bluuebunny/crossref_metadata_2025 huggingface dataset:
Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy
Authors: Basu Srijani , Običan Sarah G. , Bertaggia Enrico , Staab Hannah , Izquierdo M. Concepcion , Gyamfi-Bannerman Cynthia , Haeusler Rebecca A.
Published: August 2024

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated plasma bile acid levels. ICP is linked to adverse metabolic outcomes, including a reported increased risk of gestational diabetes. The standard therapeutic approach for managing ICP is treatment with ursodeoxycholic acid (UDCA) and induction of labor prior to 40 weeks of gestation. To investigate bile acid and metabolic parameters after UDCA treatment, we enrolled 12 ICP patients with singleton pregnancies–half with and half without gestational diabetes–and 7 controls. Our study reveals that after UDCA treatment, notwithstanding a reduction in total bile acid and ALT levels, imbalances persist in the cholic acid (CA) to chenodeoxycholic acid (CDCA) ratio in maternal and cord blood plasma. This indicates a continued dysregulation of bile acid metabolism despite therapeutic intervention. Maternal plasma lipid analysis showed a distinct maternal dyslipidemia pattern among ICP patients, marked by elevated cholesterol levels on VLDL particles and heightened triglyceride concentrations on LDL particles, persisting even after UDCA treatment. Cord plasma lipid profiles in ICP patients exhibited elevated triglyceride and free fatty acid levels alongside a tendency toward increased β-hydroxybutyrate. The changes in lipid metabolism in both maternal and cord blood correlated with the high CA/CDCA ratio, but not total bile acid levels or gestational diabetes status. Understanding the imbalances in maternal and cord bile acid and lipid profiles that persist after standard UDCA therapy provides insights for improving management strategies and mitigating the long-term consequences of ICP.

News and Noteworthy

This study uncovers that despite ursodeoxycholic acid treatment, intrahepatic cholestasis of pregnancy (ICP) is associated with increases in the ratio of cholic acid to chenodeoxycholic acid in both maternal and cord blood, suggesting ongoing dysregulation of bile acid metabolism. The high cholic to chenodeoxycholic acid ratio is correlated with maternal dyslipidemia and high cord blood lipids. These findings may inform more targeted approaches to managing ICP.
Treatment Outcomes and MRI Features of SUNA: A Systematic Review and Meta-Analysis
Authors: Verma Jay , Khanduja Sneha , Etienne Mill
Published: August 2024

Background

Trigeminal autonomic cephalalgias (TACs), including short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), are rare but debilitating headaches. The pathophysiology and optimal treatment of SUNA remain poorly defined, compounded by disparities in healthcare access.

Objectives

To systematically review and analyze the effectiveness of treatment options, clinical outcomes, and brain MRI findings for SUNA, and to identify gaps in the current evidence base.

Methodology

Following PRISMA guidelines, a systematic search was performed across multiple databases. Data from 20 studies were analyzed, focusing on treatment efficacy, patient demographics, and MRI findings. Meta-analyses were conducted on treatment effectiveness, and bias was assessed using the Newcastle-Ottawa Scale.

Results

Among 267 patients, the most commonly used treatments were lamotrigine (37.07%) and greater occipital nerve (GON) block (16.85%), showing effectiveness in over 50% of cases. Heterogeneity in lamotrigine effectiveness was high (Cochran’s Q = 63.10, p-value < 0.0001, α = 0.05). Lidocaine was effective for acute attacks (> 80%). Brain MRIs were mostly unremarkable, with some evidence suggesting neurovascular involvement.

Conclusion

Lamotrigine and GON block are effective for SUNA, though treatment responses vary widely. MRI findings often lack abnormalities, suggesting a need for further research into the pathophysiology of SUNA. Larger, high-quality studies are needed to establish standardized treatment protocols and improve patient outcomes.
Distinct functions of PAXX and MRI during chromosomal end joining
Authors: Cisneros-Aguirre Metztli , Lopezcolorado Felicia Wednesday , Ping Xiaoli , Chen Ruby , Stark Jeremy M
Published: August 2024

A key step of Canonical Nonhomologous End Joining (C-NHEJ) is synapsis of DNA double strand break (DSB) ends for ligation. The DNA-PKcs dimer mediates synapsis in a long-range complex with DSB ends remaining apart, whereas the XLF homodimer can mediate synapsis in both long-range and short-range complexes. Recent structural studies found the PAXX homodimer may also facilitate synapsis in long-range complexes with DNA-PKcs via its interactions with Ku70. Thus, we examined the influence of PAXX in C-NHEJ of chromosomal DSBs, which we compared to another Ku-binding factor, MRI. Using EJ of blunt DSBs with Cas9 reporters as a readout for C-NHEJ, we found that PAXX and/or MRI are dispensable. However, when combined with disruption of DNA-PKcs, particularly with DNA-PKcs kinase inhibition, PAXX becomes important for blunt DSB EJ. In contrast, while DNA-PKcs is also important to suppress short deletion mutations with microhomology, this effect is not magnified with PAXX loss. MRI loss had no effect combined with DNA-PKcs disruption, but becomes important for blunt DSB EJ when combined with disruption of XLF, as is PAXX. Finally, XLF loss causes an increase in larger deletions compared to DNA-PKcs inhibition, which is magnified with combined loss of MRI. Altogether, we suggest that PAXX promotes DSB end synapsis during C-NHEJ in a manner that is partially redundant with DNA-PKcs and XLF, whereas MRI appears to be mainly important in the context of XLF disruption.
Covalently linked adenovirus-AAV complexes as a novel platform technology for gene therapy
Authors: Collins Logan Thrasher , Beatty Wandy , Moyo Buhle , Alves-Bezerra Michele , Hurley Ayrea , Lagor William , Bao Gang , Lu Zhi Hong , Curiel David T.
Published: August 2024

Adeno-associated virus (AAV) has found immense success as a delivery system for gene therapy, yet the small 4.7 kb packaging capacity of the AAV sharply limits the scope of its application. In addition, high doses of AAV are frequently required to facilitate therapeutic effects, leading to acute toxicity issues. While dual and triple AAV approaches have been developed to mitigate the packaging capacity problem, these necessitate even higher doses to ensure that co-infection occurs at sufficient frequency. To address these challenges, we herein describe a novel delivery system consisting of adenovirus (Ad) covalently linked to multiple adeno-associated virus (AAV) capsids as a new way of more efficiently co-infecting cells with lower overall amounts of AAVs. We utilize the DogTag-DogCatcher (DgT-DgC) molecular glue system to construct our AdAAVs and we demonstrate that these hybrid virus complexes achieve enhanced co-transduction of cultured cells. This technology may eventually broaden the utility of AAV gene delivery by providing an alternative to dual or triple AAV which can be employed at lower dose while reaching higher co-transduction efficiency.
Cyclin C Promotes Pancreatic Development and Suppresses Cancer Initiation Through Maintenance of the Autophagy-Lysosome Pathway
Authors: Hanley Sara E. , Cai Kathy Q. , Willis Stephen D. , Stieg David C. , Klein-Szanto Andres J. , Campbell Kerry S. , Strich Randy
Published: August 2024

The cyclin C (Ccnc)-Cdk8/Cdk19 kinases are components of the Mediator that represses or activates gene transcription. The present study found that Ccnc is required for both steady state and induced autophagic gene transcription in mouse embryonic fibroblasts. In vivo, pancreatic ablation ofCcnc(CcncPanΔ) resulted in phenotypes (islet atrophy, acinar cell damage) also observed in autophagy deficient models. However,CcncPanΔanimals displayed more dramatic phenotypes including earlier death and accelerated acinar ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) precancerous lesion formation when these animals also expressed oncogenicKrasG12D. Consistent with the in vivo results, aKrasG12D;CcncPanΔpancreatic derived cell line displayed reduced autophagy lysosome pathway (ALP) activation. Although autophagy deficient acinar cells undergo Tp53-dependent cell death, histopathology revealed thatKrasG12D;Ccnc-/-(PC) pancreata did not allowing damaged cells to keep dividing. Therefore, Ccnc both supports normal ALP function protecting endocrine and exocrine cell but also kills damaged cells before they become malignant. Finally, the PC cell line displayed reduced proteasome function rendering cells hypersensitive to proteasome inhibitors. This hypersensitivity was also observed in disparateCcnc-/-tumor cell lines or inCcnc+/+tumor cells co-treated with Cdk8/Cdk19 inhibitors. These findings suggest a new avenue to target pancreatic neoplasms by inhibiting cyclin C-Cdk8/Cdk19 proteasome activity.
Catalytic transformations for thermal operations
Authors: Czartowski Jakub , de Oliveira Junior A.
Published: August 2024

What are the fundamental limits and advantages of using a catalyst to aid thermodynamic transformations between quantum systems? In this paper, we answer this question by focusing on transformations between energy-incoherent states under the most general energy-conserving interactions among the system, the catalyst, and a thermal environment. The sole constraint is that the catalyst must return unperturbed and uncorrelated with the other subsystems. More precisely, we first upper bound the set of states to which a given initial state can thermodynamically evolve (the catalyzable future) or from which it can evolve (the catalyzable past) with the help of a strict catalyst. Secondly, we derive lower bounds on the dimensionality required for the existence of catalysts under thermal process, along with bounds on the catalyst's state preparation. Finally, we quantify the catalytic advantage in terms of the volume of the catalyzable future and demonstrate its utility in an exemplary task of generating entanglement and cooling a quantum system using thermal resources.

Published by the American Physical Society
2024
Kitaev physics in the two-dimensional magnet
NiPSe3
Authors: Peng Cheng , Mardanya Sougata , Petsch Alexander N. , Sharma Vineet Kumar , Li Shuyi , Jia Chunjing , Bansil Arun , Chowdhury Sugata , Turner Joshua J.
Published: August 2024

The Kitaev interaction, found in candidate materials such as α−RuCl3, occurs through the metal (M)-ligand (X)-metal (M) paths of the edge-sharing octahedra because the large spin-orbit coupling (SOC) on the metal atoms activates directional spin interactions. Here, we show that even in 3d transition-metal compounds, where the SOC of the metal atom is negligible, heavy ligands can induce bond-dependent Kitaev interactions. In this work, we take as an example the 3d transition-metal chalcogenophosphate NiPSe3 and show that the key is found in the presence of a sizable SOC on the Se p orbital, one which mediates the super-exchange between the nearest-neighbor Ni sites. Our study provides a pathway for engineering enhanced Kitaev interactions through the interplay of SOC strength, lattice distortions, and chemical substitutions.

Published by the American Physical Society
2024
Enhancer-Insulator Pairing Reveals Heterogeneous Dynamics in Long-Distance 3D Gene Regulation
Authors: Hedström Lucas , Metzler Ralf , Lizana Ludvig
Published: August 2024

Cells regulate fates and complex body plans using spatiotemporal signaling cascades that alter gene expression. Short DNA sequences, known as enhancers (50–1500 base pairs), help coordinate these cascades by attracting regulatory proteins that enhance the transcription by binding to distal gene promoters. In humans, there are hundreds of thousands of enhancers dispersed across the genome, which poses a challenging coordination task to prevent unintended gene activation. To mitigate this problem, the genome contains insulator elements that block enhancer-promoter interactions. However, there is an open problem with how the insulation works, especially as enhancer-insulator pairs may be separated by millions of base pairs. Based on recent empirical data from Hi-C experiments, this paper proposes a new mechanism that challenges the common paradigm that rests on specific insulator-insulator interactions. Instead, this paper introduces a stochastic looping model where insulators bind weakly to chromatin rather than other insulators. After calibrating the model to experimental data, we use simulations to study the broad distribution of hitting times between an enhancer and a promoter when insulators are present. We find parameter regimes with large differences between average and most probable hitting times. This makes it difficult to assign a typical timescale and hints at highly defocused regulation times. We also map our computational model onto a resetting problem that allows us to derive several analytical results. Besides offering new insights into enhancer-insulator interactions, our paper advances the understanding of gene regulatory networks and causal connections between genome folding and gene activation.

Published by the American Physical Society
2024
Crystal structure of the Rib domain of the cell-wall-anchored surface protein from Limosilactobacillus reuteri
Authors: Xue Yi , Wu Zhen , Kang Xue
Published: August 2024

The immunoglobulin (Ig)-like domain is found in a broad range of proteins with diverse functional roles. While an essential β-sandwich fold is maintained, considerable structural variations exist and are critical for functional diversity. The Rib-domain family, primarily found as tandem-repeat modules in the surface proteins of Gram-positive bacteria, represents another significant structural variant of the Ig-like fold. However, limited structural and functional exploration of this family has been conducted, which significantly restricts the understanding of its evolution and significance within the Ig superclass. In this work, a high-resolution crystal structure of a Rib domain derived from the probiotic bacterium Limosilactobacillus reuteri is presented. This protein, while sharing significant structural similarity with homologous domains from other bacteria, exhibits a significantly increased thermal resistance. The potential structural features contributing to this stability are discussed. Moreover, the presence of two copper-binding sites, with one positioned on the interface, suggests potential functional roles that warrant further investigation.
The importance of belonging: reflections on a participatory action research project in Jacksonville, Florida
Authors: Mehdipour Haleh , Prokosch Marjorie , Williams Darien , Thomas Abdul-Hai , Seymour Brian , Conley Jacqueline , von Meding Jason
Published: August 2024

Purpose

The paper explores the implementation and process of a Participatory Action Research (PAR) project in Jacksonville, Florida. Using PAR principles, we sought to disrupt traditional dynamics in research, co-generating knowledge with the community. We aimed to elevate disenfranchised voices and foster effective solutions for neighborhood revitalization and resilience, which are designed and led by the community. In this paper we explore researcher positionality, examining how engagement with the community context profoundly influences researchers' perspectives and roles, thereby shaping the study trajectory.

Design/methodology/approach

We use reflexive and thematic approaches to analyze researcher positionalities and dynamics with the community. Researchers' reflections were scrutinized with a focus on their backgrounds, adaptability to community pace of work, lessons learned and evolving perspectives on community-centered research. We present a comprehensive discussion of emerging themes and emphasize the transformative nature of PAR and the significance of the researcher pursuing a relationship of belonging within the community.

Findings

The study uncovered key themes clarifying the transformations experienced by researchers engaged in PAR. We underwent a significant shift from a predetermined, structured PAR model to a more organic, community-driven model. This shift is illustrated under key themes in the paper: being vulnerable, valuing relationships, transforming the sense of self and solidarity, focusing on the process and recognizing and valuing community-derived knowledge. We write about the metamorphosis of researchers' roles from passive observers to active and empathic participants and about the implications for our methodological approach. As a result of this adaptation, the research process was enhanced and a symbiotic learning environment was created between the researchers and the community.

Originality/value

This paper distinguishes itself through its community-centric approach, diverging from traditional research paradigms. It explores how PAR-based community engagement can have a positive impact on those who are involved in PAR themselves, contributing to a better understanding of reciprocal dynamics in community-based research. We hope that our process of reflection can help other disaster researchers to ask better questions of themselves when engaging with communities and be open to following the lead and the pace of the community.
Financial market uncertainty and the macro economy: the role of governance and institutional quality
Authors: Abaidoo Rexford , Agyapong Elvis Kwame
Published: August 2024

Purpose

The study examines the impact of macroeconomic risk and volatility associated with key macroeconomic indicators on financial market uncertainty; and the extent to which governance and institutional structures moderate such relationships.

Design/methodology/approach

The study employs data from 33 countries in Sub-Saharan Africa (SSA) for the period between 1996 and 2019. Variable derivation techniques such as the generalized autoregressive conditional heteroskedasticity (GARCH) for deriving volatility data, and the principal component analysis (PCA) for index construction were employed. The data is examined using the two-step system generalized method of moments (TS-SGMM) technique.

Findings

Empirical results suggest that macroeconomic risk and exchange rate volatility heighten financial market uncertainty among economies in the sub-region. Further empirical estimates show that institutional quality and government effectiveness have a negative moderating effect on the nexus between macroeconomic risk, inflation uncertainty, GDP growth, exchange rate, and financial market uncertainty.

Practical implications

The key macroeconomic conditions with the propensity to foment financial market uncertainty are worth monitoring with adequate buffers to mitigate their impacts on the financial market.

Originality/value

Compared to related studies, this study focuses on uncertainty associated with financial markets among emerging economies in sub-Saharan Africa (SSA) instead of the performance of the financial markets or specific financial market indicators such as the stock market; and the extent to which a host of macroeconomic conditions influence such uncertainty. For instance, Abaidoo and Agyapong (2023) focused on the impact of macroeconomic indicators or conditions on the performance of the financial market and the efficiency of financial institutions respectively instead of the uncertainty or risk associated with the financial market as pursued in the current study. This differing approach is pursued with the goal of proffering appropriate strategies for policy makers towards assuaging the financial market risk (uncertainty) due to macroeconomic dynamics. We further examine how the various fundamental relationships may be moderated by effective governance and institutional quality.
Slow and steady or fast and furious: how movement speed in the digital medium impacts consumers’ risk judgments
Authors: Taylor Nükhet , Hingston Sean T.
Published: August 2024

Purpose

Fueled by the soaring popularity of the digital medium, consumers are increasingly relying on dynamic images to inform their decisions. However, little is known about how changes in the presentation of movement impacts these decisions. The purpose of this paper is to document whether and how movement speed–a fundamental characteristic of dynamic images in the digital medium–influences consumers' risk judgments and subsequent decisions.

Design/methodology/approach

Three experimental studies investigate the impact of movement speed displayed in the digital medium, focusing on different risk-laden domains including health (pilot study), gambling (Study 1) and stock market decisions (Study 2).

Findings

The authors find that faster movement speed displayed in the digital medium elevates consumers’ feelings of risk and elicits cautionary actions in response. The authors reveal a mechanism for this effect, showing that faster movement reduces feelings of control over outcomes, which predicts greater feelings of risk.

Research limitations/implications

Future work could expand upon these findings by systematically examining whether certain individuals are more susceptible to movement speed effects in the digital medium. Research could also investigate whether different ways of experiencing movement speed (e.g. physical movement) similarly influence risk judgments and whether movement speed can have positive connotations outside of risky domains.

Practical implications

The authors offer important insights to marketing practitioners and public policymakers seeking to guide consumers’ judgments and decisions in risk-laden contexts through the digital medium.

Originality/value

By showing how movement speed alters judgments in risk-laden contexts, the authors contribute to literature on risk perception and the growing body of literature examining how moving images shape consumers’ behaviors.
Bridging the information asymmetry in e-commerce: an intercultural perspective on sustainable clothing
Authors: Robichaud Zachary , Brand Benedikt M. , Yu Hong
Published: August 2024

Purpose

This study addresses the information asymmetry issue in e-commerce, particularly prevalent in the clothing industry, leading to high product returns and environmental harm. The research aims to fill gaps in the existing literature by holistically examining multiple information cues and considering intercultural differences, utilizing signaling theory.

Design/methodology/approach

An Adaptive Choice-Based Conjoint experiment involving German (n = 332) and Chinese (n = 331) respondents from Generation Y is conducted. This cross-cultural comparison explores consumer preferences for sustainable clothing and analyses factors influencing their choices, including price, shipping costs, sustainability labels and online customer reviews.

Findings

German online shoppers exhibit a stronger preference for sustainable clothing compared to their Chinese counterparts, with notable differences in the emphasis placed on various factors. Chinese respondents prioritize monetary aspects (e.g. price and shipping costs), while Germans attach greater importance to sustainability labels and online customer reviews.

Originality/value

This research contributes to the existing literature by providing a comprehensive analysis of information cues in e-commerce, considering cultural variations. The findings shed light on the distinct preferences of German and Chinese respondents from Generation Y, offering valuable insights for businesses aiming to address information asymmetry and enhance environmental sustainability in online clothing retail.
Digital entrepreneurship and the emergence of coopetitive affordance
Authors: Abubakre Mumin , Mkansi Marcia
Published: August 2024

Purpose

By focusing on the contextual conditions of South African digital entrepreneurs and the affordances of digital technologies, we understand how connective affordances of digital technologies enable a collective approach to digital entrepreneurship.

Design/methodology/approach

We do so through an interpretive field study of South African digital entrepreneurs operating in resource-constrained settings.

Findings

The findings highlight how entrepreneurs appropriate digital technologies in collectives to achieve connective actions and cooperate and compete simultaneously, giving rise to what we call coopetitive affordance, reflecting a fresh perspective on coopetition in increasingly digital and resource-constrained realities.

Originality/value

This paper extends the connective affordance perspective by illustrating how the concept of coopetitive affordance brings to light how contextual conditions create a humanitarian bond between entrepreneurs and a digital bond created by their appropriation of digital technologies in collectives.
Inhumane diplomacy: a systematic review on the effects of international sanctions on poverty
Authors: Koehler Anna Franziska
Published: August 2024

Purpose

This paper addresses the under-explored collateral damage of economic sanctions, shedding light on the disproportionate harm endured by the most vulnerable segments of societies, which at the same time lack political influence to effect the ruling government into change. The primary objective is to review the literature on humanitarian repercussions associated with sanctions, concluding if they really are a comparably human way of international interference.

Design/methodology/approach

Employing a systematic literature review, adhering to the PRISMA approach, and incorporating key term definitions and clear selection criteria, this review analyses 52 studies sourced from Scopus and EconBiz.

Findings

The surveyed literature reveals profound adverse impacts of sanctions on health, economic well-being, inequality, and education. Critical gaps in the literature such as disproportional focus on extreme cases like Iran and Iraq, scarce literature on effects on education and inequality, and predominantly inadequate control groups are identified, limiting the generalizability of existing findings.

Originality/value

This paper is the first systematic and replicable review of the literature on the effects of sanctions using a capabilistic approach to define poverty. Highlighting gaps in the current research landscape underscores the limited generalizability of reviewed results. Providing a well-structured summary of existing literature, this work serves as a foundation for future research.
“Keep your friends close, but your enemies closer:” ChatGPT in tourism and hospitality
Authors: Altinay Zehra , Altinay Fahriye , Tlili Ahmed , Vatankhah Sanaz
Published: August 2024

Purpose

ChatGPT has been receiving mounting research attention recently. However, its application and challenges to adopt for tourism and hospitality businesses remain relatively unexplored. To address this research gap, this study aims to systematically assess the application of ChatGPT and its challenges within the domain of tourism and hospitality.

Design/methodology/approach

This study conducts bibliometric and content analyses of papers retrieved from Web of Science and Scopus. Particularly, it systematically reviewed the tourism and hospitality research to identify critical applications of ChatGPT in the context of tourism and hospitality. In addition, this study identified challenges associated with the application of ChatGPT in this context.

Findings

It has been revealed that the use of generative artificial intelligence (AI), such as ChatGPT, in tourism and hospitality research is ascending, with an opportunity to advance the existing knowledge in customer service research. In addition, the results suggest an ongoing interest in assessing the role of AI and language modeling for tourism education and human resource management.

Research limitations/implications

The results are constrained by the used search keywords and electronic databases. Additionally, this study covered only papers published in English. However, the findings shed light on existing knowledge concerning ChatGPT’s transformative potential, identify areas for further exploration and offer guidelines for practice in the tourism and hospitality industry. The findings also revealed various challenges that various stakeholders should keep a closer eye on to ensure the effective and safe use of ChatGPT accordingly.

Originality/value

This study initiates a discussion on ChatGPT’s role in tourism and hospitality and underscores the importance of comprehensive AI integration within the sector.
Productivity improvement opportunities for metal powder bed fusion technologies: a systematic literature review
Authors: McConnell Sean , Tanner David , Kourousis Kyriakos I.
Published: August 2024

Purpose

Productivity is often cited as a key barrier to the adoption of metal laser-based powder bed fusion (ML-PBF) technology for mass production. Newer generations of this technology work to overcome this by introducing more lasers or dramatically different processing techniques. Current generation ML-PBF machines are typically not capable of taking on additional hardware to maximise productivity due to inherent design limitations. Thus, any increases to be found in this generation of machines need to be implemented through design or adjusting how the machine currently processes the material. The purpose of this paper is to identify the most beneficial existing methodologies for the optimisation of productivity in existing ML-PBF equipment so that current users have a framework upon which they can improve their processes.

Design/methodology/approach

The review method used here is the preferred reporting items for systematic review and meta-analysis (PRISMA). This is complemented by using an artificial intelligence-assisted literature review tool known as Elicit. Scopus, WEEE, Web of Science and Semantic Scholar databases were searched for articles using specific keywords and Boolean operators.

Findings

The PRIMSA and Elicit processes resulted in 51 papers that met the criteria. Of these, 24 indicated that by using a design of experiment approach, processing parameters could be created that would increase productivity. The other themes identified include scan strategy (11), surface alteration (11), changing of layer heights (17), artificial neural networks (3) and altering of the material (5). Due to the nature of the studies, quantifying the effect of these themes on productivity was not always possible. However, studies citing altering layer heights and processing parameters indicated the greatest quantifiable increase in productivity with values between 10% and 252% cited. The literature, though not always explicit, depicts several avenues for the improvement of productivity for current-generation ML-PBF machines.

Originality/value

This systematic literature review provides trends and themes that aim to influence and support future research directions for maximising the productivity of the ML-PBF machines.
Hybrid governance and intersectional discrimination: An examination of women's experiences in South Africa
Authors: van Dijk Gerda , Mangai Mary S.
Published: August 2024

This research investigates the lived experiences of women in South Africa, focusing on the concept of hybrid governance and intersectional discrimination. Hybrid governance denotes a blend of modern and traditional governance structures that coexist in many post‐colonial societies, including South Africa. Intersectional discrimination recognises that individuals face layers of discrimination simultaneously influenced by intersecting identities like race, gender, class, and ethnicity. This study utilised quantitative analysis and desktop research methods. The researchers employed theoretical and operational parameters to conduct a logistic regression analysis using data from the 2018/2019 Governance, Public Safety and Justice Survey (GPSJS) conducted by Statistics South Africa. The analysis aims to investigate how hybrid governance structures impact women's lives and the interconnectedness among forms of discrimination they encounter. The results shed light on the power dynamics, representation challenges, and discriminatory practices within the realm of hybrid governance. Women's experiences showcase how patriarchal norms, racial disparities, and socio‐economic factors intersect to heighten discrimination levels and constrain women's autonomy. Additionally, the study emphasises the significance of recognising and addressing intersectionality as a framework for comprehending and responding to the multi‐faceted challenges faced by women in South Africa.

Points for practitioners

Practitioners should appreciate the cultural diversity in South Africa and respect the varying customs and practices that come with hybrid governance. They should understand that traditional governance structures can coexist with modern ones, but also ensure that these structures do not perpetuate discriminatory practices.

Practitioners should understand that individuals may face multiple, intersecting forms of discrimination. They should therefore approach work with an intersectional lens, taking into account the ways in which factors like race, gender, and tribal affiliation can compound discrimination.

Practitioners should encourage dialogue about discrimination within the communities in which they work. They should raise awareness about what constitutes discrimination and how individuals can report it.

Practitioners should utilise available data to inform their work. They should regularly review and analyse data on discrimination to identify trends and patterns, and to inform strategies and interventions.
Global burden of vaccine‐associated rheumatic diseases and their related vaccines, 1967–2023: A comprehensive analysis of the international pharmacovigilance database
Authors: Oh Jiyeon , Jo Hyesu , Park Jaeyu , Lee Hayeon , Kim Hyeon Jin , Lee Hyeri , Kang Jiseung , Hwang Jiyoung , Woo Selin , Son Yejun , Kim Soeun , Smith Lee , Rahmati Masoud , Jacob Louis , Lee Jinseok , Lee Jun Hyuk , López Sánchez Guillermo F. , Dragioti Elena , Udeh Raphael , Veronese Nicola , Soysal Pinar , Woo Ho Geol , Yon Dong Keon
Published: August 2024

Vaccine‐associated rheumatic diseases are rare but one of the most feared adverse drug reactions (ADRs). However, this topic has been investigated less with large‐scale data in the literature. With the rapid progress in the development and approval of vaccines during the pandemic, public concerns regarding their safety have been raised. To assess the global and regional burden, long‐term trends, and potential risk factors of vaccines‐associated six types of rheumatic diseases (ankylosing spondylitis [AS], polymyalgia rheumatica [PMR], rheumatoid arthritis [RA], Sjögren's syndrome, Systemic lupus erythematosus [SLE], Systemic scleroderma), this study conducted disproportionality analysis based on the reports from the World Health Organization International Pharmacovigilance Database documented between 1967 and 2023 (n for total reports = 131 255 418) across 156 countries and territories. We estimated the reporting odds ratio (ROR) and information component (IC) to determine the disproportionality signal for rheumatic diseases. Of 198 046 reports of all‐cause rheumatic diseases, 14 703 reports of vaccine‐associated rheumatic diseases were identified. While the reporting counts have gradually increased over time globally, we observed a dramatic increase in reporting counts after 2020, potentially due to a large portion of reports of COVID‐19 mRNA vaccine‐associated rheumatic diseases. The disproportionality signal for rheumatic diseases was most pronounced in HBV vaccines (ROR, 4.11; IC025, 1.90), followed by COVID‐19 mRNA (ROR, 2.79; IC025, 1.25), anthrax (ROR, 2.52; IC025, 0.76), papillomavirus (ROR, 2.16; IC025, 0.95), encephalitis (ROR, 2.01; IC025, 0.58), typhoid (ROR, 1.91; IC025, 0.44), influenza (ROR, 1.49; IC025, 0.46), and HAV vaccines (ROR, 1.41; IC025, 0.20). From age‐ and sex‐specific perspective, young females and old males are likely to have vaccine‐associated rheumatic disease reports. Furthermore, overall vaccines showed a disproportionality signal for PMR (IC025, 3.13) and Sjögren's syndrome (IC025, 0.70), systemic scleroderma (IC025, 0.64), specifically while the COVID‐19 mRNA vaccines are associated with all six types of diseases. Although multiple vaccines are associated with rheumatic disease reports, healthcare providers should be aware of the potential of autoimmune manifestations following vaccination, particularly the COVID‐19 mRNA and HBV vaccines, and take into account for risk factors associated with these ADRs. Most ADRs exhibited an average time to onset of 11 days, underscoring the significance of monitoring and timely management by clinicians.
Sex differences in comorbid pain and opioid use disorder: A scoping review
Authors: DeVito Elise E. , Ameral Victoria , Sofuoglu Mehmet
Published: August 2024

Opioid use disorder (OUD) and chronic pain are commonly co‐occurring disorders which can exacerbate each other. Sex/gender differences have been shown in aspects of the clinical course and biological underpinnings of both OUD and chronic pain. The purpose of this scoping review is to summarize literature which has addressed sex/gender differences in relation to the confluence of OUD and chronic pain. This review focused on peer‐reviewed journal articles with human subjects and addressing (a) opioid misuse, chronic opioid use or opioid use disorder (OUD), (b) chronic or persistent pain and (c) sex/gender differences in relation to OUD and/or chronic pain. Of the 146 papers identified by the search strategy, 30 met the criteria for inclusion. Charting focused on a priori themes of chronic pain, opioid misuse/OUD and sex/gender in sample, predictor and outcome variables, and key study findings. The majority of research identified was cross‐sectional in nature, and sex/gender differences and treatment effects were largely included as post‐hoc analyses. Together, the results of this early work align with higher prevalence for OUD in men/males and chronic pain in women/females, while adding critical information with respect to potential sex/gender differences in the development and treatment of their co‐occurrence across a range of biological and psychosocial factors. Findings underline the importance of considering sex and gender in the intersection of the development and treatment of OUD and chronic pain.
Effectiveness of metformin pretreatment for stroke severity: A propensity score matching study
Authors: Zhang Bowei , Silverman Scott , Schwammn Lee H. , Ji Xunming , Singhal Aneesh B.
Published: August 2024

Background and Objective

Metformin pretreatment might have neuroprotective effects. We aimed to determine the therapeutic effects of the antidiabetic medication metformin on ischemic stroke severity and discharge outcomes.

Methods

We analyzed data on 1303 ischemic stroke patients who were on antidiabetic medications from the Massachusetts General Hospital (MGH) Advanced Comprehensive Stroke Center dataset (n = 8943, 2012–2022). We applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses to investigate the effect of current usage of metformin (versus alternate antidiabetic treatment) on acute stroke clinical severity and discharge outcomes.

Results

Of the 1303 patients who were on antidiabetic medications at the time of stroke admission, 730 (56%) were taking metformin. Metformin users were younger and more frequently had hypertension, whereas less frequently had prior CAD, AFib, and chronic kidney disease. The clinical features and laboratory values of the two groups were evenly distributed after PSM. Metformin‐treated patients had statistically significant lower stroke severity on admission [National Institutes of Health Stroke Scale (NIHSS) (median, interquartile range) 3.0 (1.0–8.0) vs. 4.0 (2.0–11.3), p = 0.011], better functional independence at discharge (modified Rankin scale score 0–2, 36.3% vs. 25.4%, p < 0.001) and less in‐hospital mortality (4.5% vs. 11.3%, p = 0.018). IPTW analysis results were consistent with PSM results.

Conclusions

Among diabetic patients with acute ischemic stroke, metformin appears to confer neuroprotection. Our results extend previous findings to the general stroke population. Stroke patients with diabetes mellitus who were treated with metformin prior to stroke, even when combined with additional antidiabetic medications, experienced less severe strokes upon admission and had better functional outcomes during hospitalization.
Pharmacokinetics, pharmacodynamics, and safety of GS‐3583, a FLT3 agonist Fc fusion protein, from single‐ascending‐dose phase I study in healthy participants
Authors: Dauki Anees M. , Rajakumaraswamy Nishanthan , Trowe Torsten , Weng Winnie , Lin Kai‐Wen , Elboudjwarej Emon , Qin Ann Ran‐Ran , Schwabe Christian , Kuhne Michelle R. , Othman Ahmed A.
Published: August 2024

Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor‐specific CD8+ T cells and their recruitment to tumor microenvironment. However, cDC1s are often underrepresented in the microenvironment. Systemic administration of Fms‐like tyrosine kinase 3 ligand, a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to cDC1 expansion in the periphery and recruitment into the microenvironment. FLT3 pathway stimulation using GS‐3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T‐cell mediated antitumor activity. This was a first‐in‐human, placebo‐controlled study of GS‐3583 in healthy participants to evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) of escalating single doses (75–2000 μg) of GS‐3583. Each dose cohort enrolled 8–12 healthy participants who received GS‐3583 or placebo as single IV infusion at 3:1 ratio. As part of the PD evaluation, the changes in the number of cDC1 cells were investigated. GS‐3583 was well‐tolerated in healthy participants up to the highest evaluated dose (2000 μg). There have been no serious or grade III or higher adverse events. PK analysis suggested a dose‐dependent increase in GS‐3583 exposure with target‐mediated disposition characteristics at low doses. PD analysis shows that administration of GS‐3583 resulted in transient, dose‐dependent increases in cDC1 cells that returned to baseline within 3 weeks of drug administration. The pharmacokinetics and pharmacodynamics of GS‐3583 following single dosing were characterized in this study which enabled subsequent phase Ib assessments in patients with advanced solid tumors.
Oral cancer screening using cytopathology: An advanced proposal with the Bethesda classification
Authors: Lepper Tatiana Wannmacher , Ferreira Prigol Renata , Ferrares Espinosa Ana Laura , Guedes Igor Cavalcante , Maciel Rönnau Maikel , Daroit Natália Batista , Haas Alex Nogueira , Visioli Fernanda , Menezes de Oliveira Neto Manuel , Rados Pantelis Varvaki
Published: August 2024

Background

Oral cancer screening requires analysis capable of detecting changes preceding the clinical manifestation. Oral cytopathology studies as an oral cancer screening have shown promising results. This study aims to evaluate the use of cytopathology in a quali‐quantitative analysis using Papanicoloau staining.

Methods

Four experimental groups were evaluated: control (CG), exposed to carcinogens (EG), potentially malignant disorder with and without epithelial dysplasia (D‐OPMDG and ND‐OPMDG) and oral squamous cell carcinoma (OSCCG). Oral smears were collected using a Cytobrush® and conventional exfoliative cytology.

Results

Oral Papanicolaou smears from 143 individuals were analysed in 8100 images. Qualitatively, non‐lesional groups exhibited minimal suspected cases (20% in CG and 5% in EG), in the OPMD groups the ability to identify altered cells was low (40% in D‐OPMDG and 0% in ND‐OPMDG). Conversely, a notable 100% accuracy was achieved in the OSCCG. Quantitatively, a higher percentage of anucleated and a lower percentage of intermediate cells were observed in the OPMDG; a higher proportion of parabasal/suspicious cells was observed in OSCCG. The optimal threshold for improved accuracy in detecting suspected malignancies occurs when the count of parabasal/suspicious cells exceeds 8/100 cells examined. Cytomorphometric analysis revealed a higher nucleus/cytoplasm ratio (N/C) in OSCCG, with a best cutoff point indicating enhanced accuracy in discerning suspected malignancies when exceeding 17% of cells exhibiting this elevated ratio.

Conclusion

It is possible to suggest updates in cytomorphometric and quantitative analysis in the modified Bethesda system for the oral cavity including objective criteria in the risk classification, therefore improving oral cancer screening.
Exploring the therapeutic potential of topical probiotics in dermatological diseases: a comprehensive review of clinical studies
Authors: Tamer Funda , Kekilli Murat
Published: August 2024

The gastrointestinal tract may contribute to the regulation of systemic inflammation and skin diseases due to the balance between the pathogenic, opportunistic, and beneficial bacterial species it contains. External supplementation of beneficial bacteria, besides its known positive effect in the treatment of digestive system diseases, also has different favorable effects such as accelerated wound healing, suppression of inflammation, lower infection risk, and reduced antibiotic requirement. It has been reported that oral use of probiotics may be effective in the treatment of skin diseases such as acne, psoriasis, and atopic dermatitis. Furthermore, topical administration of probiotics may create a positive bacterial balance, eliminate pathological conditions, and thus have a favorable impact on the management of skin diseases. Interest in the effect of the skin microbiome and topical probiotics in the treatment of skin diseases has increased recently. Herein, 21 clinical studies and a case report in the PubMed database on the use of topical probiotics in dermatological diseases were evaluated.
Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta‐analysis of randomized controlled trials
Authors: Panuccio Giuseppe , Carabetta Nicole , Torella Daniele , De Rosa Salvatore
Published: August 2024

Introduction

Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA‐2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta‐analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS.

Methods

Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all‐cause mortality, stroke, major bleeding and angina severity.

Results

Nineteen RCTs involving 8616 patients were included. Median follow‐up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62–.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow‐up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005).

Conclusions

PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow‐up duration beyond 3 years.