bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen and Phosphorus Allocation Strategies in a Chronosequence of Tropical Dry Forests: Plant Coordination and Environmental Drivers
Authors: Bretherick Emma J. M. , Dupuy Juan M. , García‐Oliva Felipe , Rivero Villar Anaitzi , Rosell Julieta A. , Campo Julio
Published: February 2025

Identifying how limited resources, such as nutrients, are allocated across plant organs can provide new insights into ecophysiological strategies, as well as ecosystem nutrient cycles. Plants may allocate different nutrients within a specific organ or the same nutrient among different organs. In this study, we explored the allocation strategies of nitrogen (N) and phosphorus (P) in the leaves, stems, and roots of nine dominant tree species in secondary tropical dry forests using scaling analysis. The results showing that N and P have different scaling relationships within and among plant organs. The scaling relationships of P versus N concentrations in non‐leaf organs were isometric across secondary succession and shifted in leaves from allometric (P concentration increased faster than N concentration) to isometric. The scaling relationships of N or P concentrations between metabolic (leaves vs. fine roots) or between structural (stems vs. coarse roots) plant organs tended to be isometric along succession. Whilst the scaling relationships of the same nutrient between metabolic versus structural plant organs tended to be allometric (N and P concentrations increased faster in woody organs than in metabolic organs) across succession. A principal component analysis suggests associations of nutrient allocation to woody organs with soil pH over the chronosequence and with vegetation structure and soil nutrient availability in the case of metabolic organs. These findings on the sensitivity in plant nutrient allocation to changes in soil and vegetation properties during secondary succession may have practical implications for carbon sequestration management and models and restoration of this threatened ecosystem.
Perceived Predation Risk Affects Mammal Behavior at Amazonian Mineral Licks
Authors: Griffiths Brian M. , Stabach Jared , Kolowski Joseph
Published: February 2025

Mineral licks are critical resources for herbivores in Amazonia and other tropical regions which may be deficient in dietary minerals or consuming alkaloid‐laced leaves which may cause gastrointestinal issues. However, mineral licks are also important locations for predators, including human hunters. Animals visiting mineral licks must balance the benefits of relief of physiological stressors with the risk of predation, and they may employ behavioral adaptations to do so. We used camera trap data on six large‐bodied mammal species at 52 mineral licks in the same watershed in the Peruvian Amazon to assess how mineral licks contribute to visiting species' perception of risk. We tested the effects of a range of covariates including direct and indirect measures of risk, habitat characteristics, and soil properties on visit duration, a behavioral adaptation species may use to mitigate risk, in a generalized linear mixed‐effects modeling framework. Tapirs, collared peccaries, and paca minimized visit duration in risky licks, while howler monkeys, red brocket deer, and black agoutis had higher visit duration in risky licks, potentially due to increased vigilance and reduced feeding efficiency. The strong relationships between risk and behavior across species demonstrates the ecological value of mineral licks for both predators and prey, as prey must seek mineral licks but at great cost. Conserving mineral licks in landscapes may be a critical component to the conservation of both herbivores and carnivores in Amazonia, and for food security of local people.
MANDALA—Visual Exploration of Anomalies in Industrial Multivariate Time Series Data
Authors: Suschnigg J. , Mutlu B. , Koutroulis G. , Hussain H. , Schreck T.
Published: February 2025

The detection, description and understanding of anomalies in multivariate time series data is an important task in several industrial domains. Automated data analysis provides many tools and algorithms to detect anomalies, while visual interfaces enable domain experts to explore and analyze data interactively to gain insights using their expertise. Anomalies in multivariate time series can be diverse with respect to the dimensions, temporal occurrence and length within a dataset. Their detection and description depend on the analyst's domain, task and background knowledge. Therefore, anomaly analysis is often an underspecified problem. We propose a visual analytics tool called MANDALA (Multivariate ANomaly Detection And expLorAtion), which uses kernel density estimation to detect anomalies and provides users with visual means to explore and explain them. To assess our algorithm's effectiveness, we evaluate its ability to identify different types of anomalies using a synthetic dataset generated with the GutenTAG anomaly and time series generator. Our approach allows users to define normal data interactively first. Next, they can explore anomaly candidates, their related dimensions and their temporal scope. Our carefully designed visual analytics components include a tailored scatterplot matrix with semantic zooming features that visualize normal data through hexagonal binning plots and overlay candidate anomaly data as scatterplots. In addition, the system supports the analysis on a broader scope involving all dimensions simultaneously or on a smaller scope involving dimension pairs only. We define a taxonomy of important types of anomaly patterns, which can guide the interactive analysis process. The effectiveness of our system is demonstrated through a use case scenario on industrial data conducted with domain experts from the automotive domain and a user study utilizing a public dataset from the aviation domain.
miR‐448‐3p/miR‐1264‐3p Participates in Intermittent Hypoxic Response in Hippocampus by Regulating Fam76b/hnRNPA2B1
Authors: Liu Chuncheng , Qu Donghui , Li Chaoxun , Pu Wenhua , Li Jun , Cai Lu
Published: February 2025

Background

Intermittent hypoxia (IH), as a key pathogenic factor of obstructive sleep apnea syndrome (OSAS), can cause many diseases, such as increased inflammation and oxidative stress, diabetes, cardiovascular disease, and Alzheimer's disease (AD). The response of cells to hypoxia involves multiple levels of regulatory mechanisms, including transcriptional regulation of gene expression, regulation of mRNA stability, post‐transcriptional regulation, and post‐translational modification regulation.

Aims

The regulation of miRNA and alternative splicing (AS) in neuronal response to intermittent hypoxia deserve further study.

Materials & Methods

By establishing a mouse model of intermittent hypoxia, we conducted functional studies on key miRNAs and splicing factor using methods such as miRNA sequencing, bioinformatics, and molecular biology.

Results

In the mouse hippocampus, intermittent hypoxia altered the expression of many miRNAs, with miR‐448‐3p and miR‐1264‐3p changing over the course of more than three time periods. Interestingly, the expression of Fam76b, the common target gene of these two miRNAs, also changed under intermittent hypoxia. Further studies showed that Fam76b may regulate the ratio of Nbr1 and Dph3 transcripts in response to hypoxia by affecting the localization of hnRNPA2B1 protein within cells.

Discussion

Research into intermittent hypoxia‐induced disorders, including Alzheimer's disease and other neurodegenerative diseases, might benefit from a better understanding of the regulatory mechanisms of miRNA and alternative splicing in hypoxic response at the animal and cell levels.

Conclusion

This study demonstrates that intermittent hypoxia alters the expression of miR‐448‐3p and miR‐1264‐3p, as well as the localization of the splicing factor hnRNPA2B1 in the cell nucleus. These findings enhance our understanding of the molecular mechanisms of neuronal responses to hypoxia and hold potential implications for treating hypoxia‐related diseases like Alzheimer's disease.
Finding the paths between job demand–resources and turnover intention of community mental health nurses in Korea
Authors: Hwang Eunmi , Yi Yeojin
Published: February 2025

Aim

This study aimed to investigate the pathways between client violence, supervision, workplace spirituality, burnout, work engagement, and turnover intention in community mental health nurses using the job demand–resources model with the goal of reducing turnover and improving workforce retention.

Background

High turnover of nurses has a negative impact on the rehabilitation and recovery of people with mental illness. While individual factors influencing turnover intention are well studied, there is a lack of research on the dynamics between variables and what should be focused on.

Methods

Participants were 243 mental health nurses working in the community health organizations. Data were collected through online questionnaires in April 2022 and analyzed using path analysis.

Results

Client violence against nurses as a job demand directly and indirectly negatively affected turnover intention through burnout. Supervision as a job resource only directly decreased turnover intention without mediating factors. Workplace spirituality as a personal resource indirectly lowered turnover intention through work engagement.

Conclusion

We need to focus more on organizational issues first, such as workplace safety (client violence) and administrative support (supervision) related to the nurses' turnover intention, and then on individual issues (workplace spirituality).

Implications for nursing practice

The worst path (client violence to burnout) to accelerate turnover intention of the nurses must be managed and disconnected, while the best path (from workplace spirituality to work engagement) to lower turnover intention should be maintained.

Implications for nursing and health policy

Policymakers should extend Workplace Safety Legislation to community organizations less well‐served by the laws and incorporate supervision into organizational evaluation items and curricula. Collaboration between community organizations and law enforcement is essential to enhance safety and support for the nurses.
How We Might Best Develop and Deliver Training and Professional Development in Positive Behaviour Support: A Systematic Review
Authors: Hall Julia R. , Newton Danielle , McVilly Keith , McKay‐Brown Lisa , Hayward Brent , Uljarevic Mirko
Published: February 2025

What constitutes good clinical practice in positive behavioural support (PBS) is well established. But how these clinical principles and practices are best translated into education, training and professional development remain unclear. To inform the development of a national blueprint to support education and professional development in PBS, we sought to better understand current approaches to training and education in PBS, its content and delivery. A systematic review of PBS interventions involving staff training was conducted within the timeframe of 1999–2023. Seven databases and one specialist journal (not otherwise indexed) were searched. Articles were identified using key search words; that is, ‘positive behaviour support’, ‘disability’ and ‘training’. Thirty‐three articles were identified whose predominant aims were to evaluate the impact and/or efficacy of PBS‐based training. Training formats included workshops, lectures, modules, classroom/group instruction and team‐based learning through the review of PBS plans. Core content focused on functional behaviour analysis, behaviour support planning, behaviour support strategies and interventions, as well as skills training. Articles reflected similar core content; however, there was a lack of consistency in training delivery, methodology and subsequent outcomes. Despite this, the literature provides evidence to inform the development of a future capabilities framework and guidance on the training, education and professional development of those involved in the delivery of PBS. Subsequently, recommendations are made to inform the education, training and professional development of PBS practitioners and those responsible for the coordination and delivery of support services for people who exhibit challenging behaviour.
Examining the Effect of Wrongful Discharge Laws on Women's Occupational Employment
Authors: Hoyt Eric , Kurtulus Fidan Ana
Published: February 2025

Previous empirical literature on US wrongful discharge laws, a judicial form of employment protection, has identified ways in which these policies have changed employers' hiring and firing practices, but has lacked a systematic analysis of the impact on workplace gender composition. This paper is the first to investigate the impact of state adoption of wrongful discharge laws on occupational gender diversity within American workplaces. We use restricted establishment‐level longitudinal data that are uniquely suited for the analysis of this topic obtained from the United States. Equal Employment Opportunity Commission (EEO‐1 Employer Information Reports). We utilize difference‐in‐differences regression methodology to first estimate the overall impact of wrongful discharge laws, and then examine the dynamics of wrongful discharge law impacts using event study regressions. We then examine the interplay between state wrongful discharge laws and state gender employment discrimination laws in shaping female employment composition at workplaces. First, we find that the adoption of one wrongful discharge law in particular, the good faith doctrine, is associated with an increase in women's employment share in laborer jobs within private‐sector establishments of 0.80 percentage points, and that this is a causal impact given the pattern of yearly impacts found using our event study analysis. Our findings suggest that the good faith doctrine has facilitated reduction in barriers women have historically faced in blue‐collar jobs. Second, while we find that the good faith doctrine is associated with a statistically significant increase in the share of women in officer and managerial jobs, and that the public policy doctrine is associated with a significant rise in women's share of professional jobs, our event study results cast doubt that these are causal impacts. Finally, our exploration of the interaction between state wrongful discharge laws and state gender discrimination laws reveals that, generally, state gender discrimination laws neither amplify nor diminish the impact of wrongful discharge laws on women's occupational employment within establishments.
Drug‐Induced Liver Injury Caused by Metamizole: Identification of a Characteristic Injury Pattern
Authors: Weber Sabine , Erhardt Franziska , Allgeier Julian , Saka Didem , Donga Nirali , Neumann Jens , Lange Christian M. , Gerbes Alexander L.
Published: February 2025

Background and Aims

Drug‐induced liver injury (DILI) due to metamizole has gained increasing attention. Causality assessment remains a challenge, especially in patients with co‐medications. We therefore aimed to further characterise metamizole DILI cases.

Methods

The data of patients with metamizole intake from our prospective study on acute liver injury with potential drug‐related causes were analysed. Diagnosis and causality assessment were based on a thorough work‐up and long‐term follow‐up.

Results

DILI was associated with metamizole in 61 of 324 DILI patients (prevalence 18.8%). A highly characteristic clinical pattern was observed in 43 of the 61 patients, characterised by marked elevation of transaminases peaking at the time of DILI recognition and a more pronounced increase of bilirubin within the first 3 days of clinical presentation. Patients fitting this picture had higher rates of jaundice, coagulopathy, and acute liver failure, however outcomes did not differ significantly when compared to non‐metamizole DILI and autoimmune hepatitis (AIH) patients. Overall, fatal adverse outcomes defined by death or liver transplantation were observed in 13.1% of metamizole DILI patients. On multivariate analysis, only aspartate aminotransferase (AST) and INR were independently associated with a fatal adverse outcome. INR, in particular, performed better than Hy's law, bilirubin, transaminases, and the model for end‐stage liver disease (MELD), with a c‐statistic of 0.85 (95% CI: 0.70–1.0). At a cut‐off of ≥ 2.1, sensitivity and specificity for a fatal adverse outcome were 75% and 96%, respectively.

Conclusions

Metamizole DILI can present with a characteristic pattern that can help clinicians to identify metamizole as the causative agent. Outcome, however, is not associated with this clinical picture and should rather be predicted by INR at onset.

Trial Registration

ClinicalTrials.gov identifier: NCT 02353455
Topological Distribution of KCNH2 Variants and Genotype‐Phenotype Relationship in Patients With Long QT Syndrome
Authors: Liu Hongyu , Jiang Zhenhong , Shen Yang , Shao Ying , Su Yuhao , Wang Daowu , Brugada Ramon , Hong Kui
Published: February 2025

Aims

The aim of this study was to investigate the topological distribution of single nucleotide variants (SNVs) in the KCNH2 gene from patients with type 2 long QT syndrome (LQT2) and to explore the genotype‐phenotype relationships.

Methods

Information on KCNH2 variants in LQT2 patients was retrospectively obtained from the HGMD, ClinVar, and PubMed databases through October 2022. Pathogenicity of SNV was classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Unpaired t‐tests and Fisher's exacts were used to analyze the SNV distributions across structural and functional domains, and their correlation with clinical phenotypes.

Results

A total of 2826 variants were obtained; 2152 were SNVs, 1328 of which were nonsynonymous SNVs (nsSNVs) associated with LQT2. Enrichment analysis revealed that 602 pathogenic (P) and likely pathogenic (LP) nsSNVs were significantly enriched at S5, H5, S6, Extra3, and Extra4. In addition, 759 nsSNVs and 289 P/LP nsSNVs within function domain were enriched at the per‐arnt‐sim (PAS) and selectivity filter (SF) functional domain. Clinical data revealed that patients with nsSNVs enriched at the N‐terminal, S5‐H5‐S6 region and PAS domain were associated with an increased risk of syncope. Moreover, nsSNVs located at the N‐terminal, S5‐H5‐S6 region, and PAS, SF domains were associated with an increased risk of life‐threatening cardiac events, including Torsade de Pointes (TdP) and sudden cardiac death (SCD), and were predominantly female.

Conclusion

KCNH2 nsSNVs located at the N‐terminal, S5‐H5‐S6 region, and the PAS and SF functional domains are associated with an increased risk of life‐threatening cardiac events in LQT2 patients.
Role of Routine Electrophysiological Study Performed During Transcatheter Aortic Valve Replacement to Predict AV Block
Authors: Pagnoni Mattia , Meier David , Luca Adrian , Fournier Stephane , Aminfar Farhang , Haddad Christelle , Maurizi Niccolo , Domenichini Giulia , Le Bloa Mathieu , Herrera Siklody Claudia , Teres Cheryl , Cook Stephane , Goy Jean‐Jacques , Togni Mario , Roguelov Christan , Girod Grégoire , Rubimbura Vladimir , Dupré Marion , Eeckhout Eric , Pruvot Etienne , Muller Olivier , Pascale Patrizio
Published: February 2025

Background

Periprocedural electrophysiological (EP) testing may be useful to predict high degree atrioventricular block (HAVB) risk in patients undergoing transcatheter aortic valve replacement (TAVR).

Objective

To determine whether pre‐ and immediate post‐TAVR ECG and HV interval findings are predictive of HAVB.

Methods

Consecutive TAVR patients without prior pacemaker (PM) implantation underwent ECG and standardized HV interval measurements pre‐ and post‐TAVR using the quadripolar catheter for rapid pacing. The primary outcome was HAVB >24 h after TAVR or ventricular pacing need

Results

Out of 97 included patients, 8 experienced the primary outcome (7 with HAVB and 1 with PM need). On univariate analysis, pre‐ and post‐TAVR PR, post‐TAVR HV, and Delta‐HV intervals were predictors of the primary outcome. A Delta‐HV interval ≥18 ms predicted HAVB with sensitivity = 50% and specificity = 90% (AUC = 0.708, PPV = 31%), while an HV interval ≥60 ms after TAVR had sensitivity = 63% and specificity = 79% (AUC = 0.681, PPV = 21%). None of the patients with a PR interval ≤180 ms post‐TAVR experienced the primary outcome. Among patients with new‐onset LBBB, an HV interval post‐TAVR >65 ms was the only predictor of HAVB (AUC = 0.776, PPV = 33%, and NPV = 97%).

Conclusion

The yield of periprocedural EP assessment during TAVR is limited considering that about half of the at‐risk patients fail to be identified. However, early periprocedural risk stratification may be more useful in the subset of patients with new‐onset LBBB. Among ECG findings, a post‐TAVR PR interval ≤180 ms identifies a subgroup at very low risk, independently of QRS interval and morphology.
Association of Cerebral Palsy With Unanticipated Admission Following Pediatric Ambulatory Surgery
Authors: Shamansky Nina , Mpody Christian , Nafiu Olubukola O. , Tobias Joseph D. , Willer Brittany L.
Published: February 2025

Background

Cerebral palsy, a neurologic disorder caused by damage to the developing brain, is a leading cause of childhood disability. Due to musculoskeletal, movement, and secondary impairments, children with cerebral palsy often require surgical care. With the growing cost of surgical care, many children with cerebral palsy are scheduled for surgery in an ambulatory setting. Whether cerebral palsy increases the risk of unanticipated admission (a critical quality indicator of care) following ambulatory surgery has not been characterized. Our objective was to determine the association of cerebral palsy with unanticipated admission following pediatric ambulatory surgery.

Methods

We used the Pediatric Health Information System (PHIS) database to evaluate a retrospective cohort of children (< 18 years) who underwent scheduled ambulatory operations between January 1, 2010 and December 31, 2022. The primary outcome was unanticipated admission. Using log‐binomial regression models, we estimated the relative risk and 95% confidence intervals for unanticipated admission, comparing patients with and without cerebral palsy. To account for confounding variables, we performed a 1:1 propensity score matching without replacement.

Results

A total of 1 954 108 children underwent ambulatory surgeries during the study period. Of these, 4.1% required unanticipated admission. The overall incidence of unanticipated admission was significantly higher among children with cerebral palsy than in those without (9.8% vs. 4.0%; p < 0.001). This association remained significant after multivariable adjustment (relative risk: 1.73; 95% CI: 1.59–1.87, p < 0.001).

Conclusion

Although cerebral palsy is not a contraindication for ambulatory surgery in children, it is significantly associated with the risk of unanticipated hospital admissions. This underscores the need for careful preoperative clinical site of care selection in this vulnerable patient population.

Level of Evidence

Level II.
Review Essay—Territorial Politics and COVID: A Comprehensive Review
Authors: Hernández‐Moreno Jorge , Harguindéguy Jean‐Baptiste , Carrasco‐Ariza Beatriz
Published: February 2025

As part of a broader research programme on the federal governance of COVID‐19 in Spain, this systematic literature review centers on the nexus between territorial politics and the coronavirus crisis. It analyses 300 publications in the Web of Science Core Collection from 2018 to 2023 through the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) method. The article contains three sections. The first one reports that these items were published during a very short period by a limited number of authors and universities supported by public funds. Second, the article stresses the importance of federal architecture by highlighting the debate on recentralization, the weight of intergovernmental relations to guarantee policy efficiency, and the dilemma of policy instruments and intersectoral action. Finally, the review points out the significance of politics during the pandemic, exemplified by the rise of polarization, the role of central leadership, and the upsurge of a new cleavage centered on COVID‐19.

Related Articles

Lauby, Fanny, and Christopher J. McKinley. 2023. “Factors of Early COVID‐19 Prevention Policy Engagement in France and in the United States.” Politics & Polciy 51(5): 830–48. https://doi.org/10.1111/polp.12556.

Robles, Pedro, and Daniel J. Mallinson. 2023. “Review Essay—Catching Up with AI: Pushing toward a Cohesive Governance Framework.” Politics & Policy 51(3): 355–72. https://doi.org/10.1111/polp.12529.

Tyner, Katie, and Farida Jalalzai. 2022. “Women Prime Ministers and COVID‐19: Within‐case Examinations of New Zealand and Iceland.” Politics & Policy 50(6): 1076–95. https://doi.org/10.1111/polp.12511.
Populism and Psychological Involvement in the 2020 US Presidential Election
Authors: Mangum Maruice
Published: February 2025

In recent election cycles, especially during the 2020 US presidential election cycle, individuals displayed a renewed and heightened sense of civic, social, and political involvement. Voter turnout was high in the 2020 presidential election, the highest for any other presidential election since 1900. I submit that the psychological influences of populism and psychological involvement foster this high turnout. Using the 2020 American National Election Study, this article examines their influences on political behavior. It places greater focus on populism because scholars of American elections rarely test it as an individual‐level force in presidential elections and because scholars do not examine it with psychological involvement simultaneously. I find that populism and psychological involvement are distinct concepts, both boost voter turnout, and they shape vote choice and candidate affect.

Related Articles

Aguado, N. A. 2022. “When Charismatic Leadership Trumps Social Networking: Searching for the Effects of Social Media on Beliefs of Electoral Legitimacy.” Politics & Policy 50, no. 5: 942–951. https://doi.org/10.1111/polp.12494

Craig, S. C., and J. Gainous. 2024. “To Vote or Not to Vote? Fake News, Voter Fraud, and Support for Postponing the 2020 U.S. Presidential Election.” Politics & Policy 52, no. 1: 33–50. https://doi.org/10.1111/polp.12577

Deegan‐Krause, K., and T. Haughton. 2009. “Toward a More Useful Conceptualization of Populism: Types and Degrees of Populist Appeals in the Case of Slovakia.” Politics & Policy 37, no. 4: 821–841. https://doi.org/10.1111/j.1747‐1346.2009.00200.x
Photon statistics and unicellular algae cultivation characteristics under continuous illumination
Authors: Zarmi Yair
Published: February 2025

Despite the complexity of the photosynthetic system, a simple explanation is proposed for the photon-flux density dependence of P–I curves (biomass production rate versus flux density) and electron transfer rate curves (delivery transfer rate of excited electrons from PS II, the first stage of the photosynthetic process, to the second stage, PS I, versus flux density). It is shown that the photon-flux density dependence of these two entities is a direct consequence of the stochastic nature of photon arrival times on the chlorophyll antenna of PS II, the existence of a rate-limiting time scale of about 10 ms in the operation of the photosystem, and the magnitude of the average photon absorption cross-sectional area of the chlorophyll antennae.
Prediction of higher ceftazidime–avibactam concentrations in the human renal interstitium compared with unbound plasma using a minimal physiologically based pharmacokinetic model developed in rats and pigs through microdialysis
Authors: Vallée Maxime , Aranzana-Climent Vincent , Moreau Jérémy , Lamarche Isabelle , Fontanier Théo , Barc Céline , Kasal-Hoc Nathalie , Debiais-Delpech Céline , Mirfendereski Hélène , Pezant Jérémy , Pinard Anne , Clarhaut Jonathan , Couet William , Cazenave-Roblot France , Marchand Sandrine
Published: February 2025

Last resort antibiotics, like ceftazidime–avibactam (CZA), were used to treat urinary tract infections caused by multidrug-resistant bacteria. However, no data on tissue distribution were available. Our aim was to describe the
in vivo
kidney distribution of CZA in healthy rats and pigs using a physiologically based pharmacokinetic model (PBPK). Microdialysis probes were inserted into the blood, muscle, and kidney of both species. The experiment started with a retrodialysis by drug period. An i.v. single dose of CZA was administered. Samples were collected for 3 h in rats and 7 h in pigs. A PBPK model was developed to describe tissue and blood CZA pharmacokinetics in animals and to predict human concentrations. The PBPK model adequately described CZA rat and pig data in each tissue and blood. In both species, the concentration profiles of CZA in muscle and blood were almost superimposed, with muscle-to-plasma area under the curve (AUC) ratios close to one. However, kidney CZA concentrations were higher than those in blood, as indicated by kidney-to-plasma AUC ratios exceeding one (respectively 2.27 in rats and 2.63 in pigs for ceftazidime [CAZ]; 2.7 in rats and 4.5 in pigs for avibacam [AVI]). Prediction of human concentrations led to same observations. This study demonstrated an excellent penetration of CZA into the renal parenchyma of rats and pigs. Our PBPK model adequately described the data, and AUCs were higher in the renal cortex interstitium compared with unbound plasma. Our data suggested that the joint PK/PD target for CZA in humans could be attained with reduced CZA doses.
Structural mapping of polyclonal IgG responses to HA after influenza virus vaccination or infection
Authors: León André Nicolás , Rodriguez Alesandra J. , Richey Sara T. , Torrents de la Pena Alba , Wolters Rachael M. , Jackson Abigail M. , Webb Katherine , Creech C. Buddy , Yoder Sandra , Mudd Philip A. , Crowe James E. , Han Julianna , Ward Andrew B.
Published: February 2025

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses against H1 predominantly targeted the central stem epitope in infected patients and vaccinated donors, whereas head epitopes were more prominently targeted on H3. Responses against H3 were less abundant, but a greater diversity of H3 epitopes were targeted relative to H1. While our analysis is limited by sample size, on average, vaccinated donors responded to a greater diversity of epitopes on both H1 and H3 than infected patients. These data establish a baseline for assessing polyclonal antibody responses in vaccination and infection, providing a context for future vaccine trials and emphasizing the need for further characterization of protective responses toward conserved epitopes. (201 words)

IMPORTANCE

Seasonal influenza viruses cause hundreds of thousands of deaths each year and up to a billion infections; under the proper circumstances, influenza A viruses with pandemic potential could threaten the lives of millions more. The variable efficacies of traditional influenza virus vaccines and the desire to prevent pandemic influenzas have motivated work toward finding a universal flu vaccine. Many promising universal flu vaccine candidates currently focus on guiding immune responses to highly conserved epitopes on the central stem of the influenza hemagglutinin viral fusion protein. To support the further development of these stem-targeting vaccine candidates, in this study, we use negative stain electron microscopy to assess the prevalence of central stem-targeting antibodies in individuals who were exposed to influenza antigens through traditional vaccination and/or natural infection during the 2018–2019 flu season.
Copper Nanoparticles and Copper-Containing Metal–Organic Coordination Polymers in the Catalytic Amination of 2-Halopyridines
Authors: Leksakov D. A. , Borisova A. S. , Murashkina A. V. , Kuliukhina D. S. , Averin A. D. , Vergun V. V. , Isaeva V. I. , Savelyev E. N. , Novakov I. A. , Beletskaya I. P.
Published: February 2025

The efficiencies of copper-containing metal–organic coordination polymers (Cu-MOFs) and com­mercially available unsupported copper nanoparticles (CuNPs) in the amination of 2-iodopyridine, 2-bromo­pyridine, 2-bromo-5-(trifluoromethyl)pyridine, and 2-bromo-6-(trifluoromethyl)pyridine with n-octylamine and adamantane-containing amines with different steric environments of the amino group have been compared. Under the optimized conditions, the yields of the amination products in the presence of both catalytic systems were generally similar. In the reactions with 2-bromopyridine, increased reactant concentration and the use of 2 equiv of the substrate were necessary to achieve good yields. The presence of a trifluoromethyl group at the 6-position of the pyridine ring improved the yield of the amination products. An increase in steric hindrances at the amino group resulted in an appreciable decrease in the yield under catalysis by Cu-MOFs; however, reactions with such amines were successfully performed in the presence of CuNPs, and CuNPs of the average size 25 nm proved to be superior to bifractional nanoparticles with average sizes of 10 and 80 nm. On the other hand, increased concentration of the reactants in the Cu-MOF-catalyzed amination provided good yields of the target compounds in the absence of a ligand.
Synthesis of 4,13-Dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl Bis[3(4)-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoates]
Authors: Kolyamshin O. A. , Mitrasov Yu. N. , Danilov V. A.
Published: February 2025

New bis-carbamates, 4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl bis[3(4)-aminoben­zoates], were synthesized by the reaction of bis(2-chloroethyl) hexane-1,6-diyldicarbamate with potassium 3- and 4-aminobenzoates. These compounds reacted with maleic anhydride at a ratio of 1:2 to give the corre­sponding bis-maleamic acids which were cyclized in acidic medium to afford 4,13-dioxo-3,14-dioxa-5,12diaza­hexa­decane-1,16-diyl bis[3(4)-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoates]. Physical and spectral properties of the obtained bis-maleimides were studied.
Improving quality and outcomes of extracorporeal cardiopulmonary resuscitation in refractory cardiac arrest: the Phoenix ECPR project
Authors: Akhtar Waqas , Galiatsou Eftychia , Pinto Sofia , Comanici Maria , Gerlando Emanuele , Pitt Timothy , Hughes Joe , Maunz Olaf , Keating Elia , Taylor Michael , McKay Anthony , Gangata Julia , Thiruthalil Sumesh , Ross Eleanor , Avetoom Sophie , Durrant Jane , Smith Jill , Collins Ciara , Akhtar Majid , Jothidasan Anand , Monteagudo-Vela Maria , Mason Mark , McGovern Ian , Mitchell Jerry , Aboumarie Hatem Soliman , Kviatkovske Orinta , Bullen Caroline , Mehta Sachin , Kaul Sundeep , Hall Donna , Hernandez Caballero Clara , Hurtado Ana , Lees Nick , Panoulas Vasileios , Rosenberg Alex
Published: February 2025

Background

Survival for cardiac arrest remains poor, and the use of extracorporeal cardiopulmonary resuscitation (ECPR) has been suggested as a potential therapy to improve outcomes. Harefield Hospital has been performing ECPR for over a decade; however outcomes have been historically poor.

Methods

A retrospective analysis was performed of all ECPR cases at Harefield Hospital between April 2018 and April 2023. A new structured system including a systematic screening process, strict exclusion criteria, assessment of resuscitation adequacy through physiological stop criteria, drilled and standardised cannulation process, post-resuscitation care and neuroprognostication was rolled out on 1 April 2023. A comparison of ECPR performed pre and post was undertaken.

Results

With the institution of the new system, 13 patients were treated with ECPR over 1 year; of which nine (69.2%) survived with good neurological outcomes at 6 months. In the preceding 3 years, there had been 22 cases; of which, two survived (9.1%). This was a statistically significant higher survival with HR of 4.56 (CI 2.1, 10.2, p<0.05).

The average length of hospital stay in the new system was 61.3 days; of which, 32.4 days were in the intensive care unit.

Conclusions

This study shows that it is possible to significantly improve outcomes in ECPR in a single centre by introducing into standard practice, a high-quality bundle of care.
An observational, multigenerational platform for health systems and population health interventions to minimise intergenerational transmission of non-communicable diseases in India: the YUVAAN cohort study protocol
Authors: Miriam Demi , Mandlik Rubina , Patwardhan Vivek , Ladkat Dipali , Khadilkar Vaman , Kajale Neha , More Chidvilas , Gondhalekar Ketan , Bhawra Jasmin , Katapally Tarun Reddy , Khadilkar Anuradha Vaman
Published: February 2025

Introduction

Non-communicable diseases (NCDs) pose a significant health burden in India, with preventable risk factors contributing to their prevalence. In rural populations, inequalities may be reinforced by health risks passed down through generations. Taking a life course perspective, this multigenerational cohort study aims to investigate behavioural, socioecological, and socioeconomic determinants of growth and NCD risk, as well as healthcare access and utilisation among preadolescents and their parents.

Methods and analysis

The study is being implemented by the Hirabai Cowasji Jehangir Medical Research Institute (HCJMRI) using a prospective, multigenerational cohort design to investigate NCD risk over 15 years. Data are being collected from 14 villages around Pune, Maharashtra, India. The target population is asymptomatic (ie, healthy) children aged 8–10 years and their parents. The study commenced on 13 September 2022. Participants (children and their parents) are being enrolled through household visits, and by arranging subsequent visits to the primary health facility of HCJMRI. After obtaining informed consent from participants (parents and their children), comprehensive data are being collected from both children and parents, including clinical, behavioural, healthcare access and utilisation, as well as socioeconomic determinants of health. Clinical assessments include anthropometric measurements, blood samples for a wide range of NCD indicators, bone health and muscle function. The long-term data analysis plan includes longitudinal modelling, time-series analyses, structural equation modelling, multilevel modelling and sex-based analyses to investigate growth trajectories and intergenerational patterns of health risks. As of November 2024, 1070 families from 14 villages have been enrolled (1264 preadolescents and 2140 parents). Given the double burden of malnutrition, with undernutrition and overweight/obesity coexisting among children and parents in India, the study findings will contribute to the development of focused interventions aimed at lowering NCDs, addressing the generational transmission of health risks, and improving health outcomes for rural communities.

Ethics and dissemination

Ethics approval was obtained from the institutional ethics committee, Ethics Committee Jehangir Clinical Development Centre, No: JCDC/BHR/24/047.

Trial registration number

NCT05603793.
Symptomatic vitamin A deficiency in a patient on long-term colesevelam
Authors: Andreyev Daniel Alexei , Gopakumar Veena , Andreyev H Jervoise N
Published: February 2025

Introduction

Bile acid sequestrants including colesevelam are increasingly used by gastroenterologists. The risk of fat-soluble vitamin deficiency when sequestrants are used is recognised. Vitamin A deficiency is uncommon in the UK, but delayed diagnosis can cause irreversible blindness. There are no guidelines for the monitoring of fat-soluble vitamin levels.

Case discussion

We describe a 63-year-old man who had a neuroendocrine tumour, treated with ileal resection and lanreotide and complicated by the development of severe bile acid malabsorption, pancreatic exocrine insufficiency and intermittent episodes of small intestinal bacterial overgrowth. Three and a half years after starting colesevelam, he developed progressive visual symptoms due to severe vitamin A deficiency. After diagnosis and parenteral vitamin A replacement, his visual symptoms improved but have not resolved.

Conclusions

Clinicians prescribing bile acid sequestrants should be aware that vitamin A deficiency may arise and should consider regular monitoring of serum levels.
TheICAM1p.K56M variant and risk of heart failure in chronic kidney disease: the Chronic Renal Insufficiency Cohort study
Authors: Culler Kasen , Zelnick Leila R , Mehta Rupal C , de Sosa Giselle R , Kansal Mayank , Rao Panduranga S , Bhat Zeenat , Taliercio Jonathan , Horwitz Edward , Chen Jing , He Jiang , Shah Sanjiv J , Isakova Tamara , Patel Ravi B
Published: February 2025

Background

Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leucocyte adhesion. Approximately 35% of Black individuals carry at least one copy of anICAM1missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure (HF) with preserved ejection fraction (HFpEF). Whether the risk of HFpEF conferred by rs5491 extends to individuals with chronic kidney disease (CKD), a cohort at high risk for HF, is unknown.

Aims

We investigated the association between rs5491 and the incidence of HF in CKD.

Methods

We estimated associations of rs5491 with incident HF and HF subtypes among Black individuals who were free from HF at baseline in the Chronic Renal Insufficiency Cohort (CRIC). The CRIC study recruited individuals who were 21–74 years old with estimated glomerular filtration rate (eGFR) of 20–70 mL/min/1.73 m2at baseline.

Results

Among 1267 Black participants (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73 m2), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7–15.0 years), there were 309 incident overall HF hospitalisations (160 HFpEF, 111 HF with reduced ejection fraction (HFrEF) and 38 HF with unknown ejection fraction). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35, 95% CI 1.03 to 1.76, p=0.029). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI 0.93 to 1.39, p=0.20) or incident HFrEF (HR 0.76, 95% CI 0.53 to 1.10, p=0.15).

Conclusion

TheICAM1p.K56M variant is specifically associated with increased risk of incident HFpEF among individuals with CKD.
miRNA-214 to predict progression and survival in ALS
Authors: Noh Min-Young , Kwon Min-Soo , Oh Ki-wook , Nahm Minyeop , Park Jinseok , Jin Hee Kyung , Bae Jae-sung , Son Bugyeong , Kim Seung Hyun
Published: February 2025

Background

Reliable biomarkers are essential for predicting the progression speed and prognosis of patients with amyotrophic lateral sclerosis (ALS). We previously identified NCK-associated protein 1 (NCKAP1) as a critical factor in the defective phagocytosis observed in induced microglia-like cells (iMGs) from patients with rapidly progressive sporadic ALS. This study explored the roles of microRNA (miRNA)-214, which targets theNCKAP1gene, in the progression of ALS.

Methods

The discovery cohort (n=29) was used to identify miR-214 targetingNCKAP1genes. The validation cohort (n=132) was used to determine the clinical usability of miR-214 for predicting disease progression speed and survival time.

Results

In the discovery cohort, miR-214 levels were increased in plasma and iMGs from rapidly progressive ALS participants. This finding was validated in another cohort of 132 ALS participants and 30 age-matched healthy volunteers. Plasma miR-214 levels correlated with disease progression, severity and survival, distinguishing between rapidly progressive and slowly progressive ALS. In addition, miR-214 levels also correlated with plasma neurofilament light chain (NfL) and cerebrospinal fluid inflammatory cytokines, showing specific associations with increased NfL and monocyte chemoattractant protein 1 (MCP-1). Survival prediction accuracy improved when miR-214 levels were considered with NfL or MCP-1 levels.

Conclusions

Plasma miRNA-214 could serve as a novel biomarker for predicting the progression and prognosis of ALS.
How do clinicians address vaping in an illegal context? A qualitative Singapore study
Authors: van der Eijk Yvette , Kwok Wei Yi , Tan Grace Ping Ping
Published: February 2025

Background

Despite a strict vaping ban also covering purchase, use and possession, vaping has become more prevalent in Singapore. As more countries seek to regulate vaping, with no tailored services or guidelines for vaping cessation, clinicians may face additional challenges in identifying or treating vaping cases due to stigma or patients’ reluctance to disclose their vaping. Few studies have explored how clinicians identify or manage vaping cases in a context where vaping is heavily regulated or stigmatised.

Methods

We conducted semistructured interviews with 12 Singapore practitioners from pharmacy, psychology, respiratory medicine, smoking cessation or youth welfare settings, all of whom had encountered vaping cases in their practice. Interviews explored how they manage vaping cases. We analysed data using inductive thematic methods.

Results

Patients were described as reluctant to disclose their vaping for fear of being reported to authorities, and some clinicians were unsure of their duty to report, making it challenging to identify vaping cases. Variability in usage patterns and inaccurate e-liquid labelling posed difficulties in estimating nicotine dependence, leaving practitioners to trial and error or to adapt from smoking cessation guidelines. Tailored quit support for people who vape was lacking, especially in the form of subsidised nicotine replacement therapy.

Conclusion

Even in contexts where vaping is heavily regulated, given the rising incidence of vaping globally, it is important to record patients’ vaping history as part of routine practice and to provide services to help people quit vaping without facing stigma or legal repercussions because of their vaping.
Improving Human-Robot Collaboration through Augmented Reality and Eye Gaze
Authors: Chan Wesley P. , Crouch Morgan , Hoang Khoa , Chen Charlie , Robinson Nicole , Croft Elizabeth
Published: February 2025

When humans work together to complete a joint task, each person builds an internal model of the situation and how it will evolve. Efficient collaboration depends on how these individual models overlap to form a shared mental model among team members; shared models are also important for collaborative processes in human-robot teams. The development and maintenance of an accurate shared mental model requires bidirectional communication of individual intent and the ability to interpret the intent of other team members. To enable effective human-robot collaboration, this paper investigates the use of augmented reality (AR) technology and user eye-gaze to enable bidirectional communication of intent in a joint action task. We tested this approach through a user study with 37 participants and found that this communication improves task efficiency, trust, as well as task fluency. We conclude that using AR and eye gaze to enable bidirectional communication and support shared mental models is a promising means for improving collaboration between humans and robots.