bluuebunny/crossref_metadata_2025 huggingface dataset:
Host metabolic pathways essential for malaria and related hemoparasites in the infection of nucleated cells
Authors: Maurizio Marina , Masid Maria , Woods Kerry , Caldelari Reto , Doench John G. , Naguleswaran Arunasalam , Joly Denis , Fernández Martín González , Zemp Jonas , Borteele Mélanie , Hatzimanikatis Vassily , Heussler Volker , Rottenberg Sven , Olias Philipp
Published: September 2023

Apicomplexan parasite diseases, including malaria (Plasmodium) and theileriosis (Theileria), pose a significant threat to global health and the socioeconomic well-being of low-income countries. Despite recent advances, the common host metabolic proteins essential for these highly auxotrophic pathogens remain elusive. Here, we present a comprehensive investigation integrating a metabolic model ofP. falciparumparasites in hepatocytes and a genome-wide CRISPR screen targetingTheileriaschizont-infected macrophages. We reveal unifying host metabolic enzymes critical for the intracellular survival of these related hematozoa. We show that pathways such as host purine and heme biosynthesis are essential for bothTheileriasurvival andPlasmodiumliver development, while genes involved in glutathione and polyamine biosynthesis are predicted to be essential forPlasmodiumonly under certain metabolic conditions. Our work highlights the importance of host porphyrins for the viability of liver-stagePlasmodium. Shared parasite vulnerabilities provide a resource for exploring alternative therapeutic approaches to combat these crippling diseases.
Reconstitution of Early Paclitaxel Biosynthetic Network
Authors: Liu Jack Chun-Ting , De La Pena Ricardo , Tocol Christian , Sattely Elizabeth S.
Published: September 2023

Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. This diverts metabolic flux away from the paclitaxel precursor, taxadien-5α-ol, thus previous attempts of reconstitution have not yielded sufficient material for characterization, regardless of the heterologous host. Here, we structurally characterized four new products of T5αH, many of which appear to be over-oxidation of the primary mono-oxidized products. By tuning the promoter strength for T5αH expression, levels of these proposed byproducts decrease with a concomitant increase in the accumulation of taxadien-5α-ol by four-fold. This engineered system enabled the reconstitution of a six step biosynthetic pathway to produce isolatable 5α,10β-diacetoxy-taxadien-13α-ol. Furthermore, we showed that this pathway may function as a metabolic network rather than a linear pathway. The engineering of the paclitaxel biosynthetic network demonstrates thatTaxusgenes can coordinatively function for the biosynthetic production of key early stage paclitaxel intermediates and serves as a crucial platform for the discovery of the remaining biosynthetic genes.
Discovering paracrine regulators of cell type composition from spatial transcriptomics using SPER
Authors: Zhao Tianxiao , Haber Adam L.
Published: September 2023

A defining characteristic of each biological tissue is its cell type composition. Many pathologies and chronic diseases are associated with perturbations from the homeostatic composition, which can lead to aberrant tissue function. Spatial transcriptomics now enables simultaneous measurement of gene expression and cell type composition, creating an opportunity to discover the transcripts most strongly associated with changes in nearby cell composition. However, no method yet exists to systematically identify such signals. Here, we develop Spatial Paired Expression Ratio (SPER), a computational approach to evaluate the spatial dependence between transcript abundance and cell type proportions in spatial transcriptomics data. We demonstrate the ability of SPER to accurately detect paracrine drivers of cellular abundance using simulated datasets. Using publicly available spatial transcriptomic data from mouse brain, we show that genes identified by SPER are highly likely to be both extracellularly secreted and to participate in known receptor-ligand interactions. This provides evidence of SPER’s ability to detect compositional regulatory signals. In addition to recovering known interactions, SPER identified novel spatial associations, such as between the Wnt ligandRpso3and its cognate receptorLgr5, not previously known to regulate neural cell type composition in the motor cortex. SPER thus presents a general approach to discovering paracrine drivers of cellular compositional changes.
Twinning and homoepitaxy cooperation in the already rich growth morphology of CaCO3 polymorphs. I. Aragonite
Authors: Aquilano Dino , Bruno Marco , Ghignone Stefano , Pastero Linda
Published: September 2023

Calcite and aragonite are the two most abundant among the CaCO3 polymorphs and are also well known for their rich morphology and habit, to which twinning relevantly contributes. Moreover, the calcite → aragonite transformation has been debated for a long time, even though the homo-epitaxies occurring within each polymorph have been overlooked, to date, from both experimental and theoretical points of view. Twinning is common and unfortunately can be deceptive as it can be mistaken for homo-epitaxy, thus leading to confusion regarding the growth mechanisms of many crystal aggregates. Here, experimental and theoretical studies were carried out to investigate the twinning and homo-epitaxy that operate in aragonite: (i) the connection between twinning and homo-epitaxy for contact and penetration aggregates made by the lateral {010} and {110} aragonite forms; (ii) the homo-epitaxial relationships among the {001} pinacoid and both the {010} pinacoid and the prismatic {110} aragonite forms. This work attempts to provide a new approach to monitoring the growth mechanisms of aragonite in cases where it is obtained not as a single crystal but as an aggregate. An analogous problem will be explored in our forthcoming work on calcite.
Crystal structure of bis(3-carboxy-1-methylpyridinium) octabromide
Authors: Sirenko Valerii Y. , Naumova Dina D. , Golenya Irina A. , Shova Sergiu , Gural'skiy Il'ya A.
Published: September 2023

The crystal structure of the title salt, bis(3-carboxy-1-methylpyridinium) octabromide, 2C7H8NO2
+·Br8
2−, consists of 3-carboxy-1-methylpyridinium (N-methylnicotinic acid) cations, which are stacked between relatively rare [Br8]2– anions. The polybromide [Br8]2– anion has point group symmetry \overline{1} and can be described as being composed of two [Br3]− anions connected with a Br2 molecule in a Z-shaped manner. Contacts between neighboring octabromide anions ensure the creation of pseudo-polymeric chains propagating along [111]. The organic cations are located between anionic chains and are connected to each other through O—H...O hydrogen bonds and to the [Br8]2– anions through π...Br interactions that induce the creation of a supramolecular tri-periodic network. In addition, the presence of weak C—H...Br contacts leads to the creation of layers, which align parallel to (11\overline{2}).
Measuring the changes: how can a perceived cultural mega-event evidence its “value”? Insights from implementing evaluation methodologies for Coventry 2021
Authors: Scott Mark , Neelands Jonothan , Beer Haley , Bharatan Ila , Healey Tim , Henry Nick , Lam Si Chun , Tomlins Richard
Published: September 2023

Purpose

It is well known that culture is a catalyst for change, helping economies respond to societal problems and demands and that culture is where people turn to in moments of crisis. In this case study around designing and implementing evaluation methodologies/frameworks for Coventry UK City of Culture 2021, it is suggested that in English public policy and within publicly invested arts there is a maturation of thinking around recognising/measuring the public value of culture including its social value. The purpose of this paper is to chart the recent policy of justifying cultural expenditure with social value claims and highlight challenges for evaluating activity within Coventry UK CoC 2021 as a change in wider policy is taking place.

Design/methodology/approach

This paper provides creative insights into the design and implementation of the evaluation methodologies/frameworks for Coventry UK City of Culture 2021. The authors of this paper as the collective team undertaking the evaluation of Coventry's year as UK City of Culture 2021 bring first-hand experiences of challenges faced and the need for a cultural mega-event to evidence its value.

Findings

The case study aims to address the concepts of measuring value within cultural events and argues that a paradigm shift is occurring in methods and concepts for evidencing the aforementioned value.

Research limitations/implications

The case study within this paper focuses on the build-up period to the UK City of Culture 2021 year and the thinking and logic behind the creation of the evaluation/measurement framework and therefore does not include findings from the actual cultural year.

Originality/value

It is acknowledged that there are papers examining measuring and evidencing the “value” of cultural mega-events, the authors bring real-life first-hand experience of the concepts being utilised by them on the ground in the delivery and evaluation design of Coventry, UK City of Culture 2021.
Assessment of the impacts of the life cycle of construction waste on human health: lessons from developing countries
Authors: Wang Li , Lv Yanhong , Wang Tao , Wan Shuting , Ye Yanling
Published: September 2023

Purpose

The purpose of this research is to address the existing gap in the study of construction and demolition waste (C&DW) by focusing on its impact on human health throughout the entire life cycle. And this research provides a comprehensive assessment model that incorporates the release of gaseous pollutants and particulate matter during the whole life cycle of C&DW, thereby contributing to a more holistic understanding of its impact on human health.

Design/methodology/approach

The research was conducted in two stages. Firstly, the quantitative model framework of pollutants emitted by C&DW was established. Three types of pollutants were considered, namely nitrogen dioxide (NO2), sulfur dioxide (SO2) and inhalable particulate matter (PM10). Second, disability-adjusted life year (DALY) and willingness to pay (WTP) assessments were used to provide a monetary quantified health impact for pollutants released by C&DW.

Findings

The results show that the WTP value of PM10 is the highest among all pollutants and 8.68E+07 dollars/a, while the WTP value in the disposal stage accounts for the largest proportion compared to the generation and transportation stage. These findings emphasize the importance of PM10 and C&DW treatment stage for pollutant treatment.

Originality/value

The results of this study are of great significance for the management department to optimize the construction management scheme to reduce the total amount of pollutants produced by C&DW and its harm to human health. Meanwhile, this study fills the gap in existing research on the impact assessment of C&DW on human health throughout the whole life cycle, and provides reference and basis for future research and policy formulation.
Towards a typology of logistics “work” beyond formal employment: a synthesised literature review
Authors: Wang Xueqin , Yuen Kum Fai
Published: September 2023

Purpose

Logistics at work is rapidly changing. The changing trend is especially prominent when considering the active involvement of individuals that perform diverse forms of formal/informal “logistics work” (e.g. crowd logistics and self-collection). Thus, by conducting a synthesised review (n = 55), this study aims to provide a typology of individuals' logistics work.

Design/methodology/approach

The total social organisation of labour is used as a guiding framework. A deductive literature analysis is performed based on the identified journal articles.

Findings

The review findings reveal three major contexts where individuals perform logistics work: formal organisation, social community and private household, with a decreased level of formality. Under each context, individuals may be engaged in paid or unpaid activities, creating six forms of logistics work, termed as paid/voluntary professional logistics, incentivised/friendly social logistics and rewarded/free consumer logistics. Furthermore, an actor–sphere–resource–value conceptualisation of individual logistics is proposed, focussing on the chains of actors, work settings, resource input and value outcome.

Originality/value

The results provide a theoretical foundation for further research in individual- or consumer-centrism in logistics. Two research directions and seven research questions are presented for future investigation.
Strategic divestment of emerging market firms: the influence of returnee managers and CEO characteristics
Authors: Kalasin Kiattichai
Published: September 2023

Purpose

This study aims to examine the role of returnee managers that can affect the strategic-divestment decision of emerging-market firms (EM firms). Drawing on arguments from the upper echelons theory and international human resource mobility perspectives, this study aims to propose that returnee managers influence corporate divestitures when the business outlook is negative. In addition, this study aims to examine the interplay between returnee managers and CEOs, whose characteristics can foster or undermine the efforts of returnee managers to engage in corporate divestments.

Design/methodology/approach

This study examines 278 firms from nine emerging economies. The negative binomial regression was employed to estimate the model. In the robustness checks, the logistic regression was adopted to confirm the earlier findings.

Findings

The empirical results support the notion that returnee managers strengthen the relationship between firm performance and divestments. Because of the limited liabilities of foreignness and outsidership, returnee managers can gain social trust and credibility through communication and social interaction. Furthermore, the results provide mixed support for the moderating effect of CEO characteristics on the performance–divestment relationship.

Practical implications

This study reveals that returnee managers are a great asset for EM firms that aim to find synergies and upgrade their capabilities through asset reconfiguration, which is an essential activity of emerging market firms to integrate themselves into the global competition. Meanwhile, CEO characteristics can foster (through their education level) or hinder (due to their age) divestment attempts, influenced by returnee managers.

Originality/value

This study explores an understudied phenomenon in international business (IB): strategic divestment of EM firms. The literature that examines strategic divestment and corporate refocusing in emerging markets is extremely limited. Furthermore, this study explores the novel topic that intersects the international business (IB) and international human resource management (IHRM) research areas. Specifically, this study investigates the impact of returnee managers on strategic divestments.
A bibliometric analysis of halal tourism: future research agenda
Authors: Supardin Lalu , Suyanto Mohammad , Hidayat Anas , Wijaya Tony
Published: September 2023

Purpose

Over the past few decades, a large number of research studies have examined tourism. However, studies that examine halal tourism are still limited. Therefore, the purpose of this study is to conduct a bibliometric analysis related to halal tourism based on the results of empirical research studies that have been published.

Design/methodology/approach

The approach in this study uses a systematic literature review related to halal tourism as a reference in “Article Title, Abstract and Keywords” based on the Scopus database from 1997 to 2023. The analysis was conducted on January 8, 2023. The data that has been collected will be analyzed bibliometrically using VOSviewer.

Findings

The research findings show that research related to halal tourism is still relatively rare, especially in countries/locations where the majority of the population is non-Muslim. This can be seen from the majority of previous studies conducted in Muslim-majority countries/locations, such as Malaysia and Indonesia. Future research should be conducted in countries/locations where the majority of the population is non-Muslim.

Research limitations/implications

This study relies on research in halal tourism literature in the Scopus database. Future studies can combine with the Web of Science database to expand generalization.

Practical implications

The results of this study include implications for managing and developing sustainable halal tourism in the future for practitioners.

Social implications

The results of this study provide a strategic perspective to practitioners and society in general to find out how the concept of sustainable halal tourism development in the future is in accordance with Islamic sharia.

Originality/value

Research related to halal tourism is currently starting to develop in various countries, both with a majority Muslim and non-Muslim population. In addition, until now research related to halal tourism is still limited literature that discusses.
The experience of hurt in the deepest part of self; a phenomenological study in young people with non-suicidal self-injury (NSSI)
Authors: AghaMohammadi Soudeh , Mazaheri Mohammad Ali , Fata Ladan , Mootabi Fereshteh , Moghadasiyan Basir
Published: September 2023

Purpose

What is happening in the perceived world of young people who have non-suicidal self-injury? The answer to this question explains many quantitative research findings in the field of NSSI. The current qualitative research design is Husserl's descriptive phenomenology.

Design/methodology/approach

The participants included 17–29-year-old youths with self-injury and were selected with a targeted sampling approach and a conspicuous sampling method based on the theoretical saturation criterion of 21 people. Data were collected in a semi-structured interview and analyzed in the MAXQDA2022 software using the Attride-Stirling (2001) method. Validation of data was done by the method of simultaneous review of colleagues and simultaneous review of participants.

Findings

The themes emerging from the analysis of the findings are the three organizing themes of “vulnerable temperament” which includes height and head, high pain sensitivity threshold and desire for nothingness, “traumatic family” which includes disorganization, crisis and devaluation in the family and “developmental injuries” that are associated with physical, sexual and emotional abuse and neglect. The content of these themes seriously harms a person's self-perception through the emotions of fear, shame, anger and despair and is integrated into the overarching theme of “damaged self”.

Originality/value

“Damaged Self” provides causal explanations related to the formation of self-injurious behaviors and these behaviors are in harmony with the damage that a person observes in his perception of himself.
Operationalising critical realism for case study research
Authors: Fuchs Olivier , Robinson Craig
Published: September 2023

Purpose

Critical realism is an increasingly popular “lens” through which complex events, entities and phenomena can be studied. Yet detailed operationalisations of critical realism are at present relatively scarce. This study's objective here is built on existing debates by developing an open systems model of reality, a basis for designing appropriate, internally consistent methodologies.

Design/methodology/approach

The authors use a qualitative case study examining changing practices for client contact management in professional services firms during restrictions imposed by the COVID-19 crisis to show how the model can be operationalised across all stages of a research study.

Findings

This study contributes to the literature on qualitative applications of critical realism by providing a detailed example of how the research paradigm influenced choices at every stage of the case study process.

Originality/value

More importantly, this model of reality as an open system provides a tool for other researchers to use in their own operationalisation of critical realism in a variety of different settings.
The best company cultures are “people first”
Authors: Hiler Kimberly
Published: September 2023

Purpose

This paper aims to prove that putting people first is a key tenet to successfully engaging with your employees and building a strong company culture. Recognizing the importance of this approach is paramount for HR professionals and company leaders.

Design/methodology/approach

With a people-first approach, employees are placed at the forefront of all business decisions. Intradiem has abided by a people-first philosophy for years, and the company has seen incredible payoff in employee engagement and business success.

Findings

In a business world increasingly characterized by technology and automation, the human element remains as vital as ever. This is especially true in customer service, which is, at its core, a quintessentially “human” exchange.

Originality/value

Appreciation for the value of prioritizing employees is not new, of course. The responsibility of people leaders is to ensure that the people they recruit, hire and train will feel secure, apprecited and valued. Because when they don’t, their performance suffers. That will be reflected in customer satisfaction and, ultimately, business performance.
Sacred Circle: Symbol of Wholeness in Traditional Persian Art and Architecture
Authors: Darabimanesh Fariba
Published: September 2023

Jung wrote extensively about the archetypal mandala symbol as an expression in many cultures of the centrality and nature of the interplay between human consciousness and divine consciousness. This article investigates—how in Persia, for millennia—the archetypal symbol of the mandala has been widespread in many expressions of the sacred arts. My research outlines the importance of the archetypal mandala symbol in Persian religio‐aesthetic history from the first unearthed stone carvings of Persia's ancient foundations until the more recent, breathtakingly marvellous ceilings of traditional Persian architecture today. From the artistic expressions of first religious beliefs of ancient Persia—Mithraism—and through the development of the Zoroastrian faith until the subsequent rise of Christianity and then Islam, Persian sacred art illustrates the Jungian idea that wholeness sought in the journey of individuation is often expressed through archetypal symbols of circles that articulate basic truths about the divine interplay with humanity.
rcontroll: An R interface for the individual‐based forest dynamics simulator TROLL
Authors: Schmitt Sylvain , Salzet Guillaume , Fischer Fabian Jörg , Maréchaux Isabelle , Chave Jerome
Published: September 2023

A central challenge in ecology is understanding the emergence of patterns as the result of interactions among individuals. Dynamic forest models can provide a fine‐scale description of the ecological, physiological and environmental processes that explain the demography of coexisting tree species. This in turn helps predict changes under future scenarios. However, model accessibility is a major obstacle to a wide use and communication across scientific disciplines and for educational purposes.

Here, we present the R package rcontroll, which provides access to the TROLL forest simulator in the R environment. TROLL is individual‐based and spatially explicit and leverages knowledge of ecology, biogeochemistry and tree ecophysiology through a trait‐based parameterisation. TROLL has been used to simulate carbon fluxes and tree diversity in tropical and subtropical forests and to explore forest resilience to disturbance and environmental changes more generally. rcontroll provides a user‐friendly environment to set up and analyse TROLL simulations with varying community compositions, ecological parameters and climate conditions.

We show how to test parameter sensitivity in TROLL using the rcontroll R package. We also demonstrate the flexibility and ease of use of rcontroll by replicating a previously published study based on the TROLL simulator. Both examples are included with reproducible code documents.

Complex forest simulators are important scientific tools for science and education, and wide access to these tools is an important condition for their adoption. TROLL is designed to address a wide range of ecological and environmental questions, and the new R package rcontroll is designed to be an entry point for TROLL model users.
Daxx knockdown promoted rDNA transcription without impairing H3.3 expression in mouse preimplantation embryos
Authors: Song Sihang , Wang Nan , Huang Xing‐wei , Jiang Qi , Cheng Xiang‐rong , Pang Nan , Lei Lei
Published: September 2023

During fertilization, DAXX (death domain‐associated protein) mediates histone variant H3.3 incorporation into heterochromatin, which plays an important role in the maintenance of genomic integrity. rDNA, the ribosomal gene, is included in the first wave of gene activation after fertilization. Our and other studies indicated that loss of Daxx disturbs rDNA heterochromatinization and promotes rDNA transcription without change in protein expression of H3.3. However, maternal and zygotic deletion of Daxx impairs blastocyst development. Whether Daxx knockdown affects H3.3 expression and improves the rDNA transcription in preimplantation development has not been reported. In the present study, we injected HA‐labelled H3.3 (H3.3‐HA) into oocytes during ICSI procedure, and detected H3.3 and DAXX by immunofluorescent staining. Then, we knockdowned Daxx and detected the gene expression levels of Daxx, H3.3, 18s and 47s rRNA. We also performed immunofluorescent staining of B23, γH2A and EdU incorporation to demonstrate nuclear structure, DNA damage and replication. We found injection of H3.3‐HA did not impair preimplantation development. Daxx siRNA did not change expression of H3.3 mRNA, and the development of two‐cell embryos and blastocysts, but the overall replication and expression levels of rRNA were increased compared with that in the control group. Finally, knockdown of DAXX did not aggravate the DNA damage but loosened the nucleolus. We concluded that Daxx knockdown promoted DNA replication and rDNA transcription, but did not affect H3.3 expression and subsequent preimplantation development.
Metabolic signature for a dysbiotic microbiome in the female genital tract: A systematic review and meta‐analysis
Authors: Gill Biban , Schwecht Ingrid , Rahman Nuzhat , Dhawan Tushar , Verschoor Chris , Nazli Aisha , Kaushic Charu
Published: September 2023

Background

The vaginal microbiome (VMB) is a critical determinant of reproductive health, where a microbial shift towards a dysbiotic environment has implications for susceptibility to, and clinical presentation of sexually transmitted infections (STIs). Metabolomic profiling of the vaginal microenvironment has led to the identification of metabolic responses to clinical conditions of dysbiosis. However, no studies have examined metabolic markers that are common across conditions and can serve as a signature for vaginal dysbiosis.

Method of Study

We have conducted a comprehensive systematic review and meta‐analysis to identify consistently deregulated metabolites along with their impact on host and microbial metabolism during dysbiosis. We employed two complementary approaches including a vote counting analysis for all eligible studies identified in the systematic review, in addition to a meta‐analysis for a subset of studies with sufficient available data. Significantly deregulated metabolites were then selected for pathway enrichment analysis.

Results

Our results revealed a total of 502 altered metabolites reported across 10 dysbiotic conditions from 16 studies. Following a rigorous, collective analysis, six metabolites which were consistently downregulated and could be generalized to all dysbiotic conditions were identified. In addition, five downregulated and one upregulated metabolite was identified from a bacterial vaginosis (BV) focused sub‐analysis. These metabolites have the potential to serve as a metabolic signature for vaginal dysbiosis. Their role in eight altered metabolic pathways indicates a disruption of amino acid, carbohydrate, and energy metabolism during dysbiosis.

Conclusion

Based on this analysis, we propose a schematic model outlining the common metabolic perturbations associated with vaginal dysbiosis, which can be potential targets for therapeutics and prophylaxis.
Impact of bisphenol A on cell viability and inflammatory cytokine production in human cervical epithelial cells
Authors: Tantengco Ourlad Alzeus G. , Vidal Manuel S. , Bento Giovana Fernanda Cosi , Menon Ramkumar
Published: September 2023

Problem

An intact cervix is a barrier that prevents pathogenic bacteria from invading the uterine and amniotic cavity during pregnancy. Its disruption is associated with ascending infection and adverse pregnancy outcomes. This study analyzed the effects of bisphenol A (BPA), a chemical used in plastics manufacturing, on cell death and inflammation in cervical epithelial cells.

Methods

Ectocervical epithelial (ecto) and endocervical epithelial (endo) cells were treated with 100 ng/mL and 300 ng/mL of BPA for 48 h. The cells were subjected to flow cytometry using annexin V and propidium iodide to determine apoptosis and necrosis, cell cycle analysis, and ELISA to determine the levels of inflammatory cytokines (IL‐6, IL‐8, and IL‐10).

Results

Low‐dose and high‐dose BPA significantly increased the live ecto cell population dose‐dependently. BPA did not have any noticeable effect on cell cycle progression in either cell type. BPA treatment also decreased the apoptotic ecto and endo cell population dose‐dependently. Lastly, high dose BPA significantly increased IL‐6 in ecto and endo cells. However, IL‐8 and IL‐10 were not affected by BPA treatments.

Conclusion

Chemical exposure damage to the cervix can lead to adverse pregnancy outcomes. Our study showed that the BPA concentrations reported in pregnant subjects do not induce cervical cell toxicity . The decrease in apoptosis and increase in live cells may be a compensatory mechanism to preserve the integrity of the cervical epithelial layer.
Editorial: Negative impact of diabetes mellitus and obesity on the prognosis of patients with chronic liver disease—Authors' reply
Authors: Paternostro Rafael , Jachs Mathias , Reiberger Thomas , Mandorfer Mattias
Published: September 2023

LINKED CONTENT

This article is linked to Paternostro et al papers. To view these articles, visithttps://doi.org/10.1111/apt.17653andhttps://doi.org/10.1111/apt.17673
Editorial: Interaction between fibre and colonic fermentation assessed with a novel gas‐sensing capsule
Authors: Spiller Robin
Published: September 2023

LINKED CONTENT

This article is linked to So et al papers. To view these articles, visit https://doi.org/10.1111/apt.17629 and https://doi.org/10.1111/apt.17704
Socioeconomic inequalities in early child development in children aged under 36 months in South Asia: A systematic review
Authors: Chandrasenage Damith , Markey Oonagh , Johnson William , Haycraft Emma , Griffiths Paula L.
Published: September 2023

Background

In South Asia, 89 million children under 5 are at risk of not reaching their developmental potential. Household socioeconomic position (SEP) is a determinant of early child development (ECD). However, synthesised evidence for the association between ECD and SEP in young children in South Asia is not available. Therefore, this review synthesises evidence on the relationship of household SEP with ECD in children under 36 months of age in South Asia.

Method

PubMed, Cochrane Library, MEDLINE and Scopus were systematically searched to identify studies from South Asian countries that reported evidence on the association between SEP and ECD. Search terms included items related to motor, cognitive, language and socioemotional development. Study quality was assessed using the QualSyst tool, with three quality levels (high/medium/low), and a narrative review for each ECD outcome was constructed (PROSPERO registration: CRD42019131533).

Results

Twelve of the 950 publications screened met the inclusion criteria (nine from India, two Nepal and one Bangladesh). The majority (n = 10, 83%) reported language development on its own or alongside another ECD outcome. Fewer articles assessed cognitive (n = 6, 50%), motor (n = 7, 58%) or socioemotional development (n = 3, 25%). Higher SEP was associated with better ECD for one third of the associations reported. One ECD outcome (socioemotional development) was negatively associated (with socioeconomic status) based on low quality evidence. Mother's education and family income were the major SEP constructs associated with ECD. One, four and seven studies were rated as having a low, medium and high risk of bias, respectively.

Conclusion

This review reveals the scarcity of evidence exploring associations between household SEP and ECD in children under 36 months in South Asia, especially outside of India. Enhancing evidence for associations between ECD and SEP is needed for evidence‐based policy making to reduce developmental delays associated with a disadvantaged SEP in the South Asian region.
Lessons from COP15 on effective scientific engagement in biodiversity policy processes
Authors: Carroll Carlos , Hoban Sean , Ray Justina C.
Published: September 2023

The Kunming–Montreal Global Biodiversity Framework was adopted by parties to the Convention on Biological Diversity in December 2022. The aftermath of these negotiations provides an opportunity to draw lessons as to how ecological and evolutionary science can more effectively inform policy. We examined key challenges that limit effective engagement by scientists in the biodiversity policy process, drawing parallels with analogous challenges within global climate negotiations. Biodiversity is multifaceted, yet represents only one framing for nature's contributions to people, complicating the nexus between evidence and values in development of the framework's targets. Processes generating biodiversity and driving its loss are multiscalar, challenging development of an evidence base for globally standardized targets. We illustrated these challenges by contrasting development of 2 key elements of the framework. The genetic diversity element of the framework's target 4 is directly related to the framework's primary goals, but its complexity required development of novel engagement skills. The target for protected areas was easily communicated but more indirectly related to biodiversity outcomes; evidence from ecological and social science was essential to communicating the context and limitations of this relationship. Scientists can strengthen the effectiveness of global agreements and address challenges arising from complexity, scaling, capacity limitations, and the interplay of science and values, if they can prioritize communication, consensus‐building, and networking skills and engage throughout the process, from development of an evidence base to implementation.
Release of glucose from dissolved and mineral‐bound organic matter by enzymatic hydrolysis
Authors: Lenhardt Katharina R. , Brandt Luise , Poll Christian , Rennert Thilo , Kandeler Ellen
Published: September 2023

Sorption of dissolved organic matter (DOM) by poorly crystalline minerals during their formation may protect large amounts of carbon in soils from mineralization. We investigated the bioavailability of carbohydrates in DOM and after co‐precipitation with short‐range ordered aluminosilicates. Carbohydrates originated from soil solutions collected in situ at two depths of a Dystric Cambisol, and from litter extracts. Quantification of substrate‐specific degradability was achieved by the addition of β‐glucosidase at an optimal concentration and subsequent determination of glucose release. Depending on DOM composition, 0.6–41.4 mg g−1 C−1 of glucose was enzymatically released from dissolved carbohydrates. Co‐precipitated carbohydrates were partially accessible, resulting in a glucose release of 0.7–5.2 mg g−1 C−1. Restricted enzymatic depolymerization due to co‐precipitation may contribute to accumulation of easily degradable substrates in soils.
Effects of larval crowding on the transcriptome of Drosophila simulans
Authors: Buchner Stephan , Hsu Sheng‐Kai , Nolte Viola , Otte Kathrin A. , Schlötterer Christian
Published: September 2023

Larval crowding is one common ecological stressor for many insect species. In Drosophila, high larval density alters multiple widely‐studied phenotypes including life‐history traits, morphology and behavior. Nevertheless, we still miss a holistic view of the full range of phenotypic changes and the underlying molecular mechanisms. In this study, we analyzed the adult transcriptomes of high and low larval density fly cohorts, and highlighted the molecular basis of the plastic traits. Increased cellular energy metabolism and locomotion, along with reduced reproductive investment, are key responses to high larval density. Moreover, we compared the expression changes among cohorts with different developmental delays caused by larval crowding. The majority of genes induced by larval crowding showed the strongest expression alterations in cohorts with intermediate delay. Furthermore, linear expression changes were observed in genes related to nutrition and detoxification. Comparing different high‐density cohorts could provide insights into the varied responses to distinct larval crowding‐induced stresses such as space competition, food degradation and waste accumulation.
Rapid weight change as a predictor of disability among community‐dwelling Japanese older adults
Authors: Tsubota‐Utsugi Megumi , Tanno Kozo , Takahashi Naomi , Onoda Toshiyuki , Yonekura Yuki , Ohsawa Masaki , Takahashi Shuko , Kuribayashi Toru , Itabashi Ryo , Tanaka Fumitaka , Asahi Koichi , Omama Shinichi , Ogasawara Kuniaki , Ishigaki Yasushi , Takahashi Fumiaki , Soma Akemi , Takanashi Nobuyuki , Sakata Kiyomi , Ohkubo Takayoshi , Okayama Akira
Published: September 2023

Aim

To fill the knowledge gap regarding weight change and the onset of disability in community‐dwelling Japanese older adults, we investigated the potential effects of rapid weight change on disability risk as defined by Japan's long‐term care insurance (LTCI) system.

Methods

We analyzed data from a longitudinal study of 10 375 community‐dwelling older Japanese adults (≥65 years) who were not LTCI needs certified at baseline and joined the study from 2002 to 2005. Weight change (percentage) was calculated by subtracting participants' weight in the previous year from that measured during a physical examination at study commencement. The five weight‐change categories ranged from sizable weight loss (≤ −8.0%) to sizable weight gain (≥ +8.0%). Disability was defined according to LTCI certifications at follow‐up. Hazard ratios (HRs) and 95% confidence intervals were calculated for new‐onset disability using a Cox proportional hazards model that fitted the proportional subdistribution hazards regression model with weights for competing risks of death.

Results

During the mean 10.5‐year follow‐up, 2994 participants developed a disability. Sizable weight loss (HR [95% confidence intervals], 1.41 [1.17–1.71]) and weight loss (1.20 [1.05–1.36]) were significant predictors of disability onset. Sizable weight gain (1.45 [1.07–1.97]) corresponded to severe disability. Stratified analyses by lifestyle and initial body mass index categories revealed more pronounced associations between weight change and disability risk in the unhealthy lifestyle and below initial normal body mass index groups.

Conclusions

Rapid and sizable weight gain could be additional criteria for disability risk in older adults. Geriatr Gerontol Int 2023; 23: 809–816.
Preclinical development and characterization of a human plasma‐derived high‐purity factor X concentrate for therapeutic use
Authors: Lloyd Joanne , Feldman Peter
Published: September 2023

Introduction

Hereditary factor X deficiency is a rare bleeding disorder, with limited treatment options. This paper describes the approach to pre‐clinical development and characterization of a high‐purity plasma‐derived factor X concentrate, to achieve orphan drug marketing authorization for the treatment of hereditary factor X deficiency.

Methods

A chromatographic process was developed, to purify factor X from human plasma for fractionation. The product was characterized using in vitro, in vivo and ex vivo tests for potency, purity, thrombogenicity, immunogenicity, toxicity and stability.

Results

The production process complied with good pharmaceutical manufacturing practice. It achieved 6000‐fold purification and 100‐fold concentration of the factor X protein compared to human plasma. The factor X protein was 94%–96% pure. Other residual plasma proteins were well below levels in plasma, minimizing potential interference in hemostasis after therapeutic administration. Effective virus‐reduction during manufacture, and the absence of thrombogenicity, toxicity and immunogenic potential were confirmed, addressing the main safety concerns historically associated with plasma‐derived therapeutics. The freeze‐dried product remained stable between +2°C and +30°C for at least three years. After reconstitution with water for injections, the factor X activity was maintained for at least 48 h at +18°C to +22°C.

Conclusion

Targeted pre‐clinical development of the first highly‐purified concentrate to treat hereditary factor X deficiency is described. Following international guidelines for nonclinical safety testing, particular strategies were adopted for unmodified products derived from human blood plasma. This approach may also be relevant to the development of other ultra‐orphan medicinal products.
The in vitro effect of anticoagulant agents on coagulation and fibrinolysis in the presence of emicizumab in the plasmas from patients with haemophilia A
Authors: Onishi Tomoko , Harada Suguru , Shimo Hanako , Tashiro Yoshihito , Soeda Tetsuhiro , Nogami Keiji
Published: September 2023

Introduction

Emicizumab is used as hemostatic prophylaxis for patients with hemophilia A (PwHA), irrespective of the presence of inhibitors. Although bacterial infection can lead to a procoagulant state, there is limited information on coagulation and fibrinolysis potentials in emicizumab‐treated PwHA and on the use of anticoagulants in such cases.

Aim

We examined whether anticoagulants affect the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab.

Methods

Plasma from PwHA was in vitro supplemented with emicizumab (50 μg/mL; emi‐plasma) and anticoagulants (recombinant thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or low‐molecular‐weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was used as a reference (ref‐plasma). The coagulation and fibrinolysis potentials in plasma was measured by thrombin and plasmin generation assay (T/P‐GA) and clot‐fibrinolysis waveform analysis (CFWA).

Results

In T/P‐GA and CFWA, coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; Th‐Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, but fibrinolytic potentials (peak plasmin; Plm‐Peak, and maximum fibrinolytic velocity; |FL‐min1|) remained unchanged. Adding rTM, NM, and UFH to emi‐plasma suppressed coagulation and fibrinolysis potentials, similar to ref‐plasma. Regarding the heparin, UFH and LMH inhibited the improved coagulation in emi‐plasma. UFH inhibited fibrinolysis as well, but LMH did not.

Conclusions

Anticoagulants could exhibit the inhibitory effects on the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to those in normal plasma.
A national assessment of standards of care for inherited bleeding disorders in Canada
Authors: Page David , Crymble Sarah , Jardine Lawrence , Nilson JoAnn , Mulder Kathy , Pardy Natasha , Pirnat Bojan , Pirnat Milena , Quinn Wendy , Sims Karen , Thompson Marie‐Hélène , Wilton Pam
Published: September 2023

Aim

The Canadian Integrated and Comprehensive Care Standards for Inherited Bleeding Disorders were adopted in June 2020. In early 2023, a self‐assessment of each of the 26 Canadian inherited bleeding disorder treatment centre's (IBDTCs) capacity to meet the Standards was conducted. The goal was to validate the standards by assessing appropriateness and adherence. As a result, centres can compare their own practices and capacity against those of all centres, identify barriers to adherence, identify opportunities for remedial actions and use the results locally as evidence for needed resources.

Methods

Healthcare providers (HCPs) in the 26 IBDTCs were provided with a checklist to assess adherence to each of the 66 standards of care. Centre participation was voluntary but strongly encouraged by the healthcare provider and patient associations.

Results

All 26 centres completed the self‐assessments. Collectively, centres reported meeting 88.8% of the standards. Adherence to each standard ranged from 40% to 100%. Forty‐one (41) of the standards were adhered to by 90% or more of the centres, 12 by 80%–89% of the centres and 13 by fewer than 80% of the centres. A report consolidating all the assessments was sent to the 26 centres.

Conclusion

None of the comments received in the self‐assessment reports indicated that a given standard was irrelevant, unrealistic or unnecessary. These data are strong indicators that the standards, as written, are appropriate. The self‐assessments, however, reveal alarming deficiencies in staffing levels, notably in physiotherapy, psychosocial support and data entry and data management. These constitute a barrier to comprehensive care for many centres. The findings echo similar conclusions from a previous assessment conducted in 2015.
Oropharyngolaryngeal manifestations in severe toxic epidermal necrolysis: a single‐center's retrospective case series
Authors: Glasson Nicolas , De Sandre Cécile , Pantet Olivier , Reinhard Antoine , Lambercy Karma , Sandu Kishore , Gorostidi François
Published: September 2023

Background

Toxic epidermal necrolysis is a rare and life‐threatening mucocutaneous disease. Although mucosal ear, nose, and throat (ENT) involvement is common, little is known about the characteristics, treatment modalities, and outcomes of these lesions. The aim of this study was to evaluate ENT mucosal lesions in severe toxic epidermal necrolysis patients and analyze their characteristics, treatment modalities, and outcomes, as well as proposing a management algorithm to prevent long‐term debilitating sequalae of these lesions.

Methods

This is a retrospective review of toxic epidermal necrolysis cases treated at the tertiary burns unit of the Lausanne University Hospital CHUV, Switzerland, between 2006 and 2019.

Results

Out of 19 patients with severe toxic epidermal necrolysis, 17 (89%) underwent a complete ENT examination at admission and 14 (82%) had ENT mucosal involvement. Five (26.3%) patients died during the stay in the intensive care unit. Of the 16 patients who received maximal care, 13 (81%) required orotracheal intubation for a median time of 16 (IQR: 14) days. Out of the 14 patients who survived, four (29%) had long‐term ENT complications consisting of synechiaes necessitating subsequent endoscopic procedures. Those four patients all required mechanical ventilation with an orotracheal tube and suffered from hypopharyngeal synechiaes as well as oral and endonasal synechiaes in individual cases.

Conclusion

This study suggests a high prevalence of ENT synechiaes in patients with severe toxic epidermal necrolysis and requiring orotracheal intubation. Periodic ENT examination could prevent mature synechiae formation in these patients. We propose an algorithm to prevent long‐term sequalae in ENT mucosal involvement.