bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and initial characterization of mice lacking full‐length BAI3 (ADGRB3) expression
Authors: Shiu Fu Hung , Wong Jennifer C. , Bhattacharya Debanjan , Kuranaga Yuki , Parag Rashed R. , Alsharif Haifa A. , Bhatnagar Sushant , Van Meir Erwin G. , Escayg Andrew 
Published: June 2023

AbstractBrain‐specific angiogenesis inhibitor 3 (ADGRB3/BAI3) belongs to the family of adhesion G protein‐coupled receptors. It is most highly expressed in the brain where it plays a role in synaptogenesis and synapse maintenance. Genome‐wide association studies have implicated ADGRB3 in disorders such as schizophrenia and epilepsy. Somatic mutations in ADGRB3 have also been identified in cancer. To better understand the in vivo physiological role of ADGRB3, we used CRISPR/Cas9 editing to generate a mouse line with a 7‐base pair deletion in Adgrb3 exon 10. Western blot analysis confirmed that homozygous mutants (Adgrb3∆7/∆7) lack full‐length ADGRB3 expression. The mutant mice were viable and reproduced in Mendelian ratios but demonstrated reduced brain and body weights and deficits in social interaction. Measurements of locomotor function, olfaction, anxiety levels and prepulse inhibition were comparable between heterozygous and homozygous mutants and wild‐type littermates. Since ADGRB3 is also expressed in organs such as lung and pancreas, this new mouse model will facilitate elucidation of ADGRB3's role in non‐central nervous system‐related functions. Finally, since somatic mutations in ADGRB3 were identified in patients with several cancer types, these mice can be used to determine whether loss of ADGRB3 function contributes to tumour development.
Conditional Inference in Cis-Mendelian Randomization Using Weak Genetic Factors
Authors: Patel Ashish , Gill Dipender , Newcombe Paul , Burgess Stephen 
Published: June 2023

Abstract
Mendelian randomization (MR) is a widely used method to estimate the causal effect of an exposure on an outcome by using genetic variants as instrumental variables. MR analyses that use variants from only a single genetic region (cis-MR) encoding the protein target of a drug are able to provide supporting evidence for drug target validation. This paper proposes methods for cis-MR inference that use many correlated variants to make robust inferences even in situations, where those variants have only weak effects on the exposure. In particular, we exploit the highly structured nature of genetic correlations in single gene regions to reduce the dimension of genetic variants using factor analysis. These genetic factors are then used as instrumental variables to construct tests for the causal effect of interest. Since these factors may often be weakly associated with the exposure, size distortions of standard t-tests can be severe. Therefore, we consider two approaches based on conditional testing. First, we extend results of commonly-used identification-robust tests for the setting where estimated factors are used as instruments. Second, we propose a test which appropriately adjusts for first-stage screening of genetic factors based on their relevance. Our empirical results provide genetic evidence to validate cholesterol-lowering drug targets aimed at preventing coronary heart disease.
Lessons from the deep: mechanisms behind diversification of eukaryotic protein complexes
Authors: Prokopchuk Galina , Butenko Anzhelika , Dacks Joel B. , Speijer Dave , Field Mark C. , Lukeš Julius 
Published: June 2023

ABSTRACTGenetic variation is the major mechanism behind adaptation and evolutionary change. As most proteins operate through interactions with other proteins, changes in protein complex composition and subunit sequence provide potentially new functions. Comparative genomics can reveal expansions, losses and sequence divergence within protein‐coding genes, but in silico analysis cannot detect subunit substitutions or replacements of entire protein complexes. Insights into these fundamental evolutionary processes require broad and extensive comparative analyses, from both in silico and experimental evidence. Here, we combine data from both approaches and consider the gamut of possible protein complex compositional changes that arise during evolution, citing examples of complete conservation to partial and total replacement by functional analogues. We focus in part on complexes in trypanosomes as they represent one of the better studied non‐animal/non‐fungal lineages, but extend insights across the eukaryotes by extensive comparative genomic analysis. We argue that gene loss plays an important role in diversification of protein complexes and hence enhancement of eukaryotic diversity.
Twenty‐nail dystrophy and alopecia areata in an adult male with thymoma‐associated myasthenia gravis: A case report
Authors: Prado Mario B. , Quinio Maria Franchesca , Adiao Karen Joy B. 
Published: June 2023

AbstractBackgroundTo date, there is no journal that reports the coexistence of thymoma‐associated myasthenia gravis, alopecia areata, and twenty‐nail dystrophy. This paper hypothesizes that the presence of thymoma increases the risk of these conditions.Case presentationThe patient was a 37‐year‐old Filipino who came in for a year of history of fluctuating, but progressive, left‐sided ptosis and diplopia; difficulty swallowing; dysarthria; and aspiration and symmetric proximal muscle weakness confirmed to be myasthenia gravis by abnormal repetitive nerve stimulation and the presence of thymoma on histology. Before his thymectomy, he also developed gradually worsening thinning and longitudinal ridging of all fingernails and toenails; and patches of bald areas on the scalp; diagnosed to be twenty‐nail dystrophy and alopecia areata, respectively, by a board‐certified dermatologist.ConclusionThymoma is the possible risk factor and link for the co‐occurrence of the three conditions in the present patient.
Featured Cover
Authors: Zhao Chong , Qian Shuaijie , Tai Yang , Guo Yangkun , Tang Chengwei , Huang Zhiyin , Gao Jinhang 
Published: June 2023

The cover image is based on the Original Article Proangiogenic role of circRNA‐007371 in liver fibrosis by Chong Zhao et al., https://doi.org/10.1111/cpr.13432.image
Of Mojave milkweed and mirrors: The population genomic structure of a species impacted by solar energy development
Authors: Wade Miranda J. , Moore‐O'Leary Kara , Grodsky Steven M. , Hernandez Rebecca R. , Meek Mariah H. 
Published: June 2023

AbstractA rapid renewable energy transition has facilitated the development of large, ground‐mounted solar energy facilities worldwide. Deserts, and other sensitive aridland ecosystems, are the second most common land‐cover type for solar energy development globally. Thus, it is necessary to understand existing diversity within environmentally sensitive desert plant populations to understand spatiotemporal effects of solar energy siting and design. Overall, few population genomic studies of desert plants exist, and much of their biology is unknown. To help fill this knowledge gap, we sampled Mojave milkweed (Asclepias nyctaginifolia) in and around the Ivanpah Solar Electric Generating Station (ISEGS) in the Mojave Desert of California to understand the species' population structure, standing genetic variation, and how that intersects with solar development. We performed Restriction‐site Associated Sequencing (RADseq) and discovered 9942 single nucleotide polymorphisms (SNPs). Using these data, we found clear population structure over small spatial scales, suggesting each site sampled comprised a genetically distinct population of Mojave milkweed. While mowing, in lieu of blading, the vegetation across the solar energy facility's footprint prevented the immediate loss of the ISEGS Mojave milkweed population, we show that the effects of land‐cover change, especially those impacting desert washes, may impact long‐term genetic diversity and persistence. Potential implications of this include a risk of overall loss of genetic diversity, or even hastened extirpation. These findings highlight the need to consider the genetic diversity of impacted species when predicting the impact and necessary conservation measures of large‐scale land‐cover changes on species with small population sizes.
Systemische Behandlung von Patienten mit Psoriasis in der täglichen Praxis: Eine retrospektive Studie auf Basis deutscher Krankenkassendaten
Authors: Heidbrede Tanja , Mevius Antje , Kessel Sebastian , Wilke Thomas , Maywald Ulf , Thiem Alexander 
Published: June 2023

ZusammenfassungHintergrund und ZielePsoriasis ist eine weit verbreitete Hauterkrankung, die für die Patienten eine große physische und psychische Belastung darstellt. Bis zu 30% der Patienten sind Kandidaten für eine systemische Behandlung. Ziel dieser Studie war es, die Merkmale und die systemische Behandlung von Psoriasis‐Patienten in der klinischen Praxis zu beschreiben.Patienten und MethodikDiese Studie basierte auf deutschen Krankenkassendaten. In einer Querschnittsanalyse wurden alle Psoriasis‐Patienten im Jahr 2020 beobachtet. In einer Längsschnittanalyse wurden Psoriasis‐Patienten betrachtet, die neu mit einer systemischen Behandlung begonnen haben.ErgebnisseInsgesamt wurden 116 507 vordiagnostizierte Psoriasis‐Patienten und 13 449 neu behandelte Patienten beobachtet. Von allen prävalenten Patienten erhielten 15,2% im Jahr 2020 eine systemische Behandlung (8,7% systemische Kortikosteroide). Von den neu behandelten Patienten begannen 95,2% mit einer konventionellen Behandlung (79,2% systemische Kortikosteroide), 4,0% mit Biologika und 0,9% mit Apremilast. Die Rate der Behandlungsabbrüche/‐wechsel nach einem Jahr war bei Kortikosteroiden am höchsten (91,3%) und bei Biologika am niedrigsten (23,1%).SchlussfolgerungenEtwa 15% der Psoriasis‐Patienten in Deutschland erhielten eine systemische Behandlung, davon wurden > 50% systemische Kortikosteroide verschrieben. Daraus schließen wir, dass die systemische Behandlung bei einer beträchtlichen Anzahl der beobachteten Patienten nicht den Leitlinienempfehlungen entspricht. Die niedrigsten Abbruch‐/Wechselraten bei Biologika sprechen für deren breiteren Einsatz.
Safety/tolerability, efficacy and pharmacokinetics of 600‐μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher: A phase I, randomized, double‐blind, placebo‐controlled study
Authors: Asano Michiko , Sekikawa Akiko , Sugeno Masatoshi , Matsuoka Osamu , Robertson Darren , Hansen Lars 
Published: June 2023

AbstractAimTo assess the safety/tolerability, efficacy and pharmacokinetics of once‐daily, 600‐μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher.Materials and MethodsThis phase I, randomized, double‐blind, placebo‐controlled study (NCT04208620) enrolled patients to receive subcutaneous cotadutide at an escalating dose to determine the highest tolerated clinical dose (Cohort 1), then applied in Cohort 2. The primary endpoint was safety, including treatment‐emergent adverse events (TEAEs); secondary endpoints included glycaemic control and body weight.ResultsSixteen patients were randomly allocated to receive cotadutide or placebo in a 3:1 ratio. All patients were Asian, 62.5% were male, and the median age and body mass index were 60 years and 27.2 kg/m2, respectively. Through the follow‐up period of the study, 11/12 (91.7%) patients in the cotadutide group experienced a TEAE versus 1/4 (25.0%) patients in the placebo group. All TEAEs were mild, except for one moderate event. There were no deaths, serious TEAEs or TEAEs leading to study discontinuation. Gastrointestinal‐related events were the most common TEAEs. Cotadutide‐treated patients achieved significantly improved 7‐day mean glucose measured by continuous glucose monitoring; the 7‐day mean (standard deviation) at the end of treatment (day 70) was 112.23 (20.79) versus 206.85 (3.62) mg/dL for placebo. Mean respective changes in HbA1c were −1.13% (0.64%) and −0.17% (0.65%); and mean percentage changes in body weight were −6.93% (3.44%) and −1.23% (1.20%).ConclusionsCotadutide was well tolerated at doses up to 600 μg; efficacy versus placebo for weight loss and glycaemic control was shown.
Assessment of the patient with heart failure symptoms and risk factors: A guide for the non‐cardiologist
Authors: Arnold Suzanne V. 
Published: June 2023

AbstractAlthough the prevalence of heart failure has been increasing over time, the presentation of heart failure has been shifting, with a greater proportion of preserved ejection fraction and more slowly progressive symptoms that require recognition in the outpatient setting. These shifts have placed more of the diagnostic responsibility onto primary care physicians, who often are challenged to determine the etiology of common symptoms in patients who often have several other potential reasons for these symptoms. Establishing a diagnosis of heart failure requires a step‐wise approach that includes physical exam (looking for multiple signs of hypervolemia), labs (B‐type natriuretic peptide levels), and echocardiography (structural and functional measures). Diagnostic algorithms are particularly challenging in patients with obesity, which limits the assessment of intravascular volume on exam, the quality of cardiac imaging, and the diagnostic accuracy of B‐type natriuretic peptide levels, which may be falsely low. In these challenging patients, the use of risk scores, invasive testing of intravascular volume, or empiric treatment of hypervolemia may be needed to determine whether symptoms are due to heart failure. Once a diagnosis of heart failure is established, several treatments can be beneficial, from diuretics to relieve congestion to various aspects of guideline‐directed medical therapy, some of which vary according to the ejection fraction of the patient. In addition, a diagnosis of heart failure may alter the treatment plan for comorbidities, including selection of anti‐hypertensive and glucose‐lowering medications, and medical or surgical treatments for obesity. While a diagnosis of heart failure may be challenging in many patients with slowly progressive and non‐specific symptoms, early recognition and treatment can be extremely effective at preventing hospitalizations, prolonging survival, and improving quality of life.
Instruments to assess students’ critical thinking—A qualitative approach
Authors: Paul Jomon A. , Sinha Mona , Cochran Justin D. 
Published: June 2023

ABSTRACTCritical thinking (CT) skills are essential to academic and professional success. Instruments to assess CT often rely on multiple‐choice formats with inherent problems. This research presents two instruments for assessing CT, an essay and open‐ended group‐discussion format, which were implemented in an undergraduate business course at a large public university. The topics were intentionally chosen to be digitally‐related (internet access and social media) since they raise complex issues, are applicable in many disciplines, and students are avid users, thereby making these instruments relevant, multidisciplinary, engaging, and multifaceted. These instruments may be adapted to enable educators to effectively assess undergraduate students’ ability to think critically. Qualitative analysis of the verbatim data with NVivo helps demonstrate the instruments’ efficacy in assessing CT, with (1) high‐quality responses receiving high grades, and (2) overarching themes identified by content analysis, that coalesce into the three dimensions of social justice theory (distributive, procedural, and interactional), thus illustrating students’ consideration of complex fairness norms and societal needs. Excerpts of student responses are provided as illustrations of the indicators/evidence of critical thinking. Educators can use these instruments to first assess students’ CT skills, and then devise targeted interventions to improve the quality of students’ thought processes.
Mean species responses predict effects of environmental change on coexistence
Authors: De Laender Frederik , Carpentier Camille , Carletti Timoteo , Song Chuliang , Rumschlag Samantha L. , Mahon Michael B. , Simonin Marie , Meszéna Géza , Barabás György 
Published: June 2023

AbstractEnvironmental change research is plagued by the curse of dimensionality: the number of communities at risk and the number of environmental drivers are both large. This raises the pressing question if a general understanding of ecological effects is achievable. Here, we show evidence that this is indeed possible. Using theoretical and simulation‐based evidence for bi‐ and tritrophic communities, we show that environmental change effects on coexistence are proportional to mean species responses and depend on how trophic levels on average interact prior to environmental change. We then benchmark our findings using relevant cases of environmental change, showing that means of temperature optima and of species sensitivities to pollution predict concomitant effects on coexistence. Finally, we demonstrate how to apply our theory to the analysis of field data, finding support for effects of land use change on coexistence in natural invertebrate communities.
Regional cerebral perfusion during the premonitory phase of triggered migraine: A double‐blind randomized placebo‐controlled functional imaging study using pseudo‐continuous arterial spin labeling
Authors: Karsan Nazia , Bose Ray Pyari , O'Daly Owen , Zelaya Fernando , Goadsby Peter J. 
Published: June 2023

AbstractObjectiveTo identify changes in regional cerebral blood flow (CBF) associated with premonitory symptoms (PS) of nitroglycerin (NTG)‐triggered migraine attacks.BackgroundPS could provide insights into attack initiation and alterations in neuronal function prior to headache onset.MethodsWe undertook a functional imaging study using a double‐blind placebo‐controlled randomized approach in patients with migraine who spontaneously experienced PS, and in whom PS and migraine‐like headache could be induced by administration of NTG. All study visits took place in a dedicated clinical research facility housing a monitoring area with clinical beds next to a 3Tesla magnetic resonance imaging scanner. Fifty‐three patients with migraine were enrolled; imaging on at least one triggered visit was obtained from 25 patients, with 21 patients completing the entire imaging protocol including a placebo visit. Whole brain CBF maps were acquired using 3D pseudo‐continuous arterial spin labeling (3D pCASL).ResultsThe primary outcome was that patients with migraine not taking preventive treatment (n = 12) displayed significant increases in CBF in anterior cingulate cortex, caudate, midbrain, lentiform, amygdala and hippocampus (p < 0.05 family‐wise error‐corrected) during NTG‐induced PS. A separate region of interest analysis revealed significant CBF increases in the region of the hypothalamus (p = 0.006, effect size 0.77). Post hoc analyses revealed significant reductions in CBF over the occipital cortices in participants with a history of migraine with underlying aura (n = 14).ConclusionsWe identified significant regional CBF changes associated with NTG‐induced PS, consistent with other investigations and with novel findings, withstanding statistical comparison against placebo. These findings were not present in patients who continually took preventive medication. Additional findings were identified only in participants who experience migraine with aura. Understanding this biological and treatment‐related heterogeneity is vital to evaluating functional imaging outcomes in migraine research.
Research on crack mechanism and kinetic model of alumina ceramic in the degreasing stage based on stereolithography
Authors: Cui Maomao , Wang Tao , Zhao Yi , Zhang Zhao , Wang Xiao , Hou Xin , Sun Wenxiang , Liu Huixia 
Published: June 2023

AbstractGiven that the kinetics of the thermal degreasing process of alumina ceramics based on stereolithography apparatus (SLA) has not been investigated, the mechanism of crack generation is still not fully revealed. This paper aims to elucidate the mechanism of crack generation in the degreasing process of alumina ceramics and to establish a kinetic model for alumina ceramics. Two sintering atmospheres, air, and argon, were selected for the degreasing tests at 100°C–700°C. The reaction products and mass changes of alumina ceramics were analyzed by TG‐FTIR and TG‐DSC (heating rates of 5, 10, and 15°C/min, respectively). Meanwhile, Boswell, Friedman, Ozawa, and DAEM model was used to describe the nonisothermal kinetics of the SLA alumina ceramic degreasing process. The results showed that setting the holding time to 400°C–425°C could promote the slow release of heat from the alumina ceramics. The thermal degreasing stage of the ceramic generated fewer cracks in the argon atmosphere than in the air atmosphere. The corresponding average activation energy values were 105.40 kJ/mol (Boswell model), 112.48 kJ/mol (Friedman model), 108.14 kJ/mol (Ozawa model), and 101.36 kJ/mol (DAEM model). The results of the study could provide an invaluable reference for the fabrication of defect‐free SLA alumina ceramics.
A paradox‐constitutive perspective of organizational gossip
Authors: Greenslade‐Yeats James , Cooper‐Thomas Helena , Corner Patricia D. , Morrison Rachel 
Published: June 2023

AbstractWe review cross‐disciplinary research on gossip and integrate it with two streams of theoretical scholarship: paradox theory and the communicative constitution of organization (CCO) perspective. In doing so, we develop what we label a paradox‐constitutive perspective of organizational gossip. Our perspective holds that gossip does not merely reflect or reveal organizational paradoxes but contributes to constituting them. Drawing on an extensive narrative literature review (N = 184), we conceptualize organizational gossip as a socially constructed category of interpersonal communication that, paradoxically, is regarded as both an exceptionally reliable and exceptionally unreliable source of social information. In turn, we illustrate how this contradictory view of gossip engenders paradoxical tensions when gossip surfaces in organizational life, and we illuminate two specific tensions to which gossip contributes: resistance‐authority tensions and inclusion‐exclusion tensions. Our work has important implications for research on organizational gossip, paradox, and communication and suggests intriguing directions for future investigations.
Comparison of wound complications between one‐stage and two‐stage brachiobasilic arteriovenous fistula: A meta‐analysis
Authors: Lu Yanyan , Xiao Jiao , Liu Chunyan , Wang Yuan 
Published: June 2023

AbstractResearch assessing the outcome of brachiobasilic arteriovenous fistulas (BB‐AVF) after a one‐ and two‐stage technique was conducted. A strict review of the comprehensive literature up to May 2023 was carried out using four databases‐PubMed，Embase, Cochrane Library and web of science. Inclusion and exclusion criteria developed for the study were then applied to assess the quality of the literature, it was decided to review 12 interrelated studies.95% confidence intervals (Cl) and odds ratios (OR) were calculated using fixed effects models. The data were meta‐analysed using RevMan 5.3 software. The results showed that two‐stage technique with BB‐AVF reduced surgical site haematoma (SSH) formation, (OR, 2.28; 95% CI, 1.24–4.17, p = 0.008), and also reduced surgical site wound infection (SSWI) (OR, 1.86; 95% CI, 1.17–2.94, p = 0.008). There are, however, several small sample sizes in the selected studies for this meta‐analysis, so caution should be used when processing their values. There are more high‐quality studies with large sample sizes that should be considered for future meta‐analyses.