bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Firms' Quality Experts Shape Canadian Public Accountability Board Inspections and Their Outcomes: An Analysis of Intraprofessional Conflicts, Third‐Party Influences, and Relational Strategies†
Authors: Couchoux Oriane , Malsch Bertrand 
Published: November 2021

ABSTRACTIn this study, we examine auditors' claims of professional disempowerment and strategic responses to Canadian Public Accountability Board (CPAB) inspections. Our research is based primarily on 27 semistructured interviews with audit partners (23) and managers (4) of large accounting firms. Drawing on key insights from institutional theory, we show that the tensions between inspectors and auditors reflect an intraprofessional tug‐of‐war between two competing but legitimate logics of professionalism. More specifically, our findings indicate that CPAB inspections have given rise to a mechanical logic of audit professionalism that is driven by the efforts of inspectors to promote a generalizable theoretical ideal of auditing that revolves around best practices and attention to technical minutiae. This mechanical logic competes with a clinical logic of audit professionalism that is driven by the efforts of audit partners and managers to promote a more relativistic, applied form of expert knowledge. To manage this dynamic of intra‐institutional complexity, quality experts (QEs) have emerged in firms' organizational structures as ambidextrous third parties—that is, professionals who master both logics and are capable of bridging the institutional divide by influencing the relationships between inspectors and auditors through a variety of brokering strategies. By considering inspectors as insiders rather than outsiders to the profession, we argue that auditors' claims of professional disempowerment should be interpreted carefully and critically. We also suggest that the professional autonomy and judgment of engagement partners and managers has been displaced significantly within firm boundaries into the hands of QEs. Our analysis offers a richer conceptualization of institutional ambidexterity by examining it as a relational process of social influence rather than as a set of individual characteristics.
Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes
Authors: Onken Brian , Sedore Christine A. , Coleman‐Hulbert Anna L. , Hall David , Johnson Erik , Jones Eleanor Grace , Banse Stephen A. , Huynh Phu , Guo Suzhen , Xue Jian , Chen Esteban , Harinath Girish , Foulger Anna C. , Chao Elizabeth A. , Hope June , Bhaumik Dipa , Plummer Todd , Inman Delaney , Morshead Mackenzie , Guo Max , Lithgow Gordon J. , Phillips Patrick C. , Driscoll Monica 
Published: November 2021

AbstractMetformin, the most commonly prescribed anti‐diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity and health effects, metformin is now the focus of the first proposed clinical trial of an anti‐aging drug—the Targeting Aging with Metformin (TAME) program. Genetic variation will likely influence outcomes when studying metformin health effects in human populations. To test for metformin impact in diverse genetic backgrounds, we measured lifespan and healthspan effects of metformin treatment in three Caenorhabditis species representing genetic variability greater than that between mice and humans. We show that metformin increases median survival in three C. elegans strains, but not in C. briggsae and C. tropicalis strains. In C. briggsae, metformin either has no impact on survival or decreases lifespan. In C. tropicalis, metformin decreases median survival in a dose‐dependent manner. We show that metformin prolongs the period of youthful vigor in all C. elegans strains and in two C. briggsae strains, but that metformin has a negative impact on the locomotion of C. tropicalis strains. Our data demonstrate that metformin can be a robust promoter of healthy aging across different genetic backgrounds, but that genetic variation can determine whether metformin has positive, neutral, or negative lifespan/healthspan impact. These results underscore the importance of tailoring treatment to individuals when testing for metformin health benefits in diverse human populations.
Repetitive transcranial magnetic stimulation modulates coupling among large‐scale brain networks in heroin‐dependent individuals: A randomized resting‐state functional magnetic resonance imaging study
Authors: Jin Long , Yuan Menghui , Zhang Wei , Su Hang , Wang Fan , Zhu Jia , Liu Tao , Wei Yixin , Li Yunbo , Bai Qianrong , Wang Wei , Wei Longxiao , Li Qiang 
Published: November 2021

AbstractThe abnormal interactions of three key large‐scale brain networks (default mode [DMN], salience and executive control [ECN]) were showed underlie dysfunctions in heroin addiction. Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a potential treatment for heroin addiction. It is unclear whether impaired coupling among the large‐scale brain networks would be improved by rTMS in treated heroin‐dependent individuals. Thirty‐five heroin‐dependent individuals were included in this sham‐controlled, randomized study. The patients received either active or sham rTMS for 1 week. The craving for heroin and resting‐state functional magnetic resonance imaging data were collected before and after 1‐week rTMS. Twenty‐two healthy subjects were included as controls not receiving rTMS. After 1‐week rTMS, only the active rTMS group showed a significant decrease in spontaneous and heroin cue‐induced craving. The coupling between left DLPFC (a key node of left ECN) and left parahippocampal gyrus (PHG, included in DMN) significantly increased for the active group with a tendency towards that of controls. The coupling between the right precentral gyrus and three key regions included in DMN (posterior cingulate cortex/precuneus and bilateral inferior parietal cortex) significantly decreased for the active group with a tendency towards that of healthy controls. For the active rTMS individuals, the left DLPFC‐PHG coupling negatively correlated with the spontaneous craving and the drug cue‐induced craving. It suggested that the rTMS could reduce heroin craving, which might be related to the modulation of ECN‐DMN coupling. This finding might shed light on the mechanism of rTMS for heroin addiction treatment.
Evaluation of a dedicated outpatient hip fracture clinic
Authors: Ratnayake Hasanka , Crabtree Amelia , Hunter Peter , Parikh Seema , Tay Brenton , Anthonisz Brian , Moran Chris 
Published: November 2021

AbstractObjectivesThere is a lack of guidance on how to manage the multiple post‐discharge issues of older people following minimal trauma hip fracture. We developed a geriatrician‐staffed outpatient service for people aged ≥65 years admitted with a hip fracture who were not discharged to a nursing home. We aimed to evaluate the potential benefits of the addition of a dedicated hip fracture follow‐up clinic by measuring the actions performed by such a clinic.MethodsWe evaluated the potential benefit of the clinic through a retrospective review of the medical records of all those referred to the clinic over a 2‐year period.ResultsA total of 80 people were provided a clinic appointment, with 43 (54%) attending. The median age of clinic attendees was 81 years. A total of 40/43 (93%) of attendees received inpatient rehabilitation in a sub‐acute facility before discharge. At the dedicated outpatient clinic, multiple issues were identified and managed including further fall reduction strategies (n = 12), commencement of anti‐resorptive medications (n = 11) and medication deprescribing (n = 11).ConclusionsWe found that the introduction of a dedicated hip fracture outpatient clinic identified and managed a broad range of issues. It is unclear if these needs would have been met by previously existing services. Further work is required to clarify whether managing these issues translates into improved patient outcomes and whether a dedicated clinic is a cost‐effective practice of achieving this.
IMB5036 inhibits human pancreatic cancer growth primarily through activating necroptosis
Authors: Zhao Qi , Zheng Yanbo , Lv Xing , Gong Jianhua , Yang Lijun 
Published: November 2021

AbstractIMB5036 is a novel pyridazinone compound with potent cytotoxicity. In this study, we reported its antitumour activity against pancreatic cancer and the underlying mechanism. We found that IMB5036 induced rapid cell swelling and increased membrane permeability in pancreatic cancer cells. IMB5036 increased the ratio of PI+ cells, which could be rescued by necroptosis inhibitor. Furthermore, MLKL inhibitor NSA attenuated the killing effect of IMB5036 on pancreatic cancer cells. IMB5036 stimulated translocation of MLKL and p‐MLKL from cytoplasm to cell membrane. IMB5036 upregulated the level of p‐RIPK1, p‐RIPK3, and p‐MLKL. At the same time, IMB5036 also partially activated apoptosis and pyroptosis. IMB5036 inhibited tumour growth in pancreatic xenograft. IMB5036 induced larger necrosis area, increased p‐MLKL level, and inhibited Ki67 expression in tumour mass. The study indicates that IMB5036 inhibits human pancreatic cancer growth primarily activating necroptosis.
R&D spillovers, output subsidies, and privatization in a mixed duopoly: Flexible versus irreversible R&D investments
Authors: Chen Jiaqi , Lee Sang‐Ho , Muminov Timur K. 
Published: November 2021

AbstractThis study examines firms’ decisions on cost‐reducing research and development (R&D) along with the government's output subsidy policy with research spillovers. We investigate flexible and irreversible R&D, where investment is sequentially chosen after the realization of output subsidy rate in the former and simultaneously chosen with the expectation of subsidy policy in the latter. We demonstrate that compared to irreversible R&D, output subsidy is larger (smaller) for relatively high (low) spillovers, and the welfare is always higher under flexible R&D. We also compare mixed and private duopolies and show that privatization increases (decreases) not only output subsidy but welfare in both cases when the spillovers rate is relatively low (high).
Pathophysiological metabolic changes associated with disease modify the proarrhythmic risk profile of drugs with potential to prolong repolarisation
Authors: TeBay Clifford , McArthur Jeffrey R. , Mangala Melissa , Kerr Nicholas , Heitmann Stewart , Perry Matthew D. , Windley Monique J. , Vandenberg Jamie I. , Hill Adam P. 
Published: November 2021

Background and PurposeHydroxychloroquine, chloroquine and azithromycin are three drugs that were proposed to treat coronavirus disease 2019 (COVID‐19). While concern already existed around their proarrhythmic potential, there are little data regarding how altered physiological states encountered in patients such as febrile state, electrolyte imbalances or acidosis might change their risk profiles.Experimental ApproachPotency of human ether‐à‐go‐go related gene (hERG) block was measured using high‐throughput electrophysiology in the presence of variable environmental factors. These potencies informed simulations to predict population risk profiles. Effects on cardiac repolarisation were verified in human induced pluripotent stem cell‐derived cardiomyocytes from multiple individuals.Key ResultsChloroquine and hydroxychloroquine blocked hERG with IC50 of 1.47 ± 0.07 and 3.78 ± 0.17 μM, respectively, indicating proarrhythmic risk at concentrations effective against severe acute respiratory syndrome‐coronovirus‐2 (SARS‐CoV‐2) in vitro. Hypokalaemia and hypermagnesaemia increased potency of chloroquine and hydroxychloroquine, indicating increased proarrhythmic risk. Acidosis significantly reduced potency of all drugs, whereas increased temperature decreased potency of chloroquine and hydroxychloroquine against hERG but increased potency for azithromycin. In silico simulations demonstrated that proarrhythmic risk was increased by female sex, hypokalaemia and heart failure and identified specific genetic backgrounds associated with emergence of arrhythmia.Conclusion and ImplicationsOur study demonstrates how proarrhythmic risk can be exacerbated by metabolic changes and pre‐existing disease. More broadly, the study acts as a blueprint for how high‐throughput in vitro screening, combined with in silico simulations, can help guide both preclinical screening and clinical management of patients in relation to drugs with potential to prolong repolarisation.
Competition between 3D structural inheritance and kinematics during rifting: Insights from analogue models
Authors: Zwaan Frank , Chenin Pauline , Erratt Duncan , Manatschal Gianreto , Schreurs Guido 
Published: November 2021

AbstractThe competition between the impact of inherited weaknesses and plate kinematics determines the location and style of deformation during rifting, yet the relative impacts of these ‘internal’ and ‘external’ factors remain poorly understood, especially in 3D. In this study, we used brittle‐viscous analogue models to assess how multiphase rifting, that is changes in plate divergence rate or direction, and the presence and orientation of weaknesses in the competent mantle and crust, influences rift evolution. We find that the combined reactivation of mantle and crustal weaknesses without any kinematic changes already creates complex rift structures. Divergence rates affect the strength of the weak lower crustal layer and hence the degree of mantle‐crustal coupling; slow rifting decreases coupling, so that crustal weaknesses can dominate deformation localisation and surface structures, whereas fast rifting increases coupling and deformation related to mantle weaknesses can have a dominant surface expression. Through a change from slow to fast rifting mantle‐related deformation can overprint structures that previously formed along (differently oriented) crustal weaknesses. Conversely, a change from fast to slow rifting may shift deformation from mantle‐controlled towards crust‐controlled. When changing divergence directions, structures from the first rifting phase may control where subsequent deformation occurs, but only when they are sufficiently well developed. We furthermore place our results in a larger framework of brittle‐viscous rift modelling results from previous experimental studies, showing the importance of general lithospheric layering, divergence rate, the type of deformation in the mantle, and finally upper crustal structural inheritance. The interaction between these parameters can produce a variety of deformation styles that may, however, lead to comparable end products. Therefore, careful investigation of the distribution of strain localisation, and to an equal extent of basin depocenter locations over time is required to properly determine the evolution of complex rift systems, providing an incentive to revisit various natural examples.
Plasma extracellular vesicle microRNA profiling and the identification of a diagnostic signature for stage I lung adenocarcinoma
Authors: Gao Shugeng , Guo Wei , Liu Tiejun , Liang Naixin , Ma Qianli , Gao Yibo , Tan Fengwei , Xue Qi , He Jie 
Published: November 2021

AbstractAt present, there is no effective noninvasive method for the accurate diagnosis of early‐stage lung adenocarcinoma (LUAD). This study examined the profile of plasma extracellular vesicle (EV)‐delivered microRNAs (miRNAs) in patients with invasive stage I LUAD. In this study, a total of 460 participants were enrolled, including 254 patients with LUAD, 76 patients with benign pulmonary nodules (BPNs), and 130 healthy control patients (HCs). miRNA sequencing was used to analyze the EV miRNA profile of the patient plasma samples (n = 150). A diagnostic signature (d‐signature) was identified by applying a stepwise logistic regression algorithm, and a single‐center training cohort (n = 150) was tested, followed by a multicenter validation cohort (n = 100). A d‐signature comprising four EV‐derived miRNAs (hsa‐miR‐106b‐3p, hsa‐miR‐125a‐5p, hsa‐miR‐3615, and hsa‐miR‐450b‐5p) was developed for the early detection of LUAD. The d‐signature had high precision with area under the curve (AUC) values of 0.917 and 0.902 in the training and test cohorts, respectively. Moreover, the d‐signature could recognize patients with adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with AUC values of 0.846 and 0.92, respectively. To sum up, our study detailed the plasma EV–derived miRNA profile in early LUAD patients and developed an EV‐derived miRNA d‐signature to detect early LUAD.
The role of oral health‐related quality of life in the association between dental caries and height, weight and BMI among children in Bangladesh
Authors: Mishu Masuma Pervin , Tsakos Georgios , Heilmann Anja , Watt Richard G 
Published: November 2021

AbstractObjectivesTo examine whether oral health‐related quality of life (OHRQoL) explained the negative associations between dental caries and anthropometric measures of child growth among a sample of 5‐ to 9‐year‐old children in Dhaka, Bangladesh, while taking potential confounding factors (maternal education, family income, study setting, child's birth weight and childhood diseases) into account. In addition, to test whether specific oral impacts had a role in explaining these associations.MethodsData collection was conducted via a cross‐sectional survey among children and their parents from both hospital and school settings in Dhaka. Dental caries and severe consequences of dental caries (defined here as dental sepsis) were the exposure variables, and age‐ and sex‐adjusted height‐z‐scores (HAZ), weight‐z‐scores (WAZ) and BMI‐z‐scores (BAZ) were the outcome variables. OHRQoL was measured using the Bengali version of the Scale of Oral Health Outcomes for 5‐year‐old children (SOHO‐5). First, associations between oral impacts (prevalence of overall impacts and specific items of the SOHO‐5) and outcome measures were assessed. Multiple linear regression was used to assess associations between caries and anthropometric measures, adjusted for potential confounders. Oral impacts were then added to test whether their inclusion attenuated the associations between exposures and outcomes. To further investigate potential mediating role of oral impacts, structural equation modelling (SEM) was used to test the hypothesis that dental caries and sepsis were associated with the outcomes directly and also indirectly via oral impacts in general. A similar approach was used to investigate mediation by specific SOHO‐5 items.ResultsThe sample consisted of 715 children, 73.1% of whom had dental caries, 37.5% presented with sepsis, and 57.3% reported at least one oral impact (SOHO‐5 score ≥1). Prevalence of overall oral impacts and also the impact on ‘eating difficulty’ (a specific item of SOHO‐5) were negatively associated with all three outcomes. Dental caries and sepsis was associated with lower HAZ, WAZ and BAZ, and adjustment for overall oral impacts considerably attenuated the associations between ‘severe dental caries’ and outcomes, and dental sepsis and outcomes. Using SEM, we found significant indirect associations between caries and sepsis and anthropometric measures via oral impacts (except for dental caries and HAZ). Considering specific oral impacts, eating difficulties explained about 44% and 65% of the associations between caries and anthropometric outcomes, and dental sepsis and anthropometric outcomes, respectively.ConclusionsOral impacts, in particular eating difficulties, appear to mediate associations between caries and markers of child growth among this population.
Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants inIMMTgene
Authors: Marco‐Hernández Ana Victoria , Tomás‐Vila Miguel , Montoya‐Filardi Alejandro , Barranco‐González Honorio , Vilchez Padilla Juan Jesus , Azorín Inmaculada , Smeyers Dura Patricia , Monfort‐Membrado Sandra , Pitarch‐Castellano Inmaculada , Martínez‐Castellano Francisco 
Published: November 2021

AbstractIMMTgene codes for mitofilin, a mitochondrial inner membrane protein that regulates the morphology of mitochondrial cristae. The phenotype associated with mutations in this gene has not been yet established, but functional studies carried out show that its loss causes a mitochondrial alteration, both in the morphology of the mitochondrial crests and in their function. We present two cousins from an extended highly consanguineous family with developmental encephalopathy, hypotonia, nystagmus due to optic neuropathy. The likely pathogenic homozygous c.895A>G (p.Lys299Glu) variant in theIMMTgene co‐segregates with the disease and associates altered mitochondrial cristae observed by electron microscopy.
Geometric Sample Reweighting for Monte Carlo Integration
Authors: Guo J. , Eisemann E. 
Published: November 2021

AbstractNumerical integration is fundamental in multiple Monte Carlo rendering problems. We present a sample reweighting scheme, including underlying theory, and analysis of numerical performance for the integration of an unknown one‐dimensional function. Our method is simple to implement and builds upon the insight to link the weights to a function reconstruction process during integration. We provide proof that our solution is unbiased in one‐dimensional cases and consistent in multi‐dimensional cases. We illustrate its effectiveness in several use cases.
Luminance Attentive Networks for HDR Image and Panorama Reconstruction
Authors: Yu Hanning , Liu Wentao , Long Chengjiang , Dong Bo , Zou Qin , Xiao Chunxia 
Published: November 2021

AbstractIt is very challenging to reconstruct a high dynamic range (HDR) from a low dynamic range (LDR) image as an ill‐posed problem. This paper proposes a luminance attentive network named LANet for HDR reconstruction from a single LDR image. Our method is based on two fundamental observations: (1) HDR images stored in relative luminance are scale‐invariant, which means the HDR images will hold the same information when multiplied by any positive real number. Based on this observation, we propose a novel normalization method called “HDR calibration“for HDR images stored in relative luminance, calibrating HDR images into a similar luminance scale according to the LDR images. (2) The main difference between HDR images and LDR images is in under‐/over‐exposed areas, especially those highlighted. Following this observation, we propose a luminance attention module with a two‐stream structure for LANet to pay more attention to the under‐/over‐exposed areas. In addition, we propose an extended network called panoLANet for HDR panorama reconstruction from an LDR panorama and build a dualnet structure for panoLANet to solve the distortion problem caused by the equirectangular panorama. Extensive experiments show that our proposed approach LANet can reconstruct visually convincing HDR images and demonstrate its superiority over state‐of‐the‐art approaches in terms of all metrics in inverse tone mapping. The image‐based lighting application with our proposed panoLANet also demonstrates that our method can simulate natural scene lighting using only LDR panorama. Our source code is available athttps://github.com/LWT3437/LANet.