bluuebunny/crossref_metadata_2025 huggingface dataset:
TheArabidopsisTNL immune receptor BNT1 localizes to the plastid envelope and mediates flg22-induced resistance againstPseudomonas
Authors: Margutti Micaela Y. Peppino , Cislaghi Ana P. , Herrera-Vásquez Ariel , Palomeque Julieta R. , Bellino Francisco , Alvarez María E. , Blanco-Herrera Francisca , Cecchini Nicolás M.
Published: January 2025

Precise localization and trafficking of plant immune receptors are critical for their function. We identify the TNL-class nucleotide-binding leucine-rich repeat receptor (NLR) BURNOUT1 (BNT1) fromArabidopsis thalianaas localized to plastids, key organelles for plant immunity. Alternative transcription start site usage generates two isoforms of BNT1: BNT1.2, which is targeted to the plastid envelope via an N-terminal signal-anchored mechanism, and BNT1.1, which resides in the cytoplasm. Moreover, BNT1.2 is predominantly expressed in epidermal cells, where it localizes to the so-called sensory plastids. Functional analysis revealed thatbnt1mutants exhibit compromised PAMP-triggered immunity (PTI) responses, including impaired callose deposition and reduced flg22-induced resistance toPseudomonas syringaepv.tomato, while flg22-induced apoplastic reactive oxygen species production remains unaffected. Notably, only the plastid-localized BNT1.2 isoform is required for these PTI responses. Our findings reveal a role for NLRs in regulating PTI responses from plastids and highlight these organelles as key hubs for signal(s) integration during plant-pathogen interactions.

Significance statement

This study identifies BNT1 as a TNL-class immune receptor localized to the plastid envelope. Two distinct isoforms of BNT1 were characterized: one with a plastid-targeting signal anchor that ensures plastid localization and another confined to the cytoplasm. Notably, only the plastid-localized isoform mediates PTI responses and confers resistance toPseudomonas, highlighting the critical role of precise NLR localization and the central role of plastids in plant immunity.
Structure and function of the EDEM:PDI ERAD checkpoint complex
Authors: Hitchman Charlie J. , Lia Andrea , Chiritoiu Gabriela N. , Munteanu Cristian V. A. , Ortigosa Juan R. , Ghenea Simona , Savva Christos , Wada Ikuo , De Benedictis Maria , Tax Gabor , Bayo Yusupha , Crescioli Irene , Alonzi Dominic L. , Quigley Andrew , Modenutti Carlos P. , Petrescu Stefana M. , Santino Angelo , Gooptu Bibek , Hosokawa Nobuko , Roversi Pietro
Published: January 2025

The ERAD glycoprotein misfolding checkpoint complex de-mannosylates misfolded glycoproteins to enable retrotranslocation, ubiquitination, and proteasomal degradation. The complex comprises an Endoplasmic Reticulum-Degradation Enhancingα-Mannosidase (EDEM) and a Protein Disulfide Isomerase (PDI). We solved Cryo-EM structures ofChaetomium thermophilum (Ct) CtEDEM:CtPDI, both as the heterodimer with no client and in complex withα1-antitrypsin (A1AT-NHK). The EDEM catalytic domain nests within the PDI arc, while A1AT-NHK binds EDEM’s C-terminal flexible domains. Mass spectrometry reveals a disulfide bond between A1AT-NHK and an exposed Cys in the PAD of the EDEM. Co-transfection of EDEM, A1AT-NHK, and PDI shifts EDEM:PDI to higher molecular weight in non-reducing SDS-PAGE. Redox chemistry between EDEM and PDI disulfide bonds generates oxidized, demannosylation-competent EDEM and reduced PDI, priming PDI to function as the ERAD reductase, facilitating client retrotranslocation.
A divergent cyclic nucleotide binding protein promotesPlasmodiumookinete infection of the mosquito
Authors: Kwecka Dominika , Eigminas Edvardas , Liu Lijia , Kim Choel , Philip Nisha
Published: January 2025

Colonisation of the mosquito by the malarial parasite is critically reliant on the invasive ookinete stage. Ookinete invasion of mosquito is coordinated by the apical complex, a specialised parasite structure containing components for secretion, attachment and penetration. While studies have investigated cytoskeletal and secretory elements, it is currently unknown if signalling modules are present or functional at the apical complex. Here we elucidate the role of a cryptic cyclic nucleotide binding protein which we name CBP-O. PbCBP-O showed a marked localisation to the ookinete apex and disruption of the protein severely compromised ookinete invasion of mosquitos. Domain dissection analysis revealed that the N- and C-termini have distinct functions. Intriguingly, PbCBP-O exhibits dual binding specificity to both cGMP and cAMP. Our findings suggest the apical tip of the ookinete is a platform to transduce cyclic nucleotide signals essential for malaria parasite transmission.

Author summary

Malaria parasites complete their life-cycle within mammalian and mosquito hosts requiring specialised forms to invade and establish infection in host tissue. In order to transmit to the mosquito, the parasite forms a motile ookinete that uses the apical end to attach and penetrate the mosquito midgut membrane. Previous studies have identified several proteins localised to the apex of the ookinete. However, functions of many of these proteins are unknown. Here, we dissect the role of a putative cyclic nucleotide binding protein, CBP-O, in establishing ookinete infection within the mosquito. We discovered that in the absence of the protein, efficiency of transmission is significantly compromised. Interestingly the ability of ookinetes to move was not affected, but the parasites were unable to pass through the midgut membrane. We also reveal that both N- and C-terminal domains of the protein perform distinct functions and are both required for parasite transmission. Sequence and spatial conservation of the protein across the phylum Apicomplexa suggests an equivalent and crucial function of CBP-O in these parasites.
Endogenous RALF peptide function is required for powdery mildew host colonization
Authors: Leicher Henriette , Schade Sebastian , Huebbers Jan W. , Munzert-Eberlein Kristina S. , Haljiti Genc , Ludwig Christina , Müller Marion , Kinoshita Toshinori , Engelsdorf Timo , Hückelhoven Ralph , Stegmann Martin
Published: January 2025

The receptor kinase FERONIA (FER) is a susceptibility factor for biotrophic powdery mildew fungal pathogens in Arabidopsis thaliana, but the underlying molecular mechanisms remain largely unknown. FER is required for the perception of endogenous RAPID ALKALINIZATION FACTOR (RALF) peptides to control various aspects of plant growth, development and immunity. RALFs are perceived by FER- LORELEI-LIKE GPI-ANCHORED PROTEIN (LLG) heterocomplexes to induce cellular responses and bind to LEUCINE-RICH REPEAT EXTENSIN (LRX) proteins as structural components of the cell wall. We show that FER‘s RALF ligands are necessary for full success of powdery mildew colonization. Our data reveals that LLGs and LRXs are also powdery mildew susceptibility factors, and that the susceptibility function of RALFs is best explained by a combination of peptide signalling and cell wall-related effects. We further reveal that cell wall and apoplastic pH homeostasis, hallmark features of RALF function, support powdery mildew reproductive success. The function of host RALF peptides is underlined by the fact that, in contrast to previously described pathogens that hijack FER for colonization, powdery mildew fungi do not produce functional RALF mimics. Surprisingly, RALF-dependent powdery mildew pathogenesis is partially independent of FER. The resistance phenotype of ralf and fer mutants is not associated with de-regulated salicylic acid and jasmonic acid signalling, important defense-related phytohormones. Collectively, powdery mildew fungi require RALF signalling for apoplastic pH regulation and cell wall structural organization for successful colonization, highlighting a novel mechanism for host susceptibility by obligate biotrophic fungi.
Fermentative yeast diversity at the northern range limit of their oak tree hosts
Authors: Pinto Javier , Haberkorn Chloé , Franzen Markus , Tack Ayco J. M. , Stelkens Rike
Published: January 2025

Fermentative yeasts play important roles in both ecological and industrial processes but their distribution and abundance in natural environments is not well understood. We investigated the diversity of yeast species associated with oak trees (Quercus spp.) in the northern range limit of oak in Sweden, and identified climatic and ecological conditions governing their distribution. We isolated yeasts from oak bark collected from 28 forests and identified them to the species level using metabarcoding. Most communities were dominated by species in the Saccharomycetaceae family, especially by species of Saccharomyces, Kluyveromyces, and Pichia. Each of these genera showed a distinct latitudinal and longitudinal distribution, and both temperature and precipitation metrics predicted significant variation in their abundance. Consistent with this, laboratory assays revealed significant effects of temperature on the growth of strains collected from different longitudes and latitudes. We further found that older trees harbour more diverse and more balanced microbial communities with more evenly distributed species abundances, and that communities across trees were more similar when sharing a common dominant genus. This work provides a baseline for future studies on the impact of climate change on the microbial biodiversity of temperate forests in northern latitudes, and contributes to a growing collection of fermentative yeasts isolated from the wild with potential for biotechnological applications.
Mdm38/LETM1 couples ion homeostasis and proteostatic mechanisms in the inner mitochondrial membrane
Authors: Bohovych Iryna , Menezes da Silva Gabriella , Ali Saieeda Fabia , Bergmeyer Emma J. , Germany Edward M. , Mayank Adarsh , Wohlschlegel James A. , Casler Jason C. , Rahman Muhammad Arifur , Nazarko Taras Y. , Tarsio Maureen , Shiota Takuya , Lackner Laura L. , Claypool Steven M. , Kane Patricia M. , Barrientos Antoni , Khalimonchuk Oleh
Published: January 2025

The mitochondrial inner membrane is among the most protein-dense cellular membranes. Its functional integrity is maintained through a concerted action of several conserved mechanisms that are far from clear. Here, using the baker’s yeast model, we functionally characterize Mdm38/LETM1, a disease-related protein implicated in mitochondrial translation and ion homeostasis, although the molecular basis of these connections remains elusive. Our findings reveal a novel role for Mdm38 in maintaining protein homeostasis within the inner membrane. Specifically, we demonstrate that Mdm38 is required for mitochondrial iron homeostasis and for signaling iron bioavailability from mitochondria to vacuoles. These processes are linked to the m- AAA quality control protease, whose unrestrained activity disrupts the assembly and stability of respiratory chain complexes in Mdm38-deficient cells. Our study highlights the central role of Mdm38 in mitochondrial biology and reveals how it couples proteostatic mechanisms to ion homeostasis across subcellular compartments.
Stiffening cells with light
Authors: Gonzalez Eva , El Husseiny Jana , Molzahn Finn Bastian , Campion Tiffany , Jalaber Hadrien , Dogniaux Stéphanie , Puech Pierre-Henri , Nüsse Oliver , Gibot Laure , Husson Julien
Published: January 2025

Fluorescence microscopy is widely used to observe structures and dynamic processes in living cells and organisms and is often used as if it were purely innocuous to the cells or structures of interest. However, it can lead to phototoxicity, which can affect the cellular behavior and lead to erroneous interpretations of the observations. The major cause of cell damage through phototoxicity is the production of reactive oxygen species (ROS), which can form crosslinks between intracellular molecules, including proteins and nucleic acids. By using profile microindentation and atomic force microscopy, we demonstrate that the excitation of various fluorescent probes leads to a large increase in the stiffness of several cell types within seconds of illumination. The stiffening exhibits a dose-dependent response, where longer exposure times to exciting light are correlated with larger stiffening.

This photostiffening effect explains why T cells loaded with the Fluo-4 Calcium probe stop emitting a protrusion within seconds after the excitation light is turned on. We observed photostiffening in different cell types and fluorophores. We showed that repeated cell indentation alone led to cell stiffening as well as excitation with blue or UV light in the absence of a fluoroph ore. However, in the latter case, the stiffening was much smaller than that when the fluorophore was excited. We used both sharp and blunt indenters to show that stiffening occurred not only at the cell cortex level but also deeper in the cell interior and that photostiffening is independent of actin cytoskeleton organization. We correlated the increase in cell stiffness with the production of intracellular reactive oxygen species and reproduced cell stiffening by incubating cells with a ROS inducer, H2O2. The excitation of the photosensitizer Pheophorbidea, which induces a specific type of reactive oxygen species, namely singlet oxygen, also led to cell stiffening. This study reminds the experimentalists that it is crucial to perform controls when using fluorescence. It further allows us to propose exploiting photostiffening as a new method for rapidly quantifying phototoxicity.

Significance

This study reveals a direct relationship between fluorescence excitation and cell mechanical properties. The generality of th is phenomenon across diverse fluorophores and cell types highlights the importance of controlling phototoxicity in fluorescence experiments, in particular in complex, quantitative cell biology and biophysical experiments, but also reveals an unexpected rol e of intracellular reactive oxygen species production and identifies cell stiffness as a proxy for assessing the efficacy of photodynamic therapy.
k-mer approaches for biodiversity genomics
Authors: Jenike Katharine M. , Campos-Domínguez Lucía , Boddé Marilou , Cerca José , Hodson Christina N. , Schatz Michael C. , Jaron Kamil S.
Published: January 2025

The wide array of currently available genomes displays a wonderful diversity in size, composition, and structure and is quickly expanding thanks to several global biodiversity genomics initiatives. However, sequencing of genomes, even with the latest technologies, can still be challenging for both technical (e.g., small physical size, contaminated samples, or access to appropriate sequencing platforms) and biological reasons (e.g., germline-restricted DNA, variable ploidy levels, sex chromosomes, or very large genomes). In recent years,k-mer-based techniques have become popular to overcome some of these challenges. They are based on the simple process of dividing the analyzed sequences (e.g., raw reads or genomes) into a set of subsequences of lengthk, calledk-mers, and then analyzing the frequency or sequences of thosek-mers. Analyses based onk-mers allow for a rapid and intuitive assessment of complex sequencing data sets. Here, we provide a comprehensive review to the theoretical properties and practical applications ofk-mers in biodiversity genomics with a special focus on genome modeling.
Nelson-Barr ultralight dark matter
Authors: Dine Michael , Perez Gilad , Ratzinger Wolfram , Savoray Inbar
Published: January 2025

We show that, in the Nelson-Barr solution to the strong CP-problem, a naturally light scalar can arise. It gives rise to a completely new phenomenology beyond that of the celebrated QCD axion, if this field constitutes dark matter, as the elements of the Cabibbo–Kobayashi–Maskawa matrix vary periodically in time. We also discuss how the model can be tested using quantum sensors, in particular using nuclear clocks, which leads to an interesting synergy between different frontiers of physics.

Published by the American Physical Society
2025
Second quantum revolution: The progressive design of an approach to value its cultural and conceptual scope
Authors: Satanassi S. , Levrini O.
Published: January 2025

[This paper is part of the Focused Collection in Investigating and Improving Quantum Education through Research.] Quantum information science and technology is a growing field. Programs like Quantum Flagship in the EU and the National Quantum Initiative Act in the U.S. have called for science education and science education research to provide efforts and competencies for preparing the workforce and the next generations of quantum experts and promoting quantum literacy. The second quantum revolution is similar to the Newtonian one in that it has the potential to question worldviews in our society. We present our approach to design a teaching module for secondary school students that aims to value the cultural scope of the second quantum revolution. The model of educational reconstruction was used as a theoretical reference to reconstruct content for educational and cultural purposes. Renn’s elaborated historical analysis of knowledge evolution provided the criteria for characterizing the cultural scope in content reconstruction. The module has been iteratively refined following a design-based approach involving back-and-forth dynamics between educational hypotheses and empirical results. The process started in 2018, and the module was refined through 5 rounds of implementation in extracurricular courses with secondary school students (for almost 130 students). The main finding underscores the importance of finding a balance between a process of simplification or elementarization of the content and its enrichment to foster learners to develop a deep understanding of quantum technologies, their conceptual intricacies, and their cultural scope.

Published by the American Physical Society
2025
Virtual influencers going head-to-head with human influencers: the impact of influencer type on trust perceptions of endorsement
Authors: Liu Xing (Stella) , Wan Lisa C. , Mattila Anna S.
Published: January 2025

Purpose

This study aims to explore how the extensive implementation of virtual influencers (VIs) in the hospitality and tourism industry shapes tourists’ trust perceptions. Specifically, it compares the differences between human influencers (HIs) and VIs based on mind perception theory and outlines the strategies for hospitality and tourism marketers to efficiently adopt influencers to enhance customers’ trust in diversified consumption contexts.

Design/methodology/approach

Three experiments were conducted with online panels (n = 799). Study 1 outlines the anticipated focal effect and the mediating role of perceived experience. Study 2 replicates the effect and investigates its downstream consequences. Study 3 examines the moderating effect of product type.

Findings

The results reveal that customers are more likely to distrust VIs than their human counterparts because the former is thought to possess a lower degree of perceived experience. This effect is more prominent in the endorsement of experiential (versus functional) products and services.

Originality/value

This research advances the understanding of how tourists perceive HIs andVIs differently in social media endorsement, enriching the growing literature on VIs. Hospitality marketers can also gain insights into the advantages and limitations of VIs, providing valuable information to optimize their marketing effectiveness.
Understanding determinants of GenAI usage and its effect on SCM performance using dynamic capability view
Authors: Gangwar Hemlata , Shameem Mohammad , Patel Sandeep , Koohang Alex , Sharma Anuj
Published: January 2025

Purpose

Generative artificial intelligence (GenAI) can potentially improve supply chain management (SCM) processes across levels and verticals. However, despite its promise, the implementation of GenAI for SCM remains challenging, mainly due to the lack of knowledge regarding its key drivers. To address this gap, this study examines the factors driving GenAI implementation in an SCM environment and how these factors optimize SCM performance.

Design/methodology/approach

A thorough literature review was followed to identify the drivers. The resultant model from the drivers was validated using a quantitative study based on partial least squares structural equation modeling (PLS-SEM) that used responses from 315 expert respondents from the field of SCM.

Findings

The results confirmed the positive effect of performance expectancy, output quality and reliability, organizational innovativeness and management commitment to GenAI usage. Further, they showed that successful GenAI usage improved SCM performance through improved transparency, better decision-making, innovative design, robust development and responsiveness.

Practical implications

This study reports the potential drivers for the contemporary development of GenAI in SCM and highlights an action plan for GenAI’s optimal performance. The findings suggest that by increasing the rate of GenAI implementation, organizations can continuously improve their strategies and practices for better SCM performance.

Originality/value

This study establishes the first step toward empirically testing and validating a theoretical model for GenAI implementation and its effect on SCM performance.
Service quality and earnings management in Brazilian electricity distributors
Authors: Souza Paulo Vitor Souza de , Paulo Edilson
Published: January 2025

Purpose

This article examines the relationship between service quality and earnings management in Brazilian electricity distributors.

Design/methodology/approach

Service quality was measured using the Global Continuity Performance Indicator, as released by the Brazilian Electricity Regulatory Agency (ANEEL). To measure earnings management, the models by Dechow et al. (1995), Kothari et al. (2005), and Pae (2005) were used.

Findings

The results show that lower service quality is related to greater opportunism in management through earnings management. Furthermore, the study shows that managing earnings can distort the true economic and financial position of companies with low operational performance.

Research limitations/implications

The research enhances comprehension regarding the correlation between service quality, measured by the Global Continuity Performance Indicator, and earnings management within a distinct industrial and regulatory framework. This could establish a foundation for prospective studies delving into analogous relationships across diverse sectors or regions.

Practical implications

The findings offer insights for regulatory authorities to promote higher standards in the generation of informational quality, which can impact the quality of services.

Social implications

Enhancing the quality of electrical service through more responsible management practices leads to increased consumer satisfaction, driven by improvements in the continuity of energy supply.

Originality/value

A gap exists in the literature due to the lack of studies examining the relationship between the quality of electrical service, measured by the continuity index, and opportunistic management practices through earnings management.
Self-directed flourishing: a conceptual meta-framework for dealing with the challenges of 21st-century learning and education
Authors: Mountbatten-O’Malley Eri , Morris Thomas Howard
Published: January 2025

Purpose

This paper aims to address the concern that humans are experiencing unprecedented, rapidly changing conditions, in part exacerbated by a recent pandemic, digitization and ongoing wartime.

Design/methodology/approach

A paper that seeks to address what the authors are calling the “Educational Malaise”. The authors achieve this through a conceptual and theoretical exploration of the social nature of human beings and learning in the context of readings of human nature, and moral and rational powers.

Findings

It is proposed that education should be designed to empower learners to meet the demands of rapidly changing conditions. The ability to adapt is of primary importance for meeting the demands of the changing world, and the “Self-Directed Flourishing” meta-framework can help educators to meet this challenge.

Originality/value

Using conceptual and theoretical lenses, in this paper, the authors identify some core problems with traditional pedagogies in formal education and advance a person-centred, humanistic approach to pedagogy. The authors advocate for a new meta-framework for educators: “Self-Directed Flourishing”. The authors propose placing co-creation, courage and conceptual insight at the heart of educational policies and practices, which the authors suggest will nurture a dynamic, adaptable and ethical microculture for human flourishing in 21st-century education and beyond.
Association of a State‐Wide Alternative Payment Model for Rural Hospitals With Bypass for Elective Surgeries
Authors: Bourne Donald S. , Sun Zhaojun , Jacobs Bruce L. , Drake Coleman , Kahn Jeremy M. , Roberts Eric T. , Sabik Lindsay M.
Published: January 2025

Objective

This study aimed to measure the changes in rural hospital bypass for 11 common elective surgeries following the implementation of the Pennsylvania Rural Health Model (PARHM), a global budget payment model.

Study Setting and Design

We leveraged a natural experiment arising from the phase‐in of PHARM in Pennsylvania. We conducted a comparative interrupted time series analysis to assess changes in rural hospital bypass, comparing trends in rural hospital bypass among patients in hospital service areas (HSAs) with PARHM‐participating hospitals to patients in control HSAs with hospitals eligible for but not participating in PARHM. Analyses accounted for staggered entry into PARHM and examined outcomes up to 4 years post‐entry.

Data Sources and Analytic Sample

We used Pennsylvania all‐payer visit‐level inpatient discharge data (2016–2022) to measure rural hospital bypass, encompassing 175,138 surgeries.

Principal Findings

The average bypass rate for elective surgeries was 59.9%, with an increasing trend observed during the study period. Overall, differential changes in bypass rates between PARHM‐participating and control HSAs were not statistically significant, from a low of 0.53 percentage points (−8.17–9.22) among Cohort 2 HSAs and a high of 5.96 percentage points (−4.63–16.55) among Cohort 1 HSAs. However, among critical access hospitals, PARHM participation was associated with a significant relative increase in levels and trends in bypass rates compared to controls, from a low of 9.12 percentage points (2.45–15.79) among Cohort 1 HSAs and a high of 29.70 percentage points (12.54–46.86) among Cohort 2 HSAs. These relative increases were largely due to a stable rate in PARHM‐participating HSAs and a marked decrease in control HSAs.

Conclusions

This study fills a gap in the relationship between global budgets and hospital bypass. Although PARHM did not broadly alter rural bypass rates overall, the differential increase in bypass among HSAs with CAHs participating in PARHM suggests meaningful effect heterogeneity, warranting further research and analysis of impacts on patient outcomes.
PR Interval as a Valuable Predictor of Tilt Table Test Results in Patients With Neurally Mediated Syncope
Authors: Nikoo Mohammad Hossein , Narimani‐Javid Roozbeh , Kamrava Alireza , Shafiei Sasan , Nozhat Salma , Fatemian Hosein , Asadzadeh Ali , Motahari Moadab Mehdi , Ghanbari Fatemeh , Arzhangzadeh Alireza
Published: January 2025

Background

Neurally mediated syncope (NMS) is the primary cause of temporary and self‐limiting loss of consciousness. The tilt table test (TTT) has been consistently employed as a supplementary diagnostic tool for syncope evaluation. However, TTT requires specialized equipment, which is lacking in several emergency room and clinic environments. We hypothesized that patients susceptible to NMS may have higher parasympathetic tone. Thus, this study investigates the correlation between PR interval and Herat rate variability parameters as indicators of parasympathetic tone and TTT results.

Methods

We included 213 patients referred to our cardiology clinic with an impression of NMS in 2022 and 2023. Data was retrospectively collected from 24‐h ambulatory electrocardiographic monitoring recordings, TTT results, and patients' history and physical examination records.

Results

The analysis of the PR interval revealed a mean duration of 155 ms (95% CI: 148.61, 161.39) in negative TTT patients and 164.21 ms (95% CI: 158.44, 169.97) in positive TTT patients, indicating a statistically significant difference between two groups (p = 0.035). We also found that patients with a PR interval duration exceeding 160 ms demonstrated a significantly higher prevalence of positive TTT compared to those with a PR interval duration of less than 160 ms (p < 0.001, OR: 3.911, 95% CI: 2.143, 7.140).

Conclusions

Our study suggests a PR interval longer than 160 milliseconds as a valuable tool for predicting TTT results and identifying patients at higher risk of NMS.
Setting of initiation and factors associated with antidepressant use on entry to long‐term care facilities
Authors: Hughes Georgina A. , Inacio Maria C. , Rowett Debra , Lang Catherine , Jorissen Robert N. , Corlis Megan , Sluggett Janet K.
Published: January 2025

Aims

Antidepressant use increases around long‐term care facility (LTCF) entry, and initiation during hospitalizations may contribute to this. This study characterized the care setting (i.e., community‐based, hospital or LTCF) where antidepressants were initiated and determined associated resident characteristics.

Methods

A cross‐sectional study including non‐Indigenous individuals aged 65–105 years who entered LTCFs in two Australian states during 2015–2019, and were dispensed an antidepressant within 2 months, was conducted. Care settings (community‐based, hospital or LTCF) were determined from linked LTCF records, and hospitalizations ≤30 days before LTCF entry. Pharmaceutical claims before and after LTCF entry were screened to determine antidepressant initiation. Multivariate multinomial logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for resident characteristics associated with care settings of antidepressant initiation.

Results

This study included 34 525 residents from 1046 LTCFs. Overall, 27 160 (78.7%) commenced antidepressants prior to entry, 2552 (7.4%) in hospital and 4813 (13.9%) in LTCFs. Mirtazapine constituted 44.8% (n = 1143) of antidepressants initiated in hospitals and 39.5% (n = 1902) in LTCFs. Residents who were aged ≥90 years were more likely to start an antidepressant in the LTCF compared to community‐based settings (aOR = 1.97, 95% CI 1.74–2.23). Residents recently using a psychotropic were more likely to start an antidepressant in community‐based settings before LTCF entry, compared to a hospital or LTCF.

Conclusions

Individuals receiving antidepressants during transition to LTCFs are often already taking antidepressants prior to entry. Future interventions to optimize antidepressant use in LTCFs should consider setting, recency and indication for antidepressant initiation, and ongoing monitoring for safety.
Slow Codes are symptomatic of ethically and legally inappropriate CPR policies
Authors: McLennan Stuart , Bak Marieke , Knochel Kathrin
Published: January 2025

Although cardiopulmonary resuscitation (CPR) was initially used very selectively at the discretion of clinicians, the use of CPR rapidly expanded to the point that it was required to be performed on all patients having in‐hospital cardiac arrests, regardless of the underlying condition. This created problems with CPR being clearly inadvisable for many patients. Do Not Resuscitate (DNR) orders emerged as a means of providing a transparent process for making decisions in advance regarding resuscitation, initially by patients and later also by clinicians. Under hospital policies in many countries, however, CPR remains the default position for all patients having cardiac arrest in the hospital if there is no DNR order in place, regardless of whether CPR is medically indicated or in the patient's best interests. “Slow Codes” are the delayed or token efforts to provide CPR when clinicians feel CPR is futile or inappropriate. After giving a historical overview of the development and the changing use of CPR, we argue that more attention needs to be given to the cause of slow codes, namely, policies requiring CPR to be performed as the default action while simultaneously lacking implementing interventions such as advance care planning as a routine policy. This is ethically and legally inappropriate, and hospital policies should be modified to allow clinicians to consider whether CPR is appropriate at the time of arrest. Such a change requires a stronger emphasis on early recognition of patients for whom CPR is not in their best interests and to improve hospital emergency planning.
Jointly modeling responses and omitted items by a competing risk model: A survival analysis approach
Authors: Guo Jinxin , Xu Xin , Fang Guanhua , Ying Zhiliang , Zhang Susu
Published: January 2025

Item response theory models are commonly adopted in educational assessment and psychological measurement. Such models need to be modified to accommodate practical situations when statistical sampling assumptions are violated. Omission is a common phenomenon in educational testing. In modern computer‐based testing, we have not only examinees' responses but also their response times. This paper utilizes response time and develops a joint model of responses and response times. The new approach is analogous to those developed in survival analysis for dealing with right‐censored data. In particular, a key ingredient is the introduction of the omission time (OT), which corresponds to the censoring time in survival analysis. By competing risk formulation, the proposed method provides an alternative narrative to how an item becomes answered versus omitted, depending on the competing relationship of response time and OT, so that the likelihood function can be constructed properly. The maximum likelihood estimator can be computed via the expectation‐maximization algorithm. Simulation studies were conducted to evaluate the performance of the proposed method and its robustness against various mis‐specifications. The method was applied to a dataset from the PISA 2015 Science Test.
α‐Adrenoreceptor blocker phentolamine inhibits voltage‐gated sodium channels via the local anaesthetic binding site
Authors: Toklucu Idil , Sudha Bhagavath Eswaran Vishal , Bott Raya Atlanta , Kesdoğan Aylin Bilge , Gaebler Arnim Johannes , Stingl Julia , Hausmann Ralf , Körner Jannis , Lampert Angelika
Published: January 2025

Background and Purpose

Phentolamine is a non‐selective α‐adrenoreceptor antagonist used to reverse local anaesthesia, for example, during dental procedures when a vasoconstrictor is co‐applied. Phentolamine‐mediated vasodilation leads to faster clearance of injected drugs. Previous electrophysiological studies hypothesized that phentolamine acts as a modulator of voltage‐gated sodium channels, which could conflict with its indication as local anaesthetic reversal agent.

Experimental Approach

We performed manual and high throughput patch‐clamp recordings on HEK and CHO cells expressing NaV1.7 and NaV1.5. We investigated the effects of phentolamine on sodium channel biophysics and the additive impact of phentolamine on cells preconditioned with the local anaesthetic mexiletine. We used site‐directed mutagenesis, homology modelling and drug docking to identify phentolamine's binding site. We compared the effect on sodium channels with other clinically established α‐adrenoreceptor antagonists.

Key Results

Phentolamine inhibits NaV1.7 in HEK and CHO cells with an IC50 value of 72 and 57 μM and NaV1.5 in CHO cells with an IC50 of 27 μM. Phentolamine enhances the tonic block induced by the local anaesthetic mexiletine. Phentolamine binds to sodium channels at the local anaesthetic receptor site. The α‐adrenoreceptor antagonists alfuzosin, urapidil and phenoxybenzamine show lower potency on NaV1.5 and NaV1.7 in patch‐clamp recordings.

Conclusions and Implications

Phentolamine blocks voltage‐gated sodium channels via the local anaesthetic receptor site. This may conflict with its current indication as an antidote for local anaesthetics. We propose alternative α‐adrenoreceptor antagonists as possible candidates for local anaesthetic reversal because these are less potent inhibitors of both cardiac and neuronal voltage‐gated sodium channels.
No Association Found Between Uric Acid Levels and Peripheral Vertigo Disorders: Results From a Two‐Sample Mendelian Randomization Study
Authors: Liu Shihan , Lin Yiyi , Zhang Lingli , Luo Wenlong
Published: January 2025

Background

The association between serum uric acid levels and peripheral vertigo diseases, namely Benign Paroxysmal Positional Vertigo (BPPV), Meniere's Disease (MD), and Vestibular Neuritis (VN), remains a subject of controversy. This study utilises the Mendelian Randomization (MR) approach to investigate the potential link between uric acid levels and these peripheral vertigo diseases, with the goal of informing preventative measures and early intervention strategies.

Methods

Datasets pertaining to uric acid levels (sample size = 343 836) and BPPV (ncase = 3834, ncontrol = 209 582), MD (ncase = 1511, ncontrol = 209 582), and VN (ncase = 1224, ncontrol = 209 582) were selected from Genome‐Wide Association Studies (GWAS). Two‐sample MR was employed to analyse the correlation between the exposure (uric acid levels) and outcomes (BPPV, MD, VN). The MR analysis methods encompassed Inverse Variance Weighting (IVW), MR‐Egger, Simple Mode, Weighted Mode, and Weighted Median methods. The results derived from the IVW analysis were considered as the primary analytical outcomes.

Result

The findings indicated no significant correlation between uric acid levels and BPPV (IVW: OR = 1.152, 95% CI: 0.971–1.367, p = 0.103), MD (IVW: OR = 1.010, 95% CI: 0.757–1.348, p = 0.943), and VN (IVW: OR = 1.005, 95% CI: 0.744–1.358, p = 0.969).

Conclusion

This study employed a two‐sample Mendelian randomization approach to conduct an in‐depth analysis of the relationship between serum uric acid levels and peripheral vestibular diseases (BPPV, MD, and VN). Our findings indicate that no significant association was found between serum uric acid levels and these diseases. The results of the study do not support the hypothesis that uric acid is an independent risk factor for these conditions.
When Do Optimistic CEOs Enhance Firm Value?
Authors: Deshmukh Sanjay , Goel Anand
Published: January 2025

We predict how the effect of CEO optimism on firm value varies across firms and model how industry competition impacts the relation between CEO optimism and firm value. Estimating optimism from option‐exercise behaviour, we find that CEO optimism increases firm value by about 17% on average. Consistent with theoretical predictions, CEO optimism is more value‐enhancing in firms that are riskier, engage in greater innovation and investment, have more internal resources and operate in industries that are more competitive or have a larger fraction of optimistic CEOs. Various endogeneity checks support a causal impact of CEO optimism on firm value.
Words of advice for young scientists in developing countries
Authors: Chavarría Max
Published: January 2025

As scientists, change is the only constant in our journey. We often find ourselves in transition from one laboratory to another, and during our training we are fortunate to experience the excitement of pursuing postgraduate studies abroad in well‐funded, high‐level research centers. However, after completing doctoral or postdoctoral training, we are frequently drawn to return to our home countries, where funding and support for science are significantly more limited. In this brief commentary, first, I would like to highlight the challenges faced by scientists from developing countries who have had the opportunity to train internationally and then choose to return home, driven both by personal motivations (e.g., family) and by the desire to contribute to the scientific advancement of their regions. Second, I would like to share some advice that has been especially useful to me in establishing my laboratory, defining research topics, and maintaining academic productivity. I hope these insights can be useful to colleagues in similar situations across different regions. Although starting a research group in regions with less investment in Research and Development is challenging, it is achievable with perseverance and the implementation of concrete actions.
Hidradenitis Suppurativa Treatment During Pregnancy and Lactation: Navigating Challenges
Authors: Özbek Laşin , Güldan Mustafa , Alpsoy Erkan , Vural Seçil
Published: January 2025

Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory skin condition primarily affecting skin folds such as the axilla, groins, and the inframammary, perineal, and perianal regions. It is characterized by painful abscesses, sinus tracts, and scarring. Predominantly affecting young adults, particularly females, HS often emerges during reproductive age, and flares are widely reported during pregnancy and postpartum, underscoring the need to consider management strategies tailored to pregnant or lactating individuals. Moreover, the chronic and relapsing nature of HS, along with challenges related to the safety and compliance of medication use during pregnancy and lactation, as well as various comorbidities and psychological distress, significantly complicate its management in pregnant or lactating women. Treatment options, including topical clindamycin, oral clindamycin‐rifampicin, adalimumab, metformin, antiseptic washes, and certolizumab pegol, have accumulated evidence supporting their relative safety in pregnant and lactating women. While certolizumab pegol has shown promising safety data among biologics, it requires more efficacy data in HS. Conversely, while newly approved HS medications such as secukinumab and bimekizumab show promise for the general population, further research is necessary to evaluate their safety profiles in pregnant and breastfeeding individuals. The scant research available on HS in pregnant and lactating women, also shown by our systematic literature review, highlights the need for a comprehensive investigation into the safety, efficacy, and suitability of management strategies.
The Modified Coronally Advanced Tunnel Technique for Coverage of Mucosal Recessions at Dental Implants
Authors: Sculean Anton , Nikou Georgios , Deppe Herbert , Allen Edward P. , Cosgarea Raluca
Published: January 2025

Objectives

To clinically evaluate the outcomes following surgical coverage of single peri‐implant mucosal recessions in the aesthetic maxillary area by means of the modified coronally advanced tunnel (MCAT) and subepithelial connective tissue graft (SCTG).

Materials and Methods

Eleven systemically healthy non‐smoking patients (8 females) each presenting a single peri‐implant mucosal recession in the anterior maxillary region were consecutively treated with MCAT in conjunction with SCTG. In all cases, the facial recession was associated with an impaired aesthetic appearance. Before reconstructive surgery and at 12 months postoperatively, clinical and aesthetic parameters were assessed. The primary outcome variable was the mean mucosal recession coverage (MRC).

Results

Healing was uneventful in all cases. At 12 months, statistically significant (p < 0.05) recession coverage (MRC 94.71%) and improvement of aesthetics (pink aesthetic score) was obtained at all implants. Complete RC was obtained in 10 out of the 11 patients (90.9%). The treatment was associated with a statistically significant gain of keratinized and attached mucosa (p < 0.05).

Conclusion

The present results demonstrate that single peri‐implant mucosal recessions in the maxillary aesthetic area can be successfully treated with MCAT and SCTG.
A new circular economy conception for sustainable product design
Authors: Klose Svenja Anja , Fröhling Magnus
Published: January 2025

The design phase has a significant impact on a product's environmental footprint. To design sustainable products effectively, designers can make use of concepts from circular economy (CE) research. A plethora of conceptions of the CE (CECs) with links to sustainable product design can be found in the literature; however, we argue that they are incomplete and thereby miss effectiveness in enabling circular and sustainable product design. The aim of this paper is threefold: (i) We analyze the strengths and weaknesses of existing CE conceptions (CECs) and derive criteria for a reconception. (ii) Based on this, we propose a novel design approach with the newly developed conceptual CE design diagram (CEDD) in the center. (iii) The link between the CEDD to sustainable product design is established via four areas of decision (AoDs), which encompass CE strategies. One AoD has an overarching position, while the remaining AoDs are located along the three life cycle stages, production, use phase, and end of life, and should be considered jointly during design. Applied together, the CEDD with our design approach supports the structured generation and selection of sustainable design alternatives. Workshops were carried out to perform an initial validation of the conception. The proposition of CEDD and AoDs is targeted at a more effective product design for sustainability, thereby supporting a timely sustainability transition of the economy.
Native state structural and chemical characterisation of Pickering emulsions: A cryo‐electron microscopy study
Authors: Fernandez Ainaga Dario Luis , Roncal‐Herrero Teresa , Ilett Martha , Aslam Zabeada , Cheng Cheng , Hitchcock James P. , Cayre Olivier J. , Hondow Nicole
Published: January 2025

Transmission electron microscopy can be used for the characterisation of a wide range of thin specimens, but soft matter and aqueous samples such as gels, nanoparticle dispersions, and emulsions will dry out and collapse under the microscope vacuum, therefore losing information on their native state and ultimately limiting the understanding of the sample.

This study examines commonly used techniques in transmission electron microscopy when applied to the characterisation of cryogenically frozen Pickering emulsion samples. Oil‐in‐water Pickering emulsions stabilised by 3 to 5 nm platinum nanoparticles were cryogenically frozen by plunge‐freezing into liquid ethane to retain the native structure of the system without inducing crystallisation of the droplet oil cores.

A comparison between the droplet morphology following different sample preparation methods has confirmed the effectiveness of using plunge‐freezing to prepare these samples. Scanning transmission electron microscopy imaging showed that dry droplets collapse under the microscope vacuum, changing their shape and size (average apparent diameter: ∼342 nm) compared to frozen samples (average diameter: ∼183 nm). Cryogenic electron tomography was used to collect additional information of the 3D shape and size of the emulsion droplets, and the position of the stabilising nanoparticles relative to the droplet surface. Cryogenic energy dispersive X‐ray and electron energy loss spectroscopy were used to successfully obtain elemental data and generate elemental maps to identify the stabilising nanoparticles and the oil phase. Elemental maps generated from spectral data were used in conjunction with electron tomography to obtain 3D information of the oil phase in the emulsion droplets.

Beam‐induced damage to the ice was the largest limiting factor to the sample characterisation, limiting the effective imaging resolution and signal‐to‐noise ratio, though careful consideration of the imaging parameters used allowed for the characterisation of the samples presented in this study. Ultimately this study shows that cryo‐methods are effective for the representative characterisation of Pickering emulsions.