bluuebunny/crossref_metadata_2025 huggingface dataset:
Repetitive execution of a reach-and-lift task is associated with inter-trial changes in movement-related EEG features and their predictive power
Authors: Paek Andrew , Prashad Shikha
Published: February 2023

Brain Machine Interfaces (BMIs) can help restore motor function to individuals with paralysis. These systems allow users to control an assistive device through the detection of movement-related brain activity. Such neural signatures are found through machine learning algorithms and training datasets that are generated from participants performing repetitive motor tasks. We anticipate that the movement-related brain waves of interest can attenuate over time due to neural efficiency, where the brain becomes more efficient with practice in a motor task. To explore this hypothesis, we used three open-access EEG datasets where participants performed a simple reach-and-lift task. From each trial, time windows associated with resting and movement periods were segmented. Alpha- and beta-band spectral power was estimated for each epoch, and event-related desynchronization (ERD) was estimated as the suppression in spectral power from rest to movement. These ERDs were compared between early and late trials in the dataset. We also used linear discriminant analysis to assess a machine learning algorithm’s accuracy in classifying whether the time windows belonged to rest or movement based on spectral power. In some cases, the ERDs were significantly different between earlier and later trials, and these differences led to changes in predicting the presence of movement from these ERDs. These results call for a reevaluation of BMI performance in datasets with numerous trials and an exploration of strategies that can compensate for longitudinal changes in movement-related brain activity used for BMIs.
Frataxin-deficient human brain microvascular endothelial cells lose polymerized actin and are paracellularly permeable –implications for blood-brain barrier integrity in Friedreich’s Ataxia
Authors: Smith Frances M. , Kosman Daniel J
Published: February 2023

Background

Friedreich’s Ataxia (FRDA) is the most prevalent inherited ataxia; the disease results from loss of Frataxin, an essential mitochondrial iron trafficking protein. FRDA presents as neurodegeneration of the dorsal root ganglion and cerebellar dentate nuclei, followed by brain iron accumulation in the latter. End stage disease includes cardiac fibrosis that contributes to hypertrophic cardiomyopathy. The microvasculature plays an essential barrier role in both the brain and heart, thus an investigation of this tissue system in FRDA is essential to the delineation of the cellular dysfunction in this genetic disorder. Here, we investigate brain microvascular endothelial cell integrity in FRDA in a model of the blood-brain barrier (BBB).

Methods

We used lentiviral mediated shRNA delivery to generate a novel FRDA model in immortalized human brain microvascular endothelial cells (hBMVEC) that compose the microcapillaries of the BBB. We verified known cellular pathophysiologies of FXN knockdown including increased oxidative stress, loss of energy metabolism, and increased cell size. Furthermore, we investigated cytoskeletal architecture including the abundance and organization of filamentous actin, and barrier physiologyviatransendothelial electrical resistance and fluorescent tracer flux.

Results

shFXN hBMVEC display the known FRDA cell morbidity including increased oxidative stress, decreased energy metabolism, and an increase in cell size. We demonstrate that shFXN hBMVEC have less overall filamentous actin, and that filamentous actin is lost at the cell membrane and cortical actin ring. Consistent with loss of cytoskeletal structure and anchorage, we found decreased barrier strength and increased paracellular tracer flux in the shFXN hBMVEC transwell model.

Conclusion

We identified that insufficient FXN levels in the hBMVEC BBB model causes changes in cytoskeletal architecture and increased barrier permeability, cell pathologies that may be related to patient brain iron accumulation, neuroinflammation, neurodegeneration, and stroke. Our findings implicate other barrier cells,e.g.,the cardiac microvasculature, likely contributory also to disease pathology in FRDA.
The interaction of the F-like plasmid-encoded TraN isoforms with their cognate outer membrane receptors
Authors: Low Wen Wen , Seddon Chloe , Beis Konstantinos , Frankel Gad
Published: February 2023

Horizontal gene transfer via conjugation plays a major role in bacterial evolution. In F-like plasmids, efficient DNA transfer is mediated by close association between donor and recipient bacteria. This process, known as mating pair stabilization (MPS), is mediated by interactions between the plasmid-encoded outer membrane (OM) protein TraN in the donor and chromosomally-encoded OM proteins in the recipient. We have recently reported the existence of seven TraN sequence types, which are grouped into four structural types, we named TraNα, TraNβ, TraNγ, TraNδ. Moreover, we have shown specific pairing between TraNα and OmpW, TraNβ and OmpK36 ofKlebsiella pneumoniae, TraNγ and OmpA and TraNδ and OmpF. In this study we found that although structurally similar, TraNα encoded by the pSLT plasmid (TraNα2) binds OmpW in bothEscherichia coliandCitrobacter rodentiumwhile TraNα encoded by the R100-1 plasmid (TraNα1) only binds OmpW inE. coli. AlphaFold2 predictions suggested that this specificity is mediated by a single amino acid difference in loop 3 of OmpW, which we confirmed experimentally. Moreover, we show that single amino acids insertions into loop 3 of OmpK36 affect TraNβ-mediated conjugation efficiency of theK. pneumoniaeresistance plasmid pKpQIL. Lastly, we report that TraNβ can also mediate MPS by binding OmpK35, making it the first TraN variant that can bind more than one OM protein in the recipient. Together, these data show that subtle sequence differences in the OM receptors can impact TraN-mediated conjugation efficiency.

Importance

Conjugation plays a central role in the spread of antimicrobial resistance genes amongst bacterial pathogens. Efficient conjugation is mediated by formation of mating pairs via a pilus, followed by mating pair stabilisation (MPS), mediated by tight interactions between the plasmid encoded outer membrane protein (OMP) TraN in the donor (of which there are seven sequence types grouped into the four structural isoforms α, β, γ, δ) and an OMP receptor in the recipient (OmpW, OmpK36, OmpA and OmpF, respectively). In this study we found that subtle differences in OmpW and OmpK36 have significant consequences on conjugation efficiency and specificity, highlighting the existence of selective pressure affecting plasmid-host compatibility and the flow of horizontal gene transfer in bacteria.
Time to lysis determines phage sensitivity to a cytidine deaminase toxin/antitoxin bacterial defense system
Authors: Hsueh Brian Y. , Sanath-Kumar Ram , Bedore Amber M. , Waters Christopher M.
Published: February 2023

Toxin-antitoxin (TA) systems are ubiquitous two-gene loci that bacteria use to regulate cellular processes such as phage defense. Here, we demonstrate the mechanism by which a novel type III TA system,avcID, is activated and confers resistance to phage infection. The toxin of the system (AvcD) is a deoxycytidylate deaminase that converts deoxycytidines (dC) to dexoyuridines (dU), while the RNA antitoxin (AvcI) inhibits AvcD activity. We have shown that AvcD deaminated dC nucleotides upon phage infection, but the molecular mechanism that activated AvcD was unknown. Here we show that the activation of AvcD arises from phage-induced shutoff of host transcription, leading to degradation of the labile AvcI. AvcD activation and nucleotide depletion not only decreases phage replication but also increases the formation of defective phage virions. Surprisingly, infection of phages such as T7 that are not inhibited by AvcID also lead to AvcI RNA antitoxin degradation and AvcD activation, suggesting that depletion of AvcI is not sufficient to confer protection against some phage. Rather, our results support that phage with a longer lysis time like T5 are sensitive to AvcID-mediated protection while those with a shorter lysis time like T7 are resistant.

AUTHOR’S SUMMARY

Numerous diverse antiphage defense systems have been discovered in the past several years, but the mechanisms of how these systems are activated upon phage infection and why these systems protect against some phage but not others are poorly understood. The AvcID toxin-antitoxin phage defense system depletes nucleotides of the dC pool inside the host upon phage infection. We show that phage inhibition of host cell transcription activates this system by depleting the AvcI inhibitory sRNA, which inhibits production of phage and leads to the formation of defective virions. Additionally, we determined that phage lysis time is a key factor that influences sensitivity to AvcID with faster replicating phage exhibiting resistance to its effects. This study has implications for understanding the factors that influence bacterial host/phage dynamics.
Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling
Authors: Boyle Kieran A. , Polgár Erika , Gutierrez-Mecinas Maria , Dickie Allen C. , Cooper Andrew H. , Bell Andrew M. , Evelline Jumolea M. , Casas-Benito Adrian , Watanabe Masahiko , Hughes David I. , Weir Greg A. , Riddell John S. , Todd Andrew J.
Published: February 2023

Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here we investigate the role of interneurons that continue to express NPY (NPY-INs) in adulthood. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen-evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY- IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.
Mapping knowledge assets categories for successful crowdfunding strategies
Authors: Lerro Antonio , Santarsiero Francesco , Schiuma Giovanni , Bartuseviciene Ilona
Published: February 2023

Purpose

Crowdfunding models recently emerged as relevant enhancing systems aimed at fostering innovation and entrepreneurial dynamics. Accordingly, great attention has been paid to seeker firms' characteristics and platforms. For this reason, adopting a holistic knowledge-based perspective on crowdfunding is essential. This paper first identifies and categorizes the potential knowledge-based dimensions grounding crowdfunding and technological scouting strategies to provide a theoretically-grounded framework potentially useful for driving decision-making processes. Then, it is applied to interpret a real crowdfunding strategy developed by an Italian platform in the field of the real estate sector.

Design/methodology/approach

The paper combines deductive and inductive approaches. After elaborating a conceptual framework identifying the potential knowledge-based dimensions for a crowdfunding strategy, it is tested and applied by re-interpreting a real crowdfunding strategy.

Findings

The study identifies the potential knowledge assets dimensions grounding a crowdfunding strategy through elaborating a dedicated conceptual framework. Then, the case study enriches the proposed conceptual arguments with a set of empirical evidence.

Research limitations/implications

The paper provides a conceptual framework capable of fostering a specific research stream and carrying out a first holistic and systematic knowledge-based perspective. The authors believe that their research may provide a relevant contribution to the existing literature, depicting a comprehensive picture of the intellectual capital components that seekers have to identify and manage in crowdfunding. While doing so, the study significantly addresses the challenge launched by Troise et al. (2021) in order to enrich prior but highly fragmented studies on the role of intellectual capital components in crowdfunding.

Practical implications

The analysis of the models and tools developed and discussed can be useful to support the elaboration and the application of practical knowledge-based approaches, protocols and routines for the value generation in the crowdfunding field and to drive the designer of crowdfunding platforms and strategies to develop more effective and impactful initiatives and campaigns. Accordingly, when elaborating a crowdfunding strategy, it should be effectively highlighted that seekers have and are capable of managing intellectual capital in different manners. This is particularly true for new ventures that are generally challenged to provide information about their quality, in particular about founders, their previous experiences, potential and real networks and partnerships, innovation capacity.

Originality/value

This paper contributes to the further development of the crowdfunding literature according to a knowledge-based perspective.
The motility of posted workers during the COVID-19 pandemic: policies, trends and worker experiences in Austria
Authors: Danaj Sonila , Kayran Elif Naz , Geyer Leonard
Published: February 2023

Purpose

To analyse the policies, posting trends and worker experiences during the pandemic, this study uses the concept of motility, i.e. workers' mobility capital, and examines how posted workers' geographical mobility, their access to and conditions of employment and social protection were impacted. The authors discuss how the measures against the pandemic undertaken at the European Union (EU) and national level have affected labour mobility, the impact these measures have had on macro trends of posting to Austria, and lastly, how the pandemic and the actions against it have influenced the lives of posted workers at the individual level.

Design/methodology/approach

In this article, the authors focus on the specific case of posting to Austria. The authors ask whether, and if so, how EU and national policies which came about during the COVID-19 pandemic influenced the motility of posted workers, and how these workers used their mobility capital in this unfolding context. The authors address the research questions with analyses of EU and national level policies, use administrative data on posting, and individual-level data based on interviews with posted workers and public authorities.

Findings

The authors find that the Austrian government's public health and economic priorities were jointly influential on the motility of cross-border workers. The specific case of the posted workers shed new light on the limits to such a national sovereignty approach when it comes to economic interests in an increasingly interdependent European labour market. This study’s findings show that despite the access provided at the policy levels, the motility of posted workers was also affected by their individual circumstances, or competences, which produced different forms of appropriation.

Originality/value

The authors apply the theoretical framework of motility by studying policy developments through the element of access options and conditions, and the posting trends to Austria and worker experiences at the individual level through the lenses of appropriation and competences. The authors find that while the EU and national public policy in enhancing access options have been successful during the COVID-19 period, amelioration attempts in access conditions have not been realised as observed in our analysis of the competence and appropriation dimensions of the posted workers in Austria. This highlights the need for a more integrated approach in the study of policies by exploring beyond the national and EU level policies and focussing on the implementation and observations at the individual level.
Seeing is buying: should offline retailers use shelf-based scarcity to sell products?
Authors: Ezhil Kumar Madhumitha , Pandey Shivendra Kumar , Sharma Dheeraj P. , Rathore Himanshu
Published: February 2023

Purpose

This study aims to examine the moderating role of two product-related variables – product type and product involvement on the relationship between shelf-based scarcity (SBS) and purchase intention.

Design/methodology/approach

The authors used four 2 × 2 between-subject experiments to test the proposed moderation.

Findings

Results from the four experimental studies provide the following insights. SBS enhances customers’ purchase intentions for utilitarian products and decreases purchase intentions for hedonic products. The positive influence of SBS cues on purchase intentions is more pronounced for low-involvement products than for high-involvement products. Perceived popularity and perceived quality mediate the relationship between SBS and perceived consumption risk for utilitarian products but not hedonic products.

Research limitations/implications

This study builds on prior research on scarcity by investigating the impact of product-related factors on the SBS-purchase intention relationship through the elaboration likelihood model.

Practical implications

The results suggest that retailers benefit from using SBS cues for utilitarian and low-involvement products to increase purchase intention. Retailers can avoid SBS cues for hedonic products to prevent them from seeming commonplace. Furthermore, retailers can boost purchase intentions by highlighting the popularity and quality of utilitarian and low-involvement products.

Originality/value

To the best of the authors knowledge, this is the first study to examine the interaction between SBS and product-related attributes, along with the serial mediation of perceived popularity, quality and consumption risk.
Positive faultlines: an unconventional perspective on team compositional dynamics
Authors: Kaur Manpreet , Ren Hong
Published: February 2023

Purpose

Faultline literature has been extensively examined for its effect on various outcomes. Barring a few exceptions, this research has primarily inferred the adverse impact of such splits. The purpose of this theoretical paper is to assert that these divisions can also be formed based on positive psychological capacities, which will cause a divide, but eventually help increase performance.

Design/methodology/approach

This paper offers a conceptual model that links employee psychological capital with the faultline literature and suggests its impact on team performance. It also explores the positive moderating effect of time and team goal orientation.

Findings

The study asserts that there will be an initial divide, but the positive faultlines will improve team performance. Several propositions are formulated that provide the opportunity for further examination.

Originality

This paper makes a contemporary and important conceptual contribution to the faultline literature by proposing a new notion: “positive faultlines.” To view the effect of faultlines from a positive perspective, a pioneering endeavor is made to explore the impact of employees’ psychological capital in teams. By integrating the faultline literature with positive organizational behavior, this study offers an alternative line of thinking on team compositional dynamics.
Analysis of the acoustic seismic energy flux propagated through synthetic models formed by different structures
Authors: Chacón‐Hernández Francisco
Published: February 2023

Seismic‐acoustic wavefield propagations on synthetic 2D models formed by different structural backgrounds are analysed in four test cases. These test cases were carried out employing staggered‐grid finite differences and absorbing boundaries of the convolutional perfectly matched layers type, which allowed analysing in a time of 7.0 s: (a) the seismic‐acoustic wavefield behaviour, (b) the kinetic seismic energy flux and potential seismic energy flux and (c) the energy differences (ΔKEF/ΔPEF) due to each type of proposed structure. In the first two test cases, a relationship was observed between average kinetic seismic energy flux/potential seismic energy flux values and the different structural densities ε of each synthetic model, which were formed by a similar type of structure (fractures). The average kinetic seismic energy flux values increased when ε decreased, whereas the average potential seismic energy flux values decreased when ε also decreased. The largest ΔKEF/ΔPEF values were observed for those models with more structures, reaching up to 0.2 × 108/0.21 × 108 J/m2 in the first test case and up to 1.95 × 108/1.91 × 108 J/m2 in the second test case. Meanwhile, for those models with less number of structures was 0.04 × 108/0 J/m2 in test case 1 and 0.26 × 108/0.61 × 108 J/m2 in test case 2. In the third test case, a relationship was observed between the average potential seismic energy flux values and the ε values, but not with the average kinetic seismic energy flux values, the synthetic models of which were formed by different types of structures (lobes and fractures under different shapes and sizes). The kinetic seismic energy fluxes were more affected by structures closer to each other than by those further apart. Meanwhile, the potential seismic energy fluxes were more affected by larger structures, maintaining a relationship with the seismic frequency and wavelength. The largest ΔKEF/ΔPEF values reached up to 3.42 × 108/3.24 × 108 J/m2 in model with the highest ε value, whereas up to 0.49 × 108/0.67 × 108 J/m2 in the model with the lowest ε value. In the fourth test case, similar types of structures (fractures) were analysed under different orientations in each model. The kinetic seismic energy fluxes/potential seismic energy fluxes were higher in the model formed by better‐oriented structures or parallel with respect to the propagation direction of the seismic‐acoustic wavefield. These energy differences between each test case show how not only the number of structures in a model and the ε values influenced the seismic‐acoustic wavefield and the kinetic seismic energy flux/potential seismic energy flux, but also the structural aspects, the intrinsic elastic properties (e.g. the density used in structures), location (separation between structures) and orientation of structures.
Genotyping of two congeneric bitterling fish species by nuclear SNP markers and the detection of hybridization in a sympatric region
Authors: Hata Hiroki , Taniguchi Rintaro , Yamashita Naoki , Hashiguchi Yasuyuki , Nakajima Jun , Takeyama Tomohiro
Published: February 2023

Bitterling fish species (subfamily: Acheilognathinae) are endangered in Japan due to habitat loss. The decline of freshwater mussels also enhances the decrease of bitterlings because bitterlings lay eggs in the gills of freshwater mussels. Furthermore, loss of unionid mussels causes hybridization between bitterling species. This study aims to analyze the frequency of hybridization between congeneric species of bitterlings—Tanakia lanceolata and Tanakia limbata—at a well‐preserved site, where both species occur naturally and compare this with other regions more severely impacted by human intervention. One part of the irrigation streams of the Asahi River System, Okayama, is inhabited by a natural monument species of Japan, a benthic cobitid, Parabotia curtus, and therefore, the natural substratum and the structurally heterogeneous stream banks are maintained. We collected Tanakia individuals and surveyed mussel density at this well‐preserved site. We also developed six nuclear single‐nucleotide polymorphism (SNP) markers on different chromosomes to distinguish T. lanceolata and T. limbata. These SNP markers effectively determined individuals as being either one of these species or a hybrid. Based on genotyping, eight individuals were determined to be hybrids, whereas 90 and 173 individuals were determined as purebreds of T. lanceolata and T. limbata, respectively. The proportion of hybrid individuals was 3.0% and was relatively low compared to other regions. In addition, five species of unionids were densely distributed in this stream. Prezygotic isolation between sympatric T. lanceolata and T. limbata was established at this well‐preserved site, where unionid mussels are densely populated and provide enough breeding substrate for both species.
Suspending failure: temporalities, ontologies, and gigantism in fusion energy development
Authors: Alexander Catherine
Published: February 2023

Tracing the history of terrestrial fusion energy to a giant multinational experimental fusion facility under construction reveals a series of consequential failures, re‐evaluations of once defunct designs, but also persistence. To account for how this vast enterprise, dogged by failure, endures, I suggest that different ontological narratives re‐orientate the enterprise both temporally and vis‐à‐vis different forms and valences of failure. Thus the rhetoric of mission‐driven project vies with that of open‐ended, present‐focused experiment: the former is positioned as the crucial solution to the threat of climate change; the latter ‘bakes in’ virtuous failure as integral to creative practice. Visionary promise moves to a focus on the meanwhile. Finally, the sheer unfurling size to which attention is constantly drawn offers a disorientating spectacle, denying perspective or closure and acting to suspend judgements of failure.
Pre‐set estimation‐based in‐silico silhouette‐based methodology for improving the robustness to viewing direction difference for assisting forensic gait analysis
Authors: Imoto Daisuke , Hirabayashi Manato , Honma Masakatsu , Kurosawa Kenji
Published: February 2023

Forensic gait analysis is used to visually and quantitatively analyze information regarding the appearance and style of walking that can be presented as evidence in the court. The demand for analyzing CCTV pedestrian footage in video surveillance has been increasing. The dependence of the accuracy of semiautomatic silhouette‐based analysis, often used in forensic science, on the differences in the viewing directions is a very challenging issue that is yet to be resolved for real case applications. Currently, the different viewing directions used in comparison footage significantly decrease the accuracy of same person analysis when using the silhouette‐based method, often used in the Japanese forensic science domain. A calibration‐based method was previously prosed to resolve this problem, but it requires performing an elaborate measurement procedure at the camera installation site for an accurate analysis. In this study, we propose a novel in‐silico silhouette‐based analysis method that significantly expands the number of viewing direction pre‐set settings to 900 from the 24 used in the previous method. Several software tools have been developed to ensure that all the procedures can be executed on a computer. The experimental results confirm that the accuracy of the proposed method is comparable to that of the calibration‐based method. Furthermore, the practical comparison results from actual consultation confirmed the effectiveness of the proposed method under existing viewing direction differences. We therefore anticipate that the proposed method will be beneficial for improving the analysis accuracy in real cases and therefore serve as a substitute of the previous method.
Captive rearing effects on the methylome of Atlantic salmon after oceanic migration: Sex‐specificity and intergenerational stability
Authors: Venney Clare J. , Bouchard Raphaël , April Julien , Normandeau Eric , Lecomte Laurie , Côté Guillaume , Bernatchez Louis
Published: February 2023

Captive rearing in salmon hatcheries can have considerable impacts on both fish phenotype and fitness within a single generation, even in the absence of genetic change. Evidence for hatchery‐induced changes in DNA methylation is becoming abundant, though questions remain on the sex‐specificity of these effects, their persistence until spawning and potential for transmission to future generations. Here we performed whole genome methylation sequencing of fin tissue for 16 hatchery and 16 wild Atlantic salmon (Salmo salar) returning to spawn in the Rimouski River, Québec, Canada. We identified two cohorts of hatchery‐reared salmon through methylation analysis, one of which was epigenetically similar to wild fish, suggesting that supplementation efforts may be able to minimize the epigenetic effects of hatchery rearing. We found considerable sex‐specific effects of hatchery rearing, with few genomic regions being affected in both males and females. We also analysed the methylome of 32 F1 offspring from four groups (pure wild, pure hatchery origin and reciprocal hybrids). We found that few epigenetic changes due to parental hatchery rearing persisted in the F1 offspring though the patterns of inheritance appear to be complex, involving nonadditive effects. Our results suggest that the epigenetic effects of hatchery rearing can be minimal in F0. There may also be minimal epigenetic inheritance and rapid loss of epigenetic changes associated with hatchery rearing. However, due to sex‐specificity and nonadditive patterns of inheritance, methylation changes due to captive rearing are rather complex and the field would benefit from further research on minimizing the epigenetic effects of captive rearing in conservation efforts.
Feeding graded levels of dried Sea buckthorn (Hippophaes rhamnoides) berries to broiler chickens
Authors: Pirgozliev Vasil , Mansbridge Stephen C. , Whiting Izzy M. , Rose Stephen P. , Kljak Kristina , Johnson Amy E. , Drijfhout Falko , Orczewska‐Dudek Sylwia , Atanasov Atanas G. , Mihova Teodora
Published: February 2023

The aim of this study was to assess the effects of graded levels (0, 3, 6, 9 and 12 g/kg) of dry Sea buckthorn (SB) berries on growth performance, gastrointestinal tract (GIT) development, jejunal histomorphology, bird antioxidant status and caecal short‐chain fatty acid concentration when fed to female Ross 308 broiler chickens. In addition, expression of cytokine biomarker genes in the jejunum was evaluated. The five experimental diets were fed from 7 to 21 days age to 8 pens (two birds in each) following randomisation. Feeding SB did not influence bird growth performance (p > .05). There was a linear decrease in butyric, acetic and valeric acid concentrations in caecal digesta (p < .05) and a decrease (p < .05) in crypt depth. The expression of IFNG and CD40LG responded quadratically (p < .05), peaking at 6–9 g/kg dietary inclusion of SB, respectively. Other studied variables were not affected by dietary SB inclusion (p > .05). Feeding dry SB berries up to 12 g/kg of diet did not improve the zootechnical variables of healthy commercial‐strain broilers in this study.
The Tpl2‐MEK pathway plays a critical role in spheroid‐cultured endometriotic stromal cells
Authors: Minami Toshiyuki , Tsuzuki Yota , Tanaka Yukiko , Kitawaki Jo , Mori Taisuke
Published: February 2023

Problem

Endometriosis is a proliferative disease characterized by cytokine‐induced inflammation. The objective of this study was to assess cell growth and PGE2 production induced by TNF‐α in endometriotic stromal cells (ESCs) in spheroid cell culture and to identify the signaling pathway involved with a view to finding new therapeutic targets for endometriosis.

Method of study

Tissue samples were collected from patients with and without endometriosis. ESCs were isolated from ovarian endometrioma (OE). Gene expression was evaluated by real‐time PCR and DNA microarray analysis, the proliferative effect on ESCs by WST‐8 assay, and PGE2 production by ELISA. Protein phosphorylation was detected using western blotting.

Results

COX‐2, aromatase and VEGFA mRNA expression and PGE2 production were significantly elevated in spheroid cell cultures compared to monolayer cell cultures. TNF‐α receptor (TNFR) 1 and TNFR2 mRNA was also significantly increased. TNF‐α promoted the proliferation and PGE2 production of ESCs in spheroid cell cultures significantly more than in monolayer cell cultures. TNF‐α increased the expression of several genes related to the pathophysiology of endometriosis in spheroid ESCs. DNA microarray analysis revealed that the Tpl2 gene, which codes for a MAPK upstream of MEK, was upregulated in OE and endometrium with endometriosis compared to normal endometrium. TNF‐α increased the phosphorylation and expression of Tpl2 and MEK, and Tpl2 and MEK inhibitors inhibited TNF‐α‐induced proliferation and PGE2 production in spheroid ESCs.

Conclusion

The Tpl2‐MEK signaling pathway may play a critical role in the cell growth and PGE2 production induced by TNF‐α in spheroid ESCs.
Interaction alerts: A comparison of classifications and recommendations for clinical management between Janusmed and three other knowledge resources
Authors: Tukukino Carina , Eriksson Anna L. , Hamdan Walaa , Wallin Hybelius Frida , Wallerstedt Susanna M.
Published: February 2023

Classifications of drug interaction alerts differ between knowledge resources, but agreement regarding recommendations for clinical management is less explored. Starting from the medication lists of 274 older patients with ≥2 drugs, all unique drug pairs that triggered a clinically significant interaction alert in Janusmed were included: 100 Category C (manageable by, e.g. dose adjustment) and nine Category D interactions (should be avoided). Out of 109 C/D alerts in Janusmed, 89 (82%), 75 (69%) and 45 (41%) drug pairs triggered an alert of similar clinical significance in Lexicomp, Micromedex® and Stockley's Drug Interactions/Checker (Stockley), respectively. Eight (7%), 20 (18%) and 10 (9%) drug pairs did not trigger any alert in these resources. For 81 (74%), 81 (74%) and 94 (86%) drug pairs, Lexicomp, Micromedex and Stockley provided at least one recommendation for clinical management similar to those provided by Janusmed. For 16 (15%), 9 (8%) and 21 (19%) drug pairs, these resources provided recommendation(s) entirely in agreement with Janusmed. Although many drug pairs elicit alerts of similar significance, and partly concordant recommendations, a non‐negligible proportion do not. The findings encourage medical/pharmaceutical reflection by prescribing clinicians and dispensing pharmacists; recommendations provided by knowledge resources vary considerably and cannot be considered definite.
Spatial genomic diversity associated with APOBEC mutagenesis in squamous cell carcinoma arising from ovarian teratoma
Authors: Tamura Ryo , Nakaoka Hirofumi , Yachida Nozomi , Ueda Haruka , Ishiguro Tatsuya , Motoyama Teiichi , Inoue Ituro , Enomoto Takayuki , Yoshihara Kosuke
Published: February 2023

Although the gross and microscopic features of squamous cell carcinoma arising from ovarian mature cystic teratoma (MCT‐SCC) vary from case to case, the spatial spreading of genomic alterations within the tumor remains unclear. To clarify the spatial genomic diversity in MCT‐SCCs, we performed whole‐exome sequencing by collecting 16 samples from histologically different parts of two MCT‐SCCs. Both cases showed histological diversity within the tumors (case 1: nonkeratinizing and keratinizing SCC and case 2: nonkeratinizing SCC and anaplastic carcinoma) and had different somatic mutation profiles by histological findings. Mutation signature analysis revealed a significantly enriched apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC) signature at all sites. Intriguingly, the spread of genomic alterations within the tumor and the clonal evolution patterns from nonmalignant epithelium to cancer sites differed between cases. TP53 mutation and copy number alterations were widespread at all sites, including the nonmalignant epithelium, in case 1. Keratinizing and nonkeratinizing SCCs were differentiated by the occurrence of unique somatic mutations from a common ancestral clone. In contrast, the nonmalignant epithelium showed almost no somatic mutations in case 2. TP53 mutation and the copy number alteration similarities were observed only in nonkeratinizing SCC samples. Nonkeratinizing SCC and anaplastic carcinoma shared almost no somatic mutations, suggesting that each locally and independently arose in the MCT. We demonstrated that two MCT‐SCCs with different histologic findings were highly heterogeneous tumors with clearly different clones associated with APOBEC‐mediated mutagenesis, suggesting the importance of evaluating intratumor histological and genetic heterogeneity among multiple sites of MCT‐SCC.
Multifactorial glial responses and their contributions to Alzheimer's disease continuum
Authors: Hijioka Masanori , Manabe Tatsuya , Saito Takashi
Published: February 2023

Alzheimer's disease (AD) is the most common neurocognitive disorder. Various factors are intricately intertwined before clinical symptoms appear, although both amyloid‐β peptide deposition and neurofibrillary tangle formation (i.e. pathological hallmarks of the AD brain) are established. Among such factors, glial responses have been increasingly recognized as important roles in the progression of these pathologies and viewed as one component of the AD continuum. However, the detailed molecular and cellular mechanisms of glial function underlying AD pathogenesis remain to be elucidated. Recent studies showed that peripheral immunity, gut microbiota or environmental factors influence brain pathophysiologies through communication with glial cells in the brain. This disease complexity makes understanding AD etiology difficult and hinders the development of effective therapeutic strategies to tackle this disease. Conversely, aged patients often suffer from multiple – not a single – diseases as multimorbidity, and AD pathogenesis might be related to pathologies caused by other diseases. Hence, investigating AD as a systemic disease has become critical for identifying therapeutic interventions. This review aimed to summarize current knowledge on AD research and share perspectives for understanding glial functions regarding AD pathophysiology.
Long‐term oncological outcomes for minimally invasive surgery versus open surgery for colon cancer—a population‐based nationwide study with a non‐inferiority design
Authors: Jadid Kaveh Dehlaghi , Cao Yang , Petersson Josefin , Sjövall Annika , Angenete Eva , Matthiessen Peter
Published: February 2023

Aim

The study aimed to compare 5‐year overall survival in a national cohort of patients undergoing curative abdominal resection for colon cancer by minimally invasive surgery (MIS) or by the open (OPEN) technique.

Methods

All patients diagnosed between 2010 and 2016 in Sweden with pathological Union International Contre le Cancer Stages I–III colon cancer localized in the caecum, ascending colon, hepatic flexure or sigmoid colon and those who underwent curative right sided hemicolectomy, sigmoid resection or high anterior resection by MIS or OPEN were included. Patients were identified in the Swedish Colorectal Cancer Registry from which all data were retrieved. The analyses were performed as intention‐to‐treat and the relationship between surgical technique (MIS or OPEN) and overall mortality within 5 years was analysed. For the primary research question a non‐inferiority hypothesis was assumed with a statistical power of 90%, a one‐side type I error of 2.5% and a non‐inferiority margin of 2%. For the secondary analyses, multilevel survival regression models with the patients matched by propensity scores were employed, adjusted for patient‐ and tumour‐related variables.

Results

A total of 11 605 pathological Union International Contre le Cancer Stages I–III patients were included with 3297 MIS (28.4%) and 8308 OPEN (71.6%) and were followed until 31 December 2020. The primary analysis demonstrated superiority for MIS compared to OPEN. The multilevel survival regression analyses confirmed that 5‐year overall survival was higher in MIS with a hazard ratio of 0.874 (95% confidence interval 0.791–0.965), and if excluding pT4 the outcome was similar, with a hazard ratio of 0.847 (95% confidence interval 0.756–0.948).

Conclusion

This observational study demonstrated that MIS was favourable to OPEN with regard to 5‐year overall survival. These results support the use of laparoscopic colon cancer surgery in routine practice.
Diabetes distress mediates the relationship between depressive symptoms and glycaemic control among adults with type 2 diabetes: Findings from a multi‐site diabetes peer support intervention
Authors: Qian Yiqing , Emmerling Dane A. , Kowitt Sarah D. , Ayala Guadalupe X. , Cherrington Andrea L. , Heisler Michele , Safford Monika M. , Tang Tricia S. , Thom David H. , Fisher Edwin B.
Published: February 2023

Aims

Diabetes distress is positively associated with HbA1c and may mediate the relationship between depressive symptoms and HbA1c. This study examined these relationships in a geographically, socioeconomically, and ethnically diverse sample of adults with type 2 diabetes.

Methods

Using data from five US sites evaluating peer support for diabetes management (n = 917), Structural Equation Modeling (SEM) examined whether diabetes distress (four items from Diabetes Distress Scale) mediated the relationship between depressive symptoms (PHQ‐8) and HbA1c. Sites compared interventions of varying content and duration with control conditions. Time from Baseline Assessment to Final Assessment varied from six to 18 months. Site characteristics were controlled by entering site as a covariate along with age, sex, education, diabetes duration, insulin use, and intervention/control assignment.

Results

Depressive symptoms, diabetes distress, and HbA1c were all intercorrelated cross‐sectionally and from Baseline to Final Assessment (rs from 0.10 to 0.57; ps <0.05). In SEM analyses, diabetes distress at Final Assessment mediated the relationship between Baseline depressive symptoms and HbA1c at Final Assessment (indirect effect: b = 0.031, p < 0.001), controlling for Baseline HbA1c and covariates. Parallel analysis of whether depressive symptoms mediated the relationship between Baseline diabetes distress and HbA1c at Final Assessment was not significant.

Conclusions

In this diverse sample, diabetes distress mediated the influence of depressive symptoms on HbA1c but the reverse, depressive symptoms mediating the effect of distress, was not found. These findings add to the evidence that diabetes distress is a worthy intervention target to improve clinical status and quality of life among individuals with type 2 diabetes.
A systematic comparison ofpan‐Trkimmunohistochemistry assays among multiple cancer types
Authors: Haberecker Martina , Töpfer Antonia , Melega Francesca , Moch Holger , Pauli Chantal
Published: February 2023

Aims

NTRK rearranged tumours are rare but can be successfully treated using anti‐TRK‐targeted therapies, making NTRK testing important for treatment choices in patients with advanced cancers. Pan‐Trk immunohistochemistry (IHC) has become a valuable and affordable screening tool in many laboratories. Unfortunately, the choice of antibodies and IHC protocols to investigate biomarkers is not standardised. In this study, we compared the performance of four pan‐Trk IHC methods, using three different clones, primarily in NTRK fusion‐positive tumours.

Methods and results

We studied the performance of four pan‐Trk IHC methods using three different clones: EPR17341 (Abcam and Ventana), EP1058Y (Abcam) and A7H6R (Cell Signaling) in 22 molecularly confirmed NTRK rearranged tumours. Additionally, selected NTRK fusion‐negative tumours were further included: NTRK mutated (n = 8) and amplified (n = 15) tumours as well as NTRK fusion‐negative tumours driven by other gene fusions, such as ALK, ROS1 and BCOR (n = 20), as well as salivary gland tumours (n = 16). Inter‐rater agreement of three pathologists was additionally calculated, including H‐score. With clone EPR17341 (Abcam in‐house and ready‐to‐use Ventana protocol), all molecularly confirmed NTRK1–3 rearranged tumours were positively detected by immunohistochemistry, while the other clones missed NTRK2–3 rearranged tumours. For the fusion‐negative cohort we found the best performance (least false‐positive cases) using the clone A7H6R (Cell Signalling).

Conclusion

Given the therapeutic importance, testing for NTRK rearrangements in daily practice has become necessary and, despite IHC being a fast and affordable tool, using it in routine diagnostics is complicated and requires a high level of expertise.
Seasonality in niche occupation revealed through bird community functional structure in the southern Atlantic rainforest
Authors: Almeida Bia A. , Bochio Gabriela M. , Calsavara Larissa C. , Marques Fernanda C. , dos Anjos Luiz
Published: February 2023

Seasonal variation in tropical and subtropical systems can have different effects on bird species depending on the resources they use and how they use them. However, despite recent research advances, knowledge of the drivers of the presence and abundance of species in different seasons is still limited for most tropical bird species. In these poorly understood systems, examining seasonal changes in species composition from the perspective of traits related to resource use can provide insight into what resources may be driving bird movements between areas throughout the year and what types of species are more subject to seasonality. Here, we explore bird community seasonality in three forest types (dense, semi‐deciduous and mixed rainforests) subjected to different climatic conditions in one of the world's biodiversity hotspots, the Atlantic Rainforest. We investigated differences between summer and winter in species richness and in the composition of resource‐related species traits (diet, foraging strata and substrates) obtained from the literature. The seasonal differences (summer and winter) between forest types were explored in terms of species and trait composition. We found that the main changes that occurred in bird composition between seasons in the southern Atlantic Rainforest were related to species traits such as diet and foraging strata. In general, the proportion of invertivores was higher in winter than in summer, and in the mixed forest, the forest type exposed to the coldest winters, the proportion of frugivores was lower in winter. Furthermore, species with a more varied diet were better represented in the summer. In general, more generalist species were better represented in the forest type subjected to higher seasonal variations in rainfall. Our results revealed seasonal changes in bird community structure that are related to niche occupation and that were more strongly apparent in the forest type subjected to colder winters.