bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcrowding kills: How COVID‐19 could reshape emergency department patient flow in the new normal
Authors: Dinh Michael M , Berendsen Russell Saartje
Published: December 2020

The ongoing public health crisis due to COVID‐19 highlights the importance of a coordinated system‐wide approach to health resource management, and the need to mitigate the risk of ED overcrowding. We provide a brief perspective on the current evidence and why a fundamental shift in approach is required. Current time‐based performance targets have hindered efforts to address core issues around patient flow in EDs. A stronger focus on optimising hospital occupancy, clinician engagement and data would facilitate more appropriate and sustainable solutions to the problem. Appropriate policy drivers are required to facilitate whole‐of‐hospital models of care, with a focus on avoidable admissions, complications and reduced hospital length of stay.
Imaging triage of acute stroke patients for endovascular clot retrieval: Effect of increased therapeutic window on the utilization of CT perfusion
Authors: Fernandez Michelle , Farmer Caitlin , Egerton–Warburton Diana , Clark Jennifer , Paul Eldho , Chong Winston , Goergen Stacy K
Published: December 2020

Introduction

Recent randomized trials showing improved outcomes for later‐presenting acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO) treated with endovascular clot retrieval (ECR) may result in substantial increases in CTP utilization. This 3‐hospital, single‐institution cohort study aimed to compare 2017 and 2018 patient cohorts for the following:

CTP use in AIS.

Prevalence of LVO in all patients having CTP.

Number and clinical characteristics of patients triaged to ECR.

Number of patients receiving CTP relative to similar‐acuity total ED presentations.

Methods

Inclusion criteria: Consecutive adult emergency (ED) patients receiving CTP for suspected AIS. Study period 1:1 January–30 June 2017; Period 2:1 January–30 June 2018. Data collection: age, gender, triage category, NIHSS (National Institute of Health Stroke Score), symptoms/signs, time elapsed since last seen well (TESLSW) to triage, disposition (home/other).

Results

A 38.7 % increase in CTP (512 in 2017, 710 in 2018) occurred with 39/512 (7.6%) and 72/710 (10.1%) having intended ECR. CTPs per intended ECR declined from 13.1 to 9.9. 36/512 (7.0%) and 58/710 (8.2%) patients had ECR (61.1% increase) and 22/36 (61.1%) and 25/58 (43.1%) of these were discharged home in 2017 and 2018, respectively, an increase of 3/22(14%).

Conclusion

Despite a 38.7% increase in CTP utilization, we experienced a reduction in the number of CTPs performed/patient triaged to ECR. This did not reflect higher LVO prevalence among later presenters but may reflect changed selection criteria for CTP and/or decision making about suitability for ECR.
SCycDB: A curated functional gene database for metagenomic profiling of sulphur cycling pathways
Authors: Yu Xiaoli , Zhou Jiayin , Song Wen , Xu Mengzhao , He Qiang , Peng Yisheng , Tian Yun , Wang Cheng , Shu Longfei , Wang Shanquan , Yan Qingyun , Liu Jihua , Tu Qichao , He Zhili
Published: December 2020

Microorganisms play important roles in the biogeochemical cycling of sulphur (S), an essential element in the Earth's biosphere. Shotgun metagenome sequencing has opened a new avenue to advance our understanding of S cycling microbial communities. However, accurate metagenomic profiling of S cycling microbial communities remains technically challenging, mainly due to low coverage and inaccurate definition of S cycling gene families in public orthology databases. Here we developed a manually curated S cycling database (SCycDB) to profile S cycling functional genes and taxonomic groups for shotgun metagenomes. The developed SCycDB contains 207 gene families and 585,055 representative sequences affiliated with 52 phyla and 2684 genera of bacteria/archaea, and 20,761 homologous orthology groups were also included to reduce false positive sequence assignments. SCycDB was applied for functional and taxonomic analysis of S cycling microbial communities from four habitats (freshwater, hot spring, marine sediment and soil). Gene families and microorganisms involved in S reduction were abundant in the marine sediment, while those of S oxidation and dimethylsulphoniopropionate transformation were abundant in the soil. SCycDB is expected to be a useful tool for fast and accurate metagenomic analysis of S cycling microbial communities in the environment.
An Ethnography of Vulnerability: A New Materialist Approach to the Apparatus of Measurement, the Algorithm
Authors: Riberi Valentina , González Erika , Rojas Lasch Carolina
Published: December 2020

During an ethnographic study of two Chilean schools over a period of three years, we observed the discursive assemblage of “what is vulnerable” emerging from an algorithm used to allocate public resources. In this article, we unravel the ways in which the algorithm intra‐acts with other elements in the process of producing what is vulnerable and how this affects our approach to ethnography. We conclude by considering two methodological dilemmas that arose from our work.
Frailty, and not medicines with anticholinergic or sedative effects, predicts adverse outcomes in octogenarians admitted for myocardial infarction: Population‐level study
Authors: Lopez Derrick , Preen David B. , Etherton‐Beer Christopher , Sanfilippo Frank M.
Published: December 2020

Objective

To determine independent associations between the use of medicines with anticholinergic or sedative effects and frailty with outcomes of length of stay (LOS), coronary artery procedure performed and 30‐day deaths in octogenarians admitted for a myocardial infarction (MI).

Methods

We quantified patient exposure to medicines with anticholinergic or sedative effects using the drug burden index (DBI) and frailty using the hospital frailty risk score (HFRS). We used multivariable regression methods to determine the association between DBI and HFRS with outcomes of LOS, coronary artery procedures performed and 30‐day deaths.

Results

HFRS and not DBI score was significantly associated with receipt of coronary artery procedures (odds ratio [OR] 0.42; 95% CI 0.28‐0.62 for high‐ versus low‐risk groups) and 30‐day deaths (OR 1.58; 95% CI 1.12‐2.24 for high‐ versus low‐risk groups).

Conclusion

Frailty risk is a more important predictor of outcomes than DBI score for octogenarians with an MI.
Two robust tools for inference about causal effects with invalid instruments
Authors: Kang Hyunseung , Lee Youjin , Cai T. Tony , Small Dylan S.
Published: December 2020

Instrumental variables have been widely used to estimate the causal effect of a treatment on an outcome. Existing confidence intervals for causal effects based on instrumental variables assume that all of the putative instrumental variables are valid; a valid instrumental variable is a variable that affects the outcome only by affecting the treatment and is not related to unmeasured confounders. However, in practice, some of the putative instrumental variables are likely to be invalid. This paper presents two tools to conduct valid inference and tests in the presence of invalid instruments. First, we propose a simple and general approach to construct confidence intervals based on taking unions of well‐known confidence intervals. Second, we propose a novel test for the null causal effect based on a collider bias. Our two proposals outperform traditional instrumental variable confidence intervals when invalid instruments are present and can also be used as a sensitivity analysis when there is concern that instrumental variables assumptions are violated. The new approach is applied to a Mendelian randomization study on the causal effect of low‐density lipoprotein on globulin levels.
Protein phosphatase, Mg2+/Mn2+‐dependent 1D (PPM1D) mutations in haematological cancer
Authors: Husby Simon , Hjermind Justesen Emma , Grønbæk Kirsten
Published: December 2020

Until recently, the protein phosphatase, Mg2+/Mn2+‐dependent 1D (PPM1D) gene had not been examined in haematological cancer, but several studies have now explored the functional role of this gene and its aberrations. It is often mutated in the context of clonal haemopoiesis (including in patients with lymphoma, myeloproliferative neoplasms and myelodysplastic syndrome) and mutations have been associated with exposure to cytotoxic and radiation therapy, development of therapy‐related neoplasms and inferior survival. The vast majority of PPM1D mutations found in haematopoietic cells are of the nonsense or frameshift type and located within terminal exon 6. These genetic defects are rarely found in the blood of healthy individuals. PPM1D encodes the PPM1D phosphatase [also named wild‐type p53‐induced phosphatase 1 (WIP1)], which negatively regulates signalling molecules within the DNA damage response pathway, including tumour suppressor p53. Clonal expansion of PPM1D mutant haematopoietic cells can potentially be prevented with inhibitors; however, human trials are awaited. In the present review, we provide a review of the literature regarding PPM1D and its role in haematological cancer.
New Interest Associations in a Neo‐Corporatist System: Adapting the Swiss Training System to the Service Economy
Authors: Strebel Alexandra , Emmenegger Patrick , Graf Lukas
Published: December 2020

Collective skill formation systems need to adapt to economic change, most notably the expansion of the service economy. However, deeply anchored in the craft and industrial sectors, these systems rely on neo‐corporatist institutions to undergird firms’ training provision, which are often missing in the service sector. We show that Switzerland's voluntaristic approach to interest intermediation provided the flexibility needed to extend vocational training to economic sectors without neo‐corporatist institutions. Yet, these adaptations resulted in the emergence of interest associations characterised by low levels of generalisability and governability. These new associations co‐exist with neo‐corporatist ones, rendering the overall training system surprisingly heterogeneous.
A disability‐based exploration of psychosocial barriers and enablers to accessing dental services for people with clinically severe obesity: A qualitative study
Authors: Malik Zanab , Holden Alexander C. L. , Sohn Woosung , Williams Kathryn
Published: December 2020

This qualitative study aimed to explore psychosocial barriers and enablers to accessing dental services for people with clinically severe obesity (PwCSO). Eight focus groups were conducted by one researcher with 40 adult participants at the Adult Healthy Weight Clinic within a hospital‐based obesity service. Thematic analysis of focus group transcripts was performed to reveal insights relating to how PwCSO experience dental care and view oral health. A total of 11 participants were male, 29 female, all between the ages of 23 to 74 (mean age of 50). The body mass index of participants ranged from 31.6 to 84.6 kg/m2. The results highlighted four key themes, including “disempowerment to act to improve oral health”, “weight‐related stigma and discrimination”, “unpredictability of the dental environment” and a “lack of tailored services for PwCSO”. A number of subthemes were identified, which reflect the six categories of barriers to access from the disability literature: availability, affordability, acceptability, accommodation, accessibility and appropriateness. These were explored to further appreciate the unique psychosocial considerations for this group. This study concluded that PwCSO face significant barriers to accessing dental services across all six categories highlighted in the disability literature. The study findings provide valuable patient‐based information regarding the psychosocial barriers to accessing dental services, which are relevant for all healthcare professionals. The study reflected an increased need for promotion of the dentist's role in obesity management and obesity‐related dental training, including familiarization with the biopsychosocial domains of obesity to reduce weight related stigma and discrimination, as an area for further study. The findings also guide the design of Specialized Bariatric Dental Services in the future, with a focus on enablers to access.
Application of least absolute shrinkage and selection operator logistic regression for the histopathological comparison of chondrodermatitis nodularis helicis and hyperplastic actinic keratosis
Authors: Narala Saisindhu , Li Shirley Q. , Klimas Natasha K. , Patel Anisha B.
Published: December 2020

Background

The distinction between chondrodermatitis nodularis helicis (CNH) and hyperplastic actinic keratosis (HAK) on the ear can pose a diagnostic challenge. We aimed to identify histopathological characteristics that could distinguish between CNH and HAK on routine sections using penalized least absolute shrinkage and selection operator (LASSO) logistic regression analysis.

Methods

Cases of CNH (n = 80) and HAK (n = 28) were analyzed for selected histopathological characteristics. Fisher's exact test and LASSO regression were performed.

Results

In univariate analyses, the following were significantly associated with CNH: ulceration, acanthosis, granular layer in the majority of the lesion, hypergranulosis at the periphery of the lesion, hyperkeratosis at the periphery of the lesion, hyperparakeratosis at the periphery of the lesion, fibrosis, increased blood vessels, vertically oriented blood vessels, and fibrin. A LASSO model excluding atypia found that fibrin, fibrosis, presence of granular layer, ulceration, and vertically oriented blood vessels were most predictive of CNH. Keratinized strap cells were not a significant predictor.

Conclusion

We have identified features that may aid in differentiating these entities and demonstrated that a LASSO regression model can identify predictors that may improve diagnostic accuracy. Our results indicate that the highest diagnostic accuracy in this dilemma is dependent on obtaining biopsy specimens with visible dermis.
Early intervention services, patterns of prescription and rates of discontinuation of antipsychotic treatment in first‐episode psychosis
Authors: Catalan Ana , García Lorena , Sanchez‐Alonso Sergio , Gil Patxi , Díaz‐Marsá Marina , Olivares José Manuel , Rivera‐Baltanás Tania , Pérez‐Martín Jorge , Torres Miguel Ángel González , Ovejero Santiago , Tost Meritxell , Bergé Daniel , Rodríguez Alfonso , Labad Javier
Published: December 2020

Aims

Non‐compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first‐episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group.

Methods

We evaluated a large sample of patients with FEP for 2 years to compare the time to all‐cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded.

Results

A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non‐compliance. There were no differences in the relapse rates between different APs. Patients treated with long‐acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs.

Conclusions

Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.
Measuring personality traits in Eurasian red squirrels: A critical comparison of different methods
Authors: Santicchia Francesca , Van Dongen Stefan , Martinoli Adriano , Preatoni Damiano , Wauters Lucas Armand
Published: December 2020

Animal personality, behavioural differences among individuals which are consistent through time and contexts, is generally described by one or more traits. Different methods are used to measure these traits, such as behavioural observations and trapping indices. Comparing several methods allows to validate different tests and to better identify which aspect of an animal's personality is being measured. Here, we measured activity, exploration and immobility of Eurasian red squirrels (Sciurus vulgaris) using observations from the open field test (OFT), and compared them with trappability and trap‐diversity indices calculated from capture–mark–recapture data in six independent study sites. Trappability measures the willingness to enter a baited trap (boldness), while trap‐diversity can be a proxy for exploration tendency. Our first aim was to test their repeatability, thus their appropriateness as candidate measures of personality traits. Next, we explored the predictions that (i) trappability, measuring boldness, does not correlate with any of the OFT personality traits, since risk‐taking cannot be expressed in our arena test; and (ii) trap‐diversity correlates with exploration obtained from the OFT. Considering the species ecology and study design, we used multivariate Bayesian models based on different time intervals (session/year) and habitat types (alpine/plain). We found significant repeatabilities for trappability, for trap‐diversity and for most OFT personality traits, except exploration in the plain sites. Independently from habitat type or time interval, trappability did not correlate with either activity, exploration or immobility from OFT, thus measuring a different personality axis, which we considered a proxy for boldness. Trap‐diversity did not correlate with exploration from OFT, but seems related to a different aspect of red squirrels' exploration tendency. Our study emphasizes that caution is needed when using behaviours from OFT to measure multiple personality traits and that applying extra methods based on animals’ responses to trapping can provide reliable proxies for boldness and exploration tendency.
Fisher behaviour in coastal and marine fisheries
Authors: Andrews Evan J. , Pittman Jeremy , Armitage Derek R.
Published: December 2020

This research systematically reviews fisher behaviour in coastal and marine fisheries. Fisher behaviour refers to individual and group level action that reflects the psychological processing and social exchange of information in fisheries. Fisher behaviour is poorly conceptualized and explained in fisheries research, and the implications of fisher behaviour for governance outcomes remain uncertain. To address this gap, we present a systematic scoping review of peer‐reviewed literature (n = 104 journal articles published from 2012 to 2017). Results highlight a typology of fisher behaviour and reveal insights into behavioural types and their explanations commonly used in conceptual and empirical models. This research reveals three major implications for governance. First, researchers can strengthen recommendations for governance by examining fisher behaviours as multilevel and multiscale phenomena. Second, researchers in governance can improve capacities to anticipate behavioural change with theoretical models that prioritize psychosocial variables, and interdisciplinary empirical research on the extrinsic factors that shape the fishers’ psychosocial responses to change in a local context. Third, social and policy sciences research is needed to reveal the governance barriers and opportunities for using new models that incorporate fisher behaviour to develop, implement and evaluate fisheries policies.
Temporal biodiversity change following disturbance varies along an environmental gradient
Authors: Kaarlejärvi Elina , Salemaa Maija , Tonteri Tiina , Merilä Päivi , Laine Anna‐Liisa
Published: December 2020

Aim

The diversity and composition of natural communities are rapidly changing due to anthropogenic disturbances. Magnitude of this compositional reorganization varies across the globe, but reasons behind the variation remain largely unknown. Disturbances induce temporal turnover by stimulating species colonizations, causing local extinctions, altering dominance structure, or all of these. We test which of these processes drive temporal community changes, and whether they are constrained by natural environmental gradients. Moreover, we assess to what degree identity shifts translate to changes in dominance structure.

Location

Finland.

Time period

Observations 1985–2006, disturbance history > 140 years.

Major taxa studied

Vascular plants.

Methods

We investigated temporal turnover of boreal forest understorey in response to disturbance, here forest management, along a soil fertility gradient. We disentangle the roles of species gains, losses and abundance changes in driving temporal turnover in response to and after disturbance by comparing turnover rates in different forest age categories along a fertility gradient. We quantify temporal turnover using richness‐based complement of Jaccard’s similarity index and proportional‐abundance based dissimilarity index. We also test whether disturbance history or fertility influence the relationship between identity shifts and dominance structure.

Results

We found that the impact of disturbance on temporal turnover depends on soil fertility. The greatest turnover occurred in the most fertile forests immediately after disturbance. There, species gains and losses strongly altered dominance structure leading to high turnover, whereas undisturbed old forests and nutrient‐poor habitats were characterized by stable dominant species even when the majority of species shifted their identity.

Main conclusions

Our results suggest that human impacts on temporal biodiversity change vary along environmental gradients. In boreal forests, the fertile habitats have a higher probability than nutrient‐poor sites of changing their composition in response to anthropogenic disturbances. Resource availability and disturbance history may thus influence consequences of temporal turnover for ecosystem functioning.
Controllable synthesis of pure monodispersed zirconia nanopowders with tetragonal phase
Authors: He Weiyan , Guo Xia , Zhao Xiaobing , Liu Jinrong
Published: December 2020

Nanopowders of pure zirconia have been synthesized using citric acid (CA)‐assisted lamellar liquid crystal template method. The microstructure of the zirconia powder prepared at the different mole ratios of CA to zirconium oxynitrate (ZN) was characterized by FT‐IR, X‐ray diffraction (XRD), laser particle size analyzer, Raman spectroscopy, and scanning electron microscope (SEM) methods. The phase structure of the sodium dodecyl sulfate (SDS)/C10H21OH/H2O system before and after adding mixing solution CA and ZN was determined by POM (Polarizing Optical Microscope). The results show that lamellar structure of the SDS/C10H21OH/H2O system after adding mixing solution CA and ZN is stable. The presence of CA inhibits agglomeration and growth of zirconia particle. The crystallite size of zirconia powders decreases and agglomerates lowly with addition of CA. Fourier transform infrared spectrometry (FI‐IR) analyses reveal that the structure of chelating organic complex is maintained in zirconia structure at high‐temperature calcination to cause oxygen vacancies which stabilizes the tetragonal phase of zirconia. The zirconia powders remained the single metastable tetragonal phase at the molar ratios of CA to ZN ranging from 1:3 to 5:1. The crystallite size of zirconia with spherical morphology varied from 32.2 to 20.1 nm with the increase of the molar ratio of CA to ZN in the range of 1:3 to 5:1.
Trends in the management of hidradenitis suppurativa in the Middle East region: a systematic review
Authors: Karvar Mehran , Panayi Adriana C. , Alavi Afsaneh , Baziar Zahra , Orgill Dennis P.
Published: December 2020

Background

Hidradenitis suppurativa (HS) is a chronic, painful, and severely debilitating inflammatory disease that affects apocrine gland‐bearing skin. There is no universal consensus on the management of hidradenitis suppurativa (HS). Current available guidelines are from western countries, which may be of limited use in other parts of the world. In this study, we aim to identify trends in the management of HS in the Middle East (ME) and its differences with the West.

Methods

A systematic literature review was performed to identify all studies in HS management performed by experts in the ME from database inception to June 2020 using PubMed, EMBASE, and Cochrane Library databases. Only original articles published in English language were included. Guidelines from western countries were used for comparison.

Results

Fifty‐four eligible studies comprising 7649 HS patients from the ME region and nine guidelines from the West were included. No established guidelines were found for the management of HS in the ME. Sex ratio of HS patients in the ME is different in that men reported to be affected at a higher rate than in the West. Different antibiotic regimens were recommended in the ME, and the experts in the ME tend to be more procedure intensive than experts in the West.

Conclusions

Establishing a guideline for HS management in the ME is recommended to address unique considerations in the countries in this region.
Noninflammatory comedones have greater diversity in microbiome and are more prone to biofilm formation than inflammatory lesions of acne vulgaris
Authors: Loss Manisha , Thompson Katherine G. , Agostinho‐Hunt Alessandra , James Garth A. , Mongodin Emmanuel F. , Rosenthal Ian , Cheng Nancy , Leung Sherry , Chien Anna L. , Kang Sewon
Published: December 2020

Background

The ability of Cutibacterium acnes strains to form biofilms has been correlated with their virulence.

Objective

This study examined biofilm and skin microbiota in acne patients in order to understand their role in the development of acne lesions.

Methods

Thin sections of punch biopsy specimens of (i) uninflamed comedones, (ii) inflammatory lesions, and (iii) uninvolved adjacent skin of acne patients were examined. Epiflourescence and confocal laser scanning microscopy were used for biofilm detection, and pyrosequencing with taxonomic classification of 16s rRNA gene amplicons was used for microbiota analysis.

Results

Of the 39 skin specimens from patients with mild‐moderate acne (n = 13) that were studied, nine (23%) contained biofilm. Among these specimens, biofilm was most frequently detected in comedones (55.6%) and less frequently in inflammatory papules (22.2%) and uninvolved skin (22.2%). Comedones demonstrated the highest mean alpha diversity of all the lesion subtypes. The relative abundance of Staphylococcus was significantly higher in comedones (11.400% ± 12.242%) compared to uninvolved skin (0.073% ± 0.185%, P = 0.024).

Conclusions

The microenvironment of the comedone differs from that of inflammatory lesions and unaffected skin. The increased frequency of biofilm in comedones may account for the lack of host inflammatory response to these lesions.
Dermoscopy for venereologists: an update on patterns of tumors, inflammatory and infectious diseases of the genitalia, and tips for differential diagnosis
Authors: Maatouk Ismael , Apalla Zoe , Errichetti Enzo , Lallas Aimilios
Published: December 2020

Introduction

Dermoscopy is an integrative part of clinical dermatologic examination. For clinicians mainly dealing with genital dermatoses and other venereal diseases, the differential diagnosis includes a broad spectrum of neoplastic, inflammatory, and infectious entities. Dermoscopy might have a valuable role to enhance the clinical differential diagnosis and help avoid some biopsies done for diagnostic purposes. Although the dermoscopic patterns of most tumors and inflammatory diseases of the trunk/face have been described, their manifestations on genital areas are less elucidated. We aimed to provide a succinct summary of existing data on dermoscopy of dermatologic diseases on genital areas.

Methods

A literature search was performed on PubMed using the terms dermoscopy OR dermatoscopy OR videodermoscopy OR video dermoscopy AND genital. All studies reporting on dermoscopic findings of at least one case of a dermatologic disease on genital areas were included in the review. Unless otherwise indicated, ×10 was the magnification used in the reported studies. The main outcome was to describe the dermoscopic feature of each disease.

Results

A total of 31 articles were identified and analyzed. They included single case reports and case series. The described entities were categorized into anatomical variants, vascular and lymphatic lesions, tumors, inflammatory disorders, and infectious conditions.

Conclusion

In diseases of the genital area, dermoscopic findings can be highly diagnostic and might establish a confident diagnosis. Limitation is that most of the criteria are based on case series, and few of them have been validated.
Transcriptional regulation of adaptive and innate lymphoid lineage specification
Authors: Spinner Camille A. , Lazarevic Vanja
Published: December 2020

Once alerted to the presence of a pathogen, activated CD4+ T cells initiate distinct gene expression programs that produce multiple functionally specialized T helper (Th) subsets. The cytokine milieu present at the time of antigen encounter instructs CD4+ T cells to differentiate into interferon‐(IFN)‐γ‐producing Th1 cells, interleukin‐(IL)‐4‐producing Th2 cells, IL‐17‐producing Th17 cells, follicular T helper (Tfh) cells, or regulatory T (Treg) cells. In each of these Th cell subsets, a single transcription factor has been identified as a critical regulator of its specialized differentiation program. In this context, the expression of the “master regulator” is necessary and sufficient to activate lineage‐specific genes while restricting the gene expression program of alternative Th fates. Thus, the transcription factor T‐bet controls Th1 differentiation program, while the development of Th2, Th17, Tfh, and Treg cells is dependent on transcription factors GATA3, RORγt, Bcl6, and Foxp3, respectively. Nevertheless, master regulators or, more precisely, lineage‐defining transcription factors do not function in isolation. In fact, they interact with a complex network of transcription factors, orchestrating cell lineage specification programs. In this review, we discuss the concept of the combinatorial interactions of key transcription factors in determining helper T cell identity. Additionally, lineage‐defining transcription factors have well‐established functions beyond their role in CD4+ Th subsets. They play critically important functions at distinct stages during T cell development in the thymus and they control the development of innate lymphoid cells (ILCs) in the bone marrow. In tracking the journey of T cells traversing from the thymus to the periphery and during the immune response, we discuss in broad terms developmental stage and context‐dependent functions of lineage‐defining transcription factors in regulating specification programs of innate and adaptive lymphocytes.
Bonbonnieres in the gallery: (re)presenting sugar in a family gallery space
Authors: Boycott‐Garnett Ruthie , MacRae Christina , Hackett Abigail , Otito Tamsho‐Thomas Tina , Holmes Rachel
Published: December 2020

This paper charts an on‐going process emerging from a collaborative project between Manchester Art Gallery, and early childhood researchers and practitioners, who are currently working together to develop a new learning space for families. It revolves around the potential of exhibiting a collection of bonbonnieres in this space. These little 18th Century pots, originally filled with sweets or breath mints, are colourful and depict fanciful animals that have an almost cartoon like quality that may resonate with younger children. Yet the contents that once lay inside would have been cut from plantations by the hands of enslaved people. Sugar, in all its sweetness, is intrinsically linked to Britain’s colonial history. Sections of a poem by Tina Otito Tamsho‐Thomas (http://revealinghistories.org.uk/smoking‐drinking‐and‐the‐british‐sweet‐tooth/objects/bonbonniere.html) are emplaced throughout to unambiguously contextualise the bonbonniere as a symbol of enslavement legacy, sugar trade history and British colonialism. Today, excess sugar consumption sits at the heart of the healthy eating agenda, a key priority area for local early years providers. In this paper, textual ‘fragments’ act as provocations in a series of interdisciplinary conversations that were initiated as a strategy to unsettle the positions of the institution and its curators, educators and practitioners, opening up discursive thinking about the potential of this particular object‐space ensemble. By considering these bonbonnieres as ‘vibrant matter’ (Bennett, 2010) that can affect and be affected within the gallery space (Tolia‐Kelly, 2016) we ask questions about how these objects might sit alongside the daily interactions that occur in the space in a way that opens up ‘discomfort zones’.
Should end‐of‐life patients be enrolled as participants in clinical research? A best‐fit framework synthesis
Authors: Oriani Anna , Fusi‐Schmidhauser Tanja , Guo Ping
Published: December 2020

Aim

To identify and appraise evidence about ethical concerns regarding conducting medical research with end‐of‐life patients.

Design

A best‐fit framework synthesis of the literature regarding ethical issues in research involving adult patients at the end of life was conducted.

Data sources

Five databases were searched (Cumulative Index to Nursing and Allied Health Literature, Web of Science, Embase, MEDLINE, and PsychINFO) between January 2000–August 2019.

Review methods

Data were synthesized and categorized according to the moral positions described by Foster.

Results

In all, 18 papers that met the inclusion criteria were included in this review. These papers provided rich knowledge not only about various ethical objections to researching the end of life but also about the social, moral, and clinical requirements to perform rigorous studies on clinical interventions in this field.

Conclusions

Research on people at end of life is not an unsolvable ethical dilemma between providing the best possible care and enhancing new therapies. It is important to find a balance between the moral duties of providing care and achieving research outcomes that are rigorous and meaningful for service users.

Impact

Research ethics committees can be challenged by the evaluation of human research. This review provides up‐to‐date evidence on key challenges and ethical considerations about researching with end‐of‐life patients.

Summary statement

This study is a review of relevant evidence and key ethical challenges and issues around palliative and end‐of‐life research. Our findings provided important recommendations for clinicians, research, and ethics committee members when evaluating clinical research with people at their end of life.
Cellular senescence, a novel therapeutic target for mesenchymal stem cells in acute kidney injury
Authors: Zhao Lingfei , Hu Chenxia , Han Fei , Chen Dajin , Ma Yanhong , Wang Junni , Chen Jianghua
Published: December 2020

Cellular senescence is a widespread cellular programme that is characterized by permanent cell cycle arrest. Senescent cells adopt a changed secretory phenotype that can alter cellular function. For years, cellular senescence has been thought to be a protective factor against cancer; however, it is now recognized that it has a dual effect on individuals. Co‐ordinated activation of cellular senescence provides advantages during embryogenesis, wound healing, tissue repair and inhibition of tumorigenesis. On the other hand, the aberrant generation and accumulation of abnormal senescent cells lead to the development of age‐related conditions and tissue deterioration. During acute kidney injury (AKI), the kidney faces multiple types of stressors and challenges, which can easily drive cellular senescence. How to appropriately progress through the cell cycle and minimize long‐term damage is of great importance to the acquisition of adaptive repair considering that no available therapeutic interventions can reliably limit injury, speedy recovery or improve the prognosis of this syndrome. Whether the manipulation of cellular senescence can become a novel therapeutic target in AKI and reignite clinical and research interest remains to be determined. Here, we share our current understanding of the role of cellular senescence in AKI, along with examples of the application of mesenchymal stem cells (MSCs) for targeting this disorder during its treatment.
Effects of IL‐18 on the proliferation and steroidogenesis of bovine theca cells: Possible roles in the pathogenesis of polycystic ovary syndrome
Authors: Zhang Hong yuan , Zhu Fu fan , Zhu Ying jun , Hu Yuan jing , Chen Xu
Published: December 2020

Interleukin 18 (IL‐18) is a pleiotropic pro‐inflammatory cytokine and is associated with arrested follicle development and anovulation which are the typical pathological changes of PCOS. Theca cells (TCs) have a key role in follicular growth and atresia. But whether IL‐18 can directly affect ovarian TCs function is unknown. Therefore, the objective of this study was to determine the effect of IL‐18 on proliferation and steroidogenesis of bovine TCs and to explore the biological effect of IL‐18 on folliculogenesis. This work revealed that at 300‐1000 pg/mL, IL‐18 led to a time‐ and dose‐dependently increase in cell proliferation (P < .05). IL‐18 increased 17‐hydroxyprogesterone (17OHP4) and androstenedione (A2) secretion with up‐regulation of key steroidogenesis‐related genes CYP11A1 and CYP17A1 (P < .05). Furthermore, our data demonstrated that the IL‐18R protein is predominantly expressed in small‐follicle (3‐6 mm) TCs than large follicles (8‐22 mm) by immunohistochemistry. We also found that the stimulation effects of IL‐18 on TCs can be reversed with the addition of IL‐18BP as early as at 4 hours of culture and reached the peak at 16 hours. We conclude that IL‐18 appears to target TCs in bovine, and suggest an important role for this cytokine in ovarian function. Present findings further validate potential effects of IL‐18 in the conditions associated with follicular dysplasia and excessive growth of ovarian TCs (such as PCOS). But additional research is needed to further understand the mechanism of action of IL‐18 in theca cells as well as its precise role in folliculogenesis.
First‐in‐human study demonstrating the safety and clinical efficacy of novel anti‐IL‐17A monoclonal antibody CJM112 in moderate to severe plaque psoriasis
Authors: Kaul M. , Jarvis P. , Rozenberg I. , Kolbinger F. , Di Padova F. , Calonder C. , Espie P. , Rondeau J.M. , Cebe R. , Huber T. , Mussmann R. , Aassi M. , Sligh T.S.
Published: December 2020

Background and objective

Anti‐IL‐17A IgG/κ monoclonal antibody CJM112 binds both IL‐17A and IL‐17AF. The purpose of this First‐in‐Human study was to assess CJM112 effects on safety and efficacy in patients with moderate to severe plaque psoriasis.

Methods

This study had two parts: single ascending doses of 5–450 mg subcutaneous (s.c.) CJM112 (SAD) and multi‐dose parallel groups of CJM112 15 mg, 50 mg and 150 mg s.c. low frequency or high frequency (MD). SAD/MD were double‐blind, randomized and placebo‐controlled; MD also included a secukinumab 150 mg s.c. arm as an active comparator. Patients 18–65 years with moderate to severe psoriasis were included in this study. The efficacy outcome was the change in Psoriasis Area Severity Index (PASI) from baseline to Week 4 in the SAD part of the study, and from baseline to Week 12 in the MD part.

Results

96 patients were enrolled in this study (SAD, n = 42; MD, n = 54). In SAD, CJM112 doses from 15 mg and above demonstrated higher PASI responses compared with placebo at Week 12. CJM112 450 mg did not add further efficacy, but efficacy duration was prolonged compared with CJM112 150 mg. CJM112 MD resulted in a dose‐dependent decrease in PASI over time to Week 12. CJM112 150 mg high frequency did not exceed the effect of CJM112 150 mg low frequency and had similar efficacy to secukinumab 150 mg. The safety profile of CJM112 was as expected for an antibody targeting IL‐17A/IL‐17AF.

Conclusions

CJM112 had clinical efficacy in moderate to severe psoriasis and was generally safe and well tolerated in the doses tested. Additional neutralization of IL‐17AF did not translate to increased clinical efficacy compared with secukinumab.
Line‐field confocal optical coherence tomography of basal cell carcinoma: a descriptive study
Authors: Suppa M. , Fontaine M. , Dejonckheere G. , Cinotti E. , Yélamos O. , Diet G. , Tognetti L. , Miyamoto M. , Orte Cano C. , Perez‐Anker J. , Panagiotou V. , Trepant A.L. , Monnier J. , Berot V. , Puig S. , Rubegni P. , Malvehy J. , Perrot J.L. , del Marmol V.
Published: December 2020

Background

Early diagnosis and subtype classification of basal cell carcinoma (BCC) are crucial to reduce morbidity and optimize treatment. Good accuracy in differentiating BCC from clinical imitators has been achieved with existing diagnostic strategies but lower performance in discriminating BCC subtypes. Line‐field confocal optical coherence tomography (LC‐OCT) is a new technology able to combine the technical advantages of reflectance confocal microscopy and OCT.

Objectives

To identify and describe LC‐OCT criteria associated with BCC and explore their association with BCC subtypes.

Methods

Basal cell carcinoma were imaged with a handheld LC‐OCT device before surgical excision. LC‐OCT images were retrospectively evaluated by three observers for presence/absence of criteria for BCC. Multivariate logistic regression models were used to find independent predictors of BCC subtypes.

Results

Eighty‐nine histopathologically proven BCCs were included, of which 66 (74.2%) were pure subtypes [superficial BCC (sBCC): 19/66 (28.8%); nodular BCC (nBCC): 31/66 (47.0%); infiltrative BCC (iBCC): 16/66 (24.2%)]. Lobules, blood vessels and small bright cells within epidermis/lobules were the most frequent criteria for BCC. LC‐OCT criteria independently associated with sBCC were presence of hemispheric lobules, absence of lobule separation from the epidermis, absence of stretching of the stroma; with nBCC were presence of macrolobules, absence of lobule connection to the epidermis; and with iBCC were presence of branched lobules.

Conclusions

This was the first study describing the characteristics of BCC under LC‐OCT examination. We proposed morphologic criteria, which could be potentially useful for diagnosis and subtype classification of BCC, as well as for its therapeutic management. Future studies are needed to assess these hypotheses.
Medicaid expansion and neonatal outcomes in Oregon
Authors: Harvey S. Marie , Gibbs Susannah , Oakley Lisa , Luck Jeff , Yoon Jangho
Published: December 2020

Rationale, aims and objectives

Low‐income women disproportionately experience preventable, adverse neonatal outcomes. Prior to the Affordable Care Act (ACA) Medicaid expansion, many low‐income women became eligible for coverage only after becoming pregnant, reducing their access to healthcare before pregnancy and creating discontinuities in care that may delay Medicaid enrollment. The objective of this study was to examine the impact of the ACA Medicaid expansion on neonatal outcomes among low‐income populations in Oregon.

Method

We used linked Oregon birth certificate and Medicaid data from 2008‐2016 to identify control and policy groups of women who gave birth both before and after implementation of the ACA Medicaid expansion (n = 21 204 births to N = 10 602 women). We conducted a difference‐in‐differences analysis of the effect of Medicaid expansion on preterm birth, low birthweight (LBW), neonatal intensive care unit (NICU) admissions, and neonatal mortality.

Results

We found policy effects on reducing LBW (interaction aOR = 0.71, 95% CI: 0.57‐0.90) and preterm birth (interaction aOR 0.77, 95% CI: 0.62 = 0.96) but not on NICU admissions or neonatal mortality.

Conclusions

This study provides evidence that expanding Medicaid coverage may have positive effects on LBW and preterm birth, which could lead to important long‐term impacts on childhood and later‐life health outcomes. States that have not expanded their Medicaid programs might improve neonatal outcomes among low‐income populations by extending insurance coverage to low‐income adults.
Self‐consistent charging of PMMA thin film induced by a penetrating electron beam in electron microscopy
Authors: Li Wei‐Qin , Qian Jun
Published: December 2020

The charging of the polymer thin film irradiated by penetrating electron beam (e‐beam) is investigated, in parallel with the numerical simulation and experiment. The simulation is performed by combining scattering, drift, diffusion, trapping and recombination. Results show that, due to the electron emission the net charge near the surface is distribution positively, but negatively inside the film because of low electron mobility. The surface potential is positive near surface and accordingly forces some of secondary electrons to return surface. As irradiation proceeds, currents flowing into and out of the film can tend to equilibrium. In the equilibrium state, with increasing beam energy, the surface potential and the efficient emission current decrease, and the electron beam‐induced current and the transmission current tend to zero and the beam current valuable, respectively. E‐beams of 10‐30 keV cause positive charging on PMMA film of 2 µm, which means the high‐energy e‐beam can effectively discharge a thin film that has been charged negatively by irradiation with low‐energy e‐beam. With the increase of the film thickness from 1 to 3 µm, the positive surface potential and the emission current decreases and increases, respectively, and the transmission current tends to zero.
Why Swedes Trust the State and Scots Do Not: An Exploration of the Diverse Protestant Roots of Modern Welfare Systems
Authors: Naumann Ingela K. , Paterson Lindsay
Published: December 2020

This paper explores how the Protestant traditions of Calvinist Presbyterianism and Lutheranism have shaped church‐state relations differently in Scotland and Sweden, resulting in different understandings of the role of the state and civil society in public welfare. It finds that high levels of public trust in the state's authority and state intervention in Sweden can be traced back to Lutheran doctrine and institutionally close links between the Swedish Church and the state, while in Scotland trusting independent civil society and its responsibility for welfare reflects the distance of the Presbyterian Scottish Kirk from the state both in theological and institutional terms.