bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the Genetic Architecture and Genomic Prediction of Powdery Mildew Resistance in Flax (Linum usitatissimum L.)
Authors: You Frank M. , Rashid Khalid Y. , Zheng Chunfang , Khan Nadeem , Li Pingchuan , Xiao Jin , He Liqiang , Yao Zhen , Cloutier Sylvie
Published: April 2022

Powdery mildew (PM), caused by the fungus Oidium lini in flax, can cause defoliation and reduce seed yield and quality. To date, one major dominant gene (Pm1) and three quantitative trait loci (QTL) on chromosomes 1, 7 and 9 have been reported for PM resistance. To fully dissect the genetic architecture of PM resistance and identify QTL, a diverse flax core collection of 372 accessions augmented with an additional 75 breeding lines were sequenced, and PM resistance was evaluated in the field for eight years (2010–2017) in Morden, Manitoba, Canada. Genome-wide association studies (GWAS) were performed using two single-locus and seven multi-locus statistical models with 247,160 single nucleotide polymorphisms (SNPs) and the phenotypes of the 447 individuals for each year separately as well as the means over years. A total of 349 quantitative trait nucleotides (QTNs) were identified, of which 44 large-effect QTNs (R2 = 10–30%) were highly stable over years. The total number of favourable alleles per accession was significantly correlated with PM resistance (r = 0.74), and genomic selection (GS) models using all identified QTNs generated significantly higher predictive ability (r = 0.93) than those constructed using the 247,160 genome-wide random SNP (r = 0.69), validating the overall reliability of the QTNs and showing the additivity of PM resistance in flax. The QTNs were clustered on the distal ends of all 15 chromosomes, especially on chromosome 5 (0.4–5.6 Mb and 9.4–16.9 Mb) and 13 (4.7–5.2 Mb). To identify candidate genes, a dataset of 3230 SNPs located in resistance gene analogues (RGAs) was used as input for GWAS, from which an additional 39 RGA-specific QTNs were identified. Overall, 269 QTN loci harboured 445 RGAs within the 200 Kb regions spanning the QTNs, including 45 QTNs located within the RGAs. These RGAs supported by significant QTN/SNP allele effects were mostly nucleotide binding site and leucine-rich repeat receptors (NLRs) belonging to either coiled-coil (CC) NLR (CNL) or toll interleukin-1 (TIR) NLR (TNL), receptor-like kinase (RLK), receptor-like protein kinase (RLP), transmembrane-coiled-coil (TM-CC), WRKY, and mildew locus O (MLO) genes. These results constitute an important genomic tool for resistance breeding and gene cloning for PM in flax.
A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation
Authors: Mattorre Benedetta , Caristi Silvana , Donato Simona , Volpe Emilia , Faiella Marika , Paiardini Alessandro , Sorrentino Rosa , Paladini Fabiana
Published: April 2022

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.
Biomarkers for Alzheimer’s Disease in the Current State: A Narrative Review
Authors: Gunes Serafettin , Aizawa Yumi , Sugashi Takuma , Sugimoto Masahiro , Rodrigues Pedro Pereira
Published: April 2022

Alzheimer’s disease (AD) has become a problem, owing to its high prevalence in an aging society with no treatment available after onset. However, early diagnosis is essential for preventive intervention to delay disease onset due to its slow progression. The current AD diagnostic methods are typically invasive and expensive, limiting their potential for widespread use. Thus, the development of biomarkers in available biofluids, such as blood, urine, and saliva, which enables low or non-invasive, reasonable, and objective evaluation of AD status, is an urgent task. Here, we reviewed studies that examined biomarker candidates for the early detection of AD. Some of the candidates showed potential biomarkers, but further validation studies are needed. We also reviewed studies for non-invasive biomarkers of AD. Given the complexity of the AD continuum, multiple biomarkers with machine-learning-classification methods have been recently used to enhance diagnostic accuracy and characterize individual AD phenotypes. Artificial intelligence and new body fluid-based biomarkers, in combination with other risk factors, will provide a novel solution that may revolutionize the early diagnosis of AD.
Exosomes Derived from Human Amniotic Fluid Mesenchymal Stem Cells Preserve Microglia and Neuron Cells from Aβ
Authors: Zavatti Manuela , Gatti Martina , Beretti Francesca , Palumbo Carla , Maraldi Tullia
Published: April 2022

Background: Neuroinflammation is involved in neuronal cell death that occurs in neurodegenerative diseases such as Alzheimer’s disease (AD). Microglia play important roles in regulating the brain amyloid beta (Aβ) levels, so immunomodulatory properties exerted by mesenchymal stem cells may be exploited to treat this pathology. The evidence suggests that the mechanism of action of human amniotic fluid stem cells (hAFSCs) is through their secretome, which includes exosomes (exo). Methods: We examined the effect of exosomes derived from human amniotic fluid stem cells (hAFSCs-exo) on activated BV-2 microglia cells by lipopolysaccharide (LPS) as a neuroinflammation model. To investigate the exo effect on the interplay between AD neurons and microglia, SH-SY5Y neuroblastoma cells treated with Aβ were exposed to a conditioned medium (CM) obtained from activated BV-2 or co-culture systems. Results: We found that the upregulation of the markers of pro-inflammatory microglia was prevented when exposed to hAFSC-exo whereas the markers of the anti-inflammatory macrophage phenotype were not affected. Interestingly, the hAFSC-exo pretreatment significantly inhibited the oxidative stress rise and apoptosis occurring in the neurons in presence of both microglia and Aβ. Conclusion: We demonstrated that hAFSC-exo mitigated an inflammatory injury caused by microglia and significantly recovered the neurotoxicity, suggesting that hAFSC-exo may be a potential therapeutic agent for inflammation-related neurological conditions, including AD.
Impact of Cerebral Amyloid Angiopathy in Two Transgenic Mouse Models of Cerebral β-Amyloidosis: A Neuropathological Study
Authors: Marazuela Paula , Paez-Montserrat Berta , Bonaterra-Pastra Anna , Solé Montse , Hernández-Guillamon Mar
Published: April 2022

The pathological accumulation of parenchymal and vascular amyloid-beta (Aβ) are the main hallmarks of Alzheimer’s disease (AD) and Cerebral Amyloid Angiopathy (CAA), respectively. Emerging evidence raises an important contribution of vascular dysfunction in AD pathology that could partially explain the failure of anti-Aβ therapies in this field. Transgenic mice models of cerebral β-amyloidosis are essential to a better understanding of the mechanisms underlying amyloid accumulation in the cerebrovasculature and its interactions with neuritic plaque deposition. Here, our main objective was to evaluate the progression of both parenchymal and vascular deposition in APP23 and 5xFAD transgenic mice in relation to age and sex. We first showed a significant age-dependent accumulation of extracellular Aβ deposits in both transgenic models, with a greater increase in APP23 females. We confirmed that CAA pathology was more prominent in the APP23 mice, demonstrating a higher progression of Aβ-positive vessels with age, but not linked to sex, and detecting a pronounced burden of cerebral microbleeds (cMBs) by magnetic resonance imaging (MRI). In contrast, 5xFAD mice did not present CAA, as shown by the negligible Aβ presence in cerebral vessels and the occurrence of occasional cMBs comparable to WT mice. In conclusion, the APP23 mouse model is an interesting tool to study the overlap between vascular and parenchymal Aβ deposition and to evaluate future disease-modifying therapy before its translation to the clinic.
Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas
Authors: Emerald Bright Starling , Mohsin Sahar , D’Souza Crystal , John Annie , El-Hasasna Hussain , Ojha Shreesh , Raza Haider , al-Ramadi Basel , Adeghate Ernest
Published: April 2022

Nitric oxide is generated from nitric oxide synthase following hyperglycemia-induced oxidative stress during the course of diabetes mellitus (DM). We examined the temporal immuno-expression of neuronal nitric oxide synthase (nNOS) in the pancreas of diabetic and non-diabetic rats using immunohistochemical, immunofluorescence and western blot techniques 12 h, 24 h, 1 week, 2 weeks, 1, 8 and 15 months after induction of DM. nNOS co-localized with pancreatic beta cells but disappears 12 h after the onset of DM. In contrast, the nNOS content of pancreatic nerves increased significantly (p < 0.001) 24 h after the induction of DM, and decreased sharply thereafter. However, nNOS-positive ganglion cells were observed even 15 months post-diabetes. ROS increased by more than 100% two months after the onset of DM compared to non-diabetic control but was significantly (p < 0.000001) reduced at 9 months after the induction of DM. The pancreatic content of GSH increased significantly (p < 0.02) after 9 months of DM. Although, TBARS content was significantly (p < 0.009; p < 0.002) lower in aged (9 months) non-diabetic and DM rats, TBARS rate was markedly (p < 0.02) higher 9 months after the induction of DM when compared to younger age group. In conclusion, nNOS is present in pancreatic beta cell, but disappears 12 h after the onset of diabetes. In contrast, the tissue level of nNOS of pancreatic nerves increased in the first week of diabetes, followed by a sharp reduction. nNOS may play important roles in the metabolism of pancreatic beta cell.
Effects of Hexagonal Boron Nitride Insulating Layers on the Driving Performance of Ionic Electroactive Polymer Actuators for Light-Weight Artificial Muscles
Authors: Park Minjeong , Chun Youngjae , Kim Seonpil , Sohn Keun Yong , Jeon Minhyon
Published: April 2022

To improve the energy efficiency and driving performance of ionic electroactive polymer actuators, we propose inserting insulating layers of 170 nm hexagonal boron nitride (h-BN) particles between the ionic polymer membrane and electrodes. In experiments, actuators exhibited better capacitance (4.020 × 10−1 F), displacement (6.01 mm), and curvature (35.59 m−1) with such layers than without them. The excellent insulating properties and uniform morphology of the layers reduced the interfacial resistance, and the ion conductivity (0.071 S m−1) within the ionic polymer improved significantly. Durability was enhanced because the h-BN layer is chemically and thermally stable and efficiently blocks heat diffusion and ion hydrate evaporation during operation. The results demonstrate a close relationship between the capacitance and driving performance of actuators. A gripper prepared from the proposed ionic electroactive polymer actuator can stably hold an object even under strong external vibration and fast or slow movement.
The SCO2102 Protein Harbouring a DnaA II Protein-Interaction Domain Is Essential for the SCO2103 Methylenetetrahydrofolate Reductase Positioning at Streptomyces Sporulating Hyphae, Enhancing DNA Replication during Sporulation
Authors: Fernández-García Gemma , González-Quiñónez Nathaly , Rioseras Beatriz , Alonso-Fernández Sergio , Fernández Javier , Lombó Felipe , Manteca Ángel
Published: April 2022

Streptomyces DNA replication starts with the DnaA binding to the origin of replication. Differently to most bacteria, cytokinesis only occurs during sporulation. Cytokinesis is modulated by the divisome, an orderly succession of proteins initiated by FtsZ. Here, we characterised SCO2102, a protein harbouring a DnaA II protein–protein interaction domain highly conserved in Streptomyces. The ΔSCO2102 knockout shows highly delayed sporulation. SCO2102-mCherry frequently co-localises with FtsZ-eGFP during sporulation and greatly reduces FtsZ-eGFP Z-ladder formation, suggesting a role of SCO2102 in sporulation. SCO2102 localises up-stream of SCO2103, a methylenetetrahydrofolate reductase involved in methionine and dTMP synthesis. SCO2102/SCO2103 expression is highly regulated, involving two promoters and a conditional transcription terminator. The ΔSCO2103 knockout shows reduced DNA synthesis and a non-sporulating phenotype. SCO2102-mCherry co-localises with SCO2103-eGFP during sporulation, and SCO2102 is essential for the SCO2103 positioning at sporulating hyphae, since SCO2103-eGFP fluorescent spots are absent in the ΔSCO2102 knockout. We propose a model in which SCO2102 positions SCO2103 in sporulating hyphae, facilitating nucleotide biosynthesis for chromosomal replication. To the best of our knowledge, SCO2102 is the first protein harbouring a DnaA II domain specifically found during sporulation, whereas SCO2103 is the first methylenetetrahydrofolate reductase found to be essential for Streptomyces sporulation.
Cell Death by Entosis: Triggers, Molecular Mechanisms and Clinical Significance
Authors: Kianfar Mostafa , Balcerak Anna , Chmielarczyk Mateusz , Tarnowski Leszek , Grzybowska Ewa A.
Published: April 2022

Entosis—a homotypic insertion of one cell into another, resulting in a death of the invading cell—has been described in many reports, but crucial aspects of its molecular mechanisms and clinical significance still remain controversial. While actomyosin contractility of the invading cell is very well established as a driving force in the initial phase, and autophagy induced in the outer cell is determined as the main mechanism of degradation of the inner cell, many details remain unresolved. The multitude of triggering factors and crisscrossing molecular pathways described in entosis regulation make interpretations difficult. The question of the physiological role of entosis also remains unanswered. In this review, we summarize the knowledge of molecular mechanisms and clinical data concerning entosis accumulated so far, highlighting both coherent explanations and controversies.
Regulatory Roles of Caspase-11 Non-Canonical Inflammasome in Inflammatory Liver Diseases
Authors: Yi Young-Su
Published: April 2022

An inflammatory response consists of two consecutive steps: priming and triggering, to prepare and activate inflammatory responses, respectively. The cardinal feature of the triggering step is the activation of intracellular protein complexes called inflammasomes, which provide a platform for the activation of inflammatory signaling pathways. Despite many studies demonstrating the regulatory roles of canonical inflammasomes in inflammatory liver diseases, the roles of newly discovered non-canonical inflammasomes in inflammatory liver diseases are still largely unknown. Recent studies have reported the regulatory roles of the caspase-11 non-canonical inflammasome in inflammatory liver diseases, providing strong evidence that the caspase-11 non-canonical inflammasome may play key roles in the pathogenesis of inflammatory liver diseases. This review comprehensively discusses the emerging roles of the caspase-11 non-canonical inflammasome in the pathogenesis of inflammatory liver diseases, focusing on non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and inflammatory liver injuries and its underlying mechanisms. This review highlights the current knowledge on the regulatory roles of the caspase-11 non-canonical inflammasome in inflammatory liver diseases, providing new insights into the development of potential therapeutics to prevent and treat inflammatory liver diseases by targeting the caspase-11 non-canonical inflammasome.
Novel Biomarkers of Atherosclerotic Vascular Disease—Latest Insights in the Research Field
Authors: Adam Cristina Andreea , Șalaru Delia Lidia , Prisacariu Cristina , Marcu Dragoș Traian Marius , Sascău Radu Andy , Stătescu Cristian
Published: April 2022

The atherosclerotic vascular disease is a cardiovascular continuum in which the main role is attributed to atherosclerosis, from its appearance to its associated complications. The increasing prevalence of cardiovascular risk factors, population ageing, and burden on both the economy and the healthcare system have led to the development of new diagnostic and therapeutic strategies in the field. The better understanding or discovery of new pathophysiological mechanisms and molecules modulating various signaling pathways involved in atherosclerosis have led to the development of potential new biomarkers, with key role in early, subclinical diagnosis. The evolution of technological processes in medicine has shifted the attention of researchers from the profiling of classical risk factors to the identification of new biomarkers such as midregional pro-adrenomedullin, midkine, stromelysin-2, pentraxin 3, inflammasomes, or endothelial cell-derived extracellular vesicles. These molecules are seen as future therapeutic targets associated with decreased morbidity and mortality through early diagnosis of atherosclerotic lesions and future research directions.
Set Operations in Python for Translational Medicine
Authors: Takefuji Yoshiyasu
Published: April 2022

This is the world’s first tutorial article on Python programing on set operations for beginners and practitioners in translational medicine or medicine in general. This tutorial will allow researchers to demonstrate and showcase their tools on PyPI packages around the world. Via the PyPI packaging, a Python application with a single source code can run on Windows, MacOS, and Linux operating systems. In addition to the PyPI packaging, the reproducibility and quality of the source code must be guaranteed. This paper shows how to publish the Python application in Code Ocean after the PyPI packaging. Code Ocean is used in IEEE, Springer, and Elsevier for software reproducibility validation. First, programmers must understand how to scrape a dataset over the Internet. Second, the dataset files must be read in Python. Third, a program must be built to compute the target values using set operations. Fourth, the Python program must be converted to the PyPI package. Finally, the PyPI package is uploaded. Code Ocean plays a key role in publishing validation for software reproducibility. This paper depicts a vaers executable package as an example for calculating the number of deaths due to COVID-19 vaccines. Calculations were based on gender (male and female), age group, and vaccine group (Moderna, Pfizer, and Novartis), respectively.
Two New Datasets for Italian-Language Abstractive Text Summarization
Authors: Landro Nicola , Gallo Ignazio , La Grassa Riccardo , Federici Edoardo
Published: April 2022

Text summarization aims to produce a short summary containing relevant parts from a given text. Due to the lack of data for abstractive summarization on low-resource languages such as Italian, we propose two new original datasets collected from two Italian news websites with multi-sentence summaries and corresponding articles, and from a dataset obtained by machine translation of a Spanish summarization dataset. These two datasets are currently the only two available in Italian for this task. To evaluate the quality of these two datasets, we used them to train a T5-base model and an mBART model, obtaining good results with both. To better evaluate the results obtained, we also compared the same models trained on automatically translated datasets, and the resulting summaries in the same training language, with the automatically translated summaries, which demonstrated the superiority of the models obtained from the proposed datasets.
Testing Phylogeographic Hypotheses in Mepraia (Hemiptera: Reduviidae) Suggests a Complex Spatio-Temporal Colonization in the Coastal Atacama Desert
Authors: Campos-Soto Ricardo , Rodríguez-Valenzuela Evelyn , Díaz-Campusano Gabriel , Boric-Bargetto Dusan , Zúñiga-Reinoso Álvaro , Cianferoni Franco , Torres-Pérez Fernando
Published: April 2022

Mepraia is a genus (Triatominae) endemic to Chile and a vector of Trypanosoma cruzi. Alternative phylogeographic hypotheses have been suggested for Mepraia. We tested different colonization routes hypothesized using mitochondrial sequences and phylogeographic approaches to select the best-supported hypothesis. Our results suggest that, after the split from the sister genus Triatoma at ~4.3 Mya, Mepraia formed two main clades at ~2.1 Mya. The northern clade diverged from Mepraia sp. ~1.7 Mya, giving rise to M. parapatrica and M. gajardoi about ~1.4 Mya. The southern clade originated M. spinolai ~1.68 Mya. We suggest that Mepraia had an origin in the north-central Andes along with orogenic processes, reinforced by hyperaridity during the Pliocene. The hyperarid cycle would have separated the southern and northern clades. Then, in the northern clade, dispersal occurred north and south from the centre through corridors during the Pleistocene Climatic Oscillations. Climate changes may have induced a major speciation process in the Atacama Desert, while the more homogeneous habitat colonized by the southern clade led to only one, but structured, species.
Inducible Expression of Several Drosophila melanogaster Genes Encoding Juvenile Hormone Binding Proteins by a Plant Diterpene Secondary Metabolite, Methyl Lucidone
Authors: Shin Sang-Woon , Jeon Jun-Hyoung , Kim Ji-Ae , Park Doo-Sang , Shin Young-Joo , Oh Hyun-Woo
Published: April 2022

Juvenile hormones prevent molting and metamorphosis in the juvenile stages of insects. There are multiple genes encoding a conserved juvenile hormone binding protein (JHBP) domain in a single insect species. Although some JHBPs have been reported to serve as carriers to release hormones to target tissues, the molecular functions of the other members of the diverse JHBP family of proteins remain unclear. We characterized 16 JHBP genes with conserved JHBP domains in Drosophila melanogaster. Among them, seven JHBP genes were induced by feeding the flies with methyl lucidone, a plant diterpene secondary metabolite (PDSM). Induction was also observed upon feeding the juvenile hormone (JH) analog methoprene. Considering that methyl lucidone and methoprene perform opposite functions in JH-mediated regulation, specifically the heterodimeric binding between a JH receptor (JHR) and steroid receptor coactivator (SRC), the induction of these seven JHBP genes is independent of JH-mediated regulation by the JHR/SRC heterodimer. Tissue-specific gene expression profiling through the FlyAtlas 2 database indicated that some JHBP genes are mainly enriched in insect guts and rectal pads, indicating their possible role during food uptake. Hence, we propose that JHBPs are induced by PDSMs and respond to toxic plant molecules ingested during feeding.
Topical Collection: Natural Enemies and Biological Control of Plant Pests
Authors: Riddick Eric Wellington
Published: April 2022

Natural enemies have an extensive history as biological control agents against crop pests worldwide [...]
Flight Capability and the Low Temperature Threshold of a Chinese Field Population of the Fall Armyworm Spodoptera frugiperda
Authors: Chen Hui , Wang Yao , Huang Le , Xu Chuan-Feng , Li Jing-Hui , Wang Feng-Ying , Cheng Wei , Gao Bo-Ya , Chapman Jason W. , Hu Gao
Published: April 2022

The fall armyworm, Spodoptera frugiperda (J. E. Smith), is capable of long-distance migration; thus, evaluation of its flight capability is relevant to the design of monitoring and control strategies for this pest. Previous studies have quantified the flight ability of lab-reared populations under controlled conditions, but less is known about the flight capability of natural populations. In addition, the low temperature threshold for flight in natural populations also needs to be determined. In this study, the flight capability of S. frugiperda adults emerging from field-collected larvae in South China was measured by a flight mill system. The results show that the flight capability of S. frugiperda moths varied greatly between individuals, and that some adults are capable of flying great distances. The longest self-powered flight distance was 116.7 km with a cumulative flight duration of 36.51 h during a 48-h period. Typically, the flight activity of tethered individuals was relatively stable during the first 12 h, indicating that migrating moths can fly through an entire night. Based on the accumulated flight duration in the first 12 h, moths can be clearly divided into two groups (<5 h and ≥5 h flight duration), and 58% of individuals belonged to the latter group with strong migratory tendency. Further, flight activity under low temperature conditions was tested, and the results of a logit generalized linear model indicate that the low temperature flight threshold of S. frugiperda is 13.1 °C under declining temperatures. Our results provide a scientific basis for further elucidating the flight biology and migration mechanism of S. frugiperda.
Actual Associations between HLA Haplotype and Graves’ Disease Development
Authors: Zawadzka-Starczewska Katarzyna , Tymoniuk Bogusław , Stasiak Bartłomiej , Lewiński Andrzej , Stasiak Magdalena
Published: April 2022

The association between HLA and the risk of Graves’ disease (GD) has been analyzed for many years. However, the results were often inconsistent and mostly regarded Asian populations. The purpose of our study was to perform HLA genotyping using a next-generation sequencing (NGS) method in Caucasians, to find out which alleles are eventually correlated with GD morbidity as well as which of them can be considered protective. HLA-A, -B, -C, -DQB1, -DRB1 were genotyped using a next-generation sequencing method in 2376 persons, including 159 GD patients and 2217 healthy controls. We have demonstrated a significant association between the risk of GD and the following alleles: HLA-B*08:01, -B*39:06, -B*37:01, -C*07:01, -C*14:02, -C*03:02, -C*17:01, -DRB1*03:01, -DRB1*11:01, -DRB1*13:03, -DRB1*01:03, -DRB1*14:01, -DQB1*03:01, DQB1*02:01. The alleles HLA-B*39:06, -B*37:01, -C*14:02, -C*03:02, -C*17:01, -DRB1*14:01 are novel GD-associated, previously not-reported independent ones with no linkage disequilibrium with other high-risk alleles. On the other hand, the frequencies of HLA-B*07:02, -C*07:02, -C*03:04, DRB1*07:01, -DQB1*02:02, -DQB1*03:03 were significantly lower in GD compared to controls. This study demonstrated the actual relationships between HLA and GD based on the NGS method and provided a novel set of alleles as a reliable tool for an individual personalized risk assessment.
Comment on Pata et al. Sclerobanding (Combined Rubber Band Ligation with 3% Polidocanol Foam Sclerotherapy) for the Treatment of Second- and Third-Degree Hemorrhoidal Disease: Feasibility and Short-Term Outcomes. J. Clin. Med. 2022, 11, 218
Authors: Jongen Johannes , Schneider Jessica , Kahlke Volker , Laubert Tilman
Published: April 2022

Dr. Pata kindly tweeted the publication of the above-mentioned paper [...]
Long-Term Growth Hormone Treatment of Children with PWS: The Earlier the Start, the Better the Outcomes?
Authors: Grootjen Lionne N. , Trueba-Timmermans Demi J. , Damen Layla , Mahabier Eva F. , Kerkhof Gerthe F. , Hokken-Koelega Anita C. S.
Published: April 2022

Long-term effects of growth hormone (GH) treatment in young children with Prader-Willi syndrome (PWS) have never been compared with untreated age-matched controls with PWS, and it is unclear if starting GH in the first year of life is safe and more effective than starting GH in early childhood. We investigated the effects of long-term GH on body composition, anthropometrics and cognition in young children with PWS compared to untreated controls and assessed whether starting GH in the first year of life is optimal and safe. An open-label, prospective study was performed, comparing GH-treated children with untreated controls, and comparing children who started GH in the first year of life (subgroup A) with children who started between 2–5 years (subgroup C). A total of 82 GH-treated children with PWS and 22 age-matched controls with PWS were included. The main outcome measures were body composition, anthropometrics, IQ, and safety parameters. After 8 years, GH-treated children had significantly better body composition and were taller than age-matched controls. Subgroup A had a lower FM% trajectory during treatment than subgroup C and showed a greater and longer-term increase in the LBM index. After 8 years, subgroup A had a lower trunk/peripheral fat ratio (p = 0.043) and higher IQ (p = 0.043). No adverse effects of starting GH in the first year were found. Children with PWS who received long-term GH had a better body composition and growth than untreated age-matched controls and starting GH in the first year of life was optimal and safe.
A Comparison of McGrath Videolaryngoscope versus Macintosh Laryngoscope for Nasotracheal Intubation: A Systematic Review and Meta-Analysis
Authors: Ho Chia-Hao , Chen Li-Chung , Hsu Wen-Hao , Lin Tzu-Yu , Lee Meng , Lu Cheng-Wei
Published: April 2022

Background: In this study, it was shown that the routine use of McGrath videolaryngoscopy may improve intubation success rates. The benefits to using a videolaryngoscope in nasotracheal intubation were also demonstrated. However, no solid evidence concerning the effectiveness of the use of McGrath videolaryngoscopes in nasotracheal intubation has previously been reported. As a result, we questioned whether, in adult patients who underwent oral and maxillofacial surgeries with nasotracheal intubation (P), the use of a McGrath videolaryngoscope (I) compared with a Macintosh laryngoscope (C) could reduce the intubation time, improve glottis visualization to a score of classification 1 in the Cormack–Lehane classification system, and improve the first-attempt success rate (O). The secondary outcomes measured were the rate of the use of Magill forceps and the external laryngeal pressure (BURP) maneuver used. Methods: An extensive literature search was conducted using databases. Only randomized controlled trials that compared the McGrath videolaryngoscopy and Macintosh laryngoscopy techniques in nasotracheal intubation in adult patients were included. Results: Five articles met the inclusion criteria and were included in the final analysis (n = 331 patients). The results showed a significant decrease in intubation time and a higher rate of classification 1 scores in the Cormack–Lehane classification system, but no difference in the first-attempt success rates were found between the McGrath group and the Macintosh group. Decreases in the rate of the use of Magill forceps and the use of the external laryngeal pressure maneuver were also found in the pooled analysis. With regard to the overall risk of bias, the selected trials were classified to have at least a moderate risk of bias, because none of the trials could blind the operator to the type of laryngoscope used. Conclusions: Our analysis suggests that the use of a McGrath videolaryngoscope in nasotracheal intubation resulted in shorter intubation times, improved views of the glottis and similar first-success rates in adult patients who received general anesthesia for dental, oral, maxillofacial, or head and neck cancer surgery, and also reduced the use of Magill forceps and the BURP maneuver.
Postsurgical Thrombotic Microangiopathy and Deregulated Complement
Authors: van Herpt Thijs T. W. , Timmermans Sjoerd A. M. E. G. , van Mook Walther N. K. A. , van Bussel Bas C. T. , van der Horst Iwan C. C. , Maessen Jos G. , Natour Ehsan , van Paassen Pieter , Heuts Samuel
Published: April 2022

Postsurgical thrombotic microangiopathy (TMA) is a complication associated with significant morbidity and mortality. Still, the pathophysiological underlying mechanism of postsurgical TMA, a diagnosis often overlooked in postoperative patients with acute kidney injury and thrombocytopenia, is largely unknown. Here, we report the case of a 56-year-old male that developed anuric acute kidney injury, Coombs-negative hemolysis, and thrombocytopenia after surgical aortic arch replacement. Massive ex vivo complement activation on the endothelium, a rare complement gene variant in C2, at-risk haplotype MCPggaac, and excellent response to therapeutic complement inhibition, points to the pivotal role of complement in the pathophysiology of disease. Moreover, the importance of a multidisciplinary team approach in (postsurgical) thrombocytopenia is emphasized.
PRISM (Pictorial Representation of Illness and Self-Measure) as Visual Tool to Support Oral Health Education Prior to Endoprosthetic Joint Replacement—A Novel Approach in Dentistry
Authors: Schmalz Gerhard , Schmidt Laura , Haak Rainer , Büchi Stefan , Goralski Szymon , Roth Andreas , Ziebolz Dirk
Published: April 2022

Objective: This study aims to evaluate the application of Pictorial Representation of Illness and Self-Measure (PRISM) in educating patients regarding oral health before endoprosthesis (EP). Methods: The study consisted of two parts: (I) a cross-sectional study, where patients received a PRISM interview, oral health briefing and oral examinations (treatment need, oral focus). (II) In an observational part, patients were randomly assigned to either PRISM task (Test) or flyer-based verbal briefing (Control). Before and after the interviews, patients answered a questionnaire regarding importance of oral health for EP. Results: (I) 122 patients were included. The distance between subject (“myself”) and objects (oral health issues or EP) in the PRISM task were mainly not associated with age, gender, and oral conditions. In part (II), 80 patients (PRISM: n = 40, Control: n = 40) were included. After the interview, the values for perceived relationship between EP and teeth (p < 0.01), EP and gums (p < 0.01), and EP and dental consultations (p < 0.01) significantly increased in both groups. Both groups perceived a high benefit of the interview and felt well educated. Conclusions: PRISM has comparable positive effects like a flyer-based verbal briefing. PRISM as a novel visual tool can support the patient education regarding oral health before EP.
Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies
Authors: Sancho-Saldaña Agustín , Gil Sánchez Anna , Quirant-Sánchez Bibiana , Nogueras Lara , Peralta Silvia , Solana Maria José , González-Mingot Cristina , Gallego Yhovanni , Quibus Laura , Ramo-Tello Cristina , Presas-Rodríguez Silvia , Martínez-Cáceres Eva , Torres Pascual , Hervás José Vicente , Valls Joan , Brieva Luis
Published: April 2022

Background: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. Methods: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. Results: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). Conclusions: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.
Atrial Fibrillation and Heart Failure
Authors: Bergau Leonard , Bengel Philipp , Sciacca Vanessa , Fink Thomas , Sohns Christian , Sommer Philipp
Published: April 2022

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and has a strong association with heart failure (HF). It often remains unclear if HF is the cause or consequence of AF due to the complexity of the processes that are involved in both the perpetuation of AF and the development of HF. To date, two therapeutic strategies are accepted as the standard of care in AF patients with heart failure. Rhythm control aims to permanently restore sinus rhythm, whereas a rate-control strategy aims to slow ventricular rate without the termination of AF. In the last 5 years a tremendous number of important studies have been published investigating the optimal therapeutic strategy in HF patients. This review highlights the important studies with respect to the involvement of AF in promoting left-ventricular dysfunction and discusses the optimal strategy in HF patients suffering from AF.
Arterial Stiffness Determinants for Primary Cardiovascular Prevention among Healthy Participants
Authors: Vallée Alexandre
Published: April 2022

Background: Arterial stiffness (AS), measured by arterial stiffness index (ASI), can be considered as a major denominator in cardiovascular (CV) diseases. Thus, it remains essential to highlight the risk factors influencing its increase among healthy participants. Methods: According to European consensus, AS is defined as ASI > 10 m/s. The purpose of this study was to investigate the determinants of the arterial stiffness (ASI > 10 m/s) among UK Biobank normotensive and healthy participants without comorbidities and previous CV diseases. Thus, a cross-sectional study was conducted on 22,452 healthy participants. Results: Participants were divided into two groups, i.e., ASI > 10 m/s (n = 5782, 25.8%) and ASI < 10 m/s (n = 16,670, 74.2%). All the significant univariate covariables were included in the multivariate analysis. The remaining independent factors associated with AS were age (OR = 1.063, threshold = 53.0 years, p < 0.001), BMI (OR = 1.0450, threshold = 24.9 kg/m2, p < 0.001), cystatin c (OR = 1.384, threshold = 0.85 mg/L, p = 0.011), phosphate (OR = 2.225, threshold = 1.21 mmol/L, p < 0.001), triglycerides (OR = 1.281, threshold = 1.09 mmol/L, p < 0.001), mean BP (OR = 1.028, threshold = 91.2 mmHg, p < 0.001), HR (OR = 1.007, threshold = 55 bpm, p < 0.001), Alkaline phosphate (OR = 1.002, threshold = 67.9 U/L, p = 0.004), albumin (OR = 0.973, threshold = 46.0 g/L, p < 0.001), gender (male, OR = 1.657, p < 0.001) and tobacco use (current, OR = 1.871, p < 0.001). Conclusion: AS is associated with multiple parameters which should be investigated in future prospective studies. Determining the markers of increased ASI among healthy participants participates in the management of future CV risk for preventive strategies.
Response to Treatment with Melatonin and Clonazepam versus Placebo in Patients with Burning Mouth Syndrome
Authors: Castillo-Felipe Candela , Tvarijonaviciute Asta , López-Arjona Marina , Pardo-Marin Luis , Pons-Fuster Eduardo , López-Jornet Pia
Published: April 2022

Objective: to evaluate the efficacy of melatonin and clonazepam versus placebo in patients with burning mouth syndrome (BMS). Methods: a prospective double-blind study was carried out in patients with BMS and randomized to three groups: melatonin (1 mg once a day), clonazepam (0.5 mg/twice a day), or a placebo once a day, for 8 weeks. The clinical changes were evaluated, including xerostomia, the Oral Health Impact Profile 14 (OHIP-14) score, Pittsburg Sleep Quality Index, and the Hospital Anxiety and Depression Scale (HADS). Oxygen saturation and heart rate were recorded, with an analysis of salivary biomarkers in the forms of oxytocin, ferritin, adenosine deaminase (ADA), total proteins, and alpha-amylase. Results: a total of 64 patients were analyzed. A significant decrease in burning sensation was recorded with melatonin (7.8 ± 1.54 pre-treatment, 5.78 ± 2.54 post-treatment; p < 0.001) and clonazepam (8.75 ± 1.2 pre-treatment, 5.5 ± 3.6 post-treatment (p < 0.01). With regard to quality of life (OHIP-14), significant improvements were observed before and after the administration of melatonin (p < 0.001) and clonazepam (p = 0.001). On the other hand, with regard to the changes in salivary biomarkers following treatment, negative correlations were found between oxytocin and drainage (r = −0.410; p = 0.009) and between the HADS-D score and ferritin (r = −0.312; p = 0.05). While salivary amylase showed positive correlation with heart rate (r = 0.346; p = 0.029) and oxygen saturation (r = 0.419; p = 0.007). Conclusions: melatonin and clonazepam were shown to be effective at reducing the burning sensation and improving quality of life. Both drugs were found to be safe, with no major adverse effects in patients with BMS. Melatonin may be regarded as an alternative treatment for patients with BMS, though further studies are needed to confirm its effectiveness.
Prediction Model of Extubation Outcomes in Critically Ill Patients: A Multicenter Prospective Cohort Study
Authors: Tanaka Aiko , Kabata Daijiro , Hirao Osamu , Kosaka Junko , Furushima Nana , Maki Yuichi , Uchiyama Akinori , Egi Moritoki , Shintani Ayumi , Morimatsu Hiroshi , Mizobuchi Satoshi , Kotake Yoshifumi , Fujino Yuji
Published: April 2022

Liberation from mechanical ventilation is of great importance owing to related complications from extended ventilation time. In this prospective multicenter study, we aimed to construct a versatile model for predicting extubation outcomes in critical care settings using obtainable physiological predictors. The study included patients who had been extubated after a successful 30 min spontaneous breathing trial (SBT). A multivariable logistic regression model was constructed to predict extubation outcomes (successful extubation without reintubation and uneventful extubation without reintubation or noninvasive respiratory support) using eight parameters: age, heart failure, respiratory disease, rapid shallow breathing index (RSBI), PaO2/FIO2, Glasgow Coma Scale score, fluid balance, and endotracheal suctioning episodes. Of 499 patients, 453 (90.8%) and 328 (65.7%) achieved successful and uneventful extubation, respectively. The areas under the curve for successful and uneventful extubation in the novel prediction model were 0.69 (95% confidence interval (CI), 0.62–0.77) and 0.70 (95% CI, 0.65–0.74), respectively, which were significantly higher than those in the conventional model solely using RSBI (0.58 (95% CI, 0.50–0.66) and 0.54 (95% CI, 0.49–0.60), p = 0.004 and <0.001, respectively). The model was validated using a bootstrap method, and an online application was developed for automatic calculation. Our model, which is based on a combination of generally obtainable parameters, established an accessible method for predicting extubation outcomes after a successful SBT.
A 10-Year Follow-Up of Ankle Syndesmotic Injuries: Prospective Comparison of Knotless Suture-Button Fixation and Syndesmotic Screw Fixation
Authors: Altmeppen Jan Niklas , Colcuc Christian , Balser Christian , Gramlich Yves , Klug Alexander , Neun Oliver , Manegold Sebastian , Hoffmann Reinhard , Fischer Sebastian
Published: April 2022

Background: Acute syndesmosis injury (ASI) is an indication for surgical stabilization if instability is confirmed. In recent years, fixation using the knotless suture-button (SB) device has become increasingly established as an alternative to set screw fixation (SF). This study directly compared the clinical long-term results after prospective randomized inclusion. Materials and Methods: Between 2011 and 2012, 62 patients with ASI were enrolled in a prospective, randomized, and monocentric study. Forty-one patients were available for a 10-year follow-up ((31 males and 10 females), including 21 treated with SB (mean age 44.4 years), and 20 with SF (mean age 47.2 years)). In addition to comparing the demographic data and syndesmosis injury etiology, follow-up assessed the Olerud–Molander Ankle Score (OMAS) and FADI-Score (Foot and Ankle Disability Index Score) with subscales for activities of daily living (ADL) and sports activity. Results: The mean OMAS was 95.98 points (SB: 98.81, SF: 93.00), the mean FADI ADL was 97.58 points (SB: 99.22, SF: 95.86), and the mean FADI Sport was 94.14 points (SB: 97.03, SF: 91.10). None of the measurements differed significantly between the groups (p > 0.05). No clinical suspicion of chronic instability remained in any of the patients, regardless of treatment. Conclusions: The short-term results showed that athletes in particular benefit from SB fixation due to their significantly faster return to sports activities. However, the available long-term results confirm a very good outcome in the clinical scores for both approaches. Chronic syndesmotic insufficiency was not suspected in any of the patients. Level of evidence: I, randomized controlled trial.
Association between Physical Activity and Telomere Length in Women with Breast Cancer: A Systematic Review
Authors: Min Jihee , Kim Ji Young , Choi Ji Yeong , Kong In Deok
Published: April 2022

The association between physical activity and telomere length (TL) has been continuously reported. However, the interplay of physical activity and TL among women with breast cancer has not been elucidated. Thus, the purpose of this systematic review was to synthesize the evidence for the association of physical activity with TL in women with breast cancer. Systematic searches were conducted to identify quantified studies using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Clinical Trials.gov. Five studies were included in this systematic review. Three of the five studies reported that physical activity has a significant relationship in delaying TL shortening, but others observed no association between physical activity and TL in breast cancer survivors. Although the heterogeneous studies acted as limitations in drawing clear conclusions, physical activity strategies show encouraging impacts in delaying TL shortening. To understand the effects of physical activity on TL shortening in breast cancer survivors, further studies are needed considering the tissue site, treatments for breast cancer, DNA extraction methods, and tools for measuring physical activity.