bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative evaluation of synthetic cytokines for enhancing production and performance of NK92 cell-based therapies
Authors: Deol Simrita , Donahue Patrick S. , Mitrut Roxanna E. , Hammitt-Kess Iva J. , Ahn Jihae , Zhang Bin , Leonard Joshua N. 
Published: May 2023

AbstractAutologous immune cell therapies are potentially curative, but cost and manufacturing complexity limit access. Off-the-shelf therapies may address these gaps, but further development is needed. The NK92 cell line has a natural killer-like phenotype, has efficacy in cancer clinical trials, and is safe after irradiation. However, NK92 lose activity post-injection, limiting efficacy. This may be addressed by engineering NK92 to express stimulatory factors, for which comparative analysis is needed. Thus, we systematically explored expression of synthetic cytokines for enhancing NK92 production and performance. All synthetic cytokines evaluated (membrane-bound IL2 and IL15, and engineered versions of Neoleukin-2/15, IL15, IL12, and decoy resistant IL18) enhanced NK92 cytotoxicity. Genetically modified cells preferentially expanded by expressing membrane-bound but not soluble synthetic cytokines, and all engineered cells remained sensitive to irradiation. Interestingly, some membrane-bound cytokines conferred cell-contact independent paracrine activity partly attributable to extracellular vesicles. Finally, we characterized interactions within consortia of differently engineered NK92.
The role of structuralvscellular remodeling in arrhythmogenesis: personalized computer models of atrial fibrillation
Authors: Pikunov Andrey V. , Syunyaev Roman A. , Ali Rheeda , Prakosa Adityo , Boyle Patrick M. , Steckmeister Vanessa , Kutschka Ingo , Rytkin Eric , Voigt Niels , Trayanova Natalia , Efimov Igor R. 
Published: May 2023

AbstractAtrial fibrillation (AF) is a progressive disease involving both structural and functional remodeling. To investigate the contribution of cell-scale functional remodeling to AF pathogenesis, we combined personalized 3D anatomical models with pathology-specific ionic models. The latter were developed using recordings in myocytes isolated from patients in sinus rhythm, paroxysmal, postoperative, and persistent AF. To quantify AF dynamics, we developed a novel algorithm for locating RDs by backtracking the conduction velocity field from the wavebreak regions. We demonstrate that our novel algorithm is at least 700 times faster than the traditional phase singularity analysis. The inducibility of simulated AF was not pathology-dependent, but pathological models demonstrate a more extensive arrhythmogenic substrate compared to the sinus rhythm. AF driver locations depend on electrophysiological remodeling; differences between pathology-specific models are explained by differences in wavebreak patterns. Specifically, RDs tend to dwell in the regions with the highest wavebreak probability.
Unrestricted Versus Regulated Open Data Governance: A Bibliometric Comparison of SARS-CoV-2 Nucleotide Sequence Databases
Authors: Sheehan Nathanael , Botta Federico , Leonelli Sabina 
Published: May 2023

AbstractTwo distinct modes of data governance have emerged in accessing and reusing viral data pertaining to COVID-19: an unrestricted model, espoused by data repositories part of the International Nucleotide Sequence Database Collaboration and a regulated model promoted by the Global Initiative on Sharing All Influenza data. In this paper, we focus on publications mentioning either infrastructure in the period between January 2020 and January 2023, thus capturing a period of acute response to the COVID-19 pandemic. Through a variety of bibliometric and network science methods, we compare the extent to which either data infrastructure facilitated collaboration from different countries around the globe to understand how data reuse can enhance forms of diversity between institutions, countries, and funding groups. Our findings reveal disparities in representation and usage between the two data infrastructures. We conclude that both approaches offer useful lessons, with the unrestricted model providing insights into complex data linkage and the regulated model demonstrating the importance of global representation.
Dual roles of crustacean female sex hormone during juvenile stage in the kuruma prawnMarsupenaeus japonicus
Authors: Toyota Kenji , Matsushima Hanako , Osanai Rei , Okutsu Tomoyuki , Yamane Fumihiro , Ohira Tsuyoshi 
Published: May 2023

ABSTRACTThe crustacean female sex hormone (CFSH) has been identified as a female-specific hormone that plays a crucial role in female phenotype developments in the blue crabCallinectes sapidus. To date, its homologous genes have been reported in various decapod species. Additionally, unlike the blue crab, several species have two different CFSH subtypes. The kuruma prawnMarsupenaeus japonicusis a representative example species of this phenomenon, having two CFSH subtypes identified from the eyestalk (MajCFSH) and ovary (MajCFSH-ov). Eyestalk-type MajCFSH is expressed predominantly in the eyestalk at the same level in both sexes, indicating no female-specificity. Here, we conducted gene knockdown analysis of eyestalk-type MajCFSH using sexually immature juveniles of kuruma prawn (average body length: ∼10 mm) to elucidate its physiological functions. As a result, MajCFSH-knockdown did not affect the development of sex-specific characteristics such as external reproductive organs, while it induced apparent growth suppression in male juveniles, implying that MajCFSH may play a male-specific juvenile growth role. Moreover, MajCFSH-knockdown female and male juveniles changed their body color to become brighter, indicating that MajCFSH has the ability to change body color by dispersing the pigment granules in the chromatophore. Overall, our present study improved our understanding of the physiological roles of CFSH using kuruma prawn.Highlights-MajCFSH-knockdown was conducted using sexually immature juveniles of kuruma prawn.-MajCFSH-knockdown male juveniles showed significant growth suppression.-MajCFSH-knockdown female and male juveniles changed their body color to become brighter.
Cul3 substrate adaptor SPOP targets Nup153 for degradation
Authors: Ong Joseph Y. , Torres Jorge Z. 
Published: May 2023

AbstractSPOP is a Cul3 substrate adaptor responsible for degradation of many proteins related to cell growth and proliferation. Because mutation or misregulation of SPOP drives cancer progression, understanding the suite of SPOP substrates is important to understanding regulation of cell proliferation. Here, we identify Nup153, a component of the nuclear basket of the nuclear pore complex, as a novel substrate of SPOP. SPOP and Nup153 bind to each other and colocalize at the nuclear envelope and some nuclear foci in cells. The binding interaction between SPOP and Nup153 is complex and multivalent. Nup153 is ubiquitylated and degraded upon expression of SPOPWTbut not its substrate binding-deficient mutant SPOPF102C. Depletion of SPOP via RNAi leads to Nup153 stabilization. Upon loss of SPOP, the nuclear envelope localization of spindle assembly checkpoint protein Mad1, which is tethered to the nuclear envelope by Nup153, is stronger. Altogether, our results demonstrate SPOP regulates Nup153 levels and expands our understanding of the role of SPOP in protein and cellular homeostasis.
Patterns of early neocortical amyloid beta accumulation: a positron emission tomography population-based study
Authors: Lecy Emily E. , Min Hoon-Ki , Apgar Christopher J. , Maltais Daniela D. , Lundt Emily S. , Albertson Sabrina M. , Senjem Matthew L. , Schwarz Christopher G. , Botha Hugo , Graff-Radford Jonathan , Jones David T. , Vemuri Prashanthi , Kantarci Kejal , Knopman David S. , Petersen Ronald C. , Jack Clifford R. , Lee Jeyeon , Lowe Val J. 
Published: May 2023

AbstractIntroductionThe widespread deposition of amyloid beta (Aβ) plaques in late-stage Alzheimer’s disease (AD) is well defined and confirmed byin vivopositron emission tomography (PET). However, there are discrepancies between which regions contribute to the earliest topographical Aβ deposition within the neocortex.MethodsThis study investigated Aβ signals in the peri-threshold SUVr range using Pittsburgh compound B (PiB) PET in a population-based study cross-sectionally and longitudinally. PiB-PET scans from 1,088 participants were assessed to determine the early patterns of PiB loading in the neocortex.ResultsEarly-stage Aβ loading is seen first in the temporal, cingulate, and occipital regions. Regional early deposition patterns are similar in both Apolipoprotein ε4 (APOE) carriers and non-carriers. Hierarchical clustering analysis shows groups with different patterns of early amyloid deposition.DiscussionThese finding of initial Aβ deposition patterns may be of significance for diagnostics and understanding the development of different AD phenotypes.
Research Paradigm of the International Classification of Functioning, Disability and Health (ICF) with Item Response Theory: Clarification, Classification, and Challenge
Authors: Feng Chun , Liu Shou-Guo , Lin Feng 
Published: May 2023

AbstractObjectivesThe purpose of this literature review was to clarify the sufficiency and efficiency needs, as well as the stratification and the assignment scoring principles of the International Classification of Functioning, Disability and Health (ICF) core set, in conjunction with the Item Response Theory (IRT)-derived functioning outcome measures.MethodsA literature search has been done on the PubMed database. We included studies involving the IRT-derived ICF evaluation tool. Our main outcome was the assignment and stratification scoring principle of IRT-derived ICF-based functioning outcome measures.Results46 relative articles met the eligibility criteria of our review. On this basis, this review was undertaken to track the research progress of the ICF-based and IRT-modeling measurement tools and screen the final core set. This review included a classification of IRT modeling for ICF studies and a summary of existing research paradigms of IRT-derived ICF outcome measures. Moreover, this review identified blind spots related to scoring assignment principles and “difficulty parameter” in current ICF-based IRT studies.ConclusionThe ICF is the worldwide terminology system for functioning categories, while ICF-based evaluation in clinical practice and scientific research has elicited the underlying challenges. However, the algorithm of the ICF-based IRT modeling may advance the understanding of ICF clinical application and enable a new paradigm for the design of IRT-derived ICF questionnaires, namely the parsimonious core set of ICF. Additionally, the Wright map has the potential to facilitate an understanding of the rehabilitation process and tailor rehabilitation goals.
Global substrate identification and high throughputin vitrodephosphorylation reactions uncover PP1 and PP2A-B55 specificity principles
Authors: Hein Jamin B. , Nguyen Hieu T. , Garvanska Dimitriya H. , Nasa Isha , Feng Yinnian , Mendez Blanca Lopez , Davey Norman , Kettenbach Arminja N , Fordyce Polly M. , Nilsson Jakob 
Published: May 2023

AbstractPhosphoprotein phosphatases (PPPs) dephosphorylate Serine (Ser)/Threonine (Thr) residues to regulate major signaling pathways and cellular transitions. Despite the central role of PPPs the substrates in most cellular processes and the determinants of phosphatase specificity are poorly understood. This is because methods to investigate this at scale are lacking. Here we develop a novelin vitroassay, MRBLE:Dephos, that allows multiplexing of dephosphorylation reactions to determine phosphatase preferences. Using MRBLE:Dephos, we establish amino acid preferences of the residues surrounding the dephosphorylation site for PP1 and PP2A- B55, which reveals common and unique preferences for the two phosphatases. To compare the MRBLE:Dephos results to cellular substrates, we focused on mitotic exit that requires extensive dephosphorylation by PP1 and PP2A-B55. We use specific inhibition of PP1 and PP2A-B55 in mitotic exit lysates coupled with quantitative phosphoproteomics to identify more than 2000 regulated phosphorylation sites. Importantly, the sites dephosphorylated during mitotic exit reveal key signatures that are consistent with the MRBLE:Dephos results. We use these insights to specifically alter INCENP dephosphorylation kinetics at mitotic exit, resulting in defective cytokinesis thus underscoring the biological relevance of our determined specificity principles. Finally, we provide a comprehensive characterization of PP1 binding motifs and demostrate how binding of phosphatases to substrates shapes dephosphorylation specificity. Collectively, we develop novel approaches to advance our ability to investigate protein phosphatases and use these to provide a framework for understanding mitotic exit regulation by dephosphorylation.
Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes inPink1/parkinmodels
Authors: Martinez Aitor , Sanchez-Martinez Alvaro , Pickering Jake T. , Twyning Madeleine J. , Terriente-Felix Ana , Chen Po-Lin , Chen Chun-Hong , Whitworth Alexander J. 
Published: May 2023

AbstractBackgroundMitochondrial dysfunction and toxic protein aggregates have been shown to be key features in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). Functional analysis of genes linked to PD have revealed that the E3 ligase Parkin and the mitochondrial kinase PINK1 are important factors for mitochondrial quality control. PINK1 phosphorylates and activates Parkin, which in turn ubiquitinates mitochondrial proteins priming them and the mitochondrion itself for degradation. However, it is unclear whether dysregulated mitochondrial degradation or the toxic build-up of certain Parkin ubiquitin substrates is the driving pathophysiological mechanism leading to PD. The iron-sulphur cluster containing proteins CISD1 and CISD2 have been identified as major targets of Parkin in various proteomic studies.MethodsWe employedin vivo Drosophilaand human cell culture models to study the role of CISD proteins in cell and tissue viability as well as aged-related neurodegeneration, specifically analysing aspects of mitophagy and autophagy using orthogonal assays.ResultsWe discovered that theDrosophilahomolog Cisd accumulates during aging, as well as inPink1andparkinmutant flies. We observed that build-up of Cisd is particularly toxic in neurons, resulting in mitochondrial defects and Ser65-phospho-Ubiquitin accumulation. Age-related increase of Cisd blocks mitophagy and impairs autophagy flux. Importantly, reduction of Cisd levels upregulates mitophagyin vitroandin vivo, and ameliorates pathological phenotypes in locomotion, lifespan and neurodegeneration inPink1/parkinmutant flies. In addition, we show that pharmacological inhibition of CISD1/2 by rosiglitazone and NL-1 induces mitophagy in human cells and rescues the defective phenotypes ofPink1/parkinmutants.ConclusionAltogether, our studies indicate that Cisd accumulation during aging and inPink1/parkinmutants is a key driver of pathology by blocking mitophagy, and genetically and pharmacologically inhibiting CISD proteins may offer a potential target for therapeutic intervention.
Single Cell Transcriptome of Stress Vulnerability Network in mouse Prefrontal Cortex
Authors: Hing Benjamin , Mitchell Sara B. , Eberle Maureen , Filali Yassine , Hultman Ian , Matkovich Molly , Kasturirangan Mukundan , Wyche Whitney , Jimenez Alli , Velamuri Radha , Johnson Micah , Srivastava Sanvesh , Hultman Rainbo 
Published: May 2023

SummaryIncreased vulnerability to stress is a major risk factor for the manifestation of several mood disorders, including major depressive disorder (MDD). Despite the status of MDD as a significant donor to global disability, the complex integration of genetic and environmental factors that contribute to the behavioral display of such disorders has made a thorough understanding of related etiology elusive. Recent developments suggest that a brain-wide network approach is needed, taking into account the complex interplay of cell types spanning multiple brain regions. Single cell RNA-sequencing technologies can provide transcriptomic profiling at the single-cell level across heterogenous samples. Furthermore, we have previously used local field potential oscillations and machine learning to identify an electrical brain network that is indicative of a predisposed vulnerability state. Thus, this study combined single cell RNA-sequencing (scRNA-Seq) with electrical brain network measures of the stress-vulnerable state, providing a unique opportunity to access the relationship between stress network activity and transcriptomic changes within individual cell types. We found especially high numbers of differentially expressed genes between animals with high and low stress vulnerability brain network activity in astrocytes and glutamatergic neurons but we estimated that vulnerability network activity depends most on GABAergic neurons. High vulnerability network activity included upregulation of microglia and mitochondrial and metabolic pathways, while lower vulnerability involved synaptic regulation. Genes that were differentially regulated with vulnerability network activity significantly overlapped with genes identified as having significant SNPs by human GWAS for depression. Taken together, these data provide the gene expression architecture of a previously uncharacterized stress vulnerability brain state, enabling new understanding and intervention of predisposition to stress susceptibility.
Label-free deep learning-based species classification of bacteria imaged by phase-contrast microscopy
Authors: Hallström Erik , Kandavalli Vinodh , Ranefall Petter , Elf Johan , Wählby Carolina 
Published: May 2023

AbstractReliable detection and classification of bacteria and other pathogens in the human body, animals, food, and water is crucial for improving and safeguarding public health. For instance, identifying the species and its antibiotic susceptibility is vital for effective bacterial infection treatment. Here we show that phase contrast time-lapse microscopy combined with deep learning is sufficient to discriminate four species of bacteria relevant to human health. The classification is performed on living bacteria and does not require fixation or staining, meaning that the bacterial species can be determined as the bacteria reproduce in a microfluidic device, enabling parallel determination of susceptibility to antibiotics. We assess the performance of convolutional neural networks and vision transformers, where the best model attained a class-average accuracy exceeding 98%. Our successful proof-of-principle results suggest that the methods should be challenged with data covering more species and clinically relevant isolates for future clinical use.Author SummaryBacterial infections are a leading cause of premature death worldwide, and growing antibiotic resistance is making treatment increasingly challenging. To effectively treat a patient with a bacterial infection, it is essential to quickly detect and identify the bacterial species and determine its susceptibility to different antibiotics. Prompt and effective treatment is crucial for the patient’s survival. Amicrofluidicdevice functions as a miniature “lab-on-chip” for manipulating and analyzing tiny amounts of fluids, such as blood or urine samples from patients. Microfluidic chips with chambers and channels have been designed for quickly testing bacterial susceptibility to different antibiotics by analyzing bacterial growth. Identifying bacterial species has previously relied on killing the bacteria and applying species-specific fluorescent probes. We introduce deep learning models as a fast and cost-effective method for identifying bacteria species directly from phase-contrast microscopy images of living bacteria simultaneously as growth is analyzed. We envision this method being employed concurrently with antibiotic susceptibility tests in future applications, significantly enhancing bacterial infection treatments.
Artificial intelligence to counteract “KPI overload” in business process monitoring: the case of anti-corruption in public organizations
Authors: Caruso Simone , Bruccoleri Manfredi , Pietrosi Astrid , Scaccianoce Antonio 
Published: May 2023

PurposeThe nature and amount of data that public organizations have to monitor to counteract corruption lead to a phenomenon called “KPI overload”, consisting of the business analyst feeling overwhelmed by the amount of information and resulting in the absence of appropriate control. The purpose of this study is to develop a solution based on Artificial Intelligence technology to avoid data overloading and, at the same time, under-controlling in business process monitoring.Design/methodology/approachThe authors adopted a design science research approach. The authors started by observing a specific problem in a real context (a healthcare organization); then conceptualized, designed and implemented a solution to the problem with the goal to develop knowledge that can be used to design solutions for similar problems. The proposed solution for business process monitoring integrates databases and self-service business intelligence for outlier detection and artificial intelligence for classification analysis.FindingsThe authors found the solution powerful to solve problems related to KPI overload in process monitoring. In the specific case study, the authors found that the combination of Business Intelligence and Artificial Intelligence can provide a significant contribution to the detection of fraud, corruption and/or policy misalignment in public organizations.Originality/valueThe authors provide a big-data-based solution to the problem of data overload in business process monitoring that does not sacrifice any monitored Key Performance Indicators and that also reduces the workload of the business analyst. The authors also developed and implemented this automated solution in a context where data sensitivity and privacy are critical issues.
Exploring the relationship between servant leadership and volunteer attitudes within a US Catholic diocese
Authors: Karickal Rojin , Richardson Katherine M. 
Published: May 2023

PurposeThe purpose of this paper is to examine the relationship between pastoral servant leadership and Church volunteer's perceptions of workplace spirituality, affective commitment, and organizational citizenship behavior in the context of the Catholic Church.Design/methodology/approachAn online survey was administered to 200 volunteer staff in a Catholic diocese located in the Northeastern US. 123 participants responded, for a 61.5% response rate.FindingsA significant positive relationship was found between volunteer staff perceptions of pastoral servant leadership and their workplace spirituality as well as affective commitment. No relationship was found between servant leadership and organizational citizenship behavior.Originality/valueThis is one of the first studies to examine servant leadership within the US Catholic Church. Findings add value to the literature on servant leadership and its importance to volunteerism, and in particular the positive benefits of servant leadership for staff volunteers in a Church environment.