bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating persistent and transient technical efficiency and their determinants in the presence of heterogeneity and endogeneity
Authors: Bokusheva Raushan , Čechura Lukáš , Kumbhakar Subal C. 
Published: September 2022

AbstractWe develop an estimation procedure that generates consistent estimates of the technology parameters, long‐run (persistent) and short‐run (transient) technical inefficiencies and the marginal effects of their determinants for the stochastic frontier model developed by Colombi et al. (2014, Journal of Productivity Analysis 42, 123) and Kumbhakar et al. (2014, Journal of Productivity Analysis 41, 321). Our approach accounts for three sources of potential endogeneity: (i) unobserved heterogeneity; (ii) simultaneity of input use with both types of technical efficiency; (iii) potential correlation of the noise term with the regressors. Using this approach we examine the effect of direct payments and farm size on the persistent and transient technical efficiency of French crop farms before and after the European Union's Common Agricultural Policy decoupling reform of 2003. Our results show that subsidy payments per hectare of utilised agricultural land had a significant positive effect on persistent technical efficiency and a significant negative effect on transient technical efficiency during the period before decoupling. For the period after the reform, the effect of subsidies is found to be significantly negative for persistent technical efficiency and insignificant for transient technical efficiency. The overall effect of subsidies on technical efficiency is found to be negative in both periods, albeit substantially lower in the period after decoupling. The effect of farm size on technical efficiency is found to be significant only for the period prior to the reform: it reduced persistent technical inefficiency but increased transient technical inefficiency during that period.
Multiplex gene precise editing and large DNA fragment deletion by the CRISPR‐Cas9‐TRAMA system in edible mushroom Cordyceps militaris
Authors: Chen Bai‐Xiong , Xue Ling‐Na , Wei Tao , Wang Na , Zhong Jing‐Ru , Ye Zhi‐Wei , Guo Li‐Qiong , Lin Jun‐Fang 
Published: September 2022

AbstractThe medicinal mushroom Cordyceps militaris contains abundant valuable bioactive ingredients that have attracted a great deal of attention in the pharmaceutical and cosmetic industries. However, the development of this valuable mushroom faces the obstacle of lacking powerful genomic engineering tools. Here, by excavating the endogenous tRNA‐processed element, introducing the extrachromosomal plasmid and alongside with homologous template, we develop a marker‐free CRISPR‐Cas9‐TRAMA genomic editing system to achieve the multiplex gene precise editing and large synthetic cluster deletion in C. militaris. We further operated editing in the synthetases of cordycepin and ergothioneine to demonstrate the application of Cas9‐TRAMA system in protein modification, promoter strength evaluation and 10 kb metabolic synthetic cluster deletion. The Cas9‐TRAMA system provides a scalable method for excavating the valuable metabolic resource of medicinal mushrooms and constructing a mystical cellular pathway to elucidate the complex cell behaviours of the edible mushroom.
What's in a Name? Investors' Reactions to Non‐GAAP Labels*†
Authors: Garavaglia Shannon 
Published: September 2022

ABSTRACTUsing a mixed‐methods approach, I investigate how the terms that firms use to label non‐GAAP earnings interact with investors' scrutiny of non‐GAAP reporting to affect investors' information search behavior and investment decisions. This study informs regulators, who have expressed concern over the mislabeling of non‐GAAP measures, and managers, who are often criticized for their misuse of discretion in non‐GAAP reporting. I first provide descriptive evidence on the non‐GAAP labels used in practice, followed by a survey to understand what investors believe these labels convey about earnings quality. Finally, drawing on theory from psychology, I predict and then find in an experiment that investors who are more likely to scrutinize non‐GAAP reporting are not affected by non‐GAAP labels when deciding to seek out the non‐GAAP reconciliation, and react positively to appropriately used labels. However, investors who are less likely to scrutinize non‐GAAP reporting rely on the cue provided by the label when deciding whether to seek out the non‐GAAP reconciliation, and are more likely to be misled by inappropriately used labels. For regulators, these findings validate concerns related to the mislabeling of non‐GAAP measures and suggest increased non‐GAAP scrutiny helps counteract mislabeling. For managers, these findings suggest investors react favorably to the appropriate use of discretion in non‐GAAP reporting.
Reduced endosomal microautophagy activity in aging associates with enhanced exocyst‐mediated protein secretion
Authors: Krause Gregory J. , Diaz Antonio , Jafari Maryam , Khawaja Rabia R. , Agullo‐Pascual Esperanza , Santiago‐Fernández Olaya , Richards Alicia L. , Chen Kuei‐Ho , Dmitriev Phillip , Sun Yan , See Stephanie K. , Abdelmohsen Kotb , Mazan‐Mamczarz Krystyna , Krogan Nevan J. , Gorospe Myriam , Swaney Danielle L. , Sidoli Simone , Bravo‐Cordero Jose Javier , Kampmann Martin , Cuervo Ana Maria 
Published: September 2022

AbstractAutophagy is essential for protein quality control and regulation of the functional proteome. Failure of autophagy pathways with age contributes to loss of proteostasis in aged organisms and accelerates the progression of age‐related diseases. In this work, we show that activity of endosomal microautophagy (eMI), a selective type of autophagy occurring in late endosomes, declines with age and identify the sub‐proteome affected by this loss of function. Proteomics of late endosomes from old mice revealed an aberrant glycation signature for Hsc70, the chaperone responsible for substrate targeting to eMI. Age‐related Hsc70 glycation reduces its stability in late endosomes by favoring its organization into high molecular weight protein complexes and promoting its internalization/degradation inside late endosomes. Reduction of eMI with age associates with an increase in protein secretion, as late endosomes can release protein‐loaded exosomes upon plasma membrane fusion. Our search for molecular mediators of the eMI/secretion switch identified the exocyst‐RalA complex, known for its role in exocytosis, as a novel physiological eMI inhibitor that interacts with Hsc70 and acts directly at the late endosome membrane. This inhibitory function along with the higher exocyst‐RalA complex levels detected in late endosomes from old mice could explain, at least in part, reduced eMI activity with age. Interaction of Hsc70 with components of the exocyst‐RalA complex places this chaperone in the switch from eMI to secretion. Reduced intracellular degradation in favor of extracellular release of undegraded material with age may be relevant to the spreading of proteotoxicity associated with aging and progression of proteinopathies.
LncRNA8276 primes cell–cell adhesion for regulation of spermatogenesis
Authors: Xiong Bohui , Jiang Yue , Wang Yandi , Han Xiao , Zhang Cong , Zhong Ruqing , Ge Wei , Han Baoquan , Ge Zhaojia , Huang Gui'an , Yin Shen , Shen Wei , Sun Qingyuang , Sun Zhongyi , Zhao Yong , Zhang Hongfu 
Published: September 2022

AbstractBackgroundHuman sperm concentration and motility have dropped dramatically (50%) in the past few decades, and environmental factors are involved in this decline. Long non‐coding RNAs (lncRNA) have been discovered to be involved in many cellular processes including spermatogenesis.ObjectiveThis investigation aimed to explore the role of lncRNA8276 in murine spermatogenesis.Materials and methodsThe expression of lncRNA8276 was modified by knockdown or overexpression in mouse testes and spermatogonial stem cells (C18‐4 cell line). Sperm quality was determined in the F0 and F1 generations of mice. Furthermore, the underlying mechanisms were studied through gene expression and/or protein expression of spermatogenesis‐related genes and cell junction‐related genes by different methods.ResultsIn the current investigation, we discovered that sperm lncRNA8276 was decreased by NH3/H2S in three generations (F0, F1, and F2) of mouse sperm. In vivo testicular knockdown of lncRNA8276 led to a decline in sperm concentration and motility in both F0 (muF0) and F1 (muF1) generations Moreover, knockdown lncRNA8276 decreased the gene and protein levels of important genes related to cell–cell junctions and spermatogenesis. The data were further confirmed in mouse spermatogonia stem cell line C18‐4 cells through knockdown of lncRNA8276.Discussion and conclusionOur study suggests that lncRNA8276 may be involved in cell–cell junction formation in the mouse testis to regulate spermatogenesis. It may be a target for the modification of spermatogenesis and male fertility, or male contraception. This investigation offers a potential therapeutic strategy for male infertility.
Effect of capmatinib on the pharmacokinetics of substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with MET‐dysregulated solid tumours
Authors: Chen Xinhui , Isambert Nicolas , López‐López Rafael , Giovannini Monica , Pognan Nathalie , Kapoor Shruti , Quinlan Michelle , You Benoit , Cui Xiaoming , Rahmanzadeh Gholamreza , Mau‐Sorensen Morten 
Published: September 2022

BackgroundPreclinical studies showed that capmatinib reversibly inhibits cytochrome P450 (CYP) 3A4 and CYP1A2 in a time‐dependent manner. In this study, we evaluated the effect of capmatinib on the exposure of sensitive substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with mesenchymal–epithelial transition (MET)‐dysregulated solid tumours. Besides pharmacokinetics, we assessed treatment response and safety.MethodsThis open‐label, multicentre, single‐sequence study consisted of a molecular prescreening period, a screening/baseline period of ≤28 days and a drug‐drug interaction (DDI) phase of 12 days. On day 1 of the DDI phase, 37 patients received a single oral dose of midazolam 2.5 mg and caffeine 100 mg as a two‐drug cocktail. Capmatinib 400 mg bid was administered from day 4 on a continuous dosing schedule. On day 9 of the DDI phase, patients were re‐exposed to midazolam and caffeine. After the DDI phase, patients received capmatinib on continuous 21‐day cycles until disease progression at the discretion of the investigator.ResultsA 22% (90% confidence interval [CI] 7‐38%) increase in the midazolam maximum plasma concentration (Cmax) was noted when administered with capmatinib, but this was deemed not clinically meaningful. Co‐administration with capmatinib resulted in 134% (90% CI 108‐163%) and 122% (90% CI 95‐153%) increases in the caffeine area under the plasma concentration‐time curve from time zero to infinity (AUCinf) and area under the plasma concentration‐time curve from time zero to the last measurable point (AUClast), respectively, with no change in Cmax. Adverse events were consistent with the known capmatinib safety profile. No new safety signals were reported in this study.ConclusionThe data from this study demonstrated that capmatinib is a moderate CYP1A2 inhibitor. Capmatinib administration did not cause any clinically relevant changes in midazolam exposure.
Ethnic and socioeconomic disparities in initiation of second‐line antidiabetic treatment for people with type 2 diabetes in England: A cross‐sectional study
Authors: Bidulka Patrick , Mathur Rohini , Lugo‐Palacios David G. , O'Neill Stephen , Basu Anirban , Silverwood Richard J. , Charlton Paul , Briggs Andrew , Smeeth Liam , Adler Amanda I. , Douglas Ian J. , Khunti Kamlesh , Grieve Richard 
Published: September 2022

AbstractAimsTo assess any disparities in the initiation of second‐line antidiabetic treatments prescribed among people with type 2 diabetes mellitus (T2DM) in England according to ethnicity and social deprivation level.Materials and methodsThis cross‐sectional study used linked primary (Clinical Practice Research Datalink) and secondary care data (Hospital Episode Statistics), and the Index of Multiple Deprivation (IMD). We included people aged 18 years or older with T2DM who intensified to second‐line oral antidiabetic medication between 2014 and 2020 to investigate disparities in second‐line antidiabetic treatment prescribing (one of sulphonylureas [SUs], dipeptidyl peptidase‐4 [DPP‐4] inhibitors, or sodium‐glucose cotransporter‐2 [SGLT2] inhibitors, in combination with metformin) by ethnicity (White, South Asian, Black, mixed/other) and deprivation level (IMD quintiles). We report prescriptions of the alternative treatments by ethnicity and deprivation level according to predicted percentages derived from multivariable, multinomial logistic regression.ResultsAmong 36 023 people, 85% were White, 10% South Asian, 4% Black and 1% mixed/other. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by ethnicity were 21% (95% confidence interval [CI] 19–23%), 20% (95% CI 18–22%), 19% (95% CI 16–22%) and 17% (95% CI 14–21%) among people with White, South Asian, Black, and mixed/other ethnicity, respectively. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by deprivation were 22% (95% CI 20–25%) and 19% (95% CI 17–21%) for the least deprived and the most deprived quintile, respectively. When stratifying by prevalent cardiovascular disease (CVD) status, we found lower predicted percentages of people with prevalent CVD prescribed SGLT2 inhibitors compared with people without prevalent CVD across all ethnicity groups and all levels of social deprivation.ConclusionsAmong people with T2DM, there were no substantial differences by ethnicity or deprivation level in the percentage prescribed either SGLT2 inhibitors, DPP‐4 inhibitors or SUs as second‐line antidiabetic treatment.
Agricultural development promises more growth and less poverty in Africa: Modelling the potential impact of implementing the Comprehensive Africa Agriculture Development Programme in six countries
Authors: Diallo Mariam , Wouterse Fleur 
Published: September 2022

SummaryMotivationCountries of Africa have, through the Maputo and Malabo declarations and the companion Comprehensive Africa Agriculture Development Programme (CAADP) committed to increased public investment in agriculture. If implemented, this should contribute substantially to realizing several development goals, including reduction of poverty and hunger and making rural populations more resilient to climate change.PurposeHow much would implementation of National Agriculture Investment Plans (NAIPs) formulated within CAADP help achieve the aims of the Sustainable Development Goals, Agenda 2063, and the Malabo Declaration—namely, to boost agricultural growth, eradicate hunger, and reduce poverty and inequality?Methods and approachWe use data from Côte d'Ivoire, Ethiopia, Malawi, Mozambique, Niger, and Rwanda compiled in a Social Accounting Matrix. We run Computable General Equilibrium models with microeconomic models for each country to simulate the potential effect of implementation of the NAIPs. Three different methods to finance increased spending on agriculture are simulated: one that reallocates public expenditure with no overall increase in spending; a second that finances extra spending by more taxes; and one that relies on external funding to increase total spending.FindingsResults show that agriculture‐led investment would significantly increase agricultural growth, raise farm productivity, reduce dependency on food imports, improve incomes of food producers, and cut poverty. In most countries, increased investment in agriculture does more to boost growth, create jobs, and cut poverty than investments in industry or services. Raising overall public spending to allow more agricultural investment is far more effective than shifting spending within a fixed budget.Policy implicationsFor the six countries modelled, an agriculture‐led investment strategy appears the best way to eradicate hunger and reduce poverty and inequality while building resilience of rural households.
Survival analysis of fragment reattachments and direct composite restorations in permanent teeth after dental traumatic injuries
Authors: Haupt Franziska , Meyerdiercks Christopher , Kanzow Philipp , Wiegand Annette 
Published: September 2022

AbstractBackground/AimIn case of crown fractures after traumatic dental injuries, the affected teeth can be restored either with reattachment of the fractured fragment or with a direct composite restoration. So far, longevity data for reattachments and direct composite restorations with regard to different failure types (pulp necrosis and infection, restoration loss) are scarce. Therefore, the aim of this retrospective study was to evaluate the restorative and biological survival of reattached fragments and composite restorations after crown fractures in permanent teeth.Material and MethodsDental records of patients treated between 2000 and 2018 were retrospectively analysed regarding the restoration (reattachment or direct composite restorations) of teeth with crown fractures. Survival (no further intervention) and restorative and/or biological failure of all restored teeth were recorded. Statistical analysis was performed using Kaplan–Meier statistics, and the mean annual failure rates for two and 5 years were calculated. Furthermore, the effect of potential risk factors on survival was assessed. Log‐rank tests and univariate Cox regression models (likelihood ratio tests) were used to assess the univariate effect of all variables of interest. Variables with a p‐value ≤.10 were included in a multivariate Cox regression model with shared frailty (p < .05).ResultsOverall, 164 patients with 235 teeth (uncomplicated crown fracture: N = 201, complicated crown fracture: N = 34) were included (1.6 ± 2.5 years observation time). Of these, 59 teeth were restored with reattachment of the fragment and 176 with a composite restoration. Overall, composite restorations had a significantly higher survival rate than reattachments (p = .002). The cumulative survival after 2 years was 42.9% and 65.0% for teeth treated with a reattachment (mAFR = 34.5%) and a composite restoration (mAFR = 19.3%), respectively. When differentiating between failure types, restoration failure and pulp necrosis were significantly more frequently detected in reattached crown fractures compared to composite restorations (restorative failure: p = .001; biological failure: p = .036). In the multivariate Cox regression model, the variable jaw and luxation significantly influenced the survival when the tooth was restored with a composite restoration. The survival was not influenced by the fracture type.ConclusionsRestorative and biological failures were more frequently detected when the tooth was restored with a reattached fragment compared to a direct composite restoration. Both, restoration failure and pulp necrosis with infection should be considered as frequent complications after restoration of crown‐fractured teeth which emphasizes the necessity of regular and short follow‐up intervals throughout the first 2 years.
General and dental injuries sustained at concerts: A questionnaire‐based study
Authors: Schifferle Anne‐Kathrin , Eggmann Florin , Mukaddam Khaled , Kühl Sebastian , Filippi Andreas 
Published: September 2022

AbstractBackground/AimEvidence on the risk of injury at concerts is scant. The aim of this study was to collect data on general and dental injuries incurred by concertgoers in Switzerland and to investigate whether the frequency of accidents was related to music genre, gender and consumption of alcohol.Materials and methodsA questionnaire‐based, cross‐sectional study comprising 451 concertgoers in Switzerland was conducted on the timeframe January 2019 to February 2021. The survey gathered data on general and dental injuries, alcohol consumption and drug use. The statistical analysis included Fisher's exact tests, chi‐squared tests, rank sum tests and logistic regressions (α = .05).ResultsThere were 28.8% of respondents who reported an injury incurred at a concert. Contusion was the most prevalent injury, accounting for 33.8% of all injuries. Legs were the most commonly injured body part (34.6%). Injuries to their mouth/lips/teeth were reported by 17.7% of respondents. Dental injuries, accounting for 4.6% of all reported injuries, comprised four tooth fractures, one lateral luxation and one avulsion. The risk of injury while attending punk rock concerts was 8.6 times higher than for pop concerts (p < .001). In comparison with pop concerts, metal and rock concerts had an increased risk of injury by factors of 5.1 and 2.3, respectively (p ≤ .029). Neither gender nor drug use had a significant effect on the injury risk (p ≥ .3). Heavy alcohol consumption (>5 standard glasses) increased the risk of injury by a factor of 2.3 (p = .028).ConclusionsThis study suggests that concert attendees at rock, metal and punk concerts face an increased risk of injury, which is likely due to the frequency of aggressive dance styles such as moshing. Heavy alcohol consumption leads to a greater risk of injury at concerts.
Clinical view versus guideline adherence in ferritin monitoring and initiating iron chelation therapy in patients with myelodysplastic syndromes
Authors: Rozema Johanne , van Asten Ivar , Kwant Beau , Kibbelaar Robby E. , Veeger Nic J. G. M. , de Wit Harry , van Roon Eric N. , Hoogendoorn Mels ,   the HemoBase Population Registry Consortium
Published: September 2022

AbstractObjectivesIn patients with myelodysplastic syndromes (MDS) with >20 transfusions and ferritin levels >1000 μg/L, international guidelines recommend iron chelation therapy (ICT). The study's objective was to determine guideline adherence and the intensity of ferritin monitoring in clinical practice.MethodsWe performed an observational population‐based study using the HemoBase Registry, which contains data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Clinical information on transfusions, ferritin measurements, ICT, and clinical performance as defined by age ≤ 80 years, Charlson Comorbidity Index <2 and lower‐risk MDS was collected from health records.ResultsTwo hundred and thirty seven of 292 patients (81.1%) received ≥1 transfusion, and 121 (41.4%) received >20 transfusions. In 57 of these 121 patients (47.1%), ferritin measurements were performed at least once. Clinical performance was significantly associated with monitoring ferritin around the 20th transfusion (RR: 2.49, p = .016). Clinical performance was also associated with initiating ICT (RR: 5.99, p < .001). ICT was offered to 22.3% (n = 25) of eligible patients.ConclusionsIn this population‐based study, ferritin levels were measured in <50% of MDS patients who received >20 transfusions, and clinical performance was significantly associated with measuring ferritin. Our study suggests that in heavily transfused MDS patients, ferritin monitoring is primarily based on patients' clinical performance rather than guideline recommendations.