bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of lipid senolytics targeting senescent cells through ferroptosis induction
Authors: Zhang Lei Justan , Salekeen Rahagir , Soto-Palma Carolina , Elsallabi Osama , Ye Hongping , Hughes Brian , Zhang Borui , Nunes Allancer , Lee Kyooa , Xu Wandi , Mohamed Abdalla , Piepgras Ellie , McGowan Sara J. , Angelini Luise , O’Kelly Ryan , Han Xianlin , Niedernhofer Laura J. , Robbins Paul D.
Published: October 2024

Cellular senescence is a key driver of the aging process and contributes to tissue dysfunction and age-related pathologies. Senolytics have emerged as a promising therapeutic intervention to extend healthspan and treat age-related diseases. Through a senescent cell-based phenotypic drug screen, we identified a class of conjugated polyunsaturated fatty acids, specifically α-eleostearic acid and its methyl ester derivative, as novel senolytics that effectively killed a broad range of senescent cells, reduced tissue senescence, and extended healthspan in mice. Importantly, these novel lipids induced senolysis through ferroptosis, rather than apoptosis or necrosis, by exploiting elevated iron, cytosolic PUFAs and ROS levels in senescent cells. Mechanistic studies and computational analyses further revealed their key targets in the ferroptosis pathway, ACSL4, LPCAT3, and ALOX15, important for lipid-induced senolysis. This new class of ferroptosis-inducing lipid senolytics provides a novel approach to slow aging and treat age-related disease, targeting senescent cells that are primed for ferroptosis.
Generation of Antibody Libraries for Phage Display: Chimeric Rabbit/Human Fab Format
Authors: Peng Haiyong , Rader Christoph
Published: October 2024

Rabbit monoclonal antibodies are attractive reagents for research, and have also found use in diagnostic and therapeutic applications. This is owed to their high affinity and specificity, along with their ability to recognize epitopes conserved between mouse and human antigens. Phage display is a powerful method for the de novo generation, affinity maturation, and humanization of rabbit monoclonal antibodies from naive, immune, and synthetic antibody repertoires. Using phagemid family pComb3, a preferred phage display format is chimeric rabbit/human Fab, which consists of rabbit variable domains (VH, Vκ, and Vλ) fused to human constant domains. The human constant domains, CH1 of IgG1 and CL(Cκor Cλ), not only provide established purification and detection handles but also facilitate higher expression inEscherichia colicompared to the corresponding rabbit constant domains. Here, we describe the use of a pComb3 derivative, phagemid pC3C, for the generation of chimeric rabbit/human Fab libraries with randomly combined rabbit variable domains of high sequence diversity, starting from the preparation of total RNA from rabbit spleen and bone marrow. Depending on the complexity of the parental antibody repertoire, the protocol can be scaled for yielding a library size of 108–1011independent chimeric rabbit/human Fab clones. As such, it can be used, for instance, for the generation of either specialized immune or large naive rabbit antibody libraries.
Generation of Antibody Libraries for Phage Display: Preparation of ElectrocompetentE. coli
Authors: Peng Haiyong , Rader Christoph
Published: October 2024

The size of an antibody library, that is, the phage display-selectable diversity, is restricted mainly by its transformation into the host bacterial cells. Electroporation is the most efficient method for transformingEscherichia coliwith plasmids, including phagemids. Here, we describe the preparation of electrocompetentE. colifor the generation of phagemid-encoded antibody libraries encompassing 109–1011independent transformants. To become electrocompetent, the bacterial suspension has to have high resistance, i.e., low ionic strength, which is achieved by gradually and gently transferring bacteria grown to mid-log phase to 10% (v/v) glycerol in highly pure water. The electrocompetentE. colimust be F plasmid-harboring bacteria, referred to as F+or male, in order to express F pili and be susceptible to infection by filamentous phage during library generation. In addition, it is necessary to apply antibiotic (e.g., tetracycline) pressure to retain the F plasmid, as it tends to segregate from bacteria. This protocol also includes assays for analyzing the prepared electrocompetentE. colifor competency, and evaluating potential contamination with helper phage, phagemid and phagemid-derived filamentous phage, and lytic phage.
Cloning, Expression, and Purification of Phage Display-Selected Fab for Biophysical and Biological Studies
Authors: Cyr Matthew G. , Peng Haiyong , Rader Christoph
Published: October 2024

The antigen-binding fragment (Fab) is the ∼50-kDa monovalent arm of an antibody molecule. In the laboratory, the Fab can be produced via either enzymatic digestion or recombinant expression, and its use facilitates the accurate assessment of affinity and specificity of monoclonal antibodies. The high melting temperature of the Fab, together with its low tendency to aggregate and ready conversion to natural and nonnatural immunoglobulin (Ig) formats (without affecting antigen binding properties), have made it a preferred format for phage display, as well as a tool for accurate assessment of affinity, specificity, and developability of monoclonal antibodies. Here, we outline a strategy to clone, express, and purify human or chimeric nonhuman/human Fabs that have previously been selected by phage display. Fabs purified using this approach, which results in milligram amounts, enable a variety of downstream biophysical and biological assays that ultimately inform the success of phage display library generation and selection.
Small-amplitude synchronization in driven Potts models
Authors: Meibohm Jan , Esposito Massimiliano
Published: October 2024

We study driven q-state Potts models with thermodynamically consistent dynamics and global coupling. For a wide range of parameters, these models exhibit a dynamical phase transition from decoherent oscillations into a synchronized phase. Starting from a general microscopic dynamics for individual oscillators, we derive the normal form of the high-dimensional Hopf bifurcation that underlies the phase transition. The normal-form equations are exact in the thermodynamic limit and close to the bifurcation. Exploiting the symmetry of the model, we solve these equations and thus uncover the intricate stable synchronization patterns of driven Potts models, characterized by a rich phase diagram. Making use of thermodynamic consistency, we show that synchronization reduces dissipation in such a way that the most stable synchronized states dissipate the least entropy. Close to the phase transition, our findings condense into a linear dissipation-stability relation that connects entropy production with phase-space contraction, a stability measure. At finite system size, our findings suggest a minimum-dissipation principle for driven Potts models that holds arbitrarily far from equilibrium.

Published by the American Physical Society
2024
Development of hard X-ray photoelectron spectroscopy in liquid cells using optimized microfabricated silicon nitride membranes
Authors: Capone F. , Muntada O. , Ramírez J. C. , Esplandiu M. J. , Dedryvère R. , Grimaud A. , Lassalle-Kaiser B. , Céolin D. , Pérez-Murano F. , Rueff J.-P. , Fraxedas Jordi
Published: October 2024

We present first hard X-ray photoelectron spectroscopy (HAXPES) results of aqueous salt solutions and dispersions of gold nanoparticles in liquid cells equipped with specially designed microfabricated thin silicon nitride membranes, with thickness in the 15–25 nm range, mounted in a high-vacuum-compatible environment. The experiments have been performed at the HAXPES endstation of the GALAXIES beamline at the SOLEIL synchrotron radiation facility. The low-stress membranes are fabricated from 100 mm silicon wafers using standard lithography techniques. Platinum alignment marks are added to the chips hosting the membranes to facilitate the positioning of the X-ray beam on the membrane by detecting the corresponding photoemission lines. Two types of liquid cells have been used, a static one built on an Omicron-type sample holder with the liquid confined in the cell container, and a circulating liquid cell, in which the liquid can flow in order to mitigate the effects due to beam damage. We demonstrate that the membranes are mechanically robust and able to withstand 1 bar pressure difference between the liquid inside the cell and vacuum, and the intense synchrotron radiation beam during data acquisition. This opens up new opportunities for spectroscopic studies of liquids.
Polymorph sampling with coupling to extended variables: enhanced sampling of polymorph energy landscapes and free energy perturbation of polymorph ensembles
Authors: Chan Eric J. , Tuckerman Mark E.
Published: October 2024

A novel approach to computationally enhance the sampling of molecular crystal structures is proposed and tested. This method is based on the use of extended variables coupled to a Monte Carlo based crystal polymorph generator. Inspired by the established technique of quasi-random sampling of polymorphs using the rigid molecule constraint, this approach represents molecular clusters as extended variables within a thermal reservoir. Polymorph unit-cell variables are generated using pseudo-random sampling. Within this framework, a harmonic coupling between the extended variables and polymorph configurations is established. The extended variables remain fixed during the inner loop dedicated to polymorph sampling, enforcing a stepwise propagation of the extended variables to maintain system exploration. The final processing step results in a polymorph energy landscape, where the raw structures sampled to create the extended variable trajectory are re-optimized without the thermal coupling term. The foundational principles of this approach are described and its effectiveness using both a Metropolis Monte Carlo type algorithm and modifications that incorporate replica exchange is demonstrated. A comparison is provided with pseudo-random sampling of polymorphs for the molecule coumarin. The choice to test a design of this algorithm as relevant for enhanced sampling of crystal structures was due to the obvious relation between molecular structure variables and corresponding crystal polymorphs as representative of the inherent vapor to crystal transitions that exist in nature. Additionally, it is shown that the trajectories of extended variables can be harnessed to extract fluctuation properties that can lead to valuable insights. A novel thermodynamic variable is introduced: the free energy difference between ensembles of Z′ = 1 and Z′ = 2 crystal polymorphs.
Assessment of the exchange-hole dipole moment dispersion correction for the energy ranking stage of the seventh crystal structure prediction blind test
Authors: Mayo R. Alex , Price Alastair J. A. , Otero-de-la-Roza Alberto , Johnson Erin R.
Published: October 2024

The seventh blind test of crystal structure prediction (CSP) methods substantially increased the level of complexity of the target compounds relative to the previous tests organized by the Cambridge Crystallographic Data Centre. In this work, the performance of density-functional methods is assessed using numerical atomic orbitals and the exchange-hole dipole moment dispersion correction (XDM) for the energy-ranking phase of the seventh blind test. Overall, excellent performance was seen for the two rigid molecules (XXVII, XXVIII) and for the organic salt (XXXIII). However, for the agrochemical (XXXI) and pharmaceutical (XXXII) targets, the experimental polymorphs were ranked fairly high in energy amongst the provided candidate structures and inclusion of thermal free-energy corrections from the lattice vibrations was found to be essential for compound XXXI. Based on these results, it is proposed that the importance of vibrational free-energy corrections increases with the number of rotatable bonds.
Eyewitness memory for person, object and action information is mediated by interview environment and the presence or absence of rapport
Authors: Taylor Donna A. , J. Dando Coral
Published: October 2024

Purpose

Obtaining accurate and reliable information from witnesses and victims of crime is essential for guiding criminal investigations and for the successful prosecution of offenders and beyond. Here, the purpose of this study is to investigate the impact of prosocial rapport behaviours and retrieval environment on mock eyewitness memory with an emphasis on the qualitative nature of information recalled in terms of persons, actions, objects and surroundings.

Design/methodology/approach

One hundred participants from the general population took part in mock witness research using a 2 (Environment: face-to-face; virtual) × 2 (Rapport: present; absent) design. Participants individually viewed an event depicting a fight in a bar and were then interviewed 48 h later according to condition.

Findings

Rapport and environment variously emerged as impactful, resulting in significant improvements in correct recall of persons, actions and object information when rapport was present and in virtual environments (VEs) when communicating via avatars. In many instances, the benefits of rapport and environment were additive, but not always. Surroundings information remained consistent across all conditions. Erroneous recall was extremely susceptible to inflation in face-to-face interviews when rapport was absent, in some instances increasing by over 100%. However, virtual interview spaces appeared to dilute the negative effects on retrieval when rapport was absent.

Research limitations/implications

This study concurs with others who have argued that comfortable witnesses are “better” witnesses; however, understanding what “comfort” looks and feels like remains a challenge.

Practical implications

The results, alongside the findings of others, have implications for applied and social cognition and reveal avenues for future research centred on widening access to justice and professional interview training.

Originality/value

This study reveals that prosocial rapport behaviours and VEs significantly enhance the accuracy of eyewitness recall. The findings suggest that virtual interviews can mitigate errors in the absence of rapport, offering valuable insights for criminal investigators and legal professionals. This research is crucial for improving witness interviewing techniques, thereby aiding in the accurate prosecution of offenders and broadening access to justice. The paper is valuable for criminal investigators, legal professionals, forensic psychologists and researchers focused on improving the reliability of eyewitness testimonies and interview methodologies.
Research trends of halal tourism: a bibliometric analysis
Authors: Ratnasari Ririn Tri , Sari Novi Sekar , Ahmi Aidi , Ismail Shafinar
Published: October 2024

Purpose

The purpose of this study is to analyze studies on halal tourism in Scopus from 2010 to 2021 and reveal trends, impacts, the most influential articles and future research trends.

Design/methodology/approach

The study used data from Scopus in 2010 to 2021 with the topic of halal tourism and obtained 122 data publications. This study uses bibliometric analysis with Biblioshiny analysis tools.

Findings

Halal tourism attracts the attention of academics and practitioners. This study analyzed 122 publications from 2010 to 2021 in Scopus, showing an increase in author contributions of 39.1% per year, peaking in 2021. The most influential article was the work of Battour and Ismail (2016), which emphasized Islamic principles in halal tourism. Mohamed Battour is the lead author, with Indonesia and Malaysia as the leading countries. Future research trends include halal tourist motivation, marketing strategies, mobile applications and artificial intelligence in supporting halal tourism. Collaboration between halal destinations and other industries is also important.

Research limitations/implications

Database searches were only performed on Scopus, so publications not scanned here could not be analyzed. The search for data from this research is also only based on the title regarding halal tourism. Thus, another article that discusses halal tourism but does not have the word “halal tourism” in the title cannot be analyzed.

Originality/value

This research is different from previous research in that this study examines literature published in Scopus on the study of halal tourism from 2010 to 2021.
Financing mode decision of characteristic tourist town based on improved G1 and Z-number-TOPSIS: the Chinese case
Authors: Fang Lingmei
Published: October 2024

Purpose

The objective is to address financing challenges with an innovative technical approach and provide financial support to facilitate the sustainable development of characteristic tourist towns.

Design/methodology/approach

In this study, a novel decision model is proposed, which utilizes the CRITIC improved G1 weighting method to analyze financing factors and applies GRA to enhance the TOPSIS model under a Z-Number fuzzy environment. Finally, sensitivity analysis and comparative assessment were conducted to validate the findings and the model.

Findings

The findings indicate that equity financing is the optimal mode of financing for characteristic tourist towns, with bond financing serving as a viable alternative. Key factors influencing financing include economic benefit, social benefit and policy risk. Managers should carefully consider these factors when selecting financing methods in order to enhance efficiency and mitigate risks.

Originality/value

As a new business model and value creation method of cultural and tourism integration, the financing decision of a characteristic tourism town has always been the key to the overall promotion and operation. The research constructs a financing index system for characteristic tourism towns based on benefit and risk considerations, using the hot spring town in Anhui Province, China, as a case study to evaluate eight financing models.
Open innovation and internationalization of SMEs: a systematic literature review
Authors: TanTai Bingyan , Senik Zizah Che , Mat Isa Rosmah , Muhamad Nur Sa′adah
Published: October 2024

Purpose

Open innovation (OI) significantly impacts the internationalization of small- and medium-sized enterprises (SMEs) by connecting them with external resources and accelerating their innovation processes. This study aims to systematically evaluate and synthesize existing knowledge on the role of OI in the internationalization of SMEs.

Design/methodology/approach

Through a systematic literature review method, this study critically evaluates 35 articles published between 2003 and 2023, synthesizing existing research from theoretical, contextual, characteristic and methodological perspectives.

Findings

This study identifies theoretical, methodological, characteristics and contextual research gaps and further proposes a research agenda for expanding knowledge in the field. Additionally, it provides an overview of the antecedents of OI adoption, SMEs internationalization outcomes and the influencing mechanisms of OI on SMEs internationalization found in the literature, thereby establishing a foundational knowledge base for future scholars and practitioners in this field.

Originality/value

This review contributes to the existing literature by consolidating current knowledge on the topic and advancing the understanding of the intersection between OI and the internationalization of SMEs.
The role of religious and financial factors in eudaimonic well-being among Indian adults
Authors: Padma Sri Lekha P. , Abdul Azeez E.P. , Sharma Jyoti , John Nijumon K.
Published: October 2024

Purpose

The available literature has explored the various psychosocial determinants of well-being to some extent. The earlier works have focused primarily on hedonic well-being with little focus on eudaimonic aspects. Therefore, this study aims to understand the role of parent–child religious attendance during childhood, religious connectedness, and financial-material stability on eudaimonic well-being among adults in India.

Design/methodology/approach

The authors used the India data from Global Flourishing Study – Wave 1 that addressed flourishing among adults above 18 years. The authors considered 9,076 Indian adults and used descriptive and correlation statistics. In addition, the authors conducted path analysis and t-test.

Findings

The likelihood of eudaimonic well-being increased with parent–child religious attendance during childhood (ß = −0.044, p < 0.01) along with religious connectedness (ß = −0.112, p < 0.01) and financial-material stability (ß = 0.145, p < 0.01) as an adult. In addition, a significant difference existed in terms of religious connectedness and eudaimonic well-being with income and perceived feelings about income.

Originality/value

This study emphasizes financial stability’s relevance in well-being and suggests the importance of considering religious factors during childhood and adulthood. Emphasizing factors influencing eudaimonic well-being is relevant due to its influence on mental health and quality of life.
Research on the origin and evolution of technical management regulations for railway
Authors: Tian Lei , Sun Yuming , Jia Yonggang
Published: October 2024

Purpose

To facilitate technical managers and field workers to master and understand the provisions of Technical Management Regulations for Railway more accurately, so as to better serve the comprehensive revision of the Regulations, this paper carries out the research on the traceability and evolution of the provisions of the Regulations.

Design/methodology/approach

This paper studies and analyzes the evolution of the 11th edition of the Regulations by analyzing the relevance of clauses and summarizes the historical background of the development of calendar editions of the Regulations. The basic research on the traceability and evolution of the Regulations is carried out from four aspects: the continuity of the development of the Regulations, the authority of contents, the relevance of clauses and the richness of historical materials.

Findings

From the first edition of the Regulations issued by the former Ministry of Railways in 1950 to the 11th edition, there have been ten comprehensive revisions. There is a strong correlation and continuity between the calendar editions of the Regulations in terms of chapter structure and clauses. Studying the context of the terms of the Regulations is an important way to understand and master the current clauses of the Regulations.

Originality/value

Through the research on the traceability and evolution of the clauses of the Regulations, one is to explore the context of the development of railway technical equipment in China, the other is to clarify the historical background when the provisions were formulated and the third is to trace the development and evolution of the provisions. The revision of the Regulations is based on an accurate grasp of the context of the provisions, which can effectively judge the possible security risks caused by the revision of the provisions and avoid the possible risks in field implementation from the source.
Hybridity as a governmental technique for designing and delivering NAPLAN in Australian schools
Authors: Savage Glenn C. , de Carvalho David
Published: October 2024

This paper explores the utility of hybrid governance as an analytical lens for understanding policy design and delivery in Australian schooling reform. Using the National Assessment Program in Literacy and Numeracy (NAPLAN) as a case study, we argue that its design and delivery processes exemplify hybridity in myriad dimensions. In a federal system in which national schooling reform relies upon negotiation and consensus building amongst a multiplicity of government and non‐government stakeholders, we argue that NAPLAN's hybridity serves as a governmental technique for managing and sustaining collaborative governance arrangements. Hybridity also supports the standardised implementation of the assessment across diverse schooling systems and sectors. While NAPLAN's hybridity generates strategic benefits for Australian governments, it also produces risks. A challenge for policymakers is to harness its benefits while ensuring transparent decision‐making and clear responsibilities and accountabilities. To address risks and leverage opportunities, we argue there are benefits to having a convening agency with authority to manage and sustain hybrid networks at the national scale.

Points for practitioners

Hybrid governance offers productive insights into how Australian governments work collaboratively to design and deliver national schooling reforms.

The National Assessment Program in Literacy and Numeracy (NAPLAN) is an exemplary case study for examining hybrid governance in the Australian federation.

Hybrid governance serves as a technique for managing and sustaining collaborative governance arrangements at the national scale and for ensuring NAPLAN's implementation is standardised across Australia's diverse subnational schooling systems and sectors.

Hybridity creates risks and opportunities. A challenge for policymakers is to harness its benefits while ensuring transparent decision‐making and clear responsibilities and accountabilities.

There are benefits to having a convening agency with authority to manage and sustain hybrid networks at the national scale.
Thoughts on the Etyma for ‘Corpse’ in Gyalrongic Languages*
Authors: Lai Yunfan
Published: October 2024

This paper studies the four distinct native terms for ‘corpse’ attested in Gyalrongic languages. Through comparative analysis, it establishes the sound correspondences among cognates and proposes preliminary reconstructions. In a second step, it hypothesises on the origins of the etyma by examining potential cognates in other Sino‐Tibetan languages. Two shared innovations can be found in the etyma for ‘corpse’. First, the Situ form *m‐g[á]m is an innovated compound meaning ‘a person that is killed’; and second, the etymon *rə̆.quʶ is a shared innovation of Horpa and Tangut. By analysing the etymologies above, this paper aims to enhance our understanding of sound correspondences and changes within the Sino‐Tibetan language family. Furthermore, it seeks to demonstrate the crucial role that etymological studies play in historical linguistics and language subgrouping. Despite their importance, such studies have not yet received sufficient attention from scholars specialising in Sino‐Tibetan languages.
Diet acts on sexual behavior development in a male moth
Authors: Force Evan , Suray Caroline , Monsempes Christelle , Danis Chloé , Bonfils Gabrielle , Debernard Stéphane , Dacher Matthieu
Published: October 2024

In many animals, drastic changes are observed during sexual maturation characterized by the reproductive system development concomitantly to the sexual behavior ontogenesis. These modifications are under the control of internal and external factors such as food. Sexual maturation requires considerable energetic investment, and diet has been shown to affect reproductive activities in many taxonomic groups, especially in insects and vertebrates. By contrast, diet effects on sexual behavior development remain largely unexplored. To elucidate this aspect, we used the male moth Agrotis ipsilon which undergoes sexual maturation occurring between the third and the fifth day postemergence. During this period, males are sensitive to female sex pheromones and a stereotypical sexual behavior characterized by female‐oriented flight takes place. In our study, we compared (1) sex pheromone detection by electroantennography recordings and (2) behavioral response in wind tunnel assays between males fed with different diets found in nature. Compared to standard sucrose diet, males fed with sucrose, fructose, and glucose supplemented with sodium (a mineral element necessary for the locomotor activity in several moths) did not respond better to female sex pheromones but clearly exhibited an earlier behavioral response. Thus, such a diet accelerates the development of sex pheromone‐mediated oriented flight, probably by facilitating the central processing of sex pheromone information in male A. ipsilon moths. Our results provide new information on the influence of nutritional intake on the ontogenesis of male sexual behavior in animals.
Review article: Measuring disease severity in inflammatory bowel disease – Beyond treat to target
Authors: Swaminathan Akhilesh , Day Andrew S. , Sparrow Miles P. , Peyrin‐Biroulet Laurent , Siegel Corey A. , Gearry Richard B.
Published: October 2024

Background

Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this.

Methods

To perform this narrative review, a Medline search was conducted for full‐text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD.

Results

Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality‐of‐life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient.

Conclusions

Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.
Review article: Novel therapies in inflammatory bowel disease – An update for clinicians
Authors: Noor Nurulamin M. , Bourke Aoibh , Subramanian Sreedhar
Published: October 2024

Background

Several new treatments including small molecules and biologics have been approved for the treatment of inflammatory bowel diseases in recent years. Clinicians and patients now have a wide variety of therapeutic options to choose from and these novel therapies provide several advantages including oral administration, lower immunogenicity, better selectivity and arguably better safety profiles. An increase in treatment options has increased the complexity of decision‐making. Both patients and clinicians have had to become rapidly familiar with efficacy of new medications balanced against a range of pre‐initiation requirements, dosing schedules and adverse event profiles.

Aims

To provide a simple guide to practising clinicians on recently approved and emerging therapies and address key challenges around treatment strategies such as optimal sequencing and timing of treatment.

Methods

We comprehensively searched the published literature and major conference abstracts to identify phase III placebo‐controlled and active comparator trials for Crohn's disease and ulcerative colitis.

Results

Data for recently approved therapies including selective Janus kinase inhibitors, sphingosine‐1 receptor modulators and p19 interleukin (IL)‐23 inhibitors have demonstrated improved patient outcomes in both Crohn's disease and ulcerative colitis. Further comparative head‐to‐head studies have improved our understanding of when and how to optimally use newer therapies, specifically for IL‐23 inhibitors. Data for emerging treatment options and novel treatment strategies such as early effective treatment, combinations of treatments and implications for sequencing are continuing to transform IBD care continually.

Conclusions

Recently approved novel therapies have expanded the range of medical options available to treat IBD. However, further data from long‐term extension studies, real‐world studies and head‐to‐head trials are warranted to better inform the long‐term safety and optimal sequencing of treatments for patients living with IBD.
Beyond the First Child: Unveiling the Reasons Behind Stopping Childbearing in Iran
Authors: Sadeghi‐Dinani Naeemeh , Moeeni Maryam , Amini‐Rarani Mostafa
Published: October 2024

Background

The determinants of the intention to stop childbearing tend to differ over time and contexts. This allows the issue of families' childbearing intentions to continually remain on the research agenda. As societal context and temporal variability will matter for second childbearing intentions, this study aimed at uncovering the reasons behind the intentions to stop childbearing from one‐child mothers' perspective.

Method

A qualitative descriptive study in Isfahan City, Iran, was used to scrutinize reasons behind the unwillingness to have a second pregnancy. A purposeful sampling with maximum variation was used to select one‐child mothers. Until reaching saturation, 48 semistructured interviews were conducted. A thematic analysis was used to analyse the qualitative data.

Results

Five themes and 19 subthemes emerged from the data analysis as structural attributes (economic, social and political conditions), parental attributes (parental (dis)agreements, childrearing troubles, having impatience and being at the inappropriate age for childbearing), husband attributes (having the intention to stop parenting, financially and emotionally nonsupportive and being busy by working), maternal attributes (health‐related problems, adverse experience during former pregnancy, being employed, self‐compassion, the fear of parity progression and being pessimistic) and child attributes (having a naughty child and having the physical or mental distress of the first child).

Conclusion

Overall, findings highlight the multifaceted nature of factors influencing second childbearing intentions. Structural reasons at macro level, intrafamily relationship, mothers' self‐related factors and challenges of raising the first child all play distinct roles in discouraging mothers from a second child intention. Understanding these key reasons can help policymakers, researchers and individuals alike to comprehend the complexities involved in family planning and fertility decisions.
Improving theories of change in conservation projects
Authors: Leisher Craig , Bugan Richard , Ngo Sarah
Published: October 2024

Theory of change has become a common tool in project design because it helps teams agree on hypothesized causal pathways to a desired goal and examine their underlying assumptions. Yet, a consensus has not emerged on the specific steps and components of a theory of change. What constitutes a theory of change? Using 22 theory of change publications, we did a structured analysis of the components of a theory of change. Where there was substantial agreement among the publications on a specific component of a theory of change, we included it in the first iteration of our approach. We then ordered the components in a logical sequence, developed guidance for each component, tested them with project teams, and revised them in an iterative process. We tested and refined our guidance over 3 years with 73 teams from 18 countries. Here, we share our learning and recommendations for those interested in developing a robust theory of change for a conservation project.
Real‐world evidence of intervention effectiveness for implementation in low‐resource settings
Authors: Asige Elizabeth , Saloojee Gillian , Andrews Carin , Namaganda Lukia H. , Kakooza‐Mwesige Angelina , Damiano Diane L. , Forssberg Hans
Published: October 2024

This letter to the editor is on the commentary by Olusanya on pages 10–11 of this issue.
Assessing Left Atrial Appendage Functions by Transesophageal Echocardiography and Speckle Tracking Imaging to Predict Recurring Atrial Fibrillation Post‐Radiofrequency Catheter Ablation
Authors: Hao Xinyu , Li Wei , Zhang Qunying , Cao Le , Wang Jinshu , Guo Ling , Zhang Qiang
Published: October 2024

Objective

To predict recurring atrial fibrillation (AF) following radiofrequency catheter ablation by assessing the attributes of the left atrium and the left atrial (LA) appendage (LAA) using transesophageal echocardiography (TEE) and speckle tracking imaging.

Methods

The structural and functional indices of the LA and LAA of 80 patients with AF who underwent preoperative transthoracic echocardiography and TEE were measured. Recurrence was recorded postoperatively at 3, 6, and 12 months. The independent determinants of recurring AF were identified by logistic regression, and their optimum cutoff values, sensitivity, and specificity were estimated from the receiver operating characteristic (ROC) curves.

Results

The recurrent and nonrecurrent groups comprised 17 and 63 patients, respectively. The LA internal diameter, LA end‐diastolic and end‐systolic volumes, LAA length, diameter and area of the opening of the LAA, and LAA end‐diastolic volume were higher in the recurrent group. The LA strain in the reservoir phase, the ejection fraction and filling velocity of the LAA, the LAA emptying velocity (LAAeV), and the LAA strain (LAAS) reduced considerably. Multifactorial regression analyses demonstrated that the LAAeV and LAAS were independent determinants of recurring AF. ROC curve analysis revealed that the LAAeV and LAAS predicted postoperative recurrence at 34.5 cm/s (area under the curve [AUC]: 0.954, sensitivity: 94.1%, and specificity: 92.1%) and 11.61% (AUC: 0.925, sensitivity: 82.4%, and specificity: 95.2%), respectively, while the AUC, sensitivity, and specificity of the combined predictors (LAAeV + LAAS) were 0.978, 94.1%, and 93.7%, respectively.

Conclusion

The LAAeV and LAAS independently influenced the postoperative recurrence of AF.
Intensity dependence of auditory evoked potentials distinguish participants with unmedicated depression from non‐depressed controls
Authors: Kangas Elina S. , Li Xueqiao , Vuoriainen Elisa , Lindeman Sari , Astikainen Piia
Published: October 2024

Depression is a heterogeneous syndrome that impacts an individual's emotional, social, cognitive and bodily functioning. Depression is associated with biases in emotional processing, but alterations in basic sensory processing have received less attention in depression research. Here, we measured event‐related potentials (ERPs) in response to changes in the intensity of auditory stimuli and the location of somatosensory stimuli in participants with depression and in non‐depressed control participants. We tested whether auditory mismatch negativity, P3a or N1 intensity dependence response or somatosensory mismatch response, P3a, P50 or N80 can dissociate depressed participants and non‐depressed controls, and we also analysed the effects of depression medication and age in this sample. N1 intensity dependence response was increased in unmedicated depressed participants relative to non‐depressed controls. When age was controlled for in the analysis, the effect of depression was only at a trend level. N1 intensity dependence response correlated with depression severity at the whole sample level. We did not observe any depression‐related alterations in auditory mismatch negativity or P3a or somatosensory ERPs. Our results may reflect an association between the N1 intensity dependence response and altered neurotransmitter activity in depression, but this should be confirmed in future studies.
Low field magnetic resonance imaging of palmar osteochondral fragmentation of the distal phalanx
Authors: Drumond B. , Schramme M. , Thomas‐Cancian A. , Ségard‐Weisse E.
Published: October 2024

Background

The presence of palmar osteochondral fragments of the distal phalanx is a newly recognised cause of foot lameness with only a few cases having been reported.

Objectives

To describe the low field magnetic resonance imaging (MRI) appearance of palmar articular fragmentation of the distal phalanx and concurrent abnormalities of the distal interphalangeal joint (DIPJ); to investigate the prevalence of these fragments in a population of sports and pleasure horses and their potential clinical significance.

Study design

Retrospective descriptive case series.

Methods

This is a retrospective descriptive case series in which all Sports and Pleasure horses undergoing standing low‐field MRI of the feet between 2015 and 2023 were reviewed. Appearance, location and number of palmar articular fragments were recorded. When a palmar fragment was present, abnormal findings of the DIPJ were graded.

Results

A total of 855 horses underwent MRI examination of one or both front feet. Palmar osteochondral fragmentation of the distal phalanx was identified in four horses (0.4% prevalence), three Lusitanos and one Warmblood. The age range was 4–17 years old. All fragments were located along the palmarolateral margin of the glenoid of the distal phalanx in front feet. Concurrent imaging abnormalities of the joint were present in all four horses.

Main limitations

Lack of histopathology.

Conclusions

The prevalence of palmar articular fragments of the distal phalanx was low in this population of horses. Palmar osteochondral fragmentation must be considered when evaluating lameness localised to the foot, since it was identified only in lame limbs and associated with other imaging abnormalities of the DIPJ.
Medication of the cervical spinal nerves for the treatment of equine cervical radiculopathy
Authors: Wood A. D. , Sinovich M. , Parker R. A.
Published: October 2024

Background

Several perineural injection techniques have been described to medicate the cervical spinal nerves of horses with suspected radiculopathy due to lesions at the intervertebral foramen (IVF). The technique and outcome have never been described in live, standing horses with suspected clinical disease.

Objectives

To assess the safety and efficacy of medication of the ventral rami of the cervical spinal nerves (VRCSNs) for the treatment of cervical radiculopathy in horses.

Study design

Case series.

Methods

Horses that underwent ultrasound‐guided perineural injection of the VRCSNs following radiographic and/or computed tomography (CT) evaluation of the cervical spine were included. Perineural injection with corticosteroids was performed using a standardised technique under ultrasound guidance as previously described. Outcome data were collected by clinical record review and unstructured follow‐up telephone conversations.

Results

Forty‐seven injections of the VRCSNs were performed in 12 horses with only two self‐limiting adverse reactions noted. All horses that underwent CT examination had at least one site of IVF narrowing with the foramina at the C6/C7 articulation most frequently affected. Nine horses improved following medication of the VRCSNs with eight returning to their previous levels of exercise. All seven horses that underwent CT of the cervical spine had an initial improvement in clinical signs. Six horses were in full work and still performing at their intended level of exercise at a median of 21.5 months post injection.

Main limitations

Lack of definitive diagnosis of spinal nerve compression without histopathology of the spinal nerves which is not possible in the live horse.

Conclusions

Medication of the VRCSNs is a safe treatment option which may provide benefit to horses with suspected spinal nerve compression but should be reserved for horses that have undergone a detailed clinical examination and CT evaluation of the cervical spine.
Study protocol of the safe driving program for the prevention of car accidents: A randomized controlled trial protocol
Authors: Shimada Hiroyuki , Ishii Hideaki , Doi Takehiko , Tsutsumimoto Kota , Nakakubo Sho , Kurita Satoshi , Arai Hidenori
Published: October 2024

Aim

Driving cessation is strongly associated with adverse health outcomes in older adults. Although numerous studies have focused on driving skill interventions for safe driving, the effects of interventions on car accidents remain unclear. We designed a randomized controlled trial to examine the effects of driving skill training on the prevention of car accidents among community‐dwelling older adults using on‐road training.

Methods

A total of 1408 community‐dwelling older drivers aged ≥65 years participated in the randomized controlled trial with blinded endpoint assessment. Participants randomized to the intervention group (n = 697) underwent four sessions, with 200 min re‐training focused on the problem of driving in the older people. Controls (n = 697) received one classroom education session. On‐road driving performance was assessed by certified driving school instructors in a driving school. The primary endpoint is an incident car accident, which will be detected based on the Japanese national car accident report data, after 24 months.

Discussion

This study has the potential to provide the first evidence of the effectiveness of on‐road driving skill training regarding the prevention of car accidents. If our trial results show a lower number of car accidents due to driving skill training, this kind of intervention will provide an effective method for maintaining safe driving. These results will be disseminated to the appropriate national transportation agencies to improve or modify safe driving policies and possibly extend the validity of driver's licenses for older adults.

Trial Registration

UMIN‐CTR (identification number: UMIN000034709). Registered 31 October 2018. Geriatr Gerontol Int 2024; 24: 1218–1222.
Accuracy of the LaserSAFE technique for detecting positive surgical margins during robot‐assisted radical prostatectomy: blind assessment and inter‐rater agreement analysis
Authors: Almeida‐Magana Ricardo , Au Matthew , Al‐Hammouri Tarek , Mathew Manju , Dinneen Kate , Mendes Larissa S T , Dinneen Eoin , Vreuls Willem , Shaw Greg , Freeman Alex , Haider Aiman
Published: October 2024

Introduction and objectives

Fluorescence confocal microscopy (FCM) is a new imaging modality capable of generating digital microscopic resolution scans of fresh surgical specimens, and holds potential as an alternative to frozen section (FS) analysis for intra‐operative assessment of surgical margins. Previously, we described the LaserSAFE technique as an application of FCM for margin assessment in robot‐assisted radical prostatectomy (RARP) using the Histolog® scanner. This study describes the accuracy and inter‐rater agreement of FCM imaging compared to corresponding paraffin‐embedded analysis (PA) among four blinded pathologists for the presence of positive surgical margins (PSM).

Materials and methods

RARP specimens from patients enrolled in the control arm of the NeuroSAFE PROOF study (NCT03317990) were analysed from April 2022 to February 2023. Prostate specimens were imaged using the Histolog® scanner before formalin fixation and PA. Four trained assessors, blinded to PA, reviewed and analysed FCM images of the posterolateral prostatic surface.

Results

A total of 31 prostate specimens were included in the study. PA per lateral side of the prostate identified 11 instances of positive margins. Among the four histopathologists included in our study, FCM achieved a sensitivity of 73–91 and specificity of 94–100% for the presence of PSM. Fleiss’ Kappa for inter‐rater agreement on PSM was 0.78 (95% confidence interval = 0.64–0.92), indicating substantial agreement.

Conclusion

This blinded analysis of FCM versus PA among histopathologists with different experience levels demonstrated high accuracy and substantial inter‐rater agreement for diagnosing PSM. This supports the role of the FCM as an alternative to FS.