bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term clinical, virological and immunological outcomes in patients hospitalized for COVID-19: antibody response predicts long COVID
Authors: García-Abellán Javier , Padilla Sergio , Fernández-González Marta , García José A. , Agulló Vanesa , Andreo María , Ruiz Sandra , Galiana Antonio , Gutiérrez Félix , Masiá Mar 
Published: March 2021

ABSTRACTObjectiveLong-term data following SARS-CoV-2 infection are limited. We aimed to characterize the medium and long-term clinical, virological, and immunological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID.MethodsProspective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2 and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID19-symptom-questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.ResultsOf 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2-months and 6-months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct=38) and 3% (median Ct=36) patients at 2-months and 6-months, respectively, but no reinfections were demonstrated.Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR [95%CI]) were lower peak S-IgG (0.80 [0.66-0.94]) and higher WHO-severity-score (2.57 [1.20-5.86]); 6-month predictors were lower peak S-IgG (0.89 [0.79-0.99]) and female sex (2.41 [1.20-4.82]); no association was found with prolonged viral shedding.ConclusionsLate clinical events and persistent symptoms in the medium and long term occurred in a significant proportion of patients hospitalized for COVID-19. Gender, severity of illness and weaker antibody responses, but not viral shedding, were associated with long-COVID.SummaryThis study characterizes the long-term clinical, virological, and immunological outcomes following COVID-19 hospitalization. We found a significant proportion of late clinical events and persistent symptoms. Gender, severity of illness and weaker antibody responses, but not viral shedding, predicted long-COVID.
BCOR and BCORL1 mutations disrupt PRC1.1 repressive function in leukemia by unlinking the RING-PCGF1 enzymatic core from target genes
Authors: Schaefer Eva J. , Wang Helen C. , Meyer Clifford A. , Cejas Paloma , Gearhart Micah D. , Adelman Emmalee R. , Fares Iman , Apffel Annie , Lim Klothilda , Xie Yingtian , Gibson Christopher J. , Schenone Monica , Murdock H. Moses , Wang Eunice S. , Gondek Lukasz P. , Carroll Martin P. , Vedula Rahul S. , Winer Eric S. , Garcia Jacqueline S. , Stone Richard M. , Luskin Marlise R. , Carr Steven A. , Long Henry W. , Bardwell Vivian J. , Figueroa Maria E. , Lindsley R. Coleman 
Published: March 2021

SummaryBCOR and its paralog BCORL1 encode subunits of the Polycomb repressive complex 1.1 (PRC1.1) and are recurrently mutated in myeloid malignancies. We show that leukemia-associated BCOR/BCORL1 mutations unlink the PRC1.1 RING-PCGF enzymatic core from the KDM2B-containing chromatin targeting auxiliary subcomplex, either by causing complete protein loss or expression of a C-terminally truncated protein lacking the PCGF Ub-like fold discriminator (PUFD) domain. By uncoupling PRC1.1 repressive function from target genes, BCOR/BCORL1 mutations activate aberrant cell signaling programs that confer acquired resistance to treatment. This study provides a mechanistic basis for Polycomb repressive dysfunction as a key oncogenic driver in myeloid malignancies and identifies a potential strategy for targeted therapy in BCOR-mutated cancer.
Mitotic H3K9ac is controlled by phase-specific activity of HDAC2, HDAC3 and SIRT1
Authors: Gandhi Shashi , Mitterhoff Raizy , Rapoport Rachel , Farago Marganit , Greenberg Avraham , Hodge Lauren , Eden Sharon , Benner Christopher , Goran Alon , Simon Itamar 
Published: March 2021

AbstractHistone acetylation levels are reduced during mitosis. To study the mitotic regulation of H3K9ac we used an array of inhibitors targeting specific histone deacetylases. We evaluated the involvement of the targeted enzymes in regulating H3K9ac during all mitotic stages by immunofluorescence and immunoblots. We identified HDAC2, HDAC3 and SIRT1 as modulators of H3K9ac mitotic levels. HDAC2 inhibition increased H3K9ac levels in prophase, whereas HDAC3 or SIRT1 inhibition increased H3K9ac levels in metaphase. Next, we performed ChIP-seq on mitotic-arrested cells following targeted inhibition of these histone deacetylases. We found that both HDAC2 and HDAC3 have a similar impact on H3K9ac, and inhibiting either of these two HDACs substantially increases the levels of this histone acetylation in promoters, enhancers and insulators. Altogether, our results support a model in which H3K9 deacetylation is a stepwise process – at prophase HDAC2 modulates most transcription-associated H3K9ac-marked loci and at metaphase HDAC3 maintains the reduced acetylation, whereas SIRT1 potentially regulates H3K9ac by impacting HAT activity.Summary blurbCombination of immunofluorescence, western blot and ChIP-seq revealed the interplay between HDAC2, HDAC3 and SIRT1 in H3K9 deacetylation during mitosis of mammalian cells.
Domain dependent orchestrated regulation of bacterial growth, persistence and chemotaxis by an essential GTPase, CgtA, inVibrio cholerae
Authors: Das Sagarika , Datta Partha P. 
Published: March 2021

SummaryCgtA, an evolutionarily conserved GTPase, associated with the 50S ribosome controls a broad spectrum of physiological processes in bacteria. It has three structural domains, viz., N-terminal domain (NTD), GTPase domain and C-terminal domain (CTD). CgtA regulates expression of several of genes during nutritional stress inVibrio cholerae. The mechanism of transcriptional regulation by CgtA is unknown, though the NTD concomitantly with the GTPase domain participates in the process. Here, we show that thein vivodeletion of the 57 amino acids long CTD of CgtA GTPase ofV. choleraeis dispensable for viability, contrary to the complete knockdown ofcgtAgene. Slower growth was observed incgtAknockdown strain with intermittent diauxic lags in minimal media than the CTD deleted strain. Irreversible defect in colony morphology was observed in the cells with CTD deletion. Resuscitation of persister cells occurred when nutritionally deprived completecgtAknockdown cells after growing for longer periods were transferred to nutritionally enriched media. The motility of thecgtAknockdown strain was significantly reduced than the wild type cells. Furthermore, CTD deleted cells were also found to be defective in motility, but comparatively lower thancgtAknockdown cells. Elongated and slenderV. choleraecells were observed by SEM imaging uponcgtAdepletion, whereas, upon CTD deletion cellular elongation did not occur. Based on our study here, we propose that the CTD of CgtA perceives the nutritional stress response, to which the NTD and GTPase responds.
Efficient graphene oxide coating improves cryo-EM sample preparation and data collection from tilted grids
Authors: Patel Avinash , Toso Daniel , Litvak Audrey , Nogales Eva 
Published: March 2021

AbstractRecent technical developments have made single particle cryo-EM a major structural biology technique, especially in the characterization of challenging samples that resist crystallization, can only be obtained in small amounts, or suffer from compositional or conformational heterogeneity. However, a number of hurdles that often challenge sample preparation still need to be overcome in order to increase the applicability and throughput of cryo-EM. These technical hurdles include obtaining enough particles per image, with close to random orientation, and without damage from interaction with the air-water interface. While coating EM grids with graphene oxide is a promising procedure for the improvement of sample preparation, it suffers from some technical problems that limit its applicability. We have modified the established drop cast method for adhering graphene oxide onto holey patterned grids to increase graphene coverage. Our method relies on the use of a polycationic polymer to coat the surface of the grid prior to graphene oxide application, thereby preventing the repulsion of the negatively charged graphene oxide sheets from the negatively charged grid surface. With this improved preparation method, we show that graphene oxide supports can increase the number of particles in the field of view by an order of magnitude with respect to open holes, while keeping them away from the damaging air-water interface. We also show how graphene oxide coated gold foil grids can be used to collect tilted cryo-EM data in order to overcome preferred orientation issues, without experiencing the large amount of drift observed with conventional amorphous carbon supports, thus allowing data collection that can lead to high-resolution reconstructions.
A rapid CRISPR competitive assay forin vitroandin vivodiscovery of potential drug targets affecting the hematopoietic system
Authors: Shen Yunbing , Jiang Long , Iyer Vaishnavi Srinivasan , Raposo Bruno , Boddul Sanjay V. , Kasza Zsolt , Wermeling Fredrik 
Published: March 2021

CRISPR/Cas9 can be used as an experimental tool to inactivate genes in cells. However, a CRISPR-targeted cell population will not show a uniform genotype of the targeted gene. Instead, a mix of genotypes is generated - from wild type to different forms of insertions and deletions. Such mixed genotypes complicate analyzing the role of the targeted gene in the studied cell population. Here, we present a rapid experimental approach to functionally analyze a CRISPR-targeted cell population that does not involve generating clonal cell lines. As a simple readout, we leverage the CRISPR-induced genetic heterogeneity and use sequencing to identify how different genotypes are enriched or depleted related to the studied cellular behavior or phenotype. The approach uses standard PCR, Sanger sequencing, and a simple sequence deconvoluting software, enabling laboratories without specific in-depth knowledge to also perform these experiments. As proof of principle, we present examples studying the role of different genes for various aspects related to hematopoietic cells (T cell developmentin vivoand activationin vitro, macrophage phagocytosis, and a leukemia-like phenotype induced by overexpressing a proto-oncogene). In conclusion, we present a rapid experimental approach to identify potential drug targets related to mature immune cells, as well as normal and malignant hematopoiesis.Highlights‐CRISPR generates genetic heterogeneity at the targeted site.‐Genetic heterogeneity complicates identifying the role of a targeted gene.‐Heterogeneity can be quantified by Sanger sequencing with sufficient sensitivity.‐Enrichment of specific genotypes can be used to identify roles for targeted genes.‐Competitive experiments show the potential of genotype enrichment as a discovery tool.Graphical representation
Control of Parallel Hippocampal Output Pathways by Amygdalar Long-Range Inhibition
Authors: AlSubaie Rawan , Wee Ryan W S , Ritoux Anne , Mishchanchuk Karyna , Passlack Jessica , Regester Daniel , MacAskill Andrew F 
Published: March 2021

ABSTRACTProjections from the basal amygdala (BA) to the ventral hippocampus (vH) are proposed to provide information about the rewarding or threatening nature of learned associations to support appropriate goal-directed and anxiety-like behaviour. Such behaviour occurs via the differential activity of multiple, parallel populations of pyramidal neurons in vH that project to distinct downstream targets, but the nature of BA input and how it connects with these populations is unclear. Using channelrhodopsin-2-assisted circuit mapping in mice, we show that BA input to vH consists of both excitatory and inhibitory projections. Excitatory input specifically targets BA- and nucleus accumbens-projecting vH neurons, and avoids prefrontal cortex-projecting vH neurons; while inhibitory input preferentially targets BA-projecting neurons. Through this specific connectivity, BA inhibitory projections gate place-value associations by controlling the activity of nucleus accumbens-projecting vH neurons. Our results define a parallel excitatory and inhibitory projection from BA to vH that can support goal-directed behaviour.
Is galactose a hormetic sugar? Evidence from rat hippocampal redox regulatory network
Authors: Homolak J , Babic Perhoc A , Knezovic A , Kodvanj I , Virag D , Osmanovic Barilar J , Riederer P , Salkovic-Petrisic M 
Published: March 2021

AbstractGalactose is a ubiquitous simple monosaccharide with yet incompletely understood biochemical and physiological role. Most of what we currently know about galactose is based on induction from the research on inherited disorders of galactose metabolism and animal models that exploit galactose-induced oxidative stress to model aging in rodents, however, recent evidence also demonstrates unique properties of galactose to conserve cellular function during the periods of starvation, and prevent and alleviate cognitive deficits in a rat model of sporadic Alzheimer’s disease. Here, we try to understand the molecular background of both detrimental and beneficial effects of galactose by exploring the acute systemic and hippocampal biochemical changes upon oral administration of galactose solution focusing primarily on the components of the redox regulatory network (RRN). Although orogastric gavage of galactose solution (200 mg/kg) was insufficient to induce systemic RRN disbalance in the first two hours upon administration, analysis of hippocampal RRN revealed a mild pro-oxidative shift accompanied by a paradoxical increase in tissue reductive capacity, suggesting overcompensation of endogenous antioxidant systems in the response to the pro-oxidative stimulus. The more thorough analysis revealed that galactose-induced increment of reductive capacity was accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1. Based on the observed findings, and in the context of previous work on galactose, we propose a hormetic hypothesis of galactose action suggesting that the protective effects of galactose might be inseparable from its pro-oxidative effects at the biochemical level.
The conflict between social role expectations and entrepreneurial role demands among women entrepreneurs in sub-Saharan Africa: empirical study from Ethiopia
Authors: Mulu Hundera , Duysters Geert , Naudé Wim , Dijkhuizen Josette 
Published: March 2021

Purpose
The purpose of this paper is to develop items for measuring the role conflict between social role expectations (SREs) and entrepreneurial role demands (ERDs) among women entrepreneurs in sub-Saharan Africa (SSA).

Design/methodology/approach
This paper uses 20 interviews and literature from SSA to develop items, a survey of 408 to conduct factor analysis and a survey of 307 to conduct criterion validity analysis.

Findings
Statistical analysis shows that the scales used adequately captured two dimensions of SRE and ERD conflict: SRE-to-ERD conflict and ERD-to-SRE conflict. It was found that the SRE-to-ERD-conflict scale is reliable and valid with the five dimensions of entrepreneurial success and that women entrepreneur’s experience significant role conflict between SREs and ERDs.

Research limitations/implications
The implication is that standard scales measuring work and family conflict, which tend to focus solely on the work and family context, cannot adequately account for role conflict among women entrepreneurs.

Practical implications
The practical implications of these findings are discussed.

Originality/value
New scale items form measuring the conflict between SREs and ERDs were developed.
Crowd-shipping for urban food rescue logistics
Authors: Mittal Anuj , Oran Gibson Nilufer , Krejci Caroline C. , Marusak Amy Ann 
Published: March 2021

PurposeThe purpose of this research is to gain a better understanding of how a crowd-shipping platform can achieve a critical mass of senders and carrier crowd members to yield network effects that are necessary for the platform to grow and thrive. Specifically, this research studies the participation decisions of both senders and carriers over time and the impacts of the resulting feedback loop on platform growth and performance.Design/methodology/approachAn agent-based model is developed and used to study dynamic behavior and network effects within a simulated crowd-shipping platform. The model allows both carriers and senders to be represented as autonomous, heterogeneous and adaptive agents, whose decisions to participate in the platform impact the participation of other agents over time. Survey data inform the logic governing agent decisions and behaviors.FindingsThe feedback loop created by individual sender and carrier agents' participation decisions generates complex and dynamic network effects that are observable at the platform level. Experimental results demonstrate the importance of having sufficient crowd carriers available when the platform is initially launched, as well as ensuring that sender and carrier participation remains balanced as the platform grows over time.Research limitations/implicationsThe model successfully demonstrates the power of agent-based modeling (ABM) in analyzing network effects in crowd-shipping systems. However, the model has not yet been fully validated with data from a real-world crowd-shipping platform. Furthermore, the model's geographic scope is limited to a single census tract. Platform behavior will likely differ across geographic regions, with varying demographics and sender/carrier density.Practical implicationsThe modeling approach can be used to provide the manager of a volunteer-based crowd-shipping program for food rescue with insights on how to achieve a critical mass of participants, with an appropriate balance between the number of restaurant food donation delivery requests and the number of crowd-shippers available and willing to make those deliveries.Social implicationsThis research can help a crowd-shipping platform for urban food rescue to grow and become self-sustainable, thereby serving more food-insecure people.Originality/valueThe model represents both senders and the carrier crowd as autonomous, heterogeneous and adaptive agents, such that network effects resulting from their interactions can emerge and be observed over time. The model was designed to study a volunteer crowd-shipping platform for food rescue, with participant motivations driven by personal values and social factors, rather than monetary incentives.
A framework for the relationship implications of additive manufacturing (3D printing) for industrial marketing: servitization, sustainability and customer empowerment
Authors: Chaney Damien , Gardan Julien , De Freyman Julien 
Published: March 2021

Purpose
The purpose of this paper is to present the relationship implications of additive manufacturing (AM), which has the ability to produce layer-by-layer three-dimensional complex products by adding material in comparison to traditional manufacturing processes which remove material – for industrial marketing.

Design/methodology/approach
After presenting the literature on customer relationships and digital technologies in business-to-business, the study uses a “zoom-out” and “zoom-in” perspective to review the extant literature on AM and then makes study propositions for industrial marketing.

Findings
Through the adoption of AM technologies, the study suggests that firms can improve their level of servitization through customized products, offer more sustainable value propositions and empower their customers through the sale of digital files, which can be considered as levers to strengthen relationships with customers.

Research limitations/implications
This paper makes several propositions regarding the relationship implications of AM for industrial marketing that further research should test.

Practical implications
This paper highlights the relational benefits that adopting AM may represent for companies.

Originality/value
While AM which is considered as an industrial revolution has generated a wide body of research in engineering and operations and technology management sciences, its impact on industrial marketing remains understudied.
Exploring frontliners' knowledge, participation and evaluation in the implementation of a pay-for-performance program (PMAQ) in primary health care in Brazil
Authors: Saddi Fabiana da Cunha , Harris Matthew , Parreira Fernanda Ramos , Pêgo Raquel Abrantes , Coelho Germano Araujo , Lozano Renata Batista , Mundim Pedro dos Santos , Peckham Stephen 
Published: March 2021

PurposeThis paper employs implementation theory and the political literature on performance measurement to understand how frontline health workers know, participate and evaluate the Brazilian National Program for Improving Access and Quality of Primary Care (PMAQ, 2nd round).Design/methodology/approachThis paper develops an implementation theory-driven qualitative analysis. The research is developed in the city of Goiania (Brazil): a challenging organizational context in primary care (PHC). Interviews were carried out with 25 frontliners – managers, doctors, nurses and community health workers. Data were thematically and hierarchically analysed according to theoretical concepts such as policy knowledge, policy adherence, forms of accountability, alternative logics, organizational capacity and policy feedback.FindingsResults show the need to foster organizational capacity, knowledge, participation and policy feedback at the frontline. Successful implementation would require those adaptations to counteract policy challenges/failures or the emergence of alternative logics.Research limitations/implicationsThe study was conducted in only one setting, however, our sample includes different types of professionals working in units with different levels of organization capacity, located in distinct HDs, expressing well the implementation of PMAQ/P4P. Qualitative researches need to be developed for further exploring the same/other factors.Social implicationsFindings can be used to improve discussions/planning and design of P4P programs in the city and State of Goias.Originality/valueThe majority of analysis of PMAQ are of a quantitative or results-based nature. This article focuses on politically significant and unanswered questions regarding the implementation of PMAQ.