bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the association between MRI and gene signatures in facioscapulohumeral dystrophy muscle: implications for clinical trial design
Authors: Wong Chao-Jen , Friedman Seth D. , Snider Lauren , Bennett Sean R. , Jones Takako I. , Jones Peter L. , Shaw Dennis W.W. , Blemker Silvia S. , Riem Lara , DuCharme Olivia , Lemmers Richard J.F.L. , van der Maarel Silvère M. , Wang Leo H. , Tawil Rabi , Statland Jeffrey M. , Tapscott Stephen J. 
Published: February 2023

ABSTRACTIdentifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression, but reproducibility across studies needs further validation. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA. Together with moderate-to-strong correlations of gene signatures and MRI characteristics between the TA muscles bilaterally, these results suggest a whole muscle model of disease progression and provide a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design.
Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2
Authors: Weeratunga Saroja , Gormal Rachel S. , Liu Meihan , Eldershaw Denaye , Livingstone Emma K. , Malapaka Anusha , Wallis Tristan P. , Bademosi Adekunle T. , Jiang Anmin , Healy Michael D. , Meunier Frederic A. , Collins Brett M. 
Published: February 2023

SUMMARYMunc18-interacting proteins (Mints) are multi-domain adaptors that regulate neuronal membrane trafficking, signalling and neurotransmission. Mint1 and Mint2 are highly expressed in the brain with overlapping roles in the regulation of synaptic vesicle fusion required for neurotransmitter release by interacting with the essential synaptic protein Munc18-1. Here, we have used AlphaFold2 to identify and then validate the mechanisms that underpin both the specific interactions of neuronal Mint proteins with Munc18-1 as well as their wider interactome. We find a short acidic α-helical motif (AHM) within Mint1 and Mint2 is necessary and sufficient for specific binding to Munc18-1 and binds a conserved surface on Munc18-1 domain3b. In Munc18-1/2 double knockout neurosecretory cells mutation of the Mint-binding site reduces the ability of Munc18-1 to rescue exocytosis, and although Munc18-1 can interact with Mint and Sx1a proteins simultaneouslyin vitrowe find they have mutually reduced affinities, suggesting an allosteric coupling between the proteins. Using AlphaFold2 to then examine the entire cellular network of putative Mint interactors provides a structural model for their assembly with a variety of known and novel regulatory and cargo proteins including ARF3/ARF4 small GTPases, and the AP3 clathrin adaptor complex. Validation of Mint1 interaction with a new predicted binder TJAP1 provides experimental support that AlphaFold2 can correctly predict interactions across such large-scale datasets. Overall, our data provides insights into the diversity of interactions mediated by the Mint family and shows that Mints may help facilitate a key trigger point in SNARE complex assembly and vesicle fusion.
Transition to the structurally vulnerable nuclear state is an integral part of mouse embryonic development
Authors: Masahito Tanaka , Sakanoue Rin , Takasu Atsushi , Watanabe Naoko , Shimamoto Yuta , Miyamoto Kei 
Published: February 2023

AbstractUpon fertilization, germ cells are reprogrammed to acquire the ability to develop into an entire organism. Whereas extensive studies have focused on epigenetic reprogramming of chromatin states during development, changes of the nucleus that surrounds chromatin are ill-defined. Here, we show that nuclei become structurally and mechanically vulnerable at the 2-cell stage during mouse embryonic development. The 2-cell stage nuclei are extraordinarily plastic and deformable in contrast to those of 1-cell and 4-cell stages. The mechanically vulnerable nuclear state is attained by autophagy-mediated loss of lamin B1 from the nuclear membrane. This developmentally programmed lamin B1 dynamics is required for chromatin organization and major zygotic genome activation. We thus demonstrate that structural reprogramming of nuclei is a major determinant of embryonic gene expression and acquisition of totipotency.
Thioredoxin‐1 regulates the autophagy induced by oxidative stress through LC3‐II in human lens epithelial cells
Authors: Hu Jianghua , Liu Jinxia , Chen Silong , Zhang Chengshou , Shen Lifang , Yao Ke , Yu Yibo 
Published: February 2023

AbstractOxidative stress plays a major role in age‐related cataract development. The cellular antioxidant protein thioredoxin‐1 (Trx‐1) and its negative regulator, thioredoxin binding protein‐2 (TBP‐2), are pivotal in the cellular redox balance during oxidative stress. The aim of this study is to investigate the effect of Trx‐1 and TBP‐2 on LC3 I/LC3 II in oxidative stress‐induced autophagy in human lens epithelial cells (LECs). In our study, LECs were treated with 50 μM H2O2 for different durations, and the expression of Trx‐1 and TBP‐2 were measured by RT‐PCR and Western blot. Trx‐1 activity was evaluated by the thioredoxin activity fluorescent assay. The subcellular localization of Trx‐1 and TBP‐2 was evaluated by cellular immunofluorescence. The interaction between Trx‐1 and TBP‐2 was examined by co‐immunoprecipitation. The cell viability was detected using CCK‐8, and the expression of LC3‐II/LC3‐I was detected to evaluate the autophagy. The results showed that the mRNA levels of the Trx‐1 and TBP‐2 were kinetically changed after treatment with H2O2 for different durations. Exposure to H2O2 increased the expression of TBP‐2 but not Trx‐1, while the exposure inhibited Trx‐1 activity. TBP‐2 was co‐localized with Trx‐1, and exposure to H2O2 increased the interaction between TBP‐2 and Trx‐1. Trx‐1 overexpression enhanced the autophagic response under normal circumstances and it might regulate autophagy in the initial phase. This study demonstrates the differential role of Trx‐1 in cellular oxidative stress response, oxidative stress increased Trx‐1 interaction with TBP‐2, and Trx‐1/TBP‐2 regulated the autophagic response in the initial phase through LC3‐II.
Demystifying the ‘gold standard’ of arms export controls: US arms exports to conflict zones
Authors: Erickson Jennifer L. 
Published: February 2023

AbstractThis article examines why US‐made and US‐supplied weapons consistently appear in conflicts around the world, despite the United States having what is commonly lauded as the ‘gold standard’ of national arms export control systems. On paper, US law and policy discourage arms transfers to areas engaged in or at risk of conflict. US arms export controls also informed the creation of the UN Arms Trade Treaty (ATT), which provides legally binding conventional arms export criteria. Yet in the recent Yemen, Syria and Libya conflicts, among many others, the United States has directly supplied or indirectly facilitated the supply of weapons to conflict parties. This article highlights two factors that help to account for this apparent policy failure: the flexible design of US law and policy and the inherent challenges of ensuring that weapons in conflict zones—especially small arms—go to and stay with their intended recipients. These findings have important implications for US foreign policy, ATT implementation and the human costs of conflict around the world.
Delivery of miR‐3529‐3p using MnO2‐SiO2‐APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A
Authors: Zhang Ying , Wang Ran‐Ran , Liu Rui , Xie Shu‐Yang , Jiao Fei , Li You‐Jie , Xin Jiaxuan , Zhang Han , Wang Zhenbo , Yan Yun‐Fei 
Published: February 2023

AbstractBackgroundThe present study aimed to investigate the function of miR‐3529‐3p in lung adenocarcinoma and MnO2‐SiO2‐APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy.MethodsExpression levels of miR‐3529‐3p were evaluated in lung carcinoma cells and tissues by qRT‐PCR. The effects of miR‐3529‐3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK‐8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT‐PCR and mitochondrial complex assay were used to determine the targeting relationship between miR‐3529‐3p and hypoxia‐inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH‐DA staining and FACS.ResultsMiR‐3529‐3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR‐3529‐3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR‐3529‐3p, HIGD1A expression was downregulated, through which miR‐3529‐3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR‐3529‐3p into cells, but also enhance the antitumor function of miR‐3529‐3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR‐3529‐3p.ConclusionsOur results establish the antioncogenic role of miR‐3529‐3p, and demonstrate that miR‐3529‐3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis.
Functional and structural brain abnormalities in substance use disorder: A multimodal meta‐analysis of neuroimaging studies
Authors: Yan Hong , Xiao Shu , Fu Siying , Gong Jiaying , Qi Zhangzhang , Chen Guanmao , Chen Pan , Tang Guixian , Su Ting , Yang Zibin , Wang Ying 
Published: February 2023

AbstractIntroductionNumerous neuroimaging studies of resting‐state functional imaging and voxel‐based morphometry (VBM) have revealed that patients with substance use disorder (SUD) may present brain abnormalities, but their results were inconsistent. This multimodal neuroimaging meta‐analysis aimed to estimate common and specific alterations in SUD patients by combining information from all available studies of spontaneous functional activity and gray matter volume (GMV).MethodsA whole‐brain meta‐analysis on resting‐state functional imaging and VBM studies was conducted using the Seed‐based d Mapping with Permutation of Subject Images (SDM‐PSI) software, followed by multimodal overlapping to comprehensively investigate function and structure of the brain in SUD.ResultsIn this meta‐analysis, 39 independent studies with 47 datasets related to resting‐state functional brain activity (1444 SUD patients; 1446 healthy controls [HCs]) were included, as well as 77 studies with 89 datasets for GMV (3457 SUD patients; 3774 HCs). Patients with SUD showed the decreased resting‐state functional brain activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). For the VBM meta‐analysis, patients with SUD showed the reduced GMV in the bilateral ACC/mPFC, insula, thalamus extending to striatum, and left sensorimotor cortex.ConclusionsThis multimodal meta‐analysis exhibited that SUD shows common impairment in both function and structure in the ACC/mPFC, suggesting that the deficits in functional and structural domains could be correlated together. In addition, a few regions exhibited only structural impairment in SUD, including the insula, thalamus, striatum, and sensorimotor areas.
Mosquitoes (Diptera: Culicidae) of the Brazilian semiarid: dynamic interactions with biotic and abiotic factors
Authors: Silva‐Inacio Cássio L. , Freire de Melo Ximenes Maria de Fátima 
Published: February 2023

AbstractMosquitoes are found worldwide; in Brazil, 530 species are distributed across all its biomes. Understanding of the biodiversity of the Caatinga biome remains incomplete, especially for Culicidae. We carried out a sampling of immature and adult mosquitoes in aquatic habitats and using Shannon traps in a seasonally dry tropical forest, in the semiarid of Rio Grande do Norte. A total of 1747 immatures of 13 species were collected during the study period (2017–2020) in groundwater sites, rock depressions, with and without vegetation, and tree holes. The maintenance of temporary breeding sites is related to the dry and rainy seasons. We collected 2132 adult mosquitoes of 12 species between 5 and 8 PM. Correlation analyses showed the effect of meteorological variables on Culicidae populations. Both immature and adult mosquitoes' abundance were significantly influenced by temperature and wind. The abundance of adult mosquitoes of the genera Aedes demonstrated a positive correlation with temperature, and a negative one with Mansonia and Uranotaenia. Our study adds information on the population dynamics of mosquitoes in the Brazilian semiarid, highlighting the bioecological relationships and breeding sites of species relevant to public health.
Managers' experiences of providing end‐of‐life care under the Home Care Package Program
Authors: Simonetti Simone , Parker Deborah , Mack Holly A. , Wise Sarah 
Published: February 2023

AbstractObjectiveThe study explored the experiences of Australian aged care providers in supporting clients on a home care package to die at home.MethodsSemistructured interviews were conducted with 13 aged care managers responsible for delivering services under the Home Care Package Program. Interviews were analysed thematically.ResultsFour themes emerged that illuminated managers' experiences: struggling to meet a preference to die at home; lack of opportunities to build workforce capacity in end‐of‐life care; challenges in negotiating fragmented funding arrangements between health and aged care providers; and mixed success in collaborating across sectors.ConclusionsAged care providers want to support older Australians who prefer to stay at home at the end of life. However, most clients are admitted to a residential facility when their care needs exceed a home care budget long before a specialist palliative care team will intervene. Budgets for health and aged care providers must be sufficient and flexible to support timely access to end‐of‐life care, to reward collaboration across sectors and to invest in building palliative care skills in the nursing and personal care workforce.
Identifying the antecedents of opportunism in agri‐food cooperatives: a comparative analysis between first‐ and second‐tier cooperatives
Authors: Sánchez‐Navarro Jorge Luis , Arcas‐Lario Narciso , Hernández‐Espallardo Miguel 
Published: February 2023

AbstractAgri‐food cooperatives allow farmers to improve their competitiveness and bargaining power. However, the specificities of their organizational form, in which owners are decision makers, suppliers, and clients, open the door to conflicts of interest. Members’ opportunism comes in the aftermath of this and adversely affects cooperatives’ performance. Hence, knowing the antecedents of these undesirable opportunistic behaviors is an important management concern. This study analyzes the factors that promote cooperative members opportunism by exploring the differences between memberships of first‐tier cooperatives and second‐tier cooperatives. To this end, an ordinary least squares linear regression model with interaction terms was estimated. The results show that in the case of first‐tier cooperatives, environmental uncertainty, members’ heterogeneity, and the cooperative's market orientation increase members’ opportunism, while members’ dependence on the cooperative, long‐term orientation of the relationship, and members’ market orientation reduce it. For second‐tier cooperatives, our results reveal that cooperative market orientation increases members’ opportunism, while members’ market orientation reduces it. Moreover, we find that members’ dependence on cooperatives, long‐term orientation, and environmental uncertainty have different effects on opportunism in each type of membership.
The massifying consumption of embodied goods in an advanced capitalist state: Capital, economic anxieties and social networks
Authors: Au Anson 
Published: February 2023

AbstractEmbodied goods like cosmetic surgery comprise a unique and growing consumer industry, most of all in the Asia‐Pacific, yet the rationalisation processes motivating their purchase are less understood. Addressing this lacuna, this article builds upon open‐ended surveys and semi‐structured interviews of consumers in Seoul, South Korea to articulate a relational approach to examine the rationalisation of purchases of cosmetic surgery as an embodied good. Theorised through the conceptual lens of Bourdieusian capital, participant accounts point to macro‐level economic anxieties that inform a micro‐level cognitive logic of competition through which consumers rationalise the purchase of embodied goods as a form of aesthetic capital. When performed, this capital is believed to offer actors social distinction that provides workplace and social networking advantages by impressing gatekeepers and alters. Participants are shown to reconceptualise their bodies in a means‐end orientation for upward mobility but stress their resignation and powerlessness in being forced to adopt this instrumental reconceptualisation as a response to intensifying economic hardships in contemporary capitalist South Korea.
Social anxiety and accumulation of status loss events: The role of adulthood experiences
Authors: Azoulay Roy , Avigadol Liat , Gilboa‐Schechtman Eva 
Published: February 2023

AbstractObjectivesThe association between social anxiety (SA) and early‐life status loss events (SLEs) is well documented. However, such an association in adulthood is yet to be examined.MethodsTwo studies (N = 166 and N = 431) were conducted to address this question. Adult participants filled out questionnaires regarding SLEs accumulation during childhood, adolescence, and adulthood, along with depression and SA severity measures.ResultsSA was associated with SLEs in adulthood over and above SLEs in childhood and adolescence, and depression.ConclusionThe adaptive role of SA in adulthood in the face of concrete and relevant status threats is discussed.
How I manage mantle cell lymphoma: indolent versus aggressive disease
Authors: Wilson Matthew R. , Barrett Aisling , Cheah Chan Yoon , Eyre Toby A. 
Published: February 2023

SummaryMantle cell lymphoma (MCL) is a mature B‐cell lymphoma with a variable clinical course and historically poor prognosis. Management is challenging in part due to the heterogeneity of the disease course, with indolent and aggressive subtypes now well recognised. Indolent MCL is often characterised by a leukaemic presentation, SOX11 negativity and low proliferation index (Ki‐67). Aggressive MCL is characterised by rapid onset widespread lymphadenopathy, extra‐nodal involvement, blastoid or pleomorphic histology and high Ki‐67. Tumour protein p53 (TP53) aberrations in aggressive MCL are recognised with clear negative impact on survival. Until recently, trials have not addressed these specific subtypes separately. With the increasing availability of targeted novel agents and cellular therapies, the treatment landscape is constantly evolving. In this review, we describe the clinical presentation, biological factors, and specific management considerations of both indolent and aggressive MCL and discuss current and potential future evidence which may help move to a more personalised approach.
Economic evaluation of next‐generation sequencing techniques in diagnosis of genetic disorders: A systematic review
Authors: Rezapour Aziz , Souresrafil Aghdas , Barzegar Mohammad , Sheikhy‐Chaman Mohammadreza , Tatarpour Parvin 
Published: February 2023

AbstractIn recent years, massively parallel sequencing or next generation sequencing (NGS) has considerably changed both the research and diagnostic fields, and rapid developments have led to the combination of NGS techniques in clinical practice, ease of analysis, and detection of genetic mutations. This article aimed at reviewing the economic evaluation studies of the NGS techniques in the diagnosis of genetic diseases. In this systematic review, scientific databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus, and CEA registry) were searched from 2005 to 2022 to identify the related literature on the economic evaluation of NGS techniques in the diagnosis of genetic diseases. Full‐text reviews and data extraction were all performed by two independent researchers. The quality of all the articles included in this study was evaluated using the Checklist of Quality of Health Economic Studies (QHES). Out of 20 521 screened abstracts, 36 studies met the inclusion criteria. The mean score of the QHES checklist for the studies was 0.78 (high quality). Seventeen studies were conducted based on modeling. Cost‐effectiveness analysis, cost‐utility analysis, and cost‐minimization analysis were done in 26 studies, 13 studies, and 1 study, respectively. Based on the available evidence and findings, exome sequencing, which is one of the NGS techniques, could have the potential to be used as a cost‐effective genomic test to diagnose children with suspected genetic diseases. The results of the present study support the cost‐effectiveness of exome sequencing in diagnosing suspected genetic disorders. However, the use of exome sequencing as a first‐ or second‐line diagnostic test is still controversial. Most studies have been conducted in high‐income countries, and research on the cost‐effectiveness of NGS methods is recommended in low‐ and middle‐income countries.