bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of methods for measuring spatial access to health care
Authors: Drake Coleman , Nagy Dylan , Nguyen Thuy , Kraemer Kevin L. , Mair Christina , Wallace David , Donohue Julie
Published: July 2021

Objective

To compare measures of spatial access to care commonly used by policy makers and researchers with the more comprehensive enhanced two‐step floating catchment area (E2SFCA) method.

Study Setting

Fourteen southwestern Pennsylvania counties.

Study Design

We estimated spatial access to buprenorphine‐waivered prescribers using three commonly used measures—Euclidean travel distance to the closest prescriber, travel time to the closest provider, and provider‐to‐population ratios—and the E2SFCA. Unlike other measures, the E2SFCA captures provider capacity, potential patient volume, and travel time to prescribers.

Data Collection/Extraction Methods

We measured provider capacity as the number of buprenorphine prescribers listed at a given address in the Drug Enforcement Agency's 2020 Controlled Substances Act Registrants Database, and we measured potential patient volume as the number of nonelderly adults in a given census tract as reported by the 2018 American Community Survey. We estimated travel times between potential patients and prescribers with Bing Maps and Mapbox application programming interfaces. We then calculated each spatial access measure using the R programming language. We used each measure of spatial access to identify census tracts in the lowest quintile of spatial access to prescribers.

Principal Findings

The Euclidean distance, travel time, and provider‐to‐population ratio measures identified 48.3%, 47.2%, and 69.9% of the census tracts that the E2SFCA measure identified as being in the lowest quintile of spatial access to care, meaning that these measures misclassify 30%–52% of study area census tracts as having sufficient spatial access to buprenorphine prescribers.

Conclusions

Measures of spatial access commonly used by policy makers do not sufficiently accurately identify geographic areas with relatively low access to prescribers of buprenorphine. Using the E2SFCA in addition to the commonly used measures would allow policy makers to precisely target interventions to increase spatial access to opioid use disorder treatment and other types of health care services.
Relative species abundance estimation in artificial mixtures of insects using mito‐metagenomics and a correction factor for the mitochondrial DNA copy number
Authors: Garrido‐Sanz Lidia , Senar Miquel Àngel , Piñol Josep
Published: July 2021

Mito‐metagenomics (MMG) is becoming an alternative to amplicon metabarcoding for the assessment of biodiversity in complex biological samples using high‐throughput sequencing. Whereas MMG overcomes the biases introduced by the PCR step in the generation of amplicons, it is not yet a technique free of shortcomings. First, as the reads are obtained from shotgun sequencing, a very low proportion of reads map into the mitogenomes, so a high sequencing effort is needed. Second, as the number of mitogenomes per cell can vary among species, the relative species abundance (RSA) in a mixture could be wrongly estimated. Here, we challenge the MMG method to estimate the RSA using artificial libraries of 17 insect species whose complete genomes are available on public repositories. With fresh specimens of these species, we created single‐species libraries to calibrate the bioinformatic pipeline and mixed‐species libraries to estimate the RSA. Our results showed that the MMG approach confidently recovers the species list of the mixtures, even when they contain congeneric species. The method was also able to estimate the abundance of a species across different samples (within‐species estimation) but failed to estimate the RSA within a single sample (across‐species estimation) unless a correction factor accounting for the variable number of mitogenomes per cell was used. To estimate this correction factor, we used the proportion of reads mapping into mitogenomes in the single‐species libraries and the lengths of the whole genomes and mitogenomes.
Lung cancer treatment patterns and factors relating to systemic therapy use in Australia
Authors: Ngo Preston , Goldsbury David E. , Karikios Deme , Yap Sarsha , Yap Mei Ling , Egger Sam , O'Connell Dianne L. , Ball David , Fong Kwun M. , Pavlakis Nick , Rankin Nicole M. , Vinod Shalini , Canfell Karen , Weber Marianne F.
Published: July 2021

Aim

Systemic therapies for lung cancer are rapidly evolving. This study aimed to describe lung cancer treatment patterns in New South Wales, Australia, prior to the introduction of immunotherapy and latest‐generation targeted therapies.

Methods

Systemic therapy utilization and treatment‐related factors were examined for participants in the New South Wales 45 and Up Study with incident lung cancer ascertained by record linkage to the New South Wales Cancer Registry (2006–2013). Systemic therapy receipt to June 2016 was determined using medical and pharmaceutical claims data from Services Australia, and in‐patient hospital records. Factors related to treatment were identified using competing risks regressions.

Results

A total of 1,116 lung cancer cases were identified with a mean age at diagnosis of 72 years and median survival of 10.6 months. Systemic therapy was received by 45% of cases. Among 400 cases with metastatic non–small cell lung cancer, 51% and 28% received first‐ and second‐line systemic therapy, respectively. Among 112 diagnosed with small‐cell lung cancer, 79% and 29% received first‐ and second‐line systemic therapy. The incidence of systemic therapy was lower for participants with indicators of poor performance status, lower educational attainment, and those who lived in areas of socioeconomic disadvantage; and was higher for participants with small‐cell lung cancer histology or higher body mass index.

Conclusion

This population‐based Australian study identified patterns of systemic therapy use for lung cancer, particularly small‐cell lung cancer. Despite a universal healthcare system, the analysis revealed socioeconomic disparities in health service utilization and relatively low utilization of systemic therapy overall.
A method for magnetocardiography functional localization based on boundary element method and Nelder–Mead simplex algorithm
Authors: Lu Zhihong , Jiang Dingsong , Yang Jianzhong
Published: July 2021

Background

The magnetocardiography (MCG) functional localization can transfer the biomagnetic signal to the electrical activity information inside the heart. The electrical activity is directly related to the physiological function of the heart.

Methods

This study proposes a practical method for MCG functional localization based on the boundary element method (BEM) and the Nelder–Mead (NM) simplex algorithm. Single equivalent moving current dipole (SEMCD) is served as the equivalent cardiac source. The parameters of SEMCD are adapted using the NM simplex algorithm by fitting the measured MCG with the calculated MCG obtained based on BEM. The SEMCD parameters are solved in the sense that the difference between measured and calculated MCG is minimized.

Results

The factors affecting the localization accuracy of this BEM–NM method were first explored with synthetic signals. Then, the results with real MCG signals show a good agreement between the SEMCD location and the region where ventricle depolarization starts, demonstrating the feasibility of this idea.

Conclusions

This is the first three‐dimensional localization of the onset of ventricular depolarization with the BEM–NM method. The method is promising in the noninvasive localization of lesions for heart diseases.
Protective effect of estradiol copreservation against kidney ischemia‐reperfusion injury
Authors: Zhou Dawei , Leung Junto , Xu Weichen , Ye Shaojun , Dong Caitao , Huang Wanbin , Ye Qifa , Wang Yanfeng
Published: July 2021

Ischemia‐reperfusion injury (IRI) is the major cause of delayed graft function (DGF) during the posttransplantation period. Estradiol (E2) prevents IRI‐induced kidney dysfunction and tissue injury. However, many side effects limit E2’s in vivo application. Recent evidence uncovers E2’s expanded use in the field of transplantation. We aimed to study if and how E2 exerts protective activity during the period of kidney organ preservation. The autologous kidney transplant model in rats was first established. Rats were divided into 5 groups: normal group (N), sham group (sham), static cold storage (SCS) 4 hours group (control), SCS 4 hours + ethanol (1 µL/mL) group (solvent), and SCS 4 hours + ethanol (1 µL/mL) + E2 (1000 ng/mL) group (E2). ERα expression under hypothermia was measured by western blotting. Moreover, biochemical analyses of plasma levels of creatinine, BUN, estradiol, and testosterone were examined. Among all groups, kidney tissues were collected and processed for further western blot analysis about ERα, eNOS, Bcl‐2, and Bax expression, histological analyses such as H&E staining to evaluate pathological severity. In addition, a TUNEL assay is performed to evaluate apoptosis. E2 copreservation upregulated ERα expression under hypothermia. Moreover, E2 copreservation reduced levels of creatinine and BUN in plasma but without affecting estradiol and testosterone. Further, E2 copreservation increased expression of eNOS and antiapoptotic Bcl‐2 and decreases expression of proapoptotic Bax. E2 copreservation significantly inhibited IRI‐induced apoptosis and evidently improved pathological severity in the kidney of rats. E2 copreservation exerts protective activity against IRI‐induced pro‐inflammatory and proapoptotic effects in kidneys during organ preservation time and improves transplanted kidney function.
PRO‐C3 and ADAPT algorithm accurately identify patients with advanced fibrosis due to alcohol‐related liver disease
Authors: Madsen Bjørn S. , Thiele Maja , Detlefsen Sönke , Kjærgaard Maria , Møller Linda S. , Trebicka Jonel , Nielsen Mette J. , Gudmann Natasja Stæhr , Leeming Diana J. , Karsdal Morten A. , Krag Aleksander ,   the GALAXY consortium
Published: July 2021

Background

Alcohol is a main cause of preventable deaths and frequently leads to the development of alcohol‐related liver disease. Due to the lack of diagnostics, patients are commonly diagnosed after developing clinical manifestations. Recently, the biomarker PRO‐C3 was shown to accurately identify fibrosis due to non‐alcoholic fatty liver disease.

Aim

To assess the diagnostic accuracy of PRO‐C3, the ADAPT score and best‐performing non‐patented serological test to detect advanced alcohol‐related liver fibrosis.

Methods

We enrolled 426 patients with alcohol overuse in a prospective biopsy‐controlled study. We evaluated the accuracy of PRO‐C3 and the PRO‐C3‐based algorithm ADAPT to detect advanced liver fibrosis.

Results

The accuracy of PRO‐C3 was good with an AUROC of 0.85 (95% CI 0.79‐0.90). The best‐performing non‐patented test was the Forns index with an AUROC of 0.83 (95% CI 0.78‐0.89). The ADAPT algorithm performed better as compared to both the Forns index and PRO‐C3 alone with an AUROC = 0.88 (95% CI 0.83‐0.93).

Conclusion

PRO‐C3 is a new marker with high accuracy to detect advanced alcohol‐related liver fibrosis. The diagnostic accuracy of PRO‐C3 can be further improved by using the ADAPT algorithm in which the test outperforms currently available non‐patented serological fibrosis markers. The study is registered in the Odense Patient Data Exploratory Network (OPEN) under study identification numbers OP_040 (https://open.rsyd.dk/OpenProjects/da/openProject.jsp?openNo=40) and OP_239 (https://open.rsyd.dk/OpenProjects/openProject.jsp?openNo=239&lang=da).
A qualitative study of dental professionals' and patients' knowledge and perceptions of the impact of periodontal disease on systemic health and quality of life
Authors: Wong Li Beng , Kunnasegaran Sree Gaithiri , Yap Adrian Ujin , Allen Patrick Finbarr
Published: July 2021

Objectives

This qualitative study of dental professionals and patients with periodontal disease: (1) explored their knowledge and perceptions on the impact of periodontal disease on systemic health and quality of life (QoL); (2) assessed their familiarity with QoL instruments used to measure the impact of periodontal disease.

Methods

In‐depth semi‐structured face‐to‐face interviews were conducted with 10 dental professionals and 10 patients selected using purposive sampling. Audio recordings of the interviews were transcribed verbatim, coded and analysed using NVivo software (version 11, QSR International), followed by an inductive thematic analysis of the data.

Results

Three themes were identified for the dental professionals: (1) knowledge of periodontal disease, systemic health and QoL; (2) experience in managing patients with periodontal disease to improve their QoL; (3) perceived value of having a disease‐specific QoL instrument for periodontal disease. Three themes were identified for patients with periodontal disease: (1) knowledge of periodontal disease, systemic health and QoL; (2) experience and perception of how periodontal treatment can improve QoL; (3) perceived value of having a disease‐specific QoL instrument for periodontal disease. Both groups were knowledgeable about the relationship between periodontal disease, systemic health and QoL and had experienced how periodontal treatment could improve QoL. Both groups also agreed that a disease‐specific QoL instrument for periodontal disease would be beneficial.

Conclusions

Both the dental professionals and patients with periodontal disease were aware of the relationship between periodontal disease, systemic health and QoL, including the benefits of periodontal treatment in improving QoL. The value of developing a disease‐specific QoL instrument for periodontal disease was recognized by both groups.
SOX2 plays a crucial role in cell proliferation and lineage segregation during porcine pre‐implantation embryo development
Authors: Lee Mingyun , Choi Kwang‐Hwan , Oh Jong‐Nam , Kim Seung‐Hun , Lee Dong‐Kyung , Choe Gyung Cheol , Jeong Jinsol , Lee Chang‐Kyu
Published: July 2021

Objectives

Gene regulation in early embryos has been widely studied for a long time because lineage segregation gives rise to the formation of a pluripotent cell population, known as the inner cell mass (ICM), during pre‐implantation embryo development. The extraordinarily longer pre‐implantation embryo development in pigs leads to the distinct features of the pluripotency network compared with mice and humans. For these reasons, a comparative study using pre‐implantation pig embryos would provide new insights into the mammalian pluripotency network and help to understand differences in the roles and networks of genes in pre‐implantation embryos between species.

Materials and methods

To analyse the functions of SOX2 in lineage segregation and cell proliferation, loss‐ and gain‐of‐function studies were conducted in pig embryos using an overexpression vector and the CRISPR/Cas9 system. Then, we analysed the morphological features and examined the effect on the expression of downstream genes through immunocytochemistry and quantitative real‐time PCR.

Results

Our results showed that among the core pluripotent factors, only SOX2 was specifically expressed in the ICM. In SOX2‐disrupted blastocysts, the expression of the ICM‐related genes, but not OCT4, was suppressed, and the total cell number was also decreased. Likewise, according to real‐time PCR analysis, pluripotency‐related genes, excluding OCT4, and proliferation‐related genes were decreased in SOX2‐targeted blastocysts. In SOX2‐overexpressing embryos, the total blastocyst cell number was greatly increased but the ICM/TE ratio decreased.

Conclusions

Taken together, our results demonstrated that SOX2 is essential for ICM formation and cell proliferation in porcine early‐stage embryogenesis.
How has access to legal cannabis changed over time? An analysis of the cannabis retail market in Canada 2 years following the legalisation of recreational cannabis
Authors: Myran Daniel T. , Staykov Emiliyan , Cantor Nathan , Taljaard Monica , Quach Bradley I. , Hawken Steven , Tanuseputro Peter
Published: July 2021

Introduction

This study describes the legal recreational cannabis market across Canada over the 2 years following legalisation. We compared changes in access to the legal cannabis retail market for all provinces and territories (jurisdictions) in Canada and explored differences between jurisdictions.

Methods

We collected data for all legal cannabis stores in Canada over five time periods following legalisation in October 2018. We examined the following measures by jurisdiction and retail model (public vs. private operation): absolute and per capita store numbers, hours of operation and store access across neighbourhoods.

Results

Two years following legalisation, there were a total of 1183 legal cannabis stores open across Canada (3.7 stores per 100 000 individuals aged 15+). There was wide variation between jurisdictions in access to retail stores, with the lowest stores per capita in Quebec and Ontario (0.6 and 1.6 per 100 000), and the highest in Alberta and Yukon (14.3 per 100 000 in both). Jurisdictions with private retail models had more stores (4.8 vs. 1.0 per 100 000), held greater median weekly hours (80 vs. 69) and experienced greater store growth over time compared to public models. After adjusting for confounders, there were 1.96 times (95% confidence intervals: 1.84, 2.09) more cannabis stores within 1000 m of the lowest‐ compared to the highest‐income quintile neighbourhoods.

Discussion and Conclusions

While access to the recreational cannabis retail market has increased following legalisation, there is substantial variation in access between jurisdictions and evidence of concentration in lower‐income neighbourhoods. These differences may contribute to disparities in cannabis use and harms.
Falling through the Cracks: Digital Infrastructures of Social Protection in Ecuador
Authors: Palacio Ludeña María Gabriela
Published: July 2021

While cash transfers gain prominence as a response to the COVID‐19 pandemic, there is a strong impulse to regard them as a stepping‐stone towards the formalization of employment and universalization of social protection. This contribution problematizes how populations in informality are included in narrowly targeted social assistance interventions, which are heavily reliant on targeted schemes and fail to make informality legible to programme administrators. The focus of the article lies in the politics of exclusion and inclusion that permeate digital infrastructures, particularly data infrastructures such as social registries, that are used to target Ecuador's most prominent social assistance programme, Bono de Desarrollo Humano, and the COVID‐related programme Bono de Protección Familiar. The article is based on ethnographic work, interviews and narrative analysis. It finds that social registries compiled for proxy means testing weaken the link between eligibility and informal employment and obscure the processes that perpetuate precarity. More recent data innovations, such as machine learning, are also insufficient to locate vulnerable workers as they learn from historical social registries data and replicate their biases, for example by overlooking non‐poor areas where informal employment also occurs. Data infrastructures have shifted attention to the technicalities of the selection of beneficiaries and away from power imbalances in the design of social assistance, despite their selectivity and politics.
Effect of donor‐specific blood transfusions on allotransplanted teeth in a monkey model: Histoquantification of periodontal healing
Authors: Schwartz Ole , Thomsen Mogens , Dickmeiss Ebbe , Andreasen Jens Ove
Published: July 2021

Background/Aims

Pre‐transplant blood transfusions have previously shown a positive effect on organ allograft survival in humans and various animal species. The aims of this study were, first, to evaluate the effect of pre‐transplant donor‐specific blood transfusions on periodontal healing of fully developed allotransplanted teeth in monkeys; and second, to investigate the immune response against donor antigens and to determine a possible correlation between alloimmune reactions and histopathological signs of rejection.

Material and Methods

Twenty monkeys (Cercopithecus aethiops) were divided into ten pairs with similar sizes of incisors. One monkey in each pair gave three transfusions to the other monkey with 1‐week intervals. One week after the last transfusion, each pair exchanged simultaneously a central maxillary incisor and a lateral mandibular incisor. The corresponding central maxillary and mandibular lateral incisors were autotransplanted to the contralateral sockets. All teeth were treated endodontically per‐operatively. Histocompatibility was evaluated by mixed lymphocyte culture before the first transfusion, while alloantibodies and cell‐mediated alloresponses were measured before transfusions and at 2 and 8 weeks after transplantation. All animals were sacrificed 8 weeks after tooth transplantation. Serial sections of the transplanted teeth were quantified histologically.

Results

Mixed lymphocyte cultures showed positive reactions in 19 of 20 cases, indicating incompatibility. The majority of the monkeys developed antibodies towards the tooth donor. Cell‐mediated cytotoxicity was negative in all monkeys. Histoquantification revealed a mean score of 70% normal periodontal ligament (PDL) in autotransplanted teeth, with 5% ankylosis. The allografts had a mean score of 17% normal PDL and 63% ankylosis, with no significant influence of transfusion. However, in the mandibular grafts, a tendency towards a positive transfusion effect was seen.

Conclusions

Donor‐specific blood transfusion did not reduce ankylosis in tooth allografts. The healing of mandibular incisor tooth allografts was improved, but not that of maxillary incisors. Donor‐specific antibodies showed no effect on the survival of allograft PDL.
Attentional modulation of neural dynamics in tactile perception of complex regional pain syndrome patients
Authors: Defina Serena , Niedernhuber Maria , Shenker Nicholas , Brown Christopher A. , Bekinschtein Tristan A.
Published: July 2021

Body perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of complex regional pain syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between “passive” (i.e., no task demands and equiprobable digit stimulation) and “active” tactile processing (i.e., where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28–56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier's training, there is an unexpected increased decodability in the CRPS group compared with healthy volunteers (280–320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision‐making and attentional control mechanisms in chronic CRPS.
Pre‐stimulus alpha oscillation and post‐stimulus cortical activity differ in localization between consciously perceived and missed near‐threshold somatosensory stimuli
Authors: Uemura Jun‐ichi , Hoshino Aiko , Igarashi Go , Matsui Yusuke , Chishima Makoto , Hoshiyama Minoru
Published: July 2021

Conscious perception of a near‐threshold (NT) stimulus is characterized by the pre‐ and post‐stimulus brain state. However, the power of pre‐stimulus neural oscillations and strength of post‐stimulus cortical activity that lead to conscious perception have rarely been examined in individual cortical areas. This is because most previous electro‐ and magnetoencephalography (EEG and MEG, respectively) studies involved scalp‐ and sensor‐level analyses. Therefore, we recorded MEG during a continuous NT somatosensory stimulus detection task and applied the reconstructed source data in order to identify cortical areas where the post‐stimulus cortical activity and pre‐stimulus alpha oscillation predict the conscious perception of NT somatosensory stimuli. We found that the somatosensory hierarchical processing areas, prefrontal areas and cortical areas belonging to the default mode network showed stronger cortical activity for consciously perceived trials in the post‐stimulus period, but the cortical activity in primary somatosensory area (SI) is independent of conscious perception during the early stage of NT stimulus processing. In addition, we revealed that the pre‐stimulus alpha oscillation only in SI is predictive of conscious perception. These findings suggest that the bottom‐up stream of somatosensory information flow following SI and pre‐stimulus alpha activity fluctuation in SI as a top‐down modulation are crucial constituents of conscious perception.
T cell composition and polygenic multiple sclerosis risk: A population‐based study in children
Authors: de Mol Casper L. , Looman Kirsten I. M. , van Luijn Marvin M. , Kreft Karim L. , Jansen Philip R. , van Zelm Menno C. , Smolders Joost J. F. M. , White Tonya J. H. , Moll Henriette A. , Neuteboom Rinze F.
Published: July 2021

Background and purpose

Patients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population.

Methods

We included genotyped participants from the population‐based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS‐PRSs on total T cell numbers (n = 1261), CD4+and CD8+lineages, and subsets therein (n= 675). In addition, T‐cell‐specific PRSs were constructed based on functional pathway data.

Results

The MS‐PRS negatively correlated with CD8+T cell frequencies (p = 2.92 × 10−3), which resulted in a positive association with CD4+/CD8+T cell ratios (p = 8.27 × 10−9). These associations were mainly driven by two of 195 genome‐wide significant MS risk variants: the main genetic risk variant for MS,HLA‐DRB1*15:01and anHLA‐Brisk variant. We observed no significant associations for the T‐cell‐specific PRSs.

Conclusions

Our results suggest that MS‐associated genetic variants affect T cell composition during childhood in the general population.
Atrial fibrosis in embolic stroke of undetermined source: A multicenter study
Authors: Kühnlein Peter , Mahnkopf Christian , Majersik Jennifer J. , Wilson Brent D. , Mitlacher Marcel , Tirschwell David , Longstreth W. T. , Akoum Nazem
Published: July 2021

Background and purpose

Left atrial (LA) cardiac disease is a suspected cause of embolic stroke of undetermined source (ESUS). We tested the hypothesis that LA fibrosis, quantified using late‐gadolinium‐enhancement magnetic resonance imaging (LGE‐MRI), predicts recurrent stroke or atrial fibrillation (AF) in patients with ESUS.

Methods

We compared atrial fibrosis in healthy controls and patients with lacunar stroke, ESUS, and known AF with or without prior stroke. We followed patients with ESUS prospectively for the primary outcome of recurrent ischemic stroke, incident AF, or both.

Results

We enrolled 203 patients from three centers: 103 patients without AF (35 healthy controls, 15 with lacunar strokes, 53 with ESUS) and 100 patients with AF (50 with and 50 without prior stroke). Patients with ESUS had significantly higher atrial fibrosis (15.0 ± 6.2%) compared to healthy controls (8.1 ± 7.9%; <0.0001) and compared to lacunar stroke patients (10.8 ± 8.4; p = 0.02), but had comparable fibrosis to patients with AF with (17.9 ± 11.4%) or without prior stroke (16.6 ± 9.2%; p = NS for both). Over a mean follow‐up of 19 months, nine of 53 patients (16.9%) with ESUS experienced the combined primary outcome, which included six patients (11.3%) with recurrent ischemic stroke and five patients with incident AF (9.4%). Patients with ESUS with fibrosis ≥12% had a higher proportion of the combined outcome: 25.0% vs. 4.8%; p = 0.039.

Conclusions

Patients with ESUS demonstrate atrial fibrosis comparable to that seen in AF. Atrial fibrosis ≥12% was associated with recurrent stroke, incident AF or both. This subgroup of ESUS patients may benefit from anticoagulation for secondary prevention of ischemic stroke.
Novel mechanisms of microbial crosstalk with skin innate immunity
Authors: Chinnappan Mahendran , Harris‐Tryon Tamia A.
Published: July 2021

Skin is an organ with a dynamic ecosystem that harbours pathogenic and commensal microbes, which constantly communicate amongst each other and with the host immune system. Evolutionarily, skin and its microbiota have evolved to remain in homeostasis. However, frequently this homeostatic relationship is disturbed by a variety of factors such as environmental stress, diet, genetic mutations, and the microbiome itself. Commensal microbes also play a major role in the maintenance of microbial homeostasis. In addition to their ability to limit pathogens, many skin commensals such as Staphylococcus epidermidis and Cutibacterium acnes have recently been implicated in disease pathogenesis either by directly modulating the host immune components or by supporting the expansion of other pathogenic microbes. Likewise, opportunistic skin pathogens such as Staphylococcus aureus and Staphylococcus lugdunensis are able to breach the skin and cause disease. Though much has been established about the microbiota's function in skin immunity, we are in a time where newer mechanistic insights rapidly redefine our understanding of the host/microbial interface in the skin. In this review, we provide a concise summary of recent advances in our understanding of the interplay between host defense strategies and the skin microbiota.
Sampling units derived from geopolitical boundaries bias biodiversity analyses
Authors: Murphy Stephen J.
Published: July 2021

Aim

Sampling decisions are known to influence the estimation and interpretation of biodiversity. The use of geopolitical and administrative boundaries (GABs) for mapping biodiversity variables and identifying hotspots has a long history in biogeography and conservation biology. However, potential biases associated with these units and their effects on conservation decisions has not been adequately explored.

Location

Global.

Time period

21,000 years ago to present day.

Major taxa studied

Amphibians, birds, mammals and reptiles.

Methods

I calculated biodiversity metrics for four major taxa at eight different spatial resolutions to understand scale‐dependencies. I then compared these estimates to those using GABs (e.g., countries and other large units) as sampling units. I also used both grid‐ and GAB‐based sampling designs to model the relationship between biodiversity patterns and relevant climate variables.

Results

Larger sampling units led to higher estimates of species richness and phylogenetic diversity. Taxonomic and phylogenetic endemism remained relatively stable across scales due to competing biases related to grain size and estimation of range size. Using GABs led to both under‐ and overestimation of endemism when compared to fine‐resolution grid‐based estimates, with differences varying across space and taxonomic groups. Importantly, using GABs resulted in different locations being identified as biodiversity hotspots when compared to grid‐based analyses. Likewise, different climate drivers of species richness and endemism were identified when using a GAB‐ versus grid‐based sampling design.

Main conclusions

Using GABs will remain an important method for mapping variation in biodiversity metrics across the globe. However, appropriate understanding of the biases associated with these and other ad‐hoc sampling designs should be better understood and accounted for in macroecology analyses, including for understanding environmental drivers of biodiversity patterns and identifying local and regional diversity hotspots. This is especially true for measures of diversity that incorporate species range size, such as taxonomic and phylogenetic endemism.
Spatio‐temporal variation in post‐recovery dynamics in a large Peregrine Falcon (Falco peregrinus) population in the Jura mountains 2000–2020†
Authors: Kéry Marc , Banderet Gabriel , Müller Claudia , Pinaud David , Savioz Jérémy , Schmid Hans , Werner Stefan , Monneret René‐Jean
Published: July 2021

After spectacular population crashes in the 1960 and 1970s, Peregrine FalconFalco peregrinuspopulations recovered worldwide, and in the 2000s many study populations were back to normal. However, post‐recovery trends have been documented less well. We combined three long‐term population studies covering the entire Jura mountain range (16 304 km2) to examine spatio‐temporal variation in population dynamics during 2000–2020 in 420 known nesting sites in five regions: Ain, Jura and Doubs in France, and Jura Sud and Jura Nord in Switzerland. Every year about 60% of all sites were surveyed at least once, and this proportion increased over time. We used Bayesian occupancy modelling to investigate site persistence and colonization probabilities and correct status and trend estimates for bias due to non‐random site coverage. Based on the average of two models correcting for preferential sampling, we estimated that population size peaked in 2002 (Jura), 2005 (Doubs), 2007 (Ain, Jura Nord) and in 2007 for the Jura as a whole. Thereafter, the population declined significantly in four regions and in the Jura as a whole, with the strongest decline found in the Jura Nord ( –38%, 95% credible interval –34%/–41%) during 2007–2020. Thus, we found considerable spatial heterogeneity in post‐recovery trends and widespread post‐recovery declines. Reasons for the latter may include Eagle OwlBubo bubopredation, illegal persecution and human disturbance. Our results illustrate how quickly positive population trends may be reversed, such that continuous long‐term monitoring even for species seemingly ‘out of danger’ remains invaluable. Our study also emphasizes the importance of correcting for both coverage bias in general and preferential sampling in particular when assessing population trends in studies where not every territory can be surveyed in all years.
MONEY METRICS IN APPLIED WELFARE ANALYSIS: A SADDLEPOINT REHABILITATION
Authors: Schlee Edward E. , Khan M. Ali
Published: July 2021

Once a popular tool to estimate welfare changes, the money metric of McKenzie‐Samuelson gradually faded from use after welfare theorists and practitioners argued that it led to inegalitarian recommendations. We prove that, at a competitive equilibrium price, any associated competitive allocation maximizes the money‐metric sum; and, as is well understood, competitive allocations can be egalitarian or inegalitarian. The result applies to economies in which individual demand is not rationalizable by any binary relation, let alone a binary relation representable by a utility function, a behavioral setting considered, for example, in Bernheim–Rangel.
Breakpoint characterization of a rare alpha0‐thalassemia deletion using targeted locus amplification on genomic DNA
Authors: Hottentot Quint P. , de Meijer Emile , Buermans Henk P. J. , White Stefan J. , Harteveld Cornelis L.
Published: July 2021

Introduction

The high‐sequence homology of the α‐globin‐gene cluster is responsible for microhomology‐mediated recombination events during meiosis, resulting in a high density of deletion breakpoints within a 10 kb region. Commonly used deletion detection methods, such as multiplex ligation‐dependent probe amplification (MLPA) and Southern blot, cannot exactly define the breakpoints. This typically requires long‐range PCR, which is not always successful. Targeted locus amplification (TLA) is a targeted enrichment method that can be used to sequence up to 70 kb of neighboring DNA sequences without prior knowledge about the target site.

Methods

Genomic DNA (gDNA) TLA is a technique that folds isolated DNA, ensuring that adjacent loci are in a close spatial proximity. Subsequent digestion and religation form DNA circles that are amplified using fragment‐specific inverse primers, creating a library that is suitable for Illumina sequencing.

Results

Here, we describe the characterization of a rare 16 771 bp deletion, utilizing gDNA TLA with a single inverse PCR primer set on one end of the breakpoint. Primers for breakpoint PCR were designed to confirm the deletion breakpoints and were consequently used to characterize the same deletion in 10 additional carriers sharing comparable hematologic data and similar MLPA results.

Conclusions

The gDNA TLA technology was successfully used to identify deletion breakpoints within the alpha‐globin cluster. The deletion was described only once in an earlier study as the ‐‐gb, but as it was not registered correctly in the available databases, it was not initially recognized as such.
Impact of centrifugation on thrombin generation in healthy subjects and in patients treated with direct oral anticoagulants
Authors: Hardy Michael , Dellanoce Claudia , Douxfils Jonathan , Carlo Audrey , Lessire Sarah , Bouvy Céline , Testa Sophie , Mullier François
Published: July 2021

Introduction

Double centrifugation before freezing is recommended before thrombin generation assays (TGA). However, this procedure is not mandatory for routine hemostasis tests, precluding the use of these samples for TGA. The aim of this study is to assess the impact of single and double centrifugation on TGA performed on frozen samples from healthy volunteers (HVs) and patients receiving direct oral anticoagulants (DOACs).

Methods

Forty HVs and 57 patients receiving a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) were included in this prospective double‐center observational study. Blood was collected into 109 mmol/L citrated tubes and frozen at −70°C before TGA using ST Genesia with STG‐DrugScreen reagent. Four pre‐analytical conditions were studied: (A) single centrifugation (2000 g, 15 minutes) before freezing; (B) one centrifugation before freezing and another after thawing (2000 g, 15 minutes for both); (C) one centrifugation before freezing(2000 g, 15 minutes) and another after thawing (2000 g, 10 minutes); (D) double centrifugation (2000 g, 15 minutes) before freezing (reference). Centrifugation conditions (A), (B), and (C) were compared with the reference condition (D). Acceptable relative differences were defined at 6%, 8%, and 10% for normalized lag time, endogenous thrombin potential, and peak height, respectively.

Results

Centrifugation conditions had a small but acceptable impact on HVs samples, but single centrifugation always resulted in unacceptable reductions in normalized lag times for DOAC samples. A second centrifugation after thawing permitted the recovery of acceptable differences for the three TGA parameters for edoxaban but not for apixaban, rivaroxaban, nor dabigatran.

Conclusion

Double centrifugation before freezing should remain the recommended pre‐analytical condition before TGA.
Influenza virus infection selectively triggers the accumulation and persistence of more potent Helios‐expressing Foxp3+ regulatory T cells in the lungs
Authors: Lu Chunni , Chen Weisan
Published: July 2021

Foxp3+ regulatory T cells (Tregs) represent a special lineage of CD4+ T cells. Analysis of Treg response during primary and secondary influenza virus infection clearly demonstrates a robust accumulation of Tregs into the infected lungs and the existence of a population of long‐lived antigen‐specific memory Tregs in the same tissues after resolution of the infection. However, it remains unknown whether these Tregs co‐express Helios, a member of the Ikaros transcription factor family. In this study, Foxp3+Helios+ and Foxp3+Helios‐ Tregs in the lungs, mLNs and spleens of influenza virus‐infected and uninfected control mice were tracked. The data show that while there is a co‐existence of Foxp3+Helios+ and Foxp3+Helios‐ Tregs in the tissues, the accumulated Tregs in the lungs and lung‐draining mediastinal lymph nodes (mLNs) of the infected mice are highly enriched for Foxp3+Helios+ cells. It was further demonstrated that, after the clearance of primary infection, Foxp3+Helios+ cells have the ability to persist in the tissues over their Helios‐ counterparts. More importantly, Foxp3+Helios+ Tregs accumulated in an accelerated kinetics during recall response to reinfection. In vitro analysis of Treg suppressive function revealed that Foxp3+Helios+ Tregs are more capable of suppressing influenza virus‐specific CD8+ T cell activation, cytokine production and proliferation. Together, the data provide new insights into Treg responses during primary and secondary influenza virus infection and suggest that Foxp3+Helios+ Tregs predominantly drive the Treg responses.
Symptom trajectories for palliative care inpatients with and without hyperactive delirium in the last week of life
Authors: Dai Yunyun , Walpole Grace , Ding Jinfeng , Scanlon Cian , Ho Luke , Khoo Ru Hui , Huang Chongmei , Cook Angus , William Leeroy , Johnson Claire E.
Published: July 2021

Aims

Hyperactive delirium (HD) is a common and distressing symptom among palliative care patients. This study aimed to describe the characteristics of HD and associated symptoms among palliative care inpatients and evaluate relationships between HD development and symptom trajectories in this population.

Design

A retrospective study was conducted.

Methods

A retrospective review of medical records was conducted for all patients who died in a large Australian specialist palliative care unit between 1 January and 31 December 2019. Patients were assessed daily using the Symptoms Assessment Scale (SAS) and Palliative Care Problem Severity Scale (PCPSS). Multilevel models were used to estimate the differences in symptoms trajectories in the last 7 days of life between the two groups.

Results

Of the 501 included patients, 64.5% (323) had an episode of HD. For 30% (95) of patients, HD occurred prior to admission. Compared with patients without HD, those with HD had significantly higher odds ratios (ORs) for four of the seven SAS symptoms (sleep problems, appetite, fatigue and pain; OR range: 1.94–4.48, p < .05), and all four PCPSS items (OR range: 2.00–3.00, p < .05) in the last week of life.

Conclusions

Palliative care inpatients commonly experience HD in their last week of life. There are higher levels of symptom distress, complexity, psychological concerns and family/carer concerns among patients with HD compared with those without HD.

Impact

The high prevalence of HD, and its association with higher levels of symptom distress, highlights the importance of routine screening and optimal management for HD among palliative care patients. Given the widely recognized challenges facing palliative care professionals in assessment and management of delirium, provision of relevant training among these professionals is recommended.
Procedural efficacy and safety of standardized, ablation index guided fixed 50 W high‐power short‐duration pulmonary vein isolation and substrate modification using the CLOSE protocol
Authors: Francke Alexander , Taha Nadja S. , Scharfe Frank , Schoen Steffen , Wunderlich Carsten , Christoph Marian
Published: July 2021

Introduction

Ablation index (AI)‐guided ablation according to the CLOSE protocol is very effective in terms of chronic pulmonary vein isolation (PVI). However, the optimal radiofrequency (RF) power remains controversial. Here, we thought to investigate the efficiency and safety of an AI‐guided fixed circumferential 50 W high‐power short‐duration (HPSD) PVI using the CLOSE protocol.

Methods and Results

In a single‐center trial, 40 patients underwent randomized PVI using AI‐guided ablation without esophageal temperature monitoring. In 20 patients a CLOSE protocol guided fixed 50 W HPSD was followed irrespective of the anatomical localization. Twenty subjects were treated according to the CLOSE protocol with standard power settings (20 W posterior and 40 W roof and anterior wall). In addition, 80 consecutive patients were treated according to the HPSD protocol to gather additional safety data. All patients underwent postprocedural esophagogastroduodenoscopy to reveal esophageal lesions (EDELs). The mean total procedural time was 80.3 ± 22.5 in HPSD compared to control 109.1 ± 27.4 min (p < .001). The total RF‐time was significantly lower in HPSD with 1379 ± 505 s versus control 2374 ± 619 s (p < .001). There were no differences in periprocedural complications. EDEL occurred in 13% in the HPSD and 10% in the control group. EDEL occurring in the 50 W HSDP patients were smaller, more superficial, and had a faster healing tendency.

Conclusion

A fixed 50 W HPSD circumferential PVI relying on the AI and CLOSE protocol reduce the total procedure time and the total RF time, without increasing the complication rates. The incidence of EDELs was similar using 50 W at the posterior atrial wall.
Safety and efficacy of cell‐free and concentrated ascites reinfusion therapy against cirrhotic ascites in comparison with malignancy‐related ascites
Authors: Ito Tetsuya , Hanafusa Norio , Soneda Noriko , Isoai Ayako , Kobayashi Ryosuke , Torii Naoko , Kato Michio
Published: July 2021

Background and Aim

Cell‐free and concentrated ascites reinfusion therapy (CART) has been performed against cirrhotic ascites, one of the most common complications seen in patients with decompensated cirrhosis. The aim of this study is to investigate its safety and efficacy, and differences in clinical profiles from CART against malignancy‐related ascites with different pathological background.

Methods

The present investigation involved a sub‐analysis of data obtained from a prospective observational study of CART performed at 22 centers. The condition of each procedure, therapeutic options, laboratory data, performance status, dietary intake, and abdominal circumference of participants were analyzed. Clinical parameters were compared between before and after CART, with or without albumin infusion, and also primary diseases including cirrhosis and malignant disease.

Results

Between January 2014 and January 2015, a total of 48 and 275 CART procedures were performed in patients with cirrhosis and malignancies. In cirrhotic patients, serum albumin concentration increased significantly in groups both with and without concomitant albumin infusion (P = 0.002 and P = 0.023), and no significant difference in CART interval was seen between these groups (P = 0.393). CART interval was not significantly different between cirrhosis and malignancy groups (P = 0.334). Dietary intake significantly improved after CART in both groups (P = 0.043 and P < 0.001). Adverse events were with no clinical significance as observed in patients with malignancies.

Conclusions

Cell‐free and concentrated ascites reinfusion therapy was performed safely and effectively in patients with ascites related to decompensated cirrhosis and offers the potential efficacy to maintain plasma colloid osmotic pressure after paracentesis as well as in patients with malignancy.