bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fenfluramine significantly reduces day‐to‐day seizure burden by increasing number of seizure‐free days and time between seizures in patients with Dravet syndrome: A time‐to‐event analysis
Authors: Sullivan Joseph , Specchio Nicola , Devinsky Orrin , Auvin Stéphane , Perry M. Scott , Strzelczyk Adam , Gil‐Nagel Antonio , Dai David , Galer Bradley S. , Gammaitoni Arnold R. 
Published: October 2021

AbstractObjectiveThe number, unpredictability, and severity of seizures experienced by patients with Dravet syndrome (DS) negatively impact quality of life (QOL) for patients, caregivers, and families. Metrics are needed to assess whether patients with residual seizures have moved meaningfully toward seizure freedom after treatment with new antiseizure medications.MethodsWe evaluated the time required postrandomization for each patient to experience the same number of seizures experienced during baseline (i.e., time‐to‐nth seizure), using a post hoc time‐to‐event (TTE) analysis of data from two Phase 3 placebo‐controlled trials of adjunctive fenfluramine for DS (Study 1,N = 119; Study 2,N = 87). Patients aged 2–19 years were randomized to placebo or adjunctive fenfluramine (Study 1: .7 mg/kg/day or .2 mg/kg/day; Study 2: .4 mg/kg/day with stiripentol). Data were analyzed by Kaplan–Meier TTE curves and waterfall plots.ResultsThe proportion of patients who never reached baseline seizure frequency was greater with fenfluramine than with placebo (Study 1: fenfluramine .7 mg/kg/day, 60%; fenfluramine .2 mg/kg/day, 31%; placebo, 13%; Study 2: fenfluramine .4 mg/kg/day, 58%; placebo, 2%). Median time‐to‐nth seizure was longer after fenfluramine than after placebo (Study 1: fenfluramine .7 mg/kg/day, 13 weeks; .2 mg/kg/day, 10 weeks; placebo, 7 weeks; Study 2: fenfluramine .4 mg/kg/day, 13 weeks; placebo, 5 weeks;p < .001). Longest duration of convulsive seizure‐free days was increased in active groups versus the placebo group (Study 1: fenfluramine .7 and .2 mg/kg/day, 25.0 and 15.0 days; placebo, 9.5 days [p = .0001;p = .0352]; Study 2: fenfluramine .4 mg/kg/day, 22.0 days; placebo, 13.0 days [p = .004]). The most common adverse events included decreased appetite, pyrexia, upper respiratory tract infection, diarrhea, and fatigue.SignificanceThese data demonstrate that fenfluramine can significantly reduce day‐to‐day seizure burden in patients with DS, providing prolonged periods of convulsive seizure‐free days, which may help reduce the physical and emotional disease toll while improving health‐related QOL for patients and caregivers.
Dynamic optimal restructuring policies under debt renegotiation with positive externalities
Authors: Luo Pengfei , Tan Yingxian , Yang Jinqiang 
Published: October 2021

AbstractThis paper develops a debt renegotiation model with positive externalities using the Nash bargaining game and explores dynamic optimal downward debt restructuring policies in times of financial distress. We derive closed‐form expressions for the optimal restructuring policies. Moreover, we provide theoretical support for the advantages of debt renegotiation with positive externalities. In addition, our model could explain the violation of the absolute priority rule for firms in financial distress. Finally, we find that debt renegotiation is facilitated among firms with relatively low risk and a high leverage ratio, as documented by empirical evidence.
A quantitative trait variant inGabra2underlies increased methamphetamine stimulant sensitivity
Authors: Goldberg Lisa R. , Yao Emily J. , Kelliher Julia C. , Reed Eric R. , Wu Cox Jiayi , Parks Cory , Kirkpatrick Stacey L. , Beierle Jacob A. , Chen Melanie M. , Johnson William E. , Homanics Gregg E. , Williams Robert W. , Bryant Camron D. , Mulligan Megan K. 
Published: October 2021

AbstractPsychostimulant (methamphetamine, cocaine) use disorders have a genetic component that remains mostly unknown. We conducted genome‐wide quantitative trait locus (QTL) analysis of methamphetamine stimulant sensitivity. To facilitate gene identification, we employed a Reduced Complexity Cross between closely related C57BL/6 mouse substrains and examined maximum speed and distance traveled over 30 min following methamphetamine (2 mg/kg, i.p.). For maximum methamphetamine‐induced speed following the second and third administration, we identified a single genome‐wide significant QTL on chromosome 11 that peaked near theCyfip2locus (LOD = 3.5, 4.2; peak = 21 cM [36 Mb]). For methamphetamine‐induced distance traveled following the first and second administration, we identified a genome‐wide significant QTL on chromosome 5 that peaked near a functional intronic indel inGabra2coding for the alpha‐2 subunit of the GABA‐A receptor (LOD = 3.6–5.2; peak = 34–35 cM [66–67 Mb]). Striatalcis‐expression QTL mapping corroboratedGabra2as a functional candidate gene underlying methamphetamine‐induced distance traveled. CRISPR/Cas9‐mediated correction of the mutant intronic deletion on the C57BL/6J background to the wild‐type C57BL/6NJ allele was sufficient to reduce methamphetamine‐induced locomotor activity toward the wild‐type C57BL/6NJ‐like level, thus validating the quantitative trait variant (QTV). These studies show the power and efficiency of Reduced Complexity Crosses in identifying causal variants underlying complex traits. Functionally restoringGabra2expression decreased methamphetamine stimulant sensitivity and supports preclinical and human genetic studies implicating the GABA‐A receptor in psychostimulant addiction‐relevant traits. Importantly, our findings have major implications for studying psychostimulants in the C57BL/6J strain—the gold standard strain in biomedical research.
The combined effects of climate and canopy cover changes on understorey plants of the Hyrcanian forest biodiversity hotspot in northern Iran
Authors: Naqinezhad Alireza , De Lombaerde Emiel , Gholizadeh Hamid , Wasof Safaa , Perring Michael P. , Meeussen Camille , De Frenne Pieter , Verheyen Kris 
Published: October 2021

AbstractUnderstanding forest understorey community response to environmental change, including management actions, is vital given the understorey's importance for biodiversity conservation and ecosystem functioning. The Natural World Heritage Hyrcanian temperate forests (Iran) provide an ideal template for furnishing an appreciation of how management actions can mitigate undesired climate change effects, due to the forests’ broad environmental gradients, isolation from colonization sources and varied light environments. We used records of 95 understorey plant species from 512 plots to model their probability of occurrence as a function of contemporary climate and soil variables, and canopy cover. For 65 species with good predictive accuracy, we then projected two climate scenarios in the context of either increasing or decreasing canopy cover, to assess whether overstorey management could mitigate or aggravate climate change effects. Climate variables were the most important predictors for the distribution of all species. Soil and canopy cover varied in importance depending on understorey growth form. Climate change was projected to negatively affect future probabilities of occurrence. However, management, here represented by canopy cover change, is predicted to modify this trajectory for some species groups. Models predict increases in light‐adapted and generalist forbs with reduced canopy cover, while graminoids and ferns still decline. Increased canopy cover is projected to buffer an otherwise significant decreasing response of cold‐adapted species to climate change. However, increasing canopy cover is not projected to buffer the predicted negative impact of climate change on shade‐adapted forest specialists. Inconsistent responses of different species and/or growth forms to climate change and canopy cover reflect their complicated life histories and habitat preferences. Canopy cover management may help prevent the climate change induced loss of some important groups for biodiversity conservation. However, for shade‐adapted forest specialists, our results imply a need to adopt other conservation measures in the face of anticipated climate change.
Ascorbic acid 2‐glucoside: An ascorbic acid pro‐drug with longer‐term antioxidant efficacy in skin
Authors: Jacques Carine , Genies Camille , Bacqueville Daniel , Tourette Amelie , Borotra Nathalie , Chaves Fernanda , Sanches Fabio , Gaudry Anne L. , Bessou‐Touya Sandrine , Duplan Hélène 
Published: October 2021

AbstractObjectiveDeleterious effects of pollutants and ultraviolet radiation on the skin can be attenuated using formulations containing antioxidants. However, these have disadvantages, including chemical instability, photodegradation, poor bioavailability or biological activity. Here, two commercial formulations were evaluated: one optimized to stabilize and deliver ascorbic acid (AA) at 15% and the other containing a glucoside form of AA, namely ascorbic acid 2‐glucoside (AA2G), at 1.8% and at a physiological pH. We compared the skin delivery, antioxidative effects and chemical stability of AA2G with AA in their respective formulations.MethodsSkin delivery was measured using fresh viable human skin explants, and oxidative stress was measured using a human reconstructed epidermal (RHE) model according to levels of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase.ResultsAscorbic acid 2‐glucoside was completely metabolized to AA by the skin before entering the receptor compartment. The skin contained parent and AA, indicating a reserve of AA2G was present for further metabolism. For AA2G and AA, maximum flux of AA‐equivalents was at 12 h, with continued absorption over 24 h. The absolute amount in µg was higher in the skin after application of AA than after application of AA2G. This may suggest a greater antioxidative effect; however, according to all three measurements of oxidative stress, the protective effect of AA and AA2G was similar. Unlike AA, AA2G was chemically stable under storage conditions.ConclusionA lower concentration of AA2G is as effective as the active metabolite, AA, in terms of antioxidant effects. AA2G was chemically stable and can be applied at a lower concentration than AA, thus avoiding the need for an acidic formulation with a pH below 3.5.
Prevalence of periapical lesions, root canal treatments and restorations in teeth adjacent to implant‐ or tooth‐supported crowns: A multi‐centre cross‐sectional study
Authors: Baruwa Abayomi O. , Martins Jorge N. R. , Pereira Beatriz , Meirinhos João , Ordinola‐Zapata Ronald , Souza Erick M. , Ginjeira António 
Published: October 2021

AbstractAimTo describe the prevalence of periapical lesions, root canal treatments and coronal restorations on teeth adjacent to either implant‐ or natural tooth‐supported crowns using cone‐beam computed tomography (CBCT) assessment compared to nonadjacent teeth.MethodologyA total of 1249 CBCT volumes were screened by five pre‐calibrated observers in 11 health centres. A step‐by‐step screening protocol was implemented and reviewed every 3 months, and mandatory setting characteristics were established for all CBCT scans using dedicated visualization software. Intra‐ and inter‐rater reliability tests were conducted. The prevalence of periapical lesions, root canal treatments and coronal restorations was recorded on both teeth adjacent and nonadjacent to implant‐ (predictor 1) or natural tooth‐supported crowns (predictor 2). A binary logistic model (Generalizing Estimating Equations test) was used to verify whether the prevalence of periapical lesion, root canal filling and the tooth restorative status are altered when the assessed tooth is adjacent or not to an implant‐supported crown (predictor 1); or to a natural tooth‐supported crown (predictor 2). Odds ratio and confidence intervals for the dependent variables at both predictors were obtained. The significance level was set at .05.ResultsA global sample of 22 899 teeth was included. Compared to nonadjacent teeth, the prevalence of periapical lesion, root canals treatments and restorative procedures when adjacent to implant‐supported crowns was 10.7%, 19.6% and 22.9% higher, respectively, and when adjacent to tooth‐supported crowns was 19.3%, 35.6% and 37.4% higher respectively. These results were significant only for variables root canal filling and coronal restoration (p < .0001). Odds ratio to present root canal treatment is 2.57 times higher (CI 1.95–3.39, p = .0001) when the tooth is adjacent to implant‐supported crown and 4.39 times (CI 3.49–5.53, p = .0001) when adjacent to tooth‐supported crown, whilst for restorative procedure, the odds are, respectively, 1.63 (CI 1.29–2.06, p = .0001) and 2.30 (CI 1.92–2.76, p = .0001).ConclusionsTeeth adjacent to both implant‐ and natural tooth‐supported crowns were associated with a higher frequency of root canal filling and coronal restorations.
Nurse‐guided incentive spirometry use and postoperative pulmonary complications among cardiac surgery patients: A randomized controlled trial
Authors: Alwekhyan Saja Ahmad , Alshraideh Jafar Alasad , Yousef Khalil Moh'd , Hayajneh Ferial 
Published: October 2021

AbstractAimsTo assess the effect of nurse‐guided use of incentive spirometer on postoperative oxygenation and pulmonary complications after coronary artery bypass graft surgery.BackgroundDeep breathing exercises have been shown to improve postoperative lung expansion and reduce pulmonary complications. An incentive spirometer is a deep breathing exercises device that imitates continuous sigh‐like maximal inspiration.DesignRandomized control trial, two groups nonblinded parallel design.MethodsA total of n = 89 eligible patients were randomized to either control or intervention group. Patients in the intervention group received bihourly nurse‐guided incentive spirometry for 48‐h postextubation. The endpoints were: the number and duration of hypoxic events during the first 24‐hr postsurgery, pneumonia and pulmonary function parameters. Data were collected May to September 2019.ResultsPatients in the intervention group had a significantly lower mean number of hypoxic events with shorter duration and shorter length of stay in the hospital and the ICU. Patients in the intervention group also had greater postoperative forced expiratory volume in 1 second.ConclusionNurse‐guided use of the incentive spirometer reduces the risk of pulmonary complications and hospital length of stay after cardiac surgery.
Social protection and the platform economy: The anomalous approach of the French legislator
Authors: Daugareilh Isabelle 
Published: October 2021

AbstractAddressing the social protection of platform workers, the French legislator in 2016 and then in 2019 made moves to incorporate these workers into the general social security regime with regard to certain covered risks (work injury and occupational diseases), and to improve adequacy (enabling possible access to complementary coverage). However, these moves rest on radically opposed perspectives. Rather than reasserting the legal responsibility of the employer vis‐à‐vis workers’ health and safety, we see responsibility placed with the platform, but only on a voluntary basis under the aegis of corporate social responsibility. This risks fragmenting social benefits, to be determined by each platform, thus weakening the practices of mutual protection and risk pooling among enterprises and workers that lie at the heart of social security. In doing so, the legislator has broken the link that had as its historic objective the goal of social inclusion and has encouraged in different ways the privatization, or a re‐commodification, of social security in the commercial interest of private insurance companies. Moreover, this has been done using the Trojan Horse of the French labour code. This approach is in contrast to the converging position of international organizations, such as the European Union, International Labour Organization or the Organisation for Economic Co‐operation and Development, recommending that States establish a right to social protection for all atypical workers and non‐salaried workers. Instead of identifying the common challenges that face workers who work for platforms, and offering responses specific to their situation, rather, it considers platform work as one of the new forms of atypical work undertaken by those who may have the status of employee or self‐employed.
Which social security regime for platform workers in Italy?
Authors: Borelli Silvia , Gualandi Sofia 
Published: October 2021

AbstractThis article highlights the debate on social security regimes applicable to platform workers in Italy. As social security regimes differ according to the type of employment or self‐employment relationship, Italian case law dealing with platform workers’ employment status will be illustrated. Italian legislation, case law and collective bargaining on health and safety at work will then be presented, clarifying the coverage to which platform workers are entitled in the event of accidents at work and occupational diseases, with a focus on the COVID‐19 pandemic impact. In turn, the two main Italian minimum income schemes and the related scholarly debate will be outlined, as well as their impact on the ability of digital labour platforms to avoid their responsibilities as regards workers’ rights, including access to adequate social protection.
Novel functions of S1P in chronic itchy and inflammatory skin diseases
Authors: Gray N. , Limberg M.M. , Bräuer A.U. , Raap U. 
Published: October 2021

AbstractS1P is a pleotropic sphingolipid signalling molecule that acts through binding to five high‐affinity G‐protein coupled receptors. S1P‐signaling affects cell fate in a multitude of ways, e.g. influencing cell differentiation, proliferation, and apoptosis, as well as playing an important role in immune cell trafficking. Though many effects of S1P‐signaling in the human body have been discovered, the full range of functions is yet to be understood. For inflammatory skin diseases such as atopic dermatitis and psoriasis, evidence is emerging that dysfunction and imbalance of the S1P‐axis is a contributing factor. Multiple studies investigating the efficacy of S1PR modulators in alleviating the severity and symptoms of skin conditions in various animal models and human clinical trials have shown promising results and validated the interest in the S1P‐axis as a potential therapeutic target. Even though the involvement of S1P‐signalling in inflammatory skin diseases still requires further clarification, the implications of the recent findings may prompt expansion of research to additional skin conditions and more S1P‐axis modulatory pharmaceuticals.
Fat‐soluble vitamin assessment, deficiency and supplementation in infants with cholestasis
Authors: Mancell Sara , Islam Maeisha , Dhawan Anil , Whelan Kevin 
Published: October 2021

AbstractBackgroundInfants with cholestasis are at risk of fat‐soluble vitamin deficiency. The present study amied to review practice relating to the assessment, deficiency and supplementation of fat‐soluble vitamins in infants with cholestasis.MethodsThe medical records of all newly diagnosed infants with cholestasis (conjugated bilirubin >17 mmol L–1/>20% total bilirubin) at King's College Hospital between 2017 and 2019 were reviewed. Data extracted included bilirubin, serum vitamin concentrations (A, D, E), international normalised ratio and evidence of supplementation at initial assessment, as well as at 3 and 6 months. Rates of vitamin assessment, deficiency and supplementation were compared using chi‐squared or Fisher's exact test.ResultsIn total, 136 infants (87 male) with idiopathic neonatal cholestasis (n = 62), biliary atresia (n = 40) and other aetiology (n = 34) were included. Assessment of serum vitamins (A, D, E) was low (33.3%–52.2%) and deficiency was initially high for vitamin D (60.6%) and vitamin E (70.9%). Supplementation prevalence at initial assessment was high (A, E, K), but dropped significantly at 3 and 6 months for vitamin E (p = 0.003) and vitamin K (p = 0.001), whereas vitamin D supplementation was consistently low throughout (25%–33.3%). Infants with biliary atresia were more likely to have vitamins assessed (3 months), be deficient initially (D, E) and supplemented (E, K) throughout. Supplementation continued in up to 80% of infants despite cholestasis resolving.ConclusionsSupplementation was generally high and continued in many despite cholestasis resolving. Deficiency of vitamin D and vitamin E was high at initial assessment, although lower at follow‐up. Actual prevalence of deficiency of all vitamins is unknown because monitoring was not consistently performed.
What kind of labour regime is contract farming? Contracting and sharecropping in Java compared
Authors: White Ben , Wijaya Hanny 
Published: October 2021

AbstractThis article compares contract farming with share tenancy, another labour regime in which smallholder farmers are bound by contract to deliver produce to another, usually more powerful party. Based on research in the Javanese village of Kaliloro, we explore contracting and sharecropping as labour regimes, each with their own specific mechanisms of surplus transfer from producers to non‐producers. The cases compared are sharecropping of irrigated rice, contract farming of watermelon, and contract farming of poultry. There are important differences in how labour inputs are organized, how decisions are made, how costs are divided between landowner/contractor and farmer, and in the mechanisms of surplus transfer between the contracting parties. Exploring these differences allows us to understand and compare the role of the two labour regimes in the penetration of capital into the rural economy. Neither contract farming nor share tenancy arein themselves“win‐win” or “win‐lose” relationships, good or bad for small‐scale cultivators. The actual balance of burdens and benefits—often contravening the provisions of written contracts or state regulation—is determined by power relations between the contracting parties.
Soft tissue filler augmentation of the orbicularis retaining ligament to improve the lid‐cheek junction
Authors: Bernardini Francesco P. , Casabona Gabriela , Alfertshofer Michael G. , Frank Konstantin , Moellhoff Nicholas , Gotkin Robert H. , Davidovic Kristina , Voropai Daria , Valli Andrea , Cotofana Sebastian 
Published: October 2021

AbstractBackgroundThe orientation of facial ligaments changes with increasing age due to the loss of bony support. Soft tissue filler injections placed in close proximity to facial ligaments can alter their orientation to help achieve an improved and younger aesthetic appearance.ObjectiveTo assess the anatomic and aesthetic effects of a standardized injection with soft tissue filler placed directly inferior to the orbicularis retaining ligament in the infraorbital region.MethodsA total of 163 patients with signs of infraorbital aging were treated with a standardized soft tissue filler injection into and in close proximity to the orbicularis retaining ligament (ORL). 2D frontal images of the infraorbital region were rated by eleven blinded and independent raters with regards to the aesthetic appearance of the infraorbital region before and after the standardized injection treatment.ResultsThe aesthetic appearance of the entire infraorbital region (lid‐cheek junction) was rated before and after the treatment. The severity of the tear trough (medial aspect of the infraorbital region) as well as the hollowing of the lateral aspect of the infraorbital region also was rated before and after the treatment. Aesthetic improvement was statistically significant when evaluated by the blinded raters, the treating physician, and the patients. All the results were “very much improved” compared to baseline.ConclusionThe effectiveness of this injection technique is thought to be due to the strategic placement of soft tissue filler that helps to reposition facial ligaments that have changed their orientation during the aging process.