bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon stimulation test as a possible predictor of residual β‐cell function
Authors: Yoshida Kei , Urakami Tatsuhiko , Morioka Ichiro
Published: May 2021

Background

We aimed to investigate the significance of the C‐peptide levels on a glucagon stimulation test (GST) conducted soon after diagnosis as a predictive marker for residual β‐cell function over time in Japanese children with type 1 diabetes (TD1).

Methods

We retrospectively enrolled 65 Japanese children (25 male, 40 female; age <16 years) with new‐onset TD1. A GST was conducted within 1 month of diagnosis, when glucose toxicity improved. One‐ to 2‐h postprandial serum C‐peptide values were measured at 0, 3, 6, 12, 24, 36, 60, and 120 months after diagnosis.

Results

Receiver operating characteristic analysis showed that the cutoff values of peak serum C‐peptide levels used to predict the complete destruction of β‐cells at 3, 6, and 12 months after diagnosis were all 0.20 ng/mL (area under the curve [AUC] 0.867, 95% confidence interval [CI] 0.745–0.990; AUC 0.774, 95% CI 0.634–0.914; and AUC 0.804, 95% CI 0.695–0.914, respectively); the values at 24, 36, and 60 months were 0.69 ng/mL (AUC 0.828, 95% CI 0.721–0.936), 0.60 ng/mL (AUC 0.777, 95% CI 0.636–0.918), and 0.70 ng/mL (AUC 0.848, 95% CI 0.715–0.982), respectively. On multivariate analysis, peak serum C‐peptide level on a GST, diabetic ketoacidosis, age, and HbA1c level at diagnosis were associated with residual β‐cell function over time.

Conclusions

Peak serum C‐peptide levels on a GST conducted soon after diagnosis in Japanese children with TD1 could predict the time to decrease in postprandial serum C‐peptide values to < 0.20 ng/mL.
Benzodiazepine‐induced photosensitivity reactions: A compilation of cases from literature review with Naranjo causality assessment
Authors: Momin Noorulain , Phan Phuong , Ali Ashmal A. , I. Ali Hamed , Seeger Christina M. , Joseph Merlyn
Published: May 2021

Objective

Benzodiazepines have been reported to cause photosensitivity reactions. We characterized the clinical presentation and diagnosis of benzodiazepine‐associated photosensitivity and adjudicated these cases for a causal association with benzodiazepines.

Methods

A literature search on PubMed's “MeSH” search feature and CINAHL (1964 to 2019) was performed using search terms: benzodiazepine, photosensitivity, and photosensitivity disorders/chemically induced. We applied the Naranjo scale, a standardized causality assessment algorithm, to identified cases.

Results

We identified eight published cases, with 50% of patients being female with a mean age of 46.3 years. Alprazolam, tetrazepam, clobazam, and clorazepate induced phototoxic reactions. Chlordiazepoxide induced one photoallergic reaction. Photosensitivity occurred between 1‐3 days (37.5%), 7‐14 days (25%), and >14 days (25%). Photosensitivity resolved after drug discontinuation within 2 weeks (62.5%). Benzodiazepine rechallenge confirmed photosensitivity in 75% of cases. Photopatch testing was negative in two patients; however, these patients had positive oral provocation testing. However, an oral photoprovocation test, an ideal diagnostic test, was not administered to several patients. Despite these challenges, the Naranjo scale identified 5 cases as definite benzodiazepine‐induced photosensitivity.

Conclusion

Five benzodiazepines induced photosensitivity reactions. Five patients showed a definite association with the Naranjo scale. Reporting to pharmacovigilance databases may help identify other benzodiazepines causing photosensitivity reactions.
Phylogenetic relationships and genetic diversity of Monilinia spp. isolated in Poland based on housekeeping‐ and pathogenicity‐related gene sequence analysis
Authors: Poniatowska Anna , Michalecka Monika , Puławska Joanna
Published: May 2021

Monilinia spp. fungi, which cause brown rot disease, are of great economic importance for pome and stone fruit production in Poland. To date, four species of this genus, M. fructicola, M. fructigena, M. laxa, and M. polystroma, have been identified in this country. However, little is known about their phylogenetic relationships and genetic diversity. In this research, β‐tubulin and three genes not previously studied in these species, heat shock protein 60 (hsp60), acid protease 1 (acp1), and a zinc finger transcription factor (pac1), were investigated to infer the phylogenetic relationships among these species. Diversity data, as well as recombination analyses of the sequenced regions, were used to assess the genetic variation of Monilinia fungi and the evolutionary forces that are currently acting upon these microorganisms. Based on the topology of the obtained dendrograms, the current study demonstrates the lack of a relationship between the phylogenetic position of the strain, the host plant, and the geographical origin of the strain. Additionally, our study provided evidence that phylogenetic analysis using a combination of tub2, hsp60, acp1, and pac1 gene sequences can be used to effectively resolve the relationships among Monilinia species. For each species analysed in this study, low genetic diversity and a lack of recombination were detected. On the basis of the obtained results, it can be concluded that variation in the population of Monilinia spp. in Poland is largely influenced by mutation rather than recombination processes.
Genotype‐ and tissue‐specific physiological and biochemical changes of two chickpea (Cicer arietinum) varieties following a rapid dehydration
Authors: Salahvarzi Mandana , Nasr Esfahani Maryam , Shirzadi Nasrin , Burritt David J. , Tran Lam‐Son Phan
Published: May 2021

In nature, plants may suffer rapid dehydration (RD), which causes significant loss of the annual global chickpea production. Thus, ascertaining more knowledge concerning the RD‐tolerance mechanisms in chickpea is crucial for developing high drought‐tolerant varieties to assure sustainable chickpea production under sudden water deficit. Here, we focused on genotype‐driven variation in leaf relative water content (RWC) and associated differences in RD‐responsive physiological and biochemical attributes in roots and leaves of two chickpea varieties, FLIP00‐21C and FLIP02‐89C, subjected to well‐watered and RD conditions. FLIP00‐21C showed higher RD‐tolerance than FLIP02‐89C, evident by its higher leaf RWC during RD. Consistently, FLIP00‐21C exhibited lower membrane injury due to lower hydrogen peroxide (H2O2) accumulation than FLIP02‐89C during RD, indicating reduced RD‐induced oxidative damage. Under RD conditions, total phenolics in roots and flavonoids in roots and leaves increased more in FLIP02‐89C compared to FLIP00‐21C; however, the increased activities of superoxide dismutase and H2O2‐scavenging enzymes were more properly coordinated in FLIP00‐21C than in FLIP02‐89C, which might contribute to more efficient antioxidant defense in FLIP00‐21C than in FLIP02‐89C. The higher leaf RWC of FLIP00‐21C versus FLIP02‐89C under RD might be associated with greater increases in the levels of the osmo‐regulators proline and total free amino acids (TFAAs) in FLIP00‐21C than in FLIP02‐89C. Collectively, the higher RD‐tolerance of FLIP00‐21C is mainly associated with the maintenance of higher RWC, stronger antioxidant defense, and greater accumulation of proline and TFAAs. These traits could be useful for evaluating the drought‐tolerance of chickpea varieties and further marker‐assisted breeding approaches for improvement of chickpea productivity.
Molecular insights into the role of plant transporters in salt stress response
Authors: Saddhe Ankush Ashok , Mishra Ajay Kumar , Kumar Kundan
Published: May 2021

Salt stress disturbs the cellular osmotic and ionic balance, which then creates a negative impact on plant growth and development. The Na+ and Cl− ions can enter into plant cells through various membrane transporters, including specific and non‐specific Na+, K+, and Ca2+ transporters. Therefore, it is important to understand Na+ and K+ transport mechanisms in plants along with the isolation of genes, their characterization, the structural features, and their post‐translation regulation under salt stress. This review summarizes the molecular insights of plant ion transporters, including non‐selective cation transporters, cyclic nucleotide‐gated cation transporters, glutamate‐like receptors, membrane intrinsic proteins, cation proton antiporters, and sodium proton antiporter families. Further, we discussed the K+ transporter families such as high‐affinity K+ transporters, HAK/KUP/KT transporters, shaker type K+ transporters, and K+ efflux antiporters. Besides the ion transport process, we have shed light on available literature on epigenetic regulation of transport processes under salt stress. Recent advancements of salt stress sensing mechanisms and various salt sensors within signaling transduction pathways are discussed. Further, we have compiled salt‐stress signaling pathways, and their crosstalk with phytohormones.
Inoculation with Bacillus amyloliquefaciens and mycorrhiza confers tolerance to drought stress and improve seed yield and quality of soybean plant
Authors: Sheteiwy Mohamed S. , Abd Elgawad Hamada , Xiong You‐Cai , Macovei Anca , Brestic Marian , Skalicky Milan , Shaghaleh Hiba , Alhaj Hamoud Yousef , El‐Sawah Ahmed M.
Published: May 2021

The present study aimed to evaluate the effect of Bacillus amyloliquefaciens and/or Arbuscular Mycorrhizal Fungi (AMF) as natural biofertilizers on biomass, yield, and seed nutritive quality of soybean (Giza 111). The conditions investigated include a well‐watered (WW) control and irrigation withholding at the seed development stage (R5, after 90 days from sowing) (DS). Co‐inoculation with B. amyloliquefaciens and AMF, resulted in the highest plant biomass and yield under WW and DS conditions. The nuclear DNA content analysis suggested that co‐inoculation with B. amyloliquefaciens and AMF decreased the inhibition of drought stress on both the size and granularity of seed cells, which were comparable to the normal level. The single or co‐inoculation with B. amyloliquefaciens and AMF increased the primary metabolites content and alleviated the drought‐induced reduction in soluble sugars, lipids, protein and oil contents. Plant inoculation induced the expression of genes involved in lipid and protein biosynthesis, whereas an opposite trend was observed for genes involved in lipid and protein degradation, supporting the observed increase in lipid and protein content. Plant inoculated with B. amyloliquefaciens showed the highest α‐amylase and β‐amylase activities, indicating improved osmolyte (soluble sugar) synthesis, particularly under drought. Interestingly, single or co‐inoculation further strengthen the positive effect of drought on the antioxidant and osmoprotectant levels, i.e. phenol, flavonoid, glycine betaine contents, and glutathione‐S‐transferase (GST) activity. As a result of stress release, there was a decrease in the level of stress hormones (abscisic acid, ABA) and an increase in gibberellin (GA), trans‐zeatin‐riboside (ZR), and indole acetic acid (IAA) in the seeds of inoculated plants. Additionally, the ATP content, hydrolytic activities of plasma membrane H+‐ATPase, Ca2+‐ATPase, and Mg2+‐ATPase were also increased by the inoculation.
Doing synthetic biology with photosynthetic microorganisms
Authors: Vavitsas Konstantinos , Kugler Amit , Satta Alessandro , Hatzinikolaou Dimitris G. , Lindblad Peter , Fewer David P. , Lindberg Pia , Toivari Mervi , Stensjö Karin
Published: May 2021

The use of photosynthetic microbes as synthetic biology hosts for the sustainable production of commodity chemicals and even fuels has received increasing attention over the last decade. The number of studies published, tools implemented, and resources made available for microalgae have increased beyond expectations during the last few years. However, the tools available for genetic engineering in these organisms still lag those available for the more commonly used heterotrophic host organisms. In this mini‐review, we provide an overview of the photosynthetic microbes most commonly used in synthetic biology studies, namely cyanobacteria, chlorophytes, eustigmatophytes and diatoms. We provide basic information on the techniques and tools available for each model group of organisms, we outline the state‐of‐the‐art, and we list the synthetic biology tools that have been successfully used. We specifically focus on the latest CRISPR developments, as we believe that precision editing and advanced genetic engineering tools will be pivotal to the advancement of the field. Finally, we discuss the relative strengths and weaknesses of each group of organisms and examine the challenges that need to be overcome to achieve their synthetic biology potential.
Untargeted metabotyping to study phenylpropanoid diversity in crop plants
Authors: Garibay‐Hernández Adriana , Kessler Nikolas , Józefowicz Anna Maria , Türksoy Gözde Merve , Lohwasser Ulrike , Mock Hans‐Peter
Published: May 2021

Plant genebanks constitute a key resource for breeding to ensure crop yield under changing environmental conditions. Because of their roles in a range of stress responses, phenylpropanoids are promising targets. Phenylpropanoids comprise a wide array of metabolites; however, studies regarding their diversity and the underlying genes are still limited for cereals. The assessment of barley diversity via genotyping‐by‐sequencing is in rapid progress. Exploring these resources by integrating genetic association studies to in‐depth metabolomic profiling provides a valuable opportunity to study barley phenylpropanoid metabolism; but poses a challenge by demanding large‐scale approaches. Here, we report an LC‐PDA‐MS workflow for barley high‐throughput metabotyping. Without prior construction of a species‐specific library, this method produced phenylpropanoid‐enriched metabotypes with which the abundance of putative metabolic features was assessed across hundreds of samples in a single‐processed data matrix. The robustness of the analytical performance was tested using a standard mix and extracts from two selected cultivars: Scarlett and Barke. The large‐scale analysis of barley extracts showed (1) that barley flag leaf profiles were dominated by glycosylation derivatives of isovitexin, isoorientin, and isoscoparin; (2) proved the workflow's capability to discriminate within genotypes; (3) highlighted the role of glycosylation in barley phenylpropanoid diversity. Using the barley S42IL mapping population, the workflow proved useful for metabolic quantitative trait loci purposes. The protocol can be readily applied not only to explore the barley phenylpropanoid diversity represented in genebanks but also to study species whose profiles differ from those of cereals: the crop Helianthus annuus (sunflower) and the model plant Arabidopsis thaliana.
Adapting to Sea‐Level Rise: Centralization or Decentralization in Polycentric Governance Systems?
Authors: Lubell Mark , Robbins Matthew
Published: May 2021

How do polycentric governance systems respond to the emergence of new collective‐action problems? We study this question in the context of the evolution of polycentric systems of sea‐level rise adaptation in the San Francisco Bay Area. We focus on how the structure of polycentric systems changes over time to support cooperation and learning and whether those changes represent a process of centralization or decentralization. The ecology of games framework provides the theoretical background for developing hypotheses about the structure of the system over time. We test the hypotheses by analyzing the polycentric system as a two‐mode network where actors are linked to policy, divided into five time periods from 1991 to 2016. The results suggest that the polycentric system for sea‐level rise adaptation started with a centralized set of actors, which evolved over time to a more decentralized structure. The research has general implications with respect to how polycentric systems manage the trade‐off between maintaining local autonomy and coordinating decisions at the regional level across fragmented policy communities.
Comparative efficiency of novel laparoscopic and routine vaginal inseminations with cryopreserved semen in rabbits
Authors: Küçük Niyazi , Uçan Uğur , Raza Sanan , Erdoğan Güneş , Aksoy Melih
Published: May 2021

Laparoscopic artificial insemination technique (LAI) is described to overcome reduced fertility problems in sheep artificial insemination (AI) programmes with frozen semen. Later on, this technology was modified for endangered non‐domestic cats to deposit low quality or reduced number of sperm cells hardly obtained by electro‐ejaculation into the oviduct. This technique by passes the complex structure of cervix and efficiently transfers the sperm cells to the point of fertilization. In recent years, rabbits are becoming popular transgenic animal models producing various therapeutic and commercial products, as well as being experimental animals for disease models. The worldwide transportation of frozen semen and re‐establishment of transgenic lines using AI technology has become a common practice. Therefore, this study was designed to describe a laparoscopic intrauterine insemination technique, which might assist in conceiving the animals with limited number of sperm cells. The female rabbits were laparoscopically (n = 22) or vaginally (n = 13) inseminated with frozen–thawed semen samples containing approximately 10 × 106 motile sperm. The laparoscopic insemination technique provided higher pregnancy rate (45.5%) than vaginal insemination technique (7.7%) (p < .05). In conclusion, the described laparoscopic AI might be a new alternative technique, thus enabling limited or low‐quality frozen sperm samples to establish pregnancy in rabbits.
Assessment of the tongue frenulum in Beckwith‐Wiedemann syndrome: Pre‐ and post‐frenectomy findings
Authors: César Carla Patrícia Hernandez Alves Ribeiro , Torres Geciane Maria Xavier , Andrade Natália Silva , Vanderlei Katharina Morant Holanda de Oliveira , Nascimento Karla Monique de Souza , Barroso Brenna Geovania Izaura Santos , Santos Emerson de Santana
Published: May 2021

Aim: To report the pre‐ and post‐frenectomy findings of a patient with Beckwith‐Wiedemann syndrome.

Methods and Results: Clinical case report of a patient with a confirmed genetic‐molecular diagnosis of the referred syndrome. The minor was evaluated and reassessed by the protocol for the evaluation of the tongue's frenulum for babies in two moments: pre‐surgical and 2 months after the frenectomy. The surgical procedure was performed using the traditional technique and, after the procedure, the minor was breastfed and received photobiomodulation with a red laser. The minor obtained 16 points in the neonatal tongue screening test, indicating the need for a frenectomy. Thus, she was referred to a dentist for surgery. After the surgical procedure, macroglossia was observed as a maternal complaint (previously not mentioned). The wound healing was satisfactory, and the total score obtained in the reapplication of the protocol (five points) showed functional results of improvements in sucking and tongue mobility, justifying the importance of the frenectomy.

Conclusion: Frenectomy, despite showing macroglossia related to the Beckwith‐Wiedemann syndrome, allowed anatomical and functional advances of the tongue in the present clinical case.
Single implant overdenture reinforced with a metallic framework: A 2‐year clinical follow‐up
Authors: Pinheiro Mayara Abreu , do Amaral Camilla Fraga , Meira Ingrid Andrade , Carletti Talita Malini , Câmara‐Souza Mariana Barbosa , Souza Carolina Santos Ventura , de Moraes Marcio , Rodrigues Garcia Renata Cunha Matheus
Published: May 2021

Introduction

To prevent single‐implant overdenture (SIO) fracture, the inclusion of a framework in the overdenture has been suggested. However, no investigations verified their benefits.

Objective

To evaluate prosthetic maintenance events, patient satisfaction, and mastication of SIO reinforced by metallic framework users.

Material and methods

Fifteen volunteers had a new set of complete dentures converted into an SIO containing a framework. Maintenance events were recorded, while patient satisfaction was assessed using a visual analog scale. Masticatory performance (MP) was evaluated using the sieving method, maximum bite force (MBF) by pressure sensors, and masseter thickness by ultrasound. Measurements were performed 2, 12, and 24 months after SIO use. Repeated‐measures ANOVA and paired Student's t‐tests (p < 0.05) were applied.

Results

Matrix exchange was the most prevalent maintenance event (83.6%), and no SIO was fractured during the entire follow‐up. Satisfaction with the SIO stability decreased (p < 0.01) after 12 months. MP did not change between evaluations (p > 0.05). Conversely, MBF and masseter thickness improved after 12 and 24 months of SIO use (p < 0.05).

Conclusions

Reinforced SIO did not fracture during 2 years but requires maintenance. It improves bite force and muscle thickness, maintaining MP values. Satisfaction with SIO stability decreased in the first year of use.
Oral and tracheal microbiota of pediatric and adolescent patients in an intensive care unit
Authors: Pinheiro Caroline Louise Sampaio , Lima Fernanda Pereira , Machado Fernanda Conceição , Santos Sara de Souza , Malheiro Allan Roberto Xavier , Ataíde Ledilce Almeida , Figueiredo Andreia Cristina Leal
Published: May 2021

Objective

To characterize the oral and tracheal microbiota of patients admitted to a pediatric intensive care unit (PICU).

Methods and results

This is an exploratory study conducted on patients aged 5 months to 13 years admitted to the PICU of a referral hospital. Two microbiological samples were collected with a swab in the posterior region of the tongue from patients receiving spontaneous and mechanical ventilation within the first 24 and 48 h after admission to the PICU. Among patients receiving mechanical ventilation, tracheal secretion was also collected in a second sampling. The caries experience was evaluated using the DMFT/dmf index, and the quality of oral hygiene was assessed based on the visual plaque index (VPI). A questionnaire was applied to obtain data on hospital routine and sample characteristics. The DMFT/dmf index was 1.66 (SD = 2.18) and the mean VPI was 43.03 (SD = 36.93). The most prevalent microorganisms were Klebsiella pneumoniae (15%). Oral colonization by opportunistic pathogens was significantly higher in patients receiving mechanical ventilation compared to those on spontaneous ventilation (p < .05). There was no relationship of VPI or DMFT/dmf with oral microbiological changes.

Conclusion

The results indicate that PICU patients are susceptible to colonization by respiratory and opportunistic pathogens since the first hours of hospitalization.
Pain on arteriovenous fistula cannulation: A narrative review
Authors: Kosmadakis George , Amara Ibrahim , Costel Ghania
Published: May 2021

Pain on arteriovenous fistula (AVF) cannulation is a rather persistent problem in the daily hemodialysis practice. Its prevalence varies from 12% to even 80% depending on the definition and the pain‐assessment tools and it affects the quality of life of hemodialysis patients. It is associated with fear of the cannulation process, the decision of hemodialysis from an AVF and sometimes the hemodialysis itself. In this narrative review, we tried to tackle the extent of the problem and to present the available published solutions. The literature suggests a large array of methods based on the application of local anesthetic creams, application of cold or hot directly on the cannulation sites or on the contralateral arm, cannulation techniques and AVF localization, distraction as well as alternative treatments. All of them have shown a relative success. There is a serious lack of large multicenter randomized trials and a gap concerning work groups and guidelines or recommendations from national or international societies on this matter. Complementary training starting from the predialysis patient education programs may be useful. Alternative prophylactic measures including counseling, hypnosis, or other physicochemical interventions could also improve our knowledge on the treatment of this seriously uncomfortable condition.
The mediating role of attention control in the link between multitasking with social media and academic performances among adolescents
Authors: Kokoç Mehmet
Published: May 2021

Prevalence of using social media services while learning, studying and doing homework is increasing rapidly among adolescents in the digital age. Although there is evidence for negative consequences of multitasking with social media, little is known about impact of social media multitasking from perspective attention control of self‐regulation. This study examined the mediating role of attention control as a component of self‐regulation in the link between social media multitasking and academic performances in a sample of adolescents who were recruited from high school students (N = 637). A correlational research design was used in the study. To examine study hypothesis, a mediation model was tested using simple mediation analysis in macro PROCESS (model 4). Results have revealed that attention control of self‐regulation mediated the negative relationship between multitasking with social media and academic performances of the students. Multitasking with social media was a negatively significant predictor of academic performance, whereas attention control positively predicted academic performance. It implies that more frequent multitasking behavior with social media had lower attention control and poorer academic performances. The conclusions of the study suggest a critical role for attention control in decreasing negative effect of multitasking with social media on academic performances of adolescents in high school setting. Implications and suggestions for future studies are proposed.
Falling between the cracks: The effect of using different levels of suicide risk exclusion criteria on sample characteristics when recruiting for an online intervention for depression
Authors: Godinho Alexandra , Schell Christina , Cunningham John A.
Published: May 2021

Background

Despite a strong link between suicide risk and depression, a recent literature review found that many effectiveness studies for online depression interventions exclude individuals at risk of suicide. This study scrutinizes how different suicide risk exclusion criteria impact recruitment rates and final sample characteristics.

Materials and Methods

Two recruitment periods for an online depression intervention trial utilized different suicide risk cutoff exclusion criteria, a one‐point difference on the last item of the Personal Health Questionnaire (i.e., more than 0 (Not at all) vs. more than 1 (Several Days)). Bivariate statistics were used to assess differences in recruitment rates and sample characteristics between these two recruitment periods, while all other eligibility criteria and recruitment strategies remained consistent.

Results

The recruitment period using the least restrictive suicide risk exclusion criteria yielded twice as many participants; however, recruited sample characteristics did not significantly differ among demographic or clinical characteristics, despite observable trends.

Discussion

Researchers should carefully select suicide risk exclusion criteria that balance recruitment rates, study budgets, and sample selection biases, while minimizing participant harm. Moreover, researchers are urged to report suicide risk exclusion rates and consider these exclusions when interpreting results. Limitations of the results are also discussed.
Chronic hyperglycemia, hypercholesterolemia, and metabolic syndrome are associated with risk of tendon injury
Authors: Skovgaard Dorthe , Siersma Volkert D. , Klausen Soren Bering , Visnes Håvard , Haukenes Inger , Bang Christine W. , Bager Peter , Grävare Silbernagel Karin , Gaida Jamie , Magnusson Stig Peter , Kjaer Michael , Couppé Christian
Published: May 2021

Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia, and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Heart Study is a prospective study of diabetic and non‐diabetic individuals from the Danish general population with different physical activity levels. The cohort was followed for 3 years via national registers with respect to tendon injuries. Data from 5856 individuals (median age 62 years) were included. The overall incidence of tendon injury in both upper and lower extremities that required an out‐patient or in‐house visit to a hospital was ~5.7/1000 person years. Individuals with elevated HbA1c (glycated hemoglobin) even in the prediabetic range (HbA1c>5.7%) had a ~3 times higher risk of tendon injury in the lower extremities only, as compared to individuals with normal HbA1C levels. Hypercholesterolemia (total cholesterol>5 mmol/L) increased risk of tendon injury in the upper extremities by ~1.5 times, and individuals with metabolic syndrome had ~2.5 times higher risk of tendon injury in both upper and lower extremities. In conclusion, these data demonstrate for the first time in a large cohort with different physical activity levels that the indicators for metabolic syndrome are a powerful systemic determinant of tendon injury, and two of its components, hyperglycemia and hypercholesterolemia, each independently make tendons susceptible for damage and injury.
Recognition of the HLA‐C*03:88 allele in a Singaporean bone marrow donor
Authors: Cho Louise , Seng Zi‐Jing , Lin Py‐Yu , Yang Kuo‐Liang
Published: May 2021

One nucleotide substitution in codon 108 of HLA‐C*03:03:01:01 results in a novel allele, HLA‐C*03:88.
Genetic mapping of the early responses to salt stress inArabidopsis thaliana
Authors: Awlia Mariam , Alshareef Nouf , Saber Noha , Korte Arthur , Oakey Helena , Panzarová Klára , Trtílek Martin , Negrão Sónia , Tester Mark , Julkowska Magdalena M.
Published: May 2021

Salt stress decreases plant growth prior to significant ion accumulation in the shoot. However, the processes underlying this rapid reduction in growth are still unknown. To understand the changes in salt stress responses through time and at multiple physiological levels, examining different plant processes within a single set‐up is required. Recent advances in phenotyping has allowed the image‐based estimation of plant growth, morphology, colour and photosynthetic activity. In this study, we examined the salt stress‐induced responses of 191 Arabidopsis accessions from 1 h to 7 days after treatment using high‐throughput phenotyping. Multivariate analyses and machine learning algorithms identified that quantum yield measured in the light‐adapted state (Fv′/Fm′) greatly affected growth maintenance in the early phase of salt stress, whereas the maximum quantum yield (QYmax) was crucial at a later stage. In addition, our genome‐wide association study (GWAS) identified 770 loci that were specific to salt stress, in which two loci associated with QYmaxandFv′/Fm′were selected for validation using T‐DNA insertion lines. We characterized an unknown protein kinase found in the QYmaxlocus that reduced photosynthetic efficiency and growth maintenance under salt stress. Understanding the molecular context of the candidate genes identified will provide valuable insights into the early plant responses to salt stress. Furthermore, our work incorporates high‐throughput phenotyping, multivariate analyses and GWAS, uncovering details of temporal stress responses and identifying associations across different traits and time points, which are likely to constitute the genetic components of salinity tolerance.
We stand ready … Blood collection organizations and the COVID‐19 pandemic
Authors: Kamel Hany
Published: May 2021

See article on page 1471–1478, in this issue
Convex vacancy creation costs and on‐the‐job search in a global economy
Authors: Holzner Christian , Larch Mario
Published: May 2021

Convex vacancy creation costs shape firms’ responses to trade liberalisation. They induce capacity constraints by increasing firms’ costs of production. A profit maximising firm will therefore not fully meet the increased foreign demand, but serve only a few export markets. More productive firms will export to more countries and profit more from trade liberalisation. To get an effect of trade liberalisation on wage inequality, we need on‐the‐job search and convex vacancy creation costs because with linear costs trade liberalisation affects all wages in equal proportion. Furthermore, with convex vacancy creation costs, not all firms export to all foreign markets even if trade is fully liberalised. This implies that wage inequality under free trade is always higher than under autarky.
Extra‐auricular lesions of proliferative and necrotizing otitis externa in three kittens
Authors: Panzuti Pauline , Jongh Olivier , Dony Manoëlle , Vial Stéphanie , Mosca Marion , Pin Didier
Published: May 2021

Background

Proliferative and necrotising otitis externa (PNOE) is a rare disorder in cats with poorly understood pathogenesis. Extra‐auricular (EA) lesions recently have been mentioned in a textbook and in one case report.

Objectives

To describe EA lesions associated with PNOE in three kittens.

Animals

A 6‐month‐old female domestic short hair (DSH) cat (Case 1), an 8‐month‐old female DSH cat (Case 2) and a 5‐month‐old female DSH cat (Case 3).

Methods and results

All cases exhibited classical lesions of PNOE associated with EA lesions, generalised (cases 1 and 3) or limited to eyelids (Case 2). Lesions were characterised by thick, adherent, hyperkeratotic papules coalescing to plaques and attempts to remove the hyperkeratotic plaques resulted in erosions. Histopathological examinations revealed classical features of PNOE: severe acanthosis associated with a marked lymphocytic exocytosis, satellitosis and apoptotic keratinocytes at all levels of the epidermis and the outer root sheath of hair follicles. Cases 2 and 3 resolved spontaneously. Case 1 remained stable with topical tacrolimus and oral prednisolone after a short course of ciclosporin.

Conclusions and clinical importance

This report describes EA lesions of PNOE in three kittens. Such lesions may be underdiagnosed, and this report emphasises the role of a thorough clinical inspection in PNOE cases.
Assessment of indigenous surrogate microorganisms for UV disinfection dose verification
Authors: Blyth James , Templeton Michael R. , Court Sarah‐Jane , Luce Cécile , Cairns William , Hazell Lucinda
Published: May 2021

This study aimed to isolate waterborne heterotrophic organisms indigenous to water treatment processes with suitable ultraviolet (UV) dose–response profiles for estimation of the UV doses delivered by operational UV disinfection systems. The UV dose–response profiles of two isolated organisms, Flavobacterium succinicans and Sphingopyxis chilensis, were determined. S. chilensis has a UV dose–response with potential for use as an indigenous surrogate for Cryptosporidium inactivation, up to 2.2‐logs in the dose range 2–7 mJ/cm2 of monochromatic UV light at 253.7 nm. F. succinicans was more sensitive and tailing was observed above 4 mJ/cm2 making it unsuitable for UV dose verification above this dose. As a single species in the water samples used in this study, S. chilensis is unlikely to be present in sufficient numbers for routine use as an indigenous surrogate. However, the Sphingomonadaceae family to which it belongs is abundant in various drinking water sources and warrants further investigation.
Keloid tissue analysis discredits a role for myofibroblasts in disease pathogenesis
Authors: Bell Rachel E. , Shaw Tanya J.
Published: May 2021

Myofibroblasts, renowned for their contractility and extracellular matrix production, are widely considered the key effector cells for nearly all scars resulting from tissue repair processes, ranging from normal scars to extreme fibrosis. For example, it is often assumed that myofibroblasts underpin the characteristics of keloid scars, which are debilitating pathological skin scars lacking effective treatments because of a poor understanding of the disease mechanisms. Here, we present primary and published transcriptional and histological evidence that myofibroblasts are not consistently present in primary keloid lesions, and when alpha‐smooth muscle actin (αSMA)‐positive cells are detected, they are not greater in number or expressing more αSMA than in normal or hypertrophic scars. In conclusion, keloid scars do not appear to require αSMA‐positive myofibroblasts; continuing to consider keloids on a quantitative spectrum with normal or hypertrophic scars, with αSMA serving as a biomarker of disease severity, is hindering advancement of understanding and therapy development.
Performance comparison of approximate dynamic programming techniques for dynamic stochastic scheduling
Authors: Göçgün Yasin
Published: May 2021

This paper focuses on the performance comparison of several approximate dynamic programming (ADP) techniques. In particular, we evaluate three ADP techniques through a class of dynamic stochastic scheduling problems: Lagrangian-based ADP, linear programming-based ADP, and direct search-based ADP. We uniquely implement the direct search-based ADP through basis functions that differ from those used in the relevant literature. The class of scheduling problems has the property that jobs arriving dynamically and stochastically must be scheduled to days in advance. Numerical results reveal that the direct search-based ADP outperforms others in the majority of problem sets generated.
Zeitgebers of skeletal muscle and implications for metabolic health
Authors: Gabriel Brendan M. , Zierath Juleen R.
Published: May 2021

Metabolic health is a crucial area of current research, and is an outcome of innate physiology, and interactions with the environment. Environmental cues, such as the Earth's day‐night rhythm, partly regulate diurnal hormones and metabolites. Circadian physiology consists of highly conserved biological processes over ∼24‐h cycles, which are influenced by external cues (Zeitgebers – ‘time‐keepers’). Skeletal muscle has diurnal variations of a large magnitude, owing in part to the strong nature of physical activity throughout the day and other external Zeitgebers. The orchestration of whole‐body and skeletal muscle metabolism is a complex, finely tuned process, and molecular diurnal variations are regulated by a transcription‐translation feedback loop controlled by the molecular clock, as well as non‐transcriptional metabolic processes. The mitochondrion may play an important role in regulating diurnal metabolites within skeletal muscle, given its central role in the regulation of NAD+/NADH, O2, reactive oxygen species and redox metabolism. These molecular pathways display diurnal variation and illustrate the complex orchestration of circadian metabolism in skeletal muscle. Probably the most robust Zeitgeber of skeletal muscle is exercise, which alters glucose metabolism and flux, in addition to a range of other diurnal metabolic pathways. Indeed, performing exercise at different times of the day may alter metabolism and health outcomes in some cohorts. The objective of this Symposium Review is to briefly cover the current literature, and to speculate regarding future areas of research. Thus, we postulate that metabolic health may be optimized by altering the timing of external cues such as diet and exercise.

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Temporal control of muscle synergies is linked with alpha‐band neural drive
Authors: Laine Christopher M. , Cohn Brian A. , Valero‐Cuevas Francisco J.
Published: May 2021

Key points

It is theorized that the nervous system controls groups of muscles together as functional units, or ‘synergies’, resulting in correlated electromyographic (EMG) signals among muscles. However, such correlation does not necessarily imply group‐level neural control.

Oscillatory synchronization (coherence) among EMG signals implies neural coupling, but it is not clear how this relates to control of muscle synergies.

EMG was recorded from seven arm muscles of 10 adult participants rotating an upper limb ergometer, and EMG–EMG coherence, EMG amplitude correlations and their relationship with each other were characterized. A novel method to derive multi‐muscle synergies from EMG–EMG coherence is presented and these are compared with classically defined synergies.

Coherent alpha‐band (8–16 Hz) drive was strongest among muscles whose gross activity levels are well correlated within a given task.

The cross‐muscle distribution and temporal modulation of coherent alpha‐band drive suggests a possible role in the neural coordination/monitoring of synergies.

During movement, groups of muscles may be controlled together by the nervous system as an adaptable functional entity, or ‘synergy’. The rules governing when (or if) this occurs during voluntary behaviour in humans are not well understood, at least in part because synergies are usually defined by correlated patterns of muscle activity without regard for the underlying structure of their neural control. In this study, we investigated the extent to which comodulation of muscle output (i.e. correlation of electromyographic (EMG) amplitudes) implies that muscles share intermuscular neural input (assessed via EMG–EMG coherence analysis). We first examined this relationship among pairs of upper limb muscles engaged in an arm cycling task. We then applied a novel multidimensional EMG–EMG coherence analysis allowing synergies to be characterized on the basis of shared neural drive. We found that alpha‐band coherence (8–16 Hz) is related to the degree to which overall muscle activity levels correlate over time. The extension of this coherence analysis to describe the cross‐muscle distribution and temporal modulation of alpha‐band drive revealed a close match to the temporal and structural features of traditionally defined muscle synergies. Interestingly, the coherence‐derived neural drive was inversely associated with, and preceded, changes in EMG amplitudes by ∼200 ms. Our novel characterization of how alpha‐band neural drive is dynamically distributed among muscles is a fundamental step forward in understanding the neural origins and correlates of muscle synergies.
Delayed KCNQ1/KCNE1 assembly on the cell surface helps IKs fulfil its function as a repolarization reserve in the heart
Authors: Wilson Zachary T. , Jiang Min , Geng Jing , Kaur Sukhleen , Workman Samuel W. , Hao Jon , Bernas Tytus , Tseng Gea‐Ny
Published: May 2021

Key points

In adult ventricular myocytes, the slow delayed rectifier (IKs) channels are distributed on the surface sarcolemma, not t‐tubules.

In adult ventricular myocytes, KCNQ1 and KCNE1 have distinct cell surface and cytoplasmic pools.

KCNQ1 and KCNE1 traffic from the endoplasmic reticulum to the plasma membrane by separate routes, and assemble into IKs channels on the cell surface.

Liquid chromatography/tandem mass spectrometry applied to affinity‐purified KCNQ1 and KCNE1 interacting proteins reveals novel interactors involved in protein trafficking and assembly.

Microtubule plus‐end binding protein 1 (EB1) binds KCNQ1 preferentially in its dimer form, and promotes KCNQ1 to reach the cell surface.

An LQT1‐associated mutation, Y111C, reduces KCNQ1 binding to EB1 dimer.

Slow delayed rectifier (IKs) channels consist of KCNQ1 and KCNE1. IKs functions as a ‘repolarization reserve’ in the heart by providing extra current for ventricular action potential shortening during β‐adrenergic stimulation. There has been much debate about how KCNQ1 and KCNE1 traffic in cells, where they associate to form IKs channels, and the distribution pattern of IKs channels relative to β‐adrenergic signalling complex. We used experimental strategies not previously applied to KCNQ1, KCNE1 or IKs, to provide new insights into these issues. ‘Retention‐using‐selected‐hook’ experiments showed that newly translated KCNE1 constitutively trafficked through the conventional secretory path to the cell surface. KCNQ1 largely stayed in the endoplasmic reticulum, although dynamic KCNQ1 vesicles were observed in the submembrane region. Disulphide‐bonded KCNQ1/KCNE1 constructs reported preferential association after they had reached cell surface. An in situ proximity ligation assay detected IKs channels in surface sarcolemma but not t‐tubules of ventricular myocytes, similar to the reported location of adenylate cyclase 9/yotiao. Fluorescent protein‐tagged KCNQ1 and KCNE1, in conjunction with antibodies targeting their extracellular epitopes, detected distinct cell surface and cytoplasmic pools of both proteins in myocytes. We conclude that, in cardiomyocytes, KCNQ1 and KCNE1 traffic by different routes to surface sarcolemma where they assemble into IKs channels. This mode of delayed channel assembly helps IKs fulfil its function of repolarization reserve. Proteomic experiments revealed a novel KCNQ1 interactor, microtubule plus‐end binding protein 1 (EB1). EB1 dimer (active form) bound KCNQ1 and increased its surface level. An LQT1 mutation, Y111C, reduced KCNQ1 binding to EB1 dimer.
Optimization of Clot Formation Methodology for Assessment of Neurothrombectomy Devices in Large Animal Thrombectomy Models
Authors: Jimenez Cedric , Polyakov Igor , Kleinert Leigh , Nelson André , Smith Mark
Published: May 2021

Neurothrombectomy devices are commonly evaluated for potential clinical success in porcine models of neurothromboembolism. The majority of preclinical evaluations for these devices are performed in the vasculature of swine or dog utilizing clots created ex vivo. This investigation was conducted to develop a faster, more reliable method for creating clots ex vivo for model development. Neurothrombectomy devices are designed to perform recanalization of arterial occlusions that cause acute ischemic stroke [1]. Recanalization can be achieved via clot disruption, aspiration, or retrieval using one or more mechanical devices. In order to evaluate these devices in vivo, a fast and reliable method for creating and delivering clots to a desired artery, thereby simulating a target site for neurothrombectomy, is essential.

Two types of clot analogs (soft or firm) were created using two different methods in order to compare both their mechanical properties and their ability to reliably occlude selected arteries. Utilizing both methods, pre-formed clots were qualitatively compared in vitro to evaluate elasticity, stiffness, and functionality of delivery through a catheter. These evaluations were performed prior to in vivo assessment of the effectiveness of the analogs occlusion of selected arterial vasculature.
Dynein Light-Chain Dynlrb2 Is Essential for Murine Leukemia Virus Traffic and Nuclear Entry
Authors: Pietrantoni Gianfranco , Gaete-Argel Aracelly , Herrera-Rojo Diego , Ibarra-Karmy Rodrigo , Bustos Fernando J. , Valiente-Echeverría Fernando , Arriagada Gloria
Published: May 2021

Different viruses use different components of cytoplasmic dynein complex to traffic to their replication site. We have found that murine leukemia virus (MLV) depends on dynein light-chain Dynlrb2 for infection, retrograde traffic, and nuclear entry. Our study provides new information regarding the molecular requirements for retrograde transport of MLV preintegration complex and demonstrates the essential role of Dynlrb2 in MLV infection.
Diverse RNA Viruses Discovered in Three Parasitoid Wasps of the Rice Weevil
Sitophilus oryzae
Authors: Wang Fei , Yuan Bo , Xiao Shan , Zhang Jiao , Jia Wenxi , Fang Qi , Wang Fang , Song Qisheng , Ye Gongyin
Published: May 2021

The enormous diversity of RNA viruses in insects is continuously validated. Parasitoid wasps, as biocontrol insects which are widely used against insect pests in agroecosystems, may also carry many “good” RNA viruses.