bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of environment on the evolution and proliferation of protocells of increasing complexity
Authors: Roy Suvam , Sengupta Supratim
Published: July 2022

The formation, growth, division and proliferation of protocells containing RNA strands is an important step in ensuring the viability of a mixed RNA-lipid world. Experiments and computer simulations indicate that RNA encapsulated inside protocells can favour the protocell promoting its growth while protecting the system from being over-run by parasites. Recent work has also shown the rolling-circle replication mechanism can be harnessed to ensure rapid growth of RNA strands and probabilistic emergence and proliferation of protocells with functionally diverse ribozymes. Despite these advances in our understanding of a primordial RNA-lipid world, key questions remain about the ideal environment for formation of protocells and its role in regulating the proliferation of functionally complex protocells. The hot spring hypothesis suggests that mineral-rich regions near hot-springs, subject to dry-wet cycles provide an ideal environment for the origin of primitive protocells. We develop a computational model to study protocellular evolution in such environments that are distinguished by the occurrence of three distinct phases, a wet phase, followed by a gel phase, and subsequently by a dry phase. We determine the conditions under which protocells containing multiple types of ribozymes can evolve and proliferate in such regions. We find that diffusion in the gel-phase can inhibit the proliferation of complex protocells with the extent of inhibition being most significant when a small fraction of protocells is eliminated during environmental cycling. Our work clarifies how the environment can shape the evolution and proliferation of complex protocells.
Myeloid mechano-metabolic programming restricts anti-tumor immunity
Authors: Tharp K.M. , Kersten K. , Maller O.M. , Timblin G.A. , Stashko C. , Canale F.P. , Hayward M-K. , Berestjuk I. , ten Hoeve-Scott J. , Samad B. , Ironside A.J. , Geiger R. , Combes A.J. , Weaver V.M.
Published: July 2022

Tumor progression is accompanied by fibrosis, which is associated with diminished anti-tumor immune infiltrate. Here, we demonstrate that tumor infiltrating myeloid cells respond to the stiffened fibrotic tumor microenvironment (TME) by initiating a TGF-beta (TGFβ)-directed, collagen biosynthesis program. A collateral effect of this programming is an untenable metabolic milieu for productive CD8 T cell anti-tumor responses, as collagen-synthesizing macrophages consume environmental arginine, synthesize proline, and secrete ornithine that compromises CD8+T cell function. Thus, a stiff and fibrotic TME may impede anti-tumor immunity not only by direct physical exclusion of CD8+T cells, but also via secondary effects of a myeloid mechano-metabolic programming we identified that creates an inhospitable metabolic milieu for CD8+T cells.
Telomere dysfunction impairs intestinal differentiation and predisposes to diet-induced colitis
Authors: Engevik Mindy , Guo Lei , Song Won-Suk , Chronowski Christopher G , Akhanov Viktor , Bosquez Navish , Engevik Amy C. , Oezguen Numan , Coarfa Cristian , Putluri Nagireddy , Catic Andre , Baur Joseph A. , Finegold Milton , Shroyer Noah , Gu Jianhua , Ferraris Ronaldo P. , Halliday Jennifer A , Herman Christophe , Colla Simona , Dierick Herman , Jang Cholsoon , Sahin Ergun
Published: July 2022

Intestinal epithelium dysfunction causes barrier defects, malabsorption and dysbiosis, predicting local and systemic disease, morbidity and mortality in humans. However, the underlying causes are not well understood. Here we show that telomere shortening is a host intrinsic factor that impairs enterocyte differentiation. The presence of such undifferentiated enterocytes is associated with barrier disruption and malabsorption of nutrients, such as fructose. A fructose-rich diet causes increased fructose spillover to the colon and induces colitis in a microbiome-dependent manner. The microbiome uses fructose to synthesize essential metabolites, including NAD precursors, that complement the host’s low NAD pool in the inflamed colon. Thus, telomere shortening drives enterocyte dysfunction and predisposes to diet-induced colitis through barrier disruption, increased nutrient flux to the colon and modulation of the microbiome. This differerentiation defect expands the canonical stem cell failure-centered view of how telomere shortening impacts the intestine and predisposes to intestinal disease in conditions associated with short telomeres.
AlphaPeptDeep: A modular deep learning framework to predict peptide properties for proteomics
Authors: Zeng Wen-Feng , Zhou Xie-Xuan , Willems Sander , Ammar Constantin , Wahle Maria , Bludau Isabell , Voytik Eugenia , Strauss Maximillian T. , Mann Matthias
Published: July 2022

Machine learning and in particular deep learning (DL) are increasingly important in mass spectrometry (MS)-based proteomics. Recent DL models can predict the retention time, ion mobility and fragment intensities of a peptide just from the amino acid sequence with good accuracy. However, DL is a very rapidly developing field with new neural network architectures frequently appearing, which are challenging to incorporate for proteomics researchers. Here we introduce AlphaPeptDeep, a modular Python framework built on the PyTorch DL library that learns and predicts the properties of peptides (https://github.com/MannLabs/alphapeptdeep). It features a model shop that enables non-specialists to create models in just a few lines of code. AlphaPeptDeep represents post-translational modifications in a generic manner, even if only the chemical composition is known. Extensive use of transfer learning obviates the need for large data sets to refine models for particular experimental conditions. The AlphaPeptDeep models for predicting retention time, collisional cross sections and fragment intensities are at least on par with existing tools. Additional sequence-based properties can also be predicted by AlphaPeptDeep, as demonstrated with a novel HLA peptide prediction model to improve HLA peptide identification for data-independent acquisition.
Sub-threshold neuronal activity and the dynamical regime of cerebral cortex
Authors: Amsalem Oren , Inagaki Hidehiko , Yu Jianing , Svoboda Karel , Darshan Ran
Published: July 2022

Cortical neurons exhibit temporally irregular spiking patterns and heterogeneous firing rates. These features arise in model circuits operating in a ‘fluctuation-driven regime’, in which fluctuations in membrane potentials emerge from the network dynamics. However, it is still unclear whether the cortex operates in this regime. We evaluated the fluctuation-driven hypothesis by analyzing spiking and sub-threshold membrane potentials of neurons in the sensory and frontal cortex recorded during a decision-making task. Standard fluctuation-driven models account for spiking statistics but fail to capture the heterogeneity in sub-threshold activity. We address this issue by effectively incorporating dendritic conductances into the standard models. Our model suggests that the frontal cortex operates in a fluctuation-driven regime. In contrast, excitatory neurons in layer 4 of the barrel cortex are not fluctuation-driven; they spike in response to occasional synchronous inputs. Our work reveals fundamental differences between cortical areas, suggesting that they operate in different dynamical regimes.
In-line swimming dynamics revealed by fish interacting with a robotic mechanism
Authors: Thandiackal Robin , Lauder George V.
Published: July 2022

Schooling in fish is linked to a number of factors such as increased foraging success, predator avoidance, and social interactions. In addition, a prevailing hypothesis is that swimming in groups provides energetic benefits through hydrodynamic interactions. Thrust wakes are frequently occurring flow structures in fish schools as they are shed behind swimming fish. Despite increased flow speeds in these wakes, recent modelling work has suggested that swimming directly in-line behind an individual may lead to increased efficiency. However, no data are available on live fish interacting with thrust wakes. Here we designed a controlled experiment in which brook trout, Salvelinus fontinalis, interact with thrust wakes generated by a robotic mechanism that produces a fish-like wake. We show that trout swim in thrust wakes, reduce their tail-beat frequencies, and synchronize with the robotic flapping mechanism. Our flow and pressure field analysis revealed that the trout are interacting with oncoming vortices and that they exhibit reduced pressure drag at the head compared to swimming in isolation. Together, these experiments suggest that trout swim energetically more efficiently in thrust wakes and support the hypothesis that swimming in the wake of one another is an advantageous strategy to save energy in a school.
Arabidopsis uses a molecular grounding mechanism and a biophysical circuit breaker to limit floral abscission signaling
Authors: Taylor Isaiah W. , Patharkar O. Rahul , Mijar Medhavinee , Hsu Che-Wei , Baer John , Niederhuth Chad E. , Ohler Uwe , Benfey Philip N. , Walker John C.
Published: July 2022

Abscission is the programmed separation of plant organs. It is widespread in the plant kingdom with important functions in development and environmental response. In Arabidopsis, abscission of floral organs (sepals, petals, and stamens) is controlled by two receptor-like protein kinases HAESA (HAE) and HAESA LIKE-2 (HSL2), which orchestrate the programmed dissolution of the abscission zone connecting floral organs to the developing fruit. In this work, we use single-cell RNA-Sequencing to characterize the coreHAE/HSL2abscission gene expression program. We identify theMAP KINASE PHOSPHATASE-1/MKP1gene as a negative regulator of this pathway. MKP1 acts prior to activation of HAE/HSL2 signaling to establish a signaling threshold required for the initiation of abscission. By analogy to electrical circuit control, we liken MKP1 to a molecular grounding mechanism that dissipates errant pathway activation absent HAE/HSL2 signaling. Furthermore, we use single-cell data to identify genes expressed in two sub-populations of abscission zone cells: those proximal and those distal to the plane of separation. We identifyINFLORESCENCE DEFICIENT IN ABSCISSION/IDA, encoding the activating ligand of HAE/HSL2, as one of the mRNAs most highly enriched in distal abscission zone cells at the base of the abscising organs. We show how this expression pattern forms a biophysical circuit breaker whereby, when the organ is shed, the source of the IDA peptide is removed, leading to cessation of HAE/HSL2 signaling. Overall, this work provides insight into the multiple control mechanisms acting on the abscission-signaling pathway.
Modulatory dynamics of periodic and aperiodic activity in respiration-brain coupling
Authors: Kluger Daniel S. , Forster Carina , Abbasi Omid , Chalas Nikos , Villringer Arno , Gross Joachim
Published: July 2022

Bodily rhythms such as respiration are increasingly acknowledged to modulate neural oscillations underlying human action, perception, and cognition. Conversely, the link between respiration and aperiodic brain activity – a non-oscillatory reflection of excitation-inhibition (E:I) balance – has remained unstudied. Aiming to disentangle potential respiration-related dynamics of periodic and aperiodic activity, we applied recently developed algorithms of time-resolved parameter estimation to resting-state MEG and EEG data from two labs (total N = 78 participants). We provide evidence that fluctuations of aperiodic brain activity (1/f slope) are phase-locked to the respiratory cycle, which suggests that spontaneous state shifts of excitation-inhibition balance are at least partly influenced by peripheral bodily signals. Moreover, differential temporal dynamics in their coupling to non-oscillatory and oscillatory activity raise the possibility of a functional distinction in the way each component is related to respiration. Our findings highlight the role of respiration as a physiological influence on brain signalling.
Trade-off between conservation of biological variation and batch effect removal in deep generative modeling for single-cell transcriptomics
Authors: Li Hui , McCarthy Davis J. , Shim Heejung , Wei Susan
Published: July 2022

Single-cell RNA sequencing (scRNA-seq) technology has contributed significantly to diverse research areas in biology, from cancer to development. Since scRNA-seq data is high-dimensional, a common strategy is to learn low-dimensional latent representations better to understand overall structure in the data. In this work, we build upon scVI, a powerful deep generative model which can learn biologically meaningful latent representations, but which has limited explicit control of batch effects. Rather than prioritizing batch effect removal over conservation of biological variation, or vice versa, our goal is to provide a bird’s eye view of the trade-offs between these two conflicting objectives. Specifically, using the well established concept of Pareto front from economics and engineering, we seek to learn the entire trade-off curve between conservation of biological variation and removal of batch effects.

A multi-objective optimisation technique known as Pareto multi-task learning (Pareto MTL) is used to obtain the Pareto front between conservation of biological variation and batch effect removal. Our results indicate Pareto MTL can obtain a better Pareto front than the naive scalarization approach typically encountered in the literature. In addition, we propose to measure batch effect by applying a neural-network based estimator called Mutual Information Neural Estimation (MINE) and show benefits over the more standard Maximum Mean Discrepancy (MMD) measure. The Pareto front between conservation of biological variation and batch effect removal is a valuable tool for researchers in computational biology. Our results demonstrate the efficacy of applying Pareto MTL to estimate the Pareto front in conjunction with applying MINE to measure the batch effect.
Multisite gating in tonic sensory circuits integrates multimodal context to control persistent behavioral states
Authors: Thapliyal Saurabh , Beets Isabel , Glauser Dominique A.
Published: July 2022

Maintaining or shifting between behavioral states according to context is essential for animals to implement fitness-promoting strategies. How integration of internal state, past experience and sensory inputs orchestrate persistent multidimensional behavior changes remains poorly understood. Here, we show that C. elegans integrates food availability and environment temperature over different timescales to engage in persistent dwelling, scanning, global or glocal search strategies matching thermoregulatory and feeding needs. Transition between states, in each case, requires lifting multiple regulatory gates including AFD or FLP tonic sensory neurons activity, neuropeptide expression and downstream circuit responsiveness. State-specific FLP-6 or FLP-5 neuropeptide signaling acts on a distributed set of inhibitory receptors to promote scanning or glocal search, respectively, bypassing dopamine and glutamate-dependent behavioral state control. Multisite gating-dependent behavioral switch by GPCRs in tonic sensory circuits might represent a conserved regulatory logic for persistent behavioral state transitions enabling a flexible prioritization on the valance of multiple inputs.
Early Path Dominance as a Principle for Neurodevelopment
Authors: Razban Rostam M , Pachter Jonathan Asher , Dill Ken A , Mujica-Parodi Lilianne R
Published: July 2022

We performtargeted attack, a systematic computational unlinking of the network, to analyze its effects on global communication across the network through itsgiant cluster. Across diffusion magnetic resonance images from individuals in the UK Biobank, Adolescent Brain Cognitive Development Study and Developing Human Connectome Project, we find that targeted attack procedures on increasing white matter tract lengths and densities are remarkably invariant to aging and disease. Time-reversing the attack computation suggests a mechanism for how brains develop, for which we derive an analytical equation using percolation theory. Based on a close match between theory and experiment, our results demonstrate that tracts are limited to emanate from regions already in the giant cluster and tracts that appear earliest in neurodevelopment are those that become the longest and densest.

Significance

As brains develop through neural growth and specialization, what mechanism ensures that new neurons are integrated into a fully connected brain, avoiding “bridges to nowhere”? Here, we study brain structure development from the perspective of percolation, a global measure of communication. Analyzing over 35,000 diffusion MRI scans on human individuals, from newborns to adults, we identify the following rules of brain neurogenesis through percolation theory: earlier tracts become longer and denser while maintaining a giant cluster. This signature, invariant to age or mental health, suggests a fundamental condition for the brain to function as an emergent whole.
Inflammatory Signaling in Pancreatic Cancer Transfers Between a Single-cell RNA Sequencing Atlas and Co-Culture
Authors: Kinny-Köster Benedict , Guinn Samantha , Tandurella Joseph A. , Mitchell Jacob T. , Sidiropoulos Dimitrios N. , Loth Melanie , Lyman Melissa R. , Pucsek Alexandra B. , Seppälä Toni T. , Cherry Christopher , Suri Reecha , Zlomke Haley , He Jin , Wolfgang Christopher L. , Yu Jun , Zheng Lei , Ryan David P. , Ting David T. , Kimmelman Alec , Gupta Anuj , Danilova Ludmila , Elisseeff Jennifer H. , Wood Laura D. , Stein-O’Brien Genevieve , Kagohara Luciane T. , Jaffee Elizabeth M. , Burkhart Richard A. , Fertig Elana J. , Zimmerman Jacquelyn W.
Published: July 2022

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by a heterogeneous tumor microenvironment (TME) that is enriched with cancer associated fibroblasts (CAFs)1. Cell-cell interactions involving these CAFs promote an immunosuppressive phenotype with altered inflammatory gene expression. While single-cell transcriptomics provides a tool to dissect the complex intercellular pathways that regulate cancer-associated inflammation in human tumors, complementary experimental systems for mechanistic validation remain limited. This study integrated single-cell data from human tumors and novel organoid co-cultures to study the PDAC TME. We derived a comprehensive atlas of PDAC gene expression from six published human single-cell RNA sequencing (scRNA-seq) datasets2–7to characterize intercellular signaling pathways between epithelial tumor cells and CAFs that regulate the inflammatory TME. Analysis of the epithelial cell compartment identified global gene expression pathways that modulate inflammatory signaling and are correlated with CAF composition. We then generated patient-derived organoid-CAF co-cultures to serve as a biological model of the cellular interactions learned from human tissue in the atlas. Transfer learning analysis to additional scRNA-seq data of this co-culture system and mechanistic experiments confirmed the epithelial response to fibroblast signaling. This bidirectional approach of complementary computational andin vitroapplications provides a framework for future studies identifying important mechanisms of intercellular interactions in PDAC.
High-Throughput Functional Assay in Cystic Fibrosis Patient-Derived Organoids Allows Drug Repurposing
Authors: Spelier S. , de Poel E. , Ithakisiou G.N. , Suen S.W.F. , Hagemeijer M.C. , Muilwijk D. , Vonk A.M. , Brunsveld J.E. , Kruisselbrink E. , van der Ent C.K. , Beekman J.M.
Published: July 2022

Cystic fibrosis (CF) is a rare hereditary disease caused by mutations in the CFTR gene. Recent therapies enable effective restoration of CFTR function of the most common F508del CFTR mutation. This shifts the unmet clinical need towards people with rare CFTR mutations such as nonsense mutations, of which G542X and W1282X are most prevalent. CFTR function measurements in patient-derived cell-based assays played a critical role in preclinical drug development for CF and may play an important role to identify new drugs for people with rare CFTR mutations.

Here, we miniaturized the previously described forskolin induced swelling (FIS) assay in intestinal organoids from a 96-wells to a 384-wells plate screening format. Using this novel assay, we tested CFTR increasing potential of a 1400-compound FDA-approved drug library in organoids from donors with W1282X/W1282X CFTR nonsense mutations.

The 384-wells FIS-assay demonstrated uniformity and robustness based on CV and Z’-factor calculations. In the primary screen, the top 5 compound combinations that increased CFTR function all contained at least one statin. In the secondary screen, we indeed verified that four out of the five statins, Mevastatin; Lovastatin; Simvastatin and Fluvastatin increased CFTR function when combined with CFTR modulators. Statin-induced CFTR rescue was W1282X specific, as increased CFTR function was not shown for patient-derived organoids harbouring R334W/R334W and F508del/F508del mutations.

Future studies should focus on elucidating genotype specificity and mode-of-action of statins into more detail. This study exemplifies proof-of-principle of large-scale compound screening in a functional assay using patient derived organoids.

Graphical abstract
Peptidoglycan recycling mediated by an ABC transporter in the plant pathogenAgrobacterium tumefaciens
Authors: Gilmore Michael C. , Cava Felipe
Published: July 2022

During growth and division, the bacterial cell wall peptidoglycan (PG) is remodelled, resulting in the liberation of PG muropeptides which are typically reinternalized and recycled. Bacteria belonging to the Rhizobiales and Rhodobacterales orders of the Alphaproteobacteria lack the canonical muropeptide transporter AmpG, despite having other key PG recycling enzymes. Here, we show that an alternative transporter, YejBEF-YepA, takes over this role in the Rhizobiales phytopathogenAgrobacterium tumefaciens. Muropeptide import by YejBEF-YepA governs expression of the β-lactamase AmpC inA. tumefaciens, contributing to β-lactam resistance. However, we show that the absence of YejBEF-YepA causes severe cell wall defects that go far beyond lowered AmpC activity. Thus, contrary to previously established Gram-negative models, PG recycling is vital for cell wall integrity inA. tumefaciens. YepA is widespread in the Rhizobiales and Rhodobacterales, suggesting that YejBEF-YepA-mediated PG recycling could represent an important but overlooked aspect of cell wall biology in these bacteria.
Indirect CRISPR screening with photoconversion revealed key factors of drug resistance with cell–cell interactions
Authors: Sugita Keisuke , Onishi Iichiroh , Nakayama Ran , Ishibashi Sachiko , Ikeda Masumi , Inoue Miori , Narita Rina , Oshima Shiori , Shimizu Kaho , Saito Shinichiro , Sato Shingo , Moriarity Branden S. , Yamamoto Kouhei , Largaespada David A. , Kitagawa Masanobu , Kurata Morito
Published: July 2022

Comprehensive screenings to clarify indirect cell–cell interactions, such as those in the tumor microenvironment, especially comprehensive assessments of supporting cells’ effects, are challenging. Therefore, in this study, indirect CRISPR screening for drug resistance with cell–cell interactions was invented. The photoconvertible fluorescent protein Dendra2 was inducted to determine the drug resistance responsible factors of supporting cells with CRISPR screenings. Random mutated supporting cells co-cultured with leukemic cells induced drug resistance with cell– cell interactions. Supporting cells responsible for drug resistance were isolated with green-to-red photoconversion, and 39 candidate genes were identified. Knocking out C9orf89, MAGI2, MLPH, or RHBDD2 in supporting cells reduced the ratio of apoptosis of cancer cells. In addition, the low expression of RHBDD2 in supporting cells, specifically fibroblasts, of clinical pancreatic cancer showed a shortened prognosis, and a negative correlation with CXCL12 was observed. Indirect CRISPR screening was established to isolate the responsible elements of cell–cell interactions. This screening method could reveal new mechanisms in all kinds of cell–cell interactions by revealing live phenotype-inducible cells, and it could be a new platform for discovering new targets of drugs for conventional chemotherapies.
The Type 9 Secretion System enables sharing of fungal mannan by human gut Bacteroides
Authors: Buzun Ekaterina , Heunis Tiaan , Cottam Curtis , Morland Carl , Trost Matthias , Lowe Elisabeth C
Published: July 2022

Degradation of complex carbohydrates in the gut is a key trait of Bacteroides species. Some glycans are metabolised ‘selfishly’ releasing few or no oligosaccharide breakdown products from complex polysaccharides, whereas others release oligosaccharides and cross feed other microbes. The outer cell wall of many fungi commonly found in the gut consists of highly α-mannosylated proteins which have been shown to be metabolised in a ‘selfish’ manner by Bacteroides thetaiotaomicron. We show that the species Bacteroides salyersiae releases branched manno-oligosaccharides during growth on mannan and that these act as a nutrient source for Bacteroides spp. that are unable to degrade polymeric mannan. Molecular characterisation of the locus responsible for mannan degradation reveals that it contains multiple glycoside hydrolases and glycan binding proteins targeted to the Type 9 Secretion System, a Bacteroidetes specific secretion system that allows the secretion of large folded proteins across the outer membrane. More commonly found in oral and environmental Bacteroidetes, here the T9SS enables B. salyersiae to locate large, multimodular enzymes and glycan binding proteins outside the cell to target a complex, branched polysaccharide. This points to a previously unknown role of the T9SS in glycan metabolism in gut Bacteroides.
Rerefinement of the crystal structure of SnTe0.73(2)Se0.27(2) from single-crystal X-ray diffraction data
Authors: Moris Silvana , Galdámez Antonio
Published: July 2022

Compounds of the solid solution series SnTe1–x
Se
x
, derived from pristine SnSe and SnTe, are considered as thermoelectric lead-free materials. The crystal structure re-refinement of NaCl-type SnTe0.73 (2)Se0.27 (2) is based on single-crystal X-ray diffraction data and results in higher precision of the bond length [Sn—(Te,Se) = 3.0798 (3) Å] compared to a previous report on basis of powder X-ray data [Krebs & Langner (1964). Z. Anorg. Allg. Chem.
334, 37–49].
How does international entrepreneurial orientation influence firms' internationalization? An exploration with Indian software product top management teams
Authors: Satyanarayana Krishna , Chandrashekar Deepak , Sukumar Arun , Jafari-Sadeghi Vahid
Published: July 2022

Purpose

The purpose of this study is to explore how international entrepreneurial orientation of top management team (TMT) of software product firms influence their firms' internationalization activities.

Design/methodology/approach

This study uses interpretive analysis techniques and examines data collected from in-depth interviews and secondary sources from 20 software product firms.

Findings

The analysis of data reveals the existence of a pathway through which the international entrepreneurial orientation of the TMT influences the firm's strategic learning functions (knowledge creation, dissemination, interpretation and implementation) which in turn influences the firm's internationalization activities.

Research limitations/implications

The authors extend the existing knowledge by demonstrating an existence of path to interpret the individual attribute of international entrepreneurial orientation of TMT with the organization's knowledge management functions. Building on the theories of knowledge-based view and organizational learning, and by leveraging the microfoundations approach, a process model is also derived based on evidence from data analysis to enable examination of the combined effects of the international entrepreneurial orientation of TMT, firm's strategic learning on internationalization.

Originality/value

The authors provide an integrative process model that connects TMTs' international entrepreneurial orientation to the firms' strategic learning processes, which in turn is linked to examine the combined influence of these constructs on the internationalization activities of a firm.
Does digital financial innovation enhance financial deepening and growth in Kenya?
Authors: Misati Roseline , Osoro Jared , Odongo Maureen , Abdul Farida
Published: July 2022

Purpose

The purpose of this paper is to examine the effect of digital financial innovation on financial depth and economic growth in Kenya.

Design/methodology/approach

The study utilized autoregressive distributed lag (ARDL) model, which is preferable over other time series methods as the model allows application of co-integration tests to time series with different integration orders and is flexible to the sample size including small and finite.

Findings

The main findings of this paper are as follows: first, there is evidence of a positive relationship between digital financial innovation and financial depth with the strongest impact emanating from Internet usage and mobile financial services and the lowest impact from bank branches; second, the results reveal a significant positive impact of financial depth on economic growth consistent with the supply-leading finance theory.

Practical implications

The results of the study imply a need for investment in technology-enabling infrastructure for digital financial services (DFS) and a redesign of strategies to avoid further financial exclusion of low-income earners due to the unaffordability of digital devices and financial and digital illiteracy.

Originality/value

The study is original and important for policymakers as the study provides insights on the components of financial innovation that are growth-enhancing in Kenya, considering that some aspects of innovation can be growth-retarding as was demonstrated during the global financial crisis.
Systematic review of MOOC research in mainland China
Authors: Cheng Jiawen , Yuen Allan H.K. , Chiu Dickson K.W.
Published: July 2022

Purpose

The popularity of massive open online courses (MOOCs) has attracted worldwide research interest. This study aims to identify and summarize the research foci (e.g. themes, methods, contexts, etc.) and discuss the new directions and trends of MOOC research in the context of Mainland China.

Design/methodology/approach

A systematic review of the published MOOC research papers in Mainland China was conducted with the following inclusion criteria: (1) papers written in English; (2) context focused on Mainland China; and (3) empirical studies. Three main issues were explored with the selected 70 papers: (1) research methods (data collection and analysis); (2) the research foci; and (3) research objects.

Findings

The results found that the major MOOC research in China was quantitative, mostly using one method to collect data. Most studies collected data through the databases of MOOC platforms and survey techniques, which was consistent with the widely used descriptive statistics for data analysis. Learner-focused themes were investigated the most, aligning with the result that learners were the most popular research objects.

Practical implications

The findings suggest that using new technology tools, such as the Big Data approach for learning analytics, may transform traditional MOOC research into new practices. Transdisciplinary research concepts may also provide an alternative evolving model for constructing collaboratively dynamic research frameworks under the changing technologies and paradigms. Meanwhile, educational research traditions, such as qualitative methods, contribute to scaffolding MOOC research for more pragmatic applications.

Originality/value

Most systematic reviews on MOOCs focus on general or regional contexts other than Mainland China, and scant MOOC review is based on published English papers about Mainland China.
Understanding citizens’ satisfaction with the government response during the COVID-19 pandemic in China: comprehensive analysis of the government hotline
Authors: Zhang Zicheng , Li Anguo , Xu Yang , Liang Yixiao , Jin Xinchen , Wu Shanshan
Published: July 2022

Purpose

The objective of this study was to analyse the influencing factors of citizens' dissatisfaction with government services during the COVID-19 pandemic to help government departments identify problems in the service process and possible countermeasures.

Design/methodology/approach

The authors first used cosine interesting pattern mining (CIPM) to analyse citizens' complaints in different periods of the pandemic. Second, the potential evaluation indices of customer satisfaction were extracted from the hotline business system through a hypothesis analysis and modelled using multiple regression analysis. During the index transformation and standardization process, a machine-learning algorithm of clustering and emotion analysis was adopted. Finally, the authors used the random forest algorithm to evaluate the importance of the indicators and obtain the indicators more important to citizen satisfaction.

Findings

The authors found that the complaint topic, appeal time, urgency of citizens' complaints, citizens' emotions, level of detail in the case record, and processing timeliness and efficiency significantly influenced citizens' satisfaction. When the government addresses complaints in a more standardized and efficient manner, citizens are more satisfied.

Originality/value

During the pandemic, government departments should be more patient with citizens, increase the speed of the case circulation and shorten the processing period of appeals. Staff should record appeals in a more standardized manner, highlighting themes and prioritizing urgent cases to appease citizens and relieve their anxiety.
Humanistic leadership and support for the sustainable development goals
Authors: Flores Gabriela , Ahmed Rawia , Wagstaff Maria F.
Published: July 2022

Purpose

This study aims to use humanistic management theory to examine the conceptual space of leaders who support sustainable development goals (SDGs) within their organizations.

Design/methodology/approach

This study analyzes interviews with four Iberoamerican leaders conducted by the creating emerging markets project at Harvard Business School. This study’s results show a range of humanistic management principles across the four leaders, coinciding with varying support for the SDGs. This study discusses the impact of cultural values on these differences.

Findings

This study finds leaders who embrace all four humanistic management principles also supported a greater number of SDGs and an increased variety of SDGs. This study’s findings support the three overarching dimensions uncovered by previous research into champions in other organizational domains, including gender equality and health. These three dimensions are depth of embracement, scope of embracement and leverage of engagement.

Originality/value

The authors’ hope is that this study will help further the discussion of how organizations can contribute to the 17 SDGs.
Identifying a pathway towards recovery for depleted wild Pacific salmon populations in a large watershed under multiple stressors
Authors: Chalifour Lia , Holt Cassandra , Camaclang Abbey E. , Bradford Michael J. , Dixon Ross , Finn Riley J. R. , Hemming Victoria , Hinch Scott G. , Levings Colin D. , MacDuffee Misty , Nishimura Derek J. H. , Pearson Michael , Reynolds John D. , Scott David C. , Spremberg Uwe , Stark Steven , Stevens John , Baum Julia K. , Martin Tara G.
Published: July 2022

Pacific salmon (Oncorhynchus spp.) support coastal and freshwater ecosystems, economies and cultures, but many populations have declined. We used priority threat management (PTM), a decision‐support framework for prioritizing conservation investments, to identify management strategies that could support thriving populations of wild salmon over 25 years. We evaluated the potential benefits of 14 strategies spanning fisheries, habitat, pollution, pathogens, hatcheries and predation management dimensions on 19 conservation units (CUs)—genetically and ecologically distinct populations—of the five Pacific salmon species in the lower Fraser River, British Columbia, Canada.

The PTM assessment indicated that under the current trajectory of ‘business as usual’, zero CUs were predicted to have >50% chance of thriving in 25 years. Implementation of all management strategies at an annual investment between 45 and 110 million CAD was, however, predicted to achieve >50% chance of thriving for most CUs (n = 16), with nearly half (seven CUs) having a > 60% chance, indicating there is a pathway towards recovery for most populations if we invest now. In fact, substantial gains could be made by investing in five combined habitat strategies, costing 20M CAD annually. These habitat strategies were estimated to bring 14 of 19 salmon CUs above this 50% threshold.

Co‐governance between First Nation and provincial and federal Canadian governments to manage salmon populations and harvest, and improved CU‐level monitoring emerged from the expert elicitation as critical ‘enabling’ strategies. By improving the feasibility of different management options, co‐governance brought an additional five CUs above the 60% threshold.

Synthesis and applications. Supporting wild salmon in the face of cumulative threats will require strategic investment in effective management strategies, as identified by this priority threat management (PTM) assessment. PTM uses the best available data to objectively assess the potential outcomes of management alternatives. With renewed commitments from provincial and federal Canadian governments to protect and restore salmon populations and their habitats, positive conservation outcomes following implementation of targeted management strategies may be within reach.
Differential resting‐state neurophysiological activity associated with game usage patterns and genres in Internet gaming disorder
Authors: Hong Da Hye , Lee Ji‐Yoon , Oh Da‐young , Park Sun‐young , Yoo So Young , Choi Jung‐Seok
Published: July 2022

We investigated differences in quantitative electroencephalogram (EEG) patterns associated with game usage patterns and genre among patients with Internet gaming disorder (IGD). Data from 140 participants (76 IGD patients and 64 healthy controls) were analysed. The IGD group was divided into subgroups based on game usage patterns (single game [SG] or multiple games [MGs]) and genre (multiplayer online battle arena, first‐person shooter [FPS], or massively multiplayer online role‐playing game [MMORPG; hereafter, MMG]). A resting‐state, eye‐closed quantitative EEG was recorded, and the absolute power and coherence of brain waves were analysed. IGD patients who played SGs showed increased beta activity compared with those who played MGs and controls. Increased absolute beta power was significantly associated with higher tendencies towards behavioural inhibition compared with controls. FPS gamers showed increased delta power in the frontal region compared with controls, which was related to the severity of IGD. Furthermore, decreased intrahemispheric coherence in the left frontoparietal region was observed in the MMG and FPS groups compared with controls. This decreased coherence was observed in the theta (MMG and FPS), delta (MMG), and beta (FPS) bands. These features were related to impairment in visuospatial working memory. Unique neurophysiological features related to preoccupation with an SG may be associated with the inhibition of behavioural changes. The present study suggests that the underlying neurophysiological networks in IGD differ according to game usage patterns and genre.
Young adult responses to taxes on cigarettes and electronic nicotine delivery systems
Authors: Friedman Abigail S. , Pesko Michael F.
Published: July 2022

Background and Aims

Although over half of United States states have passed taxes on electronic nicotine delivery systems (ENDS), recent evidence links ENDS tax rates to increases in smoking, suggesting potentially substantive health costs. Overall health implications will depend on how these taxes affect transitions from experimentation to regular smoking and vaping. Current analyses have not assessed ENDS tax rates' effects in young adulthood (ages 18–25). This study measures the relationship between ENDS and cigarette tax rates and ENDS use and smoking in young adulthood, a key period for initiation of regular tobacco use.

Design

Observational study of data from the Current Population Survey's 2010–2019 Tobacco Use Supplements.

Setting

The United States.

Participants/Cases

A total of 38 906 18 to 25 year‐olds

Measurements

Multivariable linear regressions estimated two‐way fixed effects analyses to assess ENDS and cigarette tax rates' relationships to recent and daily smoking and vaping, adjusting for an array of potential sociodemographic and policy confounders along with state and year fixed effects.

Findings

A $1 increase in ENDS taxes yielded significant reductions in young adults' daily vaping (
= −0.025; 95% CI, −0.037, −0.014) alongside increases in recent smoking (
= 0.037; 95% CI, 0.013, 0.061), primarily reflecting greater dual use (
=2.078; 95% CI, 0.890, 4.852; P = 0.09). A $1 cigarette tax increase yielded 2.1 and 2.5 percentage point increases in recent and daily vaping, with 95% CIs of (0.004, 0.038) and (0.018, 0.032) respectively.

Conclusions

In the United States, higher ENDS tax rates are associated with decreased ENDS use but increased cigarette smoking among 18‐ to 25‐year‐olds, with associations reversed for cigarette taxes.
Experiences of primary health care nurses advancing their careers in a remote Western Australian location
Authors: Kagi Elena , Rasiah Rohan , Moran Monica
Published: July 2022

Objective

The objective of the study was to explore the experiences of primary health care (PHC) nurses advancing their careers in a remote location in Western Australia.

Setting

The study was conducted in PHC organisations in one remote location in northern Western Australia.

Participants

Six registered nurses working in four PHC organisations participated in the study. All were registered with the Nursing and Midwifery Board of Australia. Participants were all female, and five had child carer responsibilities. They had worked in the region for between 8 months and 10 years.

Design

The design was based on a qualitative, interpretative phenomenological analysis methodology involving in‐depth, semi‐structured, face‐to‐face interviews.

Results

Participants faced challenges advancing their careers given the limited employment opportunities and need to balance their professional ambitions with family needs. Participants had limited capacity to support each other's learning and felt poorly supported by employers to undertake professional development not directly related to their role. Participants were not well engaged with professional associations beyond undertaking online professional development activities provided with membership. Accessing professional development was difficult given a lack of time, limited access to local learning activities and a consequent need to travel, which was challenging. Despite the challenges they faced, most nurses remained passionate about their remote nursing roles and enjoyed the lifestyle.

Conclusion

Remote PHC nurses face a range of challenges, some of which can be overcome by improved availability of local professional development and better support from employers and professional associations.
Personalized diagnostic approach and indirect quantification of extravasation in human anaphylaxis
Authors: Nuñez‐Borque Emilio , Betancor Diana , Pastor‐Vargas Carlos , Fernández‐Bravo Sergio , Martin‐Blazquez Ariadna , Casado‐Navarro Natalia , López‐Domínguez David , Gómez‐López Alicia , Rodriguez del Rio Pablo , Tramón Paloma , Beitia Juan María , Moreno‐Aguilar Carmen , González‐de‐Olano David , Goikoetxea María José , Ibáñez‐Sandín María Dolores , Laguna José Julio , Cuesta‐Herranz Javier , Esteban Vanesa
Published: July 2022

Background

Anaphylaxis is the most acute and life‐threatening manifestation of allergic disorders. Currently, there is a need to improve its medical management and increase the understanding of its molecular mechanisms. This study aimed to quantify the extravasation underlying human anaphylactic reactions and propose new theragnostic approaches.

Methods

Molecular determinations were performed in paired serum samples obtained during the acute phase and at baseline from patients presenting with hypersensitivity reactions. These were classified according to their severity as Grades 1, 2 and 3, the two latter being considered anaphylaxis. Tryptase levels were measured by ImmunoCAP, and serum protein concentration was quantified by Bradford assay. Human serum albumin (HSA) and haemoglobin beta subunit (HBB) levels were determined by Western blot and polyacrylamide gel electrophoresis, respectively.

Results

A total of 150 patients were included in the study. Of them, 112 had experienced anaphylaxis (83 and 29 with Grade 2 and 3 reactions, respectively). Tryptase diagnostic efficiency substantially improved when considering patients' baseline values (33%–54%) instead of the acute value threshold (21%). Serum protein concentration and HSA significantly decreased in anaphylaxis (p < .0001). HSA levels dropped with the severity of the reaction (6% and 15% for Grade 2 and 3 reactions, respectively). Furthermore, HBB levels increased during the acute phase of all hypersensitivity reactions (p < .0001).

Conclusions

For the first time, the extravasation underlying human anaphylaxis has been evaluated based on the severity of the reaction using HSA and protein concentration measurements. Additionally, our findings propose new diagnostic and potential therapeutic approaches for this pathological event.
Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta‐analysis of 92 studies
Authors: Archontakis‐Barakakis Paraschos , Li Weijia , Kalaitzoglou Dimitrios , Tzelves Lazaros , Manolopoulos Apostolos , Giannopoulos Stefanos , Giamouzis Grigorios , Giannakoulas George , Batsidis Apostolos , Palaiodimos Leonidas , Ntaios George , Lip Gregory Y. H. , Kokkinidis Damianos G.
Published: July 2022

Aims

Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta‐analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs.

Methods

Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random‐effects model was used.

Results

We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68–0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83–0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80–0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77–0.89) and apixaban (HR: 0.75, 95% CI: 0.65–0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03–1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31–1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44–0.52), apixaban (HR: 0.60, 95% CI: 0.49–0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65–0.81) were associated with lower risk of ICH compared to VKA.

Conclusion

Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.