bluuebunny/crossref_metadata_2025_split huggingface dataset:
Test for Trading Costs Effect in a Portfolio Selection Problem with Recursive Utility
Authors: Carrasco Marine , Koné N’Golo 
Published: May 2023

Abstract
This article addresses a portfolio selection problem with trading costs on stock market. More precisely, we develop a simple generalized method of moments (GMM)-based test procedure to test the significance of trading costs effect in the economy with a flexible form of transaction costs. We also propose a two-step procedure to test overidentifying restrictions in our GMM estimation. In an empirical analysis, we apply our test procedures to the class of anomalies used in Novy-Marx and Velikov (2016). We show that transaction costs have a significant effect on investors’ behavior for many anomalies. In that case, investors significantly improve the out-of-sample performance of their portfolios by accounting for trading costs.
A Phantom Verb: Yuttan in Biblical Hebrew
Authors: Eichler Raanan 
Published: May 2023

Abstract
The verb נתן ‘to give’ is pointed as hophal eight times in the Bible. The scholarly consensus is that these occurrences were originally intended as qal-passive, and that there was no hophal נתן in original Biblical Hebrew. It is argued here that there was neither hophal nor qal-passive נתן in original Biblical Hebrew: these occurrences were originally intended as qal, their subjects were indefinite, and they were intuitively revocalized as hophal when the third-person singular indefinite subject fell out of use in Hebrew.
Seven plant capacities to adapt to abiotic stress
Authors: Munns Rana , Millar A Harvey 
Published: May 2023

AbstractAbiotic stresses such as drought and heat continue to impact crop production in a warming world. This review distinguishes seven inherent capacities that enable plants to respond to abiotic stresses and continue growing, although at a reduced rate, to achieve a productive yield. These are the capacities to selectively take up essential resources, store them and supply them to different plant parts, generate the energy required for cellular functions, conduct repairs to maintain plant tissues, communicate between plant parts, manage existing structural assets in the face of changed circumstances, and shape-shift through development to be efficient in different environments. By illustration, we show how all seven plant capacities are important for reproductive success of major crop species during drought, salinity, temperature extremes, flooding, and nutrient stress. Confusion about the term ‘oxidative stress’ is explained. This allows us to focus on the strategies that enhance plant adaptation by identifying key responses that can be targets for plant breeding.
Protein O-glycosylation regulates diverse developmental and defense processes in plants
Authors: Xu Jin , Du Hongyu , Shi Huanran , Song Jianing , Yu Jingquan , Zhou Yanhong 
Published: May 2023

Abstract
Post-translational modifications affect protein functions and play key roles in controlling biological processes. Plants have unique types of O-glycosylation that are different from those of animals and prokaryotes, and they play roles in modulating the functions of secretory proteins and nucleocytoplasmic proteins by regulating transcription and mediating localization and degradation. O-glycosylation is complex because of the dozens of different O-glycan types, the widespread existence of hydroxyproline (Hyp), serine (Ser), and threonine (Thr) residues in proteins attached by O-glycans, and the variable modes of linkages connecting the sugars. O-glycosylation specifically affects development and environmental acclimatization by affecting diverse physiological processes. This review describes recent studies on the detection and functioning of protein O-glycosylation in plants, and provides a framework for the O-glycosylation network that underlies plant development and resistance.
Selumetinib in Japanese pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An open-label, phase I study
Authors: Suenobu Souichi , Terashima Keita , Akiyama Masaharu , Oguri Tomoyo , Watanabe Asako , Sugeno Masatoshi , Higashimori Mitsuo , So Karen , Nishida Yoshihiro 
Published: May 2023

Abstract

Background
Plexiform neurofibromas (PN) are a manifestation of neurofibromatosis type 1 (NF1) that may cause morbidity and impact health-related quality of life (HRQoL). Selumetinib (ARRY-142886, AZD6244) is an orally available, selective, mitogen-activated protein kinase kinase 1/2 inhibitor approved for children with NF1 and symptomatic, inoperable PN in regions including the USA (aged ≥2 years), EU (≥3 years), and Japan (≥3 years). This open-label, single-arm, phase I study evaluated selumetinib in Japanese children with NF1 and symptomatic, inoperable PN.

Methods
Eligible patients (aged 3–18 years) received oral selumetinib (25 mg/m2 twice daily) continuously in 28-day cycles in a fasted state. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, efficacy, PN-related morbidities, and HRQoL.

Results
Twelve patients (median age 13.3 years) were enrolled, received ≥1 selumetinib dose (data cutoff: cycle 13 day 1) with median follow-up of 11.5 months. All patients had baseline PN-related morbidities, most commonly disfigurement (91.7%) and pain (58.3%). Most frequently reported any-grade adverse events were dermatologic and gastrointestinal. Objective response rate was 33.3%; median duration of response was not reached. Most patients (83.3%) had target PN volume reduction versus baseline. No patients reported worsening of PN-related morbidities. Selumetinib was rapidly absorbed with moderate-to-high inter-patient variability in maximum plasma concentration and area under the concentration–time curve from time 0–6 hours.

Conclusions
Consistent with results of the phase II SPRINT trial, 25 mg/m2 selumetinib twice daily was well tolerated with a manageable safety profile in Japanese children with NF1 and symptomatic, inoperable PN.
Moral Grounds for Economic and Social Rights
Authors: Nickel James W. 
Published: May 2023

Abstract
This chapter considers possible moral grounds for recognizing and realizing economic and social rights (ESRs) as human rights. It begins by suggesting that ESRs fall into three families: (1) welfare-oriented ESRs, which protect adequate income, education, health, and safe and healthful working conditions; (2) freedom-oriented ESRs, which prohibit slavery, ensure free choice of employment, and protect workers’ freedoms to organize and strike: and (3) fairness-oriented ESRs, which require nondiscrimination and equal opportunity in the workplace along with fair remuneration for one’s work. To accommodate the normative diversity found in these three families, the chapter suggests a pluralistic justificatory framework that appeals to three kinds of moral reasons: human welfare, freedom, and fairness. A final section considers the possibility of subsuming all three of these approaches to justification under the idea of human dignity or the associated idea of equal respect for persons.
Spatiotemporal and microstructural characterization of heterotopic ossification in healing rat Achilles tendons
Authors: Pierantoni Maria , Hammerman Malin , Silva Barreto Isabella , Larsson Daniel , Notermans Thomas , Bodey Andrew J. , Eliasson Pernilla , Isaksson Hanna 
Published: May 2023

AbstractAchilles tendon rupture is a common debilitating medical condition. The healing process is slow and can be affected by heterotopic ossification (HO), which occurs when pathologic bone‐like tissue is deposited instead of the soft collagenous tendon tissue. Little is known about the temporal and spatial progression of HO during Achilles tendon healing. In this study we characterize HO deposition, microstructure, and location at different stages of healing in a rat model. We use phase contrast‐enhanced synchrotron microtomography, a state‐of‐the‐art technique that allows 3D imaging at high‐resolution of soft biological tissues without invasive or time‐consuming sample preparation. The results increase our understanding of HO deposition, from the early inflammatory phase of tendon healing, by showing that the deposition is initiated as early as one week after injury in the distal stump and mostly growing on preinjury HO deposits. Later, more deposits form first in the stumps and then all over the tendon callus, merging into large, calcified structures, which occupy up to 10% of the tendon volume. The HOs were characterized by a looser connective trabecular‐like structure and a proteoglycan‐rich matrix containing chondrocyte‐like cells with lacunae. The study shows the potential of 3D imaging at high‐resolution by phase‐contrast tomography to better understand ossification in healing tendons.
Integrative transcriptomics and cell systems analyses reveal protective pathways controlled by Igfbp‐3 in anthracycline‐induced cardiotoxicity
Authors: Chen Junjie , Chapski Douglas J. , Jong Jeremy , Awada Jerome , Wang Yijie , Slamon Dennis J. , Vondriska Thomas M. , Packard René R. Sevag 
Published: May 2023

AbstractAnthracyclines such as doxorubicin (Dox) are effective chemotherapeutic agents; however, their use is hampered by subsequent cardiotoxicity risk. Our understanding of cardiomyocyte protective pathways activated following anthracycline‐induced cardiotoxicity (AIC) remains incomplete. Insulin‐like growth factor binding protein (IGFBP) 3 (Igfbp‐3), the most abundant IGFBP family member in the circulation, is associated with effects on the metabolism, proliferation, and survival of various cells. Whereas Igfbp‐3 is induced by Dox in the heart, its role in AIC is ill‐defined. We investigated molecular mechanisms as well as systems‐level transcriptomic consequences of manipulating Igfbp‐3 in AIC using neonatal rat ventricular myocytes and human‐induced pluripotent stem cell‐derived cardiomyocytes. Our findings reveal that Dox induces the nuclear enrichment of Igfbp‐3 in cardiomyocytes. Furthermore, Igfbp‐3 reduces DNA damage, impedes topoisomerase IIβ expression (Top2β) which forms Top2β‐Dox‐DNA cleavage complex leading to DNA double‐strand breaks (DSB), alleviates detyrosinated microtubule accumulation—a hallmark of increased cardiomyocyte stiffness and heart failure—and favorably affects contractility following Dox treatment. These results indicate that Igfbp‐3 is induced by cardiomyocytes in an effort to mitigate AIC.
Simultaneous evaluation of treatment efficacy and toxicity for bispecific T‐cell engager therapeutics in a humanized mouse model
Authors: Yang Jiwon , Jiao Jing , Draheim Kyle M. , Yang Guoxiang , Yang Hongyuan , Yao Li‐Chin , Shultz Leonard D. , Greiner Dale L. , Rajagopal Deepa , Vessillier Sandrine , Maier Curtis C. , Mohanan Sunish , Cai Danying , Cheng Mingshan , Brehm Michael A. , Keck James G. 
Published: May 2023

AbstractImmuno‐oncology (IO)‐based therapies such as checkpoint inhibitors, bi‐specific antibodies, and CAR‐T‐cell therapies have shown significant success in the treatment of several cancer indications. However, these therapies can result in the development of severe adverse events, including cytokine release syndrome (CRS). Currently, there is a paucity of in vivo models that can evaluate dose‐response relationships for both tumor control and CRS‐related safety issues. We tested an in vivo PBMC humanized mouse model to assess both treatment efficacy against specific tumors and the concurrent cytokine release profiles for individual human donors after treatment with a CD19xCD3 bispecific T‐cell engager (BiTE). Using this model, we evaluated tumor burden, T‐cell activation, and cytokine release in response to bispecific T‐cell‐engaging antibody in humanized mice generated with different PBMC donors. The results show that PBMC engrafted NOD‐scid Il2rgnullmice lacking expression of mouse MHC class I and II (NSG‐MHC‐DKO mice) and implanted with a tumor xenograft predict both efficacy for tumor control by CD19xCD3 BiTE and stimulated cytokine release. Moreover, our findings indicate that this PBMC‐engrafted model captures variability among donors for tumor control and cytokine release following treatment. Tumor control and cytokine release were reproducible for the same PBMC donor in separate experiments. The PBMC humanized mouse model described here is a sensitive and reproducible platform that identifies specific patient/cancer/therapy combinations for treatment efficacy and development of complications.
Circulating exosomal miR‐155‐5p contributes to severe acute pancreatitis‐associated intestinal barrier injury by targeting SOCS1 to activate NLRP3 inflammasome‐mediated pyroptosis
Authors: Shao Yang , Li Yiming , Jiang Yingjian , Li Hongbo , Wang Jiang , Zhang Dianliang 
Published: May 2023

AbstractSevere acute pancreatitis (SAP) represents a common and serious disease that can cause intestinal barrier dysfunction. However, the pathogenesis of this barrier dysfunction remains unclear. Exosomes are a new intercellular communication method involved in multiple diseases. Consequently, the present study sought to determine the function of circulating exosomes in barrier dysfunction associated with SAP. A rat model of SAP was established by injecting biliopancreatic duct with 5% sodium taurocholate. Circulating exosomes were purified from SAP (SAP‐Exo) and sham operation rats (SO‐Exo) using a commercial kit. In vitro, SO‐Exo and SAP‐Exo were cocultured with rat intestinal epithelial (IEC‐6) cells. In vivo, naive rats were treated with SO‐Exo and SAP‐Exo. We found SAP‐Exo‐induced pyroptotic cell death and barrier dysfunction in vitro. In addition, miR‐155‐5p exhibited a remarkable increase in SAP‐Exo than SO‐Exo, and miR‐155‐5p inhibitor partially abolished the negative effect of SAP‐Exo on IEC‐6 cells. Furthermore, miRNA functional experiments revealed that miR‐155‐5p could induce pyroptosis and barrier loss in IEC‐6 cells. Overexpression of suppressor of cytokine signaling 1 (SOCS1), a miR‐155‐5p target, could partially reverse IEC‐6 cells from the harmful impact of miR‐155‐5p. In vivo, SAP‐Exo significantly triggered pyroptosis in intestinal epithelial cells and caused intestinal injury. In addition, blocking exosome release with GW4869 attenuated intestinal injury in SAP rats. In summary, our study demonstrated that miR‐155‐5p is highly enriched in circulating exosomes from SAP rat plasma and can be transported to intestinal epithelial cells, where it targets SOCS1 to activate NOD‐like receptor protein 3 (NLRP3) inflammasome‐mediated pyroptosis leading to intestinal barrier damage.
DMD Gene and Dystrophinopathy Phenotypes Associated With Mutations: A Systematic Review for Clinicians
Authors: Andrews Jennifer G. , Galindo Maureen Kelly , Thomas Shiny , Mathews Katherine D. , Whitehead Nedra 
Published: May 2023

Abstract
The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype–phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance.
Prognostic Analysis of Lymphovascular Invasion in Stages I–III Colorectal Cancer
Authors: Lin Zhuoqun , Zheng Yitao , Yang Jun , Jin Wei , Wang Junqi , Wang Weichen , Li Shaotang 
Published: May 2023

Introduction:
Lymphovascular invasion (LVI) is a micropathological tumor factor believed to increase the risk of tumor metastasis and spread. Propensity score matching (PSM) is a statistical method that can control confounding factors. Current research rarely considers the confounding relationship between LVI and other factors that may influence prognosis. This study aimed to investigate the relationship between LVI and prognosis in patients with stage I–III colorectal cancer (CRC) by using propensity score matching (PSM).

Methods:
This was a retrospective study involving 610 patients. PSM was used to adjust for baseline differences between the groups. The survival rates were calculated. A nomogram was constructed based on the Cox proportional hazards model before matching. The C-index, receiver operating characteristic curve (ROC), and calibration curve were used to evaluate the nomogram.

Results:
A total of 150 patients tested positive for LVI, accounting for 24.6% of the total, and 120 couples of patients were identified after PSM. The survival curve and Cox proportional hazards model after matching confirmed the adverse effects of LVI on tumor prognosis. The Cox proportional hazards model before matching showed that age, carcinoembryonic antigen level, T stage, N stage, histologic grade and LVI were independent prognostic factors. The C-index of the nomogram established based on the Cox proportional hazards model was 0.787 (95% CI=0.728–0.845). The areas under the curve were 0.796 in the 3-year ROC.

Conclusions:
LVI is an adverse prognostic factor in patients with stage I-III colorectal cancer.
Loss of toll-like receptor 5 potentiates spontaneous hepatocarcinogenesis in farnesoid X receptor–deficient mice
Authors: Golonka Rachel M. , Yeoh Beng San , Saha Piu , Gohara Amira , Tummala Ramakumar , Stepkowski Stanislaw , Tiwari Amit K. , Joe Bina , Gonzalez Frank J. , Gewirtz Andrew T. , Vijay-Kumar Matam 
Published: May 2023

Background:
HCC is the most common primary liver cancer and a leading cause of cancer-related mortality. Gut microbiota is a large collection of microbes, predominately bacteria, that harbor the gastrointestinal tract. Changes in gut microbiota that deviate from the native composition, that is, “dysbiosis,” is proposed as a probable diagnostic biomarker and a risk factor for HCC. However, whether gut microbiota dysbiosis is a cause or a consequence of HCC is unknown.

Methods:
To better understand the role of gut microbiota in HCC, mice deficient of toll-like receptor 5 (TLR5, a receptor for bacterial flagellin) as a model of spontaneous gut microbiota dysbiosis were crossed with farnesoid X receptor knockout mice (FxrKO), a genetic model for spontaneous HCC. Male FxrKO/Tlr5KO double knockout (DKO), FxrKO, Tlr5KO, and wild-type (WT) mice were aged to the 16-month HCC time point.

Results:
Compared with FxrKO mice, DKO mice had more severe hepatooncogenesis at the gross, histological, and transcript levels and this was associated with pronounced cholestatic liver injury. The bile acid dysmetabolism in FxrKO mice became more aberrant in the absence of TLR5 due in part to suppression of bile acid secretion and enhanced cholestasis. Out of the 14 enriched taxon signatures seen in the DKO gut microbiota, 50% were dominated by the Proteobacteria phylum with expansion of the gut pathobiont γ-Proteobacteria that is implicated in HCC.

Conclusions:
Collectively, introducing gut microbiota dysbiosis by TLR5 deletion exacerbated hepatocarcinogenesis in the FxrKO mouse model.
Functional diversity and team innovation
Authors: van Zijl Alissa Lysanne , Vermeeren Brenda , Koster Ferry , Steijn Bram 
Published: May 2023

Background
Bringing together professionals with different knowledge and skills comes with the opportunity to spur the innovativeness of primary care teams. Nevertheless, empirical evidence shows that it is not self-evident that these innovations are also realized. The social categorization theory suggests that a better understanding of whether these potential team innovations are realized can be obtained by looking at the social cohesion of such teams.

Purpose
The aim of this study was to study the relationship between functional diversity and team innovation in primary care teams by examining the mediating role of social cohesion.

Methodology
Survey responses and administrative data of 887 primary care professionals and 75 supervisors in 100 primary care teams were analyzed. Structural equation modeling was used to examine a curvilinear mediated relationship among functional diversity and team innovation through social cohesion.

Results
The findings show a positive relationship between social cohesion and team innovation as expected. Contrary to the expectations, the relationship between functional diversity and social cohesion is insignificant, and the results show an inverted U-shaped relationship between functional diversity and team innovation instead.

Conclusions
This study reveals an unexpected inverted U-shaped relationship between functional diversity and team innovation. This relationship is not mediated by social cohesion; however, social cohesion is still a significant predictor of team innovation.

Practice Implications
Policymakers should be aware of the relevance as well as the complexity of creating social cohesion in functionally diverse primary care teams. As long as it remains unknown how social cohesion is stimulated in functionally diverse teams, it seems best for the team innovation to prevent bringing together too many, but also too few, different functions.
Genetic risk shared across 24 chronic pain conditions: identification and characterization with genomic structural equation modeling
Authors: Zorina-Lichtenwalter Katerina , Bango Carmen I. , Van Oudenhove Lukas , Čeko Marta , Lindquist Martin A. , Grotzinger Andrew D. , Keller Matthew C. , Friedman Naomi P. , Wager Tor D. 
Published: May 2023

Abstract
Chronic pain conditions frequently co-occur, suggesting common risks and paths to prevention and treatment. Previous studies have reported genetic correlations among specific groups of pain conditions and reported genetic risk for within-individual multisite pain counts (≤7). Here, we identified genetic risk for multiple distinct pain disorders across individuals using 24 chronic pain conditions and genomic structural equation modeling (Genomic SEM). First, we ran individual genome-wide association studies (GWASs) on all 24 conditions in the UK Biobank (N ≤ 436,000) and estimated their pairwise genetic correlations. Then we used these correlations to model their genetic factor structure in Genomic SEM, using both hypothesis- and data-driven exploratory approaches. A complementary network analysis enabled us to visualize these genetic relationships in an unstructured manner. Genomic SEM analysis revealed a general factor explaining most of the shared genetic variance across all pain conditions and a second, more specific factor explaining genetic covariance across musculoskeletal pain conditions. Network analysis revealed a large cluster of conditions and identified arthropathic, back, and neck pain as potential hubs for cross-condition chronic pain. Additionally, we ran GWASs on both factors extracted in Genomic SEM and annotated them functionally. Annotation identified pathways associated with organogenesis, metabolism, transcription, and DNA repair, with overrepresentation of strongly associated genes exclusively in brain tissues. Cross-reference with previous GWASs showed genetic overlap with cognition, mood, and brain structure. These results identify common genetic risks and suggest neurobiological and psychosocial mechanisms that should be targeted to prevent and treat cross-condition chronic pain.