bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the LSD1 Inhibitor RN-1 on γ-globin and Global Gene Expression during Erythroid Differentiation in Baboons (Papio anubis)
Authors: Ibanez Vinzon , Vaitkus Kestis , Ruiz Maria Armila , Lei Zhengdeng , Mannschein-Cline Mark , Arbieva Zarema , Lavelle Donald 
Published: July 2023

AbstractIncreased levels of Fetal Hemoglobin reduce the severity of symptoms of patients with sickle cell disease and decrease the risk of death. An affordable, small molecule drug that stimulates HbF expression in vivo would be ideally suited to treat the large numbers of SCD patients that exist worldwide. Our previous work showed that administration of the LSD1 (KDM1A) inhibitor RN-1 to normal baboons increased Fetal Hemoglobin (HbF) and was tolerated over a prolonged treatment period. HbF elevations were associated with changes in epigenetic modifications that included increased levels of H3K4 di-and tri-methyl lysine at the γ-globin promoter. While dramatic effects of the loss of LSD1 on hematopoietic differentiation have been observed in murine LSD1 gene deletion and silencing models, the effect of pharmacological inhibition of LSD1 in vivo on hematopoietic differentiation is unknown. The goal of these experiments was to investigate the in vivo mechanism of action of the LSD1 inhibitor RN-1 by determining its effect on γ-globin expression in highly purified subpopulations of bone marrow erythroid cells enriched for varying stages of erythroid differentiation isolated directly from baboons treated with RN-1 and also by investigating the effect of RN1 on the global transcriptome in a highly purified population of proerythroblasts. Our results show that RN-1 administered to baboons targets an early event during erythroid differentiation responsible for γ-globin repression and increases the expression of a limited number of genes including genes involved in erythroid differentiation such as GATA2, GFi-1B, and LYN.
Generation of porcine PK-15 cells lacking theIfnar1gene to optimize the efficiency of viral isolation
Authors: Shofa Maya , Saito Akatsuki 
Published: July 2023

AbstractBecause pigs are intermediate or amplifying hosts for several zoonotic viruses, the pig-derived PK-15 cell line is an indispensable tool for studying viral pathogenicity and developing treatments, vaccines, and preventive measures to mitigate the risk of disease outbreaks. However, we must consider the possibility of contamination by type I interferons (IFNs), such as IFNα and IFNβ, or IFN-inducing substances, such as virus-derived double-stranded RNA or bacterial lipopolysaccharides, in clinical samples, leading to lower rates of viral isolation. In this study, we aimed to generate a PK-15 cell line that can be used to isolate viruses from clinical samples carrying a risk of contamination by IFN-inducing substances. To this end, we depleted the IFN alpha and beta receptor subunit 1 (Ifnar1) gene in PK-15 cells using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 method. Treatment of PK-15 cells lackingIfnar1with IFNβ resulted in no inhibitory effects on viral infection by a lentiviral vector, influenza virus, and Akabane virus. These results demonstrate that PK-15 cells lackingIfnar1could represent a valuable and promising tool for viral isolation, vaccine production, and virological investigations.
Hallucination proneness alters sensory feedback processing in self-voice production
Authors: Duggirala Suvarnalata Xanthate , Schwartze Michael , Goller Lisa K. , Linden David E. J. , Pinheiro Ana P. , Kotz Sonja A. 
Published: July 2023

AbstractBackgroundSensory suppression occurs when hearing one’s self-generated voice, as opposed to passively listening to one’s own voice. Quality changes of sensory feedback to the self-generated voice can increase attentional control. These changes affect the self-other voice distinction and might lead to hearing non-existent voices in the absence of an external source (i.e., auditory verbal hallucinations (AVH)). However, it is unclear how changes in sensory feedback processing and attention allocation interact and how this interaction might relate to hallucination proneness (HP).Study DesignParticipants varying in HP self-generated and passively listened to their voice that varied in emotional quality and certainty of recognition — 100% neutral, 60-40% neutral-angry, 50-50% neutral-angry, 40-60% neutral-angry, 100% angry, during EEG recordings.Study ResultsThe N1 auditory evoked potential was more suppressed for the self-generated than externally generated voices. Increased HP was associated with (i) an increased N1 response to the self-compared to externally generated voices, (ii) a reduced N1 response for angry compared to neutral voices, and (iii) a reduced N2 response to unexpected voice quality in sensory feedback (60-40% neutral-angry) compared to neutral voices.ConclusionsThe current study highlights an association between increased HP and systematic changes of the emotional quality and certainty in sensory feedback processing (N1) and attentional control (N2) in self-voice production in a non-clinical population. Considering that voice hearers also display these changes, these findings support the continuum hypothesis. However, additional research is needed to validate this conclusion.
Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction
Authors: Henry Rebecca J. , Barrett James P. , Vaida Maria , Khan Niaz Z. , Makarevich Oleg , Ritzel Rodney M. , Faden Alan I. , Stoica Bogdan A. 
Published: July 2023

ABSTRACTObesity increases the morbidity and mortality of traumatic brain injury (TBI). We performed a detailed analysis of transcriptomic changes in the brain and adipose tissue to examine the interactive effects between high-fat diet-induced obesity (DIO) and TBI in relation to central and peripheral inflammatory pathways, as well as neurological function. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. Combined TBI and HFD resulted in additive dysfunction in the Y-Maze, novel object recognition (NOR), and Morris water maze (MWM) cognitive function tests. We also performed high-throughput transcriptomic analysis using Nanostring panels of cellular compartments in the brain and total visceral adipose tissue (VAT), followed by unsupervised clustering, principal component analysis, and IPA pathway analysis to determine shifts in gene expression programs and molecular pathway activity. Analysis of cellular populations in the cortex and hippocampus as well as in visceral adipose tissue during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in select gene expression signatures and pathways. These data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and visceral adipose tissue macrophages, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue macrophages, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.
Sex, gender diversity, and brain structure in children ages 9 to 11 years old
Authors: Torgerson Carinna , Ahmadi Hedyeh , Choupan Jeiran , Fan Chun Chieh , Blosnich John R. , Herting Megan M. 
Published: July 2023

AbstractThere remains little consensus about the relationship between sex and brain structure, particularly in childhood. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest - many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9-11 years-old (N=7693). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. The model with sex, but not gender diversity, was the best-fitting model in 75% of gray matter regions and 79% of white matter regions examined. The addition of gender to the sex model explained significantly more variance than sex alone with regard to bilateral cerebellum volume, left precentral cortical thickness, as well as gyrification in the right superior frontal gyrus, right parahippocampal gyrus, and several regions in the left parietal lobe. For mean diffusivity in the left uncinate fasciculus, the model with sex, gender, and their interaction captured the most variance. Nonetheless, the magnitude of variance accounted for by sex was small in all cases and felt-gender score was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9-11 years-old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity.HighlightsSex-related variance in regional human brain structure is widespread at ages 9-11Together, sex and gender diversity accounted for more variance in only a few regionsFelt-gender diversity itself was not significantly related to any outcome at ages 9-11Effect sizes for sex and felt-gender estimates were small
Distinct human stem cell subpopulations drive adipogenesis and fibrosis in musculoskeletal injury
Authors: Garcia Steven M. , Lau Justin , Diaz Agustin , Chi Hannah , Lizarraga Miguel , Wague Aboubacar , Montenegro Cristhian , Davies Michael R. , Liu Xuhui , Feeley Brian T. 
Published: July 2023

AbstractFibroadipogenic progenitors (FAPs) maintain healthy skeletal muscle in homeostasis but drive muscle degeneration in chronic injuries by promoting adipogenesis and fibrosis. To uncover how these stem cells switch from a pro-regenerative to pro-degenerative role we perform single-cell mRNA sequencing of human FAPs from healthy and injured human muscles across a spectrum of injury, focusing on rotator cuff tears. We identify multiple subpopulations with progenitor, adipogenic, or fibrogenic gene signatures. We utilize full spectrum flow cytometry to identify distinct FAP subpopulations based on highly multiplexed protein expression. Injury severity increases adipogenic commitment of FAP subpopulations and is driven by the downregulation of DLK1. Treatment of FAPs bothin vitroandin vivowith DLK1 reduces adipogenesis and fatty infiltration, suggesting that during injury, reduced DLK1 within a subpopulation of FAPs may drive degeneration. This work highlights how stem cells perform varied functions depending on tissue context, by dynamically regulating subpopulation fate commitment, which can be targeted improve patient outcomes after injury.
Cocaine Regulates Antiretroviral Therapy CNS Access Through Pregnane-X Receptor-Mediated Drug Transporter and Metabolizing Enzyme Modulation at the Blood Brain Barrier
Authors: Fridman Lisa B. , Knerler Stephen , Price Amira-Storm , Ortiz Rodnie Colón , Mercado Alicia , Wilkins Hannah , Flores Bianca R. , Orsburn Benjamin C. , Williams Dionna W. 
Published: July 2023

ABSTRACTBackgroundAppropriate interactions between antiretroviral therapies (ART) and drug transporters and metabolizing enzymes at the blood brain barrier (BBB) are critical to ensure adequate dosing of the brain to achieve HIV suppression. These proteins are modulated by demographic and lifestyle factors, including substance use. While understudied, illicit substances share drug transport and metabolism pathways with ART, increasing the potential for adverse drug:drug interactions. This is particularly important when considering the brain as it is relatively undertreated compared to peripheral organs and is vulnerable to substance use-mediated damage.MethodsWe used anin vitromodel of the human BBB to determine the extravasation of three first-line ART drugs, emtricitabine (FTC), tenofovir (TFV), and dolutegravir (DTG), in the presence and absence of cocaine, which served as our illicit substance model. The impact of cocaine on BBB integrity and permeability, drug transporters, metabolizing enzymes, and their master transcriptional regulators were evaluated to determine the mechanisms by which substance use impacted ART central nervous system (CNS) availability.ResultsWe determined that cocaine had a selective impact on ART extravasation, where it increased FTC’s ability to cross the BBB while decreasing TFV. DTG concentrations that passed the BBB were below quantifiable limits. Interestingly, the potent neuroinflammatory modulator, lipopolysaccharide, had no effect on ART transport, suggesting a specificity for cocaine. Unexpectedly, cocaine did not breach the BBB, as permeability to albumin and tight junction proteins and adhesion molecules remained unchanged. Rather, cocaine selectively decreased the pregnane-x receptor (PXR), but not constitutive androstane receptor (CAR). Consequently, drug transporter expression and activity decreased in endothelial cells of the BBB, including p-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 4 (MRP4). Further, cytochrome P450 3A4 (CYP3A4) enzymatic activity increased following cocaine treatment that coincided with decreased expression. Finally, cocaine modulated adenylate kinases are required to facilitate biotransformation of ART prodrugs to their phosphorylated, pharmacologically active counterparts.ConclusionOur findings indicate that additional considerations are needed in CNS HIV treatment strategies for people who use cocaine, as it may limit ART efficacy through regulation of drug transport and metabolizing pathways at the BBB.
Stimulus representation in human frontal cortex supports flexible control in working memory
Authors: Shao Zhujun , Zhang Mengya , Yu Qing 
Published: July 2023

AbstractWhen holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.
Theories, constructs and contexts in responsible leadership: a future research agenda
Authors: Pathak Priyanka , Jha Sumi 
Published: July 2023

PurposeThe study explores the current research trends within the responsible leadership (RL) domain and proposes a future research agenda by conducting an extensive review of past research. The study aims to understand recent developments in theories, constructs and contexts in RL literature.Design/methodology/approachScopus database is used for the data collection on RL and patterns from 1998–2022. In total, 138 articles were covered for a systematic literature review (SLR) of RL behaviors. Further, the search was extended, and 109 more articles were included for bibliometric analysis of RL using R software. In total, 247 papers were reviewed.FindingsThe results present the consequences and antecedents of RL behaviors with external and internal stakeholders. Literature also indicates that researchers are more attentive to empirical studies with internal stakeholders, such as responsible leaders' impact on employee outcomes. Among theories, stakeholder theory's normative integrative and instrumental perspectives are used with RL.Research limitations/implicationsThe first limitation of the study is that this study collected data only from the Scopus database and the choice of language was English. Future studies may use other databases, languages and keywords. Instrumental and integrative RL behavioral styles would help balance organizations' financial and social goals.Originality/valueThis research enhances the literature on RL by combining content and bibliometric analysis to develop a more systematic and comprehensive understanding of integrative and instrumental leadership behaviors.
“Stay home, save SMEs”? The impact of a unique strict COVID-19 lockdown on small businesses
Authors: Mukherjee Abhishek , Scott Jonathan M. , Deakins David , McGlade Paul 
Published: July 2023

PurposeIn exploring how small and medium-sized enterprises (SMEs) overcame COVID-19 restrictions by deploying their specific dynamic capabilities to pivot their business models, this article explains the novel approaches that SMEs take and how they have responded to the financial challenges that arose from the pandemic.Design/methodology/approachThe article adopts a dynamic capabilities lens to explain: (1) the specific financial effects of the relatively “short” (seven week) COVID-19 lockdown during March and April 2020 on SMEs; (2) the barriers they faced; and (3) how they overcame these barriers. The data were collected via semi-structured interviews with the owner-manager or a senior manager in each surveyed SME. The interview data were analysed using NVivo.FindingsAnalysis of the findings revealed five key factors: (1) the capability of SMEs to access external resources, especially entrepreneurial finance; (2) their ability to reconfigure resources and plan for the longer term, yet retain flexibility; (3) how entrepreneurial learning provided the capability to deal with the “unplanned” events/uncertainty; (4) the importance of networking and sources of information; and (5) the remarkable optimism for a future recovery, despite the difficulties of the trading period.Originality/valueThis research fills a unique niche, as no previous studies have examined the resilience and dynamic capabilities of SMEs during a complete lockdown and business shutdown of this magnitude. This context, unprecedented in the history of modern economies, offers a new lens through which to understand the mechanisms of business survival and adaptation in times of severe disruptions. No previous studies have been conducted in unique circumstances during a time when SMEs were faced with such a strict lockdown with travel and business completely shut down.
The design of the mixed repetitive sampling plans based on the Cpk index
Authors: Marques Rafaela Aparecida Mendonça , Maciel Aline Cristina , Costa Antonio Fernando Branco , Santos Kleber Roberto da Silva 
Published: July 2023

PurposeThis study investigates the repetitive mixed sampling (MRS) plan based on the Cpk index that was proposed by Aslam et al. (2013a). They were the first to study the MRS plan, but they did not pay attention to the fact that submitting to the variable inspection a sample that was first submitted to the attribute inspection, truncates the X observations. In addition, they did not work with an accurate expression to calculate the probabilities of the Cpk statistic.Design/methodology/approachThe authors presented the results based on their original sampling plan through Monte Carlo simulation and defined the theoretical results of their plan when the sample submitted to the variable inspection is no longer the same one submitted to the attribute inspection.FindingsThe β risks of the optimum sampling plans presented by Aslam et al. (2013a) are pretty high, exceeding 46%, on average – this same problem was also observed in Saminathan and Mahalingam (2018), Balamurali (2020) and Balamurali et al. (2020), where the β risks of their proposed sampling plans are yet higher.Originality/valueIn terms of originality, the authors can declare the following. It is not a big deal to propose new sampling plans, if one does not know how to obtain their properties. The miscalculations of the sampling plans risks are dangerous; imagine the situation where the acceptance of bad lots exceeds 50% just because the sampling plan was incorrectly designed. Yes, it is a big deal to warn that this type of problem is arising in a growing number of papers. The authors of this study are the pioneers to discover that many studies focusing on the sampling plans need to be urgently revised.
Perceived brand localness of foreign brands and its impacts on brand trust and purchase intentions in developing countries in Asia: a social identity theory perspective
Authors: Han C. Min , Nam Hyojin , Swanepoel Danielle 
Published: July 2023

PurposeThe study draws primarily on social identity theory and conceptualizes perceived brand localness (PBL) as a signal of in-group membership to local consumers and investigates how it affects consumer trust and purchase intentions for foreign brands in developing countries in Asia. In addition, the authors examine boundary conditions for these hypothesized PBL effects.Design/methodology/approachUsing consumer survey data from three countries in Southeast Asia (the Philippines, Vietnam and Myanmar), the authors empirically validate the positive effects of PBL on consumer trust and purchase intentions for foreign brands in developing countries.FindingsThe findings support the social identity theory conceptualization of PBL for foreign brands, in which it can create identification-based trust (Tanis and Postmes, 2005) and active ownership through a process of self-stereotyping (van Veelen et al., 2015).Originality/valueThe findings suggest that social identity theory can be a promising theoretical framework for conceptualizing PBL and gaining a deeper insight into its mechanization and how it impacts consumers.