bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene‐related peptide ligand (galcanezumab) or receptor (erenumab) antagonist
Authors: Kudrow David , Nguyen Linda , Semler Jack , Stroud Chad , Samaan Karen , Hoban Deirdre B. , Wietecha Linda , Hsu Hai‐An , Pearlman Eric 
Published: September 2022

AbstractObjectiveTo compare effects of an initial dose of calcitonin gene‐related peptide (CGRP) monoclonal antibody (mAb) antagonists on gastrointestinal (GI) motility in patients with migraine and to explore if the mechanistic difference contributes to GI adverse events (AEs).BackgroundDifferent frequencies of constipation have been observed between CGRP mAbs that target the ligand (galcanezumab [GMB]) or receptor (erenumab [ERE]).MethodsPatients (n = 65) with migraine without significant GI symptoms were enrolled in a multi‐center, single‐blind phase IV clinical trial (NCT04294147) and randomized 1:1 to receive GMB (240 mg; n = 33) or ERE (140 mg; n = 32). GI whole and regional transit times were assessed using a wireless motility capsule 1 week before and 2 weeks after mAb administration. The primary endpoint was change from baseline in colonic transit time (CTT) within each treatment group. Other measures included GI Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and spontaneous bowel movement (SBM) evaluation. AEs were monitored throughout the study.ResultsBaseline characteristics indicated significant GI transit time variability with minimal GI reported symptoms. While not statistically significant, a numerical mean increase in CTT was observed in ERE patients (n = 28, mean [SD] at baseline: 33.8 [29.4] h; least square [LS] mean [SE] change: 5.8 [5.7] h, 95% confidence interval [CI] −5.7 to 17.2, p = 0.320), while GMB decreased CTT (n = 31, mean [SD] at baseline: 29.3 [24.5] h; LS mean [SE] change: −5.4 [5.4] h, 95% CI −16.2 to 5.5, p = 0.328) compared to baseline. No meaningful changes were observed in other regional transit times. ERE significantly reduced BSFS (LS mean [SE] score −0.5 [0.2], p = 0.004) and SBM (LS mean [SE] −1.2 [0.5], p = 0.0120), and increased GSRS‐constipation compared to baseline (LS mean [SE] score 0.3 [0.1], p = 0.016). GMB increased GSRS‐constipation (LS mean [SE] score 0.4 [0.1], p = 0.002). There were no discontinuations due to or serious AEs. A higher percentage of treatment‐emergent AEs were reported with ERE than GMB (ERE: nine of 32 [28.1%] versus GMB: three of 33 [9.1%]), with constipation the most frequently reported (ERE: five of 32 [15.6%] versus GMB one of 33 [3.0%]).ConclusionWhile the primary endpoint of this study was not met, secondary and tertiary endpoints support a within‐ and between‐treatment change in GI effects suggesting possible mechanistic differences between ligand (GMB) and receptor (ERE) antagonism.
Clinical outcomes amongst elderly patients with inflammatory bowel disease
Authors: Sivanathan Vithoosharan , Basnayake Chamara , Connell William , Wright Emily , Ding John Nik , Niewadomski Ola , Stanley Annalise , Wilson‐O'Brien Amy , Fry Stephanie , Samyue Tamie , Lust Mark , Flanagan Emma , Thompson Alexander J. V. , Kamm Michael A. 
Published: September 2022

AbstractBackgrounds and aimsInflammatory bowel disease (IBD) affects a growing cohort of elderly patients. Our aim was to compare the quality of care received by elderly patients with IBD with a nonelderly adult IBD population using clinical markers including steroid‐free clinical remission.MethodRetrospective audit of all consecutive patients attending a specialist IBD centre over a 1‐year period aged >60 (elderly cohort [EC]) and 50 consecutive patients aged 30–45 years (control cohort [CC]). A follow‐up survey was completed assessing current symptoms and perceptions of care.ResultsOne hundred thirty‐nine patients were evaluated (89 EC, 50 CC). Steroid‐free clinical remission was observed less commonly in the EC (58, 64%) compared with the CC (40, 80%) (P < 0.05). Biologics such as infliximab (15% EC vs 36% CC; P < 0.01) and adalimumab (14% EC vs 30% CC; P = 0.02) were used less frequently in the EC, whilst vedolizumab (6% EC vs 6% CC; P = 1) and ustekinumab (3% EC vs 2% CC; P = 1) were used at a similar frequency. Patients in the EC were less likely to have specialist IBD nursing contact (P < 0.01), smoking screening (P < 0.011) or influenza vaccinations (P < 0.006). IBD nurse contact was associated with significantly greater provision of the preventative care measures.ConclusionElderly patients with IBD were less likely to experience steroid‐free clinical remission or be prescribed biologics. Elderly patients were less likely to receive education with respect to preventative medicine. The models of care for the elderly need re‐evaluation and greater incorporation with the multidisciplinary IBD team.
Cardiovascular disease management in Australian adults with type 2 diabetes: insights from the CAPTURE study
Authors: Davis Timothy M. E. , Colman Peter G. , Hespe Charlotte , Heywood Sarah E. , d'Emden Michael 
Published: September 2022

AbstractBackgroundType 2 diabetes (T2D) is a well‐recognised cardiovascular disease (CVD) risk factor, and recent guidelines for the management of T2D include consideration of CVD risk.AimTo assess whether contemporary clinical management of Australians with T2D is in accord with recent national and international guidelines.MethodsThis Australia‐specific analysis of the CAPTURE study, a non‐interventional, cross‐sectional study included adults diagnosed with T2D ≥180 days prior to providing informed consent and visiting primary or specialist care. Main outcome measures were the use of blood glucose‐lowering medications (BGLMs), BGLMs with proven cardiovascular benefits and other CVD medications, stratified by CVD status and care setting.ResultsOf 824 Australian participants in the CAPTURE sample, 332 (40.3%) had CVD. Oral BGLMs were used by 83.9% of all participants, most commonly metformin (76.0%), dipeptidyl peptidase‐4 inhibitors (28.8%), sodium‐glucose cotransporter‐2 inhibitors (SGLT2is; 21.8%) and sulfonylureas (21.7%). Insulin was used by 29.2% of participants. BGLMs with proven CV benefit were used by 22.6%; glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) were less commonly used than SGLT2is in all CVD groups, but these drug classes were more often prescribed in specialist than primary care (SGLT2is 25.4 vs 20.7%, GLP‐1 RAs 3.2 vs 0.8% respectively). Use of non‐BGLMs for CVD risk reduction appeared consistent with guidelines.ConclusionsUse of BGLMs with CVD benefits appears low in Australia, irrespective of CVD status. This likely reflects the delay in translation of clinical evidence into contemporary care and prescribing restrictions.
Effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer: A meta‐analysis
Authors: Zheng Shuangyun , Liu Xiaole , Cheng Liqin , Wu Qiaozhu , Meng Fanhang 
Published: September 2022

AbstractWe performed a meta‐analysis to evaluate the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer. A systematic literature search up to July 2022 was performed and 10 231 subjects with cervical cancer at the baseline of the studies; 4307 of them were using the minimally invasive surgery, and 5924 were using laparotomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer using the dichotomous methods with a random or fixed‐effect model. The minimally invasive surgery had significantly lower wound infection (OR, 0.20; 95% CI, 0.13–0.30, P < .001), and postoperative complications (OR, 0.48; 95% CI, 0.37–0.64, P < .001) in subjects with cervical cancer compared laparotomy. However, minimally invasive surgery compared with laparotomy in subjects with cervical cancer had no significant difference in intraoperative complications (OR, 1.04; 95% CI, 0.80–1.36, P = 0.76). The minimally invasive surgery had significantly lower wound infection, and postoperative complications however, had no significant difference in intraoperative complications in subjects with cervical cancer compared with laparotomy. The analysis of outcomes should be with caution because of the low sample size of 22 out of 41 studies in the meta‐analysis and a low number of studies in certain comparisons.
Incorporating United Nations 2030 Sustainable Future Agenda into the Architectural Studio: A Graduation Studio Case
Authors: Erkarslan Özlem Erdoğdu , Akgün Yenal 
Published: September 2022

AbstractUnited Nations (UN) released the 2030 Agenda for Sustainable Development in 2015. This agenda has received attention from various disciplines and sectors globally; partnerships from private and public sectors were formed to play a role in this challenging ambitious plan. However, architectural education and professional organisations in Turkey have not been strongly engaged with the agenda in particular. To meet this gap and create synergy, this paper aims at presenting pedagogical paths followed in a graduation studio, integrating the studio outcomes with UN 2030 Sustainable Development Goals (SDGs), which have not been widely covered either in nationwide architectural education or professional policies. In addition, the paper focuses on how the SDG action plan is echoed in higher education as well as in the discipline of architecture in Turkey. The paper is a case study in architectural education of which the motivation is to create awareness about UN SDGs among the students; to give insights and demonstrate a realistic design policy to achieve development targets. The pedagogical path presented here is original and aims to fulfill an interlude in the literature, which is still emerging. The case presentation includes the process and the results with a sufficient number of student projects as outcomes of the studio.
Should Political Leaders Be Highly Educated?
Authors: Marley‐Payne Jack 
Published: September 2022

ABSTRACTMany liberal philosophers view elite education as a virtue of political leaders and, in addition, hold that an important role of a just education system is to create better elites. A compelling and influential articulation of this view has been offered by Elizabeth Anderson. However, this view is in conflict with a commitment to substantive democracy, given the background conditions of the United States today. This article will argue, contra Anderson, that having the highly educated disproportionately represented in political leadership is incompatible with egalitarian principles of democracy. The key reason for this is that it systematically shuts out the working class from full political participation. Therefore, in order to satisfy the constraints of democracy, we must sever the connection between elite education and political office.
Determinants of genetic diversity and species richness of North American amphibians
Authors: Schmidt Chloé , Munshi‐South Jason , Dray Stéphane , Garroway Colin J. 
Published: September 2022

AbstractAimEcological limits on population sizes and the number of species a region can sustain are thought to simultaneously produce spatial patterns in population genetic diversity and species richness due to the effects of random drift operating in parallel across population and community levels. Here, we test the extent to which resource‐based environmental limits jointly determine these patterns of biodiversity in amphibians.LocationNorth America.TaxonAmphibians.MethodsWe repurposed open, raw microsatellite data from 19 species sampled at 554 sites in North America and mapped nuclear genetic diversity at the continental scale. We then tested whether ecological limits defined by resource availability and environmental heterogeneity could simultaneously shape biogeographic patterns in genetic diversity and species richness with structural equation modelling.ResultsSpatial patterns of population genetic diversity run opposite patterns of species richness and genetic differentiation. However, while measures of resource availability and niche heterogeneity predict 89% of the variation in species richness, these landscape metrics were poor predictors of genetic diversity.Main conclusionsAlthough heterogeneity appears to be an important driver of genetic and species biodiversity patterns in amphibians, variation in genetic diversity both within and across species makes it difficult to infer general processes producing spatial patterns of amphibian genetic diversity. This result differs from those found in endotherms and may be due to the considerable life history variation found across amphibians.
Childhood family and neighbourhood socio‐economic status, psychopathy, and adult criminal behaviour
Authors: Baker Sydney , Javakhishvili Magda , Widom Cathy Spatz 
Published: September 2022

AbstractPurposeLower socio‐economic status (SES) and psychopathy are risk factors for criminal behaviour. This study examines whether psychopathic trait scores moderate the relationship between childhood family and neighbourhood SES and adult arrests.MethodsA large group of Midwest children ages 0–11 years old during 1967–1971 were interviewed as adults in 1989–1995 (N = 1144) at mean age 29. Childhood family SES was based on information collected during the interview and neighbourhood SES were based on census tract information from childhood. Psychopathic trait scores were based on information from interviews and case records. Official arrest data were used to assess criminal behaviour in adulthood.ResultsChildhood family SES, childhood neighbourhood SES, and psychopathic trait scores each independently predicted the number of adult arrests. As expected, lower childhood family SES and childhood neighbourhood SES predicted a larger number of adult arrests, and higher psychopathic trait scores were associated with a greater number of adult arrests. Childhood family SES and childhood neighbourhood SES also interacted with psychopathic trait scores to predict adult arrests. For individuals with low psychopathic trait scores, lower childhood family SES and lower childhood neighbourhood SES each predicted a higher number of adult arrests, whereas this was not the case for individuals with high psychopathic trait scores.ConclusionsChildhood SES (family and neighbourhood) continues to affect criminal behaviour long into adulthood. But neither childhood family SES, childhood neighbourhood SES, or psychopathic traits alone explain the extent of adult arrests. For people with comparably low levels of psychopathic traits, childhood family and neighbourhood socio‐economic status continued to impact adult arrests.
Adapting to climate with limited genetic diversity: Nucleotide,DNAmethylation and microbiome variation among populations of the social spiderStegodyphus dumicola
Authors: Aagaard Anne , Liu Shenglin , Tregenza Tom , Braad Lund Marie , Schramm Andreas , Verhoeven Koen J. F. , Bechsgaard Jesper , Bilde Trine 
Published: September 2022

AbstractUnderstanding the role of genetic and nongenetic variants in modulating phenotypes is central to our knowledge of adaptive responses to local conditions and environmental change, particularly in species with such low population genetic diversity that it is likely to limit their evolutionary potential. A first step towards uncovering the molecular mechanisms underlying population‐specific responses to the environment is to carry out environmental association studies. We associated climatic variation with genetic, epigenetic and microbiome variation in populations of a social spider with extremely low standing genetic diversity. We identified genetic variants that are associated strongly with environmental variation, particularly with average temperature, a pattern consistent with local adaptation. Variation in DNA methylation in many genes was strongly correlated with a wide set of climate parameters, thereby revealing a different pattern of associations than that of genetic variants, which show strong correlations to a more restricted range of climate parameters. DNA methylation levels were largely independent ofcis‐genetic variation and of overall genetic population structure, suggesting that DNA methylation can work as an independent mechanism. Microbiome composition also correlated with environmental variation, but most strong associations were with precipitation‐related climatic factors. Our results suggest a role for both genetic and nongenetic mechanisms in shaping phenotypic responses to local environments.
Semantic dispositionalism and the rule‐following paradox
Authors: Lane Elek 
Published: September 2022

AbstractIn virtue of what does a sign have meaning? This is the question raised by Wittgenstein's rule‐following considerations. Semantic dispositionalism is a (type of) theory that purports to answer this question. The present paper argues that semantic dispositionalism faces a heretofore unnoticed problem, one that ultimately comes down to its reliance on unanalyzed notions of repeated types of signs. In the context of responding to the rule‐following paradox—and offering a putative solution to it—this amounts to simply assuming a solution to the problem in one domain and using it to solve the same problem in another. Given, moreover, the level at which the rule‐following paradox undercuts dispositionalism—the level of the notion of a sign's repetition—the objections made to the view also rule out causal/informational theories of meaning as well as communitarian/assertion‐theoretic ones as potential solutions to the rule‐following paradox.
14‐3‐3 proteins regulate photomorphogenesis by facilitating light‐induced degradation of PIF3
Authors: Song Pengyu , Yang Zidan , Guo Can , Han Run , Wang Huaichang , Dong Jie , Kang Dingming , Guo Yan , Yang Shuhua , Li Jigang 
Published: September 2022

Summary

14‐3‐3s are highly conserved phosphopeptide‐binding proteins that play important roles in various developmental and signaling pathways in plants. However, although protein phosphorylation has been proven to be a key mechanism for regulating many pivotal components of the light signaling pathway, the role of 14‐3‐3 proteins in photomorphogenesis remains largely obscure. PHYTOCHROME‐INTERACTING FACTOR3 (PIF3) is an extensively studied transcription factor repressing photomorphogenesis, and it is well‐established that upon red (R) light exposure, photo‐activated phytochrome B (phyB) interacts with PIF3 and induces its rapid phosphorylation and degradation. PHOTOREGULATORY PROTEIN KINASES (PPKs), a family of nuclear protein kinases, interact with phyB and PIF3 in R light and mediate multisite phosphorylation of PIF3 in vivo.

Here, we report that two members of the 14‐3‐3 protein family, 14‐3‐3λ and κ, bind to a serine residue in the bHLH domain of PIF3 that can be phosphorylated by PPKs, and act as key positive regulators of R light‐induced photomorphogenesis.

Moreover, 14‐3‐3λ and κ preferentially interact with photo‐activated phyB and promote the phyB‐PIF3‐PPK complex formation, thereby facilitating phyB‐induced phosphorylation and degradation of PIF3 upon R light exposure.

Together, our data demonstrate that 14‐3‐3λ and κ work in close concert with the phyB‐PIF3 module to regulate light signaling in Arabidopsis.
Influence of rigid lens decentration and rotation on visual image quality in normal and keratoconic eyes
Authors: Rozema Jos J. , Hastings Gareth D. , Jiménez‐García Marta , Koppen Carina , Applegate Raymond A. 
Published: September 2022

AbstractPurposeTo investigate whether the movement of a rigid sphero‐cylindrical contact lens has a greater impact on the visual image quality in highly aberrated eyes than in normal eyes.MethodsFor 20 normal and 20 keratoconic SyntEyes, a previously determined best sphero‐cylindrical rigid lens was permitted to shift by up to ±1 mm from the line of sight and rotate up to ±15°. Each of the 52,111 lens locations sampled was ray‐traced to determine the influence on the wavefront aberration. In turn, the logarithm of visual Strehl ratio (log10[VSX]) was calculated for each aberration structure and was used to estimate the associated changes in logMAR visual acuity. Finally, contour surfaces of two‐letter change in visual acuity were plotted in three‐dimensional misalignment space, consisting of decentrations in the x and y directions and rotation, and volumes within these surfaces were calculated.ResultsThe variations in image quality within the misalignment space were unique to each eye. A two‐letter loss was generally reached with smaller misalignments in keratoconic eyes (10.5 ± 4.7° of rotation or 0.27 ± 0.13 mm of shift) than in normal eyes (13.4 ± 1.8° and 0.39 ± 0.15 mm, respectively) due to larger cylindrical errors. For keratoconic eyes, on average, 14.4 ± 14.9% of misalignment space saw VSX values above the lower normal VSX threshold, well below the values of normal eyes of 48.5 ± 18.5%. In some eyes, a specific combination of lens shift and lens rotation away from the line of sight leads to a simulated improvement in visual image quality.ConclusionVariations in visual image quality due to the misalignment of rigid sphero‐cylindrical contact lens corrections are larger for keratoconic eyes than for normal eyes. In some cases, a specific misalignment may improve visual image quality, which could be considered in the design of the next generation of rigid contact lenses.
Information sharing and state revenue forecasting performance
Authors: Spreen Thomas L. , Martinez Guzman Juan P. 
Published: September 2022

AbstractThis study evaluates whether intergovernmental information sharing enhances forecasting performance. This is accomplished by examining the accuracy of state revenue forecasts following the federal passage of the Tax Cuts and Jobs Act (TCJA) of 2017. The quantitative analysis suggests that states that shared information produced more accurate corporate income tax forecasts than nonsharing states. This result is consistent with surveys and interviews of federal and state officials that reported significant information‐sharing activity arising from uncertainty about the TCJA's corporate income tax provisions. This study demonstrates that information sharing plays an important yet overlooked role in mitigating forecast uncertainty.
The complex genome and adaptive evolution of polyploid Chinese pepper (Zanthoxylum armatum and Zanthoxylum bungeanum)
Authors: Hu Lisong , Xu Zhongping , Fan Rui , Wang Guanying , Wang Fuqiu , Qin Xiaowei , Yan Lin , Ji Xunzhi , Meng Minghui , Sim Soonliang , Chen Wei , Hao Chaoyun , Wang Qinghuang , Zhu Huaguo , Zhu Shu , Xu Pan , Zhao Hui , Lindsey Keith , Daniell Henry , Wendel Jonathan F. , Jin Shuangxia 
Published: September 2022

SummaryZanthoxylum armatum and Zanthoxylum bungeanum, known as ‘Chinese pepper’, are distinguished by their extraordinary complex genomes, phenotypic innovation of adaptive evolution and species‐special metabolites. Here, we report reference‐grade genomes of Z. armatum and Z. bungeanum. Using high coverage sequence data and comprehensive assembly strategies, we derived 66 pseudochromosomes comprising 33 homologous phased groups of two subgenomes, including autotetraploid Z. armatum. The genomic rearrangements and two whole‐genome duplications created large (~4.5 Gb) complex genomes with a high ratio of repetitive sequences (>82%) and high chromosome number (2n = 4x = 132). Further analysis of the high‐quality genomes shed lights on the genomic basis of involutional reproduction, allomones biosynthesis and adaptive evolution in Chinese pepper, revealing a high consistent relationship between genomic evolution, environmental factors and phenotypic innovation. Our study provides genomic resources and new insights for investigating diversification and phenotypic innovation in Chinese pepper, with broader implications for the protection of plants under severe environmental changes.