bluuebunny/crossref_metadata_2025 huggingface dataset:
New Approaches
Authors: Hamilton Alastair
Published: October 2023

Eliano’s was the last Jesuit mission to the Copts for some time to come. Other missions continued, however, and in the final decade of the sixteenth century it seemed that the Coptic patriarch Gabriel VIII had agreed to union with the pope, Clement VIII, and that the ambitions of so many pontiffs had at last been fulfilled.1 In March 1592 the pope dispatched Giovanni Battista Vecchietti, a man with a considerable knowledge and experience of the East. He was to approach the patriarch and two other dignitaries, and arrange for a legation to be sent to Rome.
Confessional Clashes I
Authors: Hamilton Alastair
Published: October 2023

While the Roman Catholic Church combined a condemnatory attitude with increasing overtures to the Eastern Christians, the Protestants were gradually developing an approach of their own. The Lutherans had been glancing longingly at the Levant ever since Luther, in his disputation with Johann von Eck of 1519, had expressed his admiration for the Church of Constantinople, far closer to the primitive Church than the Church of Rome.1 Subsequently Lutherans were also prepared to take an interest in the other Eastern Churches. An early sign of this was the appearance in Wittenberg in 1575 of the Oratio de statu ecclesiarum hoc tempore in Graecia, Asia, Bo¨emia etc. The author, the Swabian David Chytraeus, a follower and friend of Melanchthon, was one of the most esteemed (and most orthodox) Lutheran theologians and historians in Germany.
Introduction
Authors: Cayley Emma
Published: October 2023

In this extract, three ‘ladies ’ of the court apparently challenge Alain Chartier to defend himself and his poem La Belle Dame sans mercy (1424) at a judicial hearing in the face of growing unrest at the ‘court amoureuse ’. Chartier ’s only recorded ‘responce affinee ’ to the allegations supposedly made against him and his poem comes in written form: a debate between himself as acteur and the Dieu d‘Amours, framed as a dream sequence: L ’Excusacion aux dames.
The Defendant’ s Conduct: Intent, Negligence, Strict Liability
Authors: Gordley James
Published: October 2023

As we have seen, civil law systems have generally recognized three bases for liability in tort: intent, negligence and strict liability, although civil law jurists have often been at a loss to explain the last of these, and it was omitted by the drafters of the French and German Civil Codes. We have also seen how the common lawyers borrowed this structure from the civil law although they failed to purge it of remnants of their traditional system of writs. We will now consider why liability should be imposed on these three grounds.. According to Aristotle, one type of commutative justice is observed in transactions that are involuntary, and another in transactions that are voluntary. Involuntary transactions include those which are ‘ clandestine, such as theft, adultery, poisoning, procuring, enticement of slaves, assassination, false witness’ and others which are ‘ violent, such as assault, imprisonment, murder, robbery with violence, mutilation, abuse, insu1t’.
Promises to Make a Gift
Authors: Gordley James
Published: October 2023

In the Nicomachean Ethics, Aristotle described exchange as a type of commutative justice. While distributive justice secures for each citizen a fair share of whatever wealth and honor the society had to divide, commutative justice preserves the share he has. Thus, according to Aristotle, each party to an exchange must give something equivalent in value to what he receives. As described earlier, in another passage in the Ethics, Aristotle discussed the virtue of ‘ liberality’ : the liberal person disposes of his money wisely, giving ‘ to the right people the right amounts and at the right time’. Thomas Aquinas put these ideas together: when one person transfers a thing to another, either it is an act of commutative justice that requires an equivalent or it is an act of liberality. As already mentioned, the late scholastics built a theory of contract on this ground plan that was then borrowed by the northern natural law school in the 17th century. According to the theory, a party, by expressing his will to be bound, might enter into either of these two basic types of arrangement. Grotius and Pufendorf present elaborate schemes of classification in which they show how the contracts familiar in Roman law can be fitted into these two grand categories. This classification meant more than the tautology that a party either does or does not receive back something in return for what he gives. In a gratuitous contract, the donor ideally is exercising the virtue of liberality. He is giving away wealth in a sensible way. In a contract of exchange, a party must receive, not simply a counterperformance, but one of equivalent value. Writers in the Aristotelian traditions thought that the rules that govern the parties’ obligations should depend on which sort of agreement they had entered into. The rules should ensure, so far as practicable, that in the case of an exchange, each party receives an equivalent, and in the case of a gratuitous contract, that the donor behaves sensibly.
Lady Jane: Torture, Gender, and the Reinvention of the Tudors
Authors: Melman Billie
Published: October 2023

During the second half of the nineteenth century several miniature racks with miniature women stretched on them were made for display in the Tower. A surviving photograph of one of these exhibits, taken by Benjamin Stone in 1898, shows what appears like a doll, in a shirt-gown that reveals the legs from beneath the knees, so that the legs, tied to rollers, are clearly shown (see Fig. 6). In point of fact there had been only one recorded racking of a woman in the Tower, that of the poet and radical Protestant Anne Askew (1521–46), known mainly for her posthumous Examinations, the record of her interrogations. Incarcerated in the Tower, where she was tortured by Sir Richard Rich and Lord Chancellor Thomas Wriothesly, and burnt at Smithfield on 16 July 1546, the ‘heretical’ Askew instantaneously became a martyr.
The Revolution, Aristocrats, and the People: The Returns of the Scarlet Pimpernel, 1900–1935
Authors: Melman Billie
Published: October 2023

The development of popular histories of the monarchy as histories for a mass democracy corresponds to a class shift in the subject matter of the culture of history. The decades which saw the making of Elizabeth and the Elizabethans into modernized icons of imperial power, popular consent, and freedoms also witnessed the construction, in mass-produced histories, of the traditional landed elite as an agent of change and modernity. This shift of class emphasis and agency is typical of the third revival of interest in the French Revolution, which occurred a little after, but roughly coincided with, the discovery of the Elizabethans in the late nineteenth century and the early twentieth century.
Lawfully Audacious: A Reflective Journey
Authors: Grieve John GD
Published: October 2023

This chapter provides an account of my journey as a police officer, who had the privilege of contributing towards the development of intelligence-led policing, and particularly the exploitation of intelligence for detectives. As Howard Vincent noted in the nineteenth century, ‘every good officer will do his (sic) best to obtain reliable intelligence’ (Vincent, 1881: 202) and this remains true in the twenty-first-century where intelligence is required for an ever increasing range of activities from counterterrorism to neighbourhood policing. What follows is a contribution to an account of police intelligence as ‘fragmentary; the pieces have yet to be put together, and the full jigsaw puzzle revealed.’ (Porter, 2000: 13).
1620–1629
Authors: Randall Dale B J , Boswell Jackson C
Published: October 2023

This is the second edition of Thomas Shelton’s translation of Don Quixote, pt. 1. In the introductory matter of the first edition (1612), Shelton had complained that the printer issued the text of the book in an uncorrected state, despite Shelton’s admonitions. Now in 1620 (some scholars argue for 1617), approximately eight years had elapsed, and someone, apparently not Shelton himself, had made a good many emendations.
1640–1649
Authors: Randall Dale B J , Boswell Jackson C
Published: October 2023

James Mabbe (1572–1642?), the translator of several Spanish volumes, honed his language skills while serving as secretary to Sir John Digby in Madrid (1611– 13), when Digby, on behalf of King James, was trying to negotiate a marriage of, first, Prince Henry and then Prince Charles to the Spanish infanta. For this volume of Exemplarie Novells Mabbe chose to translate six of the twelve novelas in Cervantes’s Novelas ejemplares (1613).
Dynamic Battles
Authors: Konrad Kai A
Published: October 2023

In a contest, a group of players expend efforts up-front, trying to win some prize. The process by which the efforts translate into success probabilities is often considered a black box, and much of the analysis in previous chapters follows this spirit. However, if one looks at contest games with some high-resolution spectacles, they often reveal a finer substructure and can be decomposed into a number of smaller battles or component contests, with the overall outcome generally being a function of the outcomes in these component contests.
Surgical waitlist management: Perspectives from surgeons on surgical prioritization at a paediatric hospital
Authors: Wiebe Kayla , Kelley Simon , Fecteau Annie , Levine Mark , Blajchman Iram , Shaul Randi Zlotnik , Kirsch Roxanne
Published: October 2023

Globally exacerbated surgical waitlists have provided the opportunity to reflect on prioritization and resource allocation decisions. The unique circumstances of paediatric surgery and consequences of surgical delay prompted the study reported in this paper. As part of a larger project to attend to prioritization in our surgical waitlists, we conducted a Quality Improvement study, the purpose of which is to understand surgeon’s perspectives regarding the ethical and practical realities of surgical prioritization at our institution. The study comprises semi-structured interviews with nine full-time paediatric surgeons from a variety of subspecialties conducted at our institution, which is a tertiary paediatric hospital with ten surgical subspecialties in a publicly funded healthcare system. Participants articulated how they prioritize their waitlists, and how they understand ethical prioritization. These findings resonate with the growing public concern for ethical practice in healthcare delivery and transparency in prioritization and resource allocation practices. Specifically, more transparency, consistency, and support is required in prioritization practices. This work highlights the importance of institutional dialogue regarding surgical case prioritization. Because quality improvement work is necessarily site-specific, concrete generalizations cannot be offered. However, the insights gleaned from these interviews and the process by which they were gleaned are a valuable knowledge-sharing resource for any institution that is interested in ongoing quality improvement work. The objectives here were to clarify the goals of prioritization within the institution, improve prioritization practices, and make them more ethical and transparent.
An Atypical Calf Cyst treated with Doxycycline Sclerotherapy: A Case Report
Authors: Hassid Brandon V. , Davis Brian A.
Published: October 2023

There are many types of cysts in the leg; the most common is a popliteal (Baker’s) cyst. This occurs when synovial fluid fills the tissue plane between the medial head of the gastrocnemius and the semimembranosus muscle and is often associated with intraarticular knee pathology. Treatment for various types of cysts includes aspiration with or without fenestration, injections with corticosteroids, dextrose, or various sclerosing agents, and surgical excision. This case describes a 58-year-old man with a large cyst measuring 14.7x2.7x3.1 cm in size in the lateral calf, within the lateral gastrocnemius, with atypical size and location for a calf cyst. CT arthrogram showed intraarticular communication with the knee. The cyst recurred after two aspirations and injections with 25% dextrose/lidocaine. Aspiration and injection with doxycycline resulted in temporary relief followed by recurrence. Complete cyst resolution occurred after final aspiration without injectate. The cyst was likely synovial based on location, intraarticular communication, and fluid analysis. We suspect that complete resolution may have been due to repeated aspiration and injection, essentially performing longitudinal cyst fenestration, with possible contribution from doxycycline injection. Further study of intra-cyst doxycycline injection with re-aspiration after 10 minutes for treatment of refractory cysts may be warranted.
Identification of a specific APOE transcript and functional elements associated with Alzheimer’s disease
Authors: Chen Qiang , Aguirre Luis , Zhao Huanhuan , Borrego Felix , de Rojas Itziar , Su Lingyan , Li Pan P. , Zhang Bao , Kokovay Erzsebet , Lechleiter James D , Göring Harald H. , De Jager Philip L. , Kleinman Joel E. , Hyde Thomas M. , Ruiz Agustín , Weinberger Daniel R. , Seshadri Sudha , Ma Liang
Published: October 2023

INTRODUCTION

The APOE gene is the strongest genetic risk factor for late-onset Alzheimer’s Disease (LOAD). However, the gene regulatory mechanisms at this locus have not been fully characterized.

METHODS

To identify novel AD-linked functional elements within theAPOElocus, we integrated SNP variants with RNA-seq, DNA methylation, and ChIP-seq data from human postmortem brains.

RESULTS

We identified an AD-linkedAPOEtranscript (jxn1.2.2) observed in the dorsolateral prefrontal cortex (DLPFC). TheAPOEjxn1.2.2 transcript is associated with brain neuropathological features in DLPFC. We prioritized an independent functional SNP, rs157580, significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. rs157580 is located within active chromatin regions and predicted to affect brain-related transcriptional factors binding affinity. rs157580 shared the effects on the jxn1.2.2 transcript between European and African ethnic groups.

DISCUSSION

The novelAPOEfunctional elements provide potential therapeutic targets with mechanistic insight into the disease’s etiology.
Crowdsourcing strategies to improve access to HIV pre-exposure prophylaxis (PrEP) in Australia, the Philippines, and China
Authors: Tieosapjaroen Warittha , Ongkeko Arturo M. , Yin Zhuoheng , Termvanich Krittaporn , Tucker Joseph D. , Tang Weiming , Li Chunyan , Zhang Ying , Castillo-Carandang Nina T. , Ong Jason J.
Published: October 2023

Introduction

Many Asian countries have yet to scale up HIV pre-exposure prophylaxis (PrEP). Innovative strategies to increase PrEP uptake are needed. This study examined the use of crowdsourcing to increase PrEP uptake by describing and analysing the experiences of Australia, the Philippines, and China.

Methods

Three crowdsourcing open calls were conducted between 2021-2022 in Australia, the Philippines and China. Crowdsourcing has a group of individuals solve all or part of a problem, then share back solutions with the public. All open calls entailed: 1) problem identification; 2) committee formation with local groups; 3) community engagement for idea submission; 4) evaluation of submissions; 5) awarding incentives to finalists; and 6) solution dissemination via web and social media. We examined the number of total and high-quality submissions. We also identified themes across countries.

Results

The Australia, Philippines, and China teams received 9, 22 and 19 eligible submissions, respectively. A total of three, 10, and eight submissions had a mean score of 6/10 or greater. Three common solutions emerged across all the finalist ideas: enhancing service delivery; optimizing promotional campaigns; person-centered promotional materials. The winning ideas from the Australian, Filipino and Chinese teams were an anonymous online PrEP service, a printed ready-to-wear garment to create awareness about PrEP, and a poster on PrEP effectiveness, respectively.

Conclusions

Crowdsourcing can be a promising and versatile tool for developing PrEP strategies in Asia. Further evaluations via clinical trials can bridge the gap between idea generation and implementation, thus, creating the empirical evidence pivotal for the policy adoption of these innovations.
Brazilin is a Natural Product Inhibitor of the NLRP3 Inflammasome
Authors: McMahon Emily , El-Sayed Sherihan , Green Jack , Hoyle Christopher , Fitzpatrick Lorna , Jones Emma , Corrie Eve , Kelly Rebecca L. , Challinor Mairi , Freeman Sally , Bryce Richard A. , Lawrence Catherine B. , Brough David , Kasher Paul R.
Published: October 2023

Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no NLRP3 inflammasome inhibitors have been approved for therapeutic use in the clinic. Here we have identified that the natural product brazilin effectively inhibits both priming and activation of the NLRP3 inflammasome in cultured murine macrophages, a human iPSC microglial cell line and in a mouse model of acute peritoneal inflammation. Through computational modelling, we predict that brazilin can adopt a favourable binding pose within a site of the NLRP3 protein which is essential for its conformational activation. Our results not only encourage further evaluation of brazilin as a therapeutic agent for NLRP3-related inflammatory diseases, but also introduce this small-molecule as a promising scaffold structure for the development of derivative NLRP3 inhibitor compounds.
An alternate approach for optical solutions to the Date–Jimbo–Kashiwara–Miwa equation
Authors: Khuri Suheil
Published: October 2023

Purpose

The aim of this study is to offer a contemporary approach for getting optical soliton and traveling wave solutions for the Date–Jimbo–Kashiwara–Miwa equation.

Design/methodology/approach

The approach is based on a recently constructed ansätze strategy. This method is an alternative to the Painleve test analysis, producing results similarly, but in a more practical, straightforward manner.

Findings

The approach proved the existence of both singular and optical soliton solutions. The method and its application show how much better and simpler this new strategy is than current ones. The most significant benefit is that it may be used to solve a wide range of partial differential equations that are encountered in practical applications.

Originality/value

The approach has been developed recently, and this is the first time that this method is applied successfully to extract soliton solutions to the Date–Jimbo–Kashiwara–Miwa equation.
Decarbonization of construction projects: a review and interpretive structural modelling of carbon reduction drivers
Authors: Arogundade Suhaib , Dulaimi Mohammed , Ajayi Saheed , Saka Abdullahi , Ilori Olusegun
Published: October 2023

Purpose

Extant studies have discussed numerous carbon reduction drivers, but there is a dearth of holistic review and understanding of the dynamic interrelationships between the drivers from a system perspective. Thus, this study aims to bridge that gap.

Design/methodology/approach

The study conducted a review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses and adopted interpretive structural modelling (ISM) to analyse and prioritise the drivers.

Findings

Eighteen drivers were identified and grouped into five, namely, policy instruments, bid-related, cost and risk, education and training, and reward and penalty drivers. The ISM revealed two hierarchical levels of the drivers with only higher cost of electricity/fuel on the higher level, making it the most important driver that could influence others.

Practical implications

The study presents an overview of decarbonisation drivers in the literature and would be of benefit to the government and stakeholders towards achieving net zero emissions in the construction industry.

Originality/value

The findings of the study present drivers of carbon reduction and prioritise and categorise them for tailored interventions within the construction sector. Also, it could serve as foundational knowledge for further study in the construction process decarbonisation research area.
Revisiting brand performance metrics and its impact on customer loyalty in Indian banking sector: role of relational quality and duration
Authors: Chahal Hardeep , Bala Renu
Published: October 2023

Purpose

The purpose of this study is to revisit brand performance metrics (BPMs) (brand affinity, brand content and knowledge, brand image, brand ethics and brand value) and evaluate the moderated mediation effect of relationship quality (mediator) and relationship duration (moderator) in brand performance and customer loyalty relationship in an Indian banking context.

Design/methodology/approach

The research model was tested in the Indian banking sector. The primary data was collected from the 1,000 account holders of five Indian public and private banks. The data was analysed and validated using exploratory factor analysis and confirmatory factor analysis. Structural equation modelling and the Hayes process were used for testing the hypotheses.

Findings

The study results established BPMs as a four-dimensional structure comprising brand affinity, brand content and knowledge, brand image, brand ethics and brand value. The BPMs significantly positively impact relational quality (RQ) and customer loyalty. Further results also prove the existence of moderated mediation effect on BPMs and customer loyalty link and portray that the impact of BPMs on customer loyalty is mediated by the RQ and influenced by relationship duration.

Research limitations/implications

The study is confined to the Indian banking sector. It did not examine the dimension-wise impact of brand performance indicators on RQ and customer loyalty. Future research is required to explore their influence in banking and other sectors.

Practical implications

The study findings suggest that to enhance brand performance, banks need to follow excellence in every conduct, take immediate actions against inappropriate behaviour, consistently update their relevant and valuable contents (news, videos, white papers, e-books, case studies, FAQ’s, photos, etc.) on their websites and also introduce loyalty schemes to reimburse customers’ interests with some substantial benefits such as rebates, discounts, annual gifts and extraordinary or additional services. These strategies can pave the way for enhancing long-term quality relationships between customers and their service providers and increasing customer loyalty.

Originality/value

To the best of the authors’ knowledge, the study is a maiden attempt to assess the effect of BPMs on customer loyalty in the presence of RQ and at the value of relationship duration/length. Besides, the study results also prove the existence of moderated mediation effect and portray that the impact of customer equity and relational benefits on customer loyalty is influenced by relationship duration and mediated by RQ.
Prevention and control of money laundering crimes on know your customer principles application: empirical study of Indonesia banking sector
Authors: Meiryani Meiryani
Published: October 2023

Purpose

The purpose of this paper is to find out the role and factors that lead to efforts by banking institutions to deal with money laundering by using the principle of knowing your customer.

Design/methodology/approach

This research method uses a sociological juridical approach and descriptive analysis in analyzing the data.

Findings

The results of the study found that the implementation of the principle plays a role in identifying each transaction, and if there is a transaction that is considered suspicious, each bank is required to report the transaction to the center for reporting and analysis of financial transactions.

Practical implications

Banks must reduce the risk of being used as a means of money laundering by knowing customer identities, monitoring transactions, maintaining customer profiles and reporting suspicious transactions made by parties using bank services. The application of the know your customer principle (KYCP) is based on the consideration that KYCP is not only important in the context of eradicating money laundering but also in the context of implementing prudential banking to protect banks from various risks in dealing with customers.

Originality/value

To the best of the author’s knowledge, this is first empirical study of banking in Indonesia that conduct money laundering crimes through application of KYCPs.
Analysis of the relationship of CRM-based library services with head librarians' personal and academic variables: a survey of university libraries in Pakistan
Authors: Bahader Mir
Published: October 2023

Purpose

This study aimed to examine the relationship between customer relationship management (CRM)-based library services and head librarians' personal and academic variables. The status of CRM-based library services in the university libraries of Pakistan was also assessed.

Design/methodology/approach

A cross-sectional survey research design and quantitative research approach were applied. A structured questionnaire was emailed to the heads librarians of all university libraries recognized by the Higher Education Commission of Pakistan, and the response rate was 74 percent.

Findings

The analysis showed that a relationship to CRM-based library services was confirmed by the head librarians' age, academic qualification, professional experience, CRM awareness and training. Moreover, several CRM-based library services such as face-to-face interaction, current awareness services, orientation for new users, coordination through e-mail services, special goodwill to regular users, make telephone calls, complaints/suggestions boxes, online services, provision of a conducive learning environment, user education, selective dissemination of information services, users' participation in the collection and service development, ask a librarian services and users' help desk services were currently being practiced by the university libraries.

Originality/value

This study is a valuable resource for developing user-centered library services and culture. Findings are helpful in enhancing CRM applications in libraries and making their users satisfied and loyal. This study makes a significant contribution to the body of literature and knowledge on library CRM.
Revealing white supremacy culture in an organization that supports queer and trans youth
Authors: Christensen M. Candace , Elías María Verónica , Alcocer Érica , Vicente Shannyn
Published: October 2023

Purpose

This study aims to illustrate how white supremacy culture can be produced within nonprofit organizations with a mandate to serve marginalized communities and provide practical suggestions for preventing oppression.

Design/methodology/approach

The site of inquiry was a nonprofit organization in south central Texas that provides social support to queer and trans youth. Through critical ethnography, the researchers evaluated the organization's processes and structure (including hierarchy, decision-making, fundraising and interactions between leaders, partners and affected groups) to explore how the organization perpetuated attributes of white supremacy culture.

Findings

Data reveal that the organization alienates the youth, volunteers and employees through defensiveness, fear of open conflict, paternalism, perfectionism and power-hoarding.

Originality/value

A dearth of research focuses on how white supremacy culture manifests in organizations serving marginalized communities. This paper addresses this gap by focusing on a nonprofit organization in central Texas that supports queer and trans youth. The authors offer recommendations for addressing white supremacy culture in organizations and suggest future research opportunities.
Risk factors for the development of tinea pedis and onychomycosis: Real‐world evidence from a single‐podiatry center, large‐scale database in Japan
Authors: Ogawa Takasuke , Matsuda Akinori , Ogawa Yumi , Tanaka Rica
Published: October 2023

Dermatomycosis, including tinea pedis and onychomycosis, is frequently encountered in routine medical care in Japan. Identifying the risk factors for tinea pedis and onychomycosis development is important to encourage hospital visits by patients who may have these diseases but who are not undergoing any treatment. This approach may lead to the prevention of disease progression and the spread of infections to others. Risk factors for onychomycosis development have been reported both in and outside of Japan. However, most of the risk factors were identified based on a multicenter, questionnaire survey study and included evidence obtained from unclear or inconsistent diagnostic criteria for tinea pedis, onychomycosis, and identified risk factors. The current study analyzed the risk factors for developing tinea pedis and onychomycosis in real‐world practice in Japan using a single‐center, large‐scale database that included the data of patients managed with consistent diagnostic criteria at the Podiatry Center of Juntendo University Hospital. A total of 2476 patients (1012 males, 1464 females) with a mean age of 63.4 years were included. Among these patients, 337 (13.6%) had tinea pedis and 346 (14.0%) had onychomycosis. A total of 259 patients (~ 75% of each patient population) had both diseases concomitantly. Multivariate logistic regression analysis adjusted for the possible risk factors of age (per 10 years), sex, diabetes, dialysis, visual impairment, ulcer history, lower‐limb ischemia (LLI), and diabetic peripheral neuropathy (DPN) revealed that advanced age, male sex, diabetes, and LLI were independent risk factors for the development of tinea pedis. In addition, DPN was an independent risk factor for developing onychomycosis. We believe that these data are useful for identifying patients who are at high risk of developing tinea pedis and onychomycosis, which may result in disease prevention and suppression in real‐world clinical practice in Japan.
Trends in preterm birth in the Netherlands in 2011–2019: A population‐based study among singletons and multiples
Authors: Klumper Job , Ravelli Anita C. J. , Roos Carolien , Abu‐Hanna Ameen , Oudijk Martijn A.
Published: October 2023

Introduction

Preterm birth (PTB) is the leading cause of infant mortality and morbidity worldwide. Rates of PTB in the Netherlands are declining, possibly due to the implementation of preventive strategies. In this study we assessed the overall trend in PTB rates in the Netherlands in recent years, and in more detail in specific subgroups to investigate potential groups that require scrutiny in the near future.

Material and methods

Based on the national perinatal registry, we included all pregnancies without severe congenital abnormalities resulting in a birth from 24 to 42 completed weeks of gestation between 2011 and 2019 in the Netherlands. We assessed PTB rates in two different clinical subtypes (spontaneous vs. iatrogenic) and in five gestational age subgroups: 24–27+6 weeks (extreme), 28–31+6 weeks (very), 32–33+6 weeks (moderate, 34–36+6 weeks [late] and, in general, 24–36+6 weeks [overall PTB]). Trend analysis was performed using the Cochran Armitage test. We also compared PTB rates in different subgroups in the first 2 years compared to the last 2 years. Singleton and multiple gestations were analyzed separately.

Results

We included 1 447 689 singleton and 23 250 multiple pregnancies in our study. In singletons, we observed a significant decline in PTB from 5.5% to 5.0% (p < 0.0001), mainly due to a decrease in iatrogenic PTBs. When focusing on different gestational age subgroups, there was a decrease in all iatrogenic PTB and in moderate to late spontaneous PTB. However, in spontaneous extreme and very PTB there was an significant increase. When assessing overall PTB risk in different subgroups, the decline was only visible in women with age ≥25 years, nulliparous and primiparous women, women with a medium or high socioeconomic status and hypertensive women. In multiples, the rate of PTB remained fairly stable, from 52.3% in 2011 to 54.1% in 2019 (p = 0.57).

Conclusions

In the Netherlands, between 2011 and 2019, PTB decreased, mainly due to a reduction in late PTB, and more in iatrogenic than in spontaneous PTB. Focus for the near future should be on specific subgroups in which the decline was not visible, such as women with a low socioeconomic status or a young age.
Placental size at gestational week 36: Comparisons between ongoing pregnancies and deliveries
Authors: Peterson Helene Fjeldvik , Eskild Anne , Sommerfelt Silje , Hillestad Vigdis
Published: October 2023

Introduction

We aimed to compare placental size and placental size relative to fetal size (ratio) in ongoing pregnancies examined by magnetic resonance imaging (MRI) at gestational week 36 with placental size among all deliveries at gestational week 36 during the same time period.

Material and methods

Ongoing unselected singleton pregnancies (n = 89) were examined by MRI at median gestational week 36+5 days during 2017–2018, and placental and fetal volumes (cm3) were calculated. The placental size and ratio in ongoing pregnancies were compared with placental size and ratio among all deliveries in Norway at gestational week 36 (median gestational week 36+4 days) during 2016–2019 (n = 5582). For comparison of size, we converted volume (cm3) in ongoing pregnancies into grams as: cm3 × 1.05 (density of placental and fetal tissue).

Results

In ongoing pregnancies, median placental size was 873  (interquartile range [IQR] 265) grams and median size of all delivered placentas was 613 (IQR 290) grams. Placental size was smaller among the delivered placentas independent of delivery mode: 760 (IQR 387) grams among elective cesarean deliveries (n = 465) and 590 (IQR 189) grams among vaginal deliveries after spontaneous onset of labor (n = 2478).

Median ratio in ongoing pregnancies was higher than among deliveries: 0.31 (IQR 0.08) vs 0.21 (IQR 0.08). The ratio was higher in ongoing pregnancies independent of delivery mode: 0.24 (IQR 0.17) among elective cesarean deliveries vs 0.21 (IQR 0.05) among vaginal deliveries after spontaneous onset of labor.

Conclusions

The placenta is larger in ongoing pregnancies than among deliveries. This finding suggests that placental size decreases during labor and delivery, possibly by transfer of blood to the fetus. Our finding also suggests that reference values of placental size based on delivered placentas are not valid for ongoing pregnancies.
Should we abandon therapeutic drug monitoring of tacrolimus in whole blood and move to intracellular concentration measurements?
Authors: Udomkarnjananun Suwasin , Eiamsitrakoon Thanee , de Winter Brenda C. M. , van Gelder Teun , Hesselink Dennis A.
Published: October 2023

The measurement of whole blood (WB) concentrations has been the primary method for therapeutic drug monitoring of tacrolimus since its introduction in the field of organ transplantation. However, >99% of tacrolimus measured in WB is bound to erythrocytes and plasma proteins, which are the pharmacologically inactive fractions. The pharmacologically active fractions, the free (or unbound) tacrolimus in plasma and the intracellular tacrolimus, make up 1% or less of the WB concentration. The mechanism of action of tacrolimus is to inhibit the enzyme calcineurin within T lymphocytes and, therefore, measuring the intralymphocytic tacrolimus concentration may better reflect its pharmacodynamic effects and better correlate with clinical outcomes. However, studies on intracellular tacrolimus concentrations have shown conflicting results. In this review, we argue that we need to overcome the analytical limitations of current assays for the measurement of intracellular tacrolimus before moving this technique into the clinical setting. The validity and standardization of the cell isolation process before the measurement of the intracellular tacrolimus concentration is as important as the measurement itself but has received little attention in our view. Recent evidence suggests that the addition of an inhibitor of P‐glycoprotein, an efflux transporter expressed on lymphocytes, prevents the expulsion of tacrolimus during the cell isolation process. Refining the technique for the intracellular tacrolimus concentration measurement should be the focus followed by clinical evaluation of its association with rejection risk.
Adopting human factors in early phase and experimental medicine research: A nested pilot study observing controlled human infection with SARS‐CoV‐2
Authors: Higham Helen E. , Morgan Lauren , Cooper Cushla , Marshall Julia , Mawer Andrew , Jackson Susan , Lopez‐Ramon Raquel , Hughes Eileen , Richards Duncan , McShane Helen , Fullerton James N.
Published: October 2023

Aims

The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and safeguarded by guidelines, protocolized care and staff training; however, the real‐world interaction and implementation of these risk‐mitigating measures has never been subjected to formal system‐based assessment.

Methods

Independent structured observations, systematic review of study documents, and interviews and focus groups were used to collate data on three key tasks undertaken in a clinical research facility (CRF) during a SARS CoV‐2 controlled human infection model (CHIM) study. The Systems Engineering Initiative for Patient Safety (SEIPS) was employed to analyse and categorize findings, and develop recommendations for safety interventions.

Results

High levels of team functioning and a clear focus on participant safety were evident throughout the study. Despite this, latent risks in both study‐specific and CRF work systems were identified in all four SEIPS domains (people, environment, tasks and tools). Fourteen actionable recommendations were generated collaboratively. These included inter‐organization and inter‐study standardization, optimized checklists for safety critical tasks, and use of simulation for team training and exploration of work systems.

Conclusions

This pioneering application of human factors techniques to analyse work systems during the conduct of research in a CRF revealed risks unidentified by routine review and appraisal, and despite international guideline adherence. SEIPS may aid categorization of system problems and the formulation of recommendations that reduce risk and mitigate potential harm applicable across a trials portfolio.
Novel molecular mechanism driving neuroprotection after soluble epoxide hydrolase inhibition: Insights for Alzheimer's disease therapeutics
Authors: Griñán‐Ferré Christian , Jarné‐Ferrer Júlia , Bellver‐Sanchís Aina , Codony Sandra , Puigoriol‐Illamola Dolors , Sanfeliu Coral , Oh Yumin , Lee Seulki , Vázquez Santiago , Pallàs Mercè
Published: October 2023

Background

Neuroinflammation is widely recognized as a significant hallmark of Alzheimer's disease (AD). To combat neuroinflammation, the inhibition of the soluble epoxide hydrolase (sEH) enzyme has been demonstrated crucial. Importantly, sEH inhibition could be related to other neuroprotective pathways described in AD.

Aims

The aim of the study was to unveil new molecular pathways driving neuroprotection through sEH, we used an optimized, potent, and selective sEH inhibitor (sEHi, UB‐SCG‐51).

Materials and Methods

UB‐SCG‐51 was tested in neuroblastoma cell line, SH‐SY5Y, in primary mouse and human astrocytes cultures challenged with proinflammatory insults and in microglia cultures treated with amyloid oligomers, as well as in mice AD model (5XFAD).

Results

UB‐SCG‐51 (10 and 30 μM) prevented neurotoxic reactive‐astrocyte conversion in primary mouse astrocytes challenged with TNF‐α, IL‐1α, and C1q (T/I/C) combination for 24 h. Moreover, in microglial cultures, sEHi reduced inflammation and glial activity. In addition, UB‐SCG‐51 rescued 5XFAD cognitive impairment, reducing the number of Amyloid‐β plaques and Tau hyperphosphorylation accompanied by a reduction in neuroinflammation and apoptotic markers. Notably, a transcriptional profile analysis revealed a new pathway modulated by sEHi treatment. Specifically, the eIF2α/CHOP pathway, which promoted the endoplasmic reticulum response, was increased in the 5XFAD‐treated group. These findings were confirmed in human primary astrocytes by combining sEHi and eIF2α inhibitor (eIF2αi) treatment. Besides, combining both treatments resulted in increased in C3 gene expression after T/I/C compared with the group treated with sEHi alone in cultures.

Discussion

Therefore, sEHi rescued cognitive impairment and neurodegeneration in AD mice model, based on the reduction of inflammation and eIF2α/CHOP signaling pathway.

Conclusions

In whole, our results support the concept that targeting neuroinflammation through sEH inhibition is a promising therapeutic strategy to fight against Alzheimer's disease with additive and/or synergistic activities targeting neuroinflammation and cell stress.
Small biopsies for pancreatic lesions: Is there still room for fine needle aspiration?
Authors: Bueno Adriana , Felipe‐Silva Aloisio , Saieg Mauro
Published: October 2023

Pancreatic carcinoma is an aggressive tumour with increasing incidence in both sexes worldwide. Early detection is, therefore, essential for patient management. A recent advancement involves the utilization of larger, thicker gauge needles, which enable the collection of core‐type biopsies (FNB). Here, we investigated the role of fine needle aspiration and cytopathology in the diagnostic workflow of pancreatic lesions. A search query was designed to search for articles in the PubMed database comparing FNA and FNB for biopsy of pancreatic lesions, and detailed data were extracted from selected studies. Statistical analyses were performed using the R package meta version 6.2. Twenty‐one studies made the final cut for data extraction. Overall, median age was 64.3 years (±6.1; 47.6–71.5), male: female proportion 53.9 (±11.3; 27.6–67.4), lesion size 3.1 cm (±0.5; 1.9–4.2 cm) and percentage of malignant cases 78.3% (±26.8; 2.1–100). FNA and FNB diagnostic yield was 85.8% (±10.3; 70.0–100.0) and 89.2% (±7.7; 70.0–98.6), respectively. Average accuracy was 89.5% (±11.7; 63.0–100.0) for FNA and 90.8% (±7.1; 77.0–100.0) for FNB. Adverse effects rate was 1.0% (±1.3; 0–4.3) for FNA and 2.2% (±4.4; 0–16.1) for FNB. None of the selected variables had a significant statistical difference between both methods. FNA and FNB perform similarly for diagnostic material acquisition in pancreatic lesions. The best outcome comes from the association of both techniques, emphasizing the value of combining cytological and histological morphology for the most accurate analysis.
Differential diagnosis of small hepatocellular nodules in cirrhosis: surrogate histological criteria of TERT promoter mutations
Authors: Beaufrère Aurélie , Paisley Sarah , Ba Ibrahima , Laouirem Samira , Priori Victoria , Cazier Hélène , Favre Loëtitia , Cauchy François , Lesurtel Mickael , Calderaro Julien , Kannengiesser Caroline , Paradis Valérie
Published: October 2023

Aims

The differential diagnosis of small hepatocellular nodules in cirrhosis between dysplastic nodules and hepatocellular carcinoma (HCC) remains challenging on biopsy. As TERT promoter (pTERT) mutations may indicate the nodules already engaged in the malignant process, the aim of this study was to identify histological criteria associated with pTERT mutations by detecting these mutations by ddPCR in small formalin‐fixed paraffin‐embedded (FFPE) hepatocellular nodules arising in cirrhosis.

Methods and results

We built a bicentric cohort data set of 339 hepatocellular nodules < 2 cm from cirrhotic samples, divided into a test cohort of 299 resected samples and a validation cohort of 40 biopsies. Pathological review, based on the evaluation of 14 histological criteria, classified all nodules. pTERT mutations were identified by ddPCR in FFPE samples. Among the 339 nodules, ddPCR revealed pTERT mutations in 105 cases (31%), including 90 and 15 cases in the test and validation cohorts, respectively. On multivariate analysis, three histological criteria were associated with pTERT mutations in the test cohort: increased cell density (P = 0.003), stromal invasion (P = 0.036) and plate‐thickening anomalies (P < 0.001). With the combination of at least two of these major criteria, the AUC for predicting pTERT mutations was 0.84 in the test cohort (sensitivity: 86%, specificity: 83%) and 0.81 in the validation cohort (sensitivity: 87%, specificity: 76%).

Conclusions

We identified three histological criteria as surrogate markers of pTERT mutations that may be used in routine biopsy to more clearly classify small hepatocellular nodules arising in cirrhosis.
A Touch of Immunology: improving accessibility to the science of antibodies for people with blindness, low vision and diverse needs
Authors: Polmear Jack , Kealy Liam , Xu Hui , Good‐Jacobson Kim L
Published: October 2023

Immunology for all: Most scientific communication has historically been limited to visual imagery and the written or spoken word, often in the form of dense articles obscured by jargon. Clear communication of science is vital to enable the public to engage with important scientific discoveries and to limit medical distrust. However, scientific communication is often executed in a way which neglects people with blindness, low vision and diverse needs. Our aim for the exhibit at the Monash Sensory Science Exhibition on Autoimmunity 2023 at Monash University was to develop novel, tactile and informative models to help better communicate the scientific principles that underpin autoimmune disease and immunology. As B‐cell biologists, we decided to focus our exhibit for this workshop on antibody‐mediated autoimmunity. Antibodies are key components of the immune system, providing protection against a range of diverse pathogens. However, in the context of autoimmunity, they can also drive pathology.
Cell type‐specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases
Authors: Guo Ying , Zhou Jin , Wang Yaqi , Wu Xueliang , Mou Yakui , Song Xicheng
Published: October 2023

Necroptosis is generally considered as an inflammatory cell death form. The core regulators of necroptotic signaling are receptor‐interacting serine–threonine protein kinases 1 (RIPK1) and RIPK3, and the executioner, mixed lineage kinase domain‐like pseudokinase (MLKL). Evidence demonstrates that necroptosis contributes profoundly to inflammatory respiratory diseases that are common public health problem. Necroptosis occurs in nearly all pulmonary cell types in the settings of inflammatory respiratory diseases. The influence of necroptosis on cells varies depending upon the type of cells, tissues, organs, etc., which is an important factor to consider. Thus, in this review, we briefly summarize the current state of knowledge regarding the biology of necroptosis, and focus on the key molecular mechanisms that define the necroptosis status of specific cell types in inflammatory respiratory diseases. We also discuss the clinical potential of small molecular inhibitors of necroptosis in treating inflammatory respiratory diseases, and describe the pathological processes that engage cross talk between necroptosis and other cell death pathways in the context of respiratory inflammation. The rapid advancement of single‐cell technologies will help understand the key mechanisms underlying cell type‐specific necroptosis that are critical to effectively treat pathogenic lung infections and inflammatory respiratory diseases.