bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectral Interferences Impede the High-Resolution Mass Analysis of Recombinant Adeno-Associated Viruses
Authors: Yin Victor , Devine Paul W.A. , Saunders Janet C. , Hines Alistair , Shepherd Sam , Dembek Marcin , Dobson Claire L. , Snijder Joost , Bond Nicholas J. , Heck Albert J.R. 
Published: August 2022

AbstractRecombinant adeno-associated viruses (rAAVs) are the leading platform for in vivo delivery of gene therapies, with several already approved for clinical use. However, the heterogeneity and structural complexity of these viral particles render them challenging targets to characterize. Orbitrap-based native mass spectrometry (MS) is a method capable of directly characterizing intact megadalton protein assemblies. Here we used such an approach to characterize four different preparations of rAAV8 (two empty and two filled) differing in both their transgene and relative capsid protein isoform (i.e. VP1, VP2 and VP3) content. Interestingly, in native MS measurements of these samples, we observe complicated, unusual, and dramatically different spectral appearances between the four rAAV preparations that cannot be rationalized or interpreted using conventional approaches (i.e. charge state deconvolution). By combining high-resolution native MS, single particle charge detection MS, and spectral simulations, we reveal that these unexpected features result from a combination of stochastic assembly-induced heterogeneity and divergent gas phase charging behaviour between the four rAAV preparations. Our results stress the often-neglected heterogeneity of rAAVs, but also highlight the pitfalls of standard high-resolution mass analysis for such particles. Finally, we show that charge detection MS and spectral simulations can be used to tackle these challenges.
A Different Kind of Restraint Suitable for Molecular Dynamics Simulations
Authors: Kolossváry István , Sherman Woody 
Published: August 2022

AbstractConformational sampling of complex biomolecules is an emerging frontier in drug discovery. Indeed, advances in lab-based structural biology and related computational approaches like AlphaFold have made great strides in obtaining static protein structures. However, biology is in constant motion and many important biological processes rely on conformationally-driven events. Unrestrained molecular dynamics (MD) simulations require that the simulated time be comparable to the real time of the biological processes of interest, rendering pure MD impractical for many drug design projects, where conformationally-driven biological events can take microseconds to milliseconds or longer. An alternative approach is to accelerate the sampling of specific motions by applying restraints, guided by insights about the underlying biological process of interest. A plethora of restraints exist to limit the size of conformational search space, although each has drawbacks when simulating complex biological motions. In this work, we introduce a new kind of restraint for molecular dynamics simulations (MD) that is particularly well suited for complex conformationallydriven biological events, such as protein-ligand binding, allosteric modulations, conformational signalling, and membrane permeability. The new restraint, which relies on a barrier function (the scaled reciprocal function) is particularly beneficial to MD, where hard-wall restraints are needed with zero tolerance to restraint violation. We have implemented this restraint within a hybrid sampling framework that combines metadynamics and extended-Lagrangian adaptive biasing force (meta-eABF). We use two particular examples to demonstrate the value of this approach: (1) quantification of the approach of E3-loaded ubiquitin to a protein of interest as part of the Cullin ring ligase and (2) membrane permeability of heterobi-functional degrader molecules with a large degree of conformational flexibility. Future work will involve extension to additional systems and benchmarking of this approach compared with other methods.
Refining integrated thinking
Authors: Maroun Warren , Ecim Dusan , Cerbone Dannielle 
Published: August 2022

Purpose
Integrated thinking involves a holistic, multi-capital approach to decision-making and operations to promote value creation and sustainability. This paper aims to outline a schematic which can be used to gauge the levels of integrated thinking by organisations.

Design/methodology/approach
The researchers partnered with an independent consulting firm (“Sustain-X”) which has developed a tool for evaluating integrated thinking. A two-stage mixed-method design is used to evaluate the tool. Firstly, in keeping with the exploratory nature of the paper, the tool’s integrated thinking principles and indicators are contrasted with findings from an extensive review of the integrated thinking research and interviews with experts on how integrated thinking is understood and operationalised. Secondly, the tool was applied to a sample of South African listed firms’ integrated reports and used to generate integrated thinking scores. These scores are evaluated by testing the strength of their association with other generally accepted proxies for integrated thinking.

Findings
The principles of the schematic include integrated awareness and understanding; integrated leadership commitment and capability; integrated structures; integrated organisational performance management; and integrated external communication. Empirical results show that the integrated thinking measures generated using the Sustain-X schematic are aligned with integrated report quality scores and ratings of the sophistication of organisations’ accounting, management and governance structures.

Research limitations/implications
A combination of earlier research findings, detailed interviews (conducted independently of Sustain-X) and a battery of quantitative tests have been used to evaluate the schematic, but more refined testing using additional case studies or ethnographies has been deferred.

Practical implications
The tool offers a practical means for stakeholders to evaluate integrated thinking. It is flexible enough to be used with data collected during private engagements with companies or only publicly available information.

Social implications
The schematic is one of the first to outline the dimensions of integrated thinking and should be useful for academics and practitioners concerned with the development and application of integrated thinking.

Originality/value
This paper adds to the literature on integrated thinking and answers the call for further research to evaluate integrated thinking practices.
Impact of share pledging by controlling shareholders on firm value in the context of China's tightened regulatory reforms
Authors: Su Zili , Alexiou Constantinos 
Published: August 2022

AbstractThis study investigates the effect of the 2018 regulatory reforms of share pledging by a controlling shareholder on firm value in China. Using a dataset spanning the period 2015 to 2020, we provide robust results suggesting that tighter regulations effectively reduce firms' crash risk, relax financial constraints, reduce bankruptcy risk, and mitigate the controlling shareholder expropriation of minority shareholders' wealth via tunnelling. Additionally, controlling shareholders, by investing more pledged funds in the listed firm after reforms, foster capital investment and R&D expenditure, which benefit firm growth and competitiveness and ultimately increase firm long‐term value.
Why do bank‐affiliated mutual funds perform better in China?
Authors: Zhang Haoyue , Lv Dayong , Wu Wenfeng 
Published: August 2022

AbstractPrior literature documents that bank‐affiliated mutual funds underperform unaffiliated funds in developed markets. Using data from the Chinese mutual fund market from 2005 to 2020, we find that Chinese bank‐affiliated funds outperform unaffiliated funds by about 2.63 percent per year. In addition, our results show that bank‐affiliated fund managers have superior active management and better stock‐picking skills, which is preliminarily related to the motivational compensation policies from fund companies and the slight redemption pressure from investors. However, we find no evidence for the potential information advantage of bank‐affiliated funds. Our findings have important implications for fund companies and investors.
Impact of contracted endodontic cavities on instrumentation efficacy—A systematic review
Authors: Shroff Manan , Kishan Karkala Venkappa , Shah Nimisha , Saklecha Purnima 
Published: August 2022

AbstractThe aim of the present systematic review was to summarise and evaluate the studies comparing the role of contracted endodontic cavities (CECs) and traditional endodontic cavities (TECs) in terms of instrumentation efficacy. The present systematic review comprised of a search of the online databases of Cochrane, PubMed, Google Scholar and grey literature. The articles which were pertaining to instrumentation efficacy in contracted and traditional endodontic cavities were selected based on the PRISMA checklist. Out of the 660 articles which were obtained, irrelevant articles were excluded and a total of 17 articles were selected for this systematic review which assessed the instrumentation efficacy. Eleven studies compared the volume of dentin removed and canal transportation ability. Four studies compared the pulp debridement, and two studies compared the anti‐bacterial efficacy between the two groups. The extrusion of debris between the groups was compared by one study. Out of the 17 studies included, 11 studies proved that contracted endodontic cavities negatively impacted the instrumentation efficacy. Hence, the data suggest that the traditional endodontic access cavities have better results when comparing the instrumentation efficacy.
Light and electron microscopic studies on the influence of stress on prolactin‐immunoreactivity in rat anterior pituitary lobe
Authors: Prohaska Antje , Jirikowski Gustav F. , Oehring Hartmut , el Emam Dief Abeer , Sivukhina Elena V. 
Published: August 2022

AbstractAn increasing number of evidence suggests an important role of prolactin in the modulation of stress response. However, the mechanisms of its action on the HPA axis are not yet understood. Glucocorticoids, liberated from adrenal cortex due to hormonal signals from pituitary corticotrophs are known to play a key role in systemic stress response. Previously we found evidence that corticosteroid‐binding globulin (CBG) is involved in rapid, membrane‐mediated actions of adrenal steroids. Here we studied qualitatively immunostainings for prolactin and CBG in pituitaries of male rats that had been subjected to osmotic challenge. We also examined late pregnant, parturient and early lactating rats, assuming that parturition represents a strong physiological stress. We employed double immunofluorescencent staining of semithin sections and immunoelectron microscopy. In stressed males we found increased prolactin immunofluorescence associated with membranes while in controls this staining was predominantly cytoplasmatic. CBG immunofluorescence was found in almost all prolactin cells of stressed males while such double staining was only occasionally observed in controls. Similar observations were made in females: While parturient rats showed intense membrane associated double staining for both antigens, late pregnant and early lactating animals showed patterns similar to that of male controls. Immunoelectron microscopy revealed increased exocytosis of prolactin containing vesicles in lactating rats. CBG was localized on cell membranes and additionally within prolactin vesicles. Our observations suggest prolactin liberation from pituitary lactotrophs along with CBG upon systemic stress response. Membrane effects of glucocorticoids mediated by CBG may be linked to stimulus secretion of prolactin.
Expression of the pro‐inflammatory P2Y14 receptor in the non‐vasectomized and vasectomized human epididymis
Authors: Belardin Larissa Berloffa , Légaré Christine , Sullivan Robert , Belleannée Clémence , Breton Sylvie 
Published: August 2022

AbstractBackgroundVasectomy causes spermatozoa accumulation in the epididymis, which may cause epididymitis. Inflammation is triggered by alert molecules released following tissue stress or injury. These include uracil‐diphosphate glucose (UDP)‐glucose, which activates the pro‐inflammatory P2Y14 receptor (P2Y14), and induces immune cell recruitment. However, little is known about P2Y14 in the epididymis and its potential activation following vasectomy.Objectives(i) To localize P2Y14 in the human excurrent duct; and (ii) to examine the effect of vasectomy on P2Y14 protein and P2RY14 mRNA content, the production of selected cytokines and chemokines, and immune cell recruitment in the epididymis.Material and methodsIn situ hybridization, qRT‐PCR, western blotting, immunohistochemistry, and immunofluorescence were performed in banked human epididymis samples.ResultsP2RY14 mRNA and P2Y14 protein were detected in epithelial cells in the efferent duct, epididymis and vas deferens in non‐vasectomized men. Keratin 5 (KRT5)‐positive basal cells were strongly labeled for P2Y14 in all epididymal segments. A progressive apical localization was detected in principal cells (negative for the proton pump V‐ATPase) from the corpus to the cauda. A subset of V‐ATPase‐positive clear cells also showed strong P2Y14 labeling. Vasectomy induced an increase in P2RY14 mRNA in the corpus and cauda, and stronger apical labeling in principal cells in the corpus. CXCL10 mRNA increased in the cauda and CCL2 mRNA decreased in the corpus of vasectomized versus non‐vasectomized men. No change in IL‐8 and IL‐1β mRNA was detected. Numerous CD45+ leukocytes were detected in the interstitium of the corpus and cauda following vasectomy, while only a few were seen in non‐vasectomized men. Several CD45+ leukocytes, some of which containing spermatozoa, were detected in the corpus lumen following vasectomy.Discussion and conclusionOur study indicates that vasectomy‐induced spermatozoa congestion may lead to an inflamed‐prone local environment characterized by potential activation of P2Y14 and recruitment of immune cells in the epididymis.
Traction force profile in children with severe perinatal outcomes delivered with a digital vacuum extraction handle: A case–control study
Authors: Romero Stefhanie , Pettersson Kristina , Yousaf Khurram , Westgren Magnus , Ajne Gunilla 
Published: August 2022

AbstractIntroductionDuring the second stage of labor, vacuum‐assisted delivery is an alternative to forceps delivery and emergency cesarean section. Extensive research concerning perinatal outcomes has indicated that the risk of complications, although rare, is higher than with a spontaneous vaginal delivery. An important factor related to perinatal outcomes is the traction force applied. Our research group previously developed a digital extraction handle, the Vacuum Intelligent Handle‐3 (VIH3), that measures and records traction force. The objective of this study was to compare traction force profiles in children with and without severe perinatal outcomes delivered with the digital handle. A secondary aim was to establish a safe force limit.Material and MethodsThis was an observational case–control study at the delivery ward at Karolinska University Hospital, Sweden. In total, 573 children delivered with the digital handle between 2012 and 2018 were included. Cases were defined as a composite of severe perinatal outcomes, including subgaleal hematoma, intracranial hemorrhage, hypoxic ischemic encephalopathy 1–3, seizures or death. The cases in the cohort were matched 1:3 based on five matching variables. Traction profiles were analyzed using the MATLAB® software and conditional logistic regression.ResultsThe incidence of severe perinatal outcomes was 2.3%. The 13 cases were matched with three controls each (n = 39). A statistically significant increased odds for higher total traction forces was seen in the case group (odds ratio [OR] 1.004; 95% confidence interval [CI] 1.001–1.007) and for the peak force (OR 1.022; 95% CI 1.004–1.041). Several procedure‐related parameters were significantly increased in the case group. As expected, some neonatal characteristics also differed significantly. An upper force limit of 343 Newton minutes (Nmin) revealed an 86% reduction in severe perinatal outcomes (adjusted OR 0.14; 95% CI 0.04–0.5).ConclusionsChildren with severe perinatal outcomes had traction force profiles with significantly higher forces. The odds for severe perinatal outcomes increased for every increase in Nmin and Newton used during the extraction procedure. A calculated total force level of 343 Nmin is suggested as an upper safety limit, but this must be tested prospectively to provide validity.
Multisystem inflammatory syndrome in the context of paediatric COVID‐19 infection in the Republic of Ireland April 2020 to April 2021
Authors: Treston Bryony , Petty‐Saphon Naomi , Collins Abigail , Murray Sarah , Colgan Aoife , Fitzgerald Eoin , Hassan Mahmoud , Forde Karina , O'Farrell Anne , Sayers Gerardine , Linnane Niall , Franklin Orla , McMahon Colin , Leahy Timothy R. , Gavin Patrick 
Published: August 2022

AbstractAimOur aim was to describe the epidemiology of multisystem inflammatory syndrome in children (MIS‐C) in the Republic of Ireland, in the context of all cases of COVID‐19 in children, during the first year of the SARS‐CoV‐2 pandemic.MethodsCases of MIS‐C were identified by prospective surveillance in Irish hospitals from April 2020 to April 2021. Paediatric COVID‐19 cases and outbreaks in schools or childcare facilities were notified to and routinely investigated by Public Health. Univariate and bivariate analyses were carried out in Excel, Stata and JMP statistical package.ResultsFifty‐four MIS‐C cases (median age 7.58 years; males 57%) were identified over the study period. MIS‐C incidence was higher in certain ethnicities (‘black’ 21.3/100,000 [95% CI 4.3–38.4]; and ‘Irish Traveller’ 14.7/100,000 [95% CI −5.7‐35.1]) than those of ‘white’ ethnicity (3.4 /100,000). MIS‐C cases occurred in three temporal clusters, which followed three distinct waves of community COVID‐19 infection, irrespective of school closures. Formal contact tracing identified an epidemiological link with a COVID‐19‐infected family member in the majority of MIS‐C cases (77%). In contrast, investigation of COVID‐19 school outbreaks demonstrated no epidemiological link with MIS‐C cases during the study period.ConclusionEfforts at controlling SARS‐CoV‐2 transmission in the community may be a more effective means to reduce MIS‐C incidence than school closures. Establishing a mandatory reporting structure for MIS‐C will help delineate the role of risk factors such as ethnicity and obesity and the effect of vaccination on MIS‐C incidence.
Diagnostic utility of SOX10 immunostaining in benign lichenoid keratosis: A study of 21 cases
Authors: Levett Kaitlyn , Siatecka Hanna , Diwan A. Hafeez , Krishnan Bhuvaneswari , Huttenbach Yve T. 
Published: August 2022

AbstractBackgroundBenign lichenoid keratosis (BLK) is a cutaneous lesion that can clinically mimic malignancy and may represent regression of a pre‐existing lesion. BLK may show epidermal pseudo‐nests prompting evaluation for a melanocytic lesion. False positivity of MART‐1/Melan‐A immunostaining in pseudonests has been showed; however, the value of SRY‐related HMG‐box 10 (SOX10) staining in BLK with features suspicious for a melanocytic proliferation has not been previously reported.MethodsTwenty‐one cases of BLK from 2015 to 2020 were identified. Slides were reviewed and SOX10 immunohistochemistry was performed on each case. Subsequently, Melan‐A immunohistochemical staining was performed on all cases.ResultsIn 10 cases (47.6%), unexpected SOX10 staining was seen in rare to numerous small, single cells in the epidermis above the basal cell layer. No malignancy was identified. Of the 10 cases, 8 (80%) showed suprabasal SOX10 staining did not show similar suprabasal Melan‐A staining; 2 (20%) cases showed scattered suprabasal cells positive for Melan‐A.ConclusionSOX10 immunostaining in BLK can highlight scattered cells in the epidermis (not easily noticeable on routine stain). Performing SOX10 immunostain alone on BLK can prompt a misdiagnosis of a melanocytic lesion and should be done with caution.
Relational thinking: An overlooked component of executive functioning
Authors: Starr Ariel , Leib Elena R. , Younger Jessica W. ,   Project iLead Consortium, Uncapher Melina R. , Bunge Silvia A. 
Published: August 2022

AbstractRelational thinking, the ability to represent abstract, generalizable relations, is a core component of reasoning and human cognition. Relational thinking contributes to fluid reasoning and academic achievement, particularly in the domain of math. However, due to the complex nature of many fluid reasoning tasks, it has been difficult to determine the degree to which relational thinking has a separable role from the cognitive processes collectively known as executive functions (EFs). Here, we used a simplified reasoning task to better understand how relational thinking contributes to math achievement in a large, diverse sample of elementary and middle school students (N = 942). Students also performed a set of ten adaptive EF assessments, as well as tests of math fluency and fraction magnitude comparison. We found that relational thinking was significantly correlated with each of the three EF composite scores previously derived from this dataset, albeit no more strongly than they were with each other. Further, relational thinking predicted unique variance in students’ math fluency and fraction magnitude comparison scores over and above the three EF composites. Thus, we propose that relational thinking be considered an EF in its own right as one of the core, mid‐level cognitive abilities that supports cognition and goal‐directed behavior.Research Highlights
Relational thinking, the process of identifying and integrating relations, develops over childhood and is central to reasoning.
We collected data from nearly 1000 elementary and middle schoolers on a test of relational thinking, ten standard executive function tasks, and two math tests.
Relational thinking predicts unique variance in math achievement not accounted for by canonical EFs throughout middle childhood.
We propose that relational thinking should be conceptualized as a core executive function that supports cognitive development and learning.