bluuebunny/crossref_metadata_2025 huggingface dataset:
Extant interspecific hybridization among trematodes within theSchistosoma haematobiumspecies complex in Nigeria
Authors: Ajakaye OG , Enabulele EE , Balogun JB , Oyeyemi OT , Grigg ME
Published: July 2023

Background

Natural interspecific hybridization between the human parasite (Schistosoma haematobium[Sh]) and bovine parasites (S. bovis[Sb], S. curassoni[Sc]) is increasingly reported in Africa. We developed a multi-locus PCR DNA-Seq strategy that amplifies two unlinked nuclear (transITS,BF) and two linked organellar genome markers (CO1,NAD5) to genotypeS. haematobiumeggs collected from infected people in Ile Oluji/Oke Igbo, Ondo State (an agrarian community) and Kachi, Jigawa State (a pastoral community) in Southwestern and Northern Nigeria, respectively.

Principal Findings

We applied this methodology against 57 isolates collected from a total of 219 participants. All patients from Jigawa state were infected with just one of two haplotypes of anS. haematobium x S. bovishybrid based on sequences obtained atCO1,NAD5, transITSandBFmarkers. Whereas samples collected from Ondo state were varied. Mitonuclear discordance was observed in all 17 patients, worms possessed anSbmitochondrial genome but one of four different haplotypes at the nuclear markers, either admixed (heterozygous betweenSh x ScorSh x Sb) at both markers (n=10),ShatBFand admixed attransITS(Sh x Sc) (n=5), admixed (Sh x Sc) atBFand homozygousScattransITS(n=1) or homozygousShatBFand homozygousScattransITS(n=1).

Significance

Previous work suggested that zoonotic transmission ofS. bovisin pastoral communities, where humans and animals share a common water source, is a driving factor facilitating interspecific hybridization. However, our data showed that all isolates were hybrids, with greater diversity identified in Southwestern Nigeria, a non-pastoral site. Further, one patient possessed anS. bovismitochondrial genome but was homozygous forS. haematobiumatBFand homozygous forS. curassoniattransITSsupporting at least two separate backcrosses in its origin, suggesting that interspecific hybridization may be an ongoing process.

Author Summary

Interspecific hybridization between trematode parasites poses serious health risks to humans. Many systems have shown possible hybridization between different schistosome species. As evidence of natural hybridization between humanS. haematobiumand animalS. bovisorS. curassonihas grown in recent years, epidemiological surveys across potential hybrid zones are required, particularly in endemic African regions. According to several reports, indiscriminate human-animal water contact is a major factor contributing to hybridization of human and animal schistosomes. We collected and genotyped 57 parasite isolates from pastoral and non-pastoral communities in Kachi, Jigawa state, and Ile Oluji/Oke Igbo, Ondo state, Nigeria to screen for hybrids. In both sites, we foundSchistosomahybrids with mitonuclear discordance and repeated backcrossing betweenS. haematobium,S. bovis, andS. curassoni. Contrary to previous reports,Schistosomahybrids appear to be widespread and not solely dependent on human-animal water interactions.
Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production
Authors: King Connor R. , Berezin Casey-Tyler , Peccoud Jean
Published: July 2023

We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV’s intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understand the impact of the stochastic nature of early cellular infections on virion production between cells and how these dynamics change in response to mutations. Our model accurately predicts changes in mean virion production in gene-shuffled VSV variants and can capture the distribution of the number of viruses produced. This model has allowed us to enhance our understanding of intercellular variability in virion production, which appears to be influenced by the duration of the early phase of infection, and variation between variants, arising from balancing the time the genome spends in the active state, the speed of incorporating new genomes into virions, and the production of viral components. Being a stochastic model, we can also assess other effects of mutations beyond just the mean number of virions produced, including the probability of aborted infections and the standard deviation of the number of virions produced. Our model provides a biologically interpretable framework for studying the stochastic nature of VSV replication, shedding light on the mechanisms underlying variation in virion production. In the future, this model could enable the design of more complex viral phenotypes when attenuating VSV, moving beyond solely considering the mean number of virions produced.

Author Summary

This study presents the first complete stochastic model of vesicular stomatitis virus (VSV) replication. Our model captures the dynamic process of VSV’s replication within host cells, accounting for the stochastic nature of early cellular infections and how these dynamics change in response to mutations. By accurately predicting changes in mean virion production and the distribution of viruses in gene-shuffled VSV variants, our model enhances our understanding of viral replication and the variation we see in virion production. Importantly, our findings shed light on the mechanisms underlying the production of VSV virions, revealing the influence of factors such as the duration of the early infection phase and the interplay between the genome’s ability to switch into an inactive state and viral protein production. We go beyond assessing the mean number of virions produced and examine other effects of mutations, including the probability of aborted infections and the variability in virion production. This stochastic model provides a valuable framework for studying the complex nature of viral replication, contributing to our understanding of single-cell viral dynamics and variability. Ultimately, this knowledge could pave the way for designing more effective strategies to attenuate VSV.
A humoral stress response protectsDrosophilatissues from antimicrobial peptides
Authors: Rommelaere Samuel , Carboni Alexia , Bada Juarez Juan F. , Boquete Jean-Philippe , Abriata Luciano A. , Meireles Fernando Teixeira Pinto , Rukes Verena , Vincent Crystal , Kondo Shu , Dionne Marc S. , Dal Peraro Matteo , Cao Chan , Lemaitre Bruno
Published: July 2023

The immune response against an invading pathogen is generally associated with collateral tissue damage caused by the immune system itself. Consequently, several resilience mechanisms have evolved to attenuate the negative impacts of immune effectors. Antimicrobial peptides (AMPs) are small, cationic peptides that contribute to innate defenses by targeting negatively charged membranes of microbes1, 2. While being protective against pathogens, AMPs can be cytotoxic to host cells1, 3. Little is known of mechanisms that protect host tissues from AMP-induced immunopathology. Here, we reveal that a family of stress-induced proteins, the Turandots4, 5, protectDrosophilahost tissues from AMPs, increasing resilience to stress. Deletion of severalTurandotgenes increases fly susceptibility to environmental stresses due to trachea apoptosis and poor oxygen supply. Tracheal cell membranes expose high levels of phosphatidylserine, a negatively charged phospholipid, sensitizing them to the action of AMPs. Turandots are secreted from the fat body upon stress and bind to tracheal cells to protect them against AMPs.In vitro, Turandot A binds to phosphatidylserine on membranes and inhibits the pore-forming activity ofDrosophilaand human AMPs on eukaryotic cells without affecting their microbicidal activity. Collectively, these data demonstrate that Turandot stress proteins mitigate AMP cytotoxicity to host tissues and therefore improve their efficacy. This provides a first example of a humoral mechanism used by animals limiting host-encoded AMP collateral damages.
The WY domain of an RxLR effector drives interactions with a host target phosphatase to mimic host regulatory proteins and promotePhytophthora infestansinfection
Authors: Bentham Adam R. , Wang Wei , Trusch Franziska , Varden Freya A. , Birch Paul R. J. , Banfield Mark J.
Published: July 2023

Plant pathogens manipulate the cellular environment of the host to facilitate infection and colonization, often leading to plant diseases. To accomplish this, many specialized pathogens secrete virulence proteins called effectors into the host cell, which subvert processes such as immune signalling, gene transcription, and host metabolism.Phytophthora infestans, the causative agent of potato late blight, employs an expanded repertoire of RxLR effectors with WY domains to manipulate the host through direct interaction with protein targets. However, our understanding of the molecular mechanisms underlying the interactions between WY effectors and their host targets remains limited. In this study, we performed a structural and biophysical characterization of theP. infestansWY effector, Pi04314, in complex with the potato Protein Phosphatase 1-c (PP1c). We elucidate how Pi04314 uses a WY domain and a specialised C-terminal loop carrying a KVxF motif that interact with conserved surfaces on PP1c, known to be used by host regulatory proteins for guiding function. Through biophysical and in planta analyses, we demonstrate that Pi04314 WY or KVxF mutants lose their ability to bind PP1c. The loss of PP1c binding correlates with a reduced capacity to re-localize PP1c from the nucleolus and a decrease in lesion size in plant infection assays. This study provides insights into the manipulation of plant hosts by pathogens, revealing how effectors exploit key regulatory interfaces in host proteins to modify their function and facilitate disease.
ANOTHER TOOL IN THE TOOLBOX:Wolbachia-mediated protection against a specialized fungal pathogen of aphids
Authors: Higashi C.H.V. , Kamalaker B. , Patel V. , Inaganti R. , Bressan A. , Russell J.A. , Oliver K.M.
Published: July 2023

Aphids harbor nine heritable facultative symbionts, most mediating one or more ecological interactions. However, one aphid symbiont,Wolbachia, has eluded functional characterization despite being well-studied in other arthropods. InPentaloniaaphids, global pests of banana,Wolbachiawas hypothesized to function as a co-obligate symbiont alongside the traditional obligateBuchnera, but subsequent genomic analyses failed to support this role. Sampling across multiple aphid populations, we found that > 80% ofPentaloniaaphids carried a M-supergroup strain ofWolbachianamedwPni. While the lack of fixation confirms thatWolbachiais not a co-obligate symbiont, the high infection frequencies in these entirely asexual aphids strongly suggestedWolbachiaconfers net fitness benefits. Finding no correlation betweenWolbachiaand aphid food plants use, we challengedWolbachia-infected aphids with common natural enemies. WhileWolbachiadid not protect aphids against parasitoids, this symbiont conferred significant protection against the specialized fungal pathogen,Pandora neoaphidis,and improved aphid fitness in the absence of enemy challenge. Thus, we identified a new phenotype for the multifacetedWolbachiaand highlight a system that provides unique opportunities to merge key models of heritable symbiosis to better understand infection dynamics in nature and mechanisms underpinning symbiont-mediated phenotypes.

IMPORTANCE:Wolbachiasymbionts spread and persist in a wide range of arthropods and nematodes by using a range of functional strategies, including reproductive manipulation, providing protection against viral and bacterial pathogens or by provisioning nutrients. Despite being one of the best-studied symbionts, little is known about the strains that infect aphids. In this study, we characterized the functional role of a Supergroup MWolbachiastrain infecting strictly asexual aphids of the genusPentalonia. We report for the first time that this symbiont also defends against fungal entomopathogens and expand on the range of phenotypes conferred by this multifaceted symbiont.
Mutation in F-actin Polymerization Factor Suppresses Distal Arthrogryposis Type 5 (DA5) PIEZO2 Pathogenic Variant inCaenorhabditis elegans
Authors: Bai Xiaofei , Smith Harold E. , Romero Luis O , Bell Briar , Vásquez Valeria , Golden Andy
Published: July 2023

The mechanosensitive PIEZO channel family has been linked to over 26 disorders and diseases. Although progress has been made in understanding these channels at the structural and functional levels, the underlying mechanisms of PIEZO-associated diseases remain elusive. In this study, we engineered four PIEZO-based disease models using CRISPR/Cas9 gene editing. We performed an unbiased chemical mutagen-based genetic suppressor screen to identify putative suppressors of a conserved gain-of-function variantpezo-1[R2405P]that in humanPIEZO2causes distal arthrogryposis type 5 (DA5; p. R2718P). Electrophysiological analyses indicate thatpezo-1(R2405P)is a gain-of-function allele. Using genomic mapping and whole genome sequencing approaches, we identified a candidate suppressor allele in theC. elegansgenegex-3.This gene is an ortholog of humanNCKAP1(NCK-associated protein 1), a subunit of the Wiskott-Aldrich syndrome protein (WASP)-verprolin homologous protein (WAVE/SCAR) complex, which regulates F-actin polymerization. Depletion ofgex-3by RNAi, or with the suppressor allelegex-3(av259[L353F]), significantly restored the small brood size and low ovulation rate, as well as alleviated the crushed oocyte phenotype of thepezo-1(R2405P)mutant. Auxin-inducible degradation of GEX-3 revealed that only somatic-specific degradation of GEX-3 restored the reduced brood size in thepezo-1(R2405P)mutants. Additionally, actin organization and orientation were disrupted and distorted in thepezo-1mutants. Mutation ofgex-3(L353F)partially alleviated these defects. The identification ofgex-3as a suppressor of the pathogenic variantpezo-1(R2405P)suggests that the cytoskeleton plays an important role in regulating PIEZO channel activity and provides insight into the molecular mechanisms of DA5 and other PIEZO-associated diseases.
Synthesis and crystal structures of (E)-N′-(4-chloro-3-nitrobenzylidene)acetohydrazide and (E)-2-(4-chlorobenzylidene)-1-(quinolin-8-yl)hydrazine
Authors: Nasr Tamer , Kariuki Benson M. , Elansary Mai M. , Elhaggar Radwan , Zaghary Wafaa
Published: July 2023

The syntheses of two benzylidenehydrazine derivatives, namely, (E)-N′-(4-chloro-3-nitrobenzylidene)acetohydrazide, C9H8ClN3O3, and (E)-2-(4-chlorobenzylidene)-1-(quinolin-8-yl)hydrazine, C16H12ClN3, are reported. The molecules have been characterized using IR, 1H NMR, 13C NMR and mass spectroscopic and elemental analysis techniques, and their structures have been determined by single-crystal X-ray diffraction.
Evolution of the courtyard to the skycourt: a bibliometric analysis of research trends
Authors: Adel Rasha , Megahed Naglaa , Hassan Asmaa M. , Shahda Merhan
Published: July 2023

Purpose

Passive design strategies contribute to improving indoor comfort conditions and reducing buildings' energy consumption. For several years, courtyards have received wide attention from researchers because of their significant role in reducing energy demand. However, the abundance of multi-story buildings and the courtyards' incompatibility with them, the courtyard is currently limited. Therefore, it is necessary to search for alternatives. This paper aims to bridge the gaps in previous limited studies considering skycourt as a passive alternative on the vertical plane of the facades in contrast to the courtyard.

Design/methodology/approach

This research presents an overview and a bibliometric analysis of the evolution of the courtyard to the skycourt via VOSviewer software and the bibliometrix R package.

Findings

The research provided various concepts related to skycourt as a promising passive design strategy, which can be suitable for multi-story buildings, starting with its evolution, characteristics, configurations, benefits, and challenges.

Practical implications

The findings can urge designers, researchers and policymakers to incorporate such an important passive alternative.

Social implications

Researchers, instructors, educational specialists, faculty members, and decision-makers can provide design motivation for skycourt in buildings, in addition to achieving awareness about skycourt and its significant benefits and its role as an important passive design strategy.

Originality/value

The research highlights the possibilities of the skycourt and its role as a passive design element as an extension of the courtyard in addition to identifying design indicators that help designers determine the appropriate designs.
Effective child well-being practices, barriers and priority actions: survey findings from service providers and policymakers in 22 countries during COVID-19
Authors: Karadzhov Dimitar , Wilson Graham , Shields Sophie , Lux Erin , Davidson Jennifer C.
Published: July 2023

Purpose

The purpose of this study was to explore 232 service providers’ and policymakers’ experiences of supporting children’s well-being during the pandemic, across sectors, in 22 countries – including Kenya, the Philippines, South Africa, India, Scotland, Sweden, Canada and the USA, in the last quarter of 2020.

Design/methodology/approach

A smartphone survey delivered via a custom-built app containing mostly open-ended questions was used. Respondents were recruited via professional networks, newsletters and social media. Qualitative content analysis was used.

Findings

The findings reveal numerous system-level challenges to supporting children’s well-being, particularly virus containment measures, resource deficiencies and inadequate governance and stakeholder coordination. Those challenges compounded preexisting inequalities and poorly affected the quality, effectiveness and reach of services. As a result, children’s rights to an adequate standard of living; protection from violence; education; play; and right to be heard were impinged upon. Concurrently, the findings illustrate a range of adaptive and innovative practices in humanitarian and subsistence support; child protection; capacity-building; advocacy; digitalisation; and psychosocial and educational support. Respondents identified several priority areas – increasing service capacity and equity; expanding technology use; mobilising cross-sectoral partnerships; involving children in decision-making; and ensuring more effective child protection mechanisms.

Practical implications

This study seeks to inform resilience-enabling policies and practices that foster equity, child and community empowerment and organisational resilience and innovation, particularly in anticipation of future crises.

Originality/value

Using a novel approach to gather in-the-moment insights remotely, this study offers a unique international and multi-sectoral perspective, particularly from low- and middle-income countries.
Blockchain applications for traceability and food safety in agri-food supply chain: cherry product application
Authors: İndap Şebnem , Tanyaş Mehmet
Published: July 2023

Purpose

The primary objective of this study is to investigate the application of blockchain technology (BCT) in the agri-food supply chain, focusing on traceability and food safety.

Design/methodology/approach

The study employed a semi-structured interview method with representatives from the cherry supply chain to evaluate their awareness and acceptance of BCT's impact. Additionally, the analytic hierarchy process (AHP) was utilized to determine digital investment priorities in supply chain strategies. By applying the supply chain operations reference (SCOR) model framework to the cherry supply chain, the study aimed to address the question “Which process model is suitable for implementing BCT in the agri-food supply chain?”

Findings

The global agri-food supply chains are characterized by significant food losses, escalating prices along the chain, and food safety risks. Concurrently, consumer concerns regarding food safety, quality and transparency are on the rise. BCT, with its ability to ensure data integrity, immutability, and seamless tracking of chain movements, presents immense potential as a secure infrastructure in the agri-food supply chain traceability.

Originality/value

The developed analytic framework and the study's findings can be adapted to different sectors and different sub-sectors within agri-food supply chains.
Corruption and economic growth in Nigeria: dynamic causality and asymmetric relationships
Authors: Danlami Ibrahim Abdulhamid
Published: July 2023

Purpose

This study aims to intend to investigate the dynamic causality and asymmetric relationships between corruption and economic growth of Nigeria.

Design/methodology/approach

Toda–Yamamoto (TY) Dynamic Causality Test and Non-linear Autoregressive Distributed Lag Model (NARDL) were used for the estimations, for the period 1984–2018.

Findings

The result reveals the existence of bidirectional causality between control of corruption and economic growth, Similarly, in both the short run and long run, corruption can affect economic growth and economic growth can as well affects corruption.

Research limitations/implications

Findings of the research are limited to Nigeria whose data were used, based on TY causality test and NARDL as the econometrics techniques applied, for a period 1984–2018.

Practical implications

For a meaningful progress to be recorded in Nigeria in terms of economic growth, the country must device some means for strengthen the control of corruption.

Originality/value

The study was able to prove empirically, the existence of not only causality between corruption and economic growth but also asymmetric effect of corruption on economic growth and that of economic growth on corruption in both the long run and short run, as against the previous studies that are lopsided on the effect of corruption on economic growth only.
When identity is sanctity: servant leadership guarding against moral disengagement through building strong moral identity in the presence of organizational politics
Authors: Jameel Aqib , Khan Muhammad Mumtaz , Ahmed Syed Saad
Published: July 2023

Purpose

The study was conducted to understand how the moral identity of employees mediates the relationship between servant leadership and the moral disengagement of employees. Additionally, the study explores whether servant leadership's ability to build the moral identity of employees is contingent upon employees' perception of organizational politics.

Design/methodology/approach

The data were collected from 500 service sector-employed knowledge workers. Data analysis was done through structural equation modeling.

Findings

The study found servant leadership to be related to the moral identity of employees. Additionally, moral identity and moral disengagement were found to be negatively related. Moral identity was found to mediate the relationship between servant leadership and moral disengagement. Finally, the study found that the relationship between servant leadership and employees' moral identity was contingent upon their perception of organizational politics.

Originality/value

The study explored the previously unexplored mediating role of moral identity linking servant leadership to the moral disengagement of employees. The study also explained how the relationship between servant leadership and the moral identity of employees was contingent upon employees' perception of organizational politics.
Improving the properties of gap-filling materials for pottery artifacts with nano silica and nano kaolinite polymeric nanocomposites
Authors: Mohamed Hamdy Mohamed , Mohamed Wael Sabry
Published: July 2023

Purpose

The study aims to assess the efficiency of nanocomposite to improve the properties of gap-filling materials for pottery artifacts.

Design/methodology/approach

Five different pastes were used in the laboratory studies. The pastes consist mainly of pottery powder (grog), dental plaster, microballoons and an adhesive of Primal AC33, nano-silica and nano kaolinite in various concentrations. The prepared samples were subjected to accelerated heat and light aging. Besides, some investigations were used to evaluate the efficacy of the additive nanomaterials, such as TEM, digital and scanning electron microscopy microscopes. Contact angle, color change, shrinkage degree, physical properties and compressive strength tests were also conducted.

Findings

The results indicated that using Nano-silica considerably improves the mechanical strength and decreases the shrinkage of gap-filling materials. According to the results, a mixture of grog, microballoons and Primal AC33/Nano-silica Nanocomposites is the optimal gap-filling paste for archaeological pottery. Moreover, this paste showed a higher contact angle (120°), lower color change (ΔE = 2.62), lower shrinkage (3.3%), lower water absorption (3.36%), lower porosity (5.05%) and higher compressive strength (5124 N/mm2).

Originality/value

This paper attains to develop an economic polymer-nanocomposite that can be used with gap-filling materials for pottery artifacts.
The Pharmacist's role in dermatology: Patient medication adherence
Authors: Pathak Gaurav N. , Chandy Rithi J. , Shah Radhika , Feldman Steven R.
Published: July 2023

Medication non‐adherence is currently estimated to have caused at least 100 000 preventable deaths and over $100 billion in preventable medical costs. Adherence is particularly poor in dermatological conditions, with more than 50% of patients discontinuing topical treatments within the first year. Pharmacists are among the most accessible health‐care professionals with the potential to greatly impact medication non‐adherence through patient education, medication therapy management, and improved access to care. This review aimed to determine how pharmacists have improved medication adherence in dermatology and discuss strategies for further involvement. An extensive medical literature search using the PubMed database was conducted to evaluate clinical studies, published in the last 20 years, that have evaluated the pharmacist's role and impact on adherence of to dermatological products. PubMed search terms include: “pharmacists' role in dermatologic medication adherence”, “pharmacist‐led interventions in dermatology”, “pharmacist medication adherence dermatology” and “pharmacist intervention dermatology”. A total of 18 relevant studies were identified. Pharmacists improved dermatological medication adherence by increasing access to medications, providing medication counseling programs, and performing treatment monitoring services. However, corticophobia may contribute to pharmacists' hesitancy in making corticosteroid over‐the‐counter recommendations. Pharmacists are accessible health‐care providers with the potential to improve dermatological medication adherence. Future advanced training in dermatology medications may refine pharmacists’ knowledge of dermatological products.
The function of decidua natural killer cells in physiology and pathology of pregnancy
Authors: Jin Fangfang , Liu Wei , Cheng Guan , Cai Songchen , Yin Tailang , Diao Lianghui
Published: July 2023

The role of decidual natural killer (dNK) cells in maintaining immune tolerance at the maternal‐fetal interface during pregnancy is a significant topic in reproductive health. Immune tolerance is essential for a successful pregnancy and involves a complex immune response involving various immune cells and molecules. DNK cells comprise the largest population of lymphocyte subsets found in the decidua and play important roles in maintaining immune tolerance. These cells exert multiple functions to maintain homeostasis of the decidual microenvironment, including modulation of trophoblast invasion, promotion of fetal development, regulation of endometrial decidualization and spiral artery remodeling. DNK cells can also be divided into different subsets based on their functions as NKtolerant, NKcytotoxic, and NKregulatory cells. However, the relationship between dNK cells function and pregnancy outcomes is complex and poorly understood. In this review, we will focus on the physiological role of dNK cells during pregnancy and highlight the potential role in pathological pregnancies and therapeutic approaches.
Immunoglobulin E autoantibodies in atopic dermatitis associate with Type‐2 comorbidities and the atopic march
Authors: Kortekaas Krohn Inge , Badloe Fariza Mishaal Saiema , Herrmann Nadine , Maintz Laura , De Vriese Shauni , Ring Johannes ,   CK‐CARE Study Group, Bieber Thomas , Gutermuth Jan
Published: July 2023

Background

Autoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years).

Methods

Atopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases (“AD + Type 2”; asthma, allergic rhinitis, food allergy, n = 431) or “solely AD” (n = 115). Also, subjects without AD but with Type‐2 diseases (“atopic controls,” n = 52) and non‐atopic “healthy controls” (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples.

Results

Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. “AD + Type 2” showed a higher prevalence (16.4%) than “solely AD” (9.6%). “Atopic controls” (9.6%) were comparable with “solely AD” patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with “AD + Type 2”. AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets.

Conclusions

Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration.
Aristotle's fieldnotes*
Authors: Varzi Roxanne
Published: July 2023

This piece is part of a special section of hundreds for Kathleen Stewart. It upends genres, labels, and categories (beginning with Aristotle) using dyslexia and decoding to unfold boxes.
Effect of grandchildren on the happiness of grandparents: Does the grandparent's child's gender matter?
Authors: Yamamura Eiji , Brunello Giorgio
Published: July 2023

Using a representative sample from Japan and a difference‐in‐differences strategy, we investigate whether the effect of having grandchildren on the happiness of grandparents varies with the gender of their (own) single child. In line with our expectations, we find that maternal grandmothers have more to lose or less to gain from having grandchildren than paternal grandmothers. In contrast, grandfathers’ changes in happiness do not depend on their own child's gender. This result is explained by the fact that grandmothers are more likely to be involved in childrearing when their daughter has a child.
Real exchange rate misalignment and business cycle fluctuations in theAsia‐Pacific
Authors: Ambaw Dessie , Pundit Madhavi , Ramayandi Arief , Sim Nicholas
Published: July 2023

Real exchange rate (RER) misalignment, which is the deviation between the actual real exchange rate from its equilibrium, occurs frequently among developing countries. Studies have shown that RER misalignment may have negative economic implications, such as a decline in economic growth, exports, and export diversification and an increased risk of currency crises and political instability. Using quarterly data for 22 sample countries from 1990 to 2018, this paper investigates the impact of RER misalignment on business cycles in the Asia‐Pacific by employing a panel vector autoregression involving consumer price index (CPI) inflation, output gap, short‐term interest rates, and RER misalignment. We find that RER overvaluation may reduce CPI inflation and short‐term interest rates. We also find that the Asia‐Pacific region is highly heterogeneous in that the output gaps of some countries, particularly from the Southeast Asian region, are more susceptible to RER misalignment shocks.
Discussion of “Optimal Test Procedures for Multiple Hypotheses Controlling the Familywise Expected Loss” by Willi Maurer, Frank Bretz, and Xiaolei Xun
Authors: LaVange L.M. , Alt E.M. , Ibrahim J.G.
Published: July 2023

We provide commentary on the paper by Willi Maurer, Frank Bretz, and Xiaolei Xun entitled, “Optimal test procedures for multiple hypotheses controlling for the familywise expected loss.” The authors provide an excellent discussion of the multiplicity problem in clinical trials and propose a novel approach based on a decision-theoretic framework that incorporates loss functions that can vary across multiple hypotheses in a family. We provide some considerations for the practical use of the authors' proposed methods as well as some alternative methods that may also be of interest in this setting.
Challenges and solutions to superior chimeric antigen receptor‐T design and deployment for B‐cell lymphomas
Authors: Gao Jenny , Dahiya Saurabh , Patel Shyam A.
Published: July 2023

Chimeric antigen receptor‐T (CAR‐T) therapies represent a major breakthrough in cancer medicine, given the ex vivo‐based technology that harnesses the power of one's own immune system. These therapeutics have demonstrated remarkable success for relapsed/refractory B‐cell lymphomas. Although more than a decade has passed since the initial introduction of CAR‐T therapeutics for patients with leukaemia and lymphoma, there is still significant debate as to where CAR‐T therapeutics fit into the management paradigm, as consensus guidelines are limited. Competing interventions deployed in subsequent lines of therapy for aggressive lymphoma include novel targeted agents, bispecific antibodies, and time‐honoured stem cell transplant. In this focused review, we discuss the major obstacles to advancing the therapeutic reach for CAR‐T products in early lines of therapy. Such barriers include antigen escape, “cold” tumour microenvironments, host inflammation and CAR‐T cell exhaustion. We highlight solutions including point‐of‐care CAR‐T manufacturing and early T lymphopheresis. We review the evidence basis for early CAR‐T deployment for B‐cell lymphomas in light of the recent Food and Drug Administration (FDA) approval of three first‐in‐class anti‐CD3/CD20 bispecific antibodies—mosunetuzumab, epcoritamab and glofitamab. We propose practical recommendations for 2024.
Trends in incidence and overdiagnosis of thyroid cancer in China, Japan, and South Korea
Authors: Lin Yongtian , Wu Yu
Published: July 2023

We used data from 13 cancer registries in China, Japan, and South Korea to analyze time trends in overdiagnosis of thyroid cancer between 1998 and 2012. Age‐standardized and age‐specific incidence and annual percentage changes were calculated. The number of thyroid cancers diagnosed and the proportion attributable to overdiagnosis were estimated, with calculations stratified by sex and age group. The Spearman method was used to analyze the correlation between thyroid cancer incidence and overdiagnosis. From 1998 to 2012, both the incidence and proportions of overdiagnoses of thyroid cancer in China, Japan, and South Korea showed an increasing trend, with higher rates in women than men. South Korea had both the highest incidence for men (10.1/105) and women (46.7/105) and the highest proportions of overdiagnosis (men, 90.3%; women, 94.9%). The fastest growth in overdiagnosis was in Chinese men and women (annual percentage changes 6.1 and 4.6, respectively). We found significant positive correlations between age‐standardized incidence and proportions of overdiagnosis for both men (Spearman r = 0.98, p < 0.05) and women (Spearman r = 0.99, p < 0.05) in the three countries. Age‐specific incidence curves in Chinese and South Korean individuals were of an inverted U‐shape. Overdiagnosis of thyroid cancer in Japan was mainly concentrated in middle‐aged and older patients, whereas in China and South Korea, it occurred primarily in the middle‐aged. The incidence and overdiagnosis of thyroid cancer in China, Japan, and South Korea are increasing, necessitating the implementation of comprehensive measures to reduce these overdiagnoses.
GPI‐anchoring disorders and the heart: Is cardiomyopathy an overlooked feature?
Authors: Bayat Allan , Lindau Tobias , Aledo‐Serrano Angel , Gil‐Nagel Antonio , Barić Ivo , Bartoniček Dorotea , Mateševac Josipa , Ramadža Danijela Petković , Žigman Tamara , Pušeljić Silvija , Dorner Sanja , Bupp Caleb , Devries Seth , Møller Rikke Steensbjerre
Published: July 2023

Glycosylphosphatidylinositol anchoring disorders (GPI‐ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA‐encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy. We aimed to explore the occurrence of cardiomyopathy among patients with GPI‐ADs and to raise awareness about this potentially lethal feature. Unpublished patients with genetically proven GPI‐ADs and cardiomyopathy were identified through an international collaboration and recruited through the respective clinicians. We also reviewed the literature for published patients with cardiomyopathy and GPI‐AD and contacted the corresponding authors for additional information. We identified four novel and unrelated patients with GPI‐AD and cardiomyopathy. Cardiomyopathy was diagnosed before adulthood and was the cause of early demise in two patients. Only one patients underwent cardiac workup after being diagnosed with a GPI‐AD. All were diagnosed with PIGA‐encephalopathy and three had a disease‐causing variant at the same residue. The literature reports five additional children with GPI‐AD related cardiomyopathy, three of which died before adulthood. We have shown that patients with GPI‐ADs are at risk of developing cardiomyopathy and that regular cardiac workup with echocardiography is necessary.
Genetic erosion in an endangered desert fish during a megadrought despite long‐term supportive breeding
Authors: Osborne Megan J. , Archdeacon Thomas P. , Yackulic Charles B. , Dudley Robert K. , Caeiro‐Dias Guilherme , Turner Thomas F.
Published: July 2023

Human water use combined with a recent megadrought have reduced river and stream flow through the southwest United States and led to periodic drying of formerly perennial river segments. Reductions in snowmelt runoff and increased extent of drying collectively threaten short‐lived, obligate aquatic species, including the endangered Rio Grande silvery minnow (Hybognathus amarus). This species is subject to boom‐and‐bust population dynamics, under which large fluctuations in abundance are expected to lower estimates of effective population size and erode genetic diversity over time. Rates of diversity loss are also affected by additions of hatchery‐origin fish used to supplement the wild population. We used demographic and genetic data from wild and hatchery individuals to examine the relationship of genetic diversity and effective population size to abundance over the last two decades. Genetic diversity was low during the early 2000s, but diversity and demographic metrics stabilized after the hatchery program was initiated and environmental conditions improved. Yet, from 2017 onward, allelic diversity declined (Cohen's d = 1.34) and remained low despite hatchery stocking and brief wild population recovery. Across the time series, single‐sample estimates of effective population size based on linkage disequilibrium (LD Ne) were positively associated (r = 0.53) with wild abundance and total abundance, but as the proportion of hatchery‐origin spawners increased, LD Ne declined (r = −0.55). Megadrought limited wild spawner abundance and precluded refreshment of hatchery brood stocks with wild fish; hence, we predict a riverine population increasingly dominated by hatchery‐origin individuals and accelerated loss of genetic diversity despite supplementation. We recommend an adaptive and accelerated management plan that integrates river flow management and hatchery operations to slow the pace of genetic diversity loss exacerbated by megadrought.
Mitigating supply‐demand mismatch: The relationship between inventory sharing and demand learning
Authors: Wei Liqun , Wei Wanying , Liu Yunchuan , Zhang Jianxiong , Xu Xuanhua
Published: July 2023

By mitigating supply‐demand mismatch through advanced forecast technology, demand learning has attracted widespread attention and is increasingly adopted in conjunction with inventory sharing. However, this combination is not necessarily efficient given the unclear relationship between the two strategies. Therefore, crucially, this article investigates the strategic relationship between inventory sharing and demand learning, that is, when and whether they are substitutes or complements. We develop a theoretical game model consisting of two firms facing uncertain demand, and both of them need to determine their production quantity before demand is realized. Contrary to the intuition that demand learning is a substitute for inventory sharing, we find that these two strategies can be complements when the production cost is relatively low or high. Moreover, when forecast accuracy is relatively low, the substitutability will be weakened while the complementarity will be enhanced as forecast accuracy increases. Additionally, the substitutability first weakly decreases and then weakly increases, while the complementarity first weakly increases and then weakly decreases with the transfer price.
Adaptive bolus calculators for people with type 1 diabetes: A systematic review
Authors: Unsworth Rebecca , Avari Parizad , Lett Aaron M. , Oliver Nick , Reddy Monika
Published: July 2023

Aim

To conduct a systematic review of studies assessing adaptive insulin bolus calculators for people with type 1 diabetes (T1D).

Methods

Electronic databases (Medline, Embase and Web of Science) were systematically searched from date of inception to 13 October 2022 for single‐arm or randomized controlled studies assessing adaptive bolus calculators only, in children or adults with T1D on multiple daily injections or insulin pumps with glycaemic outcomes reported. The Clinicaltrials.gov registry was searched for recently completed studies evaluating decision support in T1D. The quality of extracted studies was assessed using the Standard Quality Assessment criteria and the Cochrane Risk of Bias assessment tool.

Results

Six studies were identified. Extracted data were synthesized in a descriptive review because of heterogeneity. All the studies were small feasibility studies or were not suitably powered, and all were deemed to be at a high risk of performance and detection bias because they were unblinded. Overall, these studies did not show a significant glycaemic improvement. Two studies showed a reduction in postprandial time below range or an incremental change in blood glucose concentration; however, these were in controlled environments over a short duration.

Conclusions

There are limited clinical trials evaluating adaptive bolus calculators. Although results from small trials or in‐silico data are promising, further studies are required to support personalized and adaptive management of T1D.
Dihydroartemisinin inhibits angiogenesis in breast cancer via regulating VEGF and MMP‐2/‐9
Authors: Rao Qi , Yu He , Li Ruochan , He Bin , Wang Yuxue , Guo Xiaohong , Zhao Gang , Wu Fenghua
Published: July 2023

Background

Dihydroartemisinin (DHA) is an artemisinin derivative known for its antimalarial properties. It has also shown potential as an anti‐tumor and anti‐angiogenic agent. However, its specific role in inhibiting angiogenesis in breast cancer is not well understood.

Objectives

We aimed to investigate the anti‐angiogenesis effect of DHA on breast cancer and explore its potential as a therapeutic drug. Our objectives were to assess the impact of DHA on neovascularization induced by MDA‐MB‐231 cells, evaluate its effects on vessel sprout and tube‐formation in vascular endothelial cells, and analyze the expression of key angiogenesis‐related proteins.

Methods

Using a chicken chorioallantoic membrane (CAM) model, we cultured MDA‐MB‐231 cells and treated them with DHA. We assessed neovascularization and cultured vascular endothelial cells with DHA‐treated cell media to evaluate vessel sprout and tube‐formation. Protein expression levels of VEGF, MMP‐2, and MMP‐9 were analyzed using Western blotting.

Results

DHA significantly attenuated neovascularization induced by MDA‐MB‐231 cells. It also suppressed vessel sprout and tube‐formation of HUVEC cells when exposed to DHA‐treated cell media. Furthermore, DHA downregulated the expression of VEGF, MMP‐2, and MMP‐9 proteins. Mechanistically, DHA inhibited the phosphorylation of PI3K, AKT, ERK, and NF‐κB proteins in tumor cells.

Conclusions

Our study provides evidence of the inhibitory effect of DHA on breast cancer angiogenesis. These findings support the potential of DHA as an anti‐breast cancer drug and warrant further investigation for its therapeutic applications.
From self‐care to compassion resilience: Extending the model of protective factors for humanitarian practitioners
Authors: Richards Julie , Shrayer Guy
Published: July 2023

Humanitarian practitioners, specifically emergency aid and relief workers, disaster responders, social workers, and crisis clinicians, are at elevated risk of experiencing trauma as a result of their professions. Approaches for responding to the silent pandemic of reactive traumatic stress, including secondary traumatic stress and vicarious traumatization among humanitarian practitioners continue to be inadequate. The current model of self‐care, emphasizing internal regulation and processes to promote positive health, wellbeing, and the ability to continue to support others, is insufficient to best equip humanitarian practitioners with protective factors to stave off reactive traumatic responses to their work. We therefore propose our theory to extend the current self‐care model to include the external focus of compassion resilience and conclude with recommendations.