bluuebunny/crossref_metadata_2025 huggingface dataset:
Se-Glargine I. Chemical Synthesis of a Basal Insulin Analog Stabilized by an Internal Diselenide Bridge
Authors: Weil-Ktorza Orit , Dhayalan Balamurugan , Weiss Michael A. , Metanis Norman
Published: June 2023

Insulin, a small globular protein, has long provided a model for studies of biophysical principles with therapeutic application. The safety and efficacy of insulin replacement therapy for the treatment for diabetes mellitus have been enhanced by protein engineering. Here, we describe the chemical synthesis of a basal insulin analog stabilized by the substitution of an internal cystine (A6-A11) by a diselenide bridge. The studies focused on insulin glargine, the active component of clinical products Lantus®and Toujeo®(Sanofi). Formulated in solution at pH 4 in the presence of zinc ions, insulin glargine exhibits a shifted isoelectric point (from pH 4.5 to neutral pH) due to a basic extension of the B chain (ArgB31-ArgB32). Subcutaneous injection of such an acidic formulation leads to pH-dependent precipitation of protein-zinc complexes to form a long-lived depot. Pairwise substitution of CysA6and CysA11by selenocysteine (Sec; the 21stencoded amino acid) was effected by solid-phase peptide synthesis. The modified A chain also contained substitution of AsnA21by Gly, introduced in glargine to avoid acid-catalyzed deamidation of the A21 carboxamide group in the formulation. Although classical chain combination of the di-Arg-extended B chain and modified A chain exhibited lower yield than does wild-type chain combination, substantial product was obtained through repeated reactions and successive purification. This strategy exemplifies the rational optimization of protein stability and may be generalizable to diverse disulfide-stabilized proteins of therapeutic interest.
Phenotypic Switching of Vascular Smooth Muscle Cells in Duchenne Muscular Dystrophy
Authors: Xuan Wanling , Cheng Feng , Han Xiaowei , Tipparaju Srinivas M. , Ashraf Muhammad
Published: June 2023

Background

Extensive studies have been conducted in skeletal muscle and myocardium affected by Duchenne Muscular Dystrophy (DMD) disease but there is a significant gap of research in the role of vascular smooth muscle cells (VSMCs) in DMD. Here, we investigated the role of dystrophin deficiency in the maintenance of VSMCs contractile phenotype.

Methods

12-14 months old mdx mice and DMD induced pluripotent stem cells (iPSC) derived VSMCs were used as disease models. Morphological and immunohistochemistry analyses were performed to determine histological changes and the expression of contractile markers. Transmission Electron Microscopy (TEM) was used to assess ultrastructural changes in the VSMCs. Mito-tracker staining and TUNEL staining were performed to determine mitochondria fission-fusion and apoptosis respectively. mRNA Sequencing for normal iPSC derived VSMCs (WT-VSMCs) and DMD iPSC derived VSMCs (DMD-VSMCs) with or without oxidative stress was performed. KEGG signaling pathway enrichment, Go function enrichment and Gene set enrichment analysis (GESA) were conducted to explore the potential mechanism responsible for these changes. In addition, transcription factor enrichment analysis was performed to unravel mechanistic pathways of regulatory networks.

Results

Spontaneous abnormal VSMCs proliferation, loss of vascular structure and degenerative changes occurred in VSMCs in aorta from 12-14 months old mdx mice. The DMD-VSMCs showed maturation defect, loss of mitochondrial hemostasis, and increased vulnerability to oxidative stress compared with WT-VSMCs. Transcriptome analysis revealed dysregulation of smooth muscle proliferation, differentiation, and vascular development in DMD-VSMCs. Transcriptional factor, target, and motif discovery analysis of the dysregulated gene set suggested potential contributions of transcriptional factors GADD45A, SOX9, TIA1, RBBP9 and FOXM to the phenotypes of DMD-VSMCs. Under oxidative stress, initiation of apoptotic process was significantly enhanced in DMD-VSMCs while their response to hypoxia and oxidative stress was downregulated.

Conclusions

Dystrophin deficiency induced VSMCs phenotype switching and disrupted mitochondrial metabolism. The findings in this study underscore the importance of vascular dysfunction in DMD disease and therapeutic interventions to restore VSMC phenotype may ameliorate the propensity of disease progression. It is suggested that the transcriptome analysis may allow the discovery of potential signaling pathways involved in the dysregulation of transcription factors.
The Na+leak channel NALCN controls spontaneous activity and mediates synaptic modulation by α2-adrenergic receptors in auditory neurons
Authors: Ngodup Tenzin , Irie Tomohiko , Elkins Sean , Trussell Laurence O.
Published: June 2023

Cartwheel interneurons of the dorsal cochlear nucleus (DCN) potently suppress multisensory signals that converge with primary auditory afferent input, and thus regulate auditory processing. Noradrenergic fibers from locus coeruleus project to the DCN, and α2-adrenergic receptors inhibit spontaneous spike activity but simultaneously enhance synaptic strength in cartwheel cells, a dual effect leading to enhanced signal- to-noise for inhibition. However, the ionic mechanism of this striking modulation is unknown. We generated a glycinergic neuron-specific knockout of the Na+leak channel NALCN, and found that its presence was required for spontaneous firing in cartwheel cells. Activation of α2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, α2-dependent enhancement of synaptic strength was also absent in the knockout. GABABreceptors mediated inhibition through NALCN as well, acting on the same population of channels as α2 receptors, suggesting close apposition of both receptor subtypes with NALCN. Thus, multiple neuromodulatory systems determine the impact of synaptic inhibition by suppressing the excitatory leak channel, NALCN.
BRG1 establishes the neuroectodermal chromatin landscape to restrict dorsal cell fates
Authors: Hoffman Jackson A , Muse Ginger W , Langer Lee F , Gandara Isabella , Ward James M , Archer Trevor K
Published: June 2023

Cell fate decisions are achieved with gene expression changes driven by lineage-specific transcription factors (TFs). These TFs depend on chromatin remodelers including the BAF complex to activate target genes. BAF complex subunits are essential for development and frequently mutated in cancer. Thus, interrogating how BAF complexes contribute to cell fate decisions is critical for human health. We examined the requirement for the catalytic BAF subunit BRG1 in neural progenitor cell (NPC) specification from human embryonic stem cells. During the earliest stages of differentiation, BRG1 was required to establish chromatin accessibility at neuroectoderm-specific enhancers. BRG1 depletion resulted in abnormal NPC populations that differentially expressed neuroectodermal TFs, were more prone to neuronal differentiation, and precociously formed neural crest lineages. These findings demonstrate that BRG1 mediates NPC specification by ensuring proper expression of lineage-specific TFs and appropriate activation of their transcriptional programs.
Deep neural networks for predicting single cell responses and probability landscapes
Authors: Klumpe Heidi E. , Lugagne Jean-Baptiste , Khalil Ahmad S. , Dunlop Mary J.
Published: June 2023

Engineering biology relies on the accurate prediction of cell responses. However, making these predictions is challenging for a variety of reasons, including the stochasticity of biochemical reactions, variability between cells, and incomplete information about underlying biological processes. Machine learning methods, which can model diverse input-output relationships without requiringa priorimechanistic knowledge, are an ideal tool for this task. For example, such approaches can be used to predict gene expression dynamics given time-series data of past expression history. To explore this application, we computationally simulated single cell responses, incorporating different sources of noise and alternative genetic circuit designs. We showed that deep neural networks trained on these simulated data were able to correctly infer the underlying dynamics of a cell response even in the presence of measurement noise and stochasticity in the biochemical reactions. The training set size and the amount of past data provided as inputs both affected prediction quality, with cascaded genetic circuits that introduce delays requiring more past data. We also tested prediction performance on a bistable auto-activation circuit, finding that our initial method for predicting a single trajectory was fundamentally ill-suited for multimodal dynamics. To address this, we updated the network architecture to predict the entire distribution of future states, showing it could accurately predict bimodal expression distributions. Overall, these methods can be readily applied to the diverse prediction tasks necessary to predict and control a variety of biological circuits, a key aspect of many synthetic biology applications.
Chronic Stress Increases Adiposity and Anxiety in Rats with Decreased Expression ofKrtcap3
Authors: Szalanczy Alexandria , Fitzpatrick Mackenzie , Beeson Angela , Bui Trangdai , Dyson Christina , Eller Seth , Landry Julia , Scott Christina , Grzybowski Michael , Klotz Jason , Geurts Aron M , Weiner Jeff L , Redei Eva E , Solberg Woods Leah C
Published: June 2023

We previously identifiedKeratinocyte-associated protein 3,Krtcap3, as a novel adiposity gene but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection betweenKrtcap3, adiposity, and stress, we exposed wild-type (WT) andKrtcap3knock-out (KO) rats to chronic stress then measured adiposity and behavioral outcomes. We found that KO rats displayed lower basal stress than WT rats under control conditions and exhibited the expected responses to chronic stress exposure. Specifically, stress-exposed KO rats gained more weight, consumed more food when socially isolated, and displayed more anxiety-like behaviors relative to control KO rats. Meanwhile, there were minimal differences between control and stressed WT rats. At study conclusion stress-exposed KO rats had increased corticosterone (CORT) relative to control KO rats with no differences between WT rats. In addition, KO rats, independent of prior stress exposure, had an increased CORT response to removal of their cage-mate (psychosocial stress), which was only seen in WT rats when exposed to chronic stress. Finally, we found differences in expression of the glucocorticoid receptor,Nr3c1, in the pituitary and colon between control and stress-exposed KO rats that were not present in WT rats. These data support thatKrtcap3expression affects stress response, potentially via interactions withNr3c1, with downstream effects on adiposity and behavior. Future work is necessary to more thoroughly understand the role ofKrtcap3in the stress response.
Parametric modeling of mechanical effects on circadian oscillators
Authors: Kennedy Keith E. , Abenza Juan F. , Rossetti Leone , Trepat Xavier , Villoslada Pablo , Garcia-Ojalvo Jordi
Published: June 2023

Circadian rhythms are archetypical examples of nonlinear oscillations. While these oscillations are usually attributed to circuits of biochemical interactions among clock genes and proteins, recent experimental studies reveal that they are also affected by the cell’s mechanical environment. Here we extend a standard biochemical model of circadian rhythmicity to include mechanical effects in a parametric manner. Using experimental observations to constrain the model, we suggest specific ways in which the mechanical signal might affect the clock. Additionally, a bifurcation analysis of the system predicts that these mechanical signals need to be within an optimal range for circadian oscillations to occur.

Cells are nonlinear dynamical elements, which in multicellular tissues are commonly coupled to one another. Much work has been done, both theoretically and experimentally, to understand this coupling and to identify its dynamical consequences from a biochemical viewpoint. In contrast, much less is known about how the mechanical interactions between cells affect these dynamics. Recent work has shown, for instance, that circadian oscillations degrade substantially in populations of cellsin vitrowhen cell density decreases sufficiently. Here we use this fact to constrain a standard model of circadian oscillations, and propose a way through which external mechanical signals and internal biochemical interactions could combine in clock cells.
Development of building defects dashboards and stochastic models for multi-storey buildings in Victoria, Australia
Authors: Gurmu Argaw , Hosseini M. Reza , Arashpour Mehrdad , Lioeng Wellia
Published: June 2023

Purpose

Building defects are becoming recurrent phenomena in most high-rise buildings. However, little research exists on the analysis of defects in high-rise buildings based on data from real-life projects. This study aims to develop dashboards and models for revealing the most common locations of defects, understanding associations among defects and predicting the rectification periods.

Design/methodology/approach

In total, 15,484 defect reports comprising qualitative and quantitative data were obtained from a company that provides consulting services for the construction industry in Victoria, Australia. Data mining methods were applied using a wide range of Python libraries including NumPy, Pandas, Natural Language Toolkit, SpaCy and Regular Expression, alongside association rule mining (ARM) and simulations.

Findings

Findings reveal that defects in multi-storey buildings often occur on lower levels, rather than on higher levels. Joinery defects were found to be the most recurrent problem on ground floors. The ARM outcomes show that the occurrence of one type of defect can be taken as an indication for the existence of other types of defects. For instance, in laundry, the chance of occurrence of plumbing and joinery defects, where paint defects are observed, is 88%. The stochastic model built for door defects showed that there is a 60% chance that defects on doors can be rectified within 60 days.

Originality/value

The dashboards provide original insight and novel ideas regarding the frequency of defects in various positions in multi-storey buildings. The stochastic models can provide a reliable point of reference for property managers, occupants and sub-contractors for taking measures to avoid reoccurring defects; so too, findings provide estimations of possible rectification periods for various types of defects.
Class cleavage electoral structuring in Western Europe (1871–2020)
Authors: EMANUELE VINCENZO
Published: June 2023

Despite the huge amount of studies on cleavages, scholars have never elaborated a dynamic model to conceptualize and measure the stages of electoral development of the class cleavage and, specifically, the stage corresponding to its full electoral structuring. To fill this gap, by combining some key electoral properties of the class cleavage, I build a model that returns, for each country in each election, the current stage of electoral development of the class cleavage. I test this model in 20 Western European countries from the late 19th century to 2020. Results show that an electorally structured class cleavage has characterized most of Western Europe's electoral history. However, contrary to conventional wisdom, it is not merely a product of socio‐structural factors that have been experiencing an irreversible decline. Conversely, its demise or resilience is a matter of the national political context, as it mostly depends upon specific party system characteristics.
Racial and ethnic differences in the consequences of school suspension for arrest
Authors: Fisher Benjamin W. , Widdowson Alex O.
Published: June 2023

A growing body of literature has demonstrated that when schools suspend students, the suspension acts not as a deterrent but as an amplifier of future punishment. Labeling theory has emerged as the predominant explanation for this phenomenon, suggesting that the symbolic label conferred along with a suspension shapes how other people perceive and respond to labeled students. Few studies, however, have attended to racial/ethnic differences in this process even though critical race theory suggests the consequences of suspension likely differ across racial/ethnic groups due to prevailing racial/ethnic stereotypes. This study uses six waves of data from the National Longitudinal Study of Youth 1997 (N = 8,634) to examine how the relationship between suspension and subsequent arrest differs for White, Black, and Hispanic students. Using a series of within‐person analyses that control for time‐stable personal characteristics, this study finds that suspension amplifies Black and Hispanic students’ risk of arrest relative to that of White students. White students’ risk of arrest was not amplified by suspension and, in some models, was diminished. This study's findings underscore the importance of understanding the labeling process as different by race/ethnicity and indicate that suspension is particularly harmful for Black and Hispanic relative to White students.
Acetobacter pasteurianus BP2201 alleviates alcohol‐induced hepatic and neuro‐toxicity and modulate gut microbiota in mice
Authors: Wen Xin , Wang Zheng , Liu Qi , Lessing Duncan James , Chu Weihua
Published: June 2023

The excessive consumption of alcohol results in a dysbiosis of the gut microbiota, which subsequently impairs the gut microbiota‐brain/liver axes and induces cognitive dysfunction and hepatic injury. This study aimed to investigate the potential effect of Acetobacter pasteurianus BP2201 in reducing the negative effects of alcohol consumption on cognitive function and liver health by modulating the gut microbiota‐brain/liver axes. Treatment with A. pasteurianus BP2201 improved alcohol‐induced hippocampal damage, suppressed neuroinflammation, promoted neuroprotein expression in the hippocampus and enhanced cognitive function. At the same time, A. pasteurianus BP2201 can also reduce serum lipid levels, relieve oxidative stress, inhibit TLR4/MyD88/NF‐κB pathway, reduce the secretion of TNF‐α and IL‐1β, so as to improve alcoholic liver injury. Concomitantly, the treatment with A. pasteurianus BP2201 leads to a shift in the intestinal microbiota structure towards that of healthy individuals, inhibiting the proliferation of harmful bacteria and promoting the recovery of beneficial bacteria. In addition, it also improves brain cognitive dysfunction and liver health by affecting the gut microbiota‐brain/liver axes by promoting the synthesis of relevant amino acids and the metabolism of nucleotide base components. These findings demonstrate the potential of regulating the gut microbiome and gut microbiota‐brain/liver axes to mitigate alcohol‐induced disease.
Slovenia: Political Developments and Data in 2022
Authors: KRAŠOVEC ALENKA
Published: June 2023

In 2022, voters in Slovenia were invited several times to the polling stations, starting with the National Assembly elections in spring, followed by presidential and local elections. In addition, three nationwide referenda were held in November. The National Assembly elections saw the victory of a newly established party and the appointment of yet another political newcomer to the position of Prime Minister. Only five parties managed to pass the parliamentary threshold, the smallest number since the country's democratic transition. The centre‐left coalition government was formed by three parties. Many reforms were promised to be prepared by the new government, including a revitalisation of democracy after several years of democratic backsliding, along with a promise that those in public office will behave differently. The new government formed in June enjoyed high public support in 2022, and by the end of the year, 45 per cent of voters assessed its work as (very) positive.
Sweden: Political Developments and Data in 2022
Authors: WIDENSTJERNA THOMAS , WIDFELDT ANDERS
Published: June 2023

The year 2022 in Swedish politics was historic for several reasons. Following the war between Russia and Ukraine, Sweden broke with its long tradition of non‐alignment and submitted an application for membership of NATO. After a closely fought election, a right‐of‐centre minority coalition took office, depending on support from the previously isolated Sweden Democrats. At least initially, the change of government seemed to signify a change to more stability, after several turbulent years since 2014. The impact of the COVID‐19 pandemic more or less disappeared, but the new government faced several other challenges, including rising energy prices and growing inflationary pressure. The Liberals changed leader. A constitutional amendment was adopted which, according to critics, would make investigative journalism more difficult.
Trusting and thinking anew
Authors: Roy Srila
Published: June 2023

This essay responds to the contributions to the forum centered on my book Changing the Subject: Feminist and Queer Politics in Neoliberal India. It addresses questions posed by the contributors, from the role of the state to the digital when it comes to a rapidly changing terrain of queer and feminist organizing in contemporary India. While the book rallied against defensiveness, in this commentary I revisit defensiveness as a queer feminist political affect. Through the provocations offered in this book forum conversation, I find renewed faith in asserting friction, inconvenience, ambivalence, and defensiveness as ways of expanding queer feminisms as ongoing sites of struggle, transformation, trust, solidarity, and hope.
Antibiotic resistance and biofilm‐forming ability of α‐toxin‐positiveClostridium septicumisolates worsen patient prognosis
Authors: Kuzma Jozef , Zavala‐Meneses Sofía Guadalupe , Skultety Ludovit , Chmelar Dittmar , Ficík Jozef , Palcová Lenka
Published: June 2023

A total of, 78Clostridium septicum(CLSE) isolates were screened for genes encoding: α‐toxin, flagellin, and resistance to vancomycin (VANg). The isolates were also tested for their ability to form biofilm and their antibiotic susceptibility. All isolates were positive for α‐toxin and flagellin genes. However, only 19 isolates (24.3%) showed prevalence forVANg. We observed the strongest capacity to form a biofilm (100%) in isolates from patients with oncologic or septic and febrile diagnoses. This percentage was also very high in patients with colitis and gastrointestinal hemorrhage (72.7%). No less than 43 isolates showed antibiotic resistance, and 21 were multidrug‐resistant (MDR). Interestingly, our studies showed a correlation between antibiotic resistance and biofilm formation. A statistically significant difference was observed between biofilm‐forming MDR isolates and those with low/no biofilm‐forming ability. However, the most impressive observation was the correlation with mortality rate. While the overall mortality rate for CLSE infections was 16.7% (13/78), the mortality rate for patients infected with MDR isolates forming biofilm moderately or strongly reached 38.1% (8/21). This number increased even further when only infections with the biofilm‐formingVANg‐positive isolates were considered (61.5%; 8/13). Therefore, the ability of aVANg‐positive CLSE isolate to form a biofilm has been suggested as a biomarker of poor prognosis.
Editorial: Functional dyspepsia in pregnancy—Distinct approaches to a special population. Authors' reply
Authors: Liu Benjamin , Song Gengqing
Published: June 2023

LINKED CONTENT

This article is linked to Liu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17534 and https://doi.org/10.1111/apt.17553
Pharmacokinetics and safety of prolonged paracetamol treatment in neonates: An interventional cohort study
Authors: Haslund‐Krog Sissel , Barry Jessica M. , Birnbaum Angela K. , Dalhoff Kim , Brink Henriksen Tine , Sherwin Catherine M. T. , Avachat Charul , Poulsen Susanne , Christensen Ulla , Remmel Rory P. , Wilkins Diana , van den Anker John N. , Holst Helle
Published: June 2023

Aims

To investigate the pharmacokinetics and safety of prolonged paracetamol use (>72 h) for neonatal pain.

Methods

Neonates were included if they received paracetamol orally or intravenously for pain treatment. A total of 126 samples were collected. Alanine aminotransferase and bilirubin were measured as surrogate liver safety markers. Paracetamol and metabolites were measured in plasma. Pharmacokinetic parameters for the parent compound were estimated with a nonlinear mixed‐effects model.

Results

Forty‐eight neonates were enrolled (38 received paracetamol for >72 h). Median gestational age was 38 weeks (range 25–42), and bodyweight at inclusion was 2954 g (range 713–4750). Neonates received 16 doses (range 4–55) over 4.1 days (range 1–13.8). The median (range) dose was 10.1 mg/kg (2.9–20.3). The median oxidative metabolite concentration was 14.6 μmol/L (range 0.12–113.5) and measurable >30 h after dose. There was no significant difference (P > .05) between alanine aminotransferase and bilirubin measures at <72 h or >72 h of paracetamol treatment or the start and end of the study. Volume of distribution and paracetamol clearance for a 2.81‐kg neonate were 2.99 L (% residual standard error = 8, 95% confidence interval 2.44–3.55) and 0.497 L/h (% residual standard error = 7, 95% confidence interval 0.425–0.570), respectively. Median steady‐state concentration from the parent model was 50.3 μmol/L (range 30.6–92.5), and the half‐life was 3.55 h (range 2.41–5.65).

Conclusion

Our study did not provide evidence of paracetamol‐induced liver injury nor changes in metabolism in prolonged paracetamol administration in neonates.
Application of the theoretical framework of acceptability in a surgical setting: Theoretical and methodological insights
Authors: Paynter Camille , McDonald Cassie , Story David , Francis Jill J.
Published: June 2023

Purpose

Methods for assessing acceptability of healthcare interventions have been inconsistent until the development of the theoretical framework of acceptability (TFA). Despite its rapid adoption in healthcare research, the TFA has rarely been used to assess acceptability of surgical interventions. We sought to explore the sufficiency of the TFA in this context and provide methodological guidance to support systematic use of this framework in research.

Method

Acceptability was assessed in a consecutive sample of 15 patients at least 3 months post‐joint replacement surgery via theory‐informed semi‐structured interviews. A detailed description of the application of the TFA is reported. This includes: development of the interview guide (including questions to assess theoretical sufficiency), analysis of interview data and interpretation of findings.

Results

Interview data were substantially codable into the TFA constructs but required the addition of a construct, labelled ‘perceived safety and risk’, and relabelling and redefining an existing construct (new label: ‘opportunity costs and gains’). Methodological recommendations for theory‐informed interview studies include producing interview support material to enhance precision of the intervention description, conducting background conversations with a range of stakeholders in the healthcare setting, and conducting first inductive and then deductive thematic analysis.

Conclusion

The sufficiency of the TFA could be enhanced for use when assessing interventions with an identifiable risk profile, such as surgery, by the inclusion of an additional construct to capture perceptions of risk and safety. We offer these methodological recommendations to guide researchers and facilitate consistency in the application of the TFA in theory‐informed interview studies.
Co‐developing guidance for conservation: An example for seabirds in the North‐East Atlantic in the face of climate change impacts
Authors: Häkkinen Henry , Taylor Nigel G. , Pettorelli Nathalie , Sutherland William J. , Aldará Jón , Anker‐Nilssen Tycho , Aulert Christophe , van Bemmelen Rob S. A. , Burnell Daisy , Cadiou Bernard , Campioni Letizia , Clark Bethany L. , Dehnhard Nina , Dias Maria P. , Enners Leonie , Furness Robert W. , Hallgrímsson Gunnar Þór , Hammer Sjúrður , Hansen Erpur Snær , Hario Martti , Hurling Stephen , Jessopp Mark , Kleinschmidt Birgit , Leivits Meelis , Maniszewska Klaudyna , Oppel Steffen , Payo‐Payo Ana , Piec Daniel , Ramos Jaime A. , Robin Frédéric , Sørensen Iben Hove , Stīpniece Antra , Thompson Danielle L. , Vulcano Antonio , Petrovan Silviu
Published: June 2023

Conservation guidance—an authoritative source of information and recommendations explicitly supporting decision‐making and action regarding nature conservation—represents an important tool to communicate evidence‐based advice to conservation actors. Given the rapidly increasing pressure that climate change poses to biodiversity, producing accessible, well‐informed guidance on how to best manage the impacts and risks of changing climatic conditions is particularly urgent. Guidance documents should ideally be produced with multistage input from stakeholders who are likely to use and implement such advice; however, this step can be complicated and costly, and remains largely unformalized. Moreover, there is currently little direct evidence synthesized for actions that specifically target climate change and guidance remains largely absent. Here, we introduce a process for co‐developing guidance for species conservation in the face of climate change, using seabirds in the North‐East Atlantic as a case study. Specifically, we collated evidence on climate change vulnerability and possible conservation actions using literature synthesis, stakeholder surveys, and ecological modeling. This evidence base was then discussed, refined, and expanded using structured stakeholder workshops. We summarize the knowledge gained through stakeholder engagement and provide recommendations for future international efforts to co‐produce conservation guidance for managing wildlife, in the context of a rapidly changing climate.
Donor supply for partial heart transplantation in the United States
Authors: Quintao Ritchelli , Kwon Jennie H. , Bishara Katherine , Rajab Taufiek Konrad
Published: June 2023

Background

Congenital heart disease (CHD) is the most common cause of birth defects worldwide. Valvular defects are a common form of CHDs, and, at this time, treatment options for children with unrepairable valve disease are limited. Issues with anticoagulation, sizing, and lack of growth in valve replacement options can lead to high mortality rates and incidence of reoperations. Partial heart transplantation, or transplantation of fresh valve allografts, has recently been described as a strategy to provide a durable and non‐thrombogenic alternative to conventional prostheses and provide growth potential in pediatric patients.

Methods

The United Network for Organ Sharing (UNOS) database was queried to analyze the number of pediatric donor hearts that were not recovered but had viable valves (n = 3565) between January 2010 and September 2021. Recoverable valves were grouped by donor age: infants (age < 1 year), toddlers (age ≥1 and <3 years), and children (age ≥3 and <18 years). Demographic characteristics of donors were analyzed between age groups.

Results

Infants, toddlers, and children had a total of 344, 465, and 2756 hearts with recoverable valves, respectively, over the study period, representing an average of 29, 39, and 230 hearts with recoverable valves per year.

Conclusion

The results of our study identify the minimum donor supply for partial heart transplantation. The actual number is likely higher because it includes hearts not entered in the UNOS database and domino transplants from orthotopic heart transplant recipients. Partial heart transplantation is logistically feasible as there are recoverable valves available for all age groups, fulfilling a clinical need in pediatric patients with unrepairable valve disease.
Association between glycaemia risk index (GRI) and diabetic retinopathy in type 2 diabetes: A cohort study
Authors: Wang Yaxin , Lu Jingyi , Ni Jiaying , Wang Ming , Shen Yun , Lu Wei , Zhu Wei , Bao Yuqian , Rodbard David , Vigersky Robert A. , Jia Weiping , Zhou Jian
Published: June 2023

Aim

To investigate the association between a new composite metric, glycaemia risk index (GRI), and incident diabetic retinopathy (DR).

Methods

A total of 1204 adults with type 2 diabetes without DR at baseline were included between 2005 and 2019 from a single centre in Shanghai, China. GRI was obtained from continuous glucose monitoring data at baseline. Cox proportion hazard regression analysis was used to assess the association between GRI and the risk of incident DR.

Results

During a median follow‐up of 8.4 years, 301 patients developed DR. The multivariable‐adjusted hazard ratios (HRs) for incident DR across ascending GRI quartiles (≤14 [reference], 15 ~ 28, 29 ~ 47 and > 47) were 1.00, 1.05 (95% CI 0.74‐1.48), 1.33 (95% confidence interval [CI] 0.96‐1.84) and 1.53 (95% CI 1.11‐2.11), respectively. For each 1‐SD increase in GRI, the risk of DR was increased by 20% (HR 1.20, 95% CI 1.07‐1.33) after adjustment for confounders.

Conclusions

In patients with type 2 diabetes, higher GRI is associated with an increased risk of incident DR. GRI has the potential to be a valuable clinical measure, which needs to be further explored in future studies.
Central vein sign and paramagnetic rim sign: From radiologically isolated syndrome to multiple sclerosis
Authors: Abou Mrad Tatiana , Naja Kim , Khoury Samia J. , Hannoun Salem
Published: June 2023

The widespread use of magnetic resonance imaging (MRI) has led to an increase in incidental findings in the central nervous system. Radiologically isolated syndrome (RIS) is a condition where imaging reveals lesions suggestive of demyelinating disease without any clinical episodes consistent with multiple sclerosis (MS). The prognosis for RIS patients is uncertain, with some remaining asymptomatic while others progress to MS. Several risk factors for disease progression have been identified, including male sex, younger age at diagnosis, and spinal cord lesions. This article reviews two promising biomarkers, the central vein sign (CVS) and the paramagnetic rim sign (PRS), and their potential role in the diagnosis and prognosis of MS and RIS. Both CVS and PRS have been shown to be accurate diagnostic markers in MS, with high sensitivity and specificity, and have been useful in distinguishing MS from other disorders. Further research is needed to validate these findings and determine the clinical utility of these biomarkers in routine practice.
Diagnosing nonconvulsive status epilepticus: Defining electroencephalographic and clinical response to diagnostic intravenous antiseizure medication trials
Authors: Leitinger Markus , Gaspard Nicolas , Hirsch Lawrence J. , Beniczky Sándor , Kaplan Peter W. , Husari Khalil , Trinka Eugen
Published: June 2023

Objective

The Salzburg criteria for nonconvulsive status epilepticus (NCSE) and the American Clinical Neurophysiology Society (ACNS) Standardized Critical Care EEG Terminology 2021 include a diagnostic trial with intravenous (IV) antiseizure medications (ASMs) to assess electroencephalographic (EEG) and clinical response as a diagnostic criterion for definite NCSE and possible NCSE. However, how to perform this diagnostic test and assessing the EEG and clinical responses have not been operationally defined.

Methods

We performed a Delphi process involving six experts to standardize the diagnostic administration of IV ASM and propose operational criteria for EEG and clinical response.

Results

Either benzodiazepines (BZDs) or non‐BZD ASMs can be used as first choice for a diagnostic IV ASM trial. However, non‐BZDs should be considered in patients who already have impaired alertness or are at risk of respiratory depression. Levetiracetam, valproate, lacosamide, brivaracetam, or (if the only feasible drug) fosphenytoin or phenobarbital were deemed appropriate for a diagnostic IV trial. The starting dose should be approximately two thirds to three quarters of the full loading dose recommended for treatment of status epilepticus, with an additional smaller dose if needed. ASMs should be administered during EEG recording under supervision. A monitoring time of at least 15 min is recommended. If there is no response, a second trial with another non‐BDZ or BDZs may be considered. A positive EEG response is defined as the resolution of the ictal–interictal continuum pattern for at least three times the longest previously observed spontaneous interval of resolution (if any), but minimum of one continuous minute. For a clinical response, physicians should use a standardized examination before and after IV ASM administration. We suggest a definite time‐locked improvement in a focal deficit or at least one‐step improvement on a new dedicated one‐domain 10‐level NCSE response scale.

Significance

The proposed standardized approach of a diagnostic IV ASM trial further refines the ACNS and Salzburg diagnostic criteria for NCSE.
What is autoimmune encephalitis‐associated epilepsy? Proposal of a practical definition
Authors: Rada Anna , Bien Christian G.
Published: June 2023

Seizures resulting from cerebral autoimmunity are either acutely symptomatic in the context of autoimmune encephalitis (AIE) with neural surface antibodies, or they are indicative of an enduring predisposition to seizures, that is, epilepsy. Here, we propose a practical definition for autoimmune encephalitis‐associated epilepsy (AEAE): Seizures associated with antibodies against glutamic acid decarboxylase, paraneoplastic syndromes, or Rasmussen encephalitis are classified as AEAE. AEAE secondary to AIE with antibodies against the N‐methyl‐D‐aspartate receptor, leucine‐rich glioma inactivated protein 1, contactin‐associated protein‐2, or γ‐aminobutyric acid‐B receptor can be diagnosed if the following criteria are met: seizures persist for at least 2 years after immunotherapy initiation; no signs of encephalitis on magnetic resonance imaging and no fluorodeoxyglucose positron emission tomography hypermetabolism; normal cerebrospinal fluid cell count; and a substantial decrease in antibody titers. This classification corresponds to different disease mechanisms. While AIE results from the pathogenic effects of neural antibodies, AEAE is probably the consequence of encephalitis‐related tissue damage and thereby mainly structurally mediated. The distinction between AIE and AEAE also has practical consequences: In AIE, immunotherapy is usually highly beneficial, whereas anti‐seizure medication has little effect. In AEAE, immunotherapy is less promising and the usual anti‐seizure interventions are preferable. In addition, the diagnosis of AEAE has social consequences in terms of driving and professional limitations.
Treatment challenges in equine fibrosarcomas: Can the harmonic scalpel help in the treatment success?
Authors: Abu‐Seida Ashraf M.
Published: June 2023

Fibrosarcoma is relatively uncommon aggressive neoplasm, representing less than 3% of all neoplasms recorded in horses. Successful treatment of fibrosarcoma can be challenging in equine and recurrence is a common late complication. The accompanying paper by Bellitto et al. (2023,Equine Veterinary Education,10.1111/eve.13808) illustrates the successful surgical treatment of a large fibrosarcoma over the medial and plantar aspect of the left distal limb in an 18‐year‐old Warmblood gelding. The authors report on the success of treatment after surgical excision of the tumour under general anaesthesia using a harmonic scalpel. The gelding recovered well after 1 year of surgery with no recurrence at that time. Further clinical studies are recommended to compare the harmonic scalpel with other modalities like surgical lasers and conventional sharp excision for treatment of fibrosarcoma in horses as well as to understand the potential benefits of using the harmonic scalpel when treating infiltrative tumours such as fibrosarcoma. The publication of this case report inEquine Veterinary Educationis of clinical importance to equine practitioners when treating equine infiltrative neoplasms such as fibrosarcomas.
Advances in remote sensing of freshwater fish habitat: A systematic review to identify current approaches, strengths and challenges
Authors: Kuiper Spencer Dakin , Coops Nicholas C. , Hinch Scott G. , White Joanne C.
Published: June 2023

Remote sensing technology offers the ability to derive information on freshwater fish habitats across broad geographic areas and has the potential to transform approaches to monitoring. However, the numerous platforms, sensors and analytical software that are available may overwhelm those interested in utilizing this important technology and thus limit its broad application and uptake. Our review is intended to shed light on the capacity of this technology to transform freshwater fish habitat monitoring by examining the fundamental characteristics of the major remote sensing technologies that have been used for characterizing freshwater habitats, conducting a systematic literature review of studies that have used remote sensing technologies to characterize freshwater fish habitats and, highlighting some of the key habitat features, fish species and regions, that have been examined. Lastly, we identify the relative strengths and weaknesses of the various remote sensing technologies that can be used, recommend future research that could help improve the use of these technologies, and, provide a series of important considerations for those who are interested in utilizing these technologies for freshwater fish habitat characterization.
Aquatic connectivity treatments increase fish and macroinvertebrate use of Typha‐invaded Great Lakes coastal wetlands
Authors: Lishawa Shane C. , Schrank Amy J. , Lawrence Beth A. , Monks Andrew M. , Albert Dennis A.
Published: June 2023

Coastal wetlands provide critical habitat for aquatic organisms and important ecosystem services for the terrestrial and aquatic landscapes that they bridge, but increasingly common invasive macrophytes disrupt plant communities, food webs, habitat structure and littoral–pelagic linkages. In Laurentian Great Lakes coastal wetlands, invasive cattails (Typha × glauca and T. angustifolia, hereafter Typha) homogenise ecosystem structure and reduce nearshore dissolved oxygen, and plant, fish and macroinvertebrate diversity. We hypothesised that management treatments which reduce Typha and its abundant litter promote structural heterogeneity and mitigate physicochemical and biodiversity impacts.

To test this hypothesis, we implemented a large‐scale (2,048 m2 treatment units), multi‐site (four coastal wetlands) experiment in northern Michigan (U.S.A.) to examine how invasive Typha mechanical harvesting treatments (biomass harvest, aquatic connectivity channels, Typha‐dominated control) altered fish, macroinvertebrate, plant, larval amphibian abundance and diversity, and water quality for 2‐year post‐treatment.

Both harvest and channel treatments reduced Typha biomass, cover and dominance; harvest increased multi‐taxa species richness, fish diversity and abundance; and channels altered plant, fish, and macroinvertebrate community structures. Dissolved oxygen was greater and litter was reduced by both treatments, indicating likely mechanisms for shifts in fish and macroinvertebrate use.

Our results suggest that harvesting invasive macrophytes can ameliorate biodiversity impacts and improve habitat quality, and that adding aquatic connectivity channels can increase community complexity.

Typha management that incorporates both harvesting and aquatic connectivity channels appears to provide the greatest benefit to several taxonomic groups, likely by reducing Typha and its litter, increasing dissolved oxygen availability, and increasing the connection between open water and wetland interiors. Increasing habitat complexity and aquatic connectivity of invaded wetlands can promote biodiversity and provides a more realistic management goal than the complete elimination of invasive macrophytes.
Association between genetic polymorphisms of NOD1, Interleukin‐1B, and cagA strain with low‐grade duodenal eosinophilia in Helicobacter pylori‐related dyspepsia
Authors: Barreyro Fernando Javier , Maiorana Facundo , Caronia Maria Virginia , Elizondo Karina , Schneider Adolfo , Zapata Pedro Darío
Published: June 2023

Background

Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)‐related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro‐inflammatory cascade, nucleotide‐binding oligomerization domain 1 (NOD‐1), and interleukin‐1 beta (IL‐1β) in HpD was not explored.

Aim

To evaluate the association of NOD1‐796G>A and IL‐1B‐511C>T gene variants and low‐grade duodenal eosinophilia in HpD.

Methods

A multicenter cross‐sectional study was conducted. A total of 253 patients who met Rome‐IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated.

Results

Sixty‐four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1‐796G>A and IL‐1B‐511C>T gene variants. Low‐grade duodenal eosinophilia was significantly increased in NOD1‐796 GG versus single A‐allele, but not in IL‐1B‐511 single T‐allele or CC‐allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low‐grade duodenal eosinophilia with isolated variants NOD1‐796 GG and IL‐1B‐511 single T‐allele, but not without cagA. When we performed combined polymorphism analysis with NOD1‐796 GG/IL‐1B‐511 single T‐allele, a synergistic effect on low‐grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD.

Conclusion

Our findings suggest that low‐grade duodenal eosinophilia is significantly associated with NOD1‐796 GG allele specially in cagA strain and with allelic combination NOD1‐796 GG/IL‐1B‐511 single T‐allele independent of cagA strain infection in HpD patients.