bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling innovative work behavior through leadership behaviors in the hospitality industry; the role of work–family enrichment
Authors: Kyei-Frimpong Michael , Berko Obeng Damoah Obi , Osafroadu Amankwah Majoreen
Published: March 2024

Purpose

This study aims to examine authentic leadership behavior (ALB) and empowering leadership behavior (ELB) as predictors of innovative work behavior (IWB) while assessing the mediating role of work-family enrichment (WFE).

Design/methodology/approach

Through the explanatory research design, data was retrieved from 303 respondents from 16 small-sized hotels in Ghana and analyzed quantitatively using descriptive and inferential statistics (hierarchical component analysis within PLS-SEM).

Findings

The study’s findings revealed that both ALB and ELB positively and significantly relate to IWB. Additionally, our study found that WFE partially mediated the nexus between ALB and IWB as well as ELB and IWB.

Practical implications

The findings of our study imply that in the pursuit of excellence, ALB and ELB in the hospitality industry are crucial, as they not only nurture employee potential but also help employees to thrive both at home and at the workplace.

Originality/value

The hospitality literature lacks a comprehensive understanding of the underlying mechanism by which ALB and ELB influence IWB. To the best of the authors' knowledge, our study is the first empirical study conducted on ALB, ELB, WFE, and IWB in the hospitality industry.
Conceptualization and validation of customer participation in health care: a study on chronic illnesses management
Authors: Junaid Muhammad , Goudarzi Kiane , Rasheed Muhammad Faisal , N’Goala Gilles
Published: March 2024

Purpose

Contrary to want-based services, customer participation has got lesser attention in high-credence services like health care. Customer participation for patients with chronic illnesses could be life-threatening and goes beyond the service organization’s physical environment. Realizing the importance of transformative service research in health-care services, this study aims to propose and validate the conceptualization of customer participation for patients with chronic illnesses.

Design/methodology/approach

The study uses sequential exploratory research design with mixed method research. The first phase is a qualitative exploration of the nature and meaning of customer participation by synthesizing theory and insights from semi-structured interviews (N = 75) with doctors, patients and paramedical staff. Next, survey data (N = 690) of patients with chronic illnesses is used to validate the proposed conceptualization. Finally, nomological validity was also tested on an additional survey data set (N = 362) using SEM and FsQCA.

Findings

The findings reveal that health-care customer participation is a three-dimensional behavioral construct in which a customer can participate by sharing information, involving in decision-making and ensuring compliance. The study also demonstrates that customer participation is a critical driver of satisfaction with life and perceived control on illness.

Practical implications

The research provides policy guidelines for owners and operators of health-care organizations in developing frameworks for collecting participation data, which can be used in strategies for seeking customer participation.

Originality/value

The research conceptualizes and validates “customer participation” as a multidimensional higher-order construct for patients with chronic illnesses, rarely focused in services marketing and management research on health care.
Do relational outcomes always generate willingness to pay for social enterprises’ products? The moderating effect of sustainability orientation
Authors: Ip Ching Yin
Published: March 2024

Purpose

This study evaluated the effects of adherence to social missions and relational outcomes on willingness to pay for products from social enterprises.

Design/methodology/approach

The study’s conceptual model was based on the social resource–based view. Three social enterprises in Taiwan were analysed, and the determinants of willingness to pay for products from these enterprises were investigated. An online survey was conducted, and 404 valid responses were collected and analysed using structural equation modelling. The moderating effect of sustainability orientation was evaluated using the multigroup method.

Findings

The results indicated that adherence to social missions was a critical predictor of relational outcomes and willingness to pay. In addition, sustainability orientation positively moderated the effect of relational outcomes on willingness to pay.

Originality/value

This study enriches the literature by applying the social resource–based view to the context of social enterprises. The study findings have key implications for managers and practitioners of social enterprises seeking to build relationships with stakeholders.
Enhancing the efficiency of a gas-fueled reheating furnace of the steelmaking industry: assessment and improvement
Authors: Sampaio Brasil João Eduardo , Piran Fabio Antonio Sartori , Lacerda Daniel Pacheco , Morandi Maria Isabel Wolf , Oliveira da Silva Debora , Sellitto Miguel Afonso
Published: March 2024

Purpose

The purpose of this study is to evaluate the efficiency of a Brazilian steelmaking company’s reheating process of the hot rolling mill.

Design/methodology/approach

The research method is a quantitative modeling. The main research techniques are data envelopment analysis, TOBIT regression and simulation supported by artificial neural networks. The model’s input and output variables consist of the average billet weight, number of billets processed in a batch, gas consumption, thermal efficiency, backlog and production yield within a specific period. The analysis spans 20 months.

Findings

The key findings include an average current efficiency of 81%, identification of influential variables (average billet weight, billet count and gas consumption) and simulated analysis. Among the simulated scenarios, the most promising achieved an average efficiency of 95% through increased equipment availability and billet size.

Practical implications

Additional favorable simulated scenarios entail the utilization of higher pre-reheating temperatures for cold billets, representing a large amount of savings in gas consumption and a reduction in CO2 emissions.

Originality/value

This study’s primary innovation lies in providing steelmaking practitioners with a systematic approach to evaluating and enhancing the efficiency of reheating processes.
Key technologies of earthquake early warning system for China’s high-speed railway
Authors: Zhang Geming , Yang Lin , Jiang Wenxiang
Published: March 2024

Purpose

The purpose of this study is to introduce the top-level design ideas and the overall architecture of earthquake early-warning system for high speed railways in China, which is based on P-wave earthquake early-warning and multiple ways of rapid treatment.

Design/methodology/approach

The paper describes the key technologies that are involved in the development of the system, such as P-wave identification and earthquake early-warning, multi-source seismic information fusion and earthquake emergency treatment technologies. The paper also presents the test results of the system, which show that it has complete functions and its major performance indicators meet the design requirements.

Findings

The study demonstrates that the high speed railways earthquake early-warning system serves as an important technical tool for high speed railways to cope with the threat of earthquake to the operation safety. The key technical indicators of the system have excellent performance: The first report time of the P-wave is less than three seconds. From the first arrival of P-wave to the beginning of train braking, the total delay of onboard emergency treatment is 3.63 seconds under 95% probability. The average total delay for power failures triggered by substations is 3.3 seconds.

Originality/value

The paper provides a valuable reference for the research and development of earthquake early-warning system for high speed railways in other countries and regions. It also contributes to the earthquake prevention and disaster reduction efforts.
Mosaic of local adaptation between white clover and rhizobia along an urbanization gradient
Authors: Murray‐Stoker David , Johnson Marc T. J.
Published: March 2024

Urbanization frequently alters the biotic and abiotic environmental context. Variation in both the biotic and abiotic environment can result in selection mosaics that lead to locally adapted phenotypes. Ecological changes to urban environments can result in evolutionary responses across a diverse array of plants and animals, but the effects of urbanization on local adaptation and coevolution between species remain largely unstudied.

Using a common garden experiment of 30 populations and 1080 plants, we tested for local adaptation in the mutualism between white clover (Trifolium repens) and rhizobia (Rhizobium leguminosarum symbiovar trifolii) along an urbanization gradient. We asked: (Q1) are white clover and rhizobia locally adapted? (Q2) Does nitrogen (N) addition mediate the strength of local adaptation? (Q3) Is the strength of local adaptation in host plants related to the strength of local adaptation in rhizobia, as expected if white clover and rhizobia are coadapting? And (Q4) how does the degree of local adaptation vary with urbanization?

We found evidence for local adaptation for both white clover and rhizobia, with stronger signatures of local adaptation for rhizobia than white clover (Q1). While N addition positively affected plant biomass and negatively affected nodule density, N addition did not consistently mediate patterns of local adaptation (Q2). The strength of local adaptation was positively related between white clover and rhizobia under N addition, suggesting that soil N mediates coadaptation between white clover and rhizobia (Q3). We did not find a consistent relationship between measures of urbanization and local adaptation (Q4). Additionally, fitness responses for white clover and rhizobia were unrelated to Rhizobium abundance and local adaptation was unrelated to the broader bacterial microbiome in the soil inoculants or root endosphere.

Synthesis. Our results show a spatial mosaic in local adaptation, with stronger local adaptation for rhizobia than white clover. While urbanization does influence the ecology of plant–microbe interactions, our study suggests urbanization does not disrupt local adaptation and coevolution among mutualists.
How good are global DNA‐based environmental surveys for detecting all protist diversity? Arcellinida as an example of biased representation
Authors: Useros Fernando , García‐Cunchillos Iván , Henry Nicolas , Berney Cédric , Lara Enrique
Published: March 2024

Metabarcoding approaches targeting microeukaryotes have deeply changed our vision of protist environmental diversity. The public repository EukBank consists of 18S v4 metabarcodes from 12,672 samples worldwide. To estimate how far this database provides a reasonable overview of all eukaryotic diversity, we used Arcellinida (lobose testate amoebae) as a case study. We hypothesised that (1) this approach would allow the discovery of unexpected diversity, but also that (2) some groups would be underrepresented because of primer/sequencing biases. Most of the Arcellinida sequences appeared in freshwater and soil, but their abundance and diversity appeared underrepresented. Moreover, 84% of ASVs belonged to the suborder Phryganellina, a supposedly species‐poor clade, whereas the best‐documented suborder (Glutinoconcha, 600 described species) was only marginally represented. We explored some possible causes of these biases. Mismatches in the primer‐binding site seem to play a minor role. Excessive length of the target region could explain some of these biases, but not all. There must be some other unknown factors involved. Altogether, while metabarcoding based on ribosomal genes remains a good first approach to document microbial eukaryotic clades, alternative approaches based on other genes or sequencing techniques must be considered for an unbiased picture of the diversity of some groups.
Self‐suasion: agents of Jewish conversion in Israel in search of religious sincerity
Authors: Kravel‐Tovi Michal
Published: March 2024

The title of this essay is intended as ironic. The irony resides in the fact that while the agents of state‐run Jewish conversion in Israel are preoccupied with the sincerity of conversion candidates, they are also troubled by the sincerity of their own religious belief and conduct. This essay will explore ethnographically how these religiopolitical actors engage with semiotic and interactive strategies of self‐suasion in order to reconcile their Zionist and religious commitments with the moral toll that they pay for knowingly facilitating less‐than‐ideal conversions. The essay demonstrates that while these actors embody the Israeli state's national missionary impetus to convert newcomers, they rely on a variety of communicative practices that help them project the constructed sincerity of converts onto their own self‐suaded religious sincerity.
‘I have it, so I understand it, I feel it’: The secondary school experiences of adolescent females with ADHD in England
Authors: Mansfield Eleanor M. G. , Soni Anita
Published: March 2024

This research explores how adolescent females who have been diagnosed with attention deficit hyperactivity disorder (ADHD) experience secondary education in England and make sense of their identity. Within schools, responsibility for supporting this population is placed in the hands of teachers, though prior research suggests that teachers feel underconfident in their ability to do so. Informed by a notion from the disability rights movement ‘nothing about us, without us’ (Charlton, Nothing about us without us: disability oppression and empowerment. Berkeley, CA: University of California Press, 2000), this study places the voice of people with ADHD at the centre of research. Using an interpretivist approach, qualitative data was gathered through unstructured interviews with five participants and was analysed using interpretative phenomenological analysis (IPA). Findings suggested that participants' experiences of education and identity formation were shaped by internal cognitive differences in skills relating to executive function (EF) and sensory differences. The implications of social construction of the ADHD label had an impact, both on how participants understood their identities, and how teaching staff were reported to respond to ADHD‐traits which participants felt they had little control over. Participants reported differences in their perceived ability to self‐advocate and described experiences of attempting to adapt their ADHD‐traits to reduce the risk of social or educational sanction in response to their differences.
An aquaporin and an aquaglyceroporin have roles in low temperature adaptation of mosquitoes (Anopheles sinensis)
Authors: Zhao Yong‐Qiao , Tang Yi‐Ying , Hu Ju‐Ping , Huang Yu‐Zheng , Wan Kai , Zhang Mei‐Hua , Li Ju‐Lin , Zhu Guo‐Ding , Tang Jian‐Xia
Published: March 2024

Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans‐cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An. sinensis: AsAQP2 (An. sinensis aquaglyceroporin) and AsAQP4 (An. sinensis aquaporin). When expressed in frog (Xenopus laevis) oocytes, AsAQP2 transported water, glycerol, and urea; AsAQP4 transported only water. Water permeation through AsAQP2 and AsAQP4 was inhibited by mercuric chloride. AsAQP2 expression was slightly higher in adult female mosquitoes than in males, and AsAQP4 expression was significantly higher in adult males. The 2 AsAQPs were highly expressed in Malpighian tubules and midgut. AsAQP2 and AsAQP4 expression was up‐regulated by blood feeding compared with sugar feeding. At freezing point (0 °C), the AsAQP4 expression level increased and An. sinensis survival time reduced compared with those at normal temperature (26 °C). At low temperature (8 °C), the AsAQP2 and AsAQP4 expression levels decreased and survival time was significantly longer compared with those at 26 °C. These results suggest that AsAQP2 and AsAQP4 have roles in water homeostasis during blood digestion and in low temperature adaptation of A. sinensis. Together, our results show that the 2 AQPs are important for mosquito diuresis after blood feeding and when exposed to low temperatures.
Immunological parameters of maternal peripheral blood as predictors of future pregnancy outcomes in patients with unexplained recurrent pregnancy loss
Authors: Li Yingrong , Wu Irene X. Y. , Wang Xuan , Song Jinlu , Chen Quan , Zhang Weiru
Published: March 2024

Introduction

Unexplained recurrent pregnancy loss (URPL), affecting approximately 1%–5% of women, exhibits a strong association with various maternal factors, particularly immune disorders. However, accurately predicting pregnancy outcomes based on the complex interactions and synergistic effects of various immune parameters without an automated algorithm remains challenging.

Material and methods

In this historical cohort study, we analyzed the medical records of URPL patients treated at Xiangya Hospital, Changsha, China, between January 2020 and October 2022. The primary outcomes included clinical pregnancy and miscarriage. Predictors included complement, autoantibodies, peripheral lymphocytes, immunoglobulins, thromboelastography findings, and serum lipids. Least absolute shrinkage and selection operator (LASSO) analysis and logistic regression analysis was performed for model development. The model's performance, discriminatory, and clinical applicability were assessed using area under the curve (AUC), calibration curve, and decision curve analysis, respectively. Additionally, models were visualized by constructing dynamic and static nomograms.

Results

In total, 502 patients with URPL were enrolled, of whom 291 (58%) achieved clinical pregnancy and 211 (42%) experienced miscarriage. Notable differences in complement, peripheral lymphocytes, and serum lipids were observed between the two outcome groups. Moreover, URPL patients with elevated peripheral NK cells (absolute counts and proportion), decreased complement levels, and dyslipidemia demonstrated a significantly increased risk of miscarriage. Four models were developed in this study, of which Model 2 demonstrated superior performance with only seven predictors, achieving an AUC of 0.96 (95% CI: 0.93–0.99) and an accuracy of 0.92. A web‐based platform was established to visually present model 2 and to facilitate its utilization by clinicians in outpatient settings (available from: https://yingrongli.shinyapps.io/liyingrong/).

Conclusions

Our findings suggest that the implementation of such prediction models could serve as valuable tools for providing comprehensive information and facilitating clinicians in their decision‐making processes.
Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation
Authors: Kacerovsky Marian , Hornychova Helena , Jaiman Sunil , Pavlikova Ladislava , Holeckova Magdalena , Jacobsson Bo , Tsiartas Panagiotis , Musilova Ivana
Published: March 2024

Introduction

This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra‐amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms‐like tyrosine kinase‐1 (sFlt‐1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations.

Material and methods

This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra‐amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra‐amniotic inflammation (by amniotic fluid interleukin‐6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt‐1 and PlGF were assessed using the Elecsys® sFlt‐1 and Elecsys® PlGF immunoassays and converted into multiples of medians.

Results

Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt‐1 and sFlt‐1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt‐1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, vs negative: median 0.4 MoM, P = 0.02; sFlt‐1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt‐1 and sFlt‐1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion.

Conclusions

Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra‐amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.
A critical activist orientation predicts lower latent ableist bias
Authors: Gravelle C. Donnan , Sawyer Jeremy E. , Rualo Gavin , Brooks Patricia J.
Published: March 2024

Despite legal efforts to reduce societal barriers, people with disabilities still face ableist bias, stereotyping, and stigma. According to the social movement hypothesis, people's participation in and identification with activist movements may reduce bias towards social outgroups. Alternatively, people's intergroup attitudes and bias may influence their participation in activist activities. This study used structural equation modeling to investigate whether reduced bias towards people with disabilities is associated with critical activism and/or personal, familial, or work experience with disability. Undergraduates (N = 497) completed an online survey including measures of ableist bias, critical activist orientation, experience with disability, and demographic characteristics. The relation between having a critical activist orientation and lower ableist bias was bidirectional, suggesting reciprocal influences between individual‐level attitudes and participation in progressive social movements. Aligning with intergroup contact theory, personal (lived) and familial experience with disability correlated with reduced ableist bias, and familial and work experience with having a critical activist orientation. Male gender correlated with increased ableist bias, and male gender, White race, and higher social class with lower endorsements of a critical activist orientation. The results suggest that disability experience and social status influence critical activist identity, which predicts lower bias.
WTAP‐induced N6‐methyladenosine of PD‐L1 blocked T‐cell‐mediated antitumor activity under hypoxia in colorectal cancer
Authors: Liu Qi‐zhi , Zhang Nan , Chen Jun‐yi , Zhou Min‐jun , Zhou De‐hua , Chen Zhuo , Huang Zhen‐xing , Xie Yu‐xiang , Qiao Guang‐lei , Tu Xiao‐huang
Published: March 2024

N6‐Methyladenosine (m6A) is a important process regulating gene expression post‐transcriptionally. Programmed death ligand 1 (PD‐L1) is a major immune inhibitive checkpoint that facilitates immune evasion and is expressed in tumor cells. In this research we discovered that Wilms' tumor 1‐associated protein (WTAP) degradation caused by ubiquitin‐mediated cleavage in cancer cells (colorectal cancer, CRC) under hypoxia was inhibited by Pumilio homolog 1 (PUM1) directly bound to WTAP. WTAP enhanced PD‐L1 expression in a way that was m6A‐dependent. m6A “reader,” Insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) identified methylated PD‐L1 transcripts and subsequently fixed its mRNA. Additionally, we found that T‐cell proliferation and its cancer cell‐killing effects were prevented by overexpression of WTAP in vitro and in vivo. Overexpression prevented T cells from proliferating and killing CRC by maintaining the expression of PD‐L1. Further evidence supporting the WTAP–PD‐L1 regulatory axis was found in human CRC and organoid tissues. Tumors with high WTAP levels appeared more responsive to anti‐PD1 immunotherapy, when analyzing samples from patients undergoing treatment. Overall, our findings demonstrated a novel PD‐L1 regulatory mechanism by WTAP‐induced mRNA epigenetic regulation and the possible application of targeting WTAP as immunotherapy for tumor hypoxia.
Complete dentures associated with frailty among edentulous older Japanese people: A prospective analysis
Authors: Castrejón‐Pérez Roberto C. , Borges‐Yáñez S. Aída , Ramírez‐Aldana Ricardo , Nasu Ikuo , Saito Yasuhiko
Published: March 2024

Objective

This study aimed to explore the cross‐sectional and prospective associations between self‐reported functionality of complete dentures (FCD), satisfaction with complete dentures (SCD) and the ability to chew hard food (ACHF) on the one hand and the frailty index (FI) on the other hand among edentulous community‐dwelling older Japanese people.

Methods

The study examined 770 edentulous participants of the Nihon University Japanese Longitudinal Study of Aging. The self‐reported FCD, SCD and ability to chew six groups of food (from hardest to softest) with complete dentures were the independent variables at the baseline. The FI was computed including 40 deficits as the dependent variable at the baseline and 4 years later. Cross‐sectional and prospective generalized linear regression models were fitted controlling for age, gender, marital status, education, working status and area of residence.

Results

The use of non‐functional complete dentures and dissatisfaction with complete dentures were both associated with a higher FI cross‐sectionally (3.9% [95% CI 2.2–5.6] and 3.2% [95% CI 1.5–4.9], respectively) and prospectively (3.9% [95% CI 2.0–6.0] and 3.3% [95% CI 1.3–5.3], respectively). Regarding the ability to chew, a higher FI at baseline was observed among those able to chew food of Group 2 (1.9%, [95% CI 0.1–3.7]) and Groups 4–6 (1.9%, [95% CI 0.1–3.7]), and a progressive increment in the FI, as the participants reported being able to chew softer groups of food at the follow‐up (Group 2: 2.2% [95% CI 0.05–4.3]; Group 3: 3.6% [95% CI 1.2–6.0]; and Groups 4–6: 3.4 [95% CI 0.7–6.1]).

Conclusion

Self‐reported use of non‐functional complete dentures, dissatisfaction with dentures and a reduced ACHF with complete dentures were associated with a higher FI both cross‐sectionally and prospectively.
Dendritic cell‐targeted delivery of antigens using extracellular vesicles for anti‐cancer immunotherapy
Authors: Dang Xuan T. T. , Phung Cao Dai , Lim Claudine Ming Hui , Jayasinghe Migara Kavishka , Ang Jorgen , Tran Thai , Schwarz Herbert , Le Minh T. N.
Published: March 2024

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large‐scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell‐derived EVs (RBCEVs) targeting splenic DEC‐205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen‐reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti‐DEC‐205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings.
Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi‐ascending dose study with a bioequivalence arm in healthy volunteers
Authors: Kirkpatrick D. Lynn , Evans Cari , Pestano Linda A. , Millard Jeffrey , Johnston Matthew , Mick Emily , Schmidt William K.
Published: March 2024

PF614, a trypsin‐activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two‐part design including a multi‐ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses. In part B, 60 subjects randomized in a four‐way crossover to evaluate BE, received PF614 100 mg and OxyContin 40 mg in fasted and fed (high‐fat diet) states. All subjects were naltrexone blocked prior to first study drug administration to protect against opioid‐related adverse effects; repeat doses were provided on days 1–5. In part A, PF614 was well‐tolerated following twice daily doses of up to 200 mg for 5 days. Plasma oxycodone maximal plasma concentration and area under the concentration time curve increased linearly with increasing doses. Part B showed that plasma oxycodone BE was achieved following 100 mg PF614 or 40 mg OxyContin under both fasted and fed conditions. Additionally, PF614 provided similar oxycodone exposures following both fasted and fed states. This study confirms findings from our single‐ascending dose study, showing that PF614 100 mg releases oxycodone with a PK profile comparable to 40 mg OxyContin under both fasted and fed conditions and with a similar safety profile under naltrexone‐blocked conditions.
The impact of skin color and tone on histamine iontophoresis and Doppler flowmetry measurements as a pharmacodynamic biomarker
Authors: Ramprasad Aarya , Ezekwe Adara , Lee Brian R. , Balasubramanian Shiva , Jones Bridgette L.
Published: March 2024

The phenotypical manifestations of asthma among children are diverse and exhibit varying responses to therapeutic interventions. There is a need to develop objective biomarkers to improve the characterization of allergic and inflammatory responses relevant to asthma to predict therapeutic treatment responses. We have previously investigated histamine iontophoresis with laser Doppler flowmetry (HILD) as a potential surrogate biomarker that characterizes histamine response and may be utilized to guide the treatment of allergic and inflammatory disease. We have identified intra‐individual variability of HILD response type among children and adults with asthma and that HILD response type varied in association with racial classification. As laser Doppler flowimetry may be impacted by skin color, we aimed to further validate the HILD method by determining if skin color or tone is associated with observed HILD response type differences. We conducted an observational study utilizing quantification of skin color and tone obtained from photographs of the skin among participants during HILD assessments via the RGB color model. We compared RGB values across racial, ethnic, and HILD response type via the Kruskal‐Wallis test and calculated Kendall rank correlation coefficient to evaluate the relationship between RGB composite scores and HILD pharmacodynamic measures. We observed that RGB scores differed among racial groups and histamine response phenotypes (p < 0.05). However, there was a lack of correlation between the RGB composite score and HILD pharmacodynamic measures (r values 0.1, p > 0.05). These findings suggest that skin color may not impact HILD response variations, necessitating further research to understand previously observed differences across identified racial groups.
Rate and characteristics of inflammatory neuropathies associated with brentuximab vedotin therapy
Authors: Matthys Arthur , Bardel Benjamin , Le Bras Fabien , Créange Alain , Nordine Tarik , Gounot Romain , Ingen‐Housz‐Oro Saskia , Carvalho Muriel , Lefaucheur Jean‐Pascal , Haioun Corinne , Planté‐Bordeneuve Violaine , Gendre Thierry
Published: March 2024

Background and purpose

Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV‐induced neuropathy (BV‐CN) is a mild distal sensory axonal polyneuropathy. Severe BV‐induced inflammatory neuropathies (BV‐IN) have been described. BV‐IN contribute to lymphoma‐associated morbidity but might be immunotherapy‐responsive. Our primary objective was to evaluate the rate of BV‐IN. Our secondary objectives were to determine risk factors and warning signs.

Methods

We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV‐induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV‐IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV‐CN.

Results

Among 83 patients, 41 (49%) developed neuropathy: 35 BV‐CN and 6 BV‐IN. Thus, the rate of BV‐IN was 7.2%. Compared to patients with BV‐CN, no predisposing factor was identified. However, patients with BV‐IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV‐IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy.

Conclusions

Brentuximab vedotin‐induced neuropathy is an overlooked complication. Based on four easily identifiable “red flags”, we provide an algorithm to help non‐neurologist physicians that care for BV‐treated patients to detect BV‐IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.
Epidermal growth factor receptor inhibition leads to cellular phenotype correction of DSP‐mutated keratinocytes
Authors: Andrei Daniela , Bremer Jeroen , Kramer Duco , Nijenhuis Albertine M. , van der Molen Marije , Diercks Gilles F. H. , van den Akker Peter C. , Vermeer Mathilde C. S. C. , van der Meer Peter , Bolling Maria C.
Published: March 2024

Desmoplakin (DSP) is a desmosomal component expressed in skin and heart, essential for desmosome stability and intermediate filament connection. Pathogenic variants in the DSP gene encoding DSP, lead to heterogeneous skin, adnexa and heart‐related phenotypes, including skin fragility, woolly hair (WH), palmoplantar keratoderma (PPK) and arrhythmogenic/dilated cardiomyopathy (ACM/DCM). The ambiguity of computer‐based prediction analysis of pathogenicity and effect of DSP variants, indicates a necessity for functional analysis. Here, we report a heterozygous DSP variant that was not previously described, NM_004415.4:c.3337C>T (NM_004415.4(NP_004406.2):p.(Arg1113*)) in a patient with PPK, WH and ACM. RNA and protein analysis revealed ~50% reduction of DSP mRNA and protein expression. Patient's keratinocytes showed fragile cell–cell connections and perinuclear retracted intermediate filaments. Epidermal growth factor receptor (EGFR) is a transmembrane protein expressed in the basal epidermal layer involved in proliferation and differentiation, processes that are disrupted in the development of PPK, and in the regulation of the desmosome. In skin of the abovementioned patient, evident EGFR upregulation was observed. EGFR inhibition in patient's keratinocytes strongly increased DSP expression at the plasma membrane, improved intermediate filament connection with the membrane edges and reduced the cell–cell fragility. This cell phenotypic recovery was due to a translocation of DSP to the plasma membrane together with an increased number of desmosomes. These results indicate a therapeutic potential of EGFR inhibitors for disorders caused by DSP haploinsufficiency.
Advancing democratic processes in Ecuador: A case study on neural network‐driven OCR for election report verification
Authors: Asimbaya José Alejandro Mosquera , Ramírez Gabriel M. , Díaz‐Arancibia Jaime
Published: March 2024

Background

In Ecuador, scepticism surrounding electoral outcomes underscores the need for a reliable system to ensure transparent election results. Manual verification demands a more efficient approach due to the vast volume of election reports. This research introduces an automated system leveraging Artificial Intelligence to process results from Ecuador's three recent national elections.

Methods

The system, designed with a three‐layer architecture, extracts, processes, analyses, classifies and compares election results. We thoroughly analysed the National Electoral Council of Ecuador (CNE) web pages for effective data extraction and processing. Rigorous unit and acceptance tests validated the system's functionality. A classifier model, trained using data augmentation techniques, achieved a 98% accuracy rate.

Results

While the system boasts high efficiency, we identified three errors, accounting for less than 5% of the total fields processed. Notably, the quality of scanned reports and illegible handwritten numbers posed challenges for the classifier.

Conclusions

The system's deployment by an authorized entity in Ecuador could enhance the CNE's information verification. Despite some errors, the system's potential is clear. Future work includes refining classifiers, verifying officer signatures, and expanding the system's scope, aiming for a more transparent electoral process.
Probabilistic interval prediction method based on shape‐adaptive quantile regression
Authors: Li Lin , Wang Hua , Liu Yepeng , Zhang Fan
Published: March 2024

This article introduces customized screening ensemble with shape‐adaptive quantile regression (CseAQR), a novel probabilistic interval forecasting method built upon the quantile regression model. CseAQR utilizes ensemble learning to perform adaptive quantile regression prediction, which can handle the heteroscedasticity feature in time series data by using a weighted adaptive allocation loss function to enhance the adaptability of the basic quantile regression model on the dataset. The model performance predictor is used to select the optimal ensemble learner combination, assign reasonable adaptive weights to it, and obtain a preliminary prediction interval through weighted aggregation. Combining ensemble learners not only improves the accuracy and robustness of prediction intervals but also ensures the commutativity required for conformal prediction. Finally, the conformal prediction method is applied to locally adjust the prediction interval, constructing a more consistently aligned prediction interval with the actual data on a narrower basis.
Bayesian joint species distribution model selection for community‐level prediction
Authors: Itter Malcolm S. , Kaarlejärvi Elina , Laine Anna‐Liisa , Hamberg Leena , Tonteri Tiina , Vanhatalo Jarno
Published: March 2024

Aim

Joint species distribution models (JSDMs) are an important tool for predicting ecosystem diversity and function under global change. The growing complexity of modern JSDMs necessitates careful model selection tailored to the challenges of community prediction under novel conditions (i.e., transferable models). Common approaches to evaluate the performance of JSDMs for community‐level prediction are based on individual species predictions that do not account for the species correlation structures inherent in JSDMs. Here, we formalize a Bayesian model selection approach that accounts for species correlation structures and apply it to compare the community‐level predictive performance of alternative JSDMs across broad environmental gradients emulating transferable applications.

Innovation

We connect the evaluation of JSDM predictions to Bayesian model selection theory under which the log score is the preferred performance measure for probabilistic prediction. We define the joint log score for community‐level prediction and distinguish it from more commonly applied JSDM evaluation metrics. We then apply the joint community log score to evaluate predictions of 1918 out‐of‐sample boreal forest understory communities spanning 39 species generated using a novel multinomial JSDM framework that supports alternative species correlation structures: independent, compositional dependence and residual dependence.

Main conclusions

The best performing JSDM included all observed environmental variables and compositional dependence modelled using a multinomial likelihood. The addition of flexible residual species correlations improved model predictions only within JSDMs applying a reduced set of environmental variables highlighting potential confounding between unobserved environmental conditions and residual species dependence. The best performing JSDM was consistent across successional and bioclimatic gradients regardless of whether interest was in species‐ or community‐level prediction. Our study demonstrates the utility of the joint community log score to compare the predictive performance of JSDMs and highlights the importance of accounting for species dependence when interest is in community composition under novel conditions.
Parental sensitivity and intrusiveness with mothers and fathers: Associations between parental behavioral activation/inhibition and infant temperament
Authors: Bailes Lauren G. , Lickenbrock Diane M. , Swift Alyssa R. , Rios Logan J.
Published: March 2024

Understanding the factors contributing to sensitive parenting is crucial to optimize infant social and emotional functioning. Research has supported the association between parents' personality and parenting quality, but findings are inconsistent when examining various global personality measures. Further, it is likely that the interaction between parent‐level (e.g., personality) and infant‐level characteristics (e.g., temperament) are more strongly associated with caregiving quality. Most studies examining predictors of parenting quality have only included mothers, compared to fathers. The current study examined the interaction between parental personality and infant temperament and associations with parental sensitivity and intrusiveness with mothers and fathers. The participants included families (n = 102) when the infants were 4, 6, and 8 months old. Using parent report measures and a face‐to‐face play task, significant main effects of maternal behavioral inhibition on parenting behaviors were observed for mothers. A Behavioral Activation X Infant Negative Reactivity interaction predicted both maternal sensitivity and intrusiveness, whereas a Behavioral Inhibition X Infant Surgency predicted paternal intrusiveness. In summary, the results revealed support for the goodness‐of‐fit perspective between parents' personality and infant temperament.
Increased safety in periodontal surgery: Doppler ultrasound for detection of relevant palatal blood vessels—A proof‐of‐concept and cross‐sectional study
Authors: Bartha Valentin , Grünfeld Dan , Kopunic Aleksandra , Klein Christian , Wolff Diana , Ratka‐Krüger Petra , Woelber Johan Peter , Meller Christian
Published: March 2024

Aim

To evaluate the suitability of a Doppler ultrasound probe in detecting the greater palatine artery or its greater branches non‐invasively.

Materials and Methods

The palatal mucosa of 108 participants (median age 34 years, 51 female) was systematically divided into transversal sectors, each aligning with the positions of the upper molars (M), premolars (P) and canine teeth (C), aiming to facilitate precise and consistent localization of the detected palatal blood vessel across different patients. Blood flow of the palatal blood vessels, presumably, was located by scanning the palatal vault bilaterally using an 8‐MHz ultrasound probe linked to a transducer. The distance to the corresponding tooth was measured using a millimetre‐scale periodontal probe.

Results

Within the regions of M2 to P1, the ultrasound transducer gave a delimitable acoustic pulse signal in 80%–98% of all measurements. The measured median distances between the determined position of the artery and the corresponding teeth ranged from 13 to 15 mm, with smaller distances in the anterior region. In several sectors, the distance was significantly higher for men (C: p = .048; P1: p = .041, M1: p < .01; M2: p = .034).

Conclusions

Use of the Doppler ultrasound transducer might be a promising approach to non‐invasively detect relevant palatine blood vessels preoperatively. It, therefore, might have the potential to reduce the risk of accidental injury during palatal surgery.
Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles
Authors: Fucà E. , Costanzo F. , Galassi P. , Celestini L. , Valentini D. , Vicari S.
Published: March 2024

Background

Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD.

Methods

Data were retrospectively collected from a database including data from 381 individuals with DS (3–18 years). The final sample included 65 participants, 27 with co‐occurring CD and 38 age, IQ, sex and body mass index‐matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires.

Results

No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems.

Conclusions

Youth with DS and co‐occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co‐occurring CD but exhibit better adaptive skills in the practical domain.