bluuebunny/crossref_metadata_2025 huggingface dataset:
Deuterated docosahexaenoic acid protects against oxidative stress and geographic atrophy‐like retinal degeneration in a mouse model with iron overload
Authors: Liu Yingrui , Bell Brent A. , Song Ying , Zhang Kevin , Anderson Brandon , Axelsen Paul H. , Bohannan Whitney , Agbaga Martin‐Paul , Park Hui Gyu , James Genevieve , Brenna J. Thomas , Schmidt Karsten , Dunaief Joshua L. , Shchepinov Mikhail S.
Published: March 2022

Oxidative stress plays a central role in age‐related macular degeneration (AMD). Iron, a potent generator of hydroxyl radicals through the Fenton reaction, has been implicated in AMD. One easily oxidized molecule is docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in photoreceptor membranes. Oxidation of DHA produces toxic oxidation products including carboxyethylpyrrole (CEP) adducts, which are increased in the retinas of AMD patients. In this study, we hypothesized that deuterium substitution on the bis‐allylic sites of DHA in photoreceptor membranes could prevent iron‐induced retinal degeneration by inhibiting oxidative stress and lipid peroxidation. Mice were fed with either DHA deuterated at the oxidation‐prone positions (D‐DHA) or control natural DHA and then given an intravitreal injection of iron or control saline. Orally administered D‐DHA caused a dose‐dependent increase in D‐DHA levels in the neural retina and retinal pigment epithelium (RPE) as measured by mass spectrometry. At 1 week after iron injection, D‐DHA provided nearly complete protection against iron‐induced retinal autofluorescence and retinal degeneration, as determined by in vivo imaging, electroretinography, and histology. Iron injection resulted in carboxyethylpyrrole conjugate immunoreactivity in photoreceptors and RPE in mice fed with natural DHA but not D‐DHA. Quantitative PCR results were consistent with iron‐induced oxidative stress, inflammation, and retinal cell death in mice fed with natural DHA but not D‐DHA. Taken together, our findings suggest that DHA oxidation is central to the pathogenesis of iron‐induced retinal degeneration. They also provide preclinical evidence that dosing with D‐DHA could be a viable therapeutic strategy for retinal diseases involving oxidative stress.
A longitudinal approach to understanding risk factors for problem alcohol use during the COVID‐19 pandemic
Authors: Baptist Mohseni Natasha , Morris Vanessa , Vedelago Lana , Kempe Tyler , Rapinda Karli , Mesmer Emily , Bilevicius Elena , Wardell Jeffrey D. , MacKillop James , Keough Matthew T.
Published: March 2022

Background

We conducted a longitudinal study to examine person‐centered heterogeneity in problem drinking risk during the 2019 Coronavirus disease (COVID‐19) pandemic. We aimed to differentiate high‐ from low‐risk subgroups of drinkers during the pandemic, to report on the longitudinal follow‐up of the baseline sample reported in Wardell et al. (Alcohol Clin Exp Res, 44, 2020, 2073), and to examine how subgroups of drinkers differed on coping‐related and pre‐pandemic alcohol vulnerability factors.

Methods

Canadian alcohol users (N = 364) were recruited for the study. Participants completed surveys at four waves (spaced 3 months apart), with the first being 7 to 8 weeks after the COVID‐19 state of emergency began in Canada. The data were analyzed using a parallel process latent growth class analysis followed by general linear mixed models analysis.

Results

We found evidence for three latent classes: individuals who increased drinking (class 1; n = 23), low‐risk drinkers (class 2; n = 311), and individuals who decreased drinking (class 3; n = 30). Participants who increased (vs. those who decreased) problem drinking during the pandemic struggled with increasing levels of social disconnection and were also increasingly more likely to report drinking to cope with these issues. Those in the increasing class (relative to low‐risk drinkers) reported increasing levels of depression during the study. Relative to low‐risk drinkers, participants in the increasing class had higher pre‐pandemic AUDIT scores, greater frequency of solitary drinking, and higher alcohol demand. Interestingly, participants in the decreasing class had the highest pre‐pandemic AUDIT scores.

Conclusions

We examined longitudinal data to identify subgroups of drinkers during the pandemic and to identify factors that may have contributed to increased problem drinking. Findings suggest that while most of the sample did not change their alcohol use, a small portion of individuals escalated use, while a small portion decreased their drinking. Identifying the vulnerability factors associated with increased drinking could aid in the development of preventative strategies and intervention approaches.
A new monocyte epigenetic clock reveals nonlinear effects of alcohol consumption on biological aging in three independent cohorts (N = 2242)
Authors: Liang Xiaoyu , Sinha Rajita , Justice Amy C. , Cohen Mardge H. , Aouizerat Bradley E. , Xu Ke
Published: March 2022

Background

Assessing the effect of alcohol consumption on biological age is essential for understanding alcohol use‐related comorbidities and mortality. Previously developed epigenetic clocks are mainly based on DNA methylation in heterogeneous cell types, which provide limited knowledge on the impacts of alcohol consumption at the individual cellular level. Evidence shows that monocytes play an important role in both alcohol‐induced pathophysiology and the aging process. In this study, we developed a novel monocyte‐based DNA methylation clock (MonoDNAmAge) to assess the impact of alcohol consumption on monocyte age.

Methods

A machine learning method was applied to select a set of chronological age‐associated DNA methylation CpG sites from 1202 monocyte methylomes. Pearson correlation was tested between MonoDNAmAge and chronological age in three independent cohorts (Ntotal = 2242). Using the MonoDNAmAge clock and four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on epigenetic aging in the three cohorts [i.e., Yale Stress Center Community Study (YSCCS), Veteran Aging Cohort Study (VACS), Women's Interagency HIV Study (WIHS)] using linear and quadratic models.

Results

The MonoDNAmAge, comprised of 186 CpG sites, was moderately to strongly correlated with chronological age in the three cohorts (r = 0.90, p = 3.12E−181 in YSCCS; r = 0.54, p = 1.75E−96 in VACS; r = 0.66, p = 1.50E−60 in WIHS). More importantly, we found a nonlinear association between MonoDNAmAge and alcohol consumption (pmodel = 4.55E−08,  = 7.80E−08 in YSCCS; pmodel = 1.85E−02,  = 3.46E−02 in VACS). Heavy alcohol consumption increased EAAMonoDNAmAge up to 1.60 years while light alcohol consumption decreased EAAMonoDNAmAge up to 2.66 years. These results were corroborated by the four established epigenetic clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge).

Conclusions

The results suggest a nonlinear relationship between alcohol consumption and its effects on epigenetic age. Considering adverse effects of alcohol consumption on health, nonlinear effects of alcohol use should be interpreted with caution. The findings, for the first time, highlight the complex effects of alcohol consumption on biological aging.
Does delirium prevention reduce risk of in‐patient falls among older adults? A systematic review and trial sequential meta‐analysis
Authors: He Steven , Rolls Kaye , Stott Katrina , Shekhar Rozina , Vueti Vaulina , Flowers Kelli , Moseley Margaret , Shepherd Bernadette , Mayahi‐Neysi Mandana , Chasle Briony , Warner Bradley , Ni Chroinin Danielle , Frost Steven A.
Published: March 2022

Objectives

To determine whether delirium prevention interventions reduce the risk of falls among older hospitalised patients.

Methods

A systematic search of health‐care databases was undertaken. Given the frequency of small sample sized trials, a trial sequential meta‐analysis was conducted to present estimate summary effects to date. A Bayesian approach was used to estimate the posterior probability of the delirium prevention interventions reducing falls risk by various clinically relevant levels.

Results

Five randomised controlled trials were included in our final meta‐analysis. There was a 43% reduction in the risk of falls among participants in the delirium prevention intervention arm, compared to the control; however, confidence intervals were wide (RE RR = 0.57, 95% CI 0.32; 1.00, p = 0.05). This result was found to be statistically significant, according to traditional significance levels (z > 1.96) and the more conservative trial sequential analysis monitoring boundaries. The posterior probabilities of the delirium prevention intervention reducing the risk of falls by 10%, 20% and 30% were 0.86, 0.63 and 0.29 respectively.

Conclusions

The results of this systematic review and trial sequential meta‐analysis suggest that delirium prevention trials may reduce the risk of in‐hospital falls among older patients by 43%. However, despite significant risk reduction found upon meta‐analysis, the variation among study populations and intervention components raised questions around its application in clinical practice. Further research is required to investigate what the necessary components of a multifactorial intervention are to reduce both delirium and fall incidence among older adult in‐patients.
Hypoxia and inflammation conditions differentially affect the expression of tissue transglutaminase spliced variants and functional properties of extravillous trophoblast cells
Authors: Arbildi Paula , Rodríguez‐Camejo Claudio , Perelmuter Karen , Bollati‐Fogolín Mariela , Sóñora Cecilia , Hernández Ana
Published: March 2022

Problem

Persistent hypoxia and inflammation beyond early pregnancy are involved in a bad outcome because of defective trophoblast invasiveness. Tissue transglutaminase (TG2) coregulates several cell functions. An aberrant expression and/or transamidation activity could contribute to placental dysfunction.

Method of study

The first‐trimester trophoblast cell line (Swan‐71) was used to study TG2 expression and cell functions in the absence or presence of inflammatory cytokines (TNF‐α, IL‐1β) or chemical hypoxia (CoCl2). We analyzed The concentration of cytokines in the supernatant by ELISA; Cell migration by scratch assay; NF‐κB activation by detection of nuclear p65 by immunofluorescence or flow cytometry using a Swan‐71 NF‐κB‐hrGFP reporter cell line. Tissue transglutaminase expression was analyzed by immunoblot and confocal microscopy. Expression of spliced mRNA variants of tissue transglutaminase was analyzed by RT‐PCR. Transamidation activity was assessed by flow cytometry using 5‐(biotinamido)‐pentylamine substrate.

Results

Chemical hypoxia and TGase inhibition, but not inflammatory stimuli, decreased Swan‐71 migration. IL‐6 production was also decreased by chemical hypoxia, but increased by inflammation. Intracellular TGase activity was increased by all stimuli, but NF‐κB activation was observed only in the presence of proinflammatory cytokines. TG2 expression was decreased by CoCl2and TNF‐α. Translocation of TG2 and p65 to nuclei was observed only with TNF‐α, without colocalization. Differential relative expression of spliced variants of mRNA was observed between CoCl2and inflammatory stimuli.

Conclusion

The observed decrease in total TG2 expression and relative increase in short variants under hypoxia conditions could contribute to impaired trophoblast invasion and impact on pregnancy outcome.
Views and practice of abortion among Queensland midwives and sexual health nurses
Authors: Desai Aakanksha , Maier Belinda , James‐McAlpine Janelle , Prentice Daniel , de Costa Caroline
Published: March 2022

Background

A significant barrier to the access of safe abortion is the lack of trained abortion providers. Recent studies show that with appropriate education, nurses and midwives can provide abortions as safely as medical practitioners.

Aims

To examine the attitudes and practices of registered midwives (RMs) and sexual health nurses (SHNs) in Queensland toward abortion.

Materials and Methods

A cross‐sectional mixed‐methods questionnaire was distributed to RMs and SHNs from the Queensland Nursing and Midwifery Union. Data were described and analysed both quantitatively and qualitatively.

Results

There was a 20% response rate (n = 624) to the survey from the overall study population. There were 53.5% who reported they would support the provision of abortion in any situation at all; 7.4% held views based on religion or conscience that would make them completely opposed to abortion. There were 92.9% who felt that education surrounding abortion should be part of the core curriculum for midwifery and/or nursing students in Australia. The qualitative responses demonstrated a variety of views and suggestions regarding the practice of abortion.

Conclusions

There was a wide variation in views toward induced abortion from RMs and SHNs in Queensland. While a proportion of respondents opposed abortion in most circumstances, a significant group was in support of abortion in any situation and felt involvement in initiating and/or performing abortion would be within the scope of RMs and SHNs.
Psychological benefits of outdoor physical activity in natural versus urban environments: A systematic review and meta‐analysis of experimental studies
Authors: Wicks Claire , Barton Jo , Orbell Sheina , Andrews Leanne
Published: March 2022

The impact of environmental context on the psychological benefits derived from physical activity has attracted research attention in recent years. Previous reviews have compared effects of indoor versus outdoor exercise. This review compares the effects of physical activity undertaken in outdoor green natural environments versus outdoor urban environments on psychological health outcomes in adult general populations. An electronic literature search identified 24 experimental studies meeting the inclusion criteria. Results were analysed via narrative synthesis (n = 24) and meta‐analysis (n = 9) of effect on six outcomes. Narrative synthesis found in favour of the natural environment for anxiety, anger/hostility, energy, affect and positive engagement. Post‐intervention effect sizes suggested duration and social context as potential moderators. The meta‐analyses revealed large or moderate effects in favour of the natural environment for anxiety, fatigue, positive affect and vigour, and a small effect for depression. Results were subject to high risk of bias and heterogeneity. Physical activity undertaken outdoors in natural environments is more beneficial for a range of psychological outcomes compared with urban environments. The various effect sizes evident in the meta‐analyses may be explained by differing mechanisms through which psychological gains are experienced during physical activity in nature.
Von Willebrand factor assays in patients with acquired immune thrombotic thrombocytopenia purpura treated with caplacizumab
Authors: Bowyer Annette , Brown Paula , Hopkins Barbara , Scully Marie , Shepherd Fiona , Lowe Anna , Mensah Patrick , Maclean Rhona , Kitchen Steve , van Veen Joost J.
Published: March 2022

Acquired immune thrombotic thrombocytopenic purpura (iTTP) is a rare disease with a poor prognosis if undiagnosed. It is caused by autoantibody production to the von Willebrand factor (VWF) cleaving protease, A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Caplacizumab, an immunoglobulin directed to the platelet glycoprotein Ibα receptor of VWF, has been reported to induce quicker resolution of iTTP compared to placebo. The laboratory measurement of VWF activity was significantly reduced in clinical trials of caplacizumab. Several VWF assays are available in the UK and this study investigated whether differences in VWF parameters were present in 11 patients diagnosed with iTTP and treated with daily caplacizumab. Chromogenic factor VIII activity, VWF antigen, collagen binding activity, VWF multimers and six VWF activity assays were measured prior to caplacizumab therapy and on several occasions during treatment. VWF antigen and collagen binding activity levels were normal or borderline normal in all patients. Ultra‐large molecular weight multimers were present in all patients following treatment. VWF activity assays were normal or reduced during treatment, but this was reagent and patient dependant. In the unusual scenario of a caplacizumab‐treated patient requiring measurement of VWF activity, it is important that laboratories understand how their local reagents perform as results cannot be predicted.
Comparison of the prognostic value of microscopically measured invasive width versus macroscopic width in cutaneous melanoma shows the superiority of microscopic invasive width measurement
Authors: Bamford Mark , Udensi Louisa , Khanna Arushi , O'Riordan Marie , Saldanha Gerald
Published: March 2022

Background

Invasive width, the distance between the most peripheral invasive melanoma cells on the section where Breslow thickness (BT) was measured, was recently identified as a prognostic feature. It is unclear whether a routine measurement is justified, given that macroscopic width is already included in many melanoma histopathology reports and may itself be a prognostic feature. This study sought to investigate this.

Methods

A retrospective cohort of 718 melanoma patients in which macroscopic width had been stated in the original histopathology report was used. Survival analysis was performed.

Results

Macroscopic and invasive widths were positively correlated (p < 0.001). Invasive width was typically smaller than the paired macroscopic width (median difference 3.7 mm,p < 0.001), a difference seen across all T groups. Both macroscopic and invasive widths were significantly associated with melanoma survival in Kaplan–Meier analysis, including overall survival, but invasive width survival curves were more widely separated. Both were significantly associated with outcome after correction for BT in Cox proportional hazards regression, but the models containing invasive width had a substantially better fit.

Conclusions

This study shows that both macroscopic and invasive widths have prognostic values, but confirms that the latter is superior. It supports further investigation of this feature's prognostic value.
Feasibility study of a prototype extended‐wear insulin infusion set in adults with type 1 diabetes
Authors: Kastner Jasmin R. , Venkatesh Nisha , Brown Katie , Muchmore Douglas B. , Ekinci Elif , Fourlanos Spiros , Joseph Jeffrey I , Shafeeq Miami , Shi Leon , Strange Poul , Strasma Paul J. , O'Neal David N.
Published: March 2022

Aim

To assess the feasibility of a prototype insulin infusion set (IIS) for extended wear in adults with type 1 diabetes.

Materials and Methods

The prototype Capillary Biomedical investigational extended‐wear IIS (CBX IIS) incorporates a soft, flexible, reinforced kink‐resistant angled nylon‐derivative cannula with one distal and three proximal ports to optimize insulin delivery. Twenty adult participants with type 1 diabetes established on insulin pump therapy used the CBX IIS for two 7‐day test periods while wearing a Dexcom G5 continuous glucose monitor.

Results

Participants were able to wear the CBX IIS for an average of 6.6 ± 1.4 days. Eighty‐eight percent (36 of 41) of sets were worn for 7 days. No serious adverse events were reported. Five infusion sets failed prematurely because of: unresolvable hyperglycaemia (three); hyperglycaemia with elevated ketones (one); or infection (one). Median time in range (3.9‐10.0 mmol/L) was 62% (54‐76). Average glucose levels per day of infusion set wear showed a statistically significant increase over time (p < .001).

Conclusions

Our preliminary observations confirm the tolerability of the prototype CBX IIS for extended wear, albeit with a deterioration in glucose control after the third day.
The impact of empirically unverified taxonomic concepts on ecological assemblage patterns across multiple spatial scales
Authors: Nekola Jeffrey C. , Horsák Michal
Published: March 2022

Accurate ecological assemblage analysis requires that underlying taxonomic divisions reflect biological reality. However, the validity of many taxonomic hypotheses have never been rigorously confronted with replicable data. As a result, these categories might say more about human psychology than biology. We consider here the ways that statistically unchallenged taxonomic concepts can bias observed ecological pattern across multiple spatial scales. We compared assemblage lists for a group of Holarctic land snail species/subspecies hypotheses both before and after empirical confrontation. Of the 124 taxa initially believed to exist, only 105 were validated, with 34 being oversplit, another 15 being incorrectly lumped within 11 taxa and a final 33 having incorrect identification features. This led to considerable scale‐dependent alteration in assemblage patterns across 2528 sites within 42 regions and 9 biogeographic zones: depending upon location up to 90% of sites had revised composition with 10% showing a reduction in richness. Additionally, 6–60% of site pairs had altered turnover. These impacts became larger and more frequent with increasing sample grain and extent: 80–90% of regions and 100% of global biogeographic zones demonstrated altered composition, with 70–80% of regions and 100% of zones having changed richness. Reductions in richness also became more prevalent with increasing scale. Likewise, 80–94% of regional and zone pairs were found to have altered turnover, with increased similarity predominating at small and decreased similarity at large extents. Because these issues appear general and are not limited to land snail taxonomy, it is crucial for macroecologists to consider how unchallenged taxonomic concepts might bias their results. The use of objective and replicable data‐driven validation of all recognized taxonomic concepts is thus an essential foundation for accurate ecological hypothesis testing.
Prevalence of disability improvement in relapsing–remitting multiple sclerosis patients treated with cladribine tablets
Authors: Signori Alessio , Ponzano Marta , Alexandri Nektaria , Giovannoni Gavin , Sormani Maria Pia
Published: March 2022

Background and purpose

The aim was to show the application of the prevalence estimator of Expanded Disability Status Scale (EDSS) improvement over time in patients treated with cladribine tablets in the phase III CLARITY/CLARITY extension trials.

Methods

Relapsing–remitting multiple sclerosis patients who entered the CLARITY extension study were evaluated. Patients originally randomized in CLARITY to cladribine tablets 3.5 mg/kg and placebo in CLARITY extension (early cladribine [EC]) were compared to patients originally randomized to placebo and then assigned to cladribine tablets 3.5 mg/kg (delayed cladribine [DC]). The EC group was compared to the DC group on the prevalence of EDSS improvement over time and on the cumulative incidence of EDSS improvement. Prevalence of improvement was assessed by a new approach based on the difference of Kaplan–Meier estimators, whilst the incidence of improvement was assessed by standard Kaplan–Meier curves.

Results

A total of 98 patients in the EC group and 244 patients in the DC group were compared. Patients in the EC group showed a significantly higher (p = 0.011) prevalence of improvement at year 2 (EC 21.3%, 95% confidence interval [CI] 13.6–29.3; DC 8.9%, 95% CI 5.5–12.8) and at year 5 (EC 15.7%, 95% CI 8.2–23.7; DC 8.3%, 95% CI 4.5–12.4). The cumulative incidence of improvement was also significantly different (hazard ratio 1.82, 95% CI 1.13–2.94, p = 0.013).

Conclusions

Assessment of the prevalence of EDSS improvement is an alternative outcome to assess if a treatment induces and maintains an improvement over the long term. This estimator was found to be more powerful than the cumulative incidence of improvement to detect a treatment effect of cladribine versus placebo over 5 years.
Searching for veterinary evidence: A guide for equine professionals
Authors: White Constance , Moberly Heather K. , Fausak Erik D. , Boulton Clare , Shrubb Julia , McGillycuddy Laura , Everitt Sally M. , Nunn Sandra D. , Brennan Marnie Louise
Published: March 2022

There is more and more online information available at our fingertips, but how do we efficiently identify and extract relevant information for good clinical decision making? The aim of this review article is to provide equine professionals with the building blocks to be able to develop skills for expertly navigating the scientific literature in a timely fashion. This includes what key questions you need to ask before starting (why am I searching and how much time do I have), where the best places are to search and how to find freely available legal copies of papers (articles, conference proceedings, book chapters and dissertations). Additionally, how to best conduct an information search and what you get from searches of varying comprehensiveness. Finally, this article will cover where to find databases of research syntheses where others have already carried out the hard work for you and some advanced techniques which are likely to save you substantial amounts of time. This article draws together expertise from a panel of veterinary clinicians, nurses and technicians, information specialists and librarians and clinical researchers.
A hybrid one‐class approach for detecting anomalies in industrial systems
Authors: Zayas‐Gato Francisco , Jove Esteban , Casteleiro‐Roca José‐Luis , Quintián Héctor , Piñón‐Pazos Andrés , Simić Dragan , Calvo‐Rolle José Luis
Published: March 2022

The significant advance of Internet of Things in industrial environments has provided the possibility of monitoring the different variables that come into play in an industrial process. This circumstance allows the supervision of the current state of an industrial plant and the consequent decision making possibilities. Then, the use of anomaly detection techniques are presented as a powerful tool to determine unexpected situations. The present research is based on the implementation of one‐class classifiers to detect anomalies in two industrial systems. The proposal is validated using two real datasets registered during different operating points of two industrial plants. To ensure a better performance, a clustering process is developed prior the classifier implementation. Then, local classifiers are trained over each cluster, leading to successful results when they are tested with both real and artificial anomalies. Validation results present in all cases, AUC values above 90%.
Population density estimates for terrestrial mammal species
Authors: Santini Luca , Benítez‐López Ana , Dormann Carsten F. , Huijbregts Mark A. J.
Published: March 2022

Aim

Population density is a key parameter in ecology and conservation, and estimates of population density are required for a wide variety of applications in fundamental and applied ecology. Yet, in terrestrial mammals these data are available for only a minority of species, and their availability is taxonomically and geographically biased. Here, we provide the most plausible predictions of average population density, their natural variability and statistical uncertainty for 4,925 terrestrial mammal species.

Location

Global.

Time period

1970–2021.

Major taxa studied

Terrestrial mammals.

Methods

We fitted an additive mixed‐effect model accounting for spatial and phylogenetic autocorrelation on a dataset including 5,412 average population density estimates for 737 species. Average density was modelled as a function of body mass, diet, locomotor habits and environmental conditions. We validated the model using spatial and taxonomic block cross‐validation and used the estimated error to quantify the uncertainty around statistical predictions of population density for 4,925 mammal species.

Results

Small body size, fossorial behaviour and herbivorous diets were associated with the highest population densities, whereas large size, aerial behaviour and carnivorous diets were related to the lowest densities. Species in non‐seasonal environments yielded higher densities than species in environments with high precipitation seasonality. Empirical estimates of population density vary by about four times on average within the same species, and statistically independent predictions for the majority of species deviate by about five times from observed values, indicating that prediction errors are similar to the natural variability in population densities.

Main conclusions

Our predictions and uncertainty estimates of average population densities open up a number of applications in macroecology and conservation biogeography, including biomass estimation, setting population targets in conservation assessments and planning, and supporting Red List assessments. The methodology can be replicated easily for other taxonomic groups with a representative sample of georeferenced density estimates.
THEORIZING AND PRACTICING HISTORY AS THE METABOLIZATION OF THE WORLD: A CONVERSATION WITH HANS ULRICH GUMBRECHT
Authors: JONES‐KATZ GREGORY
Published: March 2022

In this exchange, Gregory Jones‐Katz and Hans Ulrich Gumbrecht discuss Gumbrecht's oeuvre, his book on Denis Diderot, and what this all might offer historians as they grapple with a transforming professional and intellectual landscape in the not‐so‐early twenty‐first century. Of broad significance to the field of historical theory and practice are Gumbrecht's explorations into the “presence”‐based epistemologies embedded in often‐canonical cultural protagonists’ lives and works. In his new book on Diderot, for example, Gumbrecht creates and employs a concept of our metabolic relationship to the environment to understand Diderot's “implicit epistemology” as a way of thinking that was peripheral to Enlightenment and its “historical worldview.” Gumbrecht's concept of metabolism describes certain intellectual operations that were emblematic for Diderot (and his times) and can also prove useful for historians (and humanists) in different contemporary contexts.
Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019
Authors: Aydin Guclu Ozge , Goktas Seda S. , Gorek Dilektasli Asli , Acet Ozturk Nilufer A. , Demirdogen Ezgi , Coskun Funda , Ediger Dane , Ursavas Ahmet , Uzaslan Esra , Erol Hasim A. , Karacay Nurdan D. , Kaya Sel Umut , Karadag Mehmet
Published: March 2022

Background

Laboratory biomarkers to estimate the severity of coronavirus disease 2019 (COVID‐19) are crucial during the pandemic since resource allocation must be carefully planned.

Aims

To evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalised with COVID‐19.

Methods

Patients hospitalised with confirmed COVID‐19 were included in the study. Laboratory data and total IgE levels were measured on admission. Lymphocyte, eosinophil, ferritin, d‐dimer and C‐reactive protein parameters were recorded at baseline and on the 3rd and 14th days of hospitalisation.

Results

The study enrolled 202 patients, of which 102 (50.5%) were males. The average age was 50.17 ± 19.68 years. Of the COVID‐19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 (0–2124) vs 38.70 (0–912); P < 0.001) and serum eosinophil levels were significantly lower (0.015 (0–1.200) vs 0.040 (0–1.360); P = 0.002) in clinically worsened COVID‐19 patients when compared with stable patients. The optimal cut‐off for predicting clinical worsening was 105.2 ng/L, with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve = 0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and C‐reactive protein levels as independent predictors.

Conclusions

Our single‐centre pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalised due to COVID‐19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID‐19 infections.
Substance use among vocational trainees in Australia: differences between medical specialties
Authors: Wong Rachel X. Y. , Farrell Michael , Degenhardt Louisa , Memedovic Sonja , Harvey Samuel B. , Petrie Katherine
Published: March 2022

Background

There have been few large‐scale nationally representative studies on the prevalence of substance use among doctors. In addition, the association of different medical specialties with the use of different substances requires further research.

Aims

To investigate how the use of alcohol, tobacco and illicit drugs varied between junior doctors enrolled in different specialty training programmes.

Methods

A secondary analysis was conducted on a national survey of 12 252 Australian doctors. The population of interest was junior doctors currently enrolled in a specialty training programme, termed vocational trainees (VT; n = 1890; 15.4% of the overall sample). Self‐report prevalence of current alcohol, tobacco and illicit drug use were assessed and hazardous alcohol use was assessed using the Alcohol Use Disorders Identification Test. Logistic regression was used to examine the association between specialty and substance use, adjusting for demographic characteristics when required.

Results

One in six VT reported hazardous levels of alcohol use (n = 268; 17.3%). After adjusting for confounders, the association between the prevalence of alcohol use and the specialties of emergency medicine/intensive care unit (odds ratio (OR) 2.15; 95% confidence interval (CI) 1.40–3.32; P < 0.001), anaesthetics (OR 2.53; 95% CI 1.35–4.76; P = 0.004) and obstetrics/gynaecology (OR 1.89; 95% CI 1.19–3.02; P = 0.007) remained significant. No significant associations were found between tobacco use/illicit drug use/hazardous alcohol use and medical specialty.

Conclusions

While rates of substance use and hazardous alcohol use in VT are similar, if not lower, than the general population, it poses a concern that there are higher rates of alcohol use in certain medical specialties.
An Uncertainty Argument for the Identified Victim Bias
Authors: Zameska Jay A.
Published: March 2022

Do we have a reason to prioritize saving identified lives over statistical lives? Most philosophers say no. Many find it difficult to offer a reason for doing so that does not violate other moral constraints – for example, respect for the moral equality of persons. In this article, I provide an argument in favor of the ‘identified victim bias’. I rely on a contractualist framework to argue that in cases of ex ante uncertainty – that is, cases where individuals are unaware whether they will ultimately end up in either the identified or statistical group and, thus, do not know the exact probabilities assigned to their choices – we should prioritize saving identified lives. Further, I explain that in ‘real world’ cases, this kind of uncertainty is very common. I demonstrate the consequences of this argument by examining an applied case that deals with the question of identified versus statistical lives – choosing between providing expensive retroviral treatment for current AIDS patients or increasing the availability of preventive measures for HIV. I argue that the uncertainty argument gives us a reason to fund AIDS treatment, even though HIV prevention may be more cost effective and save more lives.
A longitudinal analysis of the growth rate and mass of tail feathers in a great tit population: ontogeny, genetic effects and relationship between both traits
Authors: de la Hera Iván , Reichert Michael S. , Davidson Gabrielle L. , Quinn John L.
Published: March 2022

Feathers have a diversity of functions in birds and are costly to produce, so their growth rate and mass can be reliable indicators of nutritional condition at the time of production. Despite the potential for feather metrics to advance our understanding of foraging, they are underused in avian ecology. One reason for this is the difficulty of interpreting whether individual variation is driven by ontogenetic, genetic or environmental effects, which is exacerbated by the fact that most analyses have been done on cross‐sectional data. We addressed this deficit using a longitudinal dataset of tail feathers collected from great titsParus majorto test for ontogenetic and genetic effects on growth rate, mass and length, while controlling for body/feather size differences and other confounding factors. First, we found that the type of moult episode and experimentally‐induced replacement differentially affected the length, mass and growth of feathers, providing evidence of an ontogenetic effect that should be considered when comparing these feather traits across individuals as a measure of condition. Second, we detected moderate to high repeatability and heritability values from parent–offspring regression for these three feather traits, which are suggestive of an underlying genetic component of variation. Third, we used a mean centring within‐individual approach to test whether feather growth rate and feather mass (length‐corrected) are indeed positively correlated with each other as overlapping indicators of body condition in birds, and found that this association, although positive, is weak and only significant between individuals. This suggests that both metrics are not so intimately linked as originally thought, and probably have different sensitivities to variation in foraging performance and ecological conditions. Together with the higher plasticity of feather growth rate compared to feather mass, our results support the idea that feather growth rate is better suited for examining short‐term responses to environmental variation.
Defining moults in migratory birds: a sequence‐based approach
Authors: Pyle Peter
Published: March 2022

Two broad nomenclatures have emerged to describe moult strategies in birds, the ‘life‐cycle' system which describes moults relative to present‐day breeding and other life‐history events, and the Humphrey–Parkes (H–P) system which reflects the evolution of moults along ancestral lineages. Using either system, challenges have arisen defining strategies in migratory species with more than one moult per year. When all or part of two moults occur in non‐breeding areas, extra moults may fail to be recognized or they may have been discriminated temporally, whether feathers are replaced in fall, winter or spring. But in some cases feather replacement can span the non‐breeding period, and this has resulted in an inability to identify inserted moults and to compare moult strategies between species. Furthermore, recent analyses on factors influencing the extent of the postjuvenile or preformative moults have either confined this moult to the summer grounds or presumed that it can be suspended and resumed on winter grounds, which has lead to quite divergent results and interpretations. Evolutionarily, the timing, extent and location of moults show phenotypic lability whereas the sequence in which feathers are replaced is comparatively conserved. As, such, I propose defining moults on the basis of feather‐replacement sequences as opposed to timing or location of replacement, including strategies in which discrete moults can be suspended for migration and overlap temporally. I provide examples illustrating the functionality of a sequence‐based definition in three migratory North American passerines that can undergo feather replacement twice in non breeding areas, and I demonstrate how this system can effectively apply to moults in many other passerine and non‐passerine species. I recommend that authors studying the evolutionary drivers of moult strategies in migratory birds adopt a sequence‐based approach and to carefully consider replacement strategies both prior to and following autumn migration.
Artificial intelligence and atrial fibrillation
Authors: Sehrawat Ojasav , Kashou Anthony H. , Noseworthy Peter A.
Published: March 2022

Background

In the context of atrial fibrillation (AF), traditional clinical practices have thus fallen short in several domains, such as identifying patients at risk of incident AF or patients with concomitant undetected paroxysmal AF. Novel approaches leveraging artificial intelligence have the potential to provide new tools to deal with some of these old problems.

Aims

To discuss the roles of artificial intelligence (AI)‐enabled electrocardiogram (ECG) pertaining to AF, potential roles of deep learning (DL) models in the context of current knowledge gaps, as well as limitations of these models.

Materials & Methods

An extensive search and review of the currently available literature on the topics.

Results

One key area where DL models can translate to better patient outcomes is through automated ECG interpretation. Challenges with regards to the benefits and harms of AF screening remain. In this context, a unique model was developed to detect underlying hidden AF from sinus rhythm.

Discussion

Knowledge gaps remain regarding the best ways to monitor patients with embolic stroke of undetermined source (ESUS) and identifying those who would benefit most from oral anticoagulation. The AI‐enabled AF model is one potential way to tackle this complex problem as it could be used to identify a subset of high‐risk ESUS patients likely to benefit from empirical oral anticoagulation. The role of DL models assessing AF burden from long‐duration ECG data is also discussed as a way of guiding management. There is a trend towards the use of consumer‐grade wristbands and watches to detect AF from photoplethysmography data. However, ECG currently remains the gold standard to detect arrythmias including AF. Lastly, the role of adequate external validation of the models and clinical trials to study true performance is discussed.

Conclusion

Algorithms using AI to interpret ECGs in various new ways have been developed. While still, much work needs to be done, these technologies have shown enormous potential in a short span of time. With further advancements and continuous research, these novel ways of interpretation may well become part of everyday clinical workflow.
Human induced pluripotent stem cells integrate, create synapses and extend long axons after spinal cord injury
Authors: Lavoie Nicolas Stoflet , Truong Vincent , Malone Dane , Pengo Thomas , Patil Nandadevi , Dutton James R. , Parr Ann M.
Published: March 2022

Numerous interventions have been explored in animal models using cells differentiated from human induced pluripotent stem cells (iPSCs) in the context of neural injury with some success. Our work seeks to transplant cells that are generated from hiPSCs into regionally specific spinal neural progenitor cells (sNPCs) utilizing a novel accelerated differentiation protocol designed for clinical translation. We chose a xenotransplantation model because our laboratory is focused on the behaviour of human cells in order to bring this potential therapy to translation. Cells were transplanted into adult immunodeficient rats after moderate contusion spinal cord injury (SCI). Twelve weeks later, cells derived from the transplanted sNPCs survived and differentiated into neurons and glia that filled the lesion cavity and produced a thoracic spinal cord transcriptional program in vivo. Furthermore, neurogenesis and ionic channel expression were promoted within the adjacent host spinal cord tissue. Transplanted cells displayed robust integration properties including synapse formation and myelination by host oligodendrocytes. Axons from transplanted hiPSC sNPC‐derived cells extended both rostrally and caudally from the SCI transplant site, rostrally approximately 6 cm into supraspinal structures. Thus, iPSC‐derived sNPCs may provide a patient‐specific cell source for patients with SCI that could provide a relay system across the site of injury.
Downregulation of MEG3 and upregulation of EZH2 cooperatively promote neuroblastoma progression
Authors: Ye Mujie , Gao Runnan , Chen Shiyu , Wei Meng , Wang Jing , Zhang Bowen , Wu Suwen , Xu Yuexin , Wu Peixuan , Chen Xin , Ma Jing , Ma Duan , Dong Kuiran
Published: March 2022

Neuroblastoma (NB), an embryonic tumour originating from sympathetic crest cells, is the most common extracranial solid tumour type in children with poor overall prognosis. Accumulating evidence has demonstrated the involvement of long non‐coding RNA (lncRNA) in numerous biological processes and their associations with embryonic development and multiple diseases. Ectopic lncRNA expression is linked to malignant tumours. Previous studies by our team indicate that MEG3 attenuates NB autophagy through inhibition of FOXO1 and epithelial‐mesenchymal transition via the mTOR pathway in vitro. Moreover, MEG3 and EZH2 negatively regulate each other. In present study, we first collected 60 NB tissues and 20 adjacent tissues for Quantitative real‐time polymerase chain reaction (Q‐PCR) experiments and performed clinical correlation analysis of the results. At the same time, nude mice were used for subcutaneous tumour formation to detect the effect of MEG3 in vivo. Two NB cell lines, SK‐N‐AS and SK‐N‐BE(2)C, were overexpressed MEG3 and rescued with EZH2 and then were subjected to proliferation, migration, invasion, apoptosis and autophagy experiments. RNA‐binding protein immunoprecipitation (RIP) and Co‐Immunoprecipitation (Co‐IP) experiments were performed to explore the molecular mechanism of MEG3 and EZH2 interaction. Q‐PCR revealed that MEG3 expression was negatively correlated with INSS stage and risk grade of NB. Moreover, MEG3 overexpression was associated with inhibition of NB growth in vivo. MEG3 exerted an anti‐cancer effect via stimulatory effects on EZH2 ubiquitination leading to its degradation. Conversely, EZH2 interacted with DNMT1 and HDAC1 to induce silencing of MEG3. The EZH2 inhibitor, DZNep, and HDAC inhibitor, SAHA, displayed synergistic activity against NB. Combined treatment with DZNep and SAHA inhibited proliferation, migration and invasion of NB through suppression of the PI3K/AKT/mTOR/FOXO1 pathway. In conclusion, downregulation of MEG3 and upregulation of EZH2 forms a feedback loop that concertedly promotes the development of NB. Combined blockage of EZH2 and HDAC1 with the appropriate inhibitors may therefore present an effective treatment strategy for NB cases with low MEG3 and high EZH2 expression.
Dual resistance to Flavobacterium psychrophilum and Myxobolus cerebralis in rainbow trout (Oncorhynchus mykiss, Walbaum)
Authors: Avila Brian W. , Winkelman Dana L. , Fetherman Eric R.
Published: March 2022

Aquatic pathogens are a major concern for fish hatchery production, fisheries management, and conservation, and disease control needs to be addressed. Two important salmonid pathogens are Myxobolus cerebralis and Flavobacterium psychrophilum that cause whirling disease and bacterial coldwater disease (BCWD), respectively. Innate disease resistance is a potential option for reducing disease‐related mortality in hatchery‐reared rainbow trout (Oncorhynchus mykiss, Walbaum). Two experiments were conducted to assess pathogen resistance of first‐generation (F1) rainbow trout created by crossing M. cerebralis‐ and F. psychrophilum‐resistant strains. In the first experiment, we exposed two rainbow trout strains and one F1 cross to six treatments: control (no exposure), mock injection, F. psychrophilum only, M. cerebralis only, F. psychrophilum then M. cerebralis, and M. cerebralis then F. psychrophilum. Results indicated that the F1 cross was not resistant to either pathogen. In the second experiment, we exposed five rainbow trout strains and four rainbow trout crosses to F. psychrophilum. The second experiment indicated that at least one rainbow trout cross was F. psychrophilum‐resistant. Achieving dual resistance may be possible using selective breeding but only some multigenerational strains are suitable candidates for further evaluation.