bluuebunny/crossref_metadata_2025_split huggingface dataset:
CEO performance‐based grants’ vesting provisions and debt contracts: Evidence from GAAP, Non‐GAAP and KPI metrics
Authors: Philip Teena Rachel , Sanchez Daniela , Sanchez Juan Manuel 
Published: May 2023

AbstractWe examine the influence of CEOs’ equity and cash grants’ vesting provisions that are based on (i) accounting performance metrics prepared under US generally accepted principles (GAAP), (ii) non‐GAAP performance metrics and (iii) key performance indicators (KPIs) on debt contracts. We find that grants with vesting provisions based on GAAP metrics and KPIs lead to a lower cost of debt, a lower likelihood of collateral requirements and less restrictive covenant terms. In contrast, performance‐based grants with non‐GAAP vesting provisions lead to a higher cost of debt, a higher likelihood of collateral requirements and more restrictive covenant terms. Supplementary analyses reveal that our results are incremental to other debtholder‐friendly features in the CEO contracts, such as grants with debt‐related performance measures and CEOs’ inside debt holdings, and robust to alternative variable definitions and specifications. Overall, our results suggest that debtholders understand the differing incentives associated with GAAP, non‐GAAP and KPI‐based performance measures, and incorporate these differences into debt contracts.
Resin composite layering on discolored substrates ensures masking ability for monolithic ceramics
Authors: Soares Pablo Machado , Pereira Gabriel Kalil Rocha , Bacchi Atais 
Published: May 2023

AbstractObjectivethe aim of this study was to evaluate the effect of resin composite layering on discolored substrates to obtain masking ability with monolithic ceramics.Materials and MethodsFour groups (n = 8) of computer‐aided design/computer aided manufacturing (CAD/CAM) monolithic ceramics, shade A1, with thicknesses of 1.0 and 1.5 mm, were tested: feldspathic (FC), leucite‐reinforced (LC), lithium disilicate‐reinforced (LD), and translucent zirconia (5YSZ). Five substrates were used: A1 (used as reference), A3.5, C4, and coppery and silvery metals. The substrates were separated as non‐layered or layered (with flowable opaque resin composite (FL), white opaque restorative resin composite (WD), and A1‐shaded opaque restorative resin composite (A1D)). Resin composite layers of 0.5 and 1.0 mm were tested. The try‐in paste, shade A1, was used as a luting agent. Translucency parameter (TP00) was assessed for the ceramics. Color differences (∆E00) were assessed for the restorative ceramics and resin composite layers over discolored substrates with the CIEDE2000 formula. The results were compared statistically, and descriptively with acceptability (AT, 1.77) and perceptibility (PT, 0.81) thresholds.ResultsFeldspathic showed the highest TP00 (for both ceramic thicknesses) and LD the lowest (for 1.5 mm of ceramic thickness) (P < 0.001). For substrate A3.5, layering with 1.0 mm of A1D or WD ensured ∆E00 below PT for all ceramics tested (P < 0.001). The use of 0.5 mm of FL or 1.0 mm of A1D associated with ceramics LC, LD, and 5YSZ ensured ∆E00 below AT for substrates C4 and coppery metal (P < 0.001). Silvery background layered with 0.5 mm of FL presented ∆E00 below AT for all ceramics and ∆E00 below PT for lithium disilicate of 1.0 mm of thickness (∆E00 = 0.72).ConclusionsLayering severely discolored substrates with selected opaque resin composites ensures masking ability for restoration with CAD/CAM monolithic ceramics.Clinical SignificanceSeverely discolored substrates are predictably restored with monolithic CAD/CAM ceramics by performing a previous layering of the substrate with opaque resin composite.
Chronic handling stress in zebrafish Danio rerio husbandry
Authors: Philippe Charlotte , Vergauwen Lucia , Huyghe Kato , De Boeck Gudrun , Knapen Dries 
Published: May 2023

AbstractThe zebrafish (Danio rerio, Hamilton, 1822) is one of the most important fish model species in scientific research, with millions of fish housed in laboratory animal facilities around the world. During husbandry, it is necessary to regularly handle the fish, which could cause short‐ and long‐term stress, possibly affecting both fish welfare and experimental outcomes. In two experiments, the authors studied effects of transferring adult zebrafish, by chasing them with a net and/or exposing them to air (netting) on different endpoints: cortisol levels, reproduction parameters and behavioural parameters. They used realistic chase and air‐exposure times to mimic normal zebrafish husbandry and investigated the potential to habituate to handling stressors. Finally, the potential welfare improvements of a nutritional reward after handling were studied. All types of handling induced a stress response, but the authors did not find a correlation with the intensity of the stressor. Realistic (short) handling routines also caused stress, both after the first time and after regular handling over a long period of time. Cortisol levels peaked after 15 min, were still elevated after 30 min and dropped to resting level after 60 min. This should be taken into account by researchers when carrying out measurements or behavioural trials within an hour after handling. There is a minor potential benefit of nutritional rewards that may contribute to a faster recovery of normal behaviour. They did not find evidence of habituation to chasing and netting stress. Taking the stress response after handling into consideration will improve fish welfare and health and minimise husbandry‐associated sources of variation.
Towards artefact‐free AFM image presentation and interpretation
Authors: Burnham Nancy A. , Lyu Lei , Poulikakos Lily 
Published: May 2023

AbstractAtomic force microscopy (AFM) is based upon a simple operational principle. However, the presentation and interpretation of AFM images can easily suffer from consequential artefacts that are easily overlooked. Here we discuss results from AFM and its companion variations AFM‐IR (AFM combined with infrared spectroscopy) and PF‐QNM (an AFM mode called peak‐force quantitative nano‐mechanical mapping) by imaging ‘bee’ structures in asphalt binder (bitumen) as examples. We show how common problems manifest themselves and provide solutions, with the intent that authors can present their results clearly and avoid interpreting artefacts as true physical properties, thereby raising the quality of AFM research.
Macrophages influence Schwann cell myelin autophagy after nerve injury and in a model of Charcot‐Marie‐Tooth disease
Authors: Weiß Eva Maria , Geldermann Miriam , Martini Rudolf , Klein Dennis 
Published: May 2023

AbstractBackground and AimsThe complex cellular and molecular interactions between Schwann cells (SCs) and macrophages during Wallerian degeneration are a prerequisite to allow rapid uptake and degradation of myelin debris and axonal regeneration after peripheral nerve injury. In contrast, in non‐injured nerves of Charcot‐Marie‐Tooth 1 neuropathies, aberrant macrophage activation by SCs carrying myelin gene defects is a disease amplifier that drives nerve damage and subsequent functional decline. Consequently, targeting nerve macrophages might be a translatable treatment strategy to mitigate disease outcome in CMT1 patients. Indeed, in previous approaches, macrophage targeting alleviated the axonopathy and promoted sprouting of damaged fibers. Surprisingly, this was still accompanied by robust myelinopathy in a model for CMT1X, suggesting additional cellular mechanisms of myelin degradation in mutant peripheral nerves. We here investigated the possibility of an increased SC‐related myelin autophagy upon macrophage targeting in Cx32def mice.MethodsCombining ex vivo and in vivo approaches, macrophages were targeted by PLX5622 treatment. SC autophagy was investigated by immunohistochemical and electron microscopical techniques.ResultsWe demonstrate a robust upregulation of markers for SC autophagy after injury and in genetically‐mediated neuropathy when nerve macrophages are pharmacologically depleted. Corroborating these findings, we provide ultrastructural evidence for increased SC myelin autophagy upon treatment in vivo.InterpretationThese findings reveal a novel communication and interaction between SCs and macrophages. This identification of alternative pathways of myelin degradation may have important implications for a better understanding of therapeutic mechanisms of pharmacological macrophage targeting in diseased peripheral nerves.
Disease‐specific wearable sensor algorithms for profiling activity, gait, and balance in individuals with Charcot–Marie–Tooth disease type 1A
Authors: Dinesh K. , White N. , Baker L. , Sowden J. E. , Behrens‐Spraggins S. , Wood E. , Charles J. , Herrmann D. N. , Sharma G. , Eichinger K. 
Published: May 2023

AbstractBackground/AimsCharcot–Marie–Tooth Disease type 1A (CMT1A), the most common inherited peripheral neuropathy, is characterized by progressive sensory loss and weakness, which results in impaired mobility. Increased understanding of the genetics and pathophysiology of CMT1A has led to development of potential therapeutic agents, necessitating clinical trial readiness. Wearable sensors may provide useful outcome measures for future trials.MethodsIndividuals with CMT1A and unaffected controls were recruited for this 12‐month study. Participants wore sensors for in‐clinic assessments and at‐home, from which activity, gait, and balance metrics were derived. Mann–Whitney U tests were used to analyze group differences for activity, gait, and balance parameters. Test–retest reliability of gait and balance parameters and correlations of these parameters with clinical outcome assessments (COAs) were examined.ResultsThirty individuals, 15 CMT1A, and 15 controls, participated. Gait and balance metrics demonstrated moderate to excellent reliability. CMT1A participants had longer step durations (p < .001), shorter step lengths (p = .03), slower gait speeds (p < .001), and greater postural sway (p < .001) than healthy controls. Moderate correlations were found between CMT‐Functional Outcome Measure and step length (r = −0.59; p = .02), and gait speed (r = 0.64; p = .01); 11 out of 15 CMT1A participants demonstrated significant increases in stride duration between the first and last quarter of the 6‐min walk test, suggesting fatigue.InterpretationIn this initial study, gait and balance metrics derived from wearable sensors were reliable and associated with COAs in individuals with CMT1A. Larger longitudinal studies are needed to confirm our findings and evaluate sensitivity and utility of these disease‐specific algorithms for clinical trial use.
Evaluation of two implant‐supported fixed partial denture abutment designs: Influence on screw surface characteristics
Authors: Alzoubi Fawaz M. , Sabti Mohammad , Alsarraf Esra , Alshahrani Faris A. , Sadowsky Steven J. 
Published: May 2023

AbstractPurposeTo compare screw surface characteristics between hemi‐engaging and non‐engaging implant‐supported fixed partial denture (FPD) designs after cyclic loading.Materials and MethodsTwenty‐four implants measuring 4.3 × 10 mm were mounted on acrylic resin blocks. Specimens were divided into two groups. An experimental group included twelve 3‐unit FPD with a hemi‐engaging design; a control group included twelve 3‐unit FPDs with the conventional design of two non‐engaging abutments. Both groups were subjected to two types of cycling loading (CL), first axial loading, and then lateral loading at 30°. Load was applied to the units one million times (1.0 × 106 cycles) for each loading axis. Data on screw surface roughness in three locations and screw thread depth were collected before (BL) and after (AL) each loading type. Screw surface roughness was measured in μm using a mechanical digital surface profilometer and optical profiler. To evaluate screw thread depth in μm, an upright optical microscope Axio‐imager 2 was used. To confirm readings made from the optical microscope, four random samples were selected from each group for scanning electron microscopy (SEM) analysis. The effect of cyclic loading was evaluated by averaging values across the two screws within each specimen, then calculating difference scores (DL) between BL and AL (DL = AL – BL). Additional difference scores were computed between the non‐engaging screws in each experimental group specimen, and one randomly selected non‐engaging screw in each control specimen. This difference was referred to as the non‐engaging DL. Statistical significance was assessed using Mann‐Whitney U tests (α = 0.05).ResultsComparisons of DL and non‐engaging DL by loading type revealed one significant difference regarding surface roughness at the screw thread. Significantly greater mean changes were observed after axial loading compared to lateral loading regarding both DL (axial M = ‐0.36 ± 0.08; lateral M = ‐0.21 ± 0.09; U = 20; p = 0.003) and non‐engaging DL (axial M = ‐0.40 ± 0.22; lateral M = ‐0.21 ± 0.11; U = 29; p = 0.013). No significant differences in screw surface roughness in other sites or thread depth were found between the experimental and control abutment designs in DL or in non‐engaging DL. No significant differences were found for DL (axial U = 13, p = 0.423; lateral U = 9, p = 0.150;) or non‐engaging DL (axial U = 13, p = 0.423; lateral U = 18, p = 1.00).ConclusionsResults suggest that overall, changes in screw surface physical characteristics did not differ between hemi‐engaging and non‐engaging designs after evaluating screw surface roughness and thread depth before and after axial and lateral cyclic loading.
The age‐varying effects of adolescent stress on impulsivity and sensation seeking
Authors: Wasserman Alexander M. , Wood Erin E. , Mathias Charles W. , Moon Tae Joon , Hill‐Kapturczak Nathalie , Roache John D. , Dougherty Donald M. 
Published: May 2023

AbstractAdolescence is defined in part by heightened exposure and sensitivity to stressors. In a longitudinal cohort of youth at risk for substance use problems, we examined the age‐varying relationship between stress exposure and traits that are central to the dual systems model. The positive associations between stress exposure, impulsivity, sensation seeking varied as function of age. Specifically, the influence of stress exposure on impulsivity strengthened during early adolescence and remained stable into early adulthood, while the influence of stress exposure on sensation seeking strengthened from early‐ to mid‐adolescence and weakened thereafter. These findings suggest that the maturational imbalance between the capacity to regulate impulsive tendencies and sensation seeking may be exaggerated for youth who are exposed to a high number of stressors.
Synergistic inhibitory effects of clopidogrel and rivaroxaban on platelet function and platelet‐dependent thrombin generation in cats
Authors: Lo Sara T. , Li Ronald H. L. , Georges Catherine J. , Nguyen Nghi , Chen Cheyenne K. , Stuhlmann Claire , Oldach Maureen Sigmund , Rivas Victor Noel , Fousse Samantha , Harris Samantha P. , Stern Joshua A. 
Published: May 2023

AbstractBackgroundDual antithrombotic treatment (DAT) with clopidogrel and rivaroxaban sometimes is prescribed to cats with hypertrophic cardiomyopathy at risk of thromboembolism. To date, no studies have evaluated their combined effects on platelet function.Objectives/HypothesisEvaluate the safety of DAT in healthy cats and compare, ex vivo, platelet‐dependent thrombin generation and agonist‐induced platelet activation and aggregation in cats treated with clopidogrel, rivaroxaban, or DAT. We hypothesized that DAT would safely modulate agonist‐induced platelet activation and aggregation more effectively than single agent treatment.AnimalsNine apparently healthy 1‐year‐old cats selected from a research colony.MethodsUnblinded, nonrandomized ex vivo cross‐over study. All cats received 7 days of rivaroxaban (0.6 ± 0.1 mg/kg PO), clopidogrel (4.7 ± 0.8 mg/kg PO), or DAT with defined washout periods between treatments. Before and after each treatment, adenosine diphosphate (ADP)‐ and thrombin‐induced platelet P‐selectin expression was evaluated using flow cytometry to assess platelet activation. Platelet‐dependent thrombin generation was measured by fluorescence assay. Platelet aggregation was assessed using whole blood impedance platelet aggregometry.ResultsNo cats exhibited adverse effects. Of the 3 treatments, only DAT significantly decreased the number of activated platelets (P = .002), modulated platelet activation in response to thrombin (P = .01), dampened thrombin generation potential (P = .01), and delayed maximum reaction velocity (P = .004) in thrombin generation. Like clopidogrel, DAT inhibited ADP‐mediated platelet aggregation. However, rivaroxaban alone resulted in increased aggregation and activation in response to ADP.Conclusion and Clinical ImportanceTreatment combining clopidogrel and rivaroxaban (DAT) safely decreases platelet activation, platelet response to agonists, and thrombin generation in feline platelets more effectively than monotherapy with either clopidogrel or rivaroxaban.
An adult‐based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents
Authors: Huang Yun , Stinson Sara E. , Juel Helene Bæk , Lund Morten A. V. , Holm Louise Aas , Fonvig Cilius E. , Nielsen Trine , Grarup Niels , Pedersen Oluf , Christiansen Michael , Chabanova Elizaveta , Thomsen Henrik S. , Krag Aleksander , Stender Stefan , Holm Jens‐Christian , Hansen Torben 
Published: May 2023

AbstractBackground & AimsGenome‐wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome‐wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents.Approach & ResultsChildren and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population‐based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1H‐MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p < .05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1‐SD unit: 2.17, p = 9.7E‐10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76–0.81). Combining the GRS with clinical measures (waist‐to‐height ratio [WHtR] SDS, ALT, and HOMA‐IR) increased the AUC up to 0.86 (95% CI 0.84–0.88).ConclusionsThe genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification.
Sleeve gastrectomy causes weight‐loss independent improvements in hepatic steatosis
Authors: McGlone Emma Rose , Siebert Matthieu , Dore Marian , Hope David C. D. , Davies Iona , Owen Bryn , Khoo Bernard , Goldin Rob , Carling Dave , Bloom Stephen , Le Gall Maude , Tan Tricia M‐M. 
Published: May 2023

AbstractBackground and AimsSleeve gastrectomy (VSG) leads to improvement in hepatic steatosis, associated with weight loss. The aims of this study were to investigate whether VSG leads to weight‐loss independent improvements in liver steatosis in mice with diet‐induced obesity (DIO); and to metabolically and transcriptomically profile hepatic changes in mice undergoing VSG.MethodsMice with DIO were treated with VSG, sham surgery with subsequent food restriction to weight‐match to the VSG group (Sham‐WM), or sham surgery with return to unrestricted diet (Sham‐Ad lib). Hepatic steatosis, glucose tolerance, insulin and glucagon resistance, and hepatic transcriptomics were investigated at the end of the study period and treatment groups were compared with mice undergoing sham surgery only (Sham‐Ad lib).ResultsVSG led to much greater improvement in liver steatosis than Sham‐WM (liver triglyceride mg/mg 2.5 ± 0.1, 2.1 ± 0.2, 1.6 ± 0.1 for Sham‐AL, Sham‐WM and VSG respectively; p = 0.003). Homeostatic model assessment of insulin resistance was improved following VSG only (51.2 ± 8.8, 36.3 ± 5.3, 22.3 ± 6.1 for Sham‐AL, Sham‐WM and VSG respectively; p = 0.03). The glucagon‐alanine index, a measure of glucagon resistance, fell with VSG but was significantly increased in Sham‐WM (9.8 ± 1.7, 25.8 ± 4.6 and 5.2 ± 1.2 in Sham Ad‐lib, Sham‐WM and VSG respectively; p = 0.0003). Genes downstream of glucagon receptor signalling which govern fatty acid synthesis (Acaca, Acacb, Me1, Acly, Fasn and Elovl6) were downregulated following VSG but upregulated in Sham‐WM.ConclusionsChanges in glucagon sensitivity may contribute to weight‐loss independent improvements in hepatic steatosis following VSG.
A circular RNA produced by LRBA promotes cirrhotic mouse liver regeneration through facilitating the ubiquitination degradation of p27
Authors: Xu Liangliang , Zhang Jinfu , Li Li , Wang Peng , Zheng Xiaobo , Luo Jianchen , Zhang Shuqi , Li Lian , Yi Pengsheng , Zhang Yanfang , Yan Tao , Xie Liang , Feng Lei , Zhang Ming , Xu Mingqing 
Published: May 2023

AbstractBackground and AimsAccumulating circular RNAs (circRNAs) play important roles in tissue repair and organ regeneration. However, the biological effects of circRNAs on liver regeneration remain largely unknown. This study aims to systematically elucidate the functions and mechanisms of circRNAs derived from lipopolysaccharide‐responsive beige‐like anchor protein (LRBA) in regulating liver regeneration.MethodsCircRNAs derived from mouse LRBA gene were identified using CircBase. In vivo and in vitro experiments were conducted to confirm the effects of circLRBA on liver regeneration. RNA pull‐down and RNA immunoprecipitation assays were used to investigate the underlying mechanisms. Clinical samples and cirrhotic mouse models were used to evaluate the clinical significance and transitional value of circLRBA.ResultsEight circRNAs derived from LRBA were registered in CircBase. The circRNA mmu_circ_0018031 (circLRBA) was significantly upregulated in the liver tissues after 2/3 partial hepatectomy (PHx). Adeno‐associated virus serotype 8 (AAV8)‐mediated knockdown of circLRBA markedly inhibited mouse liver regeneration after 2/3 PHx. In vitro experiments confirmed that circLRBA exerted its growth‐promoting function mainly through liver parenchymal cells. Mechanistically, circLRBA acted as a scaffold for the interaction between E3 ubiquitin‐protein ligase ring finger protein 123 and p27, facilitating the ubiquitination degradation of p27. Clinically, circLRBA was lowly expressed in cirrhotic liver tissues and negatively correlated with perioperative levels of total bilirubin. Furthermore, overexpression of circLRBA enhanced cirrhotic mouse liver regeneration after 2/3 PHx.ConclusionsWe conclude that circLRBA is a novel growth promoter in liver regeneration and a potential therapeutic target related to deficiency of cirrhotic liver regeneration.