bluuebunny/crossref_metadata_2025 huggingface dataset:
BRG1 generates subnucleosomes that expand OCT4 binding and function beyond DNA motifs at enhancers
Authors: Nocente Marina C. , Karamitsos Anida Mesihovic , Drouineau Emilie , Albawardi Waad , Dulary Cécile , Ribierre Florence , Picaud Hélène , Alibert Olivier , Acker Joël , Aude Jean-Christophe , Gilbert Nick , Ochsenbein Françoise , Chantalat Sophie , Gérard Matthieu
Published: September 2022

BRG1, the catalytic subunit of the mammalian SWI/SNF complexes, is essential for chromatin opening at enhancers. However, the nature of the open chromatin remains unclear. Here we show that in addition to producing histone-free DNA, BRG1 generates hemisome-like subnucleosomal particles containing the four core histones associated with 50-80 base pairs of DNA. Our genome-wide analysis indicates that BRG1 makes these particles by targeting and splitting fragile nucleosomes. In mouse embryonic stem cells, these subnucleosomes become anin vivobinding substrate for the master transcription factor OCT4 independently of the presence of OCT4 DNA motifs. At enhancers, the OCT4-subnucleosome interaction increases OCT4 occupancy and amplifies the genomic interval bound by OCT4 by up to one order of magnitude, compared to the region occupied on histone-free DNA. We suggest that BRG1-dependent subnucleosomes orchestrate an epigenetic mechanism that projects OCT4 function in chromatin opening beyond its DNA motifs.
Polar Crystal Habit and 3D Electron Diffraction Reveal the Malaria Pigment Hemozoin as a Selective Mixture of Centrosymmetric and Chiral Stereoisomers
Authors: Klar Paul Benjamin , Waterman David , Gruene Tim , Mullick Debakshi , Song Yun , Gilchrist James B. , Owen C. David , Wen Wen , Biran Idan , Houben Lothar , Regev-Rudzki Neta , Dzikowski Ron , Marom Noa , Palatinus Lukas , Zhang Peijun , Leiserowitz Leslie , Elbaum Michael
Published: September 2022

Detoxification of heme in Plasmodium depends on its crystallization into hemozoin. This pathway is a major target of antimalarial drugs. X-ray powder diffraction has established that the unit cell contains a cyclic hematin dimer, yet the pro-chiral nature of heme supports formation of four distinct stereoisomers, two centrosymmetric and two chiral enantiomers. Here we apply emerging methods of in situ cryo-electron tomography and diffraction to obtain a definitive structure of biogenic hemozoin. Individual crystals take a striking polar morphology. Diffraction analysis, supported by density functional theory, indicates a compositional mixture of one centrosymmetric and one chiral dimer, whose absolute configuration has been determined on the basis of crystal morphology and interaction with the aqueous medium. Structural modeling of the heme detoxification protein suggests a mechanism for dimer selection. The refined structure of hemozoin should serve as a guide to new drug development.
A new technology for isolating organellar membranes provides fingerprints of lipid bilayer stress
Authors: Reinhard John , Starke Leonhard , Klose Christian , Haberkant Per , Hammarén Henrik , Stein Frank , Klein Ofir , Berhorst Charlotte , Stumpf Heike , Sáenz James P. , Hub Jochen , Schuldiner Maya , Ernst Robert
Published: September 2022

Biological membranes have a stunning ability to adapt their composition in response to physiological stress and metabolic challenges. Little is known how such perturbations affect individual organelles in eukaryotic cells. Pioneering work provided insights into the subcellular distribution of lipids, but the composition of the endoplasmic reticulum (ER) membrane, which also crucially regulates lipid metabolism and the unfolded protein response, remained insufficiently characterized. Here we describe a method for purifying organellar membranes from yeast, MemPrep. We demonstrate the purity of our ER preparations by quantitative proteomics and document the general utility of MemPrep by isolating vacuolar membranes. Quantitative lipidomics establishes the lipid composition of the ER and the vacuolar membrane. Our findings have important implications for understanding the role of lipids in membrane protein insertion, folding, and their sorting along the secretory pathway. Application of the combined preparative and analytical platform to acutely stressed cells reveals dynamic ER membrane remodeling and establishes molecular fingerprints of lipid bilayer stress.
A network of Notch-dependent and -independent her genes controls neural stem and progenitor cells in the zebrafish thalamic proliferation zone
Authors: Sigloch Christian E. , Spitz Dominik , Driever Wolfgang
Published: September 2022

Neural proliferation zones mediate brain growth, and employ Delta/Notch signaling and HES/HER transcription factors to balance neural stem cell (NSC) maintenance and generation of progenitors and neurons. We investigated Notch-dependency and function of her genes in the thalamic proliferation zone of developing zebrafish larvae. Nine Notch-dependent genes, her2, her4.1-5, her12, her15.1-2, and two Notch-independent genes, her6, her9, are differentially expressed, and define distinct NSC and progenitor populations. her6 prominently executes patterning information to maintain NSCs and the zona limitans intrathalamica Shh signaling activity. her6, her9 double mutants reveal that Notch-independent her genes predominantly regulate NSC maintenance and transition into the progenitor pool. Surprisingly, combined deletion of all Notch-dependent her genes does not affect NSCs or progenitor formation. Combined genetic manipulation of up to eleven Notch-dependent and -independent her genes revealed that Notch-dependent her genes may regulate progenitor progression into neurogenesis, but not progenitor generation itself. The her gene network is partially redundant, with Notch-independent her genes better substituting for loss of Notch-dependent genes than vice versa. Together, her gene regulatory feedback loops and crossregulation contribute to the observed robustness of NSC maintenance.
The genome sequence of the Lumpy Skin Disease virus from the outbreak in India suggests a distinct lineage of the virus
Authors: Bhatt Lenin , Bhoyar Rahul C. , Jolly Bani , Israni Ravi , Vignesh Harie , Scaria Vinod , Sivasubbu Sridhar
Published: September 2022

Although previously confined to regions within Africa, Lumpy Skin Disease Virus (LSDV) infections have caused significantly large outbreaks in several regions of the world in very recent years. In 2019, an outbreak of the disease was reported from India with low rates of morbidity and no reported mortality. However, in 2022, an ongoing outbreak of LSDV spanning over 7 states in India resulted in a reported mortality of over 80,000 cattle over a short period of three months. Here, we report complete genome sequences of 6 viral isolates of LSDV collected from affected cattle during an ongoing outbreak of the disease in Rajasthan, India. Analysis of the viral sequences suggests the genomes from the 2022 outbreak harbour a large number of genetic variations compared to the reference genome and form a distinct lineage. This report also highlights the importance of genome sequencing and surveillance of transboundary infectious agents and genomic characterisation of outbreaks.
Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates
Authors: Ranganathan Srivastav , Dasmeh Pouria , Furniss Seth , Shakhnovich Eugene
Published: September 2022

Assemblies of multivalent RNA-binding protein FUS can exist in the functional liquid-like state as well as less dynamic and potentially toxic amyloid- and hydrogel-like states. How could then cells form liquid-like condensates while avoiding their transformation to amyloids? Here we show how post-translational phosphorylation can provide a “handle” that prevents liquid-solid transition of intracellular condensates containing FUS. Using residue-specific coarse-grained simulations, for 85 different mammalian FUS sequences, we show how the number of phosphorylation sites and their spatial arrangement affect intracluster dynamics preventing conversion to amyloids. All atom simulations further confirm that phosphorylation can effectively reduce the β-sheet propensity in amyloid-prone fragments of FUS. A detailed evolutionary analysis shows that mammalian FUS PLDs are enriched in amyloid-prone stretches compared to control neutrally evolved sequences suggesting that mammalian FUS proteins evolved to self-assemble. However, in stark contrast to proteins that do not phase-separate for their function, mammalian sequences have phosphosites in close proximity to these amyloid-prone regions. These results suggest that evolution uses amyloid-prone sequences in prion-like domains to enhance phase-separation of condensate proteins while enriching phosphorylation sites in close proximity to safe-guard against liquid-solid transitions.

Significance Statement

Intrinsically disordered regions and prion-like domains are widely observed in proteins that get enriched in membrane-less organelles (MLOs). Mammalian Fused in Sarcoma (FUS) sequences are significantly enriched in amyloid-prone sequences suggesting that they have evolved to self-assemble. While the amyloid-prone stretches promote self-assembly of these proteins at lower threshold concentrations, these assemblies are vulnerable to aberrant liquid-solid phase transitions. Molecular simulations and bioinformatics analyses show that evolution overcomes this challenge by placing phosphosites specifically close to amyloid-prone stretches. Introduction of negatively charged residues at phosphosite locations results in fewer amyloid-prone contacts and thereby lower beta-sheet propensity. Phosphorylation can thus allow cells to utilize amyloid-prone stretches to promote biogenesis of MLOs while protecting against liquid-solid transitions.
Comprehensive re-analysis of hairpin RNAs in fungi reveals ancestral links
Authors: Johnson Nathan R. , Larrondo Luis F. , Álvarez José M. , Vidal Elena A.
Published: September 2022

RNA interference is an ancient mechanism with many regulatory roles in eukaryotic genomes, with small RNAs acting as their functional element. While there is a wide array of classes of small-RNA-producing loci, those resulting from stem-loop structures (hairpins) have received profuse attention. Such is the case of microRNAs (miRNAs), which have distinct roles in plants and animals. Fungi also produce small RNAs, and several publications have identified miRNAs and miRNA-like (mi/milRNA) hairpin RNAs in diverse fungal species using deep sequencing technologies. Despite this relevant source of information, relatively little is known about mi/milRNA-like features in fungi, mostly due to a lack of established criteria for their annotation. To systematically assess mi/miRNA-like characteristics and annotation confidence, we searched for publications describing mi/milRNA loci and re-assessed the annotations for 40 fungal species. We extracted and normalized the annotation data for 1,677 reported mi/milRNA-like loci and determined their abundance profiles, concluding that less than half of the reported loci passed basic standards used for hairpin RNA discovery. We found that fungal mi/milRNA are generally more similar in size to animal miRNAs and were frequently associated with protein-coding genes. The compiled genomic analyses identified 18 mi/milRNA loci conserved in multiple species. Our pipeline allowed us to build a general hierarchy of locus quality, identifying around 200 loci with high-quality annotations. We provide a centralized annotation of identified mi/milRNA hairpin RNAs in fungi which will serve as a resource for future research and advance in understanding the characteristics and functions of mi/milRNAs in fungal organisms.
Emergence of plasmid-mediated RND-type efflux pump gene cluster tmexCD-toprJ in Shewanella xiamenensis in a water environment
Authors: Dao Trung Duc , Takemura Taichiro , Kasuga Ikuro , Hirabayashi Aki , Nga Nguyen Thi , Anh Pham Hong Quynh , Tu Nguyen Dong , Trang Le Thi , Tran Hoang Huy , Shibayama Keigo , Hasebe Futoshi , Suzuki Masato
Published: September 2022

The emergence of the mobile resistance-nodulation-division (RND)-type efflux pump tmexCD-toprJ gene cluster that confers multidrug resistance (MDR), including tigecycline resistance, in gram-negative bacteria poses a global public health threat. However, the spread of such clinically important antimicrobial resistance genes (ARGs) in the natural environment has not yet been well investigated. In this study, we investigated MDR aquatic bacteria in Vietnam. A carbapenem- and tigecycline-resistant Shewanella xiamenensis isolate NUITM-VS2 was obtained from urban drainage in Hanoi, Vietnam, in October 2021. S. xiamenensis NUITM-VS2 showed resistance to most antimicrobials tested, including tigecycline, tetracyclines, carbapenems, cephalosporins, fluoroquinolone, and aminoglycosides. Whole-genome analysis was performed by long- and short-read sequencing, resulting in the complete genome sequence consisting of one chromosome and five plasmid sequences. ARGs and plasmid replicons in the genome were detected using ResFinder with the custom ARG database, including all known tigecycline resistance genes, and PlasmidFinder, respectively. A 152.2-kb IncC plasmid, pNUITM-VS2_2, co-carried two mobile tigecycline resistance genes, tet(X4) and tmexC3.2D3.2-toprJ1. In addition, a 24.8-kb untypeable plasmid, pNUITM-VS2_4, carried the carbapenemase gene blaNDM-1. pNUITM-VS2_2 was transferred to Escherichia coli by conjugation, which simultaneously conferred high-level resistance against many antimicrobials, including tigecycline. To the best of our knowledge, this is the first report of the detection of the mobile RND-type efflux pump gene cluster tmexCD-toprJ in Shewanella species. Our results provide genetic evidence of the complexity of the dynamics of clinically important ARGs among aquatic bacteria, which could be important reservoirs for ARGs in the natural environment.
The patterned assembly and stepwise Vps4-mediated disassembly of composite ESCRT-III polymers drives archaeal cell division
Authors: Hurtig Fredrik , Burgers Thomas C.Q. , Cezanne Alice , Jiang Xiuyun , Mol Frank Nico , Traparić Jovan , Tarrason-Risa Gabriel , Pulschen Andre Arashiro , Harker-Kirschneck Lena , Šarić Anđela , Vlijm Rifka , Baum Buzz
Published: September 2022

ESCRT-III family proteins form composite polymers that deform and cut membrane tubes in the context of a wide range of cell biological processes across the tree of life. In reconstituted systems sequential changes in the composition of ESCRT-III polymers induced by the AAA ATPase Vps4 have been shown to remodel membranes. However, it is not known how composite ESCRT-III polymers are organised and remodelled in space and time in cells. Here, taking advantage of the relative simplicity of the ESCRT-III-dependent division system in Sulfolobus acidocaldarius, one of the closest experimentally tractable prokaryotic relative of eukaryotes, we use super-resolution microscopy and computational modelling to show how CdvB/CdvB1/CdvB2 proteins form a precisely patterned composite ESCRT-III division ring which undergoes stepwise Vps4-dependent disassembly and contracts to cut cells into two. These observations lead us to suggest sequential changes in a patterned composite polymer as a general mechanism of ESCRT-III-dependent membrane remodelling.
Performance implications of peer monitoring among suppliers
Authors: Hu Qinfang , Hu Jing , Yang Zhilin
Published: September 2022

Purpose

What are the performance implications of peer monitoring in a multiple-supplier context? Grounded in agency and social exchange theories, this study aims to examine how, when, and why peer monitoring works as a crucial control mechanism to reduce opportunism among suppliers.

Design/methodology/approach

A conceptual model and research hypotheses are tested using survey data from 246 respondents in 82 supplier groups.

Findings

Results suggest that peer monitoring is related positively to perceived deterrence (as mediator) and negatively to opportunism, whereas the mediated relationship is moderated negatively by generalized reciprocity and positively by balanced reciprocity and negative reciprocity.

Originality/value

This study introduces the application of peer monitoring into business-to-business research and shows how it reduces opportunism. Its findings have implications for manufacturers on how to use peer monitoring to control opportunism among multiple suppliers.
Reflective and composite scales in tourism and hospitality research: revising the scale development procedure
Authors: Rasoolimanesh S. Mostafa , Ali Faizan , Mikulić Josip , Dogan Seden
Published: September 2022

Purpose

The purpose of this paper is to critically review and synthesize the scale development practices in hospitality and tourism and propose updated guidelines applicable for both reflective and composite scales.

Design/methodology/approach

Using a critical review of a sample of scale development papers published in six top-tier tourism and hospitality journals, the current guidelines' weaknesses and strengths and their applications are identified. Updated procedures are proposed to overcome these weaknesses.

Findings

This review showed several issues in applying existing guidelines, including incomplete and unclear data collection processes, inconsistent data analysis processes including validity/reliability assessment and lack of criteria to identify and assess composite scales. As such, this paper proposes updated guidelines by incorporating the confirmatory composite analysis to assess composite scales.

Originality/value

This paper offers unique theoretical and methodological contributions to scale development literature, by identifying the shortcomings of current practices of scale development and propose guidelines for both reflective and composite scales. The current scale development procedures cannot be applied for composite scales, and so the results of composite scale development using the current procedures are questionable. The updated guidelines by the current study improve new scales' accuracy, reliability and validity.
Teaching a Lean masterclass in the metaverse
Authors: Hines Peter , Netland Torbjørn H.
Published: September 2022

Purpose

This paper reports exploratory findings about teaching in the metaverse using a virtual reality (VR) platform and head-mounted displays. This paper addresses three research questions: Is the metaverse an appropriate platform for teaching Lean? What are the benefits and problems of this approach over traditional classroom methods? What are the future implications for teaching Lean in the VR-enabled metaverse?

Design/methodology/approach

The research presented in this paper is exploratory. A critical realism approach is adopted using action research through the preparation, delivery and review of the first four masterclasses entitled Leading Intelligent Lean offered by Gemba (formerly The Leadership Network). The data collection methods included a pre-workshop questionnaire, participant observation, focus groups and end-of-course surveys.

Findings

It was found that Lean can be taught successfully in the metaverse. There are many related benefits, particularly in terms of the high levels of immersion and the “wow” factor. Remaining technological limitations are reduced by continually improving the metaverse platform and the course content and delivery. The authors conclude that the metaverse is a useful addition to teaching Lean – and is especially promising when used in a blended teaching approach.

Originality/value

To the best of the authors’ knowledge, this is the first report of teaching Lean in a VR-enabled metaverse and one of the first of teaching and learning in the metaverse regardless of topic. The respective problems and benefits of this approach versus teaching in a traditional classroom setting are discussed.
Authentic leadership and employee voice behavior: the effect of Chinese employees' Zhongyong thinking
Authors: Kim Sunhyuk , Noh Grimm , Miao Siyu
Published: September 2022

Purpose

Employee voice behavior is an important source of corporate competitiveness but employees often face difficulties in voicing their opinions. This research analyzes how authentic leadership may increase psychological safety perceived by employees, consequently encouraging employees to actively share their ideas. In addition, the authors explore the unique concept of Zhongyong thinking, a way of thinking that is common in cultures rooted in Confucianism. The authors analyze how Zhongyong thinking may affect the relationship between psychological safety and employee voice behavior.

Design/methodology/approach

For the empirical analysis of authentic leadership and employee voice behavior in the Chinese context, the authors distributed surveys to employees working in various different industries in various provinces in China. The authors distributed 250 surveys in total and 213 surveys were used for analyses.

Findings

The authors' empirical analyzes illustrate that authentic leadership increases employee voice behavior, partially mediated by psychological safety. The authors also analyzed how psychological safety's effect on employee voice behavior could be moderated by Zhongyong thinking. The results demonstrate that the effect of psychological safety on voice behavior is weaker when employees are capable of exercising Zhongyong thinking.

Originality/value

Zhongyong thinking is still a relatively new concept that has not been studied thoroughly, and to the authors' knowledge, Zhongyong thinking has never been studied as a moderator in the relationship between psychological safety and employee voice behavior.
Integrated care with digital health innovation: pressing challenges
Authors: Pant Kanchan , Bhatia Meena , Pant Ranjan
Published: September 2022

Purpose

Digital health care has emerged as one of the most important means to deliver integrated care by care providers in recent years. As the use of digital health increases, there are some pressing issues such as interoperability of data across different healthcare information systems, regulatory environment and security and privacy of patient’s information which need to be discussed and addressed in order to reduce information silos and to ensure efficient and seamless use of digital health technologies. The purpose of this paper is to address these issues.

Design/methodology/approach

In this paper the authors outline the key concepts of interoperability, key challenges pertaining in achieving interoperability and concepts of security and privacy in context of digital health models of integrated care.

Findings

The study suggests that standardization of digital health information systems and connecting existing systems to health network, addressing privacy and security related issues through a comprehensive but supportive regulatory environment and educating citizens and healthcare providers are some of the ways to achieve effective use of digital health in models of integrated care.

Originality/value

Although the concepts of privacy and interoperability are not new, however, as per best of the authors’ knowledge, this is the first attempt to discuss the challenges and possible actions to meet the objective of achieving integrated care through digital innovation.
Does a Government Mandate Crowd Out Voluntary Corporate Social Responsibility? Evidence from India
Authors: RAJGOPAL SHIVARAM , TANTRI PRASANNA
Published: September 2022

This study investigates the implementation of a Government of India mandate that requires firms to spend at least 2% of their profits on corporate social responsibility (CSR). The results show that qualifying firms that voluntarily engaged in CSR before the mandate reduce their CSR spending afterward. Despite increasing advertisement expenditure likely to offset the lost signaling value of voluntary CSR, stock prices and operating performance of former voluntary CSR spenders who qualify under the law decline. Our results suggest that regulatory intervention in CSR can both diminish its signaling value and lead to a reduction in voluntary CSR spending.
Drivers of coffee liking: Effect of physicochemical characteristics and aromatic profile on consumers’ acceptability of mono‐origin and mono‐variety coffees
Authors: Condelli Nicola , Cela Nazarena , Di Cairano Maria , Scarpa Teresa , Milella Luigi , Ascrizzi Roberta , Flamini Guido , Galgano Fernanda
Published: September 2022

Few studies have investigated at the same time how physicochemical, volatile, and sensory characteristics affect coffee liking. The aim of this study is to evaluate the influence of geographical origin and variety on physicochemical parameters and volatile compounds composition of mono‐origin and mono‐variety coffees. Check‐all‐that‐apply (CATA) method was used with the aim of identifying the drivers of coffee liking. Moisture content, bulk density, solubility index, color parameters, and phenols and caffeine content were useful parameters for discriminating Robusta from Arabica variety, but not samples from different origins. The hierarchical cluster and principal component analyses performed on the headspace compositions showed a quite sharp ability to group the samples based on their variety. Based on CATA results, roasted attribute, related to the presence of pyrazines, was considered a positive driver of coffee liking unlike grassy and acidic attributes (associated to the presence of acids and aldehydes, respectively). Findings from this study can be a useful tool for coffee manufacturers for a winning market strategy, helping them in the choice of the most suitable raw materials and process conditions in order to produce a well‐balanced beverage by enhancing all the possible positive drivers of acceptability and reducing the negative ones.
Did the PCAOB's 2009 Office Expansion Improve Audit Quality?*
Authors: Blann James J. , Kleppe Tyler J. , Shipman Jonathan E.
Published: September 2022

We investigate whether the PCAOB's decision to expand the number and location of its inspection offices in 2009 improved the reliability of US audits. We use a difference‐in‐differences empirical design to consider the impacts of the expansion on audit quality and find that audit quality significantly improved following the PCAOB's expansion in markets where new offices opened relative to markets without an office opening. We find that the improvement in audit quality appears to be driven by auditors' reaction to real changes in PCAOB oversight and that triennially inspected auditors appear to be impacted the most by this office expansion. Our findings provide new insights into the PCAOB's operational decision‐making and suggest that the regulator's additional investment in audit oversight was effective in improving audit quality.
Saxagliptin alleviates erectile dysfunction through increasing stromal cell‐derived factor‐1 in diabetes mellitus
Authors: Sun Taotao , Xu Wenchao , Wang Jiaxin , Wang Tao , Wang Shaogang , Liu Kang , Liu Jihong
Published: September 2022

Background

Diabetes mellitus‐induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first‐line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase‐4 inhibitor (DPP‐4i), has been officially used in the treatment of type 2 diabetes. Stromal cell‐derived factor‐1 (SDF‐1) is one of the important substrates of DPP‐4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED.

Objectives

To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED.

Methods

The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into three groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF‐1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection.

Results

We found that erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP‐4 and increased level of SDF‐1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100.

Conclusion

Sax could alleviate DMED through increasing SDF‐1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP‐4 is may be beneficial to the management of DMED.
Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study
Authors: Sborov Douglas W. , Baljevic Muhamed , Reeves Brandi , Laubach Jacob , Efebera Yvonne A. , Rodriguez Cesar , Costa Luciano J. , Chari Ajai , Silbermann Rebecca , Holstein Sarah A. , Anderson Larry D. , Kaufman Jonathan L. , Shah Nina , Pei Huiling , Patel Sharmila , Cortoos Annelore , Bartlett J. Blake , Vermeulen Jessica , Lin Thomas S. , Voorhees Peter M. , Richardson Paul G.
Published: September 2022

Patients with multiple myeloma are at increased risk of vascular thromboembolic events (VTEs). This post hoc analysis evaluated VTEs in the randomised phase 2 GRIFFIN study (ClinicalTrials.gov Identifier: NCT02874742) that investigated lenalidomide/bortezomib/dexamethasone (RVd) ± daratumumab (D). Patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation (ASCT) received D‐RVd/RVd induction, high‐dose therapy and ASCT, D‐RVd/RVd consolidation and up to 2 years of lenalidomide maintenance therapy ± D. VTE prophylaxis was recommended (at least aspirin, ≥162 mg daily) in accordance with International Myeloma Working Group guidelines. In the safety population (D‐RVd, n = 99; RVd, n = 102), VTEs occurred in 10.1% of D‐RVd patients and 15.7% of RVd patients; grade 2–4 VTEs occurred in 9.1% and 14.7%, respectively. Median time to the first onset of VTE was longer for D‐RVd versus RVd patients (305 days vs 119 days). Anti‐thrombosis prophylaxis use was similar between arms (D‐RVd, 84.8% vs RVd, 83.3%); among patients with VTEs, prophylaxis use at time of first VTE onset was 60.0% for D‐RVd and 68.8% for RVd. In summary, the addition of daratumumab to RVd did not increase the incidence of VTEs, but the cumulative VTE incidence was relatively high in this cohort and anti‐thrombotic prophylaxis use was suboptimal.
Socio‐cognitive, expertise‐based and appearance‐based accounts of the other‐‘race’ effect in face perception: A label‐based systematic review of neuroimaging results
Authors: Ficco Linda , Müller Veronika I. , Kaufmann Jürgen M. , Schweinberger Stefan R.
Published: September 2022

Two competing theories explain the other‐‘race’ effect (ORE) either by greater perceptual expertise to same‐‘race’ (SR) faces or by social categorization of other‐‘race’ (OR) faces at the expense of individuation. To assess expertise and categorization contributions to the ORE, a promising—yet overlooked—approach is comparing activations for different other‐‘races’. We present a label‐based systematic review of neuroimaging studies reporting increased activity in response to OR faces (African, Caucasian, or Asian) when compared with the SR of participants. Hypothetically, while common activations would reflect general aspects of OR perception, ‘race’‐preferential ones would represent effects of ‘race’‐specific visual appearance. We find that several studies report activation of occipito‐temporal and midcingulate areas in response to faces across different other‐‘races’, presumably due to high demand on the visual system and category processing. Another area reported in response to all OR faces, the caudate nucleus, suggests the involvement of socio‐affective processes and behavioural regulation. Overall, our results support hybrid models—both expertise and social categorization contribute to the ORE, but they provide little evidence for reduced motivation to process OR faces. Additionally, we identify areas preferentially responding to specific OR faces, reflecting effects of visual appearance.
Stakeholder interest to mitigate the agency problem in enterprise innovation and the moderating effect of ownership concentration and financial constraints
Authors: Sun Yun , Xia Jiakai
Published: September 2022

This paper first studies the impact of stakeholder interest on the agency problem by selecting different proxies for key measurements from companies listed on second‐board markets from 2013 to 2019 to investigate the effect of the equity incentive on companies' innovation levels. In addition, this paper adds two moderating variables, ownership concentration and financing constraints, to analyse their moderating effects on the relationships between equity incentives and enterprise innovation. The empirical results show a significant positive correlation between equity incentives and the level of corporate innovation output. In addition, a high degree of ownership concentration can strengthen the positive promoting effect of equity incentives on a company's innovation output. However, when a company faces financing constraints, the promotion effect of equity incentives on the company's innovation will be restrained.
‘It's rewarding because I get the love’: Grandparents raising grandchildren with foetal alcohol spectrum disorder
Authors: Clement Alexandra L. , Harding Kelly D. , Watson Shelley L.
Published: September 2022

The aim of this study was to explore the lived experiences of grandparents raising their grandchildren with foetal alcohol spectrum disorder (FASD). Specifically, we sought to identify how caregivers make meaning of their experience, what challenges are faced by grandparents while raising a second generation and what positive experiences are encountered. Ten grandparents raising a child with FASD in Ontario, Canada, participated in semi‐structured interviews. Interpretative phenomenological analysis was used to analyse the interviews to determine reoccurring themes. Three main themes were identified: (i) challenges when raising a grandchild with FASD, including kinship adoption struggles and intergenerational issues; (ii) worries about the future, including financial planning and health concerns; and (iii) rewards, such as shifts in priorities and the opportunity to raise a second generation. Grandparents raising their grandchildren with FASD face challenges and thus require specific supports so that they may adequately provide a safe and nurturing home environment for children with often challenging learning and social needs.
Risk of genetic and epigenetic alteration in children conceived following ART: Is it time to return to nature whenever possible?
Authors: Sciorio Romualdo , Tramontano Luca , Rapalini Erika , Bellaminutti Serena , Bulletti Francesco M. , D'Amato Antonio , Manna Claudio , Palagiano Antonio , Bulletti Carlo , Esteves Sandro C.
Published: September 2022

Assisted reproductive technology may influence epigenetic signature as the procedures coincide with the extensive epigenetic modification occurring from fertilization to embryo implantation. However, it is still unclear to what extent ART alters the embryo epigenome. In vivo fertilization occurs in the fallopian tube, where a specific and natural environment enables the embryo's healthy development. During this dynamic period, major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Over the past decade, concerns relating to the raised incidence of epigenetic anomalies and imprinting following ART have been raised by several authors. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period; therefore, unphysiological conditions, including ovarian stimulation, in vitro fertilization, embryo culture, cryopreservation of gametes and embryos, parental lifestyle, and underlying infertility, have the potential to contribute to epigenetic dysregulation independently or collectively. This review critically appraises the evidence relating to the association between ART and genetic and epigenetic modifications that may be transmitted to the offspring.
Blinded by the bright: How species‐poor habitats contribute to regional biodiversity across a tropical seascape
Authors: Harper Leah M. , Lefcheck Jonathan S. , Whippo Ross , Jones M. Scott , Foltz Zachary , Duffy J. Emmett
Published: September 2022

Aim

Conservation efforts have traditionally addressed the threat of biodiversity loss by prioritizing regions and habitats with high endemic species richness. However, species‐poor habitats often harbour distinct, valuable and/or functionally unique species that contribute to regional diversity. In the tropical marine realm, the ‘mangrove‐seagrass‐coral reef continuum’ has dominated both the scientific literature and marine spatial planning. Bare sediment habitats are also part of this continuum and often comprise the majority of bottom area, as they do in most regions worldwide, but are understudied and rarely considered in conservation. To address this information gap, we partition the relative contributions of five habitats in the coastal mosaic (forereefs, patch reefs, seagrass, mangroves and bare sand) to fish diversity across a tropical seascape.

Location

Carrie Bow Cay, Belize Barrier Reef.

Methods

Using diver visual censuses, we assessed fish community composition at three replicate sites from each of the five habitats annually for 5 years. We then partitioned diversity into within (α) and between (β) habitat contributions, and further partitioned β‐diversity into components attributed to species replacement and richness difference. Finally, we determined the local contributions to β‐diversity (LCBD) by each habitat and identified the key individual species behind these contributions.

Main Results

Tropical sand flats contributed uniquely and disproportionately to regional fish species diversity, despite having the fewest species overall. Sand flats also had higher‐than‐expected local contributions to β‐diversity (LCBD) and had the highest percentage of species not found in other habitats.

Main Conclusions

Our results demonstrate that previously understudied sand habitats harbour a relatively unique assemblage of species compared with other nearby habitats. Marine spatial planning aimed at maximizing the preservation of total biodiversity (including unique species) in the tropics should consider sand habitats.
Clinical and genetic spectrum of hereditary spastic paraplegia in Chinese children
Authors: Wang Jiaping , Fang Fang , Ding Changhong , Li Jiuwei , Wu Yun , Zhang Weihua , Bao Xinhua , Lv Junlan , Wang Xiaohui , Ren Xiaotun ,   Paediatric Neurology Study Group
Published: September 2022

Aim

To explore the clinical and genetic spectrum of hereditary spastic paraplegia (HSP) in Chinese children.

Method

This retrospective study was conducted between January 2014 and October 2021 in children clinically diagnosed with either pure HSP (pHSP) or complex HSP (cHSP).

Results

We investigated 45 children (32 males, 13 females; mean age [SD] at symptom onset 4 years [7 months]). clinically diagnosed with HSP and identified genetic causes in 35 patients. Most patients with autosomal dominant HSP had pHSP (16/18), whereas most patients with autosomal recessive HSP tended to have cHSP (14/16). SPG11 was the most common autosomal recessive subtype, followed by FA2H/SPG35, whereas SPAST/SPG4 was the most frequent cause of autosomal dominant HSP. Two patients with CPT1C mutations presented with a complex phenotype. Meanwhile, 10 patients were found to have likely pathogenic variants/variants of uncertain clinical significance in six genes related to HSP.

Interpretation

SPG11 and SPG4 were the most frequent subtypes in Chinese children with autosomal recessive HSP and autosomal dominant HSP. However, the prevalence of SPG4 was much lower than that in adults, which might be explained by the late onset of the disease. On the other hand, FA2H/SPG35 was common in our cohort, while it contributed to only a small proportion of adult cases, which might be explained by its rapid progression and early death in some patients. We also expanded the genetic and clinical spectra of SPG73.
Child neurology telemedicine: Analyzing 14 820 patient encounters during the first year of the COVID‐19 pandemic
Authors: Kaufman Michael C. , Xian Julie , Galer Peter D. , Parthasarathy Shridhar , Gonzalez Alexander K. , McKee Jillian L. , Prelack Marisa S. , Fitzgerald Mark P. , Helbig Ingo ,   CHOP Neuroscience Center ‐ Telemedicine Research Group
Published: September 2022

Aim

To determine the long‐term impact of telemedicine in child neurology care during the COVID‐19 pandemic and with the reopening of outpatient clinics.

Method

We performed an observational cohort study of 34 837 in‐person visits and 14 820 telemedicine outpatient visits across 26 399 individuals. We assessed differences in care across visit types, time‐period observed, time between follow‐ups, patient portal activation rates, and demographic factors.

Results

We observed a higher proportion of telemedicine for epilepsy (International Classification of Diseases, 10th Revision G40: odds ratio [OR] 1.4, 95% confidence interval [CI] 1.3–1.5) and a lower proportion for movement disorders (G25: OR 0.7, 95% CI 0.6–0.8; R25: OR 0.7, 95% CI 0.6–0.9) relative to in‐person visits. Infants were more likely to be seen in‐person after reopening clinics than by telemedicine (OR 1.6, 95% CI 1.5–1.8) as were individuals with neuromuscular disorders (OR 1.6, 95% CI 1.5–1.7). Self‐reported racial and ethnic minority populations and those with highest social vulnerability had lower telemedicine participation rates (OR 0.8, 95% CI 0.8–0.8; OR 0.7, 95% CI 0.7–0.8).

Interpretation

Telemedicine continued to be utilized even once in‐person clinics were available. Pediatric epilepsy care can often be performed using telemedicine while young patients with neuromuscular disorders often require in‐person assessment. Prominent barriers for socially vulnerable families and racial and ethnic minorities persist.
Which attributes of fishing opportunities are linked to sustainable fishing?
Authors: Oostdijk Maartje , Carpenter Griffin
Published: September 2022

To prevent the overfishing of marine fish populations, governments often limit fishing access through the allocation of fishing opportunities. While some studies have linked particular systems of fishing opportunities to sustainable outcomes (particularly individual transferable quota), it remains unclear whether it is the use of exclusive access (individual allocation), the use of a market (tradability), the duration of this access or the quota limits themselves that drive the sustainable outcomes. To determine which attributes of fishing opportunities are associated with sustainable fishing, we developed a novel method to systematically classify how fishing opportunities are allocated for 443 global fish stocks from 1990 to 2018 to produce the longest and most comprehensive dataset and longitudinal study of its kind. Our results revealed that quota limits and individual allocation are linked to a reduced probability of overfishing, with the most robust result for quota limits. No attributes were robustly linked to a reduced probability of overfished biomass. Whereas some previous studies have found that systems with market‐based features or strong property rights (i.e. a long duration) were linked to sustainable fishing, these benefits were found to be small or not significant once proper controls for other system attributes were introduced. These results highlight the importance of considering all attributes of institutional design in the governance of common pool resources.
Genetic and phenotypic characterisation of HIV‐associated aggressive B‐cell non‐Hodgkin lymphomas, which do not occur specifically in this population: diagnostic and prognostic implications
Authors: Baptista Maria Joao , Tapia Gustavo , Muñoz‐Marmol Ana‐María , Muncunill Josep , Garcia Olga , Montoto Silvia , Gribben John G , Calaminici Maria , Martinez Antonio , Veloza Luis , Martínez‐Trillos Alejandra , Aldamiz Teresa , Menarguez Javier , Terol María‐José , Ferrandez Antonio , Alcoceba Miguel , Briones Javier , González‐Barca Eva , Climent Fina , Muntañola Ana , Moraleda José‐María , Provencio Mariano , Abrisqueta Pau , Abella Eugenia , Colomo Lluis , García‐Ballesteros Carlos , Garcia‐Caro Montserrat , Sancho Juan‐Manuel , Ribera Josep‐Maria , Mate José‐Luis , Navarro José‐Tomas
Published: September 2022

The frequency of aggressive subtypes of B‐cell non‐Hodgkin lymphoma (B‐NHL), such as high‐grade B‐cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL‐DH/TH) or Burkitt‐like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV‐associated aggressive B‐NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy‐five HIV‐associated aggressive B‐NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV‐encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell‐of‐origin classification of diffuse large B‐cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV‐negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL‐DH/TH and BL‐like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV‐associated aggressive B‐NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM‐1 expression in BL, have a negative prognostic impact on HIV‐infected individuals.
Theory generation from literature reviews: A methodological guidance
Authors: Tsiotsou Rodoula H. , Koles Bernadett , Paul Justin , Loureiro Sandra Maria Correia
Published: September 2022

This article aims to assist researchers in navigating the path to theory creation by investigating how they might build theory through literature reviews. In particular, we propose and elaborate upon the Theory Generation from Literature Review (TGLR) process, capturing different methods and techniques to be applied depending on the level of development and saturation characterizing the focal area of inquiry. In the second part of the article, we briefly present the 21 articles conducting systematic literature reviews on consumer research topics selected for this special issue in IJCS.