bluuebunny/crossref_metadata_2025 huggingface dataset:
Railways redistribute plant species in mountain landscapes
Authors: Rashid Irfan , Haq Shiekh Marifatul , Lembrechts Jonas J. , Khuroo Anzar A. , Pauchard Aníbal , Dukes Jeffrey S.
Published: July 2021

The significant portion of global terrestrial biodiversity harboured in the mountains is under increasing threat from various anthropogenic impacts. Protecting fragile mountain ecosystems requires understanding how these human disturbances affect biodiversity. As roads and railways are extended further into mountain ecosystems, understanding the long‐term impacts of this infrastructure on community composition and diversity gains urgency.

We used railway corridors constructed across the mountainous landscapes of the Kashmir Himalaya from 1994 to 2013 to study the effects of anthropogenic disturbance on species distributions and community dynamics. In 2014 and 2017, we collected vegetation data along 31 T‐shaped transects laid perpendicular to the railway line, adopting the MIREN (Mountain Invasion Research Network) road survey methodology.

Plant communities shifted significantly from 2014 to 2017, potentially because of an ongoing species redistribution after railway construction, driven mainly by declines in both native and non‐native species richness, and an increasing abundance of a few non‐native species, especially in areas away from the railway track.

These patterns indicate an advancing succession, where initially—rare—pioneer species are replaced by increasingly dominant and often non‐native competitors, and potentially suggest a trend towards delayed local extinctions after the disturbance event. Native and non‐native species richness was negatively correlated with elevation, but that relationship diminished over time, with the abundance of non‐natives significantly increasing at higher elevations.

Synthesis and applications. Transport corridors seem to facilitate the spread of non‐native species to higher elevations, which has serious implications considering the warming mountain tops. Our results indicate that the plant communities next to railways do not reach equilibrium quickly after a disturbance. More than 10 years after railway establishment within Kashmir Himalaya, succession continued, and signs pointed towards a landscape increasingly dominated by non‐native species. Our study indicates that the single disturbance event associated with constructing railway in this Himalayan region had large and long‐lasting effects on plant communities at and around this transport corridor and suggests the need for a long‐term region‐wide coordinated monitoring and management program.
Light and depth dependency of nitrogen fixation by the non‐photosynthetic, symbiotic cyanobacterium UCYN‐A
Authors: Gradoville Mary R. , Cabello Ana M. , Wilson Samuel T. , Turk‐Kubo Kendra A. , Karl David M. , Zehr Jonathan P.
Published: July 2021

The symbiotic cyanobacterium UCYN‐A is one of the most globally abundant marine dinitrogen (N2)‐fixers, but cultures have not been available and its biology and ecology are poorly understood. We used cultivation‐independent approaches to investigate how UCYN‐A single‐cell N2 fixation rates (NFRs) and nifH gene expression vary as a function of depth and photoperiod. Twelve‐hour day/night incubations showed that UCYN‐A only fixed N2 during the day. Experiments conducted using in situ arrays showed a light‐dependence of NFRs by the UCYN‐A symbiosis, with the highest rates in surface waters (5–45 m) and lower rates at depth (≥ 75 m). Analysis of NFRs versus in situ light intensity yielded a light saturation parameter (Ik) for UCYN‐A of 44 μmol quanta m−2 s−1. This is low compared with other marine diazotrophs, suggesting an ecological advantage for the UCYN‐A symbiosis under low‐light conditions. In contrast to cell‐specific NFRs, nifH gene‐specific expression levels did not vary with depth, indicating that light regulates N2 fixation by UCYN‐A through processes other than transcription, likely including host–symbiont interactions. These results offer new insights into the physiology of the UCYN‐A symbiosis in the subtropical North Pacific Ocean and provide clues to the environmental drivers of its global distributions.
Invisible actors: Understanding the micro‐activities of public sector employees in the development of public–private partnerships in the United States
Authors: Opara Michael , Okafor Oliver Nnamdi , Ufodike Akolisa
Published: July 2021

Public–private partnerships (P3s) have continued to grow in importance both as an alternative infrastructure delivery model and a management practice in many jurisdictions and across institutional contexts. This study draws on theinstitutional workperspective to investigate the nature and form of micro‐activities that interact to cement a policy through the examination of the implementation of P3s as a management practice. The study advances our understanding of how the micro‐activities of governmental agents and actors affect the development, codification, and support structures of P3s. We adopt a multi‐location, field‐based case approach and a diversified institutional setting presented by P3‐adopting regions in the United States. We deploy an institutional work perspective to identify the micro‐activities that are undertaken as part of the P3 routinisation and acceptance process. Following Perkmann and Spicer's classification, and consistent with the concept of institutional work (Lawrence & Suddaby), we find that the ordinary day‐to‐day micro‐activities undertaken by government employees, categorised aspolitical work,technical work, andcultural work, are structurally, strategically, and intentionally deployed to achieve the successful implementation of P3s. In addition, we uncover a complementary managerial micro‐activity undertaken alongside institutional work, what we termorganisational restructuring, as part of the composite of activities that facilitate a successful P3 implementation. We suggest that the nature, extent, and impact of ordinary government employee micro‐activities on the implementation and acceptance of P3s deserve further empirical inquiry.
A unifying framework for quantifying and comparing n‐dimensional hypervolumes
Authors: Lu Muyang , Winner Kevin , Jetz Walter
Published: July 2021

The quantification of Hutchinson's n‐dimensional hypervolume has enabled substantial progress in community ecology, species niche analysis and beyond. However, most existing methods do not support a partitioning of the different components of hypervolume. Such a partitioning is crucial to address the ‘curse of dimensionality’ in hypervolume measures and interpret the metrics on the original niche axes instead of principal components. Here, we propose the use of multivariate normal distributions for the comparison of niche hypervolumes and introduce this as the multivariate‐normal hypervolume (MVNH) framework (R package available on https://github.com/lvmuyang/MVNH).

The framework provides parametric measures of the size and dissimilarity of niche hypervolumes, each of which can be partitioned into biologically interpretable components. Specifically, the determinant of the covariance matrix (i.e. the generalized variance) of a MVNH is a measure of total niche size, which can be partitioned into univariate niche variance components and a correlation component (a measure of dimensionality, i.e. the effective number of independent niche axes standardized by the number of dimensions). The Bhattacharyya distance (BD; a function of the geometric mean of two probability distributions) between two MVNHs is a measure of niche dissimilarity. The BD partitions total dissimilarity into the components of Mahalanobis distance (standardized Euclidean distance with correlated variables) between hypervolume centroids and the determinant ratio which measures hypervolume size difference. The Mahalanobis distance and determinant ratio can be further partitioned into univariate divergences and a correlation component.

We use empirical examples of community‐ and species‐level analysis to demonstrate the new insights provided by these metrics. We show that the newly proposed framework enables us to quantify the relative contributions of different hypervolume components and to connect these analyses to the ecological drivers of functional diversity and environmental niche variation.

Our approach overcomes several operational and computational limitations of popular nonparametric methods and provides a partitioning framework that has wide implications for understanding functional diversity, niche evolution, niche shifts and expansion during biotic invasions, etc.
Stability of schizophrenia diagnosis in a 10‐year longitudinal study on first episode of non‐affective psychosis: Conclusions from the PAFIP cohort
Authors: Suárez‐Pinilla Paula , Suárez‐Pinilla Marta , Setién‐Suero Esther , Ortiz‐García de la Foz Víctor , Mayoral‐Van Son Jacqueline , Vázquez‐Bourgon Javier , Gómez‐Revuelta Marcos , Juncal‐Ruíz María , Ayesa‐Arriola Rosa , Crespo‐Facorro Benedicto
Published: July 2021

Objective

To evaluate the 10‐year stability of schizophrenia diagnosis in a cohort of first‐episode psychosis (FEP) patients and the factors associated with it.

Methods

Changes in diagnosis of 209 FEP patients were described during 10 years of follow‐up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through binary logistic regressions, ROC and survival curves.

Results

Out of the 209 patients, 126 were diagnosed of schizophrenia 6 months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after 10 years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow‐up. Retrospectively, out of the 154 patients with schizophrenia in the 10‐year assessment, 36 had a different diagnosis at baseline, and those factors related to a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis.

Conclusions

Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after 10 years.
Autism comorbidities show elevated female‐to‐male odds ratios and are associated with the age of first autism diagnosis
Authors: Rødgaard Eya‐Mist , Jensen Kristian , Miskowiak Kamilla Woznica , Mottron Laurent
Published: July 2021

Objective

To investigate the association between the comorbidity rates in autism and sex, birth year and the age at which autism was first diagnosed and compare the relative impact of each.

Method

Using the Danish National Patient Registry, cumulative incidences up to the age of 16 for 11 comorbid conditions (psychosis, affective disorders, anxiety disorders, conduct disorder, eating disorders, obsessive‐compulsive disorder, attention‐deficit hyperactivity disorder, epilepsy, tic disorders, sleep disorders or intellectual disability) were calculated for individuals with autism (N = 16,126) and non‐autism individuals (N = 654,977). Individuals were further stratified based on the age at the first autism diagnoses and comorbid diagnoses up to the age of 16 were compared.

Results

Most comorbidities were significantly associated with birth year and sex. Female/male odds ratios for 8 of 11 comorbid conditions were up to 67% higher than the corresponding odds ratios in the non‐autism population, including conditions that are generally more common in males than in females as well as conditions that are more common in females. All comorbidity rates were significantly associated with the age at the first autism diagnosis, which was a stronger predictor than sex and birth year for 8 conditions.

Conclusions

Comorbidity rates for females exceed what would be expected based on the sex ratios among non‐autistic individuals, indicating that the association between autism and comorbidity is stronger in females. Comorbidity rates are also highly dependent on the age at the first autism diagnosis, which may contribute to autism heterogeneity in research and clinical practice.
Is neurotrauma training in rural New South Wales still required following the implementation of the New South Wales State Trauma Plan?
Authors: Yusof Vessey Johan , Shivapathasundram Ganeshwaran , Francis Nevenka , Sheridan Mark
Published: July 2021

Background

In New South Wales (NSW), Australia, trauma accounts for 6% of deaths. Trauma patients receiving definitive care in regional trauma centres are 34% more likely to have a fatal outcome compared to level 1 centres. Following the implementation of the NSW State Trauma Plan where patients with major trauma are fast tracked to regional trauma services, should NSW rural surgeons and retrieval doctors continue to receive surgical training in neurotrauma?

Methods

The study's primary objective was to ascertain which NSW regional and rural hospitals have the equipment to perform neurotrauma and when it was last used. The study also examined the outcome of those patients who had undergone an emergency neurosurgical procedure.

Results

Of the 149 regional and rural hospitals in NSW, 16 stored a Hudson brace, perforator, burr and Gigli saw sterile and ready to use in the operating theatre. Only one hospital utilised the equipment in the last year and 11 in the last 10 years. Of those patients who had undergone an emergency neurosurgical procedure, two patients died prior to transfer and three were confirmed deceased after transfer to a tertiary centre.

Conclusion

The implementation of the NSW State Trauma Plan has streamlined the trauma triage process and transport of neurotrauma patients to regional and major trauma services. However, it is likely that knowledge of how to perform burr hole and craniectomy for the evacuation of extradural haematoma remains a useful skill for the rural surgeon and retrieval doctor if transport is delayed.
Bordering and Debordering Spaces of Asylum in the City of Frankfurt: Municipal Refugee Accommodation and Neighbourhood‐Based Volunteering
Authors: Blank Martina
Published: July 2021

The segregation of refugees in collective accommodation centres represents an integral component of the European border regime and its complex interplay of inclusion and exclusion. The corresponding spatial, symbolic and discursive demarcations, however, are not simply implemented politically from above, but negotiated on the ground on a daily basis. One crucial group of actors in the German context are neighbourhood‐based volunteers. These groups frequently accompany accommodation centres with support structures. Based on contributions in the field of critical border studies and on the example of a municipal accommodation facility in Frankfurt, Germany, this paper demonstrates how volunteers, through their practices and engagement with refugees and others, on one hand, and dominant discourses, institutions and regulations on the other, participate in the production of locally specific spaces of asylum that are marked by simultaneous and contradictory processes of bordering and debordering.
Conditional intensity: A powerful tool for modelling and analysing point process data
Authors: Diggle Peter J.
Published: July 2021

The conditional intensity function of a spatial point process describes how the probability that a point of the process occurs ‘at’ a particular point in its carrier space depends on the realisation of the process in the remainder of the carrier space. Provided that the point process is simple, the conditional intensity determines all of the properties of the process, in particular its likelihood function. In this paper, we review the use of the conditional intensity function in the formulation of point process models and in making inferences from point process data, giving separate consideration to temporal, spatial and spatiotemporal settings. We argue that the conditional intensity function should take centre‐stage in spatiotemporal point process modelling and analysis.
Exposure to electronic media was negatively associated with speech and language development at 18 and 24 months
Authors: Asikainen Marja , Kylliäinen Anneli , Mäkelä Tiina E. , Saarenpää‐Heikkilä Outi , Paavonen E. Juulia
Published: July 2021

Aim

This study evaluated early speech and language development at 18 and 24 months, and associated factors, based on parental reports.

Method

We followed up the CHILD‐SLEEP birth cohort of 1667 Finnish‐speaking families, who were randomly recruited in 2011–2013 during routine visits to maternity clinics in the Pirkanmaa Hospital District of Finland. The women were approximately 32 weeks’ pregnant at enrolment. Parents reported the size of their child's expressive vocabulary, word combinations, intelligibility, finger‐pointing and adherence to instructions. A subsample was studied using the Expressive Language subscale of the Bayley Scales of Infant and Toddler Development, Third Edition.

Results

The children's vocabulary was smaller than previously reported. At 18 months of age, 68.8% of the 997 children had a vocabulary of 20 words or less and 35.7% used about five words at most. At 24 months, 32.4% of the 822 children had a vocabulary of 50 words or less and 18.4% used about 20 words at most. Longer child and parental exposure to electronic media was negatively associated with the size of the child's expressive vocabulary.

Conclusion

Vocabulary size at 18 and 24 months was smaller than previously reported and negatively associated with exposure to electronic media.
Calcineurin (PPP3CB) regulates angiotensin II‐dependent vascular remodelling by potentiating EGFR signalling in mice
Authors: Nolze Alexander , Köhler Conny , Ruhs Stefanie , Quarch Katja , Strätz Nicole , Gekle Michael , Grossmann Claudia
Published: July 2021

Aim

This study investigates the role of calcineurin for angiotensin II (AngII)‐induced vascular remodelling with the help of a mouse model lacking the catalytic beta subunit of calcineurin (PPP3CB KO).

Methods

Wildtype (WT) and PPP3CB KO mice were treated for 4 weeks with AngII followed by assessment of blood pressure, histological evaluation of aortas and mRNA analysis of aortic genes PPP3CB‐dependently regulated by AngII. Primary murine vascular smooth muscle cells (VSMCs) were used for qPCR, ELISA and Western Blot experiments as well as wound healing and cell proliferation assays.

Results

Upon AngII treatment, PPP3CB KO mice showed less aortic media thickening, lumen dilation and systolic blood pressure compared to WT mice. Next‐generation sequencing data of aortic tissue indicated an increase in extracellular matrix components (EMCs), cell migration and cell proliferation. A PPP3CB‐dependent increase in EMC was confirmed by qPCR in aorta and VSMCs. PPP3CB‐dependent stimulation of VSMC migration could be verified by wound healing assays but markers of enhanced cell proliferation were only detectable in aortic tissue of WT mice but not in isolated WT or KO VSMCs. We could demonstrate in VSMCs with pharmacological inhibitors that PPP3CB leads to enhanced heparin‐binding EGF‐like growth factor (HB‐EGF) secretion, epidermal growth factor receptor (EGFR) activation and consecutive stimulation of transforming growth factor β(TGFβ) and connective tissue growth factor (CTGF) signalling that enhances collagen expression.

Conclusion

AngII‐induced vascular remodelling involves PPP3CB, which leads to enhanced EMC production, VSMC migration and sustained increase in systolic blood pressure via HBEGF/EGFR‐TGFβ‐CTGF signalling.
Hamiltonian Monte Carlo method for estimating variance components
Authors: Arakawa Aisaku , Hayashi Takeshi , Taniguchi Masaaki , Mikawa Satoshi , Nishio Motohide
Published: July 2021

A Hamiltonian Monte Carlo algorithm is a Markov chain Monte Carlo method, and the method has a potential to improve estimating parameters effectively. Hamiltonian Monte Carlo is based on Hamiltonian dynamics, and it follows Hamilton's equations, which are expressed as two differential equations. In the sampling process of Hamiltonian Monte Carlo, a numerical integration method called leapfrog integration is used to approximately solve Hamilton's equations, and the integration is required to set the number of discrete time steps and the integration stepsize. These two parameters require some amount of tuning and calibration for effective sampling. In this study, we applied the Hamiltonian Monte Carlo method to animal breeding data and identified the optimal tunings of leapfrog integration for normal and inverse chi‐square distributions. Then, using real pig data, we revealed the properties of the Hamiltonian Monte Carlo method with the optimal tuning by applying models including variance explained by pedigree information or genomic information. Compared with the Gibbs sampling method, the Hamiltonian Monte Carlo method had superior performance in both models. We have provided the source codes of this method written in the Fortran language at https://github.com/A-ARAKAWA/HMC.
How do self‐efficacy and self‐concept impact mathematical achievement? The case of mathematical modelling
Authors: Holenstein Mathias , Bruckmaier Georg , Grob Alexander
Published: July 2021

Background

According to the self‐enhancement perspective, self‐efficacy and self‐concept are shaped by prior achievement and have a crucial impact on future development. Their role in improving performance on challenging tasks, such as mathematical modelling (i.e., solving realistic problems mathematically), has barely been studied.

Aims

We investigated patterns of self‐efficacy and self‐concept and their predictive effects on mathematical modelling while taking into account school grades as measure of prior achievement and reasoning to reveal cognitive and motivational effects on achievement.

Sample

N = 279 secondary students in Grade 8 or 9 from 16 classes and 6 schools participated in the study.

Method

The multi‐informant design consisted of teachers’ reports of school grades, students’ reports of self‐efficacy and self‐concept (questionnaire‐based), and assessment of students’ reasoning and mathematical modelling.

Results

Using random‐intercept models, we found that the predictive effect of self‐efficacy on mathematical modelling withstood taking the school‐classroom‐related nested structure into account, whereas self‐concept lost its predictive value. Further, self‐efficacy fully mediated the effect of school grades on mathematical modelling.

Conclusions

In line with the self‐enhancement perspective on self‐efficacy, our findings highlight the strength of motivational effects on mathematical modelling. When we take the nested structure into account, our results indicate an impact of school grades via self‐efficacy on mathematical modelling independent of students’ cognitive level or classroom. Given the diverse challenges such complex tasks present, important pedagogical and didactical recommendations, such as targeting the enhancement of students’ self‐efficacy by teachers and educational decision makers, can be drawn.
Designing for “challenge” in a large‐scale adaptive literacy game for primary school children
Authors: Benton Laura , Mavrikis Manolis , Vasalou Asimina , Joye Nelly , Sumner Emma , Herbert Elisabeth , Revesz Andrea , Symvonis Antonios , Raftopoulou Chrysanthi
Published: July 2021

The use of learning games within the classroom is becoming increasingly common because of their potential to positively impact learning. Recent developments in adaptivity offer further possibilities to personalise learning by tailoring the game to an individual child's level or particular learning needs. However, designing an adaptive learning game is a complex process as many different game components have an impact on the provision of optimal challenge, crucial for maintaining player engagement, with limited prior work considering the multifaceted nature of this concept. This paper explores how to design for “challenge” within large‐scale adaptive learning games through a case study focused on the design of a literacy game for three linguistically and cognitively diverse learner groups—novice readers, children with dyslexia and children learning English as a foreign language. In reflecting on our design process, we identify three key design tensions that arose: (a) supporting longer‐term learning goals through game replayability; (b) fostering either replication or innovation in pedagogy through adaptivity rules; and (c) addressing diversity between learner groups. We present a set of design recommendations to guide researchers and designers in taking a multidimensional view of challenge when designing large‐scale adaptive learning games.

Practitioner notes

What is already known about this topic?

Adaptive learning games can have a positive impact on children's learning outcomes.

Ensuring optimal challenge within games is important for maintaining engagement.

Designing adaptive learning games is a complex process.

What this paper adds?

Designing for optimal challenge within adaptive learning game should be considered as a multifaceted concept.

Identification of key tensions related to optimising challenge that can emerge during the design of large‐scale adaptive learning games.

Recommendations for adaptivity researchers and learning game designers for how to address these tensions in adaptive learning game design.

Implications for practice and/or policy?

We need a more systematic approach to adaptivity game design to ensure wider spread adoption.

Learning game designers seeking to utilise adaptive components in designing for optimal challenge should consider a focus on learners who may require a more targeted approach.

Adaptive learning games offer opportunities for pedagogical innovation in the classroom through exploiting innovative game features as well as large‐scale data collection to support adaptive learning over time.
Severe neonatal haemolytic anaemia caused by compound heterozygous KLF1 mutations: report of four families and literature review
Authors: Tangsricharoen Tanu , Natesirinilkul Rungrote , Phusua Arunee , Fanhchaksai Kanda , Ittiwut Chupong , Chetruengchai Wanna , Juntharaniyom Monthana , Charoenkwan Pimlak , Viprakasit Vip , Phokaew Chureerat , Shotelersuk Vorasuk
Published: July 2021

Mutations in the KLF1 gene, which encodes a transcription factor playing a role in erythropoiesis, have recently been demonstrated to be a rare cause of hereditary haemolytic anaemia. We described the genotypic and phenotypic spectra of four unrelated families with compound heterozygous class 2/class 3 KLF1 mutations. All patients had p.G176RfsX179 on one allele and either p.A298P, p.R301H or p.G335R on the other allele. All presented on the first day of life with severe haemolytic anaemia with abnormal red blood cell morphology, markedly increased nucleated red blood cells and hyperbilirubinaemia. Three patients later became transfusion‐dependent. All parents with heterozygous KLF1 mutation without co‐inherited thalassaemia had normal to borderline mean corpuscular volume (MCV) and normal to slightly elevated Hb F. Fifteen previously reported cases of biallelic KLF1 mutations were identified from a literature review. All except one presented with severe haemolytic anaemia in the neonatal period. Our finding substantiates that compound heterozygous KLF1 mutations are associated with severe neonatal haemolytic anaemia and expands the haematologic phenotypic spectrum. In carriers, the previously suggested findings of low MCV, high Hb A2 and high Hb F are inconsistent; thus this necessitates molecular studies for the identification of carriers.
Building Mistrust: ‘Minha Casa Minha Vida’ and its Political Effects in Rio de Janeiro
Authors: Stefani Silvia
Published: July 2021

Considering the recent decrease in Rio de Janeiro working‐class voters' support for the Partido dos Trabalhadores (PT, Workers' Party), this article investigates a largely unexplored factor behind this shift: the influence of the federal housing programme Minha Casa Minha Vida (MCMV, My House, My Life), designed by the PT. It is argued that the programme's features and its intersection with local political junctures have resulted in worsening living conditions for many residents and increasing socio‐spatial segregation. Understanding policies as a domain in which people experience politics and shape political subjectivities, the article suggests that the poor implementation of the MCMV has contributed to spreading disillusionment with the PT and politicians at large among Rio de Janeiro's working classes, a shift that made Bolsonaro with his anti‐establishment framing a viable option in 2018.
Small nucleolar RNA networks are up‐regulated during human anaphylaxis
Authors: McGrath Francesca Marina , Francis Abbie , Fatovich Daniel M. , Macdonald Stephen P. J. , Arendts Glenn , Bosco Anthony , Woo Andrew , Bosio Erika
Published: July 2021

Background

Anaphylaxis is a severe, potentially life‐threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department (ED).

Objective

This study sought to explore gene expression changes associated with anaphylaxis severity in peripheral blood leucocytes and evaluate biomarker potential.

Methods

Microarray analysis (total RNA) was performed using peripheral blood samples from ED patients with moderate (n = 6) or severe (n = 12) anaphylaxis and sepsis (n = 20) at presentation (T0) and one hour later (T1). Results were compared between groups and healthy controls (n = 10 and n = 11 matched to anaphylaxis and sepsis patients, respectively). Changes in gene expression were determined using R programming language, and pathway analysis applied to explore biological processes and pathways associated with genes. Differentially expressed genes were validated in an independent cohort of anaphylaxis (n = 30) and sepsis (n = 20) patients, and healthy controls (n = 10), using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR).

Results

Significant up‐regulation of small nucleolar RNAs (snoRNAs) was demonstrated in anaphylaxis compared to sepsis patients in the microarray cohort, at T0 and T1. qRT‐PCR analysis of the validation cohort showed five genes: SNORD61, SNORD8, SNORD69, SNORD119 and HIST1H1D to be significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to sepsis. Seven genes (SNORD61, SNORD8, SCARNA21, SNORD69, SNORD110, SNORD119 and SNORD59A) were significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to healthy controls.

Conclusion

This study demonstrates for the first time the unique involvement of snoRNAs in the pathogenesis of anaphylaxis and suggests they are not a general feature of systemic inflammation. Further investigation of snoRNA expression in anaphylaxis could provide insights into disease pathogenesis.

Clinical relevance

SnoRNAs are up‐regulated during acute anaphylaxis in humans and could potentially be used as biomarkers of severe anaphylaxis.
Impact of SGLT2 inhibitors in comparison with DPP4 inhibitors on ascites and death in veterans with cirrhosis on metformin
Authors: Saffo Saad , Kaplan David E. , Mahmud Nadim , Serper Marina , John Binu V. , Ross Joseph S. , Taddei Tamar
Published: July 2021

Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) may have favourable neurohumoral and metabolic effects in patients with chronic liver disease. However, studies examining SGLT2i in this population have been limited to patients with non‐alcoholic fatty liver disease and have focused on surrogate biomarkers. Our aim was to evaluate whether SGLT2i can reduce the incidence of ascites and death over a period of 36 months in patients with cirrhosis and diabetes mellitus. Using electronic health data from Veterans Affairs hospitals in the United States, we conducted a propensity score matched intention‐to‐treat analysis among veterans on metformin who subsequently received either SGLT2i or dipeptidyl peptidase‐4 inhibitors. Among 423 matched pairs (in total, 846 patients), we found no significant difference in the risk for ascites (hazard ratio 0.68 for SGLT2i, 95% confidence interval 0.37‐1.25; p = .22) but did find that SGLT2i users had a reduced risk for death (adjusted hazard ratio 0.33, 95% confidence interval 0.11‐0.99; p < .05). In comparison with dipeptidyl peptidase‐4 inhibitors, SGLT2i may improve survival for patients with cirrhosis who require additional pharmacotherapy for diabetes mellitus beyond metformin, but confirmatory studies are necessary.
“Don’t you care about the well‐being of your race?”: African American couples discuss racial differences involving criticisms of other Black people
Authors: Kelly Shalonda , Kellman Tara
Published: July 2021

African American couples have unique racial stress and high relationship instability, although few studies have examined the role of racial stressors in their relationships. This qualitative study used grounded theory to examine 10 African American couples’ disagreements about criticisms of other Black people. Each couple completed a standard couple problem‐solving task modified to focus solely on racial differences between the partners. Two models of couple relationships framed the approach; the general vulnerability‐stress‐adaptation model (Karney & Bradbury, Psychol. Bull., 118, 1995, 3) was combined with a comprehensive race‐focused model (Bryant et al., J. Fam. Theory Rev., 2, 2010, 157). The goal was to understand racial stress faced by African Americans, including its context, how and why it is stressful, how they cope, and its consequences in their relationship. A tentative model emerged, suggesting that some African Americans have early race‐related experiences that make them vulnerable to concerns about how Black people are seen by others. This may result in a unique minority status stressor that appears indicative of internalized stereotypes and may often include gendered criticisms of their partners. Partners seem to adapt by looking to other African Americans to take personal responsibility for their behavior and defending their racial group. Black male‐female gender role issues appear to emerge as a consequence of racial stress that also seems salient across all aspects of the model. Future studies can further examine culturally specific models involving African Americans’ criticisms of other Black people and identify successful couple‐level strategies to overcome internalized oppression.
Oncogenic KRAS creates an aspartate metabolism signature in colorectal cancer cells
Authors: Doubleday Peter F. , Fornelli Luca , Ntai Ioanna , Kelleher Neil L.
Published: July 2021

Oncogenic mutations in the KRAS gene are found in 30–50% of colorectal cancers (CRC), and recent findings have demonstrated independent and nonredundant roles for wild‐type and mutant KRAS alleles in governing signaling and metabolism. Here, we quantify proteomic changes manifested by KRAS mutation and KRAS allele loss in isogenic cell lines. We show that the expression of KRASG13D upregulates aspartate metabolizing proteins including PCK1, PCK2, ASNS, and ASS1. Furthermore, differential expression analyses of transcript‐level data from CRC tumors identified the upregulation of urea cycle enzymes in CRC. We find that expression of ASS1 supports colorectal cancer cell proliferation and promotes tumor formation in vitro. We show that loss of ASS1 can be rescued with high levels of several metabolites.
Characterization of G4 DNA formation in mitochondrial DNA and their potential role in mitochondrial genome instability
Authors: Dahal Sumedha , Siddiqua Humaira , Katapadi Vijeth K. , Iyer Divyaanka , Raghavan Sathees C.
Published: July 2021

Mitochondria possess their own genome which can be replicated independently of nuclear DNA. Mitochondria being the powerhouse of the cell produce reactive oxygen species, due to which the mitochondrial genome is frequently exposed to oxidative damage. Previous studies have demonstrated an association of mitochondrial deletions to aging and human disorders. Many of these deletions were present adjacent to non‐B DNA structures. Thus, we investigate noncanonical structures associated with instability in mitochondrial genome. In silico studies revealed the presence of > 100 G‐quadruplex motifs (of which 5 have the potential to form 3‐plate G4 DNA), 23 inverted repeats, and 3 mirror repeats in the mitochondrial DNA (mtDNA). Further analysis revealed that among the deletion breakpoints from patients with mitochondrial disorders, majority are located at G4 DNA motifs. Interestingly, ~ 50% of the deletions were at base‐pair positions 8271–8281, ~ 35% were due to deletion at 12362–12384, and ~ 12% due to deletion at 15516–15545. Formation of 3‐plate G‐quadruplex DNA structures at mitochondrial fragile regions was characterized using electromobility shift assay, circular dichroism (CD), and Taq polymerase stop assay. All 5 regions could fold into both intramolecular and intermolecular G‐quadruplex structures in a KCl‐dependent manner. G4 DNA formation was in parallel orientation, which was abolished in the presence of LiCl. The formation of G4 DNA affected both replication and transcription. Finally, immunolocalization of BG4 with MitoTracker confirmed the formation of G‐quadruplex in mitochondrial genome. Thus, we characterize the formation of 5 different G‐quadruplex structures in human mitochondrial region, which may contribute toward formation of mitochondrial deletions.
Identification of a special cell type as a determinant of the kidney tropism of SARS‐CoV‐2
Authors: Lin Hongchun , Ma Xinxin , Xiao Fang , Su Hua , Shi Yaling , Liu Yuntao , Song Lan , Zhang Zhongde , Zhang Chun , Peng Hui
Published: July 2021

The kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been well‐validated clinically and often leads to various forms of renal damage in coronavirus disease‐2019 (COVID‐19) patients. However, the underlying mechanisms and diagnostic approaches remain to be determined. We interrogated the expression of virus‐related host factors in single‐cell RNA sequencing (scRNA‐seq) datasets of normal human kidneys and kidneys with pre‐existing diseases and validated the results with urinary proteomics of COVID‐19 patients and healthy individuals. We also assessed the effects of genetic variants on kidney susceptibility using expression quantitative trait loci (eQTLs) databases. We identified a subtype of tubular cells, which we named PT‐3 cells, as being vulnerable to SARS‐CoV‐2 infections in the kidneys. PT‐3 cells were enriched in viral entry factors and replication and assembly machinery but lacked antiviral restriction factors. Immunohistochemistry confirmed positive staining of PT‐3 cell marker SCL36A2 on kidney sections from COVID‐19 patients. Urinary proteomic analyses of COVID‐19 patients revealed that markers of PT‐3 cells were significantly increased, along with elevated viral receptor angiotensin‐converting enzyme 2. We further found that the proportion of PT‐3 cells increased in diabetic nephropathy but decreased in kidney allografts and lupus nephropathy, suggesting that kidney susceptibility varied among these diseases. We finally identified several eQTLs that regulate the expression of host factors in kidney cells. PT‐3 cells may represent a key determinant for the kidney tropism of SARS‐CoV‐2, and detection of PT‐3 cells may be used to assess the risk of renal infection during COVID‐19.
Understanding humectant behaviour through their water‐holding properties
Authors: Crowther Jonathan M.
Published: July 2021

Objective

Humectants perform essential roles in the formulation of topical moisturizing products in terms of delivery of active ingredients, consumer experience and biophysical behaviour. How they retain and release water is key to understanding their behaviour.

Methods

Dynamic vapour sorption (DVS) was used to monitor the dehydration kinetics of three humectants widely used in topical formulations—glycerine, dexpanthenol and urea. Model aqueous solutions with concentrations of 20% w/w were tested and compared against pure deionized water.

Results

The three humectants varied in their ability to retain water during the dehydration process. Dexpanthenol was able to retain water most efficiently during the latter stages of dehydration. Urea demonstrated evidence of crystallization during the final stage of water loss, which was not shown by glycerine or dexpanthenol.

Conclusions

Humectants perform vital roles in the formulation of consumer acceptable topical products including the delivery of actives to the skin. Their ability to influence water movement in the skin is also essential for the maintenance of stratum corneum flexibility. DVS assessment of aqueous solutions has demonstrated how the behaviour of three commonly used humectants differs. Knowledge of the mechanisms by which these humectants operate enables the formulator to develop topical products optimized for the roles for which they are intended.
Extension of separation along the follicular epithelium and follicular basement membrane in pemphigus and bullous pemphigoid
Authors: Genedy Rasha M. , Mohamed Abdiwale , El‐Mulla Khaled
Published: July 2021

Background

The outer root sheath of hair follicle and the interfollicular epidermis are continuous and basically similar in many aspects. The expression of various basement membrane (BM) components in the upper portion of the hair follicle is similar to that of the interfollicular BM. The extension of acantholysis into the adnexal structures was highlighted in the pemphigus group of diseases. On the other hand, extension of separation down the hair follicle BM has not been studied in subepidermal autoimmune bullous dermatoses. The aim of the present work was to study the extension of separation along follicular epithelium and follicular BM in pemphigus and bullous pemphigoid.

Methods

This retrospective study was conducted on pemphigus and bullous pemphigoid cases. For each case, 4‐μm‐thick sections stained with hematoxylin and eosin were examined for the presence of hair follicles and the extension of separation down follicular epithelium and follicular BM.

Results

Positive extension of acantholysis down the follicular epithelium was seen in 23/27 (85.2%) of pemphigus vulgaris (PV) and 7/9 (77.8%) of pemphigus foliaceus (PF) cases with hair follicles. Follicular extension was limited to the infundibulum in PF but down the entire follicular length in PV. As for bullous pemphigoid (BP) cases, 20/26 cases (76.9%) that had hair follicles showed positive extension of the separation down the follicular BM. The cellular infiltrate detected was identical in its nature and density to that of subepidermal blister in all cases.

Conclusions

Extension of the separation along follicular epithelium and follicular basement membrane was observed in PV, PF, and BP without significant difference.
Tumor contact length of prostate cancer determined by a three‐dimensional method on multiparametric magnetic resonance imaging predicts extraprostatic extension and biochemical recurrence
Authors: Miyamoto Shunsuke , Goto Keisuke , Honda Yukiko , Terada Hiroaki , Fujii Shinsuke , Ueno Takeshi , Fukuoka Kenichiro , Sekino Yohei , Kitano Hiroyuki , Ikeda Kenichiro , Hieda Keisuke , Inoue Shogo , Hayashi Tetsutaro , Teishima Jun , Takeshima Yukio , Yasui Wataru , Awai Kazuo , Matsubara Akio
Published: July 2021

Objective

To evaluate the clinical benefit of tumor contact length as a predictor of pathological extraprostatic extension and biochemical recurrence in patients undergoing prostatectomy.

Methods

A total of 91 patients who underwent 3T multiparametric magnetic resonance imaging before prostatectomy from April 2014 to July 2019 were included. A total of 94 prostate cancer foci were analyzed retrospectively. We evaluated maximum tumor contact length, which was determined to be the maximum value in the three‐dimensional directions, as a predictor of pathological extraprostatic extension and biochemical recurrence.

Results

A total of 19 lesions (20.2%) had positive pathological extraprostatic extension. Areas under the curves showed maximum tumor contact length to be a significantly better parameter to predict pathological extraprostatic extension than the Prostate Imaging Reporting and Data System (P = 0.002), tumor maximal diameter (P = 0.001), prostate‐specific antigen (P = 0.020), Gleason score (P < 0.001), and clinical T stage (P < 0.001). Multivariate analysis showed maximum tumor contact length (P = 0.003) to be an independent risk factor for predicting biochemical recurrence. We classified the patients using preoperative factors (prostate‐specific antigen >10, Gleason score >3 + 4 and maximum tumor contact length >10 mm) into three groups: (i) high‐risk group (patients having all factors); (ii) intermediate‐risk group (patients having two of three factors); and (iii) low‐risk group (patients having only one or none of the factors). Kaplan–Meier curves showed that the high‐risk group had significantly worse biochemical recurrence than the intermediate‐risk group (P = 0.042) and low‐risk group (P < 0.001).

Conclusions

Our findings suggest that maximum tumor contact length is an independent predictor of pathological extraprostatic extension and biochemical recurrence. A risk stratification system using prostate‐specific antigen, Gleason score and maximum tumor contact length might be useful for preoperative assessment of prostate cancer patients.
Use of graft‐derived cell‐free DNA as a novel biomarker to predict allograft function after kidney transplantation
Authors: Di Wenjia , Ran Qing , Yang Hongji , Lu Jun , Hou Yifu , Wang Xiaoxiao , He Jiayang , Wei Liang
Published: July 2021

Objective

To investigate the association between graft‐derived cell‐free DNA and pretransplantation clinical variables, and to determine whether the former could be used as a novel biomarker to predict renal function.

Methods

A total of 87 recipients who underwent primary kidney transplantation were recruited to the study. For each recipient, 10 mL peripheral blood was collected on days 1, 7, 14–20, and 30–45 after transplantation. The fractional abundance of graft‐derived cell‐free DNA was determined using droplet digital polymerase chain reaction.

Results

For most recipients, graft‐derived cell‐free DNA fraction values were significantly elevated on the first day after transplantation, followed by a rapid decline, and reaching baseline values of graft‐derived cell‐free DNA fraction in the range of <1% at 7 days. Statistical analysis showed that longer cold ischemia time was significantly associated with higher graft‐derived cell‐free DNA fraction values (P = 0.02). Moreover, we also found that graft‐derived cell‐free DNA fraction values among recipients with delayed graft function were significantly higher than those of recipients without delayed graft function on the first day after transplantation. Kaplan–Meier analysis showed that recipients who had a graft‐derived cell‐free DNA fraction value of <1% at 7 days had a significantly lower probability of an estimated glomerular filtration rate ≤60 mL/min/1.73 m2at 90 days. Using a random forest regression model, the predicted values of estimated glomerular filtration rate at 90 days were almost the same as the actual values.

Conclusions

Our findings suggest that graft‐derived cell‐free DNA might be used as a novel biomarker to predict delayed graft function and renal function.