bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial refuges for wildlife conservation: what is the state of the science?
Authors: Cowan Mitchell A. , Callan Michael N. , Watson Maggie J. , Watson David M. , Doherty Tim S. , Michael Damian R. , Dunlop Judy A. , Turner James M. , Moore Harry A. , Watchorn Darcy J. , Nimmo Dale G.
Published: July 2021

Artificial refuges are human‐made structures that aim to create safe places for animals to breed, hibernate, or take shelter in lieu of natural refuges. Artificial refuges are used across the globe to mitigate the impacts of a variety of threats on wildlife, such as habitat loss and degradation. However, there is little understanding of the science underpinning artificial refuges, and what comprises best practice for artificial refuge design and implementation for wildlife conservation. We address this gap by undertaking a systematic review of the current state of artificial refuge research for the conservation of wildlife. We identified 224 studies of artificial refuges being implemented in the field to conserve wildlife species. The current literature on artificial refuges is dominated by studies of arboreal species, primarily birds and bats. Threatening processes addressed by artificial refuges were biological resource use (26%), invasive or problematic species (20%), and agriculture (15%), yet few studies examined artificial refuges specifically for threatened (Vulnerable, Endangered, or Critically Endangered) species (7%). Studies often reported the characteristics of artificial refuges (i.e. refuge size, construction materials; 87%) and surrounding vegetation (35%), but fewer studies measured the thermal properties of artificial refuges (18%), predator activity (17%), or food availability (3%). Almost all studies measured occupancy of the artificial refuges by target species (98%), and over half measured breeding activity (54%), whereas fewer included more detailed measures of fitness, such as breeding productivity (34%) or animal body condition (4%). Evaluating the benefits and impacts of artificial refuges requires sound experimental design, but only 39% of studies compared artificial refuges to experimental controls, and only 10% of studies used a before‐after‐control‐impact (BACI) design. As a consequence, few studies of artificial refuges can determine their overall effect on individuals or populations. We outline a series of key steps in the design, implementation, and monitoring of artificial refuges that are required to avoid perverse outcomes and maximise the chances of achieving conservation objectives. This review highlights a clear need for increased rigour in studies of artificial refuges if they are to play an important role in wildlife conservation.
Areas of endemism of Lauraceae: new insights on the biogeographic regionalization of the Espinhaço Range, Brazil
Authors: Assunção‐Silva Caroline Cristina , Assis Leandro Cézanne de Souza
Published: July 2021

Using Lauraceae as a study case, we aimed in this article to: (i) delimit areas of endemism in the Espinhaço Range, Brazil; (ii) compare these areas of endemism with those previously delimited, as well as with the centres of endemism; (iii) evaluate the association between areas of endemism and vegetation types; and (iv) classify the areas of endemism according to the International Code of Area Nomenclature (ICAN). Based on a recent survey of 99 species from the Espinhaço Range, our dataset consisted of 34 endemic species belonging to nine genera. Following previous studies, we performed parsimony analysis of endemicity (PAE) using a grid square size of 0.5° × 0.5°. We delimited four areas of endemism of Lauraceae: (i) Antônio dos Santos, (ii) Conceição do Mato Dentro, (iii) Itambé do Mato Dentro, and (iv) Rio de Contas; and confirmed six previously delimited areas of endemism: (i) Southern MG, (ii) Southern Mountains Complex, (iii) Conceição do Mato Dentro, (iv) Diamantina Plateau, (v) Serra do Cabral, and (vi) Chapada Diamantina. The areas of endemism Conceição do Mato Dentro, Serra do Cabral, Diamantina, and Serra do Cipó were classified as subdistricts in the Diamantina Plateau district of the Southern Espinhaço province. We summarized and mapped all areas of endemism corresponding to the provinces, districts, and subdistricts that cover the Espinhaço Range. Areas of endemism and centres of endemism are contrasted. Finally, we highlight that the biogeographic studies along this mountain range should embrace higher taxa with representative species in different types of vegetation in order to enrich the majority of the endemism studies mainly concentrated on the campo rupestre. Unusual distribution patterns, diversity of vegetation types, and the presence of restricted species and monophyletic groups open up opportunities to carry out integrative studies concerning the biogeographic regionalization of the ER at multiple spatio‐temporal scales.
Establishment of a nomogram with EMP3 for predicting clinical outcomes in patients with glioma: A bi‐center study
Authors: Zhang Anke , Xu Houshi , Zhang Zeyu , Liu Yibo , Han Xiaying , Yuan Ling , Ni Yunjia , Gao Shiqi , Xu Yuanzhi , Chen Sheng , Jiang Junkun , Chen Yike , Zhang Xiaotao , Lou Meiqing , Zhang Jianmin
Published: July 2021

Aim

To demonstrate the clinical value of epithelial membrane protein 3 (EMP3) with bioinformatic analysis and clinical data, and then to establish a practical nomogram predictive model with bicenter validation.

Methods

The data from CGGA and TCGA database were used to analyze the expression of EMP3 and its correlation with clinical prognosis. Then, we analyzed EMP3 expression in samples from 179 glioma patients from 2013 to 2017. Univariate and multivariate cox regression were used to predict the prognosis with multiple factors. Finally, a nomogram to predict poor outcomes was formulated. The accuracy and discrimination of nomograms were determined with ROC curve and calibration curve in training and validation cohorts.

Results

EMP3 was significantly higher in higher‐grade glioma and predicted poor prognosis. In multivariate analysis, high expression of EMP3 (HR = 2.842, 95% CI 1.984–4.071), WHO grade (HR = 1.991, 95% CI 1.235–3.212), and IDH1 mutant (HR = 0.503, 95% CI 0.344–0.737) were included. The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes.

Conclusion

This study demonstrated EMP3 as a novel predictor for clinical progression and clinical outcomes in glioma. Moreover, the nomogram with EMP3 expression represented a practical approach to provide individualized risk assessment for glioma patients.
Primary melanoma of the anorectal region: clinical and histopathological review of 17 cases. A retrospective cohort study
Authors: Kolosov Andrej , Leskauskaitė Jurgita , Dulskas Audrius
Published: July 2021

Aim

The aim of our study was to scrutinize diagnostic and treatment factors that may contribute to the low survival rate from anorectal melanoma while adding 17 more cases to the global research database.

Method

We carried out a retrospective analysis of 17 cases of anorectal melanoma treated at a single institution from 2000 to 2020. Data on patient age, sex, complaints, treatment and survival as well as tumour size, resection margins, histological and immunohistochemical features were assessed.

Results

The median age of patients was 72 ± 12.49 (45–92) years. Most of the patients were women (n = 11, 64.71%). Three (17.65%) patients underwent no radical treatment. Of eight patients treated initially with radical surgery (either total mesorectal excision or abdominoperineal resection), six (75%) were found to have positive lymph nodes. Mean survival was 20 ± 23.46 (1–84) months. The average diameter of the resected tumours was 5.43 ± 3.02 cm (1.3–10 cm). Most tumours had epithelioid or spindle cell morphology and were positive for one or more melanocytic markers (S100, HMB‐45 or MITF). More than half of the tumours contained no or very little melanin pigment. None of the tumours had significant lymphocytic infiltration. Three tumours showed positivity for keratins (PANCK or CAM5.2) and one tumour showed positivity for C‐KIT stain.

Conclusion

An aggressive surgical approach may have an effect on survival in most early stages while more advanced disease benefits from a more conservative approach. Attention to sentinel lymph nodes and further systemic research into therapy is required. For now, treatment and diagnostic modalities seem to be inconsistent, requiring further investigation to elucidate common points.
For the sake of resilience and multifunctionality, let's diversify planted forests!
Authors: Messier Christian , Bauhus Jürgen , Sousa‐Silva Rita , Auge Harald , Baeten Lander , Barsoum Nadia , Bruelheide Helge , Caldwell Benjamin , Cavender‐Bares Jeannine , Dhiedt Els , Eisenhauer Nico , Ganade Gislene , Gravel Dominique , Guillemot Joannès , Hall Jefferson S. , Hector Andrew , Hérault Bruno , Jactel Hervé , Koricheva Julia , Kreft Holger , Mereu Simone , Muys Bart , Nock Charles A. , Paquette Alain , Parker John D. , Perring Michael P. , Ponette Quentin , Potvin Catherine , Reich Peter B. , Scherer‐Lorenzen Michael , Schnabel Florian , Verheyen Kris , Weih Martin , Wollni Meike , Zemp Delphine Clara
Published: July 2021

As of 2020, the world has an estimated 290 million ha of planted forests and this number is continuously increasing. Of these, 131 million ha are monospecific planted forests under intensive management. Although monospecific planted forests are important in providing timber, they harbor less biodiversity and are potentially more susceptible to disturbances than natural or diverse planted forests. Here, we point out the increasing scientific evidence for increased resilience and ecosystem service provision of functionally and species diverse planted forests (hereafter referred to as diverse planted forests) compared to monospecific ones. Furthermore, we propose five concrete steps to foster the adoption of diverse planted forests: (1) improve awareness of benefits and practical options of diverse planted forests among land‐owners, managers, and investors; (2) incentivize tree species diversity in public funding of afforestation and programs to diversify current maladapted planted forests of low diversity; (3) develop new wood‐based products that can be derived from many different tree species not yet in use; (4) invest in research to assess landscape benefits of diverse planted forests for functional connectivity and resilience to global‐change threats; and (5) improve the evidence base on diverse planted forests, in particular in currently under‐represented regions, where new options could be tested.
Oral and intravenous pharmacokinetics of metformin with and without oral codeine intake in healthy subjects: A cross‐over study
Authors: Kuhlmann Ida , Nøddebo Nyrup Amanda , Bjerregaard Stage Tore , Hougaard Christensen Mette Marie , Korshøj Bergmann Troels , Damkier Per , Nielsen Flemming , Højlund Kurt , Brøsen Kim
Published: July 2021

The aim of the study was to investigate if there is a clinically relevant drug interaction between metformin and codeine. Volunteers were randomized to receive on four separate occasions: (A) orally administered metformin (1 g), (B) intravenously administered metformin (0.5 g), (C) five doses of tablet codeine 25 mg; the last dose was administered together with oral metformin (1 g), and (D) five doses of tablet codeine 25 mg; the last dose was administered together with metformin (0.5 g) intravenously. Blood samples were drawn for 24 h after administration of metformin, and for 6 h after administration of codeine and analyzed using liquid chromatography and tandem mass spectrometry. Healthy volunteers genotyped as CYP2D6 normal metabolizers (*1/*1) without known reduced function variants in the OCT1 gene (rs12208357, rs34130495, rs34059508, and rs72552763) were invited. The median absorption fraction of metformin was 0.31 and was not influenced by codeine intake. The median time to maximum concentration () after oral intake of metformin was 2 h without, and 3 h with codeine (p = 0.06). The geometric mean ratios of the areas under the plasma concentration time‐curve (AUCs) for morphine and its metabolites M3G and M6G for oral intake of metformin‐to‐no metformin were 1.21, 1.31, and 1.27, respectively, and for i.v. metformin‐to‐no metformin 1.28, 1.34, and 1.30, respectively. Concomitant oral and i.v. metformin increased the plasma levels of morphine, M3G and M6G. These small pharmacokinetic changes may well contribute to an increased risk of early discontinuation of metformin. Hence, a clinically relevant drug‐drug interaction between metformin and codeine seems plausible.
Applying an equity lens to pharmacogenetic research and translation to under‐represented populations
Authors: Luczak Tiana , Stenehjem David , Brown Jacob
Published: July 2021

Since the publication of the Human Genome Project, genetic information has been used as an accepted, evidence‐based biomarker to optimize patient care through the delivery of precision health. Pharmacogenetics (PGx) uses information about genes that encode proteins involved in pharmacokinetics, pharmacodynamics, and hypersensitivity reactions to guide clinical decision making to optimize medication therapy selection. Clinical PGx implementation is growing from the dramatic increase in PGx studies over the last decade. However, an overwhelming lack of genetic diversity in current PGx studies is evident. This lack of diverse representation in PGx studies will impede equitable clinical implementation through potentially inappropriate application of gene‐based dosing algorithms, whereas representing a missed opportunity for identification of population specific single nucleotide variants and alleles. In this review, we discuss the challenges of studying PGx in under‐represented populations, highlight two successful PGx studies conducted in non‐European populations, and propose a path forward through community‐based participatory research for equitable PGx research and clinical translation.
Melanocytic hyperplasia associated with surgical scars in basal cell carcinoma re‐excision specimens: A single‐center retrospective study
Authors: Farah Maya , Suzuki Shuji , Bhawan Jag
Published: July 2021

Background

Melanocytic hyperplasia (MH) overlying surgical scars has been reported but MH adjacent to the scar has not been previously addressed.

Methods

We evaluated scar‐associated MH in 489 re‐excision specimens of basal cell carcinoma. Melanocytic density, confluence, atypia, suprabasal scatter, follicular extension, distance from the scar, correlation with clinicopathologic parameters, and PRAME expression were recorded.

Results

One hundred seventy‐seven of 489 (36%) cases exhibited MH beyond the scar extending to 6.65 mm median distance, with a median density of 13 melanocytes/0.5 mm (6‐24 mm), confluence in 74 (42%) cases, atypia in 14 (8%), suprabasal melanocytes in 25 (14%), and follicular extension in 21 (12%). Mean age of MH group was significantly lower than non‐MH group (P < 0.0001). MH overlying the scar was significantly higher in specimens with elastosis than those without elastosis (P < 0.0001). PRAME expression was absent in 14 of 20 cases and present in rare melanocytes in 6 cases.

Conclusions

Increased melanocytic density with confluence, mild atypia, suprabasal scatter, and superficial follicular extension may be observed in re‐excision specimens adjacent to surgical scars in the absence of a melanocytic neoplasm. These observations are helpful for appropriate interpretation of melanoma re‐excision specimens, to avoid potential pitfalls in diagnosis and unnecessary therapeutic measures.
The role of dispersal limitation and reforestation in shaping the distributional shift of a forest herb under climate change
Authors: Van Daele Frederik , Honnay Olivier , De Kort Hanne
Published: July 2021

Aim

Forest herbs might be unable to track shifts in habitat suitability due to rapid climate change and habitat fragmentation. In this study, we quantified the role of dispersal limitation and the potential mitigating effect of large‐scale reforestation on the redistribution of the herbaceous forest plant species Primula elatior under climate change.

Location

Europe.

Methods

High resolution (100 m) landscape‐scale and macro‐climatic variables were combined to predict range‐wide habitat suitability using Maxent. Dispersal limitation was modelled, based on isolation‐by‐resistance (IBR) principles through integration of circuit theory and genomic data, to assess patch accessibility and metapopulation stability under climate change. Large‐scale reforestation was evaluated as a potential mitigating strategy by incorporating a land use change scenario into the distribution and dispersal models.

Results

Landscape‐scale variables contributed significantly to the distribution of P. elatior (78.33%) and to the accuracy of our model (AUC = 0.81). Isolation‐by‐resistance (R2cond = .92) was driven by land use (45.5%), distance from rivers (36.4%) and elevation (18.2%). It was estimated that 46.4 ± 13.9% (mean ± SD of climate change scenarios) of the total distribution area would be lost due to climate change by 2050 and an additional 15.6 ± 1.7% (mean ± SD) of the distribution would not be accessible through migration. The median latitude of the patch distribution shifted 183.2 ± 34.8 km (mean ± SD) northwards and 58.1 ± 9.3 km (mean ± SD) to more maritime regions. The patch accessibility was low in these regions and the metapopulation stability decreased considerably in the south of the distribution. Reforestation mitigated 54.1 ± 18.2% (mean ± SD) of the accessible distribution area loss and 49.5 ± 4.2% (mean ± SD) of the decrease in metapopulation stability.

Main conclusion

To alleviate the loss of the accessible distribution area of P. elatior under climate change, it will be required to integrate climate mitigation strategies (RCP 2.6), range‐wide afforestation, restoration of ecological connectivity and focused assisted migration to newly available habitat.
Representation in demoicracies. Contributions from Belgian federalism to the future of Europe
Authors: Bursens Peter , Meier Petra
Published: July 2021

This contribution assesses representation in the EU through the lens of demoicracy, focusing on how the demos and the demoi are represented and how this interacts with the executive‐legislative balance and party politics. As the Belgian polity is a living case for the EU but often as flawed as the latter when it comes to democratic standards of representation, we examine whether and how reform proposals for the Belgian polity can inspire future reforms at EU level. We demonstrate that the direction demoicracies should head for when strengthening democratic representation should include a balanced representation of the demos and demoi via a bicameral system, a polity‐wide constituency to represent the demos, involvement of the legislatives of the constituent units at the encompassing level, and a specific role for polity‐wide parties.
NLRP3 inflammasome activation contributes to development of alopecia areata in C3H/HeJ mice
Authors: Hashimoto Kei , Yamada Yoshihito , Sekiguchi Kota , Mori Sachi , Matsumoto Tatsumi
Published: July 2021

Alopecia areata (AA) is an autoimmune non‐scarring hair loss disease. Recently, several reports have suggested that innate immune systems such as interferon‐α (IFN‐α)‐producing plasmacytoid dendritic cells and NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) inflammasomes play a role in the pathogenesis of AA. However, critical studies about their involvement in the initiation of AA have not yet been reported. Therefore, we investigated the expression of innate immune cytokines in serum and skin, and examined the effect of a selective NLRP3 inhibitor, MCC950, on AA in C3H/HeJ mice, induced by transferring cultured skin‐draining lymph node cells. IFN‐α production was upregulated in lesions of AA‐affected mice, and interleukin‐1β in serum and skin was highly expressed before onset as well as postonset. Furthermore, MCC950 treatment prevented AA development and promoted hair growth in AA mouse models by reducing NLRP3 signalling and Th1/Tc1 chemokines and cytokines in the skin. These results suggest that NLRP3 inflammasome contributes to AA onset and chronicity, and NLRP3 inhibitor may be a potential therapeutic agent for AA.
Fuzzy logic control theory in clinical anesthesia
Authors: Tian Ye , Chu Zheng , Ma Gang
Published: July 2021

In the context of big data, the application of fuzzy logic control theory to clinical anesthesia will produce more research directions and new technologies. This article mainly studies the application of fuzzy logic control theory in clinical anesthesia. First, after introducing the basic content of fuzzy logic control theory, the determination method of commonly used membership functions, the relevant knowledge of clinical anesthesia, and the fuzzy logic code rate control model, this article describes in detail the basic principle diagram of the clinical anesthesia control system and the clinical anesthesia process Mechanism model. The mathematical model of clinical anesthesia control system is constructed based on the data fusion technology of the parameters of anesthesia depth monitoring. The parameters in the model are adjusted by the time domain analysis method to measure the dynamic characteristics, and the stability of the system is analyzed by root locus method. The heart rate does not change significantly when it is lower than 1 MAC, and the heart rate increases when it reaches 1.5–2 MAC. Experimental results show that the application of fuzzy logic control theory to clinical anesthesia can reduce the risk of clinical anesthesia.
Acetylation of the influenza A virus polymerase subunit PA in the N‐terminal domain positively regulates its endonuclease activity
Authors: Hatakeyama Dai , Shoji Masaki , Ogata Seiryo , Masuda Takeshi , Nakano Masahiro , Komatsu Tsugunori , Saitoh Ayaka , Makiyama Kyoko , Tsuneishi Hazuki , Miyatake Asuka , Takahira Mizuki , Nishikawa Erina , Ohkubo Ayana , Noda Takeshi , Kawaoka Yoshihiro , Ohtsuki Sumio , Kuzuhara Takashi
Published: July 2021

The post‐translational acetylation of lysine residues is found in many nonhistone proteins and is involved in a wide range of biological processes. Recently, we showed that the nucleoprotein of the influenza A virus is acetylated by histone acetyltransferases (HATs), a phenomenon that affects viral transcription. Here, we report that the PA subunit of influenza A virus RNA‐dependent RNA polymerase is acetylated by the HATs, P300/CREB‐binding protein‐associated factor (PCAF), and general control nonderepressible 5 (GCN5), resulting in accelerated endonuclease activity. Specifically, the full‐length PA subunit expressed in cultured 293T cells was found to be strongly acetylated. Moreover, the partial recombinant protein of the PA N‐terminal region containing the endonuclease domain was also acetylated by PCAF and GCN5 in vitro, which facilitated its endonuclease activity. Mass spectrometry analyses identified K19 as a candidate acetylation target in the PA N‐terminal region. Notably, the substitution of the lysine residue at position 19 with glutamine, a mimic of the acetyl‐lysine residue, enhanced its endonuclease activity in vitro; this point mutation also accelerated influenza A virus RNA‐dependent RNA polymerase activity in the cell. Our findings suggest that PA acetylation is important for the regulation of the endonuclease and RNA polymerase activities of the influenza A virus.
Simplification, not “tropicalization”, of temperate marine ecosystems under ocean warming and acidification
Authors: Agostini Sylvain , Harvey Ben P. , Milazzo Marco , Wada Shigeki , Kon Koetsu , Floc’h Nicolas , Komatsu Kosei , Kuroyama Mayumi , Hall‐Spencer Jason M.
Published: July 2021

Ocean warming is altering the biogeographical distribution of marine organisms. In the tropics, rising sea surface temperatures are restructuring coral reef communities with sensitive species being lost. At the biogeographical divide between temperate and tropical communities, warming is causing macroalgal forest loss and the spread of tropical corals, fishes and other species, termed “tropicalization”. A lack of field research into the combined effects of warming and ocean acidification means there is a gap in our ability to understand and plan for changes in coastal ecosystems. Here, we focus on the tropicalization trajectory of temperate marine ecosystems becoming coral‐dominated systems. We conducted field surveys and in situ transplants at natural analogues for present and future conditions under (i) ocean warming and (ii) both ocean warming and acidification at a transition zone between kelp and coral‐dominated ecosystems. We show that increased herbivory by warm‐water fishes exacerbates kelp forest loss and that ocean acidification negates any benefits of warming for range extending tropical corals growth and physiology at temperate latitudes. Our data show that, as the combined effects of ocean acidification and warming ratchet up, marine coastal ecosystems lose kelp forests but do not gain scleractinian corals. Ocean acidification plus warming leads to overall habitat loss and a shift to simple turf‐dominated ecosystems, rather than the complex coral‐dominated tropicalized systems often seen with warming alone. Simplification of marine habitats by increased CO2 levels cascades through the ecosystem and could have severe consequences for the provision of goods and services.
Taking the bite out of administrative burdens: How beneficiaries of a Mexican social program ease administrative burdens in street‐level interactions
Authors: Peeters Rik , Campos Sergio A.
Published: July 2021

Despite taking the citizen experience of policy implementation as starting point for analysis, the literature on administrative burdens has mostly portrayed citizens as passive victims of burdens. Based on a literature review, three hypotheses are formulated regarding citizens' capacity to ease the impact of administrative burdens through behavioral adjustment, use of social and human capital, and strategic behavior. Evidence for these strategies is found in a case study of beneficiaries' behavior in a Mexican social program, where even the most vulnerable citizens have resources to reduce the impact of administrative burdens, even if the actual causes of those burdens remain out of reach. The findings contribute to understanding (a) variance in people's experience of administrative burdens, (b) the impact of prolonged street‐level interactions on people's ability to ease administrative burdens, (c) the importance of studying informal street‐level interactions, and (d) the relevance of studying state‐citizen interactions in developmental contexts.
Molecular and phenotype characterization of an elongated β‐globin variant produced by HBB:C.313delA
Authors: Lin Wanying , Zhang Qianqian , Shen Zongrui , Qu Xiang , Wang Qi , Wei Liuyuan , Qiu Yuhao , Yang Jie , Xu Xiangmin , Lao Jinquan
Published: July 2021

Introduction

β‐thalassemia is a severe hereditary hemolytic anemia. Due to the diversity of mutations spectrum, β‐thalassemia manifests a highly heterogeneous clinical severity. We noted that a previous report characterized HBB:c.313delA, at the end of exon 2, as a β‐thalassemia trait rather than dominant β‐thalassemia, the classification given to similar mutations. We further explored the impact of this functional variant on globin structure through larger pedigree analysis and in vitro studies.

Methods

Hematological analysis and molecular genotyping were conducted on the proband and his family members. We evaluated functional effects of the variant on β‐globin gene in the proband's nucleated erythrocytes and transfected HEK‐293T cells. Three‐dimensional construction of protein structure was carried out in silico to demonstrate amino acid changes.

Results

The thalassemia major proband was identified as a compound heterozygote of HBB:c.313delA and HBB:c.126_129delCTTT. Three family members with heterozygotes of HBB:c.313delA displayed microcytic hypochromic anemia. Molecular characterization demonstrated that the frameshift mutation could give rise to retro‐positioning of the termination codon, resulting in an elongated β‐globin chain with an extension of 10 amino acids. Clinical phenotype and functional experiments indicated that HBB:c.313delA led to β0‐thalassemia phenotype.

Conclusion

We concluded that the phenotype of HBB:c.313delA was mainly related to the stability of mutant mRNA, the degradation of mutant proteins, and production of inclusion bodies according to a systematic description of clinical phenotype and a series of molecular experiments.
Additional mutations in IDH1/2‐mutated patients with acute myeloid leukemia
Authors: Lu Jingtao , Chen Meiyu , Hua Haiying , Qin Wei , Zhang Ri , Lu Xuzhang , Chao Hongying
Published: July 2021

Objective

Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) frequently emerge in acute myeloid leukemia (AML), but the clinical features and molecular characteristics of IDH mutational status and other coexisting mutations have not been investigated in a large extensively characterized AML series. The aim of this study was to gain insight into the mutational profile of IDH‐mutated patients, such as the frequency and clinical characteristics of coexisting mutated genes.

Materials and Methods

We investigated 485 newly diagnosed AML patients (range 18‐81 years). DNA was extracted from bone marrow samples at the time of diagnosis. All samples were investigated with a panel of 49 mutational genes using next‐generation sequencing (NGS). FLT3‐ITD, NPM1, and CEBPA mutations were detected by Sanger PCR sequencing.

Results

We found 84 patients (17.3%) with IDH1 or IDH2 mutations. There were 40 IDH1R132, 15 IDH2R140Q, 17 IDH2R172K, and 12 uncommon mutations. No patient was found to have both IDH1 and IDH2 mutations. Patients with IDH2R140Q mutations were more frequently older and presented with significantly lower average platelet counts, while IDH2R172K‐mutated patients had significantly lower white blood cell (WBC) counts. On the background of IDH mutations, the presence of a normal karyotype showed a balanced distribution. The four most frequently coexisting mutated genes were NPM1, DNMT3A, TET2, and FLT3‐ITD. The majority of coexisting mutated genes were involved in regulating transcription and DNA methylation. IDH mutation status had no effect on the CR rate, regardless of other molecular abnormalities.

Conclusion

Isocitrate dehydrogenases mutations are associated with a complex coexisting mutation cluster in AML. Future investigation is needed to reveal the association between IDH mutations and other genetic abnormalities, which may have an impact on the progression and prognosis of disease.
Local government efficiency: reviewing determinants and setting new trends
Authors: Milán‐García Juan , Rueda‐López Nuria , De Pablo‐Valenciano Jaime
Published: July 2021

This paper has reviewed the international literature on the explaining factors of efficiency of local governments from 1990 to June 2019. The main objective of this work is to explore the dynamics of the development of this line of research, not only to find out the terminology preferences that have dominated the pre‐ and post‐crisis period in this field but also to identify the latest worldwide research trends. For this purpose, a bibliometric and cluster analysis by fractional accounting has been carried out. The principal result of this article is twofold. First, during the whole period 1990–2019, the ranking of the most used terms is dominated by the keywords of the publications in the second subperiod 2008–2019. Second, the analysis of the latest trends, which has been extended until June 2021, shows that in recent years, the study of the determinants of local government efficiency has revolved around concepts related to environmental issues and new forms of local management.
A novel adaptive insertable cardiac monitor algorithm improves the detection of atrial fibrillation and atrial tachycardia in silico
Authors: Saha Sunipa , Perschbacher David , Jones Paul , Frost Kate , Sharma Arjun , Mittal Suneet , Richards Mark
Published: July 2021

Introduction

Insertable cardiac monitors (ICMs) provide a minimally invasive method of continuous monitoring for abnormal heart rhythms. While the benefits of ICMs are clear, current algorithm performance can be improved. The objective of this study is to assess the performance of a novel adaptive atrial fibrillation (AF) detection algorithm and separately programmable atrial tachycardia (AT) algorithm.

Methods

A dual‐stage detect‐and‐verify AF algorithm and separately programmable AT algorithm were developed. Sensitivity and PPV across a range of settings were determined in silico by comparison with an adjudicated Holter data set (n = 1966 with 229 patient days). Finally, the ability to improve performance through simulated remote programming was assessed.

Results

The dual‐stage algorithm detected AF in all true AF patients (76/76) resulting in a patient‐level sensitivity of 100%. Episode‐level sensitivity and PPV ranged from 97.6% to 100% and 79.1% to 98.5%, respectively. Thirty‐six false‐positive episodes were observed and 32 (88.9%) of these were corrected with programming changes. Decoupling of AF and AT durations improved PPV from a range of 10%–22% to a range of 95%–100%.

Conclusions

AF and AT algorithms were designed with novel features including an adaptive morphology assessment for AF detection and separately programmable durations for AT detection. In silico performance yielded improved PPVs while maintaining high sensitivity across a range of settings. Importantly, programming changes that may be made remotely with this system reduced false positives. These algorithms allow clinicians to individualize arrhythmia detection settings thereby improving data management and reducing clinic burden.
Blood pressure measurement: Should technique define targets?
Authors: Hiremath Swapnil , Ramsay Tim , Ruzicka Marcel
Published: July 2021

Accurate assessment of blood pressure (BP) is the cornerstone of hypertension management. The objectives of this study were to quantify the effect of medical personnel presence during BP measurement by automated oscillometric BP (AOBP) and to compare resting office BP by AOBP to daytime average BP by 24‐h ambulatory BP monitoring (ABPM). This study is a prospective randomized cross‐over trial, conducted in a referral population. Patients underwent measurements of casual and resting office BP by AOBP. Resting BP was measured as either unattended (patient alone in the room during resting and measurements) or as partially attended (nurse present in the room during measurements) immediately prior to and after 24‐h ABPM. The primary outcome was the effect of unattended 5‐min rest preceding AOBP assessment as the difference between casual and resting BP measured by the Omron HEM 907XL. Ninety patients consented and 78 completed the study. The mean difference between the casual and Omron unattended systolic BP was 7.0 mm Hg (95% confidence interval [CI] 4.5, 9.5). There was no significant difference between partially attended and unattended resting office systolic BP. Resting office BP (attended and partially attended) underestimated daytime systolic BP load from 24‐h ABPM. The presence or absence of medical personnel does not impact casual office BP which is higher than resting office AOBP. The requirement for unattended rest may be dropped if logistically challenging. Casual and resting office BP readings by AOBP do not capture the complexity of information provided by the 24‐h ABPM.
NOD2 deficiency confers a pro‐tumorigenic macrophage phenotype to promote lung adenocarcinoma progression
Authors: Wang Yibei , Miao Ziwei , Qin Xiaoxue , Li Bo , Han Yun
Published: July 2021

Nucleotide‐binding and oligomerization domain‐containing protein 2 (NOD2) was a member of the NOD‐like receptor family and played an important role in the innate immune response. Dysregulated NOD2 had been reported to contribute to tumorigenesis and progression. Here, we investigated that decreased NOD2 expressions could affect the phenotypic polarization of tumour‐associated macrophages and thus lead to the poor prognosis of lung adenocarcinoma patients. We clustered the patients by the single‐sample gene set enrichment analysis of tumour microenvironment and 13 prognostic differentially expressed immune‐related genes (PDEIRGs) were obtained based on prognostic analyses. After multiple assessments on the 13 PDEIRGs, NOD2 was considered to be the central immune gene and had a strong effect on suppressing tumour progression. Decreased NOD2 expression could be induced by cancer cells and lead to the phenotypic polarization of macrophages from protective M1 phenotype to pro‐tumorigenic M2 subtype which might be attributed to the down‐regulating of NF‐κB signalling pathway. This study draw attention to the role of inhibited innate immune function mediated by depletion of NOD2 in the TME. Our work also points to a potential strategy of NOD2‐mediated TAM‐targeted immunotherapy.
The Couple Relationship Scale: A brief measure to facilitate routine outcome monitoring in couple therapy
Authors: Anderson Shayne R. , Johnson Lee N. , Miller Richard B. , Barham Connor C.
Published: July 2021

Routine outcome monitoring (ROM) is an important component of evidence‐based practice. To implement ROM in their practice, couple therapists need a brief measure that can quickly assess the relevant aspects of a couple's relationship. The Couple Relationship Scale (CRS) is a 10‐item measure of relational functioning that assesses emotional intimacy, commitment, trust, safety, cohesion, acceptance, conflict, physical intimacy, overall happiness, and personal well‐being. Three studies examined the initial psychometric properties of the CRS. Study One used a sample of 300 individuals to examine the concurrent validity, factor structure, and reliability of the CRS. In Study Two, 53 individuals completed the CRS twice to establish test‐retest reliability. In Study Three, 214 distressed individuals and 135 non‐distressed individuals were used to identify a clinical cutoff and reliable change index (RCI). Results indicated that the CRS has a strong concurrent and construct validity and good reliability. The clinical cutoff was 70.9 with an RCI of 16.
Nerve ultrasound findings in Sjögren's syndrome‐associated neuropathy
Authors: Seeliger Tabea , Bönig Lena , Gingele Stefan , Prenzler Nils K. , Thiele Thea , Ernst Diana , Witte Torsten , Stangel Martin , Skripuletz Thomas , Körner Sonja
Published: July 2021

Background and Purpose

The phenotype of Sjögren's syndrome‐associated neuropathy has been better characterized in recent years. However, Sjögren's syndrome‐associated neuropathy remains an underdiagnosed entity with only few insights considering the pathomechanisms of nerve damage. Nerve ultrasound has proven to be a useful and efficient tool in detecting nerve damage of autoimmune origin. We, therefore, aimed to evaluate this method for Sjögren's syndrome‐associated neuropathy.

Methods

Patients with Sjögren's syndrome and clinical signs of neuropathy underwent sonographic examination of both median and ulnar nerves. Nerve thickening was classified for cross‐sectional areas of >12 mm² at the median nerve and for >10 mm² at the ulnar nerve. Fascicle thickening was documented for cross‐sectional areas ≥5 mm² at the median and ≥3 mm² at the ulnar nerve.

Results

Forty‐three patients were included in the analysis (median age 60 years [interquartile range 53–73 years], female rate 60%). 31/43 patients (72%) showed abnormalities on nerve ultrasound, while nerve thickening was found more frequently than fascicle thickening (90% vs. 52% of patients with sonographic abnormalities, respectively). Abnormal findings were observed more frequently at the median nerve and in proximal localization. Abnormal findings on nerve conduction studies were evident in 36/43 patients (84%). Nerve conduction studies revealed a tendency of demyelinating nerve damage patterns being associated with abnormal findings on nerve ultrasound.

Conclusions

In addition to nerve conduction studies, nerve ultrasound may have a supporting role in the diagnosis of Sjögren's syndrome‐associated neuropathy. Also, our data support an immune‐mediated inflammatory demyelinating pathogenesis of Sjögren's syndrome‐associated neuropathy.
Transcriptome changes in resistant and susceptible rose in response to powdery mildew
Authors: Chandran Neethu K. , Sriram Subbaraman , Prakash Tejaswini , Budhwar Roli
Published: July 2021

Rose is one of the most important ornamental crops worldwide and powdery mildew (Podosphaera pannosa (Wallr.: Fr.) de Bary) is the major disease of rose when grown in polyhouse or open field. Understanding of plant–pathogen interaction is important to develop strategies for disease management. We profiled transcriptomes of powdery mildew‐resistant rose line IIHRR13‐4 and susceptible cultivar Konfetti using Illumina NGS platform to understand the molecular mechanism of resistance to powdery mildew in the rose line IIHRR13‐4. Profiles of samples were collected at 0 hr after inoculation (hai), 36 hai and 72 hai from susceptible cultivar Konfetti (SCON0, SCON3 and SCON7) and 0 hai and 36 hai from resistant line IIHRR13‐4 (RPMR0 and RPMR3). The high‐quality reads were aligned to reference genome of Rosa chinensis. The transcripts of rose‐powdery mildew interaction were analysed for functions and involvement in disease resistance. Expression of receptor‐like kinases, putative disease resistance genes (RLKs, NBS‐LRR, NB‐ARC, RPP13), WRKY transcription factors and PR proteins was observed in the transcripts library and was found up‐regulated in IIHRR13‐4 samples. Differentially expressed genes coding for metabolic and cellular process, response to abiotic stress response, defence response and other biosynthetic processes were identified in the transcripts. Gene ontology term enrichment and pathway analysis revealed that transcriptome of IIHRR13‐4 was enriched with transcripts coding for plant hormone signal transduction and plant–pathogen interaction compared to transcripts of susceptible cultivar Konfetti. The transcriptome profiling proved that different defence mechanisms including hypersensitive responses were elicited as systemic acquired resistance in rose line IIHRR13‐4 when infected by powdery mildew pathogen.
The impact of direct‐acting antivirals on hepatitis C viraemia among people who inject drugs in England; real‐world data 2011–2018
Authors: Bardsley Megan , Heinsbroek Ellen , Harris Ross , Croxford Sara , Edmundson Claire , Hope Vivian , Hassan Nasra , Ijaz Samreen , Mandal Sema , Shute Justin , Hutchinson Sharon J. , Hickman Matthew , Sinka Katy , Phipps Emily
Published: July 2021

Direct‐acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled‐up in England since 2017. To assess early impacts, we investigated trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self‐reported treatment access. Bio‐behavioural data from an annual, national surveillance survey of PWID (2011–2018) estimated trends in viraemic prevalence among HCV antibody‐positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection. Between 2011 and 2016, viraemic prevalence among antibody‐positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p < 0.001). After adjustment for demographic and behavioural characteristics, there remained significant reduction in viraemia in 2017 (adjusted odds ratio [aOR] 0.79, 95% CI 0.65–0.94) and 2018 (aOR 0.79, 95% CI 0.66–0.93) compared to 2016. Other factors associated with viraemia were male gender (aOR 1.68, 95% CI 1.53–1.86), geographical region, injecting in past year (aOR 1.26, 95% CI 1.13–1.41), imprisonment (aOR 1.14, 95% CI 1.04–1.31) and homelessness (aOR 1.17, 95% CI 1.04–1.31). Among non‐viraemic PWID with known infection, the proportion reporting ever receiving treatment increased in 2017 (28.7%, p < 0.001) and 2018 (38.9%, p < 0.001) compared to 2016 (14.5%). In conclusion, there has been a small reduction in HCV viraemia among antibody‐positive PWID in England since 2016, alongside DAA scale‐up, and some indication that treatment access has improved in the same period. Population‐level monitoring and focus on harm reduction is critical for achieving and evaluating elimination.
The effects of signalment, diet, geographic location, season, and colitis associated with antimicrobial use or Salmonella infection on the fecal microbiome of horses
Authors: Arnold Carolyn E. , Pilla Rachel , Chaffin M. Keith , Leatherwood Jessica L. , Wickersham Tryon A. , Callaway Todd R. , Lawhon Sara D. , Lidbury Jonathan A. , Steiner Joerg M. , Suchodolski Jan S.
Published: July 2021

Background

The fecal microbiome of healthy horses may be influenced by signalment, diet, environmental factors, and disease.

Objectives

To assess the effects of age, breed, sex, geographic location, season, diet, and colitis caused by antibiotic use (antimicrobial‐associated diarrhea [AAD]) and Salmonella infection on fecal microbiota.

Animals

Healthy horses (n = 80) were sampled from nonhospital environments across multiple geographical locations in the United States. Horses with AAD (n = 14) were defined as those that developed diarrhea secondary to antimicrobial use. Horses with Salmonella infection (n = 12) were presented with spontaneous onset of colitis and subsequently tested positive on Salmonella quantitative polymerase chain reaction. All horses were >1 year of age and stratified by a dietary scale that included forages (pasture and hay) and concentrates grouped by percentage of fiber and amount.

Methods

Illumina sequencing of 16S rRNA genes was performed on fecal DNA.

Results

Healthy horses fed higher amounts of grain clustered separately from those fed lower amounts of grain (analysis of similarities [ANOSIM], R = 0.356‐0.385, Q = 0.002). Horses with AAD and Salmonella had decreased richness and evenness compared to healthy horses (P < .05). Univariable analysis of the 3 groups identified increases in Bacteroidetes (Q = 0.002) and Protebacteria (Q = 0.001) and decreases in Verrucomicrobia (Q = 0.001) in AAD horses whereas Salmonella horses had less Firmicutes (Q = 0.001) when compared to healthy horses.

Conclusions and Clinical Importance

Although the amount of grain in the diet had some impact on the fecal microbiome, colitis had a significantly larger influence. Horses with ADD have a more severe dysbiosis than do horses with Salmonella.