bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-destructive X-ray tomography of brain tissue ultrastructure
Authors: Bosch Carles , Aidukas Tomas , Holler Mirko , Pacureanu Alexandra , Müller Elisabeth , Peddie Christopher J. , Zhang Yuxin , Cook Phil , Collinson Lucy , Bunk Oliver , Menzel Andreas , Guizar-Sicairos Manuel , Aeppli Gabriel , Diaz Ana , Wanner Adrian A. , Schaefer Andreas T.
Published: November 2023

Maps of dense subcellular features in biological tissue are the key to understanding the structural basis of organ function. Electron microscopy provides the necessary resolution, yet - as electrons penetrate samples for only a few 100s of nm - requires physical sectioning or ablation, which strongly challenges anatomical investigations of entire organs such as mammalian brains. As demonstrated for the engineering and physical sciences, X-ray nanotomography represents a promising alternative for ultrastructural 3d imaging without physical sectioning1–15. Leveraging the high brilliance of 4th generation synchrotron X-ray sources, it has the potential to non-destructively image mm³-sized samples at ultrastructural resolution within a few days16. A fundamental barrier to application to the life sciences is that, when irradiated with high-intensity X-rays, biological samples deform and ultimately disintegrate, prohibiting reaching sufficient resolution. Here, we introduce a combination of engineering solutions which defeat this barrier for X-ray ptychography17, a coherent diffractive X-ray imaging technique. The solutions include a cryogenic sample stage with high stability, high-precision interferometric positioners and tailored non-rigid tomographic reconstruction algorithms18. Furthermore, adapting an epoxy resin developed for the nuclear and aerospace industry, we demonstrate radiation resistance to X-ray doses exceeding 1010Gy. The resulting sub-40 nm isotropic resolution makes it possible to densely resolve axon bundles, boutons, dendrites and reliably identify synapses without physical sectioning. Moreover, we validated the X-ray technique using the current gold standard, namely focused ion beam scanning electron microscopy (FIB-SEM)19,20to demonstrate intact ultrastructure in tissue volumes first imaged by X-rays. This unlocks the potential of X-ray tomography for high-resolution tissue imaging, coinciding with the transformative advancements of next-generation synchrotrons worldwide21.
Lesions to different regions of frontal cortex have dissociable effects on voluntary persistence
Authors: van Geen Camilla , Chen Yixin , Kazinka Rebecca , Vaidya Avinash R. , Kable Joseph W. , McGuire Joseph T.
Published: November 2023

Deciding how long to keep waiting for uncertain future rewards is a complex problem. Previous research has shown that choosing to stop waiting results from an evaluative process that weighs the subjective value of the awaited reward against the opportunity cost of waiting. In functional neuroimaging data, activity in ventromedial prefrontal cortex (vmPFC) tracks the dynamics of this evaluation, while activation in the dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI) ramps up before a decision to quit is made. Here, we provide causal evidence of the necessity of these brain regions for successful performance in a willingness-to-wait task.

28 participants with frontal lobe lesions were tested on their ability to adaptively calibrate how long they waited for monetary rewards. We grouped the participants based on the location of their lesions, which were primarily in ventromedial, dorsomedial, or lateral parts of their prefrontal cortex (vmPFC, dmPFC, and lPFC, respectively), or in the anterior insula. We compared the performance of each subset of lesion participants to behavior in a control group without lesions (n=18). Finally, we fit a newly developed computational model to the data to glean a more mechanistic understanding of how lesions affect the cognitive processes underlying choice.

We found that participants with lesions to the vmPFC waited less overall, while participants with lesions to the dmPFC and anterior insula were specifically impaired at calibrating their level of persistence to the environment. These behavioral effects were accounted for by systematic differences in parameter estimates from a computational model of task performance: while the vmPFC group showed reduced initial willingness to wait, lesions to the dmPFC/anterior insula were associated with slower learning from negative feedback.

These findings corroborate the notion that failures of persistence can be driven by sophisticated cost-benefit analyses rather than lapses in self-control. They also support the functional specialization of different parts of the prefrontal cortex in service of voluntary persistence.
Simulating cell-free chromatin using preclinical models for cancer-specific biomarker discovery
Authors: De Michino Steven D. , Main Sasha C. , Penny Lucas , Kridel Robert , Cescon David W. , Hoffman Michael M. , Lupien Mathieu , Bratman Scott V.
Published: November 2023

Cell-free chromatin (cf-chromatin) is a rich source of biomarkers across various conditions, including cancer. Tumor-derived circulating cf-chromatin can be profiled for epigenetic features, including nucleosome positioning and histone modifications that govern cell type-specific chromatin conformations. However, the low fractional abundance of tumor-derived cf-chromatin in blood and constrained access to plasma samples pose challenges for epigenetic biomarker discovery. Conditioned media from preclinical tissue culture models could provide an unencumbered source of pure tumor-derived cf-chromatin, but large cf-chromatin complexes from such models do not resemble the nucleosomal structures found predominantly in plasma, thereby limiting the applicability of many analysis techniques. Here, we developed a robust and generalizable framework for simulating cf-chromatin with physiologic nucleosomal distributions using an optimized nuclease treatment. We profiled the resulting nucleosomes by whole genome sequencing and confirmed that inferred nucleosome positioning reflected gene expression and chromatin accessibility patterns specific to the cell type. Compared with plasma, simulated cf-chromatin displayed stronger nucleosome positioning patterns at genomic locations of accessible chromatin from patient tissue. We then utilized simulated cf-chromatin to develop methods for genome-wide profiling of histone post-translational modifications associated with heterochromatin states. Cell-free chromatin immunoprecipitation and sequencing (cf-ChIP-Seq) of H3K27me3 identified heterochromatin domains associated with repressed gene expression, and when combined with H3K4me3 cfChIP-Seq revealed bivalent domains consistent with an intermediate state of transcriptional activity. Combining cfChIP-Seq of both modifications provided more accurate predictions of transcriptional activity from the cell of origin. Altogether, our results demonstrate the broad applicability of preclinical simulated cf-chromatin for epigenetic liquid biopsy biomarker discovery.
PRC1 directs PRC2-H3K27me3 deposition to shield adult spermatogonial stem cells from differentiation
Authors: Hu Mengwen , Yeh Yu-Han , Maezawa So , Nakagawa Toshinori , Yoshida Shosei , Namekawa Satoshi H.
Published: November 2023

Spermatogonial stem cell functionality resides in the slow-cycling and heterogeneous undifferentiated spermatogonia cell population. This pool of cells supports lifelong fertility in adult males by balancing self-renewal and differentiation to produce haploid gametes. However, the molecular mechanisms underpinning long-term stemness of undifferentiated spermatogonia during adulthood remain unclear. Here, we discover that an epigenetic regulator, Polycomb repressive complex 1 (PRC1), shields adult undifferentiated spermatogonia from differentiation, maintains slow cycling, and directs commitment to differentiation during steady-state spermatogenesis in adults. We show that PRC2-mediated H3K27me3 is an epigenetic hallmark of adult undifferentiated spermatogonia. Indeed, spermatogonial differentiation is accompanied by a global loss of H3K27me3. Disruption of PRC1 impairs global H3K27me3 deposition, leading to precocious spermatogonial differentiation. Therefore, PRC1 directs PRC2-H3K27me3 deposition to maintain the self-renewing state of undifferentiated spermatogonia. Importantly, in contrast to its role in other tissue stem cells, PRC1 negatively regulates the cell cycle to maintain slow cycling of undifferentiated spermatogonia. Our findings have implications for how epigenetic regulators can be tuned to regulate the stem cell potential, cell cycle, and differentiation to ensure lifelong fertility in adult males.
Toxoplasma gondiiharbors a hypoxia-responsive coproporphyrinogen dehydrogenase-like protein
Authors: Key Melanie , Baptista Carlos Gustavo , Bergmann Amy , Floyd Katherine , Blader Ira J. , Dou Zhicheng
Published: November 2023

Toxoplasma gondiiis an apicomplexan parasite that is the cause of toxoplasmosis, a potentially lethal disease for immunocompromised individuals. Duringin vivoinfection, the parasites encounter various growth environments, such as hypoxia. Therefore, the metabolic enzymes in the parasites must adapt to such changes to fulfill their nutritional requirements.Toxoplasmacande novobiosynthesize some nutrients, such as heme. The parasites heavily rely on their own heme production for intracellular survival. Notably, the antepenultimate step within this pathway is facilitated by coproporphyrinogen III oxidase (CPOX), which employs oxygen to convert coproporphyrinogen III to protoporphyrinogen IX through oxidative decarboxylation. Conversely, some bacteria can accomplish this conversion independently of oxygen through coproporphyrinogen dehydrogenase (CPDH). Genome analysis found a CPDH ortholog inToxoplasma. The mutantToxoplasmalacking CPOX displays significantly reduced growth, implying that TgCPDH potentially functions as an alternative enzyme to perform the same reaction as CPOX under low oxygen conditions. In this study, we demonstrated that TgCPDH exhibits coproporphyrinogen dehydrogenase activity by complementing it in a heme synthesis-deficientSalmonellamutant. Additionally, we observed an increase in TgCPDH expression inToxoplasmawhen it grew under hypoxic conditions. However, deletingTgCPDHin both wildtype and heme-deficient parasites did not alter their intracellular growth under both ambient and low oxygen conditions. This research marks the first report of a coproporphyrinogen dehydrogenase-like protein in eukaryotic cells. Although TgCPDH responds to hypoxic conditions and possesses enzymatic activity, our findings suggest that it does not directly affect intracellular infection or the pathogenesis ofToxoplasmaparasites.

IMPORTANCE

Toxoplasma gondiiis a ubiquitous parasite capable of infecting a wide range of warm-blooded hosts, including humans. During its lifecycle, these parasites must adapt to varying environmental conditions, including situations with low oxygen levels. Our research, in conjunction with studies conducted by other laboratories, has revealed thatToxoplasmaprimarily relies on its own heme production during acute infections. Intriguingly, in addition to this classical heme biosynthetic pathway, the parasites encode a putative oxygen-independent coproporphyrinogen dehydrogenase, suggesting its potential contribution to heme production under varying oxygen conditions, a feature typically observed in simpler organisms like bacteria. Notably, so far, coproporphyrinogen dehydrogenase has only been identified in some bacteria for heme biosynthesis. Our study discovered thatToxoplasmaharbors a functional enzyme displaying coproporphyrinogen dehydrogenase activity, which alters its expression in the parasites when they face fluctuating oxygen levels in their surroundings.
Following the p63/Keratin5 Basal Cells in the Sensory and Non-sensory Epithelia of The Vomeronasal Organ
Authors: LeFever Noah M. , Katreddi Raghu Ram , Dolphin Nikki M. , Mathias Nick A. , Forni Paolo E.
Published: November 2023

The Vomeronasal organ (VNO) is a part of the accessory olfactory system, which is responsible for detecting pheromones, chemical factors that trigger a spectrum of sexual and social behaviors. The vomeronasal epithelium (VNE) shares several features with the epithelium of the main olfactory epithelium (MOE). However, it is a distinct neuroepithelium populated by chemosensory neurons that differ from the olfactory sensory neurons (OSNs) in cellular structure, receptor expression, and connectivity.

The vomeronasal organ of rodents comprises a sensory epithelium and a thin non-sensory epithelium that morphologically resembles the respiratory epithelium.

Sox2-positive cells have been previously identified as the stem cell population that gives rise to neuronal progenitors in MOE and VNE. In addition to these, the MOE also comprises p63 positive horizontal basal cells (HBCs), a second pool of quiescent stem cells that become active in response to injury.

Immunolabeling against the transcription factor p63, Keratin-5 (Krt5), Krt14 and Krt5Cre tracing experiments highlighted the existence of horizontal basal cells distributed along the basal lamina of the VNO forming from progenitors along the basal lamina of the marginal zones. Moreover, these experiments revealed that the NSE of rodents is, like the respiratory epithelium, a stratified epithelium where the p63/Krt5+ basal cells self-replicate and give rise to the apical columnar cells facing the lumen of the VNO.
A non-invasive method to sample immune cells in the lower female genital tract using menstrual discs
Authors: Quinn Peters M. , Domenjo-Vila Eva , Carlson Marc , Armistead Blair , Edlefsen Paul T. , Gasper Melanie , Dabee Smritee , Whidbey Christopher , Jaspan Heather B. , Prlic Martin , Harrington Whitney E.
Published: November 2023

T cells in the human female genital tract (FGT)2are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare provider and are expensive, limiting the ability to study these populations longitudinally. To address these challenges, we have developed a method to sample immune cells from the FGT utilizing disposable menstrual discs which are non-invasive, self-applied, and low-cost. To demonstrate reproducibility, we sampled the cervicovaginal fluid (CVF)3of healthy, reproductive-aged individuals using menstrual discs over three sequential days. CVF was processed for cervicovaginal cells, and high parameter flow cytometry was used to characterize immune populations. We identified large numbers of live, CD45+ leukocytes, as well as distinct populations of T cells and B cells. Within the T cell compartment, activation and suppression status of T cell subsets were consistent with previous studies of the FGT utilizing current approaches, including identification of both tissue resident and migratory populations. In addition, the T cell population structure was highly conserved across days within individuals but divergent across individuals. Our approach to sample immune cells in the FGT with menstrual discs will decrease barriers to participation and empower longitudinal sampling in future research studies.
DNA from non-viable bacteria biases diversity estimates in the coralsAcropora loripesandPocillopora acuta
Authors: Dungan Ashley M. , Geissler Laura , Williams Amanda , Gotze Cecilie Ravn , Flynn Emily C. , Blackall Linda L. , van Oppen Madeleine J. H.
Published: November 2023

Background

Nucleic acid-based analytical methods have greatly expanded our understanding of global prokaryotic diversity, yet standard metabarcoding methods provide no information on the most fundamental physiological state of bacteria, viability. Scleractinian corals harbour a complex microbiome in which bacterial symbionts play critical roles in maintaining health and functioning of the holobiont. However, the coral holobiont contains both dead and living bacteria. The former can be the result of corals feeding on bacteria, rapid swings from hyper- to hypoxic conditions in the coral tissue, the presence of antimicrobial compounds in coral mucus, and an abundance of lytic bacteriophages.

Results

By combining propidium monoazide (PMA) treatment with high-throughput sequencing on six coral species (Acropora loripes,A. millepora,A. kenti,Platygyra daedalea,Pocillopora acuta, andPorites lutea) we were able to obtain information on bacterial communities with little noise from non-viable microbial DNA. Metabarcoding of the 16S rRNA gene showed significantly higher community evenness (85%) and species diversity (31%) in untreated compared with PMA-treated tissue forA. loripesonly. While PMA-treated coral did not differ significantly from untreated samples in terms of observed number of ASVs, >30% of ASVs were identified in untreated samples only, suggesting that they originated from cell-free/non-viable DNA. Further, the bacterial community structure was significantly different between PMA-treated and untreated samples forA. loripesandP. acutaindicating that DNA from non-viable microbes can bias community composition data in coral species with low bacterial diversity.

Conclusions

Our study is highly relevant to microbiome studies on coral and other host organisms as it delivers a solution to excluding non-viable DNA in a complex community. These results provide novel insights into the dynamic nature of host-associated microbiomes and underline the importance of applying versatile tools in the analysis of metabarcoding or next-generation sequencing data sets.
Mapping the physiological changes in sleep regulation across infancy and young childhood
Authors: Webb Lachlan , Phillips Andrew JK , Roberts James A
Published: November 2023

Sleep patterns in infancy and early childhood vary greatly and change rapidly during development. In adults, sleep patterns are regulated by interactions between neuronal populations in the brainstem and hypothalamus, driven by the circadian and sleep homeostatic processes. However, the neurophysiological mechanisms underlying the sleep patterns and their variations across infancy and early childhood are poorly understood. We investigated whether a well-established mathematical model for sleep regulation in adults can model infant sleep characteristics and explain the physiological basis for developmental changes. By fitting longitudinal sleep data spanning 2 to 540 days after birth, we inferred parameter trajectories across age. We found that the developmental changes in sleep patterns are consistent with a faster accumulation and faster clearance of sleep homeostatic pressure in infancy and a weaker circadian rhythm in early infancy. We also find greater sensitivity to phase-delaying effects of light in infancy and early childhood. These findings reveal fundamental mechanisms that regulate sleep in infancy and early childhood. Given the critical role of sleep in healthy neurodevelopment, this framework could be used to pinpoint pathophysiological mechanisms and identify ways to improve sleep quality in early life.
CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning
Authors: Eckenwiler Elizabeth A. , Ingebretson Anna E. , Stolley Jeffrey J. , Fusaro Maxine A. , Romportl Alyssa M. , Ross Jack M. , Petersen Christopher L. , Kale Eera M. , Clark Michael S. , Schattauer Selena S. , Zweifel Larry S. , Lemos Julia C.
Published: November 2023

Background

The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning.

Methods

To do this, we took a multidisciplinary approach that included florescent in situ hybridization (Nmice≥ 3), tract tracing (Nmice= 5), ex vivo electrophysiology (Ncells≥ 30), in vivo calcium imaging with fiber photometry (Nmice≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (Nmice≥ 4). Behaviors used were instrumental learning, sucrose preference and spontaneous exploration in an open field.

Results

Here we show that the vast majority of NAc CRF-containing (NAcCRF) neurons are spiny projection neurons (SPNs) comprised of dopamine D1-, D2- or D1/D2-containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrate that NAcCRFneurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning, and at the same time facilitates flexibility in the face of changing contingencies.

Conclusion

We conclude that CRF release from this sparse population of SPNs is critical for reward learning under normal conditions.
Intervention Characteristics and Mechanisms and their Relationship with the Influence of Social Prescribing: a Systematic Review
Authors: Dubbeldeman Eveline M. , Kiefte-de Jong Jessica C. , Ardesch Frank H. , Boelens Mirte , van der Velde Laura A. , van der Steen Sophie G.L. , Heijnders Miriam L. , Crone Mathilde R.
Published: November 2023

Introduction

Social Prescribing (SP) is an integrated care program aimed to improve individuals’ health and wellbeing. Understanding the influence of SP and determining best practices and processes is challenging due to variability in its delivery, implementation, and intervention characteristics between different studies and countries. This study aimed to identify the intervention characteristics, mechanisms, and outcomes associated with SP research, and explore how these factors relate to the influence of SP on health and wellbeing, healthcare utilization, and care experiences.

Method

A comprehensive search was conducted in 12 databases, Google Scholar, and reference lists of relevant studies published from January 2010 up to April 2023. Searches were limited to literature written in English or Dutch. The methodological quality of the included studies was assessed using the Mixed Methods Appraisal Tool and the risk of bias was evaluated using the Cochrane RoB2 and the ROBINS-I. We coded all intervention characteristics, mechanisms, and relevant outcomes. Qualitative data were visually presented using Harvest Plots and qualitative data were narratively summarized.

Results and discussion

In total, 49 papers were included, of which seven qualitative, seventeen quantitative, and 25 mixed method studies. Moreover, the findings highlights the importance of social-related mechanisms, including loneliness and social connectedness, in contributing to the observed positive influence of SP on mental health and wellbeing. The observed outcomes seem to be influenced by various characteristics, including gender, age, the presence of a link worker, and the use of behavior change techniques. However, we should be cautious when interpreting these results due to limitations in study designs, such as the lack of controlled trials and statistical considerations. Further rigorous research is needed to comprehensively understand the impact and potential benefits of SP.
Brain signaling becomes less integrated and more segregated with age
Authors: Razban Rostam M , Antal Botond B , Dill Ken A , Mujica-Parodi Lilianne R
Published: November 2023

The integration-segregation framework is a popular first step to understand brain dynamics because it simplifies brain dynamics into two states based on global vs. local signaling patterns. However, there is no consensus for how to best define what the two states look like. Here, we map integration and segregation to order and disorder states from the Ising model in physics to calculate state probabilities,PintandPseg, from functional MRI data. We find that integration/segregation decreases/increases with age across three databases, and changes are consistent with weakened connection strength among regions rather than topological connectivity based on structural and diffusion MRI data.

AUTHOR SUMMARY

The integration-segregation framework succinctly captures the tradeoff brains face between seamless function (more integration) in light of energetic constrains (more segregation). Despite its ubiquitous use in the field, there is no consensus on its definition with various graph theoretical properties being proposed. Here, we define the two states based on the underlying mechanism of neuronal coupling strength to provide a physical foundation for the framework. We find that younger adults’ brains are close to perfectly balancing between integration and segregation, while older adults’ brains veer off towards random signaling.
An NMR-guided approach for identifying co-factors in boosting the Pfu DNA polymerase
Authors: Chen Yihao , Zhu Mingjun , Zhao Xiaoling , Tao Zhiqing , Xiang Dan , Zhang Xu , Liu Maili , He Lichun
Published: November 2023

With rapid developments of emerging technologies like synthetic biology, the demand for DNA polymerases with superior activities including higher thermostability and processivity has increased significantly. Thus, rational optimization of the performance of DNA polymerase is of great interest. Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique used for studying protein structure and dynamics. It provides the atomic resolution information of enzymes under its functional solution environment to reveal the active sites (hot spots) of the enzyme, which could be further used for optimizing the performance of enzymes. Here we applied NMR spectroscopy to determine hot spots of the Pfu polymerase. Employing these hot spots as probes, two new co-factors, the heat shock protein TkHSP20 fromThermococcus Kodakaraensisand the chemical chaperone L-arginine, are identified to interact with Pfu polymerase to boost its performance in amplifying long DNA fragments by enhancing the thermal stability and the processivity of the Pfu polymerase. This NMR-guided approach requires no prior assignment information of target enzymes, simplifying the exploration of novel co-factors for Pfu polymerase. Moreover, our approach is not dependent on structural data or bioinformatics. Therefore, it has significant potential for application in various enzymes to expedite the progress in enzyme engineering.

GRAPHICAL ABSTRACT
Modelling variability and heterogeneity of EMT scenarios highlights nuclear positioning and protrusions as main drivers of extrusion
Authors: Plunder Steffen , Danesin Cathy , Glise Bruno , Ferreira Marina A. , Aceituno Sara Merino , Theveneau Eric
Published: November 2023

Epithelial-Mesenchymal Transition (EMT) is a key process in physiological and pathological settings (i.e. development, fibrosis, cancer). EMT is often presented as a linear sequence of events including (i) disassembly of cell-cell junctions, (ii) loss of epithelial polarity and (iii) reorganization of the cytoskeleton leading to basal extrusion from the epithelium. Once out, cells can adopt a migratory phenotype with a front-rear polarity and may additionally become invasive. While this stereotyped sequence can occur, many in vivo observations have challenged this notion. It is now accepted that there are multiple EMT scenarios and that cell populations implementing EMT are often heterogeneous. However, the relative importance of each EMT step towards extrusion is unclear. Similarly, the overall impact of variability and heterogeneity on the efficiency and directionality of cell extrusion has not been assessed. Here we used computational modelling of a pseudostratified epithelium to model multiple EMT-like scenarios. We confronted these in silico data to the EMT occurring during neural crest delamination. Overall, our simulated and biological data point to a key role of nuclear positioning and protrusive activity to generate timely basal extrusion of cells and suggest a non-linear model of EMT allowing multiple scenarios to co-exist.
Whole organism and tissue specific analysis of pexophagy inDrosophila
Authors: Barone Francesco G. , Marcello Marco , Urbé Sylvie , Sanchez-Soriano Natalia , Clague Michael J.
Published: November 2023

Peroxisomes are essential organelles involved in critical metabolic processes in animals such as fatty acid oxidation, ether phospholipid production and reactive oxygen species detoxification. We have generated transgenicDrosophila melanogastermodels expressing fluorescent reporters for the selective autophagy of peroxisomes, a process known as pexophagy. Using light sheet microscopy, we have been able to obtain a global overview of pexophagy levels, across the entire organism at different stages of development. Tissue specific control of pexophagy is exemplified by areas of peroxisome abundance but minimal pexophagy observed in clusters of oenocytes, which are the major site of long chain fatty acid synthesis. They are surrounded by epithelial cells where pexophagy is much more evident. Enhancement of pexophagy was achieved by feeding flies with the iron chelator deferiprone, in line with past results using mammalian cells. Specific drivers were used to visualise pexophagy in neurons, in which we tested the role of two proteins proposed to regulate pexophagy. Firstly, depletion of CG8814, theDrosophilahomologue of the yeast protein Atg37, had no noticeable impact on pexophagy. In contrast, specific depletion in the larval central nervous system of Hsc70-5, theDrosophilahomologue of the chaperone HSPA9/Mortalin, led to a substantial elevation in pexophagy.
Business processes management as a tool to enhance intellectual capital in the digitalization era: the new challenges to face
Authors: Broccardo Laura , Vola Paola , Alshibani Safiya Mukhtar , Tiscini Riccardo
Published: November 2023

Purpose

Digitalization is affecting business management and pushing for new strategies, innovative products, new ways to communicate with stakeholders and new channels. This phenomenon is unavoidable, and companies have to face it in a holistic and integrated way. One holistic and interconnected approach, when studying enterprise challenges, is represented by the business process management method, a fitting mechanism when digitalization needs to be amalgamated in business practices, enhancing the intellectual capital (IC), therefore, this study researches digitalization under business process lens, in a sample of small and medium enterprises (SMEs), that constitute an under-explored set, as regard digitalization, process management and IC. The research aims to explore the digital tools and business processes link and the related impact on performance, benefits and IC.

Design/methodology/approach

In exploring digitalization, a sample of Italian SMEs was scrutinized. The data were elaborated using two types of tests: (1) the binomial tests for the categorical questions and (2) the zeta test was used for quantitative variables. Furthermore, the partial least square (PLS)-SEM model was applied.

Findings

Findings reveal that some digital tools are more adopted in the sample analysed, and also some particular digital tools are more inclined to support certain business processes. Furthermore, not only performance benefits emerge, but also benefits in terms of better communication and faster decisions, supporting the decision making process of managers, also considering that business processes approach is one way to manage IC.

Practical implications

Thanks to the conducted research it is possible to make aware managers and owners of SMEs to consciously choose the right type of digitalization investments, without neglecting training programme, to realize the company digital transformation, providing a map and bearing in mind the value added creation, protecting their IC.

Originality/value

The paper's originality is represented by the contribution in opening the black box about digitalization, business process management and IC in small and medium companies.
Metaverse: shifting the reality of services
Authors: Gleim Mark , McCullough Heath , Ferrell O.C. , Gabler Colin
Published: November 2023

Purpose

This research aims to focus on the impact of the metaverse on services marketing. After reviewing the past, current and anticipated future of the metaverse, the authors offer multiple research opportunities in accordance with theories germane to the services literature.

Design/methodology/approach

The current research uses a conceptual approach focused on key service theories and their relevance in the metaverse.

Findings

The metaverse presents a new paradigm of the customer experience, thus providing an opportunity for service researchers to advance this developing field. Further, the potential shortcomings of existing theory are explored, both within and external to services, to discover important areas for service scholars to examine. This results in research opportunities and questions for scholars to pursue as the metaverse continues to develop and shape consumer experiences.

Originality/value

Technological advancements have enabled the service sector to grow and thrive in the metaverse. It is evident that despite the metaverse’s growth, there remains a tremendous amount left to examine. Existing theories need to be reexamined and modified, or alternative theories reviewed to inform service research on the metaverse. Thus, the present research seeks to provide insight into opportunities for theory development by service researchers and identifies important areas of future scholarly work on the metaverse.
Conceptualising reflexivity within critical discourse of social marketing
Authors: Millard Rachael , Akbar M. Bilal
Published: November 2023

Purpose

This paper aims to understand what reflexivity means and explores which types of reflexivity could be applied within social marketing practice as a critical approach to overcoming failures.

Design/methodology/approach

This paper is a critical literature review.

Findings

The study proposes a typology for a reflexive approach to social marketing practice to overcome failures. The typology is built on self and critical reflexivity, simultaneously allowing social marketers to reflect on external and internal factors that may affect the individual's role and could negatively affect social marketing practice unless otherwise considered. The types of reflexivity discussed are not prescriptive; instead, the authors intend to provoke further discussion on an under-researched but vital area of social marketing.

Research limitations/implications

The proposed typology is conceptual; an empirical investigation to gain social marketer's views would further enhance the effectiveness of the applications of the typology.

Practical implications

Social marketers could use the proposed typology for future practice.

Originality/value

This is the first study that conceptualises various types of reflexivity within social marketing practice to overcome failures.
Analysis of the spatial urbanization effect of digital finance in China
Authors: Hao Yunping , Zhao Wei
Published: November 2023

Purpose

This study aims to empirically examine the impact of digital finance on spatial urbanization and elucidate its underlying mechanisms.

Design/methodology/approach

Using panel data of Chinese prefecture-level cities from 2011 to 2021, and using a spatial dynamic panel model, the authors analyzed the effects of digital finance on spatial urbanization and the mechanism of its action.

Findings

The findings of the study reveal that digital finance, along with its sub-dimensions, namely coverage breadth, usage depth and digitization degree, all contribute to the enhancement of spatial urbanization. The information channel effect generated by the development of postal and telecommunication businesses, the goods delivery effect generated by the development of retail businesses and the wealth accumulation effect generated by the accumulation of household wealth are all important channels through which digital finance promotes spatial urbanization. Digital finance exerts a significant promotional effect on spatial urbanization in second-tier cities, third-tier cities and their subsequent tiers. This observation alludes to the regionally inclusive nature of spatial urbanization promotion facilitated by digital finance.

Originality/value

The present study endeavors to fill this void by employing empirical analysis to investigate the ramifications of digital finance on spatial urbanization, thereby shedding light on the pivotal role played by digital finance in expediting the progression of spatial urbanization. This study undertakes an examination of the spatial spillover effects, thus providing a comprehensive exposition of the influence of digital finance on spatial urbanization. This study introduces this crucial dimension, and the empirical findings elucidate that digital finance fosters the evolution of spatial urbanization by broadening the coverage of information channels, augmenting the efficiency of goods distribution and enhancing wealth accumulation efficacy.
An exploratory study on emotional consequents of visceral food pleasure
Authors: Donato Carmela , Monsurrò Luigi
Published: November 2023

Purpose

This study aims to explore the phenomenon of visceral food pleasure, described as a unitary experience that, after an initial sense of pleasure and relief generated by the satisfaction of eating impulses, is followed by negative feelings – such as guilt and worry – linked to the consumption of hedonic or unhealthy foods.

Design/methodology/approach

An exploratory approach has been adopted. In particular, the critical incident technique among 87 individuals has been used to extract insights about visceral food pleasure.

Findings

Contrary to previous research results, this study shows that viscearl food pleasure is not a unitary phenomenon, identifying four types of different facets, two of which have a negative valence in terms of felt emotions post-consumption and psychological well-being (i.e. the “greedy” and the “maladaptive” experiences). More importantly, the other two facets are associated with positive consequences in terms of emotions felt post-consumption and perceived psychological well-being (i.e. the “social” and the “fair sin” experiences).

Practical implications

Companies that provide food experiences can prime meanings that influence consumers’ perceptions of the episode to elicit positive emotions post-consumption and psychological well-being.

Social implications

Promoting a more holistic view of food consumption and psychological well-being can free consumers from negative emotions during food consumption episodes. Priming a particular meaning can be a way to do that. However, as visceral experience can still lead to health issues, this must be combined with an education process that makes consumers aware of their food habits.

Originality/value

This research challenges the idea that visceral food experiences are always negative. Indeed, when associated with particular meanings (i.e. social and reward), they have a positive valence post-consumption.
Peri‐operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists
Authors: Armstrong R. A. , Soar J. , Kane A. D. , Kursumovic E. , Nolan J. P. , Oglesby F. C. , Cortes L. , Taylor C. , Moppett I. K. , Agarwal S. , Cordingley J. , Davies M. T. , Dorey J. , Finney S. J. , Kendall S. , Kunst G. , Lucas D. N. , Mouton R. , Nickols G. , Pappachan V. J. , Patel B. , Plaat F. , Scholefield B. R. , Smith J. H. , Varney L. , Wain E. , Cook T. M. ,   collaborators
Published: November 2023

The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12‐month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri‐operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0–3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5–80.5) vs. 50.5 (30.5–70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3–5 vs. 27% ASA physical status 1–2). The surgical case‐mix included more weekend (14% vs. 11%), out‐of‐hours (19% vs. 10%), non‐elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.
Peri‐operative cardiac arrest: management and outcomes of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists
Authors: Armstrong R. A. , Cook T. M. , Kane A. D. , Kursumovic E. , Nolan J. P. , Oglesby F. C. , Cortes L. , Taylor C. , Moppett I. K. , Agarwal S. , Cordingley J. , Davies M. T. , Dorey J. , Finney S. J. , Kendall S. , Kunst G. , Lucas D. N. , Mouton R. , Nickols G. , Pappachan V. J. , Patel B. , Plaat F. , Scholefield B. R. , Smith J. H. , Varney L. , Wain E. , Soar J. ,   collaborators
Published: November 2023

The 7th National Audit Project of the Royal College of Anaesthetists studied peri‐operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. We report the results of the 12‐month registry phase, from 16 June 2021 to 15 June 2022, focusing on management and outcomes. Among 881 cases of peri‐operative cardiac arrest, the initial rhythm was non‐shockable in 723 (82%) cases, most commonly pulseless electrical activity. There were 665 (75%) patients who survived the initial event and 384 (52%) who survived to hospital discharge. A favourable functional outcome (based on modified Rankin Scale score) was reported for 249 (88%) survivors. Outcomes varied according to arrest rhythm. The highest rates of survival were seen for bradycardic cardiac arrests with 111 (86%) patients surviving the initial event and 77 (60%) patients surviving the hospital episode. The lowest survival rates were seen for patients with pulseless electrical activity, with 312 (68%) surviving the initial episode and 156 (34%) surviving to hospital discharge. Survival to hospital discharge was worse in patients at the extremes of age with 76 (40%) patients aged > 75 y and 9 (45%) neonates surviving. Hospital survival was also associated with surgical priority, with 175 (88%) elective patients and 176 (37%) non‐elective patients surviving to discharge. Outcomes varied with the cause of cardiac arrest, with lower initial survival rates for pulmonary embolism (5, 31%) and bone cement implantation syndrome (9, 45%), and hospital survival of < 25% for pulmonary embolism (0), septic shock (13, 24%) and significant hyperkalaemia (1, 20%). Overall care was rated good in 464 (53%) cases, and 18 (2%) cases had overall care rated as poor. Poor care elements were present in a further 245 (28%) cases. Care before cardiac arrest was the phase most frequently rated as poor (92, 11%) with elements of poor care identified in another 186 (21%) cases. These results describe the management and outcomes of peri‐operative cardiac arrest in UK practice for the first time.
Ventricular assist devices and sleep‐disordered breathing—A mechanical heart stimulating a sleepy brain
Authors: Durland Justin , Angles Jacqueline , Hoyland Frank , Hajj Jennifer M. , Houston Brian A. , Jackson Gregory R.
Published: November 2023

Sleep‐disordered breathing, including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is common in severe heart failure (HF) patients. There is limited data on the effect of left ventricular assist devices (LVAD) on sleep apnea. We performed a retrospective review of 350 durable LVAD patients and found 5 with a history of pre‐ and post‐LVAD sleep studies. All five patients had OSA, and three had concomitant CSA. We observed reduced apnea‐hypopnea index following LVAD placement. This was due to a near abolishment of CSA in three mixed sleep apnea patients—as seen by a central apnea index improvement from an average of 25.9 ± 13.1 to 1.4 ± 2.5 events per hour (p = 0.063). LVAD placement was associated with an increase in thermodilution cardiac output from 2.7 ± 0.6 to 4.1 ± 1.1 L/min (p = 0.014). These findings support chemoreception physiology seen in patients with poor circulation and the effect of restoring this circulation with LVAD support.
The microbiome in the pathogenesis of lung cancer
Authors: Miao Sainan , Qiu Huan
Published: November 2023

As one of the malignant tumors with high incidence rate and high mortality, lung cancer seriously threatens the life safety of patients. Research shows that microorganisms are closely related to lung cancer. The microbiome is symbiotic with the host and plays a vital role in the functions of the human body. Microbiota dysbiosis is correlated with development of lung cancer. However, the underlying mechanisms are poorly understood. This paper summarizes the composition characteristics of the gut–lung axis microbiome and intratumoral microbiome in patients with lung cancer. We then expound five potential carcinogenic mechanisms based on microorganisms, such as genotoxicity, metabolism, inflammation, immune response, and angiogenesis. Next, we list three high‐throughput sequencing methods, and finally looks forward to the prospect of microorganisms as novel targets for early diagnosis and treatment of lung cancer.