bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis ofDiplolepis rosae: revealing overexpression of genes potentially associated with insect immune response and gall formation at early larval stages
Authors: Mozhaitseva¹ Ksenia , Tourrain¹ Zoé , Branca¹ Antoine
Published: November 2023

Insect parasites can provoke drastic changes in host plant physiology by affecting cell differentiation pathways and various metabolic processes. An intriguing example of such interaction is a gall, a novel outgrowing plant organ, induced by another organism for its own benefit. Cynipidae is a family of gall-inducing hymenopterans that induce galls with a complex anatomical structure. Gall formation involves three stages: initiation, growth, and maturation. Until today, the mechanism of gall initiation remains unknown. In this study, we aimed to reveal candidate genes involved in gall induction inDiplolepis rosae, a gall wasp inducing bedeguars in wild roses. We performed differential expression analysis of the gall wasp larva transcriptome. We observed the overexpression of genes encoding plant cell wall degrading enzymes. These enzymes may contribute to the formation of a chamber for a developing larva by lysing plant tissues. We also demonstrated the overexpression of genes encoding podocan, vasorin-like protein, toll-like receptor 7, tetraspanin, lipase, peroxidase, phospholipase A2, and venom acid phosphatase. These genes may be involved in insect development and the immune response against parasitoids, host plant microbiome, and host plant defense systems. Additionally, we performed a test for selection to detectD. rosaegenes under positive selection. However, we detected only one gene encoding a transposable element. This can be explained by the mostly asexual reproductive mode of this species. Thus, our study contributes to understanding the processes occurring in cynipid wasps during gall formation and creates opportunities for further investigations of other candidate genes.
Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of Phosphodiesterase 2A
Authors: Delhaye Sébastien , Jarjat Marielle , Boulksibat Asma , Sanchez Clara , Tempio Alessandra , Turtoi Andrei , Giorgi Mauro , Lacas-Gervais Sandra , Baj Gabriele , Rovere Carole , Trezza Viviana , Pellegrini Manuela , Maurin Thomas , Lalli Enzo , Bardoni Barbara
Published: November 2023

Phosphodiesterase 2A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cortex and hippocampus, PDE2A expression level is upregulated inFmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacological inhibition of PDE2A has been associated to its pro-cognitive role in normal animals and in models of ID and ASD, homozygousPDE2Amutations have been identified in patients affected by ID, ASD and epilepsy. To clarify this apparent paradox about the role of PDE2A in brain development, we characterized herePde2a+/−mice (homozygote animals being not viable) at the behavioral, cellular, molecular and electrophysiological levels.Pde2a+/−females display a milder form of the disorder with reduced cognitive performance in adulthood, conversely males show severe socio-cognitive deficits throughout their life. In males, these phenotypes are associated with microglia activation, elevated glutathione levels and increased externalization of GluR1 in CA1, producing reduced mGluR-dependent LTD. Overall, our results reveal molecular targets of the PDE2A-dependent pathway underlying socio-cognitive performance. These results clarify the mechanism of action of pro-cognitive drugs based on PDE2A inactivation, which have been shown to be promising therapeutic approaches for Alzheimer Disease, schizophrenia, FXS as well as other forms of ASD.
Revisiting the Briggs ancient DNA damage model: a fast regression method to estimate postmortem damage
Authors: Zhao Lei , Heriksen Rasmus Amund , Ramsøe Abigail Daisy , Nielsen Rasmus , Korneliussen Thorfinn Sand
Published: November 2023

Motivation

One essential initial step in the analysis of ancient DNA is to authenticate its ancientness to ensure reliable conclusions. That is, meticulously assessing whether next-generation sequencing reads exhibit ancient characteristics, with a particular focus on the postmortem damage (PMD) signal induced by cytosine deamination in the fragments termini. We present a novel statistical method implementation in a fast multithreaded program ngsBriggs that enables the rapid quantification of PMD by calculation of the Briggs ancient damage model parameters (Briggs parameters).

Results

Using a fast multinomial regression approach, ngsBriggs accurately models the Briggs parameters, quantifying the PMD signal from single and double-stranded DNA regions. We revisit and extend the original Briggs model, with ngsBriggs modeling PMD signals for contemporary sequencing platforms. Furthermore, ngsBriggs asserts itself as a reliable and consistent tool, by accurately estimating the Briggs parameters across a variety of contamination levels. The classification accuracy of ngsBriggs significantly exceeds the current tool available when discerning ancient-from modern sequencing reads to decontaminate samples. Our novel method and implementation ngsBriggs outperforms existing tools regarding computational speed and accuracy, establishing its practicality and usability. Our tool, ngsBriggs offers a practical and accurate toolset for researchers seeking to authenticate ancient DNA and improve the quality of their data.

Availability

https://github.com/lz398/metadamage_briggs
Knowledge by omission: the significance of omissions in the 5-choice serial reaction time task
Authors: Vouillac-Mendoza Caroline , Durand Audrey , Ahmed Serge H. , Guillem Karine
Published: November 2023

The 5-choice serial reaction time task (5-CSRTT) is commonly used to assess attention in rodents. Manipulation of this task by decreasing the light stimulus duration is often used to probe attentional capacity and causes a decrease in accuracy and an increase in omissions. However, although a decrease in response accuracy is commonly interpreted as a decrease in attention, it is more difficult to interpret an increase in omissions in terms of attentional performance. Here we present a series of experiments in rats that seeks to investigate the origins of these key behavioral measures of attention in the 5-CSRTT. After an initial training in the 5-CSRTT, rats were tested in a variable stimulus duration procedure to increase task difficulty and probe visual attentional capacity under several specific controlled conditions. We found that response accuracy reflects visuospatial sustained attentional processing, as commonly interpreted, while response omission reflects rats’ ignorance about the stimulus location, presumably due to failure to pay attention to the curved wall during its presentation. Moreover, when rats lack of relevant information, they choose not to respond instead of responding randomly. Overall, our results indicate that response accuracy and response omission thus correspond to two distinct attentional states.
Host influence on the eukaryotic virome of sympatric mosquitoes and abundance of diverse viruses with a broad host range
Authors: Morel Côme , Gil Patricia , Exbrayat Antoni , Loire Etienne , Charriat Florian , Prepoint Baptiste , Condachou Celine , Gimonneau Geoffrey , Fall Assane G. , Biteye Biram , Seck Momar Talla , Eloit Marc , Gutierrez Serafin
Published: November 2023

Mosquitoes harbor a large diversity of eukaryotic viruses. Those viromes probably influence mosquito physiology and the transmission of human pathogens. Nevertheless, their ecology remains largely unstudied. Here, we address two key questions in virome ecology. First, we assessed the influence of mosquito species on virome taxonomic diversity and relative abundance. Contrary to most previous studies, the potential effect of the habitat was explicitly included. Thousands of individuals ofCulex poicilipesandCulex tritaeniorhynchus,two vectors of viral diseases, were concomitantly sampled in three habitats over two years. A total of 95 viral taxa from 25 families were identified with meta-transcriptomics, with 75% of taxa shared by both mosquitoes. Viromes significantly differed by mosquito species but not by habitat. Differences were largely due to changes in relative abundance of shared taxa. Then, we studied the diversity of viruses with a broad host range. We searched for viral taxa shared by the twoCulexspecies andAedes vexans, another disease vector, present in one of the habitats. Twenty-six out of the 163 viral taxa were found in the three mosquitoes. These taxa encompassed 14 families. A database analysis supported broad host ranges for many of those viruses, as well as a widespread geographical distribution. Thus, the viromes of mosquitoes from the same genera mainly differed in the relative abundance of shared taxa, whereas differences in viral diversity dominated between mosquito genera. Whether this new model of virome diversity and structure applies to other mosquito communities remains to be determined.
ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy
Authors: Wang Mingchao , Ran Xiaojuan , Leung Wendy , Kawale Ajinkya , Saxena Sneha , Ouyang Jian , Patel Parasvi S. , Dong Yuting , Yin Tao , Shu Jian , Manguso Robert T. , Lan Li , Wang Xiao-Fan , Lawrence Michael S. , Zou Lee
Published: November 2023

The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need for alternative approaches to target MMR-d cancer cells. Here, we show that inhibition of the ATR kinase preferentially kills MMR-d cancer cells. Mechanistically, ATR inhibitor (ATRi) imposes synthetic lethality on MMR-d cells by inducing DNA damage in a replication- and MUS81 nuclease-dependent manner. The DNA damage induced by ATRi is colocalized with both MSH2 and PCNA, suggesting that it arises from DNA structures recognized by MMR proteins during replication. In syngeneic mouse models, ATRi effectively reduces the growth of MMR-d tumors. Interestingly, the antitumor effects of ATRi are partially due to CD8+T cells. In MMR-d cells, ATRi stimulates the accumulation of nascent DNA fragments in the cytoplasm, activating the cGAS-mediated interferon response. The combination of ATRi and anti-PD-1 antibody reduces the growth of MMR-d tumors more efficiently than ATRi or anti-PD-1 alone, showing the ability of ATRi to augment the immunotherapy of MMR-d tumors. Thus, ATRi selectively targets MMR-d tumor cells by inducing synthetic lethality and enhancing antitumor immunity, providing a promising strategy to complement and augment MMR deficiency-guided immunotherapy.
Implications of digital risks on teachers' motivation and intention to use digital tools: a PLS-POS perspective in Romanian preuniversity education system
Authors: Tilibașa Maria Andreea , Boncilică Alina Nicoleta , Popa Ion , Ștefan Simona Cătălina , Tărăban Irina
Published: November 2023

Purpose

The study aims to analyze the different types of risks related to the use of technology and determine their positive or negative influence on teachers' motivation and behavioral intention to use digital tools.

Design/methodology/approach

The research is based on survey data from 200 teachers in the Romanian preuniversity education system. The data analysis followed a four-step approach, using a partial least squares structural equation modeling (PLS-SEM) model for hypothesized relationships among research concepts and a PLS prediction-oriented segmentation (POS) procedure.

Findings

This study showed that increased risk awareness influences both motivation and, consequently, the intention to adopt digital tools in the preuniversity education system.

Research limitations/implications

The scope of research remains constrained with regard to the examined population, considering the substantial number of teachers within the preuniversity education system. Another limit lies in the basic classification of identified risk types.

Practical implications

School managers should design a strategy to increase the level of motivation for integrating digital tools in the educational process.

Originality/value

Little scholarly attention has been devoted to investigating the risks associated with digitalization in the preuniversity education system. In addition, no prior research has been conducted to assess the influence of risk perception on people's motivation and intention to use digital tools in preuniversity education.
Multinationals’ value chain configuration for product diversification in emerging markets: Western firms in China
Authors: Franz Sarah , Giroud Axele , Ivarsson Inge
Published: November 2023

Purpose

This study aims to analyse how multinational corporations (MNCs) organise value chain activities to penetrate new market segments. It contributes by expanding traditional decisions regarding the vertical fine-slicing of value chain activities (whether performed internally or externally) and the consideration of resource-sharing decisions (integration or separation) for each value chain function.

Design/methodology/approach

The authors draw on primary data collected from two case study firms operating in the large emerging Chinese market: Volvo Construction Equipment AB and Epiroc AB. In-depth cases illustrate how foreign MNCs expand into new market segments and simultaneously target both the lower-priced mid-market and the premium segments in the Chinese mining and construction industry.

Findings

The results reveal that product diversification creates challenges for managers who must oversee new (vertical) value chains, often simultaneously. Beyond geography and modes of governance, managers must decide whether to integrate or separate value chain activities for the new product lines. The study identifies four main strategic choices for firms to address this complexity, focusing on the decision to internalise or externalise (i.e. within or across organisational boundaries) and integrate or separate value chain activities between different product lines.

Originality/value

This study builds upon the internalisation theory and recent international business contributions that focus on value chain configurations to explain MNCs’ product diversification as a growth strategy in a host emerging market. It also sheds light on the choice of conducting new activities in-house or externally and elucidates firms’ managerial decisions to operationally integrate or separate individual value chain activities. The study provides insights into the drivers explaining managerial decisions to configure value chain activities across product lines and contributes to the growing body of literature on MNC activities in emerging economies by highlighting that product diversification impacts entry mode diversity and resource sharing across units.
Efficacy of intracytoplasmic sperm injection in women with non‐male factor infertility: A systematic review and meta‐analysis
Authors: Yang Liu , Liang Fuxiang , Zhu Rongyan , Wang Qi , Yao Liang , Zhang Xuehong
Published: November 2023

Introduction

The use of intracytoplasmic sperm injection (ICSI) has dramatically increased in patients with non‐male factor infertility during the last decades. However, whether ICSI provides a significant benefit over in vitro fertilization (IVF) in these patients is still controversial. In this study, we aimed to investigate the efficacy of ICSI on reproductive outcomes with non‐male factor infertility and to provide updated evidence for clinical practice.

Material and methods

We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2023. Randomized controlled trials (RCTs) comparing the efficacy between ICSI and IVF in patients with non‐male factor infertility were included. The main outcomes were the live birth rate (LBR), fertilization rate (FR), and total fertilization failure (TFF). The pooled estimates were calculated using the random‐effects models as relative risk (RR) with 95% confidence intervals (CIs). This systematic review and meta‐analysis was registered in PROSPERO (CRD42023427004).

Results

We included 18 RCTs with 3249 cycles and 30 994 oocytes. The results demonstrated that ICSI reduced the risk of TFF (RR = 0.26, 95% CI: 0.13–0.50, I2 = 58%) and increased FR per oocyte inseminated/injected (RR = 1.14, 95% CI: 1.08–1.20, I2 = 69%), but it did not improve LBR (RR = 1.11, 95% CI: 0.94–1.30, I2 = 0%) or other outcomes compared with IVF. However, the difference in fertilization failure reduction between ICSI and IVF may be explained by different randomization methods (randomization based on patients vs. sibling oocytes). When considering only studies with randomization based on patients, we found no evidence of the difference between the groups (RR = 0.72, 95% CI: 0.48–1.06, I2 = 0%). Furthermore, no differences were observed in subgroup analyses based on other factors, including female age, study period, and controlled ovarian stimulation protocols.

Conclusions

Our findings suggest that ICSI leads to no difference in reproductive outcomes compared to IVF in patients with non‐male factor infertility. Considering the cost and safety of ICSI, we have no evidence to support the routine use of ICSI in these populations. High‐quality RCTs with large sample sizes will be needed to confirm our results and explore clinical and neonatal outcomes.
Workplace heating and gender discrimination
Authors: Albertsen Andreas , Pedersen Viki M. L.
Published: November 2023

Across Europe, countries are reducing CO2 emissions and energy demand by lowering the temperature in public office buildings. These measures affect men and women unequally because the latter prefer and, indeed, perform better under higher temperatures than the standard temperature. Lowering the temperature thus further increases an already existing inequality. We show that the philosophical literature on discrimination provides an interesting theoretical approach to understanding such measures. On prominent understandings of what discrimination is, the policy would be considered direct discrimination against women if it could be shown to reflect a broader inattentiveness to the needs of women in society. Alternatively, and more straightforwardly, the policies can be considered indirect discrimination because of their disparate effects on men and women. The final part of the paper shows that the policies are also wrong for the reasons it is often argued that discrimination is wrong—to wit, that it harms or disrespects those who are discriminated against. The final section suggests a range of measures to offset the discriminatory aspects of the policy.
Maternal beliefs about the benefits and costs of child and adolescent friendship
Authors: Weingarten Jenna P. , Bowker Julie C. , Coplan Robert J. , Rubin Kenneth H.
Published: November 2023

The goals of this study were to examine maternal beliefs about the primary benefits and costs of their children's time spent with friends, and to explore child age and gender differences in these beliefs. Participants were N = 512 mothers (Mchildage = 10.18 years; 11% ethnic minority). Open‐ended responses to questions about the benefits and costs were coded and analysed, with results indicating that mothers consider opportunities for social skills and social‐cognitive development a primary benefit of spending time with friends. Negative friend influence was the most commonly cited cost of friendship. Child age was associated with a number of maternal beliefs (e.g., mothers of adolescents were more likely than mothers of young children to report intimacy as a benefit), but child gender was not. Findings highlight the importance of considering child age in studies of maternal beliefs about friendship and set the stage for future research in this area.
Authoring Terrains with Spatialised Style
Authors: Perche Simon , Peytavie Adrien , Benes Bedrich , Galin Eric , Guérin Eric
Published: November 2023

Various terrain modelling methods have been proposed for the past decades, providing efficient and often interactive authoring tools. However, they seldom include any notion of style, which is critical for designers in the entertainment industry. We introduce a new generative network method that bridges the gap between automatic terrain synthesis and authoring, providing a versatile set of authoring tools allowing spatialised style. We build upon the StyleGAN2 architecture and extend it with authoring tools. Given an input sketch or existing elevation map, our method generates a terrain with features that can be authored, enhanced, and augmented using interactive brushes and style manipulation tools. The strength of our approach lies in the versatility and interoperability of the different tools. We validate our method quantitatively with drainage calculation against other previous techniques and qualitatively by asking users to follow a prompt or freely create a terrain.
Controllable Garment Image Synthesis Integrated with Frequency Domain Features
Authors: Liang Xinru , Mo Haoran , Gao Chengying
Published: November 2023

Using sketches and textures to synthesize garment images is able to conveniently display the realistic visual effect in the design phase, which greatly increases the efficiency of fashion design. Existing garment image synthesis methods from a sketch and a texture tend to fail in working on complex textures, especially those with periodic patterns. We propose a controllable garment image synthesis framework that takes as inputs an outline sketch and a texture patch and generates garment images with complicated and diverse texture patterns. To improve the performance of global texture expansion, we exploit the frequency domain features in the generative process, which are from a Fast Fourier Transform (FFT) and able to represent the periodic information of the patterns. We also introduce a perceptual loss in the frequency domain to measure the similarity of two texture pattern patches in terms of their intrinsic periodicity and regularity. Comparisons with existing approaches and sufficient ablation studies demonstrate the effectiveness of our method that is capable of synthesizing impressive garment images with diverse texture patterns while guaranteeing proper texture expansion and pattern consistency.
Continuous Layout Editing of Single Images with Diffusion Models
Authors: Zhang Zhiyuan , Huang Zhitong , Liao Jing
Published: November 2023

Recent advancements in large‐scale text‐to‐image diffusion models have enabled many applications in image editing. However, none of these methods have been able to edit the layout of single existing images. To address this gap, we propose the first framework for layout editing of a single image while preserving its visual properties, thus allowing for continuous editing on a single image. Our approach is achieved through two key modules. First, to preserve the characteristics of multiple objects within an image, we disentangle the concepts of different objects and embed them into separate textual tokens using a novel method called masked textual inversion. Next, we propose a training‐free optimization method to perform layout control for a pre‐trained diffusion model, which allows us to regenerate images with learned concepts and align them with user‐specified layouts. As the first framework to edit the layout of existing images, we demonstrate that our method is effective and outperforms other baselines that were modified to support this task. Code is available at our project page.
Non‐invasive oral implant position assessment: An ex vivo study using a 3D industrial scan as the reference model to mimic the clinical situation
Authors: Tarce Mihai , Becker Kathrin , Lahoud Pierre , Shujaat Sohaib , Jacobs Reinhilde , Quirynen Marc
Published: November 2023

Aim

To introduce an objective method to evaluate the accuracy of implant position assessment in partially edentulous patients by comparing different techniques (conventional impression, intraoral scan, CBCT) to a reference 3D model obtained with an industrial scanner, the latter mimicking the clinical situation.

Materials and Methods

Twenty‐nine implants were placed in four human cadaver heads using a fully guided flapless protocol. Implant position was assessed using (a) a conventional impression, (b) an intraoral scan, and (c) CBCT and compared to an industrial scan. Three‐dimensional models of intraoral scan body and implant were registered to the arch models and the deviation at implant shoulder, apex, and the angle of deviation were compared to each other as well as to the reference model.

Results

The three assessment techniques showed statistically significant deviations (p < .01) from the industrial scan, for all measurements, with no difference between the techniques. The maximum deviation at the implant shoulder was 0.16 mm. At the implant apex this increased to 0.38 mm. The intraoral scan deviated significantly more than the CBCT (0.12 mm, p < .01) and the conventional impression (0.10 mm, p = .02). The maximum implant angle deviation was 1.0°. The intraoral scan deviated more than the conventional impression (0.3°, p = .02).

Conclusion

All assessment techniques deviated from the reference industrial scan, but the differences were relatively small. Intraoral scans were slightly less accurate than both conventional impressions and CBCT. Depending on the application, however, this inaccuracy may not be clinically relevant.
A TTC19 mutation associated with progressive movement disorders and peripheral neuropathy: Case report and systematic review
Authors: Xuan Xianjun , Ruan Jie , Wu Chunhong , Gao Yiyi , Li Lingfei , Lei Xiaoguang
Published: November 2023

Background

Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia. Multiple genes are associated with complex III defects. Among them, the mutation of TTC19 is a rare subtype.

Methods

We screened a Chinese boy with weakness of limbs and his non‐consanguineous parents by whole exome sequencing and targeted sequencing.

Results

We report a Chinese boy diagnosed with mitochondrial complex III defect type 2 carrying a homozygous variant (c.719‐732del, p.Leu240Serfs*17) of the TTC19 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. We provide his clinical manifestation.

Conclusions

A new type of TTC19 mutation (c.719‐732del, p.Leu240Serfs*17) was found, which enriched the TTC19 gene mutation spectrum and provided new data for elucidating the pathogenesis of CIII‐deficient diseases.
“Hitch‐and‐ride” for the major to minor rendezvous in a patient with groove pancreatitis
Authors: Kurihara Kohei , Nakai Yousuke , Fujishiro Mitsuhiro
Published: November 2023

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Glomerular and tubular effects of dapagliflozin, eplerenone and their combination in patients with chronic kidney disease: A post‐hoc analysis of the ROTATE‐3 study
Authors: Lieverse Tom T. G. F. , Puchades Maria J. , Mulder Udo D. J. , Provenzano Michele , Krenning Guido , Jongs Niels , Wink Simon E. , Slart Riemer H. J. A. , Andreucci Michele , D'Marco Luis , De Nicola Luca , Gorriz Jose L. , Heerspink Hiddo J. L.
Published: November 2023

Aim

Sodium‐glucose co‐transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function.

Methods

This post‐hoc analysis utilized data of the ROTATE‐3 study, a randomized cross‐over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro‐hormonal markers and tubular sodium handling were assessed with mixed repeated measures models.

Results

The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin‐eplerenone was −34.8% (95% CI −52.2, −10.9), −5.9% (95% CI −32.5, 31.3) and −28.1% (95% CI −48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin‐eplerenone [32.2% (95% CI −1.5, 77.4)], compared with dapagliflozin [−12.5% (95% CI −35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin‐eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI −10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI −879.2, −32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI −926.1, −120.0). Dapagliflozin‐eplerenone decreased proximal absolute sodium reabsorption [−971.0 mmol/min (95% CI −1411.0, −531.0)], but did not affect distal absolute sodium reabsorption [−9.2 mmol/min (95% CI −402.0, 383.6)].

Conclusions

Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.
Platelet‐associated biomarkers in nonalcoholic steatohepatitis: Insights from a female cohort with obesity
Authors: Duran‐Bertran Joan , Rusu Elena Cristina , Barrientos‐Riosalido Andrea , Bertran Laia , Mahmoudian Razieh , Aguilar Carmen , Riesco David , Martínez Salomé , Ugarte Chicote Javier , Sabench Fàtima , Richart Cristóbal , Auguet Teresa
Published: November 2023

Background

There is a lack of noninvasive diagnostic methods for nonalcoholic steatohepatitis (NASH), the severe condition of metabolic dysfunction‐associated steatotic liver disease (MASLD). Platelet activation, evaluated through certain related parameters, is associated with liver disease and inflammation, but previous results are inconclusive.

Aim

To investigate the potential utility of platelet‐related indices as noninvasive diagnostic markers for the detection and prediction of MASLD, focusing on NASH.

Results

We found that mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW) were increased in the severe and morbidly obese (SMO) group compared to the normal weight (NW) group. We found decreased levels of MPV in steatosis and NASH patients. MPV and PCT values were decreased in the presence of mild liver inflammation. Platelet count (PLA) and PCT values were lower in the presence of ballooning. We obtained an area under the ROC curve of 0.84 using MPV and three other variables to predict MASLD.

Conclusions

Some platelet‐related indices vary depending on liver condition. Here, we reported decreased MPV in MASLD presence. Moreover, we presented for the first time a predictive model using MPV, ALT levels and the presence of diabetes mellitus and metabolic syndrome to predict MASLD in obese women. Also, MPV is closely related to early liver inflammation in NASH, and PLA and PCT are related to hepatic ballooning. These indices could be widely used for the early detection of NASH since they are usually determined in routine laboratory tests.
New evidence on crude oil market efficiency
Authors: Hu Liang , Lee Yoon‐Jin
Published: November 2023

This paper examines the Efficient Market Hypothesis (EMH) in crude oil amid the “financialization of commodity markets” and the “fracking revolution”. It applies the generalized spectral derivative test (Hong and Lee 2005) on both West Texas Intermediate and Brent spot and futures markets, alongside a stochastic dominance test (Linton et al., 2005) to investigate arbitrage opportunities across markets and benchmarks. The findings indicate that financialization has made each market more efficient but also created more arbitrage opportunities in spot‐futures markets at both benchmarks. The fracking revolution has fragmented oil markets but had little impact on EMH in individual markets or across markets.
Impact and management of Opogona sacchari (Bojer, 1856) (Lepidoptera: Tineidae) in a display glasshouse in the United Kingdom
Authors: Drizou Fryni , Redstone Sara , Salisbury Andrew
Published: November 2023

Opogona sacchari (Bojer, 1856), or the banana moth, EPPO code OPOGSC, is an EPPO A2‐listed polyphagous insect. In Northern Europe this pest is mainly confined to glasshouses. The Royal Horticultural Society (RHS) Garden Wisley is located in Surrey, GB. In 2007, a new high‐specification glasshouse was built to host plants from temperate and tropical zones. Soon after the opening of the glasshouse to the public, the banana moth was detected. Different methods were used to understand and manage this infestation, which caused significant losses of plant specimens. Here we share our experience of different management approaches, a list of plants damaged or killed by the insect and our main conclusions on tackling future outbreaks.
Keratinocyte proline‐rich protein modulates immune and epidermal response in imiquimod‐induced psoriatic skin inflammation
Authors: Matsuno Ai , Sumida Hayakazu , Nakanishi Hirofumi , Ikeyama Yoshifumi , Ishii Tsuyoshi , Omori Issei , Saito Hinako , Iwasawa Okuto , Sugimori Ayaka , Yoshizaki Ayumi , Katoh Hiroto , Ishikawa Shumpei , Sato Shinichi
Published: November 2023

Psoriasis is a persistent inflammatory skin disease thought to arise as a result of the infiltration of inflammatory cells and activation of keratinocytes. Recent advances in basic research and clinical experience revealed that the interleukin (IL)‐23/IL‐17 axis has been identified as a major immune pathway in psoriasis. However, it remains unclear how keratinocyte factors contribute to the pathology of psoriasis. Keratinocyte proline‐rich protein (KPRP) is a proline‐rich insoluble protein, which is present in the epidermis and is likely to be involved in the skin barrier function. Here, to investigate the potential roles of KPRP in psoriatic skin inflammation, Kprp‐modified mice were applied in the imiquimod (IMQ)‐induced skin inflammation model, which develops psoriasis‐like epidermal hyperplasia and cutaneous inflammation features. Then, heterozygous knockout (Kprp+/−) but not homozygous knockout (Kprp−/−) mice displayed attenuated skin erythema compared to control wild‐type mice. In addition, RNA sequencing, quantitative PCR and/or histological analysis detected changes in the expression of several molecules related to psoriatic inflammation or keratinocyte differentiation in Kprp+/− mice, but not Kprp−/− mice. Further analysis exhibited reduced IL‐17‐producing γδlow T cells and amplified epidermal hyperplasia in Kprp+/− mice, which were implied to be related to decreased expression of β‐defensins and increased expression of LPAR1 (Lysophosphatidic acid receptor 1), respectively. Thus, our results imply that KPRP has the potential as a therapeutic target in psoriatic skin inflammation.
Serum miRNA profiling identified miRNAs associated with disease severity in psoriasis
Authors: Ganguly Torsa , Laha Sayantan , Senapati Swapan , Chatterjee Gobinda , Chatterjee Raghunath
Published: November 2023

Psoriasis vulgaris is a chronic, autoimmune skin disease involving a complex interplay of epidermal keratinocytes, dermal fibroblast and infiltrating immune cells. Differential expressions of miRNAs are observed in psoriasis and the deregulated miRNAs are sometimes associated with disease severity. This study aims to identify miRNAs altered in the serum of psoriasis patients that are associated with the Psoriasis Area and Severity Index (PASI). In order to assess miRNA levels in the serum of psoriasis patients, we selected 24 differentially expressed miRNAs in the psoriatic skin are possibly derived from the skin and immune cells, as well as five miRNAs that are enriched in other tissues. We identified 16 miRNAs that exhibited significantly (p < 0.05) altered levels in the serum of psoriasis patients compared to healthy individuals. Among these, 13 miRNAs showed similar expression pattern in the serum of psoriasis patients as also observed in the psoriatic skin tissues. Ten miRNAs showed an accuracy of greater than 75% in classifying the psoriasis patients from healthy individuals. Further analysis of differential miRNA levels between the low PASI group and the high PASI group identified three miRNAs (miR‐147b, miR‐3614‐5p, and miR‐125a‐5p) with significantly altered levels between the low severity and the high severity psoriasis patients. Our systematic investigation of skin and immune cell‐derived miRNAs in the serum of psoriasis patients revealed alteration in miRNA levels to be associated with disease severity, which may help in monitoring the disease progression and therapeutic response.
Weighted gene co‐expression network analysis and machine learning identified the lipid metabolism‐related gene LGMN as a novel biomarker for keloid
Authors: Wang Qirui , Huang Xingtai , Zeng Siyi , Zhou Renpeng , Wang Danru
Published: November 2023

The aetiology of keloid formation remains unclear, and existing treatment modalities have not definitively established a successful approach. Therefore, it is necessary to identify reliable and novel keloid biomarkers as potential targets for therapeutic interventions. In this study, we performed differential expression analysis and functional enrichment analysis on the keloid related datasets, and found that multiple metabolism‐related pathways were associated with keloid formation. Subsequently, the differentially expressed genes (DEGs) were intersected with the results of weighted gene co‐expression network analysis (WGCNA) and the lipid metabolism‐related genes (LMGs). Then, three learning machine algorithms (SVM‐RFE, LASSO and Random Forest) together identified legumain (LGMN) as the most critical LMGs. LGMN was overexpressed in keloid and had a high diagnostic performance. The protein–protein interaction (PPI) network related to LGMN was constructed by GeneMANIA database. Functional analysis of indicated PPI network was involved in multiple immune response‐related biological processes. Furthermore, immune infiltration analysis was conducted using the CIBERSORT method. M2‐type macrophages were highly infiltrated in keloid tissues and were found to be significantly and positively correlated with LGMN expression. Gene set variation analysis (GSVA) indicated that LGMN may be related to promoting fibroblast proliferation and inhibiting their apoptosis. Moreover, eight potential drug candidates for keloid treatment were predicted by the DSigDB database. Western blot, qRT‐PCR and immunohistochemistry staining results confirmed that LGMN was highly expressed in keloid. Collectively, our findings may identify a new biomarker and therapeutic target for keloid and contribute to the understanding of the potential pathogenesis of keloid.
Transcriptomics reveal how circadian regulation contributes to starch hyperaccumulation in marine alga Tetraselmis helgolandica
Authors: Shi Qianwen , Zhou Zuodong , Hong Zhiwei , Yang Zhi , Gao Zhengquan , Sun Liyun , Fan Jianhua
Published: November 2023

Tetraselmis helgolandica var. Tsingtaoensis is a marine microalga. It can produce a large amount of starch, especially amylose, with addition of carbon source and specific circadian rhythm. The mechanism behind this phenomenon is still unclear. Analysis of this mechanism can help to develop T. helgolandica into a new green bioengineering chassis organism. We explained how circadian rhythm and glucose affect the rate of starch accumulation and starch structure in T. helgolandica based on the transcriptome. The glucose inhibited the photosynthetic system of T. helgolandica, while the circadian rhythm can alleviate the inhibition. Circadian rhythm induced the upregulation of Embden–Meyerhof–Parnas pathway and pentose phosphate pathway (PPP) in T. helgolandica, but had little effect on the tricarboxylic acid cycle. PPP pathway provides Ribulose‐1,5‐bisphosphate, which may be beneficial for dark reactions and nucleotide synthesis. And PPP pathway provides Nicotinamide adenine dinucleotide phosphate, which facilitates energy substance synthesis. This will further upregulate the starch metabolic pathway. The transcript level of the key gene ADP‐Glucose pyrophosphorylase is mainly regulated by glucose. The granule‐bound starch synthase (gbss), a key gene for amylose synthesis, is mainly influenced by circadian rhythm. In general, the increase of starch synthesis and amylose ratio requires both glucose addition and circadian rhythm. We report the first referenced transcriptome of T. helgolandica. Differences between transcripts reveal how circadian rhythm and glucose addition affected the rate of starch synthesis and structural variation. It provides a reference for an in‐depth study of starch synthesis in green algae.
Linkage‐ and structure‐based technological proximity and interregional spillovers of innovation growth
Authors: Li Yuanxi , Sun Tieshan , Sun Yukang
Published: November 2023

This paper explores the roles of different types of technological proximity on the interregional spillovers of innovation growth. Using a panel dataset containing Chinese province patents and R&D inputs from 2002 to 2019, this paper estimates a knowledge production function with the spatial weight matrices constructed based on the linkage‐based and structure‐based technological proximity. We find that the two types of technological proximity are significantly different and their contributions to interregional innovation spillovers differ. The structure‐based proximity shows a lower influence on spillovers and its effect in the process of interregional innovation spillovers is affected by the regional development level. This paper originates to clarify two conceptualizations of technological proximity, compare their influences on innovation spillovers, and explore their regional differences.
Presence of leukemic clone‐specific immunoglobulin heavy chain rearrangements in neonatal blood spots of children with B‐cell precursor acute lymphoblastic leukemia
Authors: Kacanski Natasa , Kolarovic Jovanka , Kostic Tatjana , Marjanovic Irena , Janic Dragana , Pavlovic Sonja , Karan‐Djurasevic Teodora
Published: November 2023

Introduction

Childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) can be traced back to birth using leukemic clone‐specific immunoglobulin heavy chain (IGH) rearrangements, implying prenatal origin of this disease.

Methods

We retrospectively analyzed neonatal blood spots (Guthrie cards) of 24 patients with childhood BCP‐ALL aged 1–9.6 years (median 3.1 years) for the presence of clonotypic IGH rearrangements identified in diagnostic bone marrow samples. Based on the sequences of IGH rearrangements, 2 patient‐specific primers were designed for each patient and used in semi‐nested polymerase chain reaction for the detection of preleukemic clones at birth.

Results

Clonotypic IGH rearrangements were detected in neonatal blood spots of 54.2% of patients (13/24). In two cases with double IGH rearrangements detected at diagnosis, only one rearrangement was present at birth, while in the third case both leukemic rearrangements were detected in neonatal blood. Guthrie card‐positive findings were significantly more frequent in children ≤5 years of age than in older children (p = 0.011). Regarding patients' characteristics at birth and at diagnosis, Guthrie card‐positivity was not associated with sex, birth weight and mother's age, as well as with white blood cell count, percentage of bone marrow blasts, immunophenotype and the presence of ETV6/RUNX1 and TCF3/PBX1 fusion genes at diagnosis.

Conclusion

Our study confirms that a large proportion of childhood BCP‐ALL originates in utero, regardless of the molecular subtype defined by chromosomal aberrations. The observed trend toward younger age at diagnosis in Guthrie card‐positive versus Guthrie card‐negative patients implies that the age at diagnosis depends on the presence of preleukemic clone at birth, as well as on the timing of postnatal transforming genetic events.
Transvenous versus subcutaneous implantable cardioverter defibrillators in young cardiac arrest survivors
Authors: Morton Matthew B. , Mariani Justin A. , Kistler Peter M. , Patel Hitesh , Voskoboinik Aleksandr
Published: November 2023

Secondary prevention implantable cardioverter defibrillators (ICDs) are indicated in young patients presenting with aborted sudden cardiac death (SCD) because of ventricular arrhythmias. Transvenous‐ICDs (TV‐ICDs) are effective, established therapies supported by evidence. The significant morbidity associated with transvenous leads led to the development of the newer subcutaneous‐ICD (S‐ICD). This review discusses the clinical considerations when selecting an ICD for the young patient presenting with out‐of‐hospital cardiac arrest. The major benefits of TV‐ICDs are their ability to pace (antitachycardia pacing [ATP], bradycardia support and cardiac resynchronisation therapy [CRT]) and the robust evidence base supporting their use. Other benefits include a longer battery life. Significant complications associated with transvenous leads include pneumothorax and tamponade during insertion and infection and lead failure in the long term. Comparatively, S‐ICDs, by virtue of having no intravascular leads, prevent these complications. S‐ICDs have been associated with a higher incidence of inappropriate shocks. Patients with an indication for bradycardia pacing, CRT or ATP (documented ventricular tachycardia) are seen as unsuitable for a S‐ICD. If venous access is unsuitable or undesirable, S‐ICDs should be considered given the patient is appropriately screened. There is a need for further randomised controlled trials to directly compare the two devices. TV‐ICDs are an effective therapy for preventing SCD limited by significant lead‐related complications. S‐ICDs are an important development hindered largely by an inability to pace. Young patients stand to gain the most from a S‐ICD as the cumulative risk of lead‐related complications is high. A clinical framework to aid decision‐making is presented.
Five Components of a Basic Suicide Syndrome*
Authors: Breed Warren
Published: November 2023

ABSTRACT: To the question “Why suicide?” a tentative framework is proposed, taking the form of a syndrome of five components: (a) commitment; (b) rigidity; (c) failure; (d) shame; and (e) isolation. These are quite similar to the conclusions of a study by Dorothy Miller. The syndrome is psychological as well as sociological, deals with the response of the suicider to crisis, and suggests mechanisms lacking in other theoretical frameworks. Quantitative and qualitative data taken from interviews with survivors of well over 100 suiciders support the framework. Also discussed are possible further refinements of the syndrome, its adequacy, and its applications to intervention with suicidal persons.
Family Dynamics and Drug Overdoses*
Authors: Rosenbaum Milton , Richman Joseph
Published: November 2023

ABSTRACT: In a study of 40 patients who had taken an overdose, and with the relatives of 18 of these subjects, a pattern of family factors that appeared relevant to the choice of drugs was found. These family factors included: (a) a specific expectation that the person would use drugs; (b) an identification with another suicidal family member; (c) a high level of oral preoccupation and oral fixation; (d) trauma in the life history associated with food or orality; and (e) a direct participation of other family members in the suicidal act. The direct study of family interactions in evaluating suicidal potential is recommended for its unique diagnostic and therapeutic implications.