bluuebunny/crossref_metadata_2025 huggingface dataset:
CAG repeat-selective compounds reduce abundance of expanded CAG RNAs in patient cell and murine models of SCAs
Authors: Shorrock Hannah K. , Aliyeva Asmer , Frias Jesus A. , DeMeo Victoria A. , Lennon Claudia D. , DeMeo Cristina C. , Mascorro Amy K. , Shaughnessy Sharon , Mazdiyasni Hormoz , Cleary John D. , Reddy Kaalak , Vangaveti Sweta , Shin Damian S. , Berglund J. Andrew
Published: August 2024

Spinocerebellar ataxias (SCAs) are a genetically heterogenous group of devastating neurodegenerative conditions for which clinical care currently focuses on managing symptoms. Across these diseases there is an unmet need for therapies that address underlying disease mechanisms. We utilised the shared CAG repeat expansion mutation causative for a large subgroup of SCAs, to develop a novel disease-gene independent and mechanism agnostic small molecule screening approach to identify compounds with therapeutic potential across multiple SCAs. Using this approach, we identified the FDA approved microtubule inhibitor Colchicine and a novel CAG-repeat binding compound that reduce expression of disease associated transcripts across SCA1, 3 and 7 patient derived fibroblast lines and theAtxn1154Q/2QSCA1 mouse model in a repeat selective manner. Furthermore, our lead candidate rescues dysregulated alternative splicing inAtxn1154Q/2Qmice. This work provides the first example of small molecules capable of targeting the underlying mechanism of disease across multiple CAG SCAs.
The genetic architecture of cell-type-specific cis-regulation in maize
Authors: Marand Alexandre P. , Jiang Luguang , Gomez-Cano Fabio , Minow Mark A.A. , Zhang Xuan , Mendieta John P. , Luo Ziliang , Bang Sohyun , Yan Haidong , Meyer Cullan , Schlegel Luca , Johannes Frank , Schmitz Robert J.
Published: August 2024

Abstract

Gene expression and complex phenotypes are determined by the activity of cis-regulatory elements. However, an understanding of how extant genetic variants affect cis regulation remains limited. Here, we investigated the consequences of cis-regulatory diversity using single-cell genomics of >0.7 million nuclei across 172Zea mays(maize) inbreds. Our analyses pinpointed cis-regulatory elements distinct to domesticated maize and revealed how historical transposon activity has shaped the cis-regulatory landscape. Leveraging population genetics principles, we fine-mapped ∼22,000 chromatin accessibility-associated genetic variants with widespread cell-type-specific effects. Variants in TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR binding sites were the most prevalent determinants of chromatin accessibility. Finally, integrating chromatin accessibility-associated variants, organismal trait variation, and population differentiation revealed how local adaptation has rewired regulatory networks in unique cellular context to alter maize flowering.
The MRE11-RAD50-NBS1 complex both starts and extends DNA end resection in mouse meiosis
Authors: Kim Soonjoung , Yamada Shintaro , Li Tao , Canasto-Chibuque Claudia , Kim Jun Hyun , Marcet-Ortega Marina , Xu Jiaqi , Eng Diana Y. , Feeney Laura , Petrini John H. J. , Keeney Scott
Published: August 2024

Nucleolytic resection of DNA ends is critical for homologous recombination, but its mechanism is not fully understood, particularly in mammalian meiosis. Here we examine roles of the conserved MRN complex (MRE11, RAD50, and NBS1) through genome-wide analysis of meiotic resection in mice with various MRN mutations, including several that cause chromosomal instability in humans. Meiotic DSBs form at elevated levels but remain unresected ifMre11is conditionally deleted, thus MRN is required for both resection initiation and regulation of DSB numbers. Resection lengths are reduced to varying degrees in MRN hypomorphs or if MRE11 nuclease activity is attenuated in a conditional nuclease-deadMre11model. These findings unexpectedly establish that MRN is needed for longer-range extension of resection, not just resection initiation. Finally, resection defects are additively worsened by combining MRN andExo1mutations, and mice that are unable to initiate resection or have greatly curtailed resection lengths experience catastrophic spermatogenic failure. Our results elucidate multiple functions of MRN in meiotic recombination, uncover unanticipated relationships between short- and long-range resection, and establish the importance of resection for mammalian meiosis.
Dynamic coding and sequential integration of multiple reward attributes by primate amygdala neurons
Authors: Grabenhorst Fabian , Báez-Mendoza Raymundo
Published: August 2024

The value of visual stimuli guides learning, decision-making and motivation. Although stimulus values often depend on multiple attributes, how neurons extract and integrate distinct value components from separate cues remains unclear. Here we recorded the activity of amygdala neurons while monkeys viewed sequential cues indicating the probability and magnitude of expected rewards. Amygdala neurons frequently signalled reward probability in an abstract, stimulus-independent code that generalized across cue formats. While some probability-coding neurons were insensitive to magnitude, signalling ‘pure’ probability rather than value, many neurons showed biphasic responses that signalled probability and magnitude in a dynamic (temporally-patterned) and flexible (reversible) value code. Specific neurons integrated these reward attributes into risk signals that quantified the uncertainty of expected rewards, distinct from value. Population codes were accurate, mutually transferable between value components and expressed differently across amygdala nuclei. Our findings identify amygdala neurons as a substrate for the sequential integration of multiple reward attributes into value and risk.
Delineating bacterial genera based on gene content analysis: a case study of the Mycoplasmatales-Entomoplasmatales clade within the class Mollicutes
Authors: Yan Xiao-Hua , Pei Shen-Chian , Yen Hsi-Ching , Blanchard Alain , Sirand-Pugnet Pascal , Baby Vincent , Gasparich Gail E. , Kuo Chih-Horng
Published: August 2024

Genome-based analysis allows for large-scale classification of diverse bacteria and has been widely adopted for delineating species. Unfortunately, for higher taxonomic ranks such as genus, establishing a generally accepted approach based on genome analysis is challenging. While core-genome phylogenies depict the evolutionary relationships among species, determining the correspondence between clades and genera may not be straightforward. For genotypic divergence, percentage of conserved proteins (POCP) and genome-wide average amino acid identity (AAI) are commonly used, but often do not provide a clear threshold for classification. In this work, we investigated the utility of global comparisons and data visualization in identifying clusters of species based on their overall gene content, and rationalized that such patterns can be integrated with phylogeny and other information such as phenotypes for improving taxonomy. As a proof of concept, we selected 177 representative genome sequences from the Mycoplasmatales-Entomoplasmatales clade within the class Mollicutes for a case study. We found that the clustering patterns corresponded to the current understanding of these organisms, namely the split into three above-genus groups: Hominis, Pneumoniae, and Spiroplasma-Entomoplasmataceae-Mycoides (SEM). However, at the genus level, several important issues were found. For example, recent taxonomic revisions that split the Hominis group into three genera and Entomoplasmataceae into five genera are problematic, as those newly described or emended genera lack clear differentiations in gene content from one another. Moreover, several cases of mis-classification were identified. These findings demonstrated the utility of this approach and the potential application for other bacteria.
Phase Separation Clustering of Poly Ubiquitin Cargos on the Ternary Mixture Lipid Membranes by Synthetically Cross-Linked Ubiquitin Binder Peptides.
Authors: Kim Soojung , Okafor Kamsy K. , Tabuchi Rina , Briones Cedric , Lee Il-Hyung
Published: August 2024

Ubiquitylation is involved in various physiological processes in our bodies such as signaling and vesicle trafficking, thus Ubiquitin (UB) is an important medical target system of interest. Polymeric addition of UB allows cargo molecules to be recognized specifically by multivalent binding interaction with UB binding proteins leading to various downstream processes. Recently, implication of protein condensate formation by Ubiquitylated proteins have been reported in many independent UB processes suggesting its potential role in governing the spatial organization of Ubiquitylated cargo proteins. We created modular polymeric UB binder motifs and polymeric UB cargos by synthetic bioconjugation and protein purification. Giant unilamellar vesicles with lipid raft composition were created to reconstitute polymeric UB cargo organization on the membranes. Fluorescence imaging was used to observe the outcome. We found that polymeric UB cargos clustered on the membranes by forming phase separation codomains in interaction with multivalent UB binder conjugate. This phase separation was valency dependent and was strongly correlated to their potency to form protein condensate droplets in solution. Multivalent UB binding interactions showed a general trend toward the formation of phase separated condensates, and the resulting condensates were either in liquid-like or solid-like state depending on the conditions and interactions used. It implies that polymeric UB cargos on the plasma and endosomal membranes may use the codomain phase separation to assist clustering of UB cargos on the membranes for cargo sorting. Our work also shows that model systems of such phase behavior can be created by modular synthetic approach that can potentially be used to further engineer biomimetic interactions in vitro.
A triple dissociation across the medial, ventral, and lateral orbitofrontal cortex in rats making sequential foraging decisions
Authors: Cunningham Paul J. , Redish A. David
Published: August 2024

The orbitofrontal cortex (OFC) is functionally heterogeneous across its medial-to-lateral axis, though the nature of this heterogeneity is unclear. The present study leveraged high-density neural recording across the medial-to-lateral span of the OFC using a neuroeconomic task in rats to clarify how functional heterogeneity within the OFC participates in sequential cost-benefit foraging. Lateral and ventral OFC contained opposing representations of an encountered reward’s subjective benefit and its associated opportunity costs, respectively. These representations directly competed to make accept-reject decisions during reward evaluation. If a poor-quality reward was mistakenly accepted, ventral and medial OFC participated in reevaluation processes during change-of-mind decisions. Collectively, these results suggest a triple dissociation in representational content and timing across the medial-to-lateral OFC during sequential foraging.
Chinese women’s entrepreneurial career choices: exploring factors
Authors: Niu Yuanlu , Zhu Yidan , Hughes Claretha
Published: August 2024

Purpose

The purpose of this study is to explore Chinese women’s pursuit of entrepreneurship as a career choice through the intersectional lens of gender and culture. The study aims to identify factors that influenced Chinese women’s decisions to pursue entrepreneurship.

Design/methodology/approach

In this exploratory qualitative study, we conducted qualitative, in-depth, semi-structured and one-on-one interviews with 16 Chinese women entrepreneurs.

Findings

We identified various factors that influenced Chinese women’s career choice of entrepreneurship. The factors include entrepreneurial attributes, rapid economic growth, societal and cultural influences, the dual role of family influences and strategic entrepreneurship.

Originality/value

Our study provides a contextualized understanding of the experience of Chinese women’s entrepreneurship career choices. It enriches the existing literature on career choices within the career development for Chinese women entrepreneurs. By applying social cognitive career theory (SCCT) to a specific cultural and gendered setting, we proposed the social cognitive women’s entrepreneurial career theory, which offers fresh insights into the interplay of personal, contextual and behavioral dimensions in shaping Chinese women’s entrepreneurial career choices.
Revisiting oil-stock nexus in the time of health crisis: a wavelet approach
Authors: Mezui-Mbeng Pamphile , Kouassi Eugene , Salisu Afees , Yobouet Loukou Landry Eric
Published: August 2024

Purpose

The paper aims at analyzing the co-movements between stock returns and oil prices (West Texas Intermediate, Brent) controlling or not for COVID-19.

Design/methodology/approach

It uses continuous wavelet transforms and wavelet coherence over the period July 19, 2019 to August 16, 2021 based on daily data. Continuous wavelet transforms provide an over complete representation of stock returns signals by letting the translation and scale parameters of the wavelets vary continuously.

Findings

There are not significant evidence supporting the fact that the COVID-19 has altered the relationship between stock returns and oil prices except perhaps in the case of South Africa. In fact, Southern African Development Community stock markets react more to oil prices than to health shock such as the COVID-19.

Originality/value

The findings of the study are original and have not been published anywhere prior.
Unfolding the resource configuration and interaction in digital servitization: an exploratory two-stage research design
Authors: Fang Keyi , Wu Xiaobo , Zhang Weiqi , Lei Linan
Published: August 2024

Purpose

This article aims to unfold digital servitization by exploring the key resources and resource orchestration (i.e. resource configuration and interaction).

Design/methodology/approach

This article conducted an explorative two-stage research strategy of Chinese servitized manufacturers using a preliminary case study and fuzzy-set Qualitative Comparative Analysis (fsQCA) design. The data collection was conducted between 2016 and 2021.

Findings

This article identifies five key resources – radical, complex technological resources, complementary, specific market resources and digital resources – and their configurations – leveraging market opportunities, leveraging innovation integration and leveraging resource advantages – to facilitate servitization in the digital age. The findings underscore the interaction between technological and market resources as well as the role of digital resources in promoting the servitization journey.

Originality/value

This article contributes to the understanding of servitization in the digital context by examining the key resources and their interactions involved. It builds upon the configurational logic of servitization, expanding the existing framework in the digital context and highlighting the significance of technological and market resource orchestration and interaction in servitization research. Moreover, the paper contributes through its exploratory two-stage approach, going beyond a conceptual understanding of servitization by focusing on both the factors that enable servitization (WHAT) and the configurations that lead to servitization (HOW). Additionally, the article investigates the attributes of resources as lower-level components, addressing the need to explore the micro-level practice of resource realignment. By providing clarity on the configurations of servitization, the paper offers practical guidelines for practitioners on how to effectively utilize resources and benefit from digital servitization.
Cognitive capabilities of moral leaders in turbulent environments: a review, theory integration and way forward
Authors: Bacha Eliane , Niesten Eva
Published: August 2024

Purpose

This paper’s purpose is to challenge the traditional assumption in leadership studies that leaders’ traits and capabilities impact effectiveness irrespective of the environment in which they operate. We identify the cognitive capabilities (CCs) of moral leaders that increase their efficacy in turbulent environments. To identify these capabilities, we integrate the strategic management literature on dynamic managerial capabilities (DMCs) into the field of moral leadership. We explore the micro-foundations of DMCs—that is, the CCs of moral leaders that underpin their abilities to sense and seize opportunities and reconfigure organizations—and show that CCs are effective in environmental turbulence.

Design/methodology/approach

We review 74 articles on moral leaders—including ethical, authentic, and servant leaders—and analyze their CCs that enable effectiveness in turbulent environments.

Findings

Moral leaders sense opportunities by drawing on their CCs for attention and perception. They seize opportunities with intuitive moral judgment and conscious moral reasoning, and by considering diverse perspectives and followers’ needs when problem solving. They reconfigure with vision-inspired storytelling, collaboration, and trust-building among stakeholders.

Practical implications

Organizations should use coaching, mentoring, and training to develop the CCs of moral leaders, and institutionalize these skills in their organizations.

Originality/value

We illustrate that the environment is an important determinant of the effectiveness of moral leaders’ capabilities. By integrating the DMC literature into the moral leadership field, we identify the distinctive CCs of ethical, authentic, and servant leaders that make them effective in turbulent environments.
Howdy, Robo-Partner: exploring artificial companionship and its stress-alleviating potential for service employees
Authors: Le Khanh Bao Quang , Cayrat Charles
Published: August 2024

Purpose

The emergence of new generations of artificial intelligence (AI), such as ChatGPT or Copilot has brought about a wave of innovation in the service workplace. These robotic agents can serve as companions, helping employees cope with work-related stress. This research introduces the concept of “artificial companionship,” which explains how robotic agents can function as partners in assisting service employees to fulfill their job responsibilities and maintain their mental well-being.

Design/methodology/approach

This research uses a mixed methods approach grounded in social support theory from psychology and management to develop a conceptual framework for the stress-alleviating implications of artificial companionship. A qualitative employee survey is conducted to justify the relevance of the propositions.

Findings

This research delineates the concept of artificial companionship. It highlights four distinct roles that AI can play in companionship – instrumental, informative, caring, and intimate. Building on this foundation, the research presents a series of propositions that elucidate the potential of artificial companionship in mitigating stress among employees.

Practical implications

Firms should consider aligning the types of artificial companionship with the demands inherent in employees’ job responsibilities to better reinforce their resilience and sustainment in overcoming work-related challenges.

Originality/value

This research introduces a new perspective on artificial companionship through the lens of social support theory. It extends the current understanding of human-robot collaboration in service workspaces and derives a set of propositions to guide future investigations.
Unveiling product imagination and decision comfort through personalized virtual try-on: the moderating role of spatial processing perception
Authors: Kim Seeun , Park Hyejune , Lim Rachel Esther
Published: August 2024

Purpose

This study explored the influence of personalized virtual try-on (PVTO) technology on consumer behavior in the apparel industry, focusing on decision comfort. It investigated how individuals’ spatial processing perception acts as a moderator in this context. Additionally, it examined the ease with which individuals imagine a product within the framework of this psychological mechanism.

Design/methodology/approach

Two experimental studies were conducted to evaluate the effects of PVTO technology on consumer decision comfort, with spatial processing perception as a moderating variable. The first experiment (n = 252) explored the impact of PVTO on decision comfort using photo-based simulations across various apparel items. The second experiment (n = 125) further examined these effects using measurement-based PVTO technologies to provide a deeper understanding of the role of spatial processing. Both studies employed a between-subjects design to isolate the influence of PVTO technology from other variables, ensuring a focused analysis of its effects on consumer behavior.

Findings

The findings indicated that the effects of PVTO are stronger for consumers with lower spatial perception abilities. Ease of imagining a product was identified as a mediator in the interactive effect between PVTO and spatial perception on decision comfort, demonstrating its pivotal role in online apparel shopping.

Originality/value

The findings indicated that the effects of PVTO are stronger for consumers with lower spatial perception abilities. Ease of imagining a product was identified as a mediator in the relationship between PVTO and decision comfort, demonstrating its pivotal role in online apparel shopping.
Empowerment to commitment: how live-streaming atmosphere and relational bonds drive impulse consumption?
Authors: Lai Pu , Aw Eugene Cheng-Xi , Tan Garry Wei-Han
Published: August 2024

Purpose

This study examines the effects and driving mechanisms of relational bonds (i.e. financial, social, and structural bonds), live-streaming shopping atmosphere factors (i.e. suspense, entertainment, perceived crowdedness, and vicarious experience), consumer empowerment and customer commitment on consumers’ impulse consumption behavior. Additionally, the study examines the moderating influence of product involvement and collectivism.

Design/methodology/approach

An online survey was conducted with 665 valid respondents. The authors empirically validated the collected data through the partial least squares structural equation modeling (PLS-SEM) technique, complemented by the artificial neural network (ANN) analysis.

Findings

The results suggest that financial bonds, structural bonds, suspense, entertainment, and vicarious experience promote consumer empowerment, which in turn leads to customer commitment and impulse consumption behavior. Second, collectivism moderates the relationship between customer commitment and impulse consumption behavior.

Originality/value

This study provides empirical evidence that relational bonds and live-streaming shopping atmosphere factors play predictive roles in enhancing consumer empowerment, which further promotes impulse consumption behavior through customer commitment. Also, collectivism is found as a moderator.
Net zero performance evaluation of European Continent Countries considering Paris Agreement climate goals
Authors: Dursun Mehtap , Alkurt Rana Duygu
Published: August 2024

Purpose

Today’s one of the most important difficulties is tackling climate change and its effects on the environment. The Paris Agreement states that nations must balance the amount of greenhouse gases they emit and absorb until 2050 to contribute to the mitigation of greenhouse gases and to support sustainable development. According to the agreement, each country must determine, plan and regularly report on its contributions. Thus, it is important for the countries to predict and analyze their net zero performances in 2050. Therefore, the aim of this study is to evaluate European Continent Countries' net zero performances at the targeted year.

Design/methodology/approach

The European Continent Countries that ratified the Paris Agreement are specified as decision making units (DMUs). Input and output indicators are specified as primary energy consumption, freshwater withdrawals, gross domestic product (GDP), carbon-dioxide (CO2) and nitrous-oxide (N2O) emissions. Data from 1980 to 2019 are obtained and forecasted using autoregressive integrated moving average (ARIMA) until 2050. Then, the countries are clustered based on the forecasts of primary energy consumption and freshwater withdrawals using k-means algorithm. As desirable and undesirable outputs arise simultaneously, the performances are computed using Pure Environmental Index (PEI) and Mixed Environmental Index (MEI) data envelopment analysis (DEA) models.

Findings

It is expected that by 2050, CO2 emissions of seven countries remain constant, N2O emissions of seven countries remain stable and five countries’ both CO2 and N2O emissions remain constant. While it can be seen as success that many countries are expected to at least stabilize one emission, the likelihood of achieving net zero targets diminishes unless countries undertake significant reductions in emissions. According to the results, in Cluster 1, Turkey ranks last, while France, Germany, Italy and Spain are efficient countries. In Cluster 2, the United Kingdom ranks at last, while Greece, Luxembourg, Malta and Sweden are efficient countries.

Originality/value

In the literature, generally, CO2 emission is considered as greenhouse gas. Moreover, none of the studies measured the net-zero performance of the countries in 2050 employing analytical techniques. This study objects to investigate how well European Continent Countries can comply with the necessities of the Agreement. Besides CO2 emission, N2O emission is also considered and the data of European Continent Countries in 2050 are estimated using ARIMA. Then, countries are clustered using k-means algorithm. DEA models are employed to measure the performances of the countries. Finally, forecasts and models validations are performed and comprehensive analysis of the results is conducted.
Investigating the impact of restaurants’ CSR activities on customer satisfaction: a focus on CSR dimensions
Authors: Omidvar Mohammadsadegh , Palazzo Maria
Published: August 2024

Purpose

This study explores how the various aspects of corporate social responsibility (CSR) impact customer satisfaction (CS) within the restaurant sector. Furthermore, it seeks to reveal if there is a moderating role played by gender in the relationship between CSR dimensions and CS in the realm of restaurant services.

Design/methodology/approach

The findings of this research were obtained by analysing 352 questionnaires collected from Iranian restaurants. Structural equation modelling was used to test the conceptual model.

Findings

According to this research, responsibility (economic, legal, ethical and environmental) is related to CS. Additionally, this study delves into the specific influence of each facet of CSR on CS, a departure from prior research which treated CSR as a singular entity. Consequently, the findings of this study offer clarity on which dimension of CSR can impact CS. Prior studies examining the correlation between CSR and CS typically encompassed various CSR aspects, including economic, legal, ethical and philanthropic dimensions, with the environmental dimension often subsumed under ethical CSR. This research, however, recognises environmental CSR as the fifth distinct dimension. The results of this research show that CS is directly and significantly influenced by all aspects of CSR (except philanthropy). Also, the findings of this research show that gender does not make a difference on the impact of different dimensions of CSR on CS.

Practical implications

The findings of this study provide restaurant managers with a deeper understanding of CSR and how it can influence CS. The research demonstrates that environmental CSR had the strongest impact on Iranian CS among the five CSR dimensions investigated. The findings also support the notion that Iranian consumers are beginning to use CSR information to evaluate restaurants.

Originality/value

This research represents an early exploration of how individual facets of CSR affect CS. As part of this investigation, Carroll’s initial model was modified to include a novel element, environmental responsibility, to address environmental concerns' growing importance. This study contributes to the literature by demonstrating that CSR activities are not all equally effective.
Left Conservatism: Sahra Wagenknecht's Challenge to the German Party System
Authors: Dostal Jörg Michael
Published: August 2024

This article reviews the record of Germany’s current coalition government consisting of the SPD, Greens and liberal FDP under chancellor Olaf Scholz, a member of the SPD. Since 2021, the coalition’s failure to set a coherent policy agenda, permanent infighting and external challenges, such as the Ukraine war and immigration, have led to a dramatic decay in support for the governing parties. The opposition CDU/CSU has profited little from the government’s weakness, while the rightist AfD rides high in opinion polls and elections. Conversely, Die Linke experienced a split in December 2023 when a group of its legislators—led by Sahra Wagenknecht, the former co‐chair of the left’s parliamentary group, decided to found a new political party, the ‘Alliance Sahra Wagenknecht—Reason and Justice’. The article evaluates Wagenknecht’s political discourse which aims to combine progressive welfare and conservative migration policies. It is suggested that Wagenknecht’s ‘left conservatism’ is a promising electoral project filling a representation gap in German politics.
Hydroxychloroquine and risk of osteoporosis in patients with rheumatoid arthritis: A population‐based retrospective study of 6408 patients
Authors: Dong Chen , Chen Brian Shiian , Wu Chun Hsien , Chiu Yi‐Ming , Liao Pei‐Lun , Perng Wuu‐Tsun
Published: August 2024

Aim

Patients with rheumatoid arthritis (RA) are at a higher risk of osteoporotic fractures. Studies have shown that patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) experienced an increase in bone mineral density (BMD) after receiving hydroxychloroquine (HCQ) treatment, indicating a potential protective effect against osteoporosis. Therefore, this study is to examine the relationship between HCQ usage and the risk of osteoporosis in patients diagnosed with RA.

Methods

The retrospective cohort study used data from Taiwan's National Health Insurance Research Database (NHIRD) covering the period from January 2010 to December 2018, which included 14 050 newly diagnosed RA patients, subsequently divided into two groups: HCQ users and non‐users. Propensity score matching (PSM) based on sex, age, urbanization, insured unit type, insured area, and comorbidities was conducted to match the groups. The primary outcome assessed was the evaluation of the risk of osteoporosis by employing a multivariable Cox proportional hazard regression model to calculate the adjusted hazard ratio (aHR).

Results

After PSM, a total of 6408 RA patients were included in the analysis (3204 HCQ users and 3204 non‐users). There was no significantly higher risk of osteoporosis in HCQ users compared with non‐users, aHR = 0.99 (95% CI: 0.82–1.196). Additionally, different durations of HCQ usage demonstrated a neutral effect on the risk of osteoporosis [HCQ <90 days, aHR = 0.88 (95% CI: 0.585–1.324); HCQ 90–180 days, aHR = 0.941 (95% CI: 0.625–1.418); HCQ >180 days, aHR = 1.019 (95% CI: 0.832–1.249)].

Conclusions

The study indicates that there is no significant association between the use of HCQ and the risk of osteoporosis in patients with RA.
Contraindications in national guidelines for vaginal breech delivery at term: Comparison, consensus, and controversy
Authors: van Dijk Merle R. , Papatsonis Christiaan , Ganzevoort Wessel , Moll Etelka , Scheele Fedde , Velzel Joost
Published: August 2024

Introduction

The optimal mode of delivery for vaginal breech presentation remains a clinical dilemma. Planned vaginal delivery offers maternal advantages because it avoids major abdominal surgery and has no consequences for following pregnancies, while elective cesarean delivery proves advantageous for the neonate because adverse outcomes are less frequent. Patient selection for vaginal breech delivery is important based on the individual risk balance. A lack of consensus exists regarding the specific contraindications for vaginal breech delivery, largely due to limited scientific evidence. This systematic review aims to give an overview of contraindications for vaginal breech delivery, as presented in guidelines, analyze relevant literature, and offer evidence‐based recommendations for the contraindications stated in the guidelines.

Material and Methods

To identify national guidelines PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, NICE, UpToDate, and ClinicalKey were searched using two keywords: “breech presentation” and “vaginal delivery.” We systematically reviewed the literature for existing evidence for contraindications for term vaginal breech delivery. The following databases were searched: PubMed (April 2024), the Cochrane Central Register of Controlled Trials, and EMBASE (1947 to 2024).

Results

Our search identified eight guidelines that stated a total of 11 contraindications for vaginal breech delivery. Among these guidelines, agreement was limited, with the sole consensus in all guidelines on the contraindication of footling breech. Our comprehensive literature search yielded 43 articles discussing 14 potential contraindications. We found supportive evidence for 7 of 11 contraindications from the guidelines, with only substantial and satisfactory evidence for two contraindications.

Conclusions

The findings of this study underscore the lack of consensus among national guidelines regarding contraindications for term vaginal breech delivery. Furthermore, we found a notable lack of substantial scientific evidence to support these contraindications. In light of these findings, we suggest a reduced list of contraindications in vaginal breech deliveries.
Unveiling the interoception impairment in various major depressive disorder stages
Authors: Zhou Hongliang , Liu Jikang , Wu Yuqing , Huang Zixuan , Wang Wenliang , Ma Yuhang , Zhu Haohao , Zhou Zhenhe , Wang Jun , Jiang Chenguang
Published: August 2024

Background

The intricate pathophysiological mechanisms of major depressive disorder (MDD) necessitate the development of comprehensive early indicators that reflect the complex interplay of emotional, physical, and cognitive factors. Despite its potential to fulfill these criteria, interoception remains underexplored in MDD. This study aimed to evaluate the potential of interoception in transforming MDD's clinical practices by examining interoception deficits across various MDD stages and analyzing their complex associations with the spectrum of depressive symptoms.

Methods

This study included 431 healthy individuals, 206 subclinical depression individuals, and 483 MDD patients. Depressive symptoms and interoception function were assessed using the PHQ‐9 and MAIA‐2, respectively.

Results

Interoception dysfunction occurred in the preclinical phase of MDD and further impaired in the clinical stage. Antidepressant therapies showed limited efficacy in improving interoception and might damage some dimensions. Interoceptive dimensions might predict depressive symptoms, primarily enhancing negative thinking patterns. The predictive model based on interoception was built with random split verification and demonstrated good discrimination and predictive performance in identifying MDD.

Conclusions

Early alterations in the preclinical stage, multivariate associations with depressive symptoms, and good discrimination and predictive performance highlight the importance of interoception in MDD management, pointing to a paradigm shift in diagnostic and therapeutic approaches.
Parabrachial nucleus Vglut2 expressing neurons projection to the extended amygdala involved in the regulation of wakefulness during sevoflurane anesthesia in mice
Authors: Yan Yan , Jiao Yingfu , Liang Enpeng , Lei Xiaolu , Zhang Nan , Xu Shimao , Zhang Lin , Wang Jiedong , Luo Tianyuan , Yuan Jie , Yuan Chengdong , Yang Hao , Dong Hongxin , Yu Tian , Yu Weifeng
Published: August 2024

Aims

The parabrachial nucleus (PBN) promotes wakefulness states under general anesthesia. Recent studies have shown that glutamatergic neurons within the PBN play a crucial role in facilitating emergence from anesthesia. Our previous study indicates that vesicular glutamate transporter 2 (vglut2) expression neurons of the PBN extend into the extended amygdala (EA). However, the modulation of PBNvglut2‐EA in general anesthesia remains poorly understood. This study aims to investigate the role of PBNvglut2‐EA in alterations of consciousness during sevoflurane anesthesia.

Methods

We first validated vglut2‐expressing neuron projections from the PBN to the EA using anterograde tracing. Then, we conducted immunofluorescence staining of c‐Fos to investigate the role of the EA involved in the regulation of consciousness during sevoflurane anesthesia. After, we performed calcium fiber photometry recordings to determine the changes in PBNvglut2‐EA activity. Lastly, we modulated PBNvglut2‐EA activity under sevoflurane anesthesia using optogenetics, and electroencephalogram (EEG) was recorded during specific optogenetic modulation.

Results

The expression of vglut2 in PBN neurons projected to the EA, and c‐Fos expression in the EA was significantly reduced during sevoflurane anesthesia. Fiber photometry revealed that activity in the PBNvglut2‐EA pathway was suppressed during anesthesia induction but restored upon awakening. Optogenetic activation of the PBNvglut2‐EA delayed the induction of anesthesia. Meanwhile, EEG recordings showed significantly decreased δ oscillations and increased β and γ oscillations compared to the EYFP group. Furthermore, optogenetic activation of the PBNvglut2‐EA resulted in an acceleration of awakening from anesthesia, accompanied by decreased δ oscillations on EEG recordings. Optogenetic inhibition of PBNvglut2‐EA accelerated anesthesia induction. Surprisingly, we found a sex‐specific regulation of PBNvglut2‐EA in this study. The activity of PBNvglut2‐EA was lower in males during the induction of anesthesia and decreased more rapidly during sevoflurane anesthesia compared to females. Photoactivation of the PBNvglut2‐EA reduced the sensitivity of males to sevoflurane, showing more pronounced wakefulness behavior and EEG changes than females.

Conclusions

PBNvglut2‐EA is involved in the promotion of wakefulness under sevoflurane anesthesia. Furthermore, PBNvglut2‐EA shows sex differences in the changes of consciousness induced by sevoflurane anesthesia.
Can Large Language Models Counter the Recent Decline in Literacy Levels? An Important Role for Cognitive Science
Authors: Huettig Falk , Christiansen Morten H.
Published: August 2024

Literacy is in decline in many parts of the world, accompanied by drops in associated cognitive skills (including IQ) and an increasing susceptibility to fake news. It is possible that the recent explosive growth and widespread deployment of Large Language Models (LLMs) might exacerbate this trend, but there is also a chance that LLMs can help turn things around. We argue that cognitive science is ideally suited to help steer future literacy development in the right direction by challenging and informing current educational practices and policy. Cognitive scientists have the right interdisciplinary skills to study, analyze, evaluate, and change LLMs to facilitate their critical use, to encourage turn‐taking that promotes rather than hinders literacy, to support literacy acquisition in diverse and equitable ways, and to scaffold potential future changes in what it means to be literate. We urge cognitive scientists to take up this mantle—the future impact of LLMs on human literacy skills is too important to be left to the large, predominately U.S.‐based tech companies.
Short‐ and long‐term prognostic performance of exercise ECG and myocardial perfusion SPECT
Authors: Kraen M. , Akil S. , Hedén B. , Kjellström B. , Berg J. , Ostenfeld E. , Arheden H. , Carlsson M. , Engblom H.
Published: August 2024

Background

Myocardial perfusion SPECT (MPS) and exercise electrocardiography (Ex‐ECG) results are of prognostic importance for short‐term follow up duration. However, the value of MPS or Ex‐ECG findings for long‐term risk assessment is less evident as underlying risk factors for ischemic heart disease (IHD) gain in importance.

Objectives

To assess the short‐ and long‐term prognostic value of MPS and Ex‐ECG in relation to known risk factors.

Methods and Materials

An observational study of 908 patients (age 63 years, 49% male, 45% prior IHD) referred for MPS and Ex‐ECG. Follow‐up was divided into two periods (short‐term: <5 years and long‐term: >5 years). Cardiac events were defined as a composite of acute myocardial infarction, unstable angina, unplanned revascularization and cardiovascular death.

Results

The composite endpoint occurred in 95 patients (short‐term follow up) and in 94 patients (long‐term follow up). In multivariable models stress testing had a strong predictive value for short‐term follow up (HR for MPS = 2.9, CI = 1.9–4.5, p < 0.001 and HR for Ex‐ECG = 2.1, CI 1.3–3.3, p = 0.002), but no predictive value for long‐term follow up (HR for MPS = 0.9, CI = 0.5–1.5, p = 0.70 and HR for Ex‐ECG = 1.0, CI = 0.6–1.6, p = 0.92). Male sex and prior IHD were significant predictors regardless of follow up duration. Age, diabetes and decreased exercise capacity were risk factors for long‐term follow up.

Conclusions

The prognostic value of MPS and Ex‐ECG results are strong for short‐term follow up but diminish over time and do not contribute significantly in multivariable models after 5 years. Long‐term prognosis is primarily governed by underlying risk factors and exercise capacity.
In court we trust? Political affinity and citizen's attitudes toward court's decisions
Authors: Pereira Carlos , Klevenhusen André , Barros Lúcia
Published: August 2024

This article investigates the role of citizen political affinities in shaping attitudes towards judicial decisions in corruption cases involving politicians. Although emerging research suggests that decisions regarding a high‐ranking politician can reduce general citizen trust in courts, there is no systematic evidence examining how political affinities differentially affect confidence in court decisions depending on the accused politician. We conducted a survey experiment during a 2022 presidential election rally in Brazil at a time of heightened affective polarization and corruption. We presented respondents with vignettes detailing a fictional corruption scheme and trial outcomes (acquittal or conviction) involving key political figures, including Presidents Luiz Inácio Lula da Silva and Jair Bolsonaro. The results indicate that when a court decision is consistent with citizens' electoral preferences, they are more inclined to trust the court decision and vice versa.
Preparation and optimization of silicon nitride slurries for digital light processing
Authors: Sha Qi , Xie Jianjun , Duan Yesen , Tang Wenyu , Zhang Jingxian
Published: August 2024

Digital light processing (DLP) three‐dimensional printing has the advantages of both high printing resolution and efficiency and has been used to manufacture high‐precision, small, and complex shaped ceramic parts. One of the challenges of DLP is to develop photosensitive ceramic slurries with high solid content and low viscosity, especially for non‐oxide ceramics such as silicon nitride due to the dispersion and light absorption problem. This study mainly explores the dispersibility of silicon nitride in ultraviolet (UV)‐cured resins and the photocured properties of the slurry. Rheological measurements were utilized to characterize and screen different dispersants in the resin. It was found that DISPERMP is an effective dispersant. In order to improve the curing depth of Si3N4 photosensitive paste, the surface of silicon nitride powder was treated by oxidation, and organic compounds with different refractive indices were also introduced to increase the light penetration depth. It was found that glycerol with a refractive index of 1.474 resulted in the greatest improvement in the curing depth of Si3N4 photosensitive paste. Finally, a proposed slurry composition was developed to successfully print silicon nitride ceramics through UV‐curing molding technology.
31‐GEP (DecisionDx): a review of clinical utility and performance in a Mayo Clinic cohort
Authors: Pazhava Ani , Kim Yong‐hun , Jing Frank Z. , Pittelkow Mark R.
Published: August 2024

Background

Cutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31‐GEP test (DecisionDx‐Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31‐GEP test in a real‐world setting.

Methods

Patients with CM who underwent 31‐GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31‐GEP testing on clinical decision‐making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan–Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse‐free survival (RFS) and melanoma‐specific survival (MSS).

Results

The study included 65 CM patients. Dermatologists ordered more than 80% of 31‐GEP tests. In 81.5% of cases, 31‐GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre‐SLNB 31‐GEP results. Among patients with stage I‐IIA melanoma, 25% of those with high‐risk 31‐GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low‐risk than in high‐risk 31‐GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31‐GEP classes, suggesting limited prognostic value.

Conclusions

The 31‐GEP test has a limited impact on clinical management decisions and shows limited prognostic value.
Growth selection induced residual stresses and fracture behavior of as‐deposited thermal barrier coatings
Authors: Neog Suruj Protim , Pai Namit , Yadav Deepesh , Curry Nicholas , Joshi Shrikant , Jaya B. Nagamani , Samajdar Indradev
Published: August 2024

This study explored the impact of microstructure and residual stresses on the fracture behavior of as‐deposited thermal barrier coatings (TBCs). Two distinct air plasma sprayed TBCs, Coating A (conventional lamellar porous) and Coating B (dense vertically cracked), were investigated. Coating A involved coarser but less dense powders as feedstock and a lower substrate temperature during deposition. Further, Coating A had times higher randomly oriented porosities, finer grains, lower hardness, and elastic stiffness. Strikingly, however, the fracture strength was higher for the porous as‐deposited Coating A. The answer to this apparent contradiction emerged from the intergranular residual stresses. These were measured using both X‐ray diffraction and high‐resolution‐electron backscattered diffraction. Coating B, deposited at a higher substrate temperature, had clear growth selection of oriented grains. These also had more out‐of‐plane normal and shear residual stresses. The growth selection induced residual stresses appeared responsible for the decohesion of Coating B from the substrate and, correspondingly, lower fracture strength.