bluuebunny/crossref_metadata_2025 huggingface dataset:
Nosocomial SARS‐CoV‐2 infection in urology departments: Results of a prospective multicentric study
Authors: Sánchez María Dolores , Sánchez Miguel , De La Morena José Manuel , Ogaya‐Pinies Gabriel , Mateo Erika , Moscatiello Pietro , Sánchez Susana , Rubio Victor , Bueno Carolina , Barba Raquel , Carracedo David
Published: October 2020

Objective

To evaluate the coronavirus disease 2019 perioperative infection rate and mortality rate of patients undergoing urological surgeries during the early pandemic period in Spain.

Methods

This was a non‐interventional multicenter prospective study carried out from 9 March to 3 May 2020 in two urology departments in Madrid, Spain. Clinical, microbiological and radiological data of patients who underwent surgery were collected from computerized medical records.

Results

A total of 148 patients were included in the study, and 141 were analyzed for nosocomial infection risk, after excluding previous and concomitant severe acute respiratory syndrome coronavirus type 2 infections. Elective surgeries represented 76.6% of the procedures, whereas emergent surgeries represented 23.4%. Preoperative screening was carried out with polymerase chain reaction test in 34 patients, all were negative. A total of 14 patients also had chest X‐ray (not suspicious in all cases). Three patients (2.1%) developed severe acute respiratory syndrome coronavirus type 2 nosocomial infection (symptoms developed between the third day after surgery to the 14th day after hospital discharge). Time from admission to a compatible clinical case was 5.5 days (4–12 days). Two patients underwent surgery with concomitant diagnosis of coronavirus disease. The mortality rate due to severe acute respiratory syndrome coronavirus type 2 infection is 0.7%, and the specific mortality rate in patients undergoing surgery with community‐acquired coronavirus disease 2019 infection was 50% (1/2).

Conclusions

The nosocomial severe acute respiratory syndrome coronavirus type 2 infection rate was low in patients undergoing urological surgical procedures during the peak of the pandemic in Madrid. With appropriate perioperative screening, urological surgical activity can be carried out in safety conditions.
Differential COVID‐19 case positivity in New York City neighborhoods: Socioeconomic factors and mobility
Authors: Lamb Matthew R. , Kandula Sasikiran , Shaman Jeffrey
Published: October 2020

Background

New York City (NYC) has been one of the hotspots of the COVID‐19 pandemic in the United States. By the end of April 2020, close to 165 000 cases and 13 000 deaths were reported in the city with considerable variability across the city's ZIP codes.

Objectives

In this study, we examine: (a) the extent to which the variability in ZIP code‐level case positivity can be explained by aggregate markers of socioeconomic status (SES) and daily change in mobility; and (b) the extent to which daily change in mobility independently predicts case positivity.

Methods

COVID‐19 case positivity by ZIP code was modeled using multivariable linear regression with generalized estimating equations to account for within‐ZIP clustering. Daily case positivity was obtained from NYC Department of Health and Mental Hygiene and measures of SES were based on data from the American Community Survey. Changes in human mobility were estimated using anonymized aggregated mobile phone location systems.

Results

Our analysis indicates that the socioeconomic markers considered together explained 56% of the variability in case positivity through April 1 and their explanatory power decreased to 18% by April 30. Changes in mobility during this time period are not likely to be acting as a mediator of the relationship between ZIP‐level SES and case positivity. During the middle of April, increases in mobility were independently associated with decreased case positivity.

Conclusions

Together, these findings present evidence that heterogeneity in COVID‐19 case positivity during NYC’s spring outbreak was largely driven by residents’ SES.
Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
Authors: Xiao Boduan , Ying Chang , Chen Yongyi , Huang Fang , Wang Binrong , Fang Huiling , Guo Wan , Liu Tao , Zhou Xiumei , Huang Biao , Liu Xinyuan , Wang Yigang
Published: October 2020

Oncolytic adenovirus (OA) has attracted increasing attention due to their specific proliferation in tumour cells and resulting in lysis of tumour cells. To further improve the antitumour effect of OA, in this study, we combined CD55‐TRAIL‐IETD‐MnSOD (CD55‐TMn), a CEA‐controlled OA constructed previously, and chemotherapy to investigate their synergistic effect and possible mechanisms. MTT assay was performed to detect antitumour effects. Hoechst 33 342 and flow cytometric analysis were used to examine cell apoptosis. Western blotting was performed to examine cell pyroptosis and apoptosis mechanism. Animal experiment was used to detect antitumour effect of doxorubicin hydrochloride (Dox) combined with CD55‐TMn in vivo. We firstly found that Dox promotes gene expression mediated by CEA‐regulated OA and virus progeny replication by activating phosphorylation of Smad3, and Dox can enhance antitumour effect of CEA‐regulated CD55‐TMn by promoting cell apotopsis and cell pyroptosis. Thus, our results provide an experimental and theoretical basis on tumour therapy by combination treatment of the oncolytic virotherapy and chemotherapy and it is expected to become a novel strategy for liver cancer therapy.
The biological function and potential mechanism of long non‐coding RNAs in cardiovascular disease
Authors: Zhang Chengmeng , Han Bing , Xu Tongda , Li Dongye
Published: October 2020

Long non‐coding RNAs (lncRNAs), as part of the family of non‐protein‐coding transcripts, are implicated in the occurrence and progression of several cardiovascular diseases (CVDs). With recent advances in lncRNA research, these molecules are purported to regulate gene expression at multiple levels, thereby producing beneficial or detrimental biological effects during CVD pathogenesis. At the transcriptional level, lncRNAs affect gene expression by interacting with DNA and proteins, for example, components of chromatin‐modifying complexes, or transcription factors affecting chromatin status. These potential mechanisms suggest that lncRNAs guide proteins to specific gene loci (eg promoter regions), or forestall proteins to specific genomic sites via DNA binding. Additionally, some lncRNAs are required for correct chromatin conformation, which occurs via chromatin looping in enhancer‐like models. At the post‐transcriptional level, lncRNAs interact with RNA molecules, mainly microRNAs (miRNAs) and mRNAs, potentially regulating CVD pathophysiological processes. Moreover, lncRNAs appear to post‐transcriptionally modulate gene expression by participating in mRNA splicing, stability, degradation and translation. Thus, the purpose of this review is to provide a comprehensive summary of lncRNAs implicated in CVD biological processes, with an emphasis on potential mechanisms of action.
Robust Estimation of Ability and Mental Speed Employing the Hierarchical Model for Responses and Response Times
Authors: Ranger Jochen , Kuhn Jörg‐Tobias , Wolgast Anett
Published: October 2020

Van der Linden's hierarchical model for responses and response times can be used in order to infer the ability and mental speed of test takers from their responses and response times in an educational test. A standard approach for this is maximum likelihood estimation. In real‐world applications, the data of some test takers might be partly irregular, resulting from rapid guessing or item preknowledge. The maximum likelihood estimator is not robust against contamination with irregular data. In this article, we propose a robust estimator of ability and mental speed. The estimator consists of two steps. In the first step, the mental speed is estimated with the estimator of Gervini and Yohai that ignores outlying response times. In the second step, the ability is estimated with an M‐estimator that down weights unusual responses given at unusual response times. This is achieved by combining the hard‐rejection weights of Gervini and Yohai with the M‐estimator suggested by Croux and Haesbroeck for the logistic regression model. The proposed estimator is consistent, almost as efficient as the maximum likelihood estimator in uncontaminated data and robust in contaminated data. The performance of the estimator is analyzed in a simulation study and an empirical example.
Cost effectiveness of dietitian‐led nutrition therapy for people with type 2 diabetes mellitus: a scoping review
Authors: Siopis G. , Wang L. , Colagiuri S. , Allman‐Farinelli M.
Published: October 2020

Background

The management of diabetes costs in excess of $1.3 trillion per annum worldwide. Diet is central to the management of type 2 diabetes. It is not known whether dietetic intervention is cost effective. This scoping review aimed to map the existing literature concerning the cost effectiveness of medical nutrition therapy provided by dietitians for people with type 2 diabetes.

Methods

Thirteen scientific databases, including MEDLINE, EMBASE and CINAHL, as well as multiple official websites, were searched to source peer‐reviewed articles, reports, guidelines, dissertations and other grey literature published from 2008 to present. Eligible articles had to have assessed and reported the cost effectiveness of dietetic intervention for adults with type 2 diabetes in developed countries. Experimental, quasi‐experimental, observational and qualitative studies were considered.

Results

Of 2387 abstracts assessed for eligibility, four studies combining 22 765 adults with type 2 diabetes were included. Dietetic intervention was shown to be cost‐effective in terms of diabetes‐related healthcare costs and hospital charges, at the same time as also reducing the risk of cumulative days at work lost to less than half and the risk of disability ‘sick’ days at work to less than one‐seventh.

Conclusions

The findings highlight the importance of advocacy for medical nutrition therapy for people with type 2 diabetes, with respect to alleviating the great global economic burden from this condition. Further studies are warranted to elucidate the factors that mediate and moderate cost effectiveness and to allow for the generalisation of the findings.
What effects does material flow cost accounting have for companies?: Evidence from a case studies analysis
Authors: Walz Matthias , Guenther Edeltraud
Published: October 2020

Material Flow Cost Accounting (MFCA) is a new cost accounting method which enables the identification of improvement opportunities in terms of material consumption and accrual of costs. Until now, no meta‐analysis concerning MFCA has been undertaken. 73 case studies about MFCA use in companies have been analyzed and synthesized in order to determine the effects and drawbacks experienced by these companies when implementing and applying MFCA. The focus of the case studies was MFCA, although, the reported effects cover a broad spectrum. By comparing and synthesizing over 700 statements in the case studies, a clear picture of the experiences reported by companies after having applied MFCA is presented. Whilst the majority of the case studies describe positive effects of MFCA, the reader must consider the described effects with caution, as the insights provided are the best that can be achieved given the limited availability of data. This research may be helpful in practice when considering whether to use MFCA, and in theory as a basis for further research due to its rich description of aspects of the application of MFCA in practice.
Do material efficiency improvements backfire?: Insights from an index decomposition analysis about the link between CO2emissions and material use for Austria
Authors: Plank Barbara , Eisenmenger Nina , Schaffartzik Anke
Published: October 2020

To keep global heating and other negative consequences of socioeconomic activities within manageable boundaries, industrialized countries must undergo substantial decarbonization, requiring the exploitation of synergies with other environmental endeavors. Improving resource efficiency—that is, reducing the resources required to generate a unit of economic output—is a prominent goal pursued across levels of scale. How does resource efficiency relate to decarbonization? Do economies decrease their emissions as they become more efficient? We examine this relationship for Austria from 2000 to 2015 by conducting an index decomposition analysis at the sectoral level by using consumption‐based indicators from the multi‐regional input–output model Exiobase. Our analysis shows that for Austria, the currently popular pursuit of material efficiency appears to run the risk of coinciding with higher emissions, suggesting that the opportunities to achieve both decarbonization and dematerialization are limited. The Austrian service sectors could contribute to a reduction of the CO2footprint via material efficiency improvements, but strong economic growth foils this possibility coming to fruition. The Austrian economy would do well to either curb demand for goods and services driving global CO2emissions or to produce imported goods and services domestically in an environmentally more benign manner.
Comparative anatomy of the brachial plexus and shoulder nerves of the Sapajus
Authors: Figueredo‐da‐Silva Sylla , Vasconcelos‐da‐Silva Ediana , Abreu Tainá , Aversi‐Ferreira Tales Alexandre
Published: October 2020

Background

The capuchin is a neotropical primate that presents easy reproduction in captivity and is used in scientific research. The objective of this work was to describe the structure and the branching pattern of the brachial plexus of the capuchin and to compare the results with data from the literature for humans, chimpanzees, baboons and Callithrix.

Methods

Twelve specimens were used: eight males and four females. No animals were killed for the purpose of this study.

Results

The brachial plexus of Sapajus sp was constituted mainly from the ventral roots of the last four cervical spinal nerves, from C5 to C8, mainly, and the first thoracic nerve (T1).

Conclusions

The pattern of formation of the brachial plexus of the capuchin monkey was more similar to that of Callithrix and baboons, perhaps because they are the only primates in this study to be essentially quadrupedal.
Effect of shock wave therapy associated with aerobic exercise on cellulite: A randomized controlled trial
Authors: Troia Sara , Moreira Ana Maria , Pisco Daniela , Noites Andreia , Vale Ana Luisa , Carvalho Paulo , Vilarinho Rui
Published: October 2020

Background

Cellulite is a multifactor and controversial condition. Several methods have been explored to reduce it, not always with favorable results. Shock Wave Therapy has been shown to be effective, but the results of its association with an Aerobic Exercise Program are unknown.

Aims

To verify whether Shock Wave Therapy in association with an Aerobic Exercise Program reduces the degree of severity of Cellulite in the gluteal region and in the ⅓ of the proximal posterior of the thigh.

Methods

Forty‐five healthy women, aged from 18 to 32, randomly assigned, considering the severity degree in the Cellulite Severity Scale and the level of physical activity, in three groups: two experimental and one control group. The control group performed the evaluations. The experimental group 1 performed an Aerobic Exercise Program, and the experimental group 2 associated this program with a Radial Shock Wave Therapy protocol. The experimental groups completed six interventions within 3 weeks. In addition, the degree of severity in the Cellulite Severity Scale, height, body composition, skin temperature, and subcutaneous adipose tissue thickness were assessed. One‐way ANOVA test and Kruskal‐Wallis were used to obtain the results, with level of significance of 0.05.

Results

Forty‐two women completed the study. There was a significant reduction in the severity of Cellulite between experimental group 2 and group 1 (P = 0.032), and from group 2 to the control group (P = 0.042).

Conclusion

The association of Shock Wave Therapy and Aerobic Exercise was shown to be effective in reducing the severity of cellulite.
Are the Institute of Medicine guidelines for optimal gestational weight gain in twin pregnancies applicable to Japanese women?
Authors: Shimura Mai , Obata Soichiro , Misumi Toshihiro , Miyagi Etsuko , Aoki Shigeru
Published: October 2020

Aims

To investigate whether the Institute of Medicine (IOM) guidelines for optimal gestational weight gain (GWG) in twin pregnancies are applicable to Japanese women.

Methods

This was a retrospective study involving women who delivered full‐term twins at our tertiary center diagnosed with a normal prepregnancy body mass index. The women were divided into two groups, according to the optimal GWG recommended by the IOM (16.8–24.5 kg): the adequate GWG (AGWG) group with GWG meeting the guidelines and the low GWG (LGWG) group with GWG below the guidelines. Next, the women were divided into two groups according to birthweight: a group with both twins born appropriate for gestational age (AGA group) and a group with one or both twins born small for gestational age (SGA group). Their GWG as well as their pregnancy outcomes were compared.

Results

A total of 265 women were included. The AGWG group had a significantly higher proportion of hypertensive disorders of pregnancy than the LGWG group. There was no significant difference in the proportion of women with both twins born AGA or the rate of admission to the neonatal intensive care unit. Meanwhile, the median GWG in the AGA group was 13.6 kg, which was significantly higher than 12.0 kg in the SGA group. And even the median GWG in the AGA group was below the lower limit of the IOM guidelines.

Conclusion

The optimal GWG for Japanese women with twin pregnancies may be below the IOM guidelines.
Physical, psychological and socio‐demographic predictors related to patients’ self‐belief of their temporomandibular disorders’ aetiology
Authors: Chung Joey , Lobbezoo Frank , van Selms Maurits K. A. , Chattrattrai Thiprawee , Aarab Ghizlane , Mitrirattanakul Somsak
Published: October 2020

Background

The aetiology of temporomandibular disorders (TMDs) has been widely discussed in literature, but little is known about patients’ self‐belief of their TMD aetiology.

Objective

For six categories of self‐believed aetiology of the TMD complaint (viz., occlusal factors, physical trauma, emotional stress, deep pain input, parafunctions and unknown), associations with physical, psychological and socio‐demographic predictors were assessed.

Methods

In this retrospective study, medical records of 328 TMD patients who had visited a clinic for Orofacial Pain and Dental Sleep Medicine were analysed.

Results

The most frequently reported self‐believed TMD aetiology was ‘unknown’ (42.3%). The category ‘occlusal factors’ was associated with pain worsening with emotion. ‘Physical trauma’ as self‐believed aetiology was associated with TMD dysfunction score. ‘Emotional stress’ was associated with awake bruxism and age 18‐49 years. ‘Deep pain input’ was associated with TMD dysfunction score, sleep bruxism, and arthritis or joint pain. ‘Parafunctions’ were associated with sleep bruxism. ‘Unknown’ was associated with TMD symptoms severity and work disability.

Conclusion

For each category of self‐believed aetiology of the TMD complaint, different associations with physical, psychological and socio‐demographic predictors were identified. This may suggest that individual phenotypes play a role in the patient's belief in the cause of the TMD complaint. Determination of phenotypic risk factors associated with aetiological self‐belief might help clinicians to provide better treatment, including counselling, to their patients.
Creating systems aligned with the triple‐aim and value‐based care
Authors: Gesko David S. , Worley Don , Rindal Brad D.
Published: October 2020

HealthPartners is an integrated health care system in the upper Midwest striving to provide value‐based care that aligns with the triple‐aim care. The dental delivery system at HealthPartners is focused on prevention by utilizing risk assessment tools (caries, periodontal disease, and oral cancer) built in to our record system. Integration with medical delivery system is facilitated by a shared electronic health record. Measurement is critical to determining if we accomplish our goals. The dentist compensation system is aligned with our care agenda. Implementation strategies, lessons learned, and future directions are discussed in the context of journey to achieve the triple‐aim and value‐based care.
Phylogeny and taxonomy of Afrocayratia, a new genus of Vitaceae from continental Africa and Madagascar
Authors: Rabarijaona Romer Narindra , Dang Viet‐Cuong , Parmar Gaurav , Liu Bing , Wen Jun , Chen Zhi‐Duan , Lu Li‐Min
Published: October 2020

The genus Cayratia Juss. in the traditional sense (i.e., Cayratia s.l.) of the grape family has been shown to be non‐monophyletic. Previous studies supported the splitting of Cayratia s.l. into three genera, that is, Cayratia s.s., Causonis Raf., and a new genus representing the African Cayratia clade. However, the morphology of the African Cayratia clade has not been studied carefully and its phylogenetic position within Vitaceae remains unclear. Our study integrates molecular, distributional, and morphological data and supports the recognition of the new genus Afrocayratia from continental Africa and Madagascar. Phylogenetic analyses strongly support the monophyly of Afrocayratia and resolve it as a sister of Cayratia s.s. based on the chloroplast data, but it is placed sister to Cyphostemma based on the internal transcribed spacer dataset. Molecular dating suggests that Afrocayratia split with Cayratia s.s. during the Paleocene, but that the extant species of Afrocayratia did not diversify until the early Miocene. Afrocayratia differs from its allied genera in having short stigmas and seeds with subcircular ventral infold cavities in cross‐section. Three clades are detected within Afrocayratia, with A. debilis (Baker) J.Wen & L.M.Lu as the first diverged lineage. The second diverged lineage includes A. delicatula (Willems) J.Wen & Z.D.Chen and A. gracilis (Guill. & Perr.) J.Wen & Z.D.Chen. The third diverged lineage includes A. imerinensis (Baker) J.Wen & L.M.Lu, A. longiflora (Desc.) J.Wen & Rabarijaona, and A. triternata (Baker) J.Wen & Rabarijaona from Madagascar, which form a monophyletic group that diverged from the second lineage in the middle Miocene. Combining the morphological and molecular evidence, we formally describe the new genus Afrocayratia, make seven new combinations, and provide a key to species of the genus.
Genome‐wide methylation profiling of HCV pathogenesis to develop diabetes and diabetic complications
Authors: Rafique Shazia , Zahid Sadia , Ali Amjad , Tariq Muhammad , Saeed Maham , Iqbal Sahibzada Kashif , Ali Shahid Ahmad , Idrees Muhammad
Published: October 2020

HCV is key pathological factor for inducting insulin resistance. Such HCV‐induced insulin resistance is linked with metabolic syndrome, type 2 diabetes mellitus, extrahepatic manifestations, hepatic fibrosis progression and development of hepatocellular carcinoma. DNA methylation alterations can cause developmental abnormalities, tumours and other diseases. In our study, PBMCs were isolated and genomic DNA was extracted. DNA fragmentation was achieved by sonication to 200‐400 bp; subsequently, end repair and adenylation was performed. Manufacturer's guidelines were followed to ligate Cytosine‐methylated barcodes to sonicated DNA. EZ DNA Methylation‐GoldTM Kit was then employed to treat these DNA segments twice with bisulphite. A Library was maintained, sequenced on an Illumina platform and 150/125 bp paired‐end reads generated. GO seq R package was used to perform Gene Ontology (GO) enrichment analysis for genes linked to DMRs and DMPs; gene length bias was corrected. We identified 12 945 significant hypermethylated DMRs among all samples that were screened as those with at least 0.1 methylation level differences and P‐value less than 0.05. Fisher's exact test with FDR multiple test correction is used for identification of DMPs and DMRs. High throughput bisulphite sequencing (Illumina) was carried out, and bioinformatics analysis was performed to analyse methylation status. Gene ontology (GO) and KEGG pathway enrichment analysis showed differentially methylated regions enriched in various pathways that include PI3K‐AKT/IRS1 signalling pathway, metabolic pathway, oxidative phosphorylation, Renin‐angiotensin system that are all involved in developing type‐2 diabetes (T2D). Our study provides supporting evidence for significant involvement of HCV infection in development of epigenetic modifications in regulation of metabolic disorders like T2D and its complications.
Effects of surgery on free and total 25 hydroxyvitamin D concentrations in dogs
Authors: Clements Dylan N. , Bruce Gemma , Ryan John M. , Handel Ian G. , Oikonomidis Ioannis L. , Gow Adam G. , Evans Helen , Campbell Susan , Hurst Emma , Mellanby Richard J.
Published: October 2020

Background

It is unclear whether a low total 25(OH)D concentration is a cause or consequence of illnesses. To address this knowledge gap, studies measuring free and total 25(OH)D during the evolution and resolution of an inflammatory process are required.

Objectives

Serum total and free 25(OH)D concentrations would transiently decline after cruciate surgery in dogs.

Animals

Seventeen client‐owned dogs with a spontaneous cranial cruciate ligament rupture (CCLR).

Methods

A longitudinal cohort study involving the measurement of serum concentrations of total and free 25(OH)D, total calcium, creatinine, albumin, phosphate, C‐reactive protein and plasma ionized calcium, at 1 day before and a median time of 1 and 60 days after surgical treatment of CCLR.

Results

Median serum concentrations of total 25(OH)D before surgery (80.3 nmoL/L [range, 43.5‐137.3]) significantly declined immediately after surgery; (64.8 nmoL/L [range, 36.3‐116.5] 1 day after surgery, P < .005) before increasing to become nonsignificantly different from concentrations before surgery at day 60 after surgery (median 78.0 nmoL/L [range, 24.2‐115.8], P = .14). In contrast, median free 25(OH)D concentrations before surgery (7.6 pg/mL [range, 3.8‐12.2]) significantly increased immediately after surgery (9.2 pg/mL [range, 5.2‐15.7], P < .05) before declining to become nonsignificantly different from before surgery concentrations at day 60 after surgery (median 6.2 pg/mL [range, 4.0‐15.8], P = .37).

Conclusion and Clinical Importance

This study reveals the difficulties of assessing vitamin D status in dogs following elective surgery.
Mineralogical and oxygen isotopic study of a new ultrarefractory inclusion in the Northwest Africa 3118 CV3 chondrite
Authors: Xiong Yong , Zhang Ai‐Cheng , Kawasaki Noriyuki , Ma Chi , Sakamoto Naoya , Chen Jia‐Ni , Gu Li‐Xin , Yurimoto Hisayoshi
Published: October 2020

Calcium‐aluminum‐rich inclusions (CAIs) are the first solid materials formed in the solar nebula. Among them, ultrarefractory inclusions are very rare. In this study, we report on the mineralogical features and oxygen isotopic compositions of minerals in a new ultrarefractory inclusion CAI 007 from the CV3 chondrite Northwest Africa (NWA) 3118. The CAI 007 inclusion is porous and has a layered (core–mantle–rim) texture. The core is dominant in area and mainly consists of Y‐rich perovskite and Zr‐rich davisite, with minor refractory metal nuggets, Zr,Sc‐rich oxide minerals (calzirtite and tazheranite), and Fe‐rich spinel. The calzirtite and tazheranite are closely intergrown, probably derived from a precursor phase due to thermal metamorphism on the parent body. The refractory metal nuggets either exhibit thin exsolution lamellae of Fe,Ni‐dominant alloy in Os,Ir‐dominant alloy or are composed of Os,Ir,Ru,Fe‐alloy and Fe,Ni,Ir‐alloy with troilite, scheelite, gypsum, and molybdenite. The later four phases are apparently secondary minerals. The Zr,Sc,Y‐rich core is surrounded by a discontinuous layer of closely intergrown hibonite and spinel. The CAIs are rimmed by Fe‐rich spinel and Al‐rich diopside. Perovskite has high concentrations of the most refractory rare earth elements (REEs) but is relatively depleted in the moderately refractory and volatile REEs, consistent with the ultrarefractory REE pattern. Based on this unusual Zr,Sc,Y‐rich mineral assemblage, the layered distribution in CAI 007, and the REE concentrations in perovskite, we suggest that CAI 007 is an ultrarefractory inclusion of condensation origin. In CAI 007, hibonite, spinel, and probably Al‐rich diopside are 16O‐rich (Δ17O ~–22‰) whereas perovskite and davisite are 16O‐poor (Δ17O ~–3‰). Such oxygen isotope heterogeneity suggests that the UR inclusion formed in the various degrees of 16O‐rich nebular setting or was originally 16O‐rich and then experienced oxygen isotope exchange with 16O‐poor fluid on the CV3 chondrite parent body.
Extrachromosomal DNA amplicons in antimalarial‐resistant Plasmodium falciparum
Authors: McDaniels Jennifer M. , Huckaby Adam C. , Carter Sabrina A. , Lingeman Sabrina , Francis Audrey , Congdon Molly , Santos Webster , Rathod Pradipsinh K. , Guler Jennifer L.
Published: October 2020

Extrachromosomal (ec) DNAs are genetic elements that exist separately from the genome. Since ecDNA can carry beneficial genes, they are a powerful adaptive mechanism in cancers and many pathogens. For the first time, we report ecDNA contributing to antimalarial resistance in Plasmodium falciparum, the most virulent human malaria parasite. Using pulse field gel electrophoresis combined with PCR‐based copy number analysis, we detected two ecDNA elements that differ in migration and structure. Entrapment in the electrophoresis well and low susceptibility to exonucleases revealed that the biologically relevant ecDNA element is large and complex in structure. Using deep sequencing, we show that ecDNA originates from the chromosome and expansion of an ecDNA‐specific sequence may improve its segregation or expression. We speculate that ecDNA is maintained using established mechanisms due to shared characteristics with the mitochondrial genome. Implications of ecDNA discovery in this organism are wide‐reaching due to the potential for new strategies to target resistance development.
Oral adverse effects: drug‐induced tongue disorders
Authors: Aziz Yalda , Rademacher Willem Maria Hubertus , Hielema Atty , Wishaw Scott Bradley Patton , van Diermen Denise Edwina , de Lange Jan , Vissink Arjan , Rozema Frederik Reinder
Published: October 2020

Objectives

Due to a worldwide increase in drug consumption, oral healthcare professionals are frequently confronted with patients using one or more drugs. A large number of drugs can be accompanied with adverse drug reactions in the orofacial region, amongst others of the tongue. This paper aims to give an overview of drugs that are known to be accompanied with tongue disorders.

Materials and methods

The national drug information database for Dutch pharmacists, composed of scientific drug information, guidelines and summaries of product characteristics, was analysed for drug‐induced tongue disorders. “MedDRA classification” and “Anatomical Therapeutic Chemical codes” were used to categorize the disorders.

Results

The database comprises of 1645 drugs of which 121 (7.4%) are documented to be accompanied with tongue disorders as an adverse effect. Drug‐induced tongue disorders are predominantly observed in the following drug categories: “nervous systems,” “anti‐infectives for systemic use” and “alimentary tract and metabolism”. The most common drug‐induced tongue disorders are glossitis, tongue oedema, tongue discoloration and burning tongue.

Conclusion

Healthcare professionals are frequently confronted with drugs that can cause tongue disorders. The overview of drugs reported in this article supports clinicians in their awareness, diagnosis and treatment of drug‐induced tongue disorders.
Chance and the Continuum Hypothesis
Authors: Hoek Daniel
Published: October 2020

This paper presents and defends an argument that the continuum hypothesis is false, based on considerations about objective chance and an old theorem due to Banach and Kuratowski. More specifically, I argue that the probabilistic inductive methods standardly used in science presuppose that every proposition about the outcome of a chancy process has a certain chance between 0 and 1. I also argue in favour of the standard view that chances are countably additive. Since it is possible to randomly pick out a point on a continuum, for instance using a roulette wheel or by flipping a countable infinity of fair coins, it follows, given the axioms of ZFC, that there are many different cardinalities between countable infinity and the cardinality of the continuum.
Characterization of the novel HLA‐DQB1*03:400N allele by next‐generation sequencing
Authors: Genebrier Steve , Elsermans Vincent , Texeraud Emeric , Bertrand Gerald , Renac Virginie
Published: October 2020

DQB1*03:400N differs from DQB1*03:01:01:03 by one nucleotide insertion at position 535 in exon 3.
Clinical relevance of donor‐specific antibodies directed at HLA‐C: A long road to acceptance
Authors: Visentin Jonathan , Couzi Lionel , Taupin Jean‐Luc
Published: October 2020

In solid organ transplantation (SOT), the clinical relevance of donor‐specific antibodies (DSA) directed at anti‐HLA‐A, ‐B, ‐DR and ‐DQ antigens is largely recognized while it is still a matter of debate for DSA directed at HLA‐C. In this review, we summarize the peculiarities of HLA‐C among class I HLA antigens as well as their immunogenicity, which underlie the clinical relevance of HLA‐C locus and anti‐HLA‐C DSA in SOT. Many factors, both intrinsic and extrinsic to the HLA‐C gene and HLA‐C protein, explain its lower expression in comparison with HLA‐A and ‐B. This lower expression can explain the apparent lower immunogenicity of HLA‐C leading to a lower prevalence and strength of anti‐HLA‐C antibodies. Nevertheless, HLA‐C antigens are truly immunogenic and preformed anti‐HLA‐C DSA are clinically relevant. Indeed, anti‐HLA‐C DSA are able to bind donor cells and to activate the complement pathway both ex vivo and in vivo. In line with this, numerous clinical studies now show that preformed DSA directed at native HLA‐C molecules induce poorer graft outcomes. We then plead for the inclusion of HLA‐C in all transplant allocation systems and we propose a strategy to cope with anti‐HLA‐C DSA in SOT. Beyond SOT, anti‐HLA‐C antibodies generate a growing interest in the allo‐HCT, transfusion and obstetrics fields, while new concepts such as the role of the “missing‐self” in solid organ rejection places HLA‐C as an inescapable actor in transplant tolerance.
Intercellular movement of plant RNA viruses: Targeting replication complexes to the plasmodesma for both accuracy and efficiency
Authors: Wu Xiaoyun , Cheng Xiaofei
Published: October 2020

Replication and movement are two critical steps in plant virus infection. Recent advances in the understanding of the architecture and subcellular localization of virus‐induced inclusions and the interactions between viral replication complex (VRC) and movement proteins (MPs) allow for the dissection of the intrinsic relationship between replication and movement, which has revealed that recruitment of VRCs to the plasmodesma (PD) via direct or indirect MP‐VRC interactions is a common strategy used for cell‐to‐cell movement by most plant RNA viruses. In this review, we summarize the recent advances in the understanding of virus‐induced inclusions and their roles in virus replication and cell‐to‐cell movement, analyze the advantages of such coreplicational movement from a viral point of view and discuss the possible mechanical force by which MPs drive the movement of virions or viral RNAs through the PD. Finally, we highlight the missing pieces of the puzzle of viral movement that are especially worth investigating in the near future.
From fragmentation to integration and back again: The politics of water infrastructure in Accra’s peripheral neighbourhoods
Authors: Uitermark Justus , Tieleman Joris
Published: October 2020

This paper examines the dynamics of fragmentation and integration in Accra’s water infrastructure. Inspired by figurational sociology, we analyse infrastructure as both reflective and constitutive of interdependencies between different class fractions and parts of the urban region. We draw on historical archives, the in‐depth ethnographic study of one suburban neighbourhood, a survey of eight additional neighbourhoods, and statistics from Ghana’s census to investigate the mechanisms and drivers of infrastructural integration as well as fragmentation. Our analysis shows that, following Ghana’s independence, the piped water network gradually expanded to integrate different class fractions and parts of the urban region. But this process has more recently hit its limits on Accra’s peri‐urban fringe, where the wealthy are disconnecting from the public piped water network and, by implication, from those who still depend on it. The progressive expansion of the pipe network thus grinds to a halt, giving way to a fragmented constellation of water infrastructures.
Mind the evidence gap: The need for trials in the prevention and management of perioperative anemia in noncardiac surgery
Authors: Fergusson Dean A. , Lalu Manoj M.
Published: October 2020

See article on page 2250–2259, in this issue
Knowledge of and attitude toward xenotransplantation among medical students in China: A cross‐sectional study
Authors: Liu Chang , Liu Shiqing
Published: October 2020

Background

There are great challenges in the psychosocial aspects of xenotransplantation. The aim of this study was to investigate the knowledge of and attitude toward xenotransplantation among medical students in China.

Methods

A questionnaire consisting of 12 questions was distributed to 1000 first‐to‐fifth grade medical students, with 200 students in each grade. The questionnaire was self‐administered and completed anonymously with no information beforehand.

Results

The response rate of the questionnaire was 91.5%. Most students had a good knowledge about xenotransplantation. If the results of xenotransplantation were similar with human donation, the acceptance was 63.9% when both organs were available, 70.3% to shorten the waiting time, and 86.4% to save one's life. As for the risks of xenotransplantation, 46.2%, 46.1%, and 36.9% of the respondents were worried about the risk of disease transmission, immunosuppressants, and other unknown risks, respectively. With regard to the psychosocial impacts, 38.4%, 31.9%, and 52.3% were worried about changing one's nature as a human being, changing one's personality, and discrimination by others, respectively.

Conclusion

Most medical students in China had a favorable attitude toward xenotransplantation. Students in the clinical years had a better knowledge of and more favorable attitude toward xenotransplantation. Their concern about the risks of xenotransplantation resolved slightly with seniority, but their concern about psychosocial impacts did not resolve with seniority.
Emerging roles of the TRPV4 channel in bladder physiology and dysfunction
Authors: Wu Yanyuan , Qi Jun , Wu Changhao , Rong Weifang
Published: October 2020

The transient receptor potential vanilloid type 4, TRPV4, is a polymodal cation channel which can be activated by diverse stimuli including mechanical, thermal and chemical cues. In the urinary bladder, TRPV4 is not only abundantly expressed in the urothelium but may also be localized in subepithelium, detrusor smooth muscles and afferent neurons. Emerging evidence indicates that the TRPV4 channel plays a sensory role in the uroepithelium, where it may regulate the release of sensory mediators such as ATP, which in turn modulates afferent nerve activity in response to bladder filling during the urination cycle. TRPV4 may also directly regulate detrusor contractility and the urothelial barrier function. Altered TRPV4 expression has been detected in various pathological bladder conditions. As such, TRPV4 may be a promising therapeutic target for bladder dysfunctions.

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Regulation of microRNA‐221, ‐222, ‐21 and ‐27 in articular cartilage subjected to abnormal compressive forces
Authors: Stadnik Paulina S. , Gilbert Sophie J. , Tarn Jessica , Charlton Sarah , Skelton Andrew J. , Barter Matthew J. , Duance Victor C. , Young David A. , Blain Emma J.
Published: October 2020

Key points

microRNAs (miRs) are small non‐coding molecules that regulate post‐transcriptional target gene expression.

miRs are involved in regulating cellular activities in response to mechanical loading in all physiological systems, although it is largely unknown whether this response differs with increasing magnitudes of load.

miR‐221, miR‐222, miR‐21‐5p and miR‐27a‐5p were significantly increased in ex vivo cartilage explants subjected to increasing load magnitude and in in vivo joint cartilage exposed to abnormal loading.

TIMP3 and CPEB3 are putative miR targets in chondrocytes

Identification of mechanically regulated miRs that have potential to impact on tissue homeostasis provides a mechanism by which load‐induced tissue behaviour is regulated, in both health and pathology, in all physiological systems.

MicroRNAs (miRs) are small non‐coding molecules that regulate post‐transcriptional target gene expression and are involved in mechano‐regulation of cellular activities in all physiological systems. It is unknown whether such epigenetic mechanisms are regulated in response to increasing magnitudes of load. The present study investigated mechano‐regulation of miRs in articular cartilage subjected to ‘physiological’ and ‘non‐physiological’ compressive loads in vitro as a model system and validated findings in an in vivo model of abnormal joint loading. Bovine full‐depth articular cartilage explants were loaded to 2.5 MPa (physiological) or 7 MPa (non‐physiological) (1 Hz, 15 min) and mechanically‐regulated miRs identified using next generation sequencing and verified using a quantitative PCR. Downstream targets were verified using miR‐specific mimics or inhibitors in conjunction with 3′‐UTR luciferase activity assays. A subset of miRs were mechanically‐regulated in ex vivo cartilage explants and in vivo joint cartilage. miR‐221, miR‐222, miR‐21‐5p and miR‐27a‐5p were increased and miR‐483 levels decreased with increasing load magnitude. Tissue inhibitor of metalloproteinase 3 (TIMP3) and cytoplasmic polyadenylation element binding protein 3 (CPEB3) were identified as putative downstream targets. Our data confirm miR‐221 and ‐222 mechano‐regulation and demonstrates novel mechano‐regulation of miR‐21‐5p and miR‐27a‐5p in ex vivo and in vivo cartilage loading models. TIMP3 and CPEB3 are putative miR targets in chondrocytes. Identification of specific miRs that are regulated by increasing load magnitude, as well as their potential to impact on tissue homeostasis, has direct relevance to other mechano‐sensitive physiological systems and provides a mechanism by which load‐induced tissue behaviour is regulated, in both health and pathology.
Study of a Gamma Radiation Impact on Concrete Properties Under Severe Accident Conditions
Authors: Hlaváč Zbyněk , Zatloukalová Jaroslava , Košťál Michal , Losa Evžen
Published: October 2020

Concrete is an important structural material used in nuclear power plant (NPP) design. Due to relatively high amount of hydrogen as well as the presence of heavier elements, it also acts as a biological shielding. One of the important tasks for prolongation of operational life time is the determination of concrete components' condition after long-term irradiation. The paper aims to present the current activities in the CV Řež institute (Research Centre Řež—CVR) regarding the investigation of ionizing radiation effects on concrete properties. In its first part, the paper deals with experimental identification of the character of mixed neutron and gamma spectra in the concrete part of the VVER-1000 Mock-Up. Using the knowledge, the radiation field character can be scaled up to the commercial power plants with VVER-1000 light water reactor. It also provides justification for usage of the 60Co source for performed irradiation experiments with concrete. The second part of the article describes the experimental studies of the properties of gamma-irradiated concrete samples by strong 60Co source. This irradiation experiment can be understood as the first step in characterizing concrete degradation as gamma flux in biological shielding is significantly higher than that of neutron flux. In order to better understand the concrete properties and the behavior under irradiation, nondestructive as well as destructive testing methods were applied. We found that after 48 days of irradiation by the 60Co source the sample obtained dose from gamma corresponding to approximately 1% of the total during the NPP lifetime operation. Concrete microstructure degraded and the modulus of elasticity slightly decreased within 5%. Conversely, destruction tests prove significant flexural strength decrease by 27% in case of normal test and by 63% at the loss of coolant accident (LOCA) test.
Modeling of Welded Joints in a Pyramidal Truss Sandwich Panel Using Beam and Shell Finite Elements
Authors: Yuan Ke , Zhu Weidong
Published: October 2020

Pyramidal truss sandwich panels (PTSPs) are widely used in engineering structures and their face sheets and core parts are generally bonded by the welding process. A large number of solid elements are usually required in the finite element (FE) model of a PTSP with welded joints to obtain its accurate modal parameters. Ignoring welded joints of the PTSP can save many degrees of freedom (DOFs), but significantly change its natural frequencies. This study aims to accurately determine modal parameters of a PTSP with welded joints with much fewer DOFs than those of its solid element model and to obtain its operational modal analysis results by avoiding missing its modes. Two novel methods that consider welded joints as equivalent stiffness are proposed to create beam-shell element models of the PTSP. The main step is to match stiffnesses of beam and shell elements of a welded joint with those of its solid elements. Compared with the solid element model of the PTSP, its proposed models provide almost the same levels of accuracy for natural frequencies and mode shapes for the first 20 elastic modes, while reducing DOFs by about 98% for the whole structure and 99% for each welded joint. The first 14 elastic modes of a PTSP specimen that were measured without missing any modes by synchronously capturing its two-faced vibrations through use of a three-dimensional scanning laser vibrometer (SLV) and a mirror experimentally validate its beam-shell element models created by the two proposed methods.