Tara L. E. , D'Amico Vince , Avolio Meghan L. , Mitchell J. Christina , Moore Eric
Published: April 2020

Temperate deciduous forests in the United States are located in the most densely populated states across the northern and mid-Atlantic east coast. Land development and associated human activities result in small forests that are susceptible to anthropogenic influences, such as urbanization and non-native plant invasion.

The overall objective of this study was to assess spatial and temporal drivers of forest vegetation structure and diversity in small forests embedded across developed landscapes. We assessed woody plant composition across spatial gradients (i.e., urbanization and non-native plant invasion) and a temporal gradient (i.e., time since canopy closure) across 38 forests along the east coast of the United States in northern Delaware and southeastern Pennsylvania.

Surprisingly, we found the invasion gradient was not related to the urban gradient across our forests. Across all forests, the canopy consisted of native species (98% of all trees), whereas the forest understory was most vulnerable to non-native plant invasion (65% of all woody plant stems). Greater native species richness in forest canopies and understories with increasing urbanization supports the conclusion that urban forests maintain native species and are not inherently degraded ecosystems. Non-native plant invasion has a strong influence on understory plant communities, and the duration of intact forest canopy had a strong negative correlation with non-native plant invasion suggesting intact forests can resist invasion.

Synthesis. This is the first study to compare simultaneously the importance of invasion and urbanization in determining plant community composition in forests embedded across developed landscapes, and to discover that younger forests harbor more invasive plants and urban forests maintain native plants.
Overuse of opioids for acute migraine in an Australian emergency department
Authors: Gunasekera Lakshini , Akhlaghi Hamed , Sun‐Edelstein Christina , Heywood John , Sanders Lauren
Published: April 2020

Objective

Acute migraine is associated with significant personal, economic and work‐related disability. Management guidelines advise the use of simple analgesia, triptans, chlorpromazine and anti‐emetics based on severity, with avoidance of opioids. We aimed to determine consistency of prescribing patterns in our ED with national guidelines.

Methods

We performed a retrospective cohort analysis of migraine presentations (ICD‐10‐AM G439) between 2012 and 2016. Exclusion criteria included migraine without headache, other primary headaches and secondary headaches. Demographic and prescribing data were extracted from medical records. Results have been reported as proportions.

Results

Of 4769 headache presentations, the application of exclusion criteria led to a total of 744 patients who received a migraine diagnosis (G439). Most were female (558/744, 75%), young (mean age 36.4 years) and had a self‐reported migraine history (558/744, 75%). There were 54 different medications prescribed. Paracetamol was more frequently prescribed (385/744, 52%) than aspirin (134/744, 18%). Opioid prescription occurred in nearly half of all presentations (345/744, 46%). Similar opioid prescriptions were also observed in those with a documented history of migraines (253/558, 45%). A minority of patients received triptans (51/744, 7%). Overall, a quarter of patients (189/744, 25%) received no guideline‐recommended medications.

Conclusion

We observed considerable polypharmacy in ED migraine management with inconsistent prescribing patterns. Recommended medications were infrequently used and opioid use was common. Factors influencing prescribing patterns require further investigation in order to improve rates of guideline recommended treatment.
Population genomic SNPs from epigenetic RADs: Gaining genetic and epigenetic data from a single established next‐generation sequencing approach
Authors: Crotti Marco , Adams Colin E. , Elmer Kathryn R.
Published: April 2020

Epigenetics is increasingly recognized as an important molecular mechanism underlying phenotypic variation. To study DNA methylation in ecological and evolutionary contexts, epiRADseq is a cost‐effective next‐generation sequencing (NGS) technique based on reduced representation sequencing of genomic regions surrounding non‐/methylated sites. EpiRADseq for genome‐wide methylation abundance and ddRADseq for genome‐wide single‐nucleotide polymorphism (SNP) genotyping follow very similar library and sequencing protocols, but to date these two types of dataset have been handled separately. Here we test the performance of using epiRADseq data to generate SNPs for population genomic analyses.

We tested the robustness of using epiRADseq data for population genomics with two independent datasets: a newly generated single‐end dataset for the European whitefish Coregonus lavaretus, and a re‐analysis of publicly available, previously published paired‐end data on corals. Using standard bioinformatic pipelines with a reference genome and without (i.e. de novo catalogue loci), we compared the number of SNPs retained, population genetic summary statistics and population genetic structure between data drawn from ddRADseq and epiRADseq library preparations.

We found that SNPs drawn from epiRADseq are similar in number to those drawn from ddRADseq, with 55%–83% of SNPs being identified by both methods. Genotyping error rate was <5% in both approaches. EpiRADseq‐specific allele dropout was low (~1%). For summary statistics, such as heterozygosity and nucleotide diversity, there is a strong correlation between methods (Spearman's rho > 0.88). Furthermore, identical patterns of population genetic structure were recovered using SNPs from epiRADseq and ddRADseq approaches.

We show that SNPs obtained from epiRADseq are highly similar to those from ddRADseq and are equivalent for estimating genetic diversity and population structure. This finding is particularly relevant to researchers interested in genetics and epigenetics on the same individuals because using a single epigenomic approach to generate two datasets greatly reduces the time and financial costs compared to using these techniques separately. It also efficiently enables correction of epigenetic estimates with population genetic data. Many studies will benefit from a combinatorial approach with genetic and epigenetic markers and this demonstrates a single, efficient method to do so.
A preliminary study to identify the likely risk for sarcopenia in older hospitalised patients with cardiovascular disease in Vietnam
Authors: Van Nguyen Tan , Tran Khuong Dang , Bui Khai Xuan , Le Duong , Nguyen Tu Ngoc
Published: April 2020

Objective

To investigate the prevalence of sarcopenia, its associated factors and its impact on readmission in older hospitalised patients with cardiovascular diseases (CVD) in Vietnam.

Methods

Patients aged ≥60 with CVD were recruited from 12/2018 to 6/2019 at a tertiary hospital in Vietnam. Sarcopenia was defined by the criteria proposed by the Asian Working Group for Sarcopenia (AWGS).

Results

There were 251 participants, with a mean age of 73.7 ± 8.8, 39.4% were female, and 34.3% had sarcopenia. On multivariable logistic regression, heart failure, chronic kidney disease and being currently unmarried were significantly associated with sarcopenia. The incidence of 5‐month readmission was 35.7% (50.0% in sarcopenic participants and 27.9% in non‐sarcopenic participants, P = .001). Sarcopenia independently increased the risk of readmission (adjusted OR 2.19, 95% CI 1.08‐4.42).

Conclusion

Sarcopenia was present in one‐third of older hospitalised patients with CVD and increased their risk of readmission. This finding suggests the need to raise awareness of sarcopenia among clinicians and older patients in Vietnam.
Ranger perceptions of the role of local communities in providing actionable information on wildlife crime
Authors: Anagnostou Michelle , Mwedde Geoffrey , Roe Dilys , Smith Robert J. , Travers Henry , Baker Julia
Published: April 2020

Wildlife crime in protected areas remains a major challenge to conservation. However, little is known about the role of local communities in providing information on illegal activities to help improve law enforcement efforts in protected areas. As an initial exploration of this complex topic, we aimed to understand the perceptions of law enforcement authorities working directly with local communities on the conditions under which local people provide information to park rangers, using Murchison Falls Protected Area in Uganda as a case study. We used semi‐structured interviews and questionnaires to understand the perceptions of staff from the Uganda Wildlife Authority and nongovernmental organizations. There was consensus among participants that people who provide information are those who have trusted relationships with rangers; interact regularly with community outreach rangers (either formally through community programs or informal socializing); and believe that the protected area benefits them and their community. All respondents believed that information provided by local people can enable the success of wildlife crime investigations, but that associated ethical issues must be addressed. This study indicates that engaging communities in protected area conservation is crucial for law enforcement efforts to be effective in addressing wildlife crime.
Induction immunosuppression strategies and long‐term outcomes after heart transplantation
Authors: Nozohoor Shahab , Stehlik Josef , Lund Lars H. , Ansari David , Andersson Bodil , Nilsson Johan
Published: April 2020

Although the use of induction therapy has reduced the risk of acute rejection after heart transplantation, its use may be associated with other adverse outcomes. We aimed to examine the effect of no induction (NoInd), induction with basiliximab (BAS), or induction with antithymocyte globulin (ATG) on outcome after heart transplantation. We analyzed data from the International Society for Heart and Lung Transplantation (ISHLT) registry for adult heart transplants performed between 2000 and 2013. The primary outcome was cumulative all‐cause mortality, and the secondary outcome was cause‐specific death. We identified 27 369 transplants whose recipients received NoInd (n = 15 688), ATG (n = 6830), or BAS (n = 4851). Over a median follow‐up of 1497 days, overall 30‐day mortality was 5% and 1‐year mortality was 11%. Survival after transplant was similar in patients treated with NoInd compared with ATG. The survival was improved using NoInd compared with BAS (log‐rank P = .040), adjustment HR = 1.11 (95% CI, 1.04‐1.19). Compared to NoInd, BAS was associated with higher risk of graft failure‐related deaths, HR = 1.27 (95% CI, 1.02‐1.58), and ATG was associated with higher risk of malignancy‐related deaths, HR = 1.18 (95% CI, 1.01‐1.39). Survival of patients who received NoInd was similar to ATG and better compared with BAS. Further, the use of ATG may be associated with increased malignancy‐related mortality, compared with NoInd.
Impact of CYP2C9‐Interacting Drugs on Warfarin Pharmacogenomics
Authors: Agrawal Saaket , Heiss Meredith S. , Fenter Remington B. , Abramova Tatiana V. , Perera Minoli A. , Pacheco Jennifer A. , Smith Maureen E. , Rasmussen‐Torvik Laura J. , George Alfred L.
Published: April 2020

Precise dosing of warfarin is important to achieve therapeutic benefit without adverse effects. Pharmacogenomics explains some interindividual variability in warfarin response, but less attention has been paid to drug‐drug interactions in the context of genetic factors. We investigated retrospectively the combined effects of cytochrome P450 (CYP)2C9 and vitamin K epoxide reductase complex (VKORC)1 genotypes and concurrent exposure to CYP2C9‐interacting drugs on long‐term measures of warfarin anticoagulation. Study participants predicted to be sensitive responders to warfarin based on CYP2C9 and VKORC1 genotypes, had significantly greater international normalized ratio (INR) variability over time. Participants who were concurrently taking CYP2C9‐interacting drugs were found to have greater INR variability and lesser time in therapeutic range. The associations of INR variability with genotype were driven by the subgroup not exposed to interacting drugs, whereas the effect of interacting drug exposure was driven by the subgroup categorized as normal responders. Our findings emphasize the importance of considering drug interactions in pharmacogenomic studies.
Myosin affects the structure and volatile flavour compounds binding of G‐actin in grass carp
Authors: Lin Rufei , Xiao Xiao , Yue Yi , Wang Ying , Pan Daodong , Wang Daoying , Yang Qiuli , He Jun , Cao Jinxuan
Published: April 2020

The effects of myosin (0, 0.2, 0.4, and 0.6 mg mL−1) on the protein structure and volatiles adsorption capacity of G‐actin from grass carp were investigated. The results showed that the myosin addition increased the surface hydrophobicity and sulfhydryl contents of G‐actin. The Raman spectroscopy analysis showed that the α‐helix and β‐sheet of G‐actin were converted into β‐turn and random coil with 0.2 and 0.4 mg mL−1 of myosin, while only the β‐turn content increased with 0.6 mg mL−1 of myosin. The GC‐MS analysis indicated that with myosin addition, the adsorption capacities of G‐actin on alcohols (1‐pantanol, 1‐hexanol, 1‐octen‐3‐ol, and 1‐octanol) and ketones (2‐pentanone, 2‐heptanone, 2‐octanone, and 2‐nonanone) were enhanced; meanwhile, the binding of G‐actin to aldehydes (pentanal, hexanal, octanal, and nonanal) was weakened. It was probably due to the formation of actomyosin, and also the excess myosin when treated with high concentrations (0.4 and 0.6 mg mL−1) of myosin.
Evaluation of stroke incidence with duty‐cycled multielectrode‐phased radiofrequency ablation of persistent atrial fibrillation results of the VICTORY AF Study
Authors: Hummel John , Verma Atul , Calkins Hugh , Schwamm Lee H. , Gress Daryl , Wells Darryl , Souza Joseph , Hokanson Robert B. , Hemingway Lauren , Stromberg Kurt , Hoyt Robert , Wickliffe Andrew , DeLurgio David , Boersma Lucas
Published: April 2020

Introduction

The VICTORY AF Study was designed to evaluate the risk of the procedure and/or device‐related strokes in patients with PersAF on warfarin undergoing ablation with a phased radiofrequency (RF) system.

Methods

The VICTORY AF trial was a prospective, multicenter, single‐arm, investigational study. PersAF patients on vitamin K antagonism without major structural heart disease or history of stroke/transient ischemic attack undergoing phased RF ablation for atrial fibrillation (AF) were included. The primary outcome was the incidence of the procedure and/or device‐related stroke within 30 days of the ablation by a board‐certified neurologist's assessment. The secondary outcomes were an acute procedural success, 6 months effectiveness (defined as the reduction in AF/atrial flutter episodes lasting ≥10 minutes by 48‐hour Holter 6 months postablation) and the number of patients with pulmonary vein (PV) stenosis.

Results

A total of 129 (108 PersAF, 21 long‐standing PersAF) patients were treated (mean age: 60.6 ± 7.7; 79.8% male, 54.3% CHA2Ds2‐VASc score ≥ 2). Two nondisabling strokes were reported (1.6%); one before discharge and the second diagnosed at the 30‐day visit. Due to slow enrollment, the study was terminated before reaching the 95% one‐sided upper confidence boundary for stroke incidence. Acute procedural success was 93.8%, and at 6 months, 72.8% of patients demonstrated ≥90% reduction in AF burden, 78.9% were off all antiarrhythmic drugs. There were no patients with PV stenosis of greater than 70%.

Conclusions

VICTORY AF demonstrated a 1.6% incidence of stroke in PersAF undergoing ablation with a phased RF system which did not meet statistical confidence due to poor enrollment. The secondary outcomes suggest comparable efficacy to phased RF in the tailored treatment of permanent AF trial. Rigorous clinical evaluation of the stroke risk of new AF ablation technologies as well as restriction to Vitamin K antagonist anticoagulation appears to be unachievable goals in a clinical multicenter IDE trial of AF ablation in the current era.
Clinical value of multiorgan damage in hypertensive crises: A prospective follow‐up study
Authors: Ma Hongkun , Jiang Mengdi , Fu Zongjie , Wang Zhiyu , Shen Pingyan , Shi Hao , Feng Xiaobei , Chen Yongxi , Ding Xiaoyi , Wu Zhiyuan , Zhang Wen
Published: April 2020

Hypertensive crises are associated with high rates of target organ complications and poor outcomes. A recent shift from the definition of malignant hypertension to hypertension‐multiorgan damage (MOD) contributes to the diagnosis and management of hypertensive crises. Here, we prospectively included 166 adult (≥18 years old) patients with hypertensive crises (blood pressure >180/120 mm Hg). Target organs and causes of hypertension were assessed. Patients who were diagnosed with malignant hypertensive retinopathy, the absence of malignant hypertensive retinopathy but the presence of damage to at least 3 organs, and the absence of both retinopathy and MOD were classified as the malignant hypertension (n = 48), hypertension‐MOD (n = 42), and hypertension without MOD (n = 76) groups, respectively. Patients were followed to evaluate renal and cardiovascular prognoses. At baseline, patients with malignant hypertension had worse renal function, higher level of albuminuria, and more severe microvascular damage than those with hypertension‐MOD. Both had similar proportions of malignant arteriolar nephrosclerosis (83% vs 64%), left ventricular hypertrophy (90% vs 88%), abnormal repolarization (71% vs 60%), and left ventricular dysfunction (12% vs 21%). At the twenty months of follow‐up, both the malignant hypertension and hypertension‐MOD groups had similar blood pressure control rates and proteinuria. Both groups had worse renal outcomes than the hypertension without MOD group (P = .002). Patients with hypertension‐MOD (HR = 0.67, [95% CI: 0.30‐1.46], P = .31) had similar renal event‐free survival than patients with MHT after adjustments of age, sex, blood pressure, and proteinuria control. These results suggest that in hypertensive crises, both malignant hypertension and hypertension‐MOD have impact on adverse renal outcomes.
Tofacitinib in psoriatic arthritis patients: skin signs and symptoms and health‐related quality of life from two randomized phase 3 studies
Authors: Merola J.F. , Papp K.A. , Nash P. , Gratacós J. , Boehncke W.H. , Thaçi D. , Graham D. , Hsu M‐A. , Wang C. , Wu J. , Young P.
Published: April 2020

Background

Psoriatic arthritis (PsA) is a chronic, systemic immune‐mediated inflammatory musculoskeletal disease. The onset of dermatologic symptoms often precedes rheumatic manifestations. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA that has been shown to improve dermatologic symptoms in patients with PsA.

Objectives

To investigate the efficacy of tofacitinib in improving dermatologic endpoints in adult patients with active PsA.

Methods

This analysis included data from two placebo‐controlled, double‐blind, phase 3 studies in patients with active PsA and an inadequate response (IR) to ≥1 conventional synthetic disease‐modifying antirheumatic drug (csDMARD) who were tumor necrosis factor inhibitor (TNFi)‐naïve (OPAL Broaden; NCT01877668) or an IR to ≥1 TNFi (OPAL Beyond; NCT01882439). Patients had active plaque psoriasis at screening and received a stable dose of one csDMARD during the study. Patients were randomized to tofacitinib 5 mg twice daily (BID), 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only) or placebo (to Month 3). Dermatologic endpoints: Psoriasis Area and Severity Index (PASI) total score; PASI90 overall; PASI75 and PASI90 by baseline PASI severity; Physician’s Global Assessment of Psoriasis; Nail Psoriasis Severity Index; Dermatology Life Quality Index total and sub‐dimension scores; Itch Severity Item; and Patient’s Global Joint and Skin Assessment‐Visual Analog Scale‐Psoriasis question.

Results

In patients with active PsA, including those stratified by mild or moderate/severe dermatologic symptoms, greater improvements from baseline and percentage of responders were observed in tofacitinib‐treated patients vs. placebo for the majority of analyzed dermatologic endpoints at Months 1 and 3, and improvements were maintained to Month 12 in OPAL Broaden and Month 6 in OPAL Beyond. Similar effects were observed in adalimumab‐treated patients vs. placebo in OPAL Broaden across dermatologic endpoints.

Conclusions

Tofacitinib provides a treatment option for patients with active PsA, including the burdensome dermatologic symptoms of PsA.
Circulating trimethyllysine and risk of acute myocardial infarction in patients with suspected stable coronary heart disease
Authors: Bjørnestad E. Ø. , Olset H. , Dhar I. , Løland K. , Pedersen E. K. R. , Svingen G. F. T. , Svardal A. , Berge R. K. , Ueland P. M. , Tell G. S. , Nilsen D. W. T. , Nordrehaug J. E. , Nygaard E. , Nygård O.
Published: April 2020

Background

The carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine‐N‐oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modifications by riboflavin status.

Methods

By Cox modelling, risk associations were examined amongst 4098 patients (71.8% men) with suspected stable angina pectoris. Subgroup analyses were performed according to median plasma riboflavin.

Results

During a median follow‐up of 4.9 years, 336 (8.2%) patients experienced an AMI. The age‐ and sex‐adjusted hazard ratio (HR) (95% CI) comparing the 4th vs. 1st TML quartile was 2.19 (1.56–3.09). Multivariable adjustment for traditional cardiovascular risk factors and indices of renal function only slightly attenuated the risk estimates [HR (95% CI) 1.79 (1.23–2.59)], which were particularly strong amongst patients with riboflavin levels above the median (Pint = 0.035). Plasma TML and TMAO were strongly correlated (rs = 0.41; P < 0.001); however, plasma TMAO was not associated with AMI risk in adjusted analyses [HR (95% CI) 0.81 (0.58–1.14)]. No interaction between TML and TMAO was observed.

Conclusion

Amongst patients with suspected stable angina pectoris, plasma TML, but not TMAO, independently predicted risk of AMI. Our results motivate further research on metabolic processes determining TML levels and their potential associations with cardiovascular disease. We did not adjust for multiple comparisons, and the subgroup analyses should be interpreted with caution.
The factors related to decreases in masticatory performance and masticatory function until swallowing using gummy jelly in subjects aged 20‐79 years
Authors: Ohno Keitaro , Fujita Yuko , Ohno Yoma , Takeshima Tomohiro , Maki Kenshi
Published: April 2020

Background

There is growing international interest in the prevention of decreased oral function for managing oral health in older people.

Objective

The aims of the present study were to identify factors related to decreases in masticatory performance and masticatory function until swallowing in subjects aged 20‐79 years old.

Methods

A total of 152 subjects, ranging in age from 20 to 79 years, were divided into six groups according to their chronological age: 20‐29, 30‐39, 40‐49, 50‐59, 60‐69 and 70‐79 years. Grip strength, maximum occlusal force, maximum tongue pressure, masticatory performance and swallowing threshold were measured in all subjects. Masticatory performance and swallowing threshold were determined according to the concentration of dissolved glucose obtained from gummy jellies; decreased masticatory performance and decreased swallowing threshold were defined as glucose concentrations in the lowest 20th percentile. A multivariate binary logistic regression analysis was used to identify factors associated with decreased masticatory performance and decreased swallowing threshold. A self‐administered lifestyle questionnaire was also completed.

Results

Logistic regression analyses revealed that factors related to decreased masticatory performance included use of more than one kind of medicine for treating chronic diseases and removable denture use, while factors related to decreased swallowing threshold included eating between meals once or more per day, poorer mental health and decreased saliva flow.

Conclusions

Different factors are related to decreased masticatory performance and decreased swallowing threshold, although both of these phenomena are closely associated with general health status.
Static and Fatigue Loading of Veneered Implant‐Supported Fixed Dental Prostheses
Authors: Rayyan Mohammad M. , Abdallah Jihad , Segaan Lucette G. , Bonfante Estevam A. , Osman Essam
Published: April 2020

Purpose

This study aimed to compare the load to failure and the probability of survival of porcelain fused to zirconia (PFZ) three‐unit, implant‐supported, fixed dental prostheses (FDPs) to those of indirect composites veneered to either zirconia (CVZ) or milled fiber‐reinforced composite (FRC) frameworks under static and fatigue loading.

Materials and Methods

One‐hundred and twenty posterior three‐unit FDP (second premolar pontic) frameworks were fabricated via milling from a single Standard Tessellation Language (STL) file. The FDPs were divided into three groups. Each group (n = 40) was subjected to static (n = 20) and fatigue (n = 20) loading tests, as follows: (1) PFZ: zirconia framework layered with porcelain veneer; (2) CVZ: zirconia framework veneered with indirect composite resin; and (3) FRC: FRC framework veneered with indirect composite resin. After porcelain veneering onto sintered zirconia frameworks, or resin composite veneering onto zirconia or FRC frameworks, FDPs were cemented on their abutments using self‐adhesive resin cement. After thermal cycling, half of the FDPs were subjected to an accelerated fatigue test. The other half of the FDPs were subjected to single load‐to‐failure (SLF) testing at a crosshead speed (1 mm/min). Lifetime analysis was conducted to determine the probability of survival, and fractographic analysis was performed.

Results

Significant differences were observed among the studied groups for SLF with the highest characteristic strength values observed for PFZ (2154 N), followed by 1905.47 N for CVZ and 1679.56 N for FRC. The probability of survival for 100,000 cycles at 500 N was the highest for FRC (98%) and CVZ (100%) and was significantly lower for PFZ (88%). Different fracture patterns were observed in the fractography.

Conclusions

In fatigue testing, which simulates masticatory function better than static tests, a higher probability of survival was observed for FRC and CVZ than for PFZ. Framework fractures were not observed only for the FRC group, indicating that chairside repair with the addition of indirect composite could be performed for continued function.
Primula subansirica G.D. Pal is not a Primula (Primulaceae), but rather belongs to Gesneriaceae
Authors: Xu Yuan , Choudhary Ritesh Kumar , Hao Gang , Hu Chi‐Ming
Published: April 2020

Examination of type specimens has shown that Primula subansirica G.D. Pal is a Gesneriad and conspecific with Beccarinda cordifolia (Anthony) B.L. Burtt (Gesneriaceae), thus a reduction is made and a new synonymy is proposed.
Being English in multilingual South Africa
Authors: Coetzee‐Van Rooy Susan
Published: April 2020

The multilingual repertoires of African home language and bilingual Afrikaans‐English speakers in South Africa have been investigated comprehensively in the recent past. Less attention has been paid to the language repertoires of English home language speakers. Very little is known about the nature of their repertoires and their attitudes towards the languages in their repertoires. These Inner Circle users of English are immersed in a deeply multilingual Outer Circle society where most individuals know at least two languages and the majority of the citizens know more than four languages. The use of English as a home language is also expanding in this context. In this paper, the language repertoires of urban English home language students that participated in a longitudinal language repertoire survey and a group who created language portraits are examined with a view to understand the nature of their language repertoires better. The main finding is that being English in multilingual South Africa means to be at least bilingual with a multilingual mindset. English home language repertoires in South Africa therefore differ from English home language repertoires in Inner Circle contexts like the USA and Australia; and from Outer Circle contexts like Kenya.
The gut hormone secretin triggers a gut–brown fat–brain axis in the control of food intake
Authors: Schnabl Katharina , Li Yongguo , Klingenspor Martin
Published: April 2020

New Findings

What is the topic of this review?

Brown fat's role in meal‐associated thermogenesis and the related consequences for energy balance regulation with a focus on the gut hormone secretin, which has been identified as the endocrine molecular mediator of meal‐associated brown fat thermogenesis.

What advances does it highlight?

The finding of the secretin‐induced gut–brown fat–brain axis creates new opportunities to manipulate brown fat and thereby energy balance in a natural way while living in a thermoneutral environment. The role of brown fat as a mere catabolic heater organ needs to be revised and more attention should be directed towards the regulatory role of brown fat beyond energy expenditure.

Brown fat research concentrates on the energy expenditure function of this heating organ, whereas previous evidence for a role of brown fat in regulating energy intake has been mostly neglected. Ingestion of a single mixed meal activates human brown fat thermogenesis to the same degree as cold. In mice, activation of brown fat thermogenesis with a β3‐adrenergic receptor agonist inhibits food intake. Pharmacological β‐blockade, however, inhibits neither meal‐associated thermogenesis nor food intake. We recently identified the gut hormone secretin as a non‐adrenergic activator of brown fat. In vivo, secretin treatment acutely increases energy expenditure and inhibits food intake in wild‐type, but not in uncoupling protein 1 (UCP1)‐knockout (KO) mice, which lack thermogenic brown fat function. Concurrently, secretin alters gene expression of melanocortinergic peptides of hypothalamic neurons in wild‐type mice, but not UCP1‐KO. Blocking endogenous secretin with a neutralizing antibody attenuates brown fat thermogenesis during refeeding, increases food intake of mice, and alters ad libitum feeding behaviour. Taken together, these findings demonstrate that secretin triggers an endocrine gut–brown adipose tissue–brain axis in the control of satiation. We hypothesize that meal‐associated activation of brown adipose tissue thermogenesis induced by secretin results in a rise in brain temperature and increased melanocortinergic signalling. Taken together, brown fat is not a mere heating organ dissipating excess calories but also involved in gut–brain communication in the control of food intake.