bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of IV fluid restriction according to site‐specific intensity of standard fluid treatment—protocol
Authors: Sivapalan Praleene , Kaas‐Hansen Benjamin Skov , Meyhoff Tine Sylvest , Hjortrup Peter Buhl , Kjær Maj‐Brit N. , Laake Jon Henrik , Cronhjort Maria , Jakob Stephan M. , Cecconi Maurizio , Nalos Marek , Ostermann Marlies , Malbrain Manu L. N. G. , Møller Morten Hylander , Perner Anders , Granholm Anders
Published: April 2024

Background

Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site‐specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics.

Methods

We will assess the effects of heterogeneity in treatment intensity across one primary (all‐cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90 days. We will classify sites based on the site‐specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24 h in the standard‐fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup.

Discussion

This study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock.

Registrations

The European Clinical Trials Database (EudraCT): 2018‐000404‐42, ClinicalTrials. gov: NCT03668236.
Aged‐vascular niche hinders osteogenesis of mesenchymal stem cells through paracrine repression of Wnt‐axis
Authors: Fleischhacker Viviane , Milosic Filip , Bricelj Marko , Kührer Kristina , Wahl‐Figlash Katharina , Heimel Patrick , Diendorfer Andreas , Nardini Eleonora , Fischer Irmgard , Stangl Herbert , Pietschmann Peter , Hackl Matthias , Foisner Roland , Grillari Johannes , Hengstschläger Markus , Osmanagic‐Myers Selma
Published: April 2024

Age‐induced decline in osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) potentiates osteoporosis and increases the risk for bone fractures. Despite epidemiology studies reporting concurrent development of vascular and bone diseases in the elderly, the underlying mechanisms for the vascular‐bone cross‐talk in aging are largely unknown. In this study, we show that accelerated endothelial aging deteriorates bone tissue through paracrine repression of Wnt‐driven‐axis in BMSCs. Here, we utilize physiologically aged mice in conjunction with our transgenic endothelial progeria mouse model (Hutchinson‐Gilford progeria syndrome; HGPS) that displays hallmarks of an aged bone marrow vascular niche. We find bone defects associated with diminished BMSC osteogenic differentiation that implicate the existence of angiocrine factors with long‐term inhibitory effects. microRNA‐transcriptomics of HGPS patient plasma combined with aged‐vascular niche analyses in progeria mice reveal abundant secretion of Wnt‐repressive microRNA‐31‐5p. Moreover, we show that inhibition of microRNA‐31‐5p as well as selective Wnt‐activator CHIR99021 boosts the osteogenic potential of BMSCs through de‐repression and activation of the Wnt‐signaling, respectively. Our results demonstrate that the vascular niche significantly contributes to osteogenesis defects in aging and pave the ground for microRNA‐based therapies of bone loss in elderly.
Do Interactions Between Investors and Management Result in More Conservative Accounting Information?*
Authors: Li Yaoyao , Wang Tianmei , Zhao Yang
Published: April 2024

Within the context of the investor–management interaction platforms “E‐Interaction” and “Interaction Easy,” this paper investigates the influence of investor and management interaction on accounting conservatism and explores the strategic response behavior of management. The findings indicate that both the intensity and depth of investor inquiries contribute to the enhancement of accounting conservatism. Moreover, compared to “template” responses, management's “targeted” responses to investors significantly increase the accounting conservatism of companies. Mechanism tests reveal that investor–management interaction, by enhancing investor monitoring capabilities and increasing the litigation and reputational risks faced by companies, subsequently enhances the accounting conservatism of companies. Further analysis shows that in cases where companies are audited by non‐Big Four auditor and have lower analyst coverage, indicating a weaker external information environment, investor–management interaction can yield better governance effects.
Does the Textual Tone of Analyst Reports Have Valuable Information? Korean Evidence*
Authors: Cho Su‐Ji , Lee Ki‐Kwang , Yang Cheol‐Won
Published: April 2024

We investigate whether the text of analyst reports can provide additional information beyond the recommendation and target price. Positive and negative word lexicons are generated through an automated Bayesian learning method applied to Korean analyst reports spanning from 2016 to 2018. Then, the textual tone of an analyst report is quantified as the difference between the frequencies of positive and negative words in the text. The announcement returns of portfolios sorted by textual tone exhibit significant differences ranging from 1.14% to 2.82% within the same recommendation or target price revision group. Regression analysis also reveals significant association between the textual tone of analyst reports and stock announcement returns, even when controlling for the recommendation and target price. Notably, the text proves to be more informative in negative tones and within firms with limited analyst coverage. Our results indicate that textual analysis can unveil nuanced analyst opinions not captured by numerical information.
Understanding Corporate Bond Defaults in Korea Using Machine Learning Models*
Authors: Park Dojoon , Auh Jun Kyung , Song Giwan , Eom Young Ho
Published: April 2024

We investigate corporate bond defaults from 1995 to 2020 using hand‐collected data from hard‐copy publications in Korea. Using an under‐sampling method, we construct default prediction models based on machine learning models as well as a logistic model. The empirical results show that the random forest model outperforms the others. However, regardless of the models used, model performance in financial crisis periods is significantly worse than it is in non‐crisis periods. This finding suggests the need for additional information to improve model performance during crises when the default prediction is the most relevant. Furthermore, the dominant predictor of defaults before the global financial crisis was the debt ratio, while subsequently, the coverage ratio has become the most important predictor.
Outcomes of outflow graft stenting in HeartMate 3 left ventricular assist devices: A systematic review and individual patient data meta‐analysis
Authors: Patil Sanath , Ahmad Danial , Shah Kishori , Vishnevsky Alec , Ruggiero Nicholas J. , Rajapreyar Indranee N. , Rame J. Eduardo , Alvarez Rene J. , Rajagopal Keshava , Entwistle John W. , Massey Howard T. , Tchantchaleishvili Vakhtang
Published: April 2024

Purpose

LVAD outflow graft stenosis continues to remain prevalent with a high complication rate. We sought to pool the existing evidence on indications, utilization patterns, and outcomes of transcatheter interventions for outflow graft stenosis in the HeartMate 3 LVAD.

Methods

An electronic search was performed to identify all studies in the English literature reporting on HeartMate 3 LVAD outflow graft stenting. Patient‐level data were extracted for analysis.

Results

Thirteen published reports and one unpublished case comprising a total of 28 patients were included. Median patient age was 68.5 years [Interquartile range: 58, 71] and 25.9% (7/27) were female. Dyspnea [60.7% (17/28)] was the most common presenting symptom. Low flow alarms were present in 60% (15/25) of patients. Findings included external compression [35.7% (10/28)], graft twist [21.4% (6/28)], graft twist and external compression [14.3% (4.28)], intraluminal thrombus [10.7% (3/28)], graft twist and intraluminal thrombus [3.6% (1/28)], and pseudoaneurysm of outflow graft [3.6% (1/28)]. Median time from LVAD implantation to stenting was 2.1 years [1.4, 3]. Immediate flow normalization after stenting was observed in 85.7% (24/28). The 30‐day mortality was 12% (3/25). Overall mortality was 12% (3/25) at a median follow‐up of 3.9 months [1, 17].

Conclusion

Outflow graft stenting in the HeartMate 3 LVAD appears to be a reasonable treatment option for outflow graft stenosis, with low overall rates of complications and mortality. Further refinement of indications and approaches may improve outcomes.
Intrapartum prophylactic efficacy of ampicillin versus clindamycin in preventing vertical transmission of group B Streptococcus
Authors: Ujiie Gakuto , Murase Masahiko , Asai Hideyuki , Igawa Mio , Okuyama Ayumi , Seo Kohei , Ichizuka Kiyotake , Ikeda Hirokazu
Published: April 2024

Aim

To compare the prophylactic efficacy of ampicillin and clindamycin against vertical transmission of group B Streptococcus from mothers to their infants by evaluating the rates of group B Streptococcus colonisation.

Methods

We retrospectively extracted data for mothers who delivered at Showa University Northern Yokohama Hospital between 1 October 2017 and 31 March 2021 and tested positive for antepartum group B Streptococcus, and their infants. The chi‐square test was used to compare the rates of group B Streptococcus colonisation, sepsis, and meningitis. We conducted a multivariate logistic regression analysis, including the time interval between membrane rupture and delivery, chorioamnionitis, and maternal intrapartum fever (≥38.0°C).

Results

Two hundred fifty‐nine mothers and their infants were eligible. Ampicillin and clindamycin were administered to 150 and 109 mothers, respectively. In the ampicillin and clindamycin groups, 12.0% (18/150) and 37.6% (41/109) infants were group B Streptococcus positive, respectively. The rate of group B Streptococcus colonisation among infants was significantly lower in the ampicillin group (p < 0.001). Multivariate regression analysis showed similar results (p < 0.001). No sepsis or meningitis cases were observed in either group.

Conclusion

Prophylactic efficacy of clindamycin against the vertical transmission of group B Streptococcus is lower than that of ampicillin.
Targeted therapy in Burkitt lymphoma: Small molecule inhibitors under investigation
Authors: Atallah‐Yunes Suheil Albert , Habermann Thomas M. , Khurana Arushi
Published: April 2024

Multiagent chemoimmunotherapy remains the standard of care treatment for Burkitt lymphoma leading to a cure in the majority of cases. However, frontline treatment regimens are associated with a significant risk of treatment related toxicity especially in elderly and immunocompromised patients. Additionally, prognosis remains dismal in refractory/relapsed Burkitt lymphoma. Thus, novel therapies are required to not only improve outcomes in relapsed/refractory Burkitt lymphoma but also minimize frontline treatment related toxicities. Recurrent genomic changes and signalling pathway alterations that have been implicated in the Burkitt lymphomagenesis include cell cycle dysregulation, cell proliferation, inhibition of apoptosis, epigenetic dysregulation and tonic B‐cell receptor‐phosphatidylinositol 3‐kinase (BCR‐PI3K) signalling. Here, we will discuss novel targeted therapy approaches using small molecule inhibitors that could pave the way to the future treatment landscape based on the understanding of recurrent genomic changes and signalling pathway alterations in the lymphomagenesis of adult Burkitt lymphoma.
Evaluating thromboprophylaxis in the sickle cell disease population: Navigating the evidence gap
Authors: Davila Jennifer , O'Brien Sarah H. , Mitchell William B. , Manwani Deepa
Published: April 2024

Sickle cell disease (SCD) arises from beta‐globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape. This leads to complications like vascular occlusion, haemolytic anaemia, inflammation and organ damage. Beyond erythrocyte abnormalities however, there is a body of literature highlighting the hypercoagulable state that is likely a contributor to many of the complications we see in SCD. The persistent activation of the coagulation cascade results in thromboembolic events, notably venous thromboembolism (VTE) which is independently associated with increased mortality in both adults and children with SCD. While the increased risk of VTE in the SCD population seems well established, there is a lack of guidelines for thromboprophylaxis in this population. This Wider Perspective will describe the hypercoagulable state and increased thrombosis risk in the SCD population, as well as advocate for the development of evidence‐based guidelines to aid in the prevention of VTE in SCD.
Mismatched related donor allogeneic haematopoietic cell transplantation compared to other donor types for Ph+ chronic myeloid leukaemia: A retrospective analysis from the Chronic Malignancies Working Party of the EBMT
Authors: Onida Francesco , Gras Luuk , Ge Junran , Koster Linda , Hamladji Rose‐Marie , Byrne Jenny , Avenoso Daniele , Aljurf Mahmoud , Robin Marie , Halaburda Kazimierz , Passweg Jakob , Salmenniemi Urpu , Sengeloev Henrik , Apperley Jane , Clark Andrew , Reményi Péter , Morozova Elena , Kinsella Francesca , Lenhoff Stig , Ganser Arnold , Wu Ka Lung , Perez‐Martinez Antonio , Hayden Patrick J. , Raj Kavita , Drozd‐Sokolowska Joanna , OrtÍ Guillermo , de Lavallade Hugues , Yakoub‐Agha Ibrahim , McLornan Donal P. , Chalandon Yves
Published: April 2024

Allogeneic haematopoietic cell transplantation (allo‐HCT) remains an option for tyrosine kinase inhibitor‐resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high‐risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry‐based study of 1686 CML patients undergoing first allo‐HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo‐HCT was 46 years (IQR 36–55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse‐free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non‐relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft‐versus‐host disease (GvHD)‐free/relapse‐free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.
The presence of attentional and interpretation biases in patients with severe MS‐related fatigue
Authors: de Gier Marieke , Oosterman Joukje M. , Hughes Alicia M. , Moss‐Morris Rona , Hirsch Colette , Beckerman Heleen , de Groot Vincent , Knoop Hans
Published: April 2024

Objective

Severe fatigue is a prevalent and disabling symptom in multiple sclerosis (MS). This study tested if a fatigue‐ and physical activity‐related attentional bias (AB) and a somatic interpretation bias (IB) are present in severely fatigued patients with MS. Biases were compared to healthy controls and patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Method

Severely fatigued patients with MS or ME/CFS and healthy controls completed a Visual Probe Task (VPT) assessing fatigue‐ and physical activity‐related AB and an IB task that assesses the tendency to interpret ambiguous information in either a somatically threatening way or in a more neutral manner. The VPT was completed by 38 MS patients, 44 ME/CFS patients, and 46 healthy controls; the IB task was completed by 156, 40 and 46 participants respectively.

Results

ANOVA showed no statistically significant group differences in a fatigue‐related AB or physical activity‐related AB (omnibus test of interaction between topic × condition: F2,125 = 1.87; p = .159). Both patient groups showed a tendency to interpret ambiguous information in a somatically threatening way compared to healthy controls (F1,2 = 27.61, p < .001). This IB was significantly stronger in MS patients compared to ME/CFS patients. IB was significantly correlated with cognitive responses to symptoms in MS patients.

Conclusion

MS patients tend to interpret ambiguous information in a somatically threatening way. This may feed into unhelpful ways of dealing with symptoms, possibly contributing to the perpetuation of severe fatigue in MS.
Acoustic monitoring of anurans and birds in tropical biomes
Authors: De Araújo C. B. , Lima M. R. , Albuquerque P. , Alquezar R. D. , Barreiros M. , Jardim M. , Gangenova E. , Machado R. B. , Phalan B. T. , Roos A. L. , Rosa G. L. M. , Saturnino N. , Simões C. R. , Torres I. M. D. , Varela D. , Zurano J. P. , Marques P. A. M. , dos Anjos L.
Published: April 2024

Passive acoustic monitoring (PAM) is increasingly popular in ecological research, but recording and analyzing large amounts of data is still a critical bottleneck for the long‐term monitoring of multiple species. We evaluated how temporal and spatial sampling effort affects species diversity estimates using a set of 14,045 1‐min recordings from various neotropical birds and anuran communities. Our goals were to evaluate (i) the daily vocal activity cycle of birds and anurans, (ii) the effect of temporal structure (e.g., number of minutes listened each hour; continuous versus intermittent recordings) on determining the species composition, and (iii) the species–area relationship, and how the number of recorders affects species richness estimates. Based on sampling coverage and completeness, we (iv) evaluate manual inspection schedules for birds and anurans across four biomes of Brazil. We found marked diel variation in vocal activity between taxonomic groups, indicating that birds and anurans are more efficiently detected during early periods of the day and night, respectively. For proper diversity estimates, biomes with higher biodiversity required longer inspecting periods and a larger number of replicates, irrespective of taxa. Although fewer recordings per hour are less informative than full‐hour sampling, species diversity is better estimated when inspected minutes are interspersed over longer periods than inspecting minutes recorded over shorter timespans. Based on our findings, we recommend how to set PAM programs over highly diverse ecosystems.

Abstract in Portuguese is available with online material.
Associations between the number of siblings, parent–child relationship and positive youth development of adolescents in mainland China: A cross‐sectional study
Authors: Ke Jingyuan , Luo Biru , Huang Chuanya , Tong Yunxuan , Wang Yan , Li Xiang , Ma Wenlin , Zhao Li , Liao Shujuan
Published: April 2024

Background

Positive development plays an important role in youth when dealing with stressful circumstances. According to the resource dilution theory, adolescents with or without siblings may receive different levels of emotional and material resources from their parents. The purpose of this study is to examine the association between the positive development of adolescents in China today with their family characteristics such as the number of siblings.

Methods

A total of 2072 junior high and senior high school students (13 to 18 years old) in Chengdu, Sichuan, China, were investigated by cluster sampling. The Chinese Positive Youth Development scales (CPYDs) were used to measure positive youth development. The generalized linear model was used to explore the relationships among the number of siblings, parent–child relationships and positive youth development.

Results

Adolescents from only‐child families had better performance on positive development (H = 21.87, P < 0.001) and better relationships with parents (H = 15.1, P < 0.05). The positive development of male and female adolescents does not significantly differ in families with different numbers of siblings. The generalized linear model showed that a positive parent–child relationship is positively correlated with adolescent positive development (P < 0.05).

Conclusion

Positive youth development is not only associated with the number of siblings but also other modifiable familial factors. The positive relationship between parents and adolescents is of great practical value in daily life to improve youth development, and this might be the real lesson the resource dilution theory tells.
Systematic review of the impact of restrictive wildlife trade measures on conservation of iconic species in southern Africa
Authors: Hiller Christina , ’t Sas‐Rolfes Michael
Published: April 2024

Trade restrictions are often advocated and implemented as measures to protect wild species threatened by overexploitation. However, in some instances, their efficacy has been questioned, notably by governments in the southern African (SADC) region, which tend to favor a sustainable use approach to wildlife management. We conducted a systematic review of published literature guided by the PRISMA process to examine the effectiveness of trade restrictions and directly related control measures in addressing threats to species conservation in the SADC region, with a focus on elephants (Loxodonta sp.), rhinoceroses (Ceratotherium simum, Diceros bicornis), lions (Panthera leo), and pangolins (Manis sp.). We focused in particular on the direct conservation impact of trade restrictions at species or population level, indirect conservation impact at human behavior or attitude level, and socioeconomic impact on rural livelihoods and well‐being and on national economies. Research on these topics was uneven and focused strongly on the effects of trade restrictions and law enforcement on crime‐related behavior. Research gaps include socioeconomic impacts of trade restrictions, including effects of international restrictions on local livelihoods and consequent secondary conservation impacts, and evaluations of attempts to disrupt criminal networks. Based on the reviewed impact evidence, the effectiveness of international trade restrictions depends on a range of fully aligned measures in countries of origin, transit, and consumption. For example, our results suggest positive ecological short‐term but negative or unknown long‐term socioeconomic impacts of domestic restrictions. Based on these findings, key policy requirements include more nuanced approaches to incorporate a range of appropriate measures in range, transit, and consumer countries, that focus on capacity development for early detection and apprehension of incursions inside protected areas; measures for constructive engagement with relevant local communities outside protected areas; and future research to improve understanding of the socioeconomic contribution of wildlife.
Effects of coastal development on sawfish movements and the need for marine animal crossing solutions
Authors: Lear Karissa O. , Ebner Brendan C. , Fazeldean Travis , Bateman Rebecca L. , Morgan David L.
Published: April 2024

Although human‐made barriers to animal movement are ubiquitous across many types of ecosystems, the science behind these barriers and how to ameliorate their effects lags far behind in marine environments compared with terrestrial and freshwater realms. Using juvenile sawfish in an Australian nursery habitat as a model system, we aimed to assess the effects of a major anthropogenic development on the movement behavior of coastal species. We compared catch rates and movement behavior (via acoustic telemetry) of juvenile green sawfish (Pristis zijsron) before and after a major coastal structure was built in an important nursery habitat. Acoustic tracking and catch data showed that the development did not affect levels of sawfish recruitment in the nursery, but it did constrain movements of juveniles moving throughout the nursery, demonstrating the reluctance of shoreline‐associated species to travel around large or unfamiliar coastal structures. Given the current lack of information on human‐made movement barriers in the marine environment, these findings highlight the need for further research in this area, and we propose the development of and experimentation with marine animal crossings as an important area of emerging research.
Collective effects of rising average temperatures and heat events on oviparous embryos
Authors: Ma Liang , Wu Dan‐Yang , Wang Yang , Hall Joshua M. , Mi Chun‐Rong , Xie Hong‐Xin , Tao Wei‐Jie , Hou Chao , Cheng Kun‐Ming , Zhang Yong‐Pu , Wang Ji‐Chao , Lu Hong‐Liang , Du Wei‐Guo , Sun Bao‐Jun
Published: April 2024

Survival of the immobile embryo in response to rising temperature is important to determine a species’ vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population‐specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species’ range shifts under climate change. Embryos’ tolerance of chronic heat (T‐chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T‐acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low‐latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species’ vulnerability to climate change.
Subclinical immune responses to nickel in sensitized individuals—a dose–response study
Authors: Wennervaldt Michael , Vaher Helen , Ahlström Malin G. , Bischofberger Nuno , Menné Torkil , Thyssen Jacob P. , Johansen Jeanne D. , Bonefeld Charlotte M.
Published: April 2024

Background

Nickel is the leading cause of contact allergy in Europe, with 14.5% of the adult population being sensitized. Despite regulations limiting nickel release from consumer items, the incidence and prevalence of nickel allergy remain high.

Objective

To investigate the clinical and subclinical immune response to low‐dose nickel exposure on nickel pre‐exposed skin to assess the adequacy of current regulatory limits.

Method

Nickel‐allergic and healthy controls were patch tested with nickel twice with a 3–4 weeks interval. The first exposure used the diagnostic concentration of 2000 μg/cm2 nickel sulphate, and the same skin areas were then re‐exposed to 0.2, 0.5, 12.8 and 370 μg/cm2 nickel sulphate. After 48 h, the patch reactions were examined for clinical signs of eczema, and skin biopsies were collected. The transcriptomic immune profile was analysed with Nanostring nCounter and quantitative polymerase chain reaction.

Results

Two nickel‐allergic participants (15%) had clinical reactions to the regulatory limiting doses for nickel (0.2/0.5 μg/cm2) following re‐exposure. There was immune activation in all skin areas following re‐exposure to nickel, predominantly mediated by up‐regulation of cytokines and chemokines. In all nickel re‐exposed skin areas, 81 genes were up‐regulated independent from the clinical response. In skin areas exposed to 0.2 μg/cm2, 101 immune‐related genes were differentially expressed, even when no clinical response was observed. Healthy controls showed up‐regulation of three genes in response to nickel re‐exposures without any clinical reactions.

Conclusion

Immune activation can be induced in skin with local memory to nickel upon challenge with nickel doses within the regulatory limits. Our findings suggest that the regulatory limits in the European nickel regulation may not provide sufficient protection for consumers against low‐dose exposures.
Who prioritizes what? A cross‐jurisdictional comparative analysis of salmon fish passage strategies in Western Washington
Authors: Burch Catalina A. , Jardine Sunny L. , Lewis‐Smith Connor , Van Deynze Braeden
Published: April 2024

Conservation planners often rely on heuristic indices when challenged with prioritizing potential projects under a constrained budget. This paper presents a comparative analysis of several prioritization indices (PIs) of culvert fish passage barriers, which can contribute to declines in anadromous fish populations. A federal injunction requires Washington state to restore 90% of habitat blocked by state‐owned culverts by 2030, prompting the development of numerous PIs, by various entities (i.e., counties, cities) within the injunction area. Our comparative analysis of PIs within the injunction Case Area investigates their ability to distinguish between barriers, their transferability in terms of scoring metrics, how scoring weights differ, and the preferences implied thereby. We document the use of six distinct PI methods by 10 entities and find that some PIs used many shared metrics, whereas others used a high percentage of unique metrics that would be difficult to replicate outside the entity's jurisdiction. Although habitat potential, habitat quantity, and connectivity were considered across all PIs, we found a high level of variation in terms of the metric weights. Our methods can be employed in other geographies or for other restoration PI planning efforts, and our results may facilitate the development and refinement of future PIs.
Peer support for adults with type 2 diabetes starting continuous glucose monitoring—An exploratory randomised controlled trial
Authors: Lind Nanna , Christensen Merete Bechmann , Hansen Dorte Lindqvist , Willaing Ingrid , Nørgaard Kirsten
Published: April 2024

Aims

To explore the feasibility and potential benefits of a peer support programme for adults with insulin‐treated type 2 diabetes (T2D) starting continuous glucose monitoring (CGM).

Methods

This part of the Steno2tech study is an exploratory, single‐centre, open‐labelled, prospective, randomised controlled trial (RCT). A total of 60 participants were randomised 2:1 to 12 months of CGM with or without peer support. All participants received a 3‐h diabetes self‐management education course including a CGM part on how to use the CGM and interpret the CGM‐derived data. Peer support consisted of three 3‐h peer support meetings over the first 6 months of the study period with groups of three to six people. The exploratory outcomes included the acceptability and feasibility of the peer support intervention, and the between‐group difference in change in several glycaemic, metabolic and participant‐reported outcomes measured at baseline, 6 and 12 months.

Results

The peer support intervention was found acceptable and feasible. Participants shared their experiences of using and interpreting CGM data and its association with health behaviour. While both groups had improvements in glycaemic, metabolic and participant‐reported outcomes, there were no significant between‐group differences.

Conclusions

Although feasible, we found no measured additional benefits when adding a peer support programme after starting CGM in this exploratory RCT including adults with insulin‐treated T2D. Understanding the perceived effect of and preferences for a peer support intervention from the participants' points of view, including why individuals declined to participate, would be of value for future research.
Unraveling microbial community structure–function relationships in the horizontal and vertical spatial dimensions in extreme environments
Authors: Jing Xin , Classen Aimée T. , Li Daijiang , Lin Litao , Lu Mingzhen , Sanders Nathan J. , Wang Yugang , Feng Wenting
Published: April 2024

A fundamental challenge in soil macroecology is to understand how microbial community structure shapes ecosystem function along environmental gradients of the land surface at broad spatial scales (i.e. the horizontal dimension). However, little is known about microbial community structure–function relationships in extreme environments along environmental gradients of soil depth at finer spatial scales (i.e. the vertical dimension). Here, we propose a general spatial dimension partitioning approach for assessing the patterns and drivers of soil microbial community structure–function relationships across horizontal and vertical spatial gradients simultaneously. We leveraged a 200‐km desert soil salinity gradient created by a 12‐year saline‐water irrigation in the Tarim basin of Taklamakan Desert. Specifically, using a general linear model, hierarchical variance partitioning, and a path model, we assessed the patterns and key ecological processes controlling spatial turnover in microbial community structure (i.e. β‐diversity) and enzymatic activity relevant to carbon, nitrogen, and phosphorus cycling along soil salinity gradients across study sites (horizontal dimension) and soil depths (vertical dimension). We found a decoupled relationship between soil microbial β‐diversity and enzymatic activity. Differences in soil depth (on the scale of meters) were as important as geographic distance (on the scale of kilometers) in shaping bacterial and fungal β‐diversity. However, the vertical and horizontal turnover in enzymatic activity was largely attributed to an increase in the heterogeneity of soil properties, such as soil texture, water content, and pH. Our findings suggest that dispersal limitation controls microbial community β‐diversity and that environmental heterogeneity, rather than soil salinization, controls enzymatic activity. Taken together, this work highlights that in the face of ongoing environmental alterations, soil depth is an under‐explored spatial dimension that must be considered in soil conservation efforts as a critical factor in determining microbial community structure and function in extreme environments.
Metabolic disorders exacerbate the formation of glial scar after stroke
Authors: Clain Julien , Couret David , Bringart Matthieu , Lecadieu Arnaud , Meilhac Olivier , Lefebvre d'Hellencourt Christian , Diotel Nicolas
Published: April 2024

Metabolic disorders are risk factors for stroke exacerbating subsequent complications. Rapidly after brain injury, a glial scar forms, preventing excessive inflammation and limiting axonal regeneration. Despite the growing interest in wound healing following brain injury, the formation of a glial scar in the context of metabolic disorders is poorly documented. In this study, we used db/db mice to investigate the impact of metabolic perturbations on brain repair mechanisms, with a focus on glial scarring. First, we confirmed the development of obesity, poor glucose regulation, hyperglycaemia and liver steatosis in these mice. Then, we observed that 3 days after a 30‐min middle cerebral artery occlusion (MCAO), db/db mice had larger infarct area compared with their control counterparts. We next investigated reactive gliosis and glial scar formation in db/+ and db/db mice. We demonstrated that astrogliosis and microgliosis were exacerbated 3 days after stroke in db/db mice. Furthermore, we also showed that the synthesis of extracellular matrix (ECM) proteins (i.e., chondroitin sulphate proteoglycan, collagen IV and tenascin C) was increased in db/db mice. Consequently, we demonstrated for the first time that metabolic disorders impair reactive gliosis post‐stroke and increase ECM deposition. Given that the damage size is known to influence glial scar, this study now raises the question of the direct impact of hyperglycaemia/obesity on reactive gliosis and glia scar. It paves the way to promote the development of new therapies targeting glial scar formation to improve functional recovery after stroke in the context of metabolic disorders.
Mutational landscape, inhibitor development, and health‐care burden in non‐severe haemophilia A: A single‐centre Australian experience
Authors: Ramanan Radha , Evans Natalie , Kaplan Zane , McFadyen James D. , Tran Huyen A.
Published: April 2024

Aim

To characterise non‐severe haemophilia A (HA) patients enrolled on the Australian Bleeding Disorders Registry (ABDR) treated through a state‐wide Haemophilia Treatment Centre (HTC) with respect to their mutational profile, inhibitor risk and health‐care burden.

Method

We conducted a single‐centre observational study of all non‐severe HA patients treated at the Alfred Health HTC registered on the ABDR as of the 26th July 2023. Data were extracted from the ABDR and electronic medical record (EMR) regarding demographics, severity, genetic testing, treatment, inhibitors, bleeding events and procedures. Inhibitor risk was calculated as a function of exposure days (EDs) of FVIII replacement.

Results

There were 289 non‐severe HA patients treated at the Alfred HTC registered on the ABDR as of July 2023, all of whom were adult patients aged > 18 years old. Genotyping had been performed in 228/289 (78.9%). Of the inhibitor analysis population, 14/193 (7.3%) had an inhibitor. The cumulative incidence of inhibitor development at 75 EDs was 31% (95% CI 13%–46%). The median cost of bypassing agents per inhibitor patient was $57,087.50/year.

Conclusion

These results demonstrate a relatively high inhibitor prevalence and incidence risk in non‐severe HA compared to previously published work, although this may partly reflect a smaller population size. High rates of genotyping have allowed representative mutational characterisation. The burden of care imposed by non‐severe HA in terms of bleeding events, procedures and bypassing agent cost is larger than expected, particularly within the inhibitor population.
Predicting joint involvement through tailored prophylaxis in severe haemophilia A, is it possible?
Authors: Meijon‐Ortigueira Maria del Mar , Alvarez‐Roman Maria Teresa , De La Corte Hortensia , Butta Nora , Jimenez‐Yuste Victor
Published: April 2024

Introduction

Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately. In this paper, we present a model that considers together the characteristics of prophylaxis and the relevance of each.

Methods

The age at initiation of prophylaxis, number of bleeding events, treatment regimen, therapeutic adherence, FVIII trough levels, and joint status were analyzed in 59 patients followed at La Paz University Hospital between January 2000 and December 2019.

Results

The mean duration of primary prophylaxis of 113.37 ± 57.79 months. Eighty‐three percent (n = 49) had no joint status involvement at the end of follow‐up (HJHS and HEAD‐US = 0). The median ABR was 0.7 (IQR 0.2 –1.0) and 54.2% presented trough levels of FVIII during follow‐up >1 IU/dL. 72,9% engaged in some type of physical activity and overall adherence was over 85% in all patients evaluated. The regression analysis performed, considering all these factors, showed that the initiation of prophylaxis before 21 months of age was the most relevant protective factor against the appearance of joint involvement (OR 88.33 p.031 CI 95% 1.49‐5224.40)

Conclusion

Early initiation of prophylaxis was the most relevant factor in the protection of joint status. More comprehensive analysis models adapted to the characteristics of each population, are needed to adequately individualize treatment.
Bleeding control improves after switching to emicizumab: Real‐world experience of 177 children in the PedNet registry
Authors: van der Zwet Konrad , de Kovel Marloes , Motwani Jayashree , van Geet Chris , Nolan Beatrice , Glosli Heidi , Escuriola Ettingshausen Carmen , Königs Christoph , Kenet Gili , Fischer Kathelijn ,   the PedNet Investigators
Published: April 2024

Introduction

Despite the rapid uptake of emicizumab in the paediatric haemophilia A (HA) population, real‐world data on the safety and efficacy is limited.

Aim

To report on bleeding and safety in paediatric patients receiving emicizumab prophylaxis.

Methods

Data were extracted from the multicentre prospective observational PedNet Registry (NCT02979119). Children with haemophilia A, and ≥50 FVIII exposures or inhibitors present receiving emicizumab maintenance therapy were analysed. Data were summarized as medians with interquartile range (IQR, P25–P75). Mean (95% confidence interval (CI)), annualized (joint) bleeding rate (A(J)BR) during emicizumab and ≤2 years before emicizumab prophylaxis were modelled and compared using negative binomial regression.

Results

Total of 177 patients started emicizumab at median 8.6 years (IQR 4.8–13.1), most had no FVIII inhibitors (64%). Follow up before emicizumab was median: 1.68 years (IQR: 1.24–1.90) and during emicizumab: 1.32 years (IQR: .94–2.11).

In patients without inhibitors, mean ABR reduced after starting emicizumab from 2.41 (CI 1.98–2.95) to 1.11 (CI .90–1.36, p < .001), while AJBR reduced from.74 (CI .56–.98) to.31 (CI .21–.46, p < .001). Concordantly, in patients with inhibitors, mean ABR reduced from 5.08 (CI 4.08–6.38) to .75 (CI .56–1.01, p < .001), while AJBR reduced from 1.90 (CI 1.42–2.58) to .34 (CI .21–.56, p < .001). Five emicizumab‐related adverse events were reported (3% of the cohort), including one patient with antidrug antibodies.

Conclusion

This study showed improved bleeding control compared to previous treatment and a favourable safety profile during emicizumab therapy in paediatric haemophilia A patients.
The role of multidisciplinary MS care teams in supporting lifestyle behaviour changes to optimise brain health among people living with MS: A qualitative exploration of clinician perspectives
Authors: Wills Olivia , Probst Yasmine , Haartsen Jodi , McMahon Anne‐Therese
Published: April 2024

Introduction

Healthcare professionals have an important role in advocating for the adoption of a brain‐healthy lifestyle for optimal multiple sclerosis (MS) care. Nonetheless, studies to date have mainly focussed on the consumer perspective. Herein, we aimed to explore the current practices of how healthcare professionals support protective, lifestyle‐related behaviour changes to optimise brain health among people living with MS (plwMS), and their perspectives of professional roles.

Methods

Australian healthcare professionals were recruited via study advertisements, purposive and snowball sampling, to participate in an online, semi‐structured and audio‐recorded interview. Clinicians were eligible if they had a minimum of a tertiary Bachelor's degree and 12‐months experience working with plwMS, access to the Internet and sufficient time to participant. An inductive, data‐driven form of reflexive thematic analysis was undertaken before thematic categorisation of the quotes from transcripts. Data analysis was guided by the methods of Braun and Clark and the study's underpinnings drew on the constructs of the Social Cognitive Theory (SCT).

Results

Six physicians, 10 MS nurses, 18 allied health professionals, one exercise therapist and one alternative therapist were interviewed. Three primary themes encompassing the perceived role of healthcare professionals in supporting a brain‐healthy lifestyle were identified: (1) the empowering role, (2) collaborative role and (3) communicative role. External factors/forces including time constraints, professional expertise, training and skill set, power dynamics, consumer readiness, health literacy, self‐efficacy and motivation are at play, and affect how/when healthcare professionals may support behaviour change to optimise lifelong brain health for plwMS.

Conclusion

Healthcare professionals recognise their critical role in encouraging and supporting the adoption of a brain‐healthy lifestyle to optimise lifelong brain health for plwMS. However, discord is evident when they underestimate the complexity of translating knowledge of lifestyle‐related behaviour change(s) into action. Greater awareness must be made in recognising and addressing the bidirectionality of external factors such as those in the SCT, that may influence how behaviour change occurs.

Public Contribution

Healthcare professionals volunteered to be interviewed as part of the data collection phase of this study.
Periodontal health literacy in Germany—Results of a telephone survey
Authors: Deinzer Renate , Jordan Andreas Rainer
Published: April 2024

Objective

Assess the periodontal health literacy of German adolescents, adults and senior residents.

Background

The prevalence of periodontitis is high. One explanation for this may be that people lack periodontal health literacy (PHL).

Methods

This was a cross‐sectional descriptive study. Former participants of the 5th German Oral Health Study (n = 333 16‐year‐olds, n = 307 39–48‐year‐olds, n = 332 69–78‐year‐olds) participated in a computer‐assisted telephone interview. Open‐ended questions (OEQs) were used to assess the participants' current knowledge. Corresponding single‐ and multiple‐choice questions (SCQs and MCQs) supplemented the OEQs to allow detailed analyses of the nature of the knowledge gaps.

Results

Less than 10% of the participants in the three age groups could explain the term ‘periodontitis’ or select the correct answer in an SCQ. Responding to the OEQs, 89% of 16‐year olds, 64% of 39‐48‐year‐olds, and 59% of 69–78‐year‐olds, could not name any consequence of periodontitis, and 83%, 51%, and 60%, respectively, could not name any risk factors. The OEQs regarding proper oral hygiene behaviour revealed that participants lacked awareness regarding important aspects of oral hygiene (e.g., systematics) or areas to which they should pay attention to (e.g., interdental spaces and gingival margins).

Conclusions

The survey revealed PHL deficits in German adolescents, adults, and seniors and a need for community‐based measures to improve PHL in all age groups. Dental teams should be aware that their patients might lack the PHL necessary for understanding and adherence to professional dental advice, and that they might even lack PHL regarding the proper use of oral hygiene devices.