bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel exotic alleles of EARLY FLOWERING 3 determine plant development in barley
Authors: Zahn Tanja , Zhu Zihao , Ritoff Niklas , Krapf Jonathan , Junker Astrid , Altmann Thomas , Schmutzer Thomas , Tüting Christian , Kastritis Panagiotis L , Babben Steve , Quint Marcel , Pillen Klaus , Maurer Andreas 
Published: April 2023

Abstract
EARLY FLOWERING 3 (ELF3) is an important regulator of various physiological and developmental processes and hence may serve to improve plant adaptation which will be essential for future plant breeding. To expand the limited knowledge on barley ELF3 in determining agronomic traits, we conducted field studies with heterogeneous inbred families (HIFs) derived from selected lines of the wild barley nested association mapping population HEB-25. During two growing seasons, phenotypes of nearly isogenic HIF sister lines, segregating for exotic and cultivated alleles at the ELF3 locus, were compared for 10 developmental and yield-related traits. We determine novel exotic ELF3 alleles and show that HIF lines, carrying the exotic ELF3 allele, accelerated plant development compared with the cultivated ELF3 allele, depending on the genetic background. Remarkably, the most extreme effects on phenology could be attributed to one exotic ELF3 allele differing from the cultivated Barke ELF3 allele in only one single nucleotide polymorphism (SNP). This SNP causes an amino acid substitution (W669G), which as predicted has an impact on the protein structure of ELF3. Consequently, it may affect phase separation behaviour and nano-compartment formation of ELF3 and, potentially, also its local cellular interactions causing significant trait differences between HIF sister lines.
A Phase I Study of a Combination of Liposomal Irinotecan and Veliparib in Solid Tumors
Authors: LaRose Meredith , Connolly Roisin M , O’Sullivan Ciara C , Velcheti Vamsidhar , Vilimas Rasa , Gano Katherine , Bates Susan E , Pommier Yves , Thomas Anish 
Published: April 2023

Abstract

Background
Multiple preclinical studies have shown cytotoxic synergy involving combinations of poly (ADP-ribose) polymerase (PARP) inhibitors and topoisomerase 1 (TOP1) inhibitors, but such combinations have proven too toxic in clinical trials. Liposomal irinotecan (nal-IRI) achieved similar intratumoral exposure with better antitumor activity than the conventional TOP1 inhibitor irinotecan in preclinical models. Tumor targeted delivery of TOP1 inhibitor using nal-IRI and an intermittent schedule of administration of PARP inhibitor may provide a tolerable combination.

Methods
A phase I study was performed to evaluate the safety and tolerability of escalating doses of nal-IRI and the PARP inhibitor veliparib in patients with solid tumors resistant to standard treatments. Nal-IRI was administered on days 1 and 15 and veliparib on days 5-12 and 19-25 in 28-day cycles.

Results
Eighteen patients were enrolled across 3 dose levels. Five patients encountered dose–limiting toxicities, including grade 3 diarrhea lasting more than 72 h in 3 patients and 1 patient each with grade 4 diarrhea and grade 3 hyponatremia. The most common grade 3 or 4 toxicities included diarrhea (50% of patients), nausea (16.6%), anorexia, and vomiting (11.1% each) (Table 1). There was no difference in frequencies of adverse events based on UGT1A1*28 status or prior opioid use (Table 1).

Conclusion
The clinical trial was terminated due to high frequency of unacceptable gastrointestinal toxicities, which precluded dose escalation of veliparib in combination with nal-IRI (ClinicalTrials.gov Identifier: NCT02631733).
The transcription factor PbrMYB24 regulates lignin and cellulose biosynthesis in stone cells of pear fruits
Authors: Xue Yongsong , Shan Yanfei , Yao Jia-Long , Wang Runze , Xu Shaozhuo , Liu Dongliang , Ye Zhicheng , Lin Jing , Li Xiaogang , Xue Cheng , Wu Jun 
Published: April 2023

Abstract
Lignified stone cell content is a key factor used to evaluate fruit quality, influencing the economic value of pear (Pyrus pyrifolia) fruits. However, our understanding of the regulatory networks of stone cell formation is limited due to the complex secondary metabolic pathway. In this study, we used a combination of co-expression network analysis, gene expression profiles, and transcriptome analysis in different pear cultivars with varied stone cell content to identify a hub MYB gene, PbrMYB24. The relative expression of PbrMYB24 in fruit flesh was significantly correlated with the contents of stone cells, lignin, and cellulose. We then verified the function of PbrMYB24 in regulating lignin and cellulose formation via genetic transformation in homologous and heterologous systems. We constructed a high-efficiency verification system for lignin and cellulose biosynthesis genes in pear callus. PbrMYB24 transcriptionally activated multiple target genes involved in stone cell formation. On the one hand, PbrMYB24 activated the transcription of lignin and cellulose biosynthesis genes by binding to different cis-elements [AC-I (ACCTACC) element, AC-II (ACCAACC) element and MYB-binding sites (MBS)]. On the other hand, PbrMYB24 bound directly to the promoters of PbrMYB169 and NAC STONE CELL PROMOTING FACTOR (PbrNSC), activating the gene expression. Moreover, both PbrMYB169 and PbrNSC activated the promoter of PbrMYB24, enhancing gene expression. This study improves our understanding of lignin and cellulose synthesis regulation in pear fruits through identifying a regulator and establishing a regulatory network. This knowledge will be useful for reducing the stone cell content in pears via molecular breeding.
Public Opinion and Cyberterrorism
Authors: Shandler Ryan , Kostyuk Nadiya , Oppenheimer Harry 
Published: April 2023

Abstract
Research into cyber-conflict, public opinion, and international security is burgeoning, yet the field suffers from an absence of conceptual agreement about key terms. For instance, every time a cyberattack takes place, a public debate erupts as to whether it constitutes cyberterrorism. This debate bears significant consequences, seeing as the ascription of a “terrorism” label enables the application of heavy-handed counterterrorism powers and heightens the level of perceived threat among the public. In light of widespread conceptual disagreement in cyberspace, we assert that public opinion plays a heightened role in understanding the nature of cyber threats. We construct a typological framework to illuminate the attributes that drive the public classification of an attack as cyberterrorism, which we test through a ratings-based conjoint experiment in the United States, the United Kingdom, and Israel (N = 21,238 observations). We find that the public (1) refrains from labeling attacks by unknown actors or hacker collectives as cyberterrorism; and (2) classifies attacks that disseminate sensitive data as terrorism to a greater extent even than physically explosive attacks. Importantly, the uniform public perspectives across the three countries challenge a foundational tenet of public opinion and international relations scholarship that divided views among elites on foreign policy matters will be reflected by a divided public. This study concludes by providing a definitive conceptual baseline to support future research on the topic.
Anti-SAE autoantibody in dermatomyositis: original comparative study and review of the literature
Authors: Demortier Juliette , Vautier Mathieu , Chosidow Olivier , Gallay Laure , Bessis Didier , Berezne Alice , Cordel Nadège , Schmidt Jean , Smail Amar , Duffau Pierre , Jachiet Marie , Begon Edouard , Gottlieb Jeremy , Chasset François , Graveleau Julie , Marque Myriam , Cesbron Elise , Forestier Amandine , Josse Séverine , Kluger Nicolas , Beauchêne Caroline , Le Corre Yannick , Pagis Valentine , Rigolet Aude , Guillaume-Jugnot Perrine , Authier François-Jérôme , Guilain Nelly , Streichenberger Nathalie , Leonard-Louis Sarah , Boussouar Samia , Landon-Cardinal Océane , Benveniste Olivier , Allenbach Yves 
Published: April 2023

Abstract

Objective
Among specific autoantibodies in DM, the anti–small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE–positive DM.

Methods
Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE–negative DM and a review of the literature.

Results
Of the patients in the study (n = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis; 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE–negative DM (n = 85) showed less and milder muscle weakness (P = 0.02 and P = 0.006, respectively), lower creatinine kinase levels (P &lt; 0.0001) and less dyspnoea (P = 0.003).

Conclusion
Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population.

Trial registration
ClinicalTrials.gov, http://clinicaltrials.gov, NCT04637672.
Director Expertise and Corporate Sustainability
Authors: Iliev Peter , Roth Lukas 
Published: April 2023

Abstract
We show that US firms increase their sustainability performance when their directors acquire expertise through their exposure to sustainability reforms in foreign countries where they serve as directors. Our results suggest that a board that gains sustainability expertise increases a firm’s overall sustainability performance by 7.1%. The increase in sustainability comes both from improvements in environmental and social practices. Directors also consider the tradeoffs between sustainability improvements and firm characteristics, with boards having a stronger impact on sustainability in firms from clean industries and firms that face fewer operational and financial constraints.
The rise and fall of ordoliberalism
Authors: Hien Josef 
Published: April 2023

Abstract
Ordoliberalism has been accused of being the ideational blueprint for Germany’s fiscal stance during the Eurozone-crisis. While the literature that debates the influence of ordoliberalism on crisis politics is growing, there is a lack of studies tracing the ordoliberal influence within Germany. This study shows that ordoliberalism had very limited influence on the creation of German institutions and its economic knowledge regime. Where ordoliberalism can be found is in the bureaucracy. This influence will come to an end with the last ordoliberals retiring. The article reconstructs how the reorientation of German economics towards the global economics profession crowded out ordoliberalism. Ordoliberalism, publishing mostly in German and not being able to formalize its theory, could not keep up with modern German economics. This will also dry up the supply of ordoliberal staff for the bureaucracy. The article shows also that ordoliberalism lives on as part of the German conservative political tradition.
Elm tree defences against a specialist herbivore are moderately primed by an infestation in the previous season
Authors: Schott Johanna , Jantzen Friederike , Hilker Monika 
Published: April 2023

Abstract
The studies of the long-term effects of insect infestations on plant anti-herbivore defences tend to focus on feeding-induced damage. Infestations by an entire insect generation, including egg depositions as well as the feeding insects, are often neglected. Whilst there is increasing evidence that the presence of insect eggs can intensify plants’ anti-herbivore defences against hatching larvae in the short term, little is known about how insect infestations, including insect egg depositions, affect plant defences in the long term. We addressed this knowledge gap by investigating long-term effects of insect infestation on elm’s (Ulmus minor Mill. cv. ‘Dahlem’) defences against subsequent infestation. In greenhouse experiments, elms were exposed to elm leaf beetle (ELB, Xanthogaleruca luteola) infestation (adults, eggs and larvae). Thereafter, the trees cast their leaves under simulated winter conditions and were re-infested with ELB after the regrowth of their leaves under simulated summer conditions. Elm leaf beetles performed moderately worse on previously infested elms with respect to several developmental parameters. The concentrations of the phenylpropanoids kaempferol and quercetin, which are involved in egg-mediated, short-term effects on elm defences, were slightly higher in the ELB-challenged leaves of previously infested trees than in the challenged leaves of naïve trees. The expression of several genes involved in the phenylpropanoid pathway, jasmonic acid signalling, and DNA and histone modifications appeared to be affected by ELB infestation; however, prior infestation did not alter the expression intensities of these genes. The concentrations of several phytohormones were similarly affected in the currently challenged leaves of previously infested trees and naïve trees. Our study shows that prior infestation of elms by a specialised insect leads to moderately improved defences against subsequent infestation in the following growing season. Prior infestation adds a long-term effect to the short-term enhancer effect that plants show in response to egg depositions when defending against hatching larvae.
Minimum Wages around Birth and Child Health
Authors: Majid Muhammad Farhan , Behrman Jere R 
Published: April 2023

Abstract
This paper studies the effects of minimum wages in Indonesia around the time of birth on child height-for-age Z scores (HAZ) up to five years of age. Using variations in annual fluctuations in real minimum wages in different Indonesian provinces, it finds that children exposed to increases in minimum wages in their birth years have higher HAZ in the first five years of their lives. The estimated impacts are based on difference-in-differences models with biological-mother fixed effects and year-of-birth fixed effects and are robust to inclusion of multiple time-varying factors. The impacts are prominent particularly among male children.
Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation*
Authors: Zaaqoq Akram M. , Griffee Matthew J. , Kelly Thu-Lan , Fanning Jonathon P. , Heinsar Silver , Suen Jacky Y. , Mariani Silvia , Li Bassi Gianluigi , Jacobs Jeffrey P. , White Nicole , Fraser John F. , Lorusso Roberto , Peek Giles J. , Cho Sung-Min ,   COVID-19 Critical Care Consortium (COVID Critical)
Published: April 2023

OBJECTIVES:
Evidence of cerebrovascular complications in COVID-19 requiring venovenous extracorporeal membrane oxygenation (ECMO) is limited. Our study aims to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on venovenous ECMO.

DESIGN:
We analyzed prospectively collected observational data, using univariable and multivariable survival modeling to identify risk factors for stroke. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks.

SETTING:
Three hundred eighty institutions in 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry.

PATIENTS:
Adult COVID-19 patients who were supported by venovenous ECMO.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Five hundred ninety-five patients (median age [interquartile range], 51 yr [42–59 yr]; male: 70.8%) had venovenous ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity (adjusted hazard ratio [aHR], 2.19; 95% CI, 1.05–4.59) and use of vasopressors before ECMO (aHR, 2.37; 95% CI, 1.08–5.22) were associated with an increased risk of stroke. Forty-eight-hour post-ECMO Paco
2–pre-ECMO Paco
2/pre-ECMO Paco
2 (relative ΔPaco
2) of negative 26% and 48-hour post-ECMO Pao
2–pre-ECMO Pao
2/pre-ECMO Pao
2 (relative ΔPao
2) of positive 24% at 48 hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPaco
2 of negative 17% and relative ΔPao
2 of positive 7% in the nonstroke group. Patients with acute stroke had a 79% in-hospital mortality compared with 45% mortality for stroke-free patients.

CONCLUSIONS:
Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on venovenous ECMO. Also, the importance of relative decrease in Paco
2 and moderate hyperoxia within 48 hours after ECMO initiation were additional risk factors.
Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial
Authors: Gu Chengyuan , Wang Zengjun , Lin Tianxin , Liu Zhiyu , Han Weiqing , Zhang Xuhui , Liang Chao , Liu Hao , Yu Yang , Xu Zhenzhou , Liu Shuang , Wang Jingen , Jia Linghua , Yao Xin , Liao Wenfeng , Fu Cheng , Tan Zhaohui , He Guohua , Zhu Guoxi , Fan Rui , Yang Wenzeng , Chen Xin , Liu Zhizhong , Zhong Liqiang , Shi Benkang , Ding Degang , Chen Shubo , Wei Junli , Yao Xudong , Chen Ming , Lu Zhanpeng , Xie Qun , Hu Zhiquan , Wang Yinhuai , Guo Hongqian , Fan Tiwu , Liang Zhaozhao , Chen Peng , Wang Wei , Xu Tao , Li Chunsheng , Xing Jinchun , Liao Hong , He Dalin , Wu Zhibin , Yu Jiandi , Feng Zhongwen , Yang Mengxiang , Dou Qifeng , Zeng Quan , Li Yuanwei , Gou Xin , Zhou Guangchen , Wang Xiaofeng , Zhu Rujian , Zhang Zhonghua , Zhang Bo , Tan Wanlong , Qu Xueling , Sun Hongliang , Gan Tianyi , Ye Dingwei 
Published: April 2023

AbstractBackground:LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.Results:On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9%, 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3%, 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0%vs. 1.4% [2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.Trial registration:ClinicalTrials.gov, NCT04563936.
Treatment Outcomes of Adjunct and Stand-alone Photodynamic Therapy in Patients With Extramammary Paget Disease: A Literature Review
Authors: Sachdeva Muskaan , Tai Felicia , Bargman Howard 
Published: April 2023

BACKGROUND
Extramammary Paget disease (EMPD) is a rare malignant neoplasm arising from apocrine gland–bearing skin. The surgical management of EMPD is often coupled with noninvasive techniques including cryotherapy, ablative lasers, topical chemotherapies, and photodynamic therapy (PDT). The specificity and preservation of tissue that PDT with photosensitizers 5-aminolevulinic acid or 5-methyl aminolevulinate allows makes it a potential treatment of EMPD.

METHODS
The authors present a review of 13 studies, from 2002 to 2019, examining the reported efficacy of PDT alone and adjunctive PDT in EMPD treatment.

RESULTS
In the 52 patients with 56 lesions who received stand-alone PDT, 20 lesions (35.7%, n = 20/56) experienced complete resolution, 31 lesions (55.4%, n = 31/56) experienced partial resolution, 5 lesions (8.9%, n = 5/56) failed to demonstrate response to treatment, and 23 lesions (41.1%, n = 23/56) had recurrence. In the 56 patients with 66 lesions that received adjunctive PDT paired with surgery (n = 55/66), imiquimod (n = 4/66), holmium laser and surgery (n = 1/66), Mohs surgery (n = 2/66), and combined surgery, imiquimod, and 5-fluorouracil (n = 1/66), 34 lesions (51.5%) experienced complete resolution, 27 lesions (40.9%) experienced partial resolution, 5 lesions (7.6%) failed to demonstrate any response to treatment, and 16 lesions (24.2%) had EMPD recurrence.

CONCLUSION
Further studies with larger sample size are needed to consolidate these findings and inform clinical decisions.
Multidisciplinary team approach for treating recurrent gastrointestinal bleeding caused by a Dieulafoy lesion
Authors: Lezama Tamara , Phelan Liam , Parmar Jitesh , Karandikar Sharad 
Published: April 2023

Abstract
A Dieulafoy lesion is a histologically normal arteriole whose lumen diameter persists along the entire wall of its end organ. They are reported to account for 1% to 2% of all gastrointestinal bleeds. The etiology is largely unknown, with some reports of lesions in children suggesting a congenital origin (Ann R Coll Surg Engl 2010;92(7):548–554). Mortality rates are approximately 10% compared with the previous rate of 80%, and this is attributed to the vast advancement in endoscopic techniques. This case highlights the need for multidisciplinary team approach to the assessment and management of these patients and investigation with the breadth of modalities available. The potential for open operative intervention by emergency surgical teams needs to be identified early in cases where minimal access measures are unable to gain definitive control.