bluuebunny/crossref_metadata_2025 huggingface dataset:
A proximity complementation assay to identify small molecules that enhance the traffic of ABCA4 misfolding variants
Authors: Piccolo Davide , Zarouchlioti Christina , Bellingham James , Guarascio Rosellina , Ziaka Kalliopi , Molday Robert S. , Cheetham Michael E.
Published: March 2024

ABCA4-related-retinopathy is the most common inherited Mendelian eye disorder worldwide, caused by biallelic variants in the ATP-binding cassette transporter ABCA4. To date, over 2,200ABCA4variants have been identified, including missense, nonsense, indels, splice site and deep intronic defects. Notably, more than 60% are missense variants that can lead to protein misfolding, mistrafficking and degradation. Currently no approved therapies target ABCA4. In this study, we demonstrate that ABCA4 misfolding variants are temperature-sensitive and reduced temperature growth (30°C) improves their traffic to the plasma membrane, suggesting the folding of these variants could be rescuable. Consequently, anin vitroplatform was developed for the rapid and robust detection of ABCA4 traffic to the plasma membrane in transiently transfected cells. The system was used to assess selected candidate small molecules that were reported to improve the folding or traffic of other ABC transporters. Two candidates, 4-PBA and AICAR, were identified and validated for their ability to enhance both wild-type ABCA4 and variant trafficking to the cell surface in cell culture. We envision that this platform could serve as a primary screen for more sophisticatedin vitrotesting, enabling the discovery of breakthrough agents to rescue ABCA4 protein defects and mitigate ABCA4-related retinopathy.
Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation
Authors: Worthan Sarah B. , McCarthy Robert D. P. , Delaleau Mildred , Stikeleather Ryan , Bratton Benjamin P. , Boudvillain Marc , Behringer Megan G.
Published: March 2024

Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. TherhoR109H mutation frequently arose inE. colipopulations experimentally evolved under repeated long-term starvation conditions, during which feast and famine result in drastic environmental pH fluctuations. Metagenomic sequencing revealed that populations containing therhomutation also possess putative loss-of-function mutations inydcI, which encodes a recently characterized transcription factor associated with pH homeostasis. Genetic reconstructions of these mutations show that therhoallele confers a plastic alkaline-induced reduction of Rho function that, when found in tandem with a ΔydcIallele, leads to intracellular alkalinization and genetic assimilation of Rho mutant function. We further identify Arg to His substitutions at analogous sites inrhoalleles from species originating from fluctuating alkaline environments. Our results suggest that Arg to His substitutions in global regulators of gene expression can serve to rapidly coordinate complex responses through pH sensing and shed light on how cellular populations across the tree of life use environmental cues to coordinate rapid responses to complex, fluctuating environments.
The riboflavin biosynthetic pathway as a novel target for antifungal drugs againstCandidaspecies
Authors: Nysten Jana , Peetermans Arne , Vaneynde Dries , Demuyser Liesbeth , Van Dijck Patrick
Published: March 2024

In recent decades, there has been an increase in the occurrence of fungal infections, yet the arsenal of drugs available to fight invasive infections remains very limited. The development of new antifungal agents is hindered by the restricted number of molecular targets that can be exploited, given the shared eukaryotic nature of fungi and their hosts which often leads to host toxicity. In this paper, we examine the riboflavin biosynthetic pathway as a potential novel drug target.

Riboflavin is an essential nutrient for all living organisms. Its biosynthetic pathway does not exist in humans, who obtain riboflavin through their diet. Our findings demonstrate that all enzymes in the pathway are essential forCandida albicans,Candida glabrata,andSaccharomyces cerevisiae.Among these enzymes, Rib1 and Rib3 are the most promising targets. Auxotrophic strains, which mimic a drug targeting the biosynthesis pathway, experience rapid mortality in the absence of supplemented riboflavin. Nevertheless, the cells can still take up external riboflavin when supplemented. We identified Orf19.4337 as the riboflavin importer inC. albicansand named it Rut1. We found that Rut1 only facilitates growth at external riboflavin concentrations that exceed the physiological concentrations in the human body, making it unlikely that riboflavin uptake to act as a potential resistance mechanism for a drug targeting the biosynthesis pathway. Interestingly, the uptake system inS. cerevisiaeis more effective than inC. albicansandC. glabrata,enabling an auxotrophicS. cerevisiaestrain to outcompete an auxotrophicC. albicansstrain in lower riboflavin concentrations.

Importance

Candidaspecies are a common cause of invasive fungal infections.Candida albicans,in particular, poses a significant threat to immunocompromised individuals. This opportunistic pathogen typically lives as a commensal on mucosal surfaces of healthy individuals, but it can also cause invasive infections associated with high morbidity and mortality. Currently, there are only three major classes of antifungal drugs available to treat these infections. Additionally, the efficacy of these antifungal agents is restricted by host toxicity, suboptimal pharmacokinetics, a narrow spectrum of activity, intrinsic resistance of fungal species, such asCandida glabrata, to certain drugs, and the acquisition of resistance over time. Therefore, it is crucial to identify new antifungal drug targets with novel modes of action to add to the limited armamentarium.
Single nucleus transcriptomics supports a role for CCNA2-induced human adult cardiomyocyte cytokinesis
Authors: Bouhamida Esmaa , Vadakke-Madathil Sangeetha , Mathiyalagan Prabhu , Ranjan Amaresh K. , Sherman Cherrie D. , Miller Paul E , Ghetti Andre , Abi-Gerges Najah , Chaudhry Hina W.
Published: March 2024

Cyclin A2 (CCNA2) is a master regulatory gene of the cell cycle that is normally silenced in postnatal mammalian cardiomyocytes. We have previously demonstrated that it can induce significant cardiac repair in both small and large animals when delivered to the heart via a viral vector. To date, whether CCNA2 gene delivery can induce cytokinesis in isolated cardiomyocytes from adult human hearts has not been investigated. Therefore, we designed a human gene therapy vector featuring a replication-deficient, E1/E3-deleted human adenovirus five encoding human CCNA2 driven by the cardiac Troponin T promoter to enable the expression of CCNA2 in freshly isolated human cardiomyocytes. Utilizing time-lapse microscopy live imaging of cultured adult human cardiomyocytes isolated from a 21-year-old male, 41-year-old female, and 55-year-old male, we now report that human adult cardiomyocytes can be induced to undergo complete cytokinesis in response to CCNA2 gene delivery with preservation of sarcomere integrity in the resulting daughter cells. To elucidate the mechanistic underpinnings of CCNA2-dependent gene regulation in governing cardiomyocyte cytokinesis, we conducted single nucleus transcriptomics (snRNA-seq, 10X Genomics) analysis in hearts isolated from adult transgenic mice that constitutively express CCNA2 in cardiomyocytes (CCNA2-Tg) and non-transgenic mice (nTg). Remarkably, we identified a subpopulation of cardiomyocytes enriched with cytokinesis, proliferative, and reprogramming genes in hearts obtained from CCNA2-Tg mice as compared to hearts obtained from nTg mice. We also performed bulk RNA sequencing of human adult and fetal hearts, and we identified key reprogramming genes that are involved in CCNA2-induced cytokinesis. These results provide a compelling path forward for the clinical development of cardiac regenerative therapy based on strategic manipulation of the cardiomyocyte cell cycle.

Graphical Abstract

CCNA2 gene expression in primary adult cardiomyocytes induces cytokinesis while eliciting expression of proliferative and reprogramming genes in both humans and mice.
Media-induced emotions and message sidedness in corporate crises
Authors: Kong Sining , Tao Weiting , Chen Zifei Fay
Published: March 2024

Purpose

This study examines the interplay between media-induced emotional crisis framing (anger vs sadness) and message sidedness of crisis response on publics’ attribution of crisis responsibility as well as subsequent company evaluation and supportive behavioral intention.

Design/methodology/approach

A 2 (emotion: anger vs sadness) x 2 (crisis response: one-sided vs two-sided) online experiment was conducted among 161 participants in the USA.

Findings

Results showed that anger-inducing media framing of the crisis elicited higher levels of crisis responsibility attribution and more negative company evaluation, compared with sadness-inducing media framing. One-sided message response was more effective than two-sided message response in lowering attribution of crisis responsibility when sadness was induced, but no difference was found under the anger-induced condition. Attribution of crisis responsibility fully mediated the effects of emotional crisis framing on company evaluation and supportive behavioral intention toward the company.

Originality/value

This study is among the first to examine the interaction effect between emotional media framing and response message sidedness in an ambiguous crisis. Drawing on the interdisciplinary theoretical frameworks, this study integrates the situational crisis communication theory, appraisal-tendency framework and message sidedness in persuasion literature. As such, it contributes to theoretical development in crisis communication and offers communication managers guidance on how to effectively address emotionally framed crises.
Green finance when stakeholders’ interests collide with each other: the case of Bangladesh
Authors: Agha Mahmoud , Hossain Md Mosharraf , Islam Md Shajul
Published: March 2024

Purpose

This study examines the impact of chief executive officer (CEO) power, institutional investors and their interaction on green financing provided by Bangladeshi financial institutions and the moderating effect of government policy and CEO political connections on these relations.

Design/methodology/approach

We employ ordinary least squares (OLS) regressions and interaction terms among variables of interest for the empirical analysis.

Findings

Green financing decreases with CEO power, implying that CEOs of this country’s financial institutions are averse to green loans, whereas institutional investors increase green financing extended by these institutions. The government policy, which includes financial incentives for complying financial institutions, strengthens institutional investors' positive impact on green financing, but it does not change CEOs' aversion to green loans. Institutional investors have a positive moderating effect on the relationship between green finance (GF) and CEO power, but this positive moderating effect is negated in banks where the government owns a stake, possibly because CEOs of state-owned financial institutions are politically connected, which reduces institutional investors’ influence over them.

Originality/value

This study is unique in that it is the first to examine how the interaction among different stakeholders affects green financing in a unique setting. As the literature is almost silent on this topic, the findings of this paper are expected to raise policymakers’ awareness of the obstacles that hamper the efforts of developing countries to go green.
Another look at the price clustering behavior: evidence from the Muscat stock exchange
Authors: Chebbi Tarek , Migdady Hazem , Hmedat Waleed , Shehadeh Maha
Published: March 2024

Purpose

The price clustering behavior is becoming a core part of the market efficiency theory especially with the development of trading strategies and the occurrence of major and unprecedented shocks which have led to severe inquiry regarding asset price dynamics and their distribution. However, research on emerging stock market is scant. The study contributes to the literature on price clustering by investigating an active emerging stock market, the Muscat stock market one of the Arabian Gulf Markets.

Design/methodology/approach

This research adopts the artificial intelligence technique and other statistical estimation procedure in understanding the price clustering patterns in Muscat stock market and their main determinants.

Findings

The findings reveal that stock prices are marked by clustering behavior as commonly highlighted in the previous studies. However, we found strong evidence of price preferences to cluster on numbers closer to zero than to one. We also show that the nature of firm’s activity matters for price clustering behavior. In addition, firms with traded bonds in Oman market experienced a substantial less stock price clustering than other firms. Clustered stock prices are more likely to have higher prices and higher volatility of price. Finally, clustering raised when the market became highly uncertain during the Covid-19 crisis especially for the financial firms.

Originality/value

This study provides novel results on price clustering literature especially for an active emerging market and during the Covid-19 pandemic crisis.
Plant geographic distribution influences chemical defences in native and introduced Plantago lanceolata populations
Authors: Medina‐van Berkum Pamela , Schmöckel Eric , Bischoff Armin , Carrasco‐Farias Natalia , Catford Jane A. , Feldmann Reinart , Groten Karin , Henry Hugh A. L. , Bucharova Anna , Hänniger Sabine , Luong Justin C. , Meis Julia , Oetama Vincensius S. P. , Pärtel Meelis , Power Sally A. , Villellas Jesus , Welk Erik , Wingler Astrid , Rothe Beate , Gershenzon Jonathan , Reichelt Michael , Roscher Christiane , Unsicker Sybille B.
Published: March 2024

Plants growing outside their native range may be confronted by new regimes of herbivory, but how this affects plant chemical defence profiles has rarely been studied.

Using Plantago lanceolata as a model species, we investigated whether introduced populations show significant differences from native populations in several growth and chemical defence traits. Plantago lanceolata (ribwort plantain) is an herbaceous plant species native to Europe and Western Asia that has been introduced to numerous countries worldwide.

We sampled seeds from nine native and 10 introduced populations that covered a broad geographic and environmental range and performed a greenhouse experiment, in which we infested half of the plants in each population with caterpillars of the generalist herbivore Spodoptera littoralis. We then measured size‐related and resource‐allocation traits as well as the levels of constitutive and induced chemical defence compounds in roots and shoots of P. lanceolata.

When we considered the environmental characteristics of the site of origin, our results revealed that populations from introduced ranges were characterized by an increase in chemical defence compounds without compromising plant biomass. The concentrations of iridoid glycosides and verbascoside, the major anti‐herbivore defence compounds of P. lanceolata, were higher in introduced populations than in native populations. In addition, introduced populations exhibited greater rates of herbivore‐induced volatile organic compound emission and diversity, and similar chemical diversity based on untargeted analyses of leaf methanol extracts.

In conclusion, the geographic origin of the populations had a significant influence on morphological and chemical plant traits, suggesting that P. lanceolata populations are not only adapted to different environments in their native range, but also in their introduced range.

Read the free Plain Language Summary for this article on the Journal blog.
Degrees of difference: Do college credentials earned behind bars improve labor market outcomes?
Authors: Ballou Abby
Published: March 2024

It is widely held that providing postsecondary education programs to incarcerated individuals will improve postrelease labor market outcomes. Little research evidence exists, however, to support this view. To test the effect of postsecondary carceral education credentials on employer perceptions of hireability, the current study uses a factorial design to survey a sample of employers nationwide (N = 2,538). Employers were presented with résumés of fictional applicants applying to a job as a customer service representative at a large call center. The résumés randomized education credentials earned while incarcerated. Results indicate that employers were significantly more willing to interview applicants with postsecondary education credentials relative to applicants with only a General Educational Development (GED) diploma. Although Black applicants who had earned a sub‐baccalaureate certificate saw improvements in hireability relative to GED holders, Black applicants who had earned a bachelor's degree did not. In contrast, White applicants benefited both from sub‐baccalaureate certificates and bachelor's degrees. Results from a mediation analysis suggest that these credentials signal important information to employers about applicant attributes and that improved perceptions of applicant ability and likelihood to reoffend drive the overall effect. Implications for future research and policy are explored.
Development and validation of a DNA‐based multi‐species biomonitoring toolkit using a high‐throughput qPCR platform: A case study of Irish shellfish species
Authors: van der Pouw Kraan Dennis , Graham Conor T. , Kavanagh Fiona , Mirimin Luca
Published: March 2024

Biomonitoring of marine life has been enhanced in recent years by the integration of innovative DNA‐based approaches, which offer advantages over more laborious techniques (e.g. microscopy). However, trade‐offs between throughput, sensitivity and quantitative measurements must be made when choosing between the prevailing molecular methodologies (i.e. metabarcoding or qPCR/dPCR). Thus, the aim of the present study was to demonstrate the utility of a microfluidic‐enabled high‐throughput quantitative PCR platform (HTqPCR) for the rapid and cost‐effective development and validation of a DNA‐based multi‐species biomonitoring toolkit, using larvae of 23 commercially targeted bivalve and crustacean species as a case study. The workflow was divided into three main phases: definition of (off‐) target taxa and establishment of reference databases (PHASE 1); selection/development and assessment of molecular assays (PHASE 2); and protocol optimization and field validation (PHASE 3). 42 assays were eventually chosen and validated. Genetic signal not only showed good correlation with direct visual counts by microscopy but also showed the ability to provide quantitative data at the highest taxonomic resolution (species level) in a time‐ and cost‐effective fashion. This study developed a biomonitoring toolkit, demonstrating the considerable advantages of this state‐of‐the‐art technology in boosting the developmental testing and application of panels of molecular assays for the monitoring and management of natural resources. Once developed, this approach provides a cost and time‐effective alternative compared to other multi‐species approaches (e.g. metabarcoding). In addition, it is transferable to a wide range of species and will aid future monitoring programmes.
Epigenetic aging of human blood cells is influenced by the age of the host body
Authors: Holland Petter , Istre Mette , Ali Maryan M. , Gedde‐Dahl Tobias , Buechner Jochen , Wildhagen Mari , Brunvoll Sonja H. , Horvath Steve , Matsuyama Shigemi , Dahl John Arne , Stölzel Friedrich , Søraas Arne
Published: March 2024

Allogenic hematopoietic stem cell transplantation is a therapeutic procedure performed over a wide range of donor and recipient age combinations, representing natural experiments of how the age of the recipient affects aging in transplanted donor cells in vivo. We measured DNA methylation and epigenetic aging in donors and recipients and found that biological epigenetic clocks are accelerated in cells transplanted into an older body and decelerated in a younger body. This is the first evidence that the age of the circulating environment influences human epigenetic aging in vivo.
A pilot study of virtual reality for inpatients with opioid use disorder
Authors: Greenwald Herbert J. , Berger Amy , Wilson Ronan L. H. , Greenwald Daniel J. , Lannon Eileen , Johnson‐Smith Phyllis , Bergman Brandon G. , Wilens Timothy E.
Published: March 2024

Background and Objectives

While inpatient withdrawal management/acute stabilization can improve outcomes for individuals with opioid use disorder (OUD), patients often leave treatment early due to mood, tension, and cravings associated with opioid withdrawal. The aim of this study was to evaluate the feasibility and preliminary effectiveness of a novel virtual reality (VR) based intervention; 3D Therapy Thrive (3DTT).

Methods

Subjects with OUD (N = 32) were recruited from a community acute stabilization program and received up to two sessions of 3DTT. They completed questionnaires related to their overall satisfaction with the experience and side effects; as well as those related to mood, tension, and cravings.

Results

There were no reported side effects and the majority of subjects (94%) reported high satisfaction with the experience. Out of 62 patients approached, 33 patients agreed to participate (53%) 33 patients completed one, and 17 of these patients (52%) completed both sessions of 3DTT, with 19 participants (58%) completing their treatment protocols. Compared to baseline, 3DTT participants reported significant reductions in depression, tension, and cravings (p's < 0.001).

Discussion and Conclusions

This pilot study supports the feasibility and preliminary effectiveness of 3DTT for improving outcomes for inpatients with OUD. Future randomized controlled trials are necessary to evaluate the efficacy of 3DTT for improving retention, reducing cravings, and improving mood and tension.

Scientific Significance

This is the first study to evaluate the feasibility of a psychologically informed VR intervention in inpatients with OUD.
Commodity price volatility and the psychological well‐being of farmers
Authors: Singhal Saurabh , Tarp Finn
Published: March 2024

We examine the effects of income uncertainty on mental health in Vietnam. We assess this issue using volatility in the price of coffee, a key export commodity, that exposes small coffee farmers to income uncertainty. Using household panel data collected over 2016–2020, we find an increase in volatility of the international coffee price to be positively associated with psychological distress among coffee farmers. The magnitude is greater for men, and the findings are robust to several checks. These results are further substantiated by corresponding estimates for related health measures and self‐reported happiness. Channels include an increase in mental stress due to pessimistic expectations of future economic well‐being, increased cognitive load and alcohol consumption, and reduced social capital. The results highlight the psychological toll of living with income uncertainty and provide support for the provision of social safety nets that protect farmers from frequent commodity price fluctuations.
NUM‐score: A clinical‐analytical model for personalised imaging after urinary tract infections
Authors: González‐Bertolín Isabel , Barbas Bernardos Guillermo , Zarauza Santoveña Alejandro , García Suarez Leire , López López Rosario , Plata Gallardo Marta , De Miguel Cáceres Cristina , Calvo Cristina
Published: March 2024

Aim

To identify predictive variables and construct a predictive model along with a decision algorithm to identify nephrourological malformations (NUM) in children with febrile urinary tract infections (fUTI), enhancing the efficiency of imaging diagnostics.

Methods

We performed a retrospective study of patients aged <16 years with fUTI at the Emergency Department with subsequent microbiological confirmation between 2014 and 2020. The follow‐up period was at least 2 years. Patients were categorised into two groups: ‘NUM’ with previously known nephrourological anomalies or those diagnosed during the follow‐up and ‘Non‐NUM’ group.

Results

Out of 836 eligible patients, 26.8% had underlying NUMs. The study identified six key risk factors: recurrent UTIs, non‐Escherichia coli infection, moderate acute kidney injury, procalcitonin levels >2 μg/L, age <3 months at the first UTI and fUTIs beyond 24 months. These risk factors were used to develop a predictive model with an 80.7% accuracy rate and elaborate a NUM‐score classifying patients into low, moderate and high‐risk groups, with a 10%, 35% and 93% prevalence of NUM. We propose an algorithm for approaching imaging tests following a fUTI.

Conclusion

Our predictive score may help physicians decide about imaging tests. However, prospective validation of the model will be necessary before its application in daily clinical practice.
CEO career horizons, foreign experience, and state ownership impact on the adoption of the Global Reporting Initiative standards for corporate social responsibility reporting
Authors: Ashraf Adnan , Qi Baolei , Meile Zhu , Marie Mohamed
Published: March 2024

This study investigates the influence of chief executive officers' (CEOs) career horizon on the adoption of Global Reporting Initiative (GRI) standards for corporate social responsibility (CSR) reporting. Using data from A‐share Chinese listed firms on the Shanghai and Shenzhen stock exchanges from 2010 to 2020, we employ logistic regression analysis to examine the empirical relationship. Our findings indicate that companies led by CEOs with shorter career horizons (older CEOs) are less inclined to adopt GRI reporting standards for CSR reporting. This association is particularly pronounced in non‐state‐owned enterprises compared to state‐owned enterprises. Additionally, we observe a weaker relationship between CEO career horizon and GRI adoption when the CEO possesses foreign experience. These results remain robust across various measures of CEO career horizons and econometric methodologies as well. The implications of our findings are significant for understanding the development and implementation of GRI standards for CSR reporting, particularly within the context of China.
Smouldering multiple myeloma: To seek or not to seek? To treat or not to treat. That is the question
Authors: Vaxman Iuliana , Gatt Moshe E.
Published: March 2024

In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence‐based approach to managing these patients. Key questions remain yet unsolved.

Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193‐1206.
Direct vagus nerve stimulation: A new tool to control allergic airway inflammation through α7 nicotinic acetylcholine receptor
Authors: Sévoz‐Couche Caroline , Liao Wupeng , Foo Hazel Y. C. , Bonne Isabelle , Lu Thong Beng , Tan Qi Hui Caris , Azhar Syaza Hazwany , Peh Wendy Yen Xian , Yen Shih‐Cheng , Wong W. S. Fred
Published: March 2024

Background and Purpose

Asthma is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The use of nicotinic agents to mimic the cholinergic anti‐inflammatory pathway (CAP) controls experimental asthma. Yet, the effects of vagus nerve stimulation (VNS)‐induced CAP on allergic inflammation remain unknown.

Experimental Approach

BALB/c mice were sensitized and challenged with house dust mite (HDM) extract and treated with active VNS (5 Hz, 0.5 ms, 0.05–1 mA). Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts and cytokine levels. Lungs were examined by histopathology and electron microscopy.

Key Results

In the HDM mouse asthma model, VNS at intensities equal to or above 0.1 mA (VNS 0.1) but not sham VNS reduced BAL fluid differential cell counts and alveolar macrophages expressing α7 nicotinic receptors (α7nAChR), goblet cell hyperplasia, and collagen deposition. Besides, VNS 0.1 also abated HDM‐induced elevation of type 2 cytokines IL‐4 and IL‐5 and was found to block the phosphorylation of transcription factor STAT6 and expression level of IRF4 in total lung lysates. Finally, VNS 0.1 abrogated methacholine‐induced hyperresponsiveness in asthma mice. Prior administration of α‐bungarotoxin, a specific inhibitor of α7nAChR, but not propranolol, a specific inhibitor of β2‐adrenoceptors, abolished the therapeutic effects of VNS 0.1.

Conclusion and Implications

Our data revealed the protective effects of VNS on various clinical features in allergic airway inflammation model. VNS, a clinically approved therapy for depression and epilepsy, appears to be a promising new strategy for controlling allergic asthma.
Aberrant dynamic properties of whole‐brain functional connectivity in acute mild traumatic brain injury revealed by hidden Markov models
Authors: Lu Liyan , Li Fengfang , Li Hui , Zhou Leilei , Wu Xinying , Yuan Fang
Published: March 2024

Objectives

This study aimed to investigate the temporal dynamics of brain activity and characterize the spatiotemporal specificity of transitions and large‐scale networks on short timescales in acute mild traumatic brain injury (mTBI) patients and those with cognitive impairment in detail.

Methods

Resting‐state functional magnetic resonance imaging (rs‐fMRI) was acquired for 71 acute mTBI patients and 57 age‐, sex‐, and education‐matched healthy controls (HCs). A hidden Markov model (HMM) analysis of rs‐fMRI data was conducted to identify brain states that recurred over time and to assess the dynamic patterns of activation states that characterized acute mTBI patients and those with cognitive impairment. The dynamic parameters (fractional occupancy, lifetime, interval time, switching rate, and probability) between groups and their correlation with cognitive performance were analyzed.

Results

Twelve HMM states were identified in this study. Compared with HCs, acute mTBI patients and those with cognitive impairment exhibited distinct changes in dynamics, including fractional occupancy, lifetime, and interval time. Furthermore, the switching rate and probability across HMM states were significantly different between acute mTBI patients and patients with cognitive impairment (all p < 0.05). The temporal reconfiguration of states in acute mTBI patients and those with cognitive impairment was associated with several brain networks (including the high‐order cognition network [DMN], subcortical network [SUB], and sensory and motor network [SMN]).

Conclusions

Hidden Markov models provide additional information on the dynamic activity of brain networks in patients with acute mTBI and those with cognitive impairment. Our results suggest that brain network dynamics determined by the HMM could reinforce the understanding of the neuropathological mechanisms of acute mTBI patients and those with cognitive impairment.
Challenges to epilepsy management in Rwandan women living with epilepsy
Authors: Teuwen Dirk E. , Ndayisenga Arlène , Garrez Ieme , Sebera Fidèle , Mutungirehe Sylvestre , Umwiringirwa Josiane , Ndiaye Mustapha , Umuhoza Georgette , Boon Paul A. J. M. , Dedeken Peter
Published: March 2024

Background and purpose

In Rwanda, epilepsy prevalence ranges between 29‰ and 49‰. Many women living with epilepsy (WwE) are of childbearing age. Epilepsy characteristics and management, contraception, pregnancy, puerperium and stigma in WwE presenting at the neurology clinic of Ndera, Rwanda, were investigated.

Methods

This prospective cross‐sectional study investigated demographics, epilepsy characteristics, treatment, contraception, folic acid use, pregnancy, puerperium and stigma in WwE aged ≥18 years. Subgroups were analysed by status of any pregnancy and time of epilepsy diagnosis relative to pregnancy, with significant differences expected.

Results

During December 2020 and January 2021, a hundred WwE were enrolled (range 18–67 years). Fifty‐two women had never been pregnant, 39 women had epilepsy onset before pregnancy and nine were diagnosed after pregnancy. No significant differences in age, marital status or occupation were observed. Contraception was used by 27%, of whom 50% were taking enzyme‐inducing anti‐epileptic medication. Valproate was used by 46% of WwE of reproductive age. Thirty‐nine women with epilepsy onset before pregnancy reported 91 pregnancies, with 14% spontaneous abortions. None used folic acid before conception, and 59% only during pregnancy. Five of 78 newborns were preterm. No offspring had major congenital malformations. Nearly 25% of WwE were not compliant with their anti‐epileptic medication schedule during pregnancy or breastfeeding. Internalized stigma was observed in more than 60%. Up to 25% had been discriminated against at school or work.

Conclusion

A comprehensive strategy considering the reproductive health and societal challenges of WwE is needed to drive optimal epilepsy management, reproductive health outcomes and societal inclusion.
Characterization of the agonistic behavior of the weakly electric fish Gymnotus sylvius
Authors: Perrone Rossana , Hurtado Alejandra , Silva Ana , Black‐Décima Patricia
Published: March 2024

Electric fish are good models in neuroethology as any behavior in electric fish involves both locomotor and electrical displays, which are experimentally accessible and controlled by well‐known neural circuits. The agonistic behavior within the genus Gymnotus has been evaluated in Gymnotus carapo and Gymnotus omarorum, providing an advantageous model system to address comparative analyses. Gymnotus sylvius is a weakly electric fish which occurs in sympatry with G. omarorum in freshwater environments of Argentina. Here, we describe the agonistic behavior of G. sylvius in laboratory conditions. All dyads engaged in intense fights, with a latency to the first attack of 8 ± 7.8 s and a contest phase of 42.71 ± 31.7 s. Individual initiative in the first attack predicted contest outcome with no apparent influence of body weight asymmetry between contenders. Contenders did not escalate in their aggression during the short contest; in turn, subordinates tended to retreat in response to dominants' attacks. Submission and dominance were expressed by electric signals: dominants increased their basal electric organ discharge (EOD) rate after contest resolution, resulting in a persistent EOD rate rank. Subordinates also emitted chirps and offs during the contest and post‐resolution phases without a clear temporal pattern. The agonistic behavior of G. sylvius presents some similarities with other species of the genus Gymnotus: EOD rank between dominants and subordinates, electric signals of submission, and the presence of attacks in the post‐resolution phase. On the other hand, it also presents differences: a shorter evaluation phase in G. sylvius, initiative as a determinant of outcome, a higher attack rate of dominants in G. sylvius, a different temporal pattern of chirps, and different mechanisms to separate EOD rate of dominants and subordinates. These facts open a promising road to analyze the evolution of different neuroendocrine strategies, operating on homologous neural pathways, to command the same behavior.
Introducing ‘ministerial politics’: Analyzing the role and crucial redistributive impact of individual ministries in policy‐making
Authors: Garritzmann Julian L. , Siderius Katrijn
Published: March 2024

Policy‐making is a complex business. While scholars have studied the politics of policy‐making for decades, we know surprisingly little about the role of individual ministries. We argue that and why individual ministries crucially shape policies' content, particularly their distributive profiles. We explain that it matters whether for example, a Ministry of Labor, of Finance, or of Home Affairs designs a policy. First, we systematically review existing literature on the factors that influence preferences of ministries and their power in policy‐making. Second, we develop a theory explaining that and why ministries have substantive policy impact and introducing a typology of three different ministerial ideal‐types: ministries follow a “social logic”, an “efficiency logic”, or a “law‐and‐order logic”. Third, we offer systematic empirical evidence: Using the least likely case of Germany, we introduce a novel content‐coded dataset on all social policies in the Bundestag since 1969, showing that ministries shape policies' distributive profiles, even when controlling for rival explanations, such as the partisan affiliation of ministers, the policy field, or cabinet type. We conclude by developing a research agenda on ministerial politics and highlight important implications for representation and responsiveness.
Mapping wing morphs of Tetrix subulata using citizen science data: Flightless groundhoppers are more prevalent in grasslands near water
Authors: Willighagen Lars G. , Jongejans Eelke
Published: March 2024

The slender groundhopper (Orthoptera: Tetrigidae) Tetrix subulata (Linnaeus, 1758), like several other taxa of winged insects, has a long‐winged and a short‐winged form, the latter incapable of flight.

The optimal habitat of T. subulata consists of wet meadows and flat shores, as they feed mostly on algae and mosses in damp, sun‐exposed, open patches. Contrasting hypotheses predict either short‐ or long‐winged morphs to be relatively more prevalent in optimal habitats.

Previous investigations were limited in their spatial extent. To strongly increase the number of study locations, we obtained, through the Global Biodiversity Information Facility (GBIF), geo‐referenced observations made by citizen scientists in the Netherlands.

We determined individuals' wing form based on photographs accompanying these observations and related wing‐form patterns to large‐ and medium‐scale landscape characteristics.

Our analyses revealed that in grasslands near the major rivers, relatively more short‐winged individuals were found. In drier landscapes consisting of coniferous forests and heath on the higher sand areas, more long‐winged individuals were observed. Built‐up areas had no significant effect on the wing length.

These patterns might be caused by the oogenesis‐flight syndrome or small‐scale spatial sorting, but the exact mechanism is yet unknown, as size‐dependency might also play a role.

Although opportunistic observations are biased by where and when observers prefer to go, and by reporting probabilities varying between species groups, these biases are not likely to have affected our conclusions. Citizen science data appear to be suitable for analyses of spatial distribution and sorting of morphological types within species.
A functional variant of ALDH1A2 is associated with hand osteoarthritis in the Chinese population
Authors: Dai Jian , Jiang Haitao , Yang Zhaoqi , Chen Chuan , Tang Xiaoming
Published: March 2024

Genome‐wide association study identified common variants within the ALDH1A2 gene as the susceptible loci of hand osteoarthritis (HOA) in UK and Iceland populations. Located in chromosome 15, ALDH1A2 encodes aldehyde dehydrogenase family 1 member A2, which is an enzyme that catalyses the synthesis of retinoic acid from retinaldehyde. Our purposes were to replicate the association of functional variant in ALDH1A2 with the development of HOA in the Chinese population. Variant rs12915901 of ALDH1A2 was genotyped in 872 HOA patients and 1223 healthy controls. Subchondral bone samples were collected from 40 patients who had undergone a trapeziectomy, and the tissue expression of ALDH1A2 was analysed. The chi‐square analysis was used to compare the frequency of genotype and risk allele between the HOA cases and controls. The Student t test was used to compare the mRNA expression of ALDH1A2 between patients with genotype AA/AG and those with genotype GG. The frequency of genotype AA was significantly higher in HOA patients than in the controls (7.6% vs. 5.1%, p = .01). The frequency of allele A was significantly higher in the patients than in the controls (28.9% vs. 24.6%, p = .005). The mRNA expression of ALDH1A2 was 1.31‐folds higher in patients with genotype GG than in the patients with genotype AA/AG (0.000617 ± 0.000231 vs. 0.000471 ± 0.000198, p = .04). Variant rs12915901 of ALDH1A2 contributed to the susceptibility of HOA in the Chinese population. Allele A of rs12915901 can add to the risk of HOA possibly via down‐regulation of ALDH1A2 expression.
Methyl‐supplemented nutrition delays the development of autoimmune disease in pristane‐induced murine lupus
Authors: Bradyanova Silviya , Manoylov Iliyan , Boneva Gabriela , Kechidzhieva Lidiya , Tchorbanov Andrey , Nikolova‐Ganeva Kalina
Published: March 2024

The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl‐supplemented nutrition on the development of SLE was studied in the pristane‐induced mouse model of the disease. The results clearly demonstrated decreased anti‐dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl‐containing micronutrients with possible anti‐inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.
Functional neutrophil disorders: Chronic granulomatous disease and beyond
Authors: Zerbe Christa S. , Holland Steven M.
Published: March 2024

Since their description by Metchnikoff in 1905, phagocytes have been increasingly recognized to be the entities that traffic to sites of infection and inflammation, engulf and kill infecting organisms, and clear out apoptotic debris all the while making antigens available and accessible to the lymphoid organs for future use. Therefore, phagocytes provide the gateway and the first check in host protection and immune response. Disorders in killing and chemotaxis lead not only to infection susceptibility, but also to autoimmunity. We aim to describe chronic granulomatous disease and the leukocyte adhesion deficiencies as well as myeloperoxidase deficiency and G6PD deficiency as paradigms of critical pathways.
Comparing urine point‐of‐care tests to screen preeclampsia: Congo‐red dot paper test versus dipstick urinalysis
Authors: Wang Liying , Gao Jinsong , Tang Pingping , Hu Huiying , Chen Xiaoxu , Chen Ziyi , Sun Yin
Published: March 2024

To compare the urine Congo‐red dot paper test (CRD) with dipstick urinalysis to screen preeclampsia (PE). A total of 409 paired spot urine samples were obtained prospectively from women with suspected pre‐eclampsia attending for routine hospital visits. Congo‐red dot paper test and dipstick urinalysis were examined and compared to screen pre‐eclampsia. The agreement between the two urinary test is modest (kappa coefficient = 0.28, 95% CI 0.14–0.42). The specificity of CRD was higher than urinalysis (97.4% vs. 90.4%, p < .001). Urinalysis performed better in sensitivity (77.3% vs. 40.9%, p = .04) and the area under the receiver operating characteristic curves (AUC) (0.84 [95% CI 0.74–0.94] vs. 0.69 [95% CI 0.55–0.83], p = .04) than CRD, respectively. The sensitivity, specificity, AUC of the parallel test of them is 86.4% (64.0%–96.4%), 89.1% (85.5%–92.0%), and 0.88 (95% CI 0.79–0.96). And the serial test is 31.8% (14.7%–54.9%), 98.7% (96.8%–99.5%), 0.65 (95% CI 0.51–0.79), accordingly. The urinalysis is a better diagnosing test for preeclampsia. CRD could aid in the diagnosis of patients with preeclampsia. Combined the two tests in suspected patients may further improve the performance in the diagnosis of preeclampsia. Further study need to be made for its potential clinical practice.
Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis
Authors: Li Zi‐Hao , Li Jia‐Yi , Wu Zuo‐Tao , Zhu Yong‐Jie , Zhuo Ting , Nong Ju‐Sen , Qian Jing , Peng Hua‐Jian , Dai Lei , Wang Yong‐Yong , Chen Ming‐Wu , Zeng Xiao‐Chun
Published: March 2024

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan–Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real‐time quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late‐stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.