bluuebunny/crossref_metadata_2025 huggingface dataset:
Lead-Cooled Fast Reactor Annular UN Fuel Design and Development of Performance Analysis Program
Authors: Yuan He , Wang Guan , Yu Rui , Tao Yujie , Wang Zhaohao , Guo Shaoqiang , Liu Wenbo , Yun Di , Gu Long
Published: July 2021

A kind of annular uranium nitride (UN) fuel suitable for lead-cooled fast reactor applications has been designed in this study. The design is directly targeting two main issues of UN fuel: severe swelling and thermal decomposition of UN fuel at high temperatures. A performance analysis program based on FORTRAN programming language has been developed for UN fuel in fast reactors. The program contains heat transfer, fuel stress-strain analysis, cladding stress-strain analysis, fission gas release and fuel-cladding mechanical interaction (FCMI) modules, etc. Extensive code verification has been performed by comparing simulation results obtained with the code and those obtained via the COMSOL Multiphysics platform. Preliminary code validation has been conducted as well by comparing code simulation results with experimental data. The results showed that this program could predict the fuel temperature, stress-strain, and displacement of UN fuel during reactor operation with a reasonable accuracy.
Elevated Cranial Sutural Complexity in Burrowing Dicynodonts
Authors: Kammerer Christian F.
Published: July 2021

Relationships between the complexity of the cranial sutures and the inferred ecology of dicynodont synapsids are explored. Simple complexity indices based on degree of sutural interdigitation were calculated for 70 anomodont species and indicate that the naso-frontal sutures of Cistecephalidae, a clade inferred to be dedicated fossors based on aspects of postcranial morphology, are substantially more complex than those of other dicynodonts. The elevated complexity of the naso-frontal suture in this clade is interpreted as being related to compressive forces sustained during burrowing, paralleling the condition in some other fossorial vertebrate groups (e.g., amphisbaenians). The most highly interdigitated sutures in the cistecephalid skull are those oriented transversely to its long axis, which would experience the greatest longitudinal stresses from contact with the substrate. Although it is uncertain to what degree cistecephalid burrowing was based on scratch vs. head-lift digging, it is argued that the head played an important role during locomotion in this group. Increased sutural complexity, rather than cranial fusion, as an adaptation to resisting compressive forces during burrowing may be related to indeterminate growth in dicynodonts.
Hiding in Plain Sight: How a Fallow Forestry Supply Chain Remains Illegitimate in the Eyes of the State
Authors: Sears Robin R. , Cronkleton Peter , Miranda Ruiz Medardo , Pérez-Ojeda del Arco Matías
Published: July 2021

On-farm timber production is an important subsistence and economic activity of smallholder farmers around the world. Farmer investment in wood production and the degree of formality in the sector depends on access to and conditions of the market, the nature of the regulatory frameworks that govern rights to and movement of timber, and access to financing. We evaluate the process of formalization of a thriving and adaptive existing supply chain for small-dimension lumber originating in the fallows of smallholder farmers in the Peruvian Amazon. Through field research over three years based in semi-structured interviews with diverse actors in the Amazon, we found that the supply chain for fallow timber is driven entirely by informal and some illegal transactions. A key reason for this is the lack of an appropriate regulatory mechanism by which producers can gain authorization to harvest and sell this timber. We identify conditions necessary to formalize this sector, and evaluate the degree to which these are met under several scenarios. We recommend that the state develop mechanisms that recognize property rights of long-term residents and establish a simple fallow forestry registration mechanism; and that local governments or non-governmental organizations adopt adaptive and collaborative approaches to support farmers and provide training, information and networking among actors. State recognition of and support for fallow forestry, coupled with producers organizing for collective action on processing and marketing their timber, could result in the formalization of a significant volume of timber, improvements in income security for rural people, and the development of local entrepreneurial activities.
Discovery of Novel Entomopathogenic Fungi for Mosquito-Borne Disease Control
Authors: Accoti Anastasia , Engdahl Cecilia Springer , Dimopoulos George
Published: July 2021

The increased application of chemical control programs has led to the emergence and spread of insecticide resistance in mosquitoes. Novel environmentally safe control strategies are currently needed for the control of disease vectors. The use of entomopathogenic fungi could be a suitable alternative to chemical insecticides. Currently, Beauveria spp. and Metarhizium spp. are the most widely used entomopathogenic fungi for mosquito control, but increasing the arsenal with additional fungi is necessary to mitigate the emergence of resistance. Entomopathogenic fungi are distributed in a wide range of habitats. We have performed a comprehensive screen for candidate mosquitocidal fungi from diverse outdoor environments in Maryland and Puerto Rico. An initial screening of 22 fungi involving exposure of adult Anopheles gambiae to 2-weeks-old fungal cultures identified five potent pathogenic fungi, one of which is unidentified and the remaining four belonging to the three genera Galactomyces sp., Isaria sp. and Mucor sp. These fungi were then screened against Aedes aegypti, revealing Isaria sp. as a potent mosquito killer. The entomopathogenic effects were confirmed through spore-dipping assays. We also probed further into the killing mechanisms of these fungi and investigated whether the mosquitocidal activities were the result of potential toxic fungus-produced metabolites. Preliminary assays involving the exposure of mosquitoes to sterile filtered fungal liquid cultures showed that Galactomyces sp., Isaria sp. and the unidentified isolate 1 were the strongest producers of factors showing lethality against An. gambiae. We have identified five fungi that was pathogenic for An. gambiae and one for Ae. aegypti, among these fungi, four of them (two strains of Galactomyces sp., Mucor sp., and the unidentified isolate 1) have never previously been described as lethal to insects. Further characterization of these entomopathogenic fungi and their metabolites needs to be done to confirm their potential use in biologic control against mosquitoes.
Detection of Cell Types Contributing to Cancer From Circulating, Cell-Free Methylated DNA
Authors: Barefoot Megan E. , Loyfer Netanel , Kiliti Amber J. , McDeed A. Patrick , Kaplan Tommy , Wellstein Anton
Published: July 2021

Detection of cellular changes in tissue biopsies has been the basis for cancer diagnostics. However, tissue biopsies are invasive and limited by inaccuracies due to sampling locations, restricted sampling frequency, and poor representation of tissue heterogeneity. Liquid biopsies are emerging as a complementary approach to traditional tissue biopsies to detect dynamic changes in specific cell populations. Cell-free DNA (cfDNA) fragments released into the circulation from dying cells can be traced back to the tissues and cell types they originated from using DNA methylation, an epigenetic regulatory mechanism that is highly cell-type specific. Decoding changes in the cellular origins of cfDNA over time can reveal altered host tissue homeostasis due to local cancer invasion and metastatic spread to distant organs as well as treatment responses. In addition to host-derived cfDNA, changes in cancer cells can be detected from cell-free, circulating tumor DNA (ctDNA) by monitoring DNA mutations carried by cancer cells. Here, we will discuss computational approaches to identify and validate robust biomarkers of changed tissue homeostasis using cell-free, methylated DNA in the circulation. We highlight studies performing genome-wide profiling of cfDNA methylation and those that combine genetic and epigenetic markers to further identify cell-type specific signatures. Finally, we discuss opportunities and current limitations of these approaches for implementation in clinical oncology.
Genome-Wide Analyses Reveal the Genetic Architecture and Candidate Genes of Indicine, Taurine, Synthetic Crossbreds, and Locally Adapted Cattle in Brazil
Authors: Verardo Lucas Lima , e Silva Fabyano Fonseca , Machado Marco Antonio , do Carmo Panetto João Cláudio , de Lima Reis Faza Daniele Ribeiro , Otto Pamela Itajara , de Almeida Regitano Luciana Correia , da Silva Luiz Otávio Campos , do Egito Andréa Alves , do Socorro Maués Albuquerque Maria , Zanella Ricardo , da Silva Marcos Vinicius Gualberto Barbosa
Published: July 2021

Cattle population history, breeding systems, and geographic subdivision may be reflected in runs of homozygosity (ROH), effective population size (Ne), and linkage disequilibrium (LD) patterns. Thus, the assessment of this information has become essential to the implementation of genomic selection on purebred and crossbred cattle breeding programs. In this way, we assessed the genotype of 19 cattle breeds raised in Brazil belonging to taurine, indicine, synthetic crossbreds, and Iberian-derived locally adapted ancestries to evaluate the overall LD decay patterns, Ne, ROH, and breed composition. We were able to obtain a general overview of the genomic architecture of cattle breeds currently raised in Brazil and other tropical countries. We found that, among the evaluated breeds, different marker densities should be used to improve the genomic prediction accuracy and power of genome-wide association studies. Breeds showing low Ne values indicate a recent inbreeding, also reflected by the occurrence of longer ROH, which demand special attention in the matting schemes to avoid extensive inbreeding. Candidate genes (e.g., ABCA7, PENK, SPP1, IFNAR1, IFNAR2, SPEF2, PRLR, LRRTM1, and LRRTM4) located in the identified ROH islands were evaluated, highlighting biological processes involved with milk production, behavior, rusticity, and fertility. Furthermore, we were successful in obtaining the breed composition regarding the taurine and indicine composition using single-nucleotide polymorphism (SNP) data. Our results were able to observe in detail the genomic backgrounds that are present in each breed and allowed to better understand the various contributions of ancestor breeds to the modern breed composition to the Brazilian cattle.
Case Report: Safe and Effective Sublingual Birch Allergen Immunotherapy in Two HIV-Positive Patients
Authors: Latysheva Elena , Nazarova Evgeniya , Latysheva Tatiana , Ilina Natalia
Published: July 2021

Allergen-specific immunotherapy (AIT) is a safe, effective treatment for respiratory allergies (such as moderate-to-severe allergic rhinoconjunctivitis) that are not controlled by symptomatic medications. The indications and contraindications for AIT have been defined in international guidelines and consensus statements. However, some of these contraindications are not evidenced- based but have been deduced from the theoretical risk of an interaction between AIT disease-modifying effect and immune or inflammatory comorbidities. In the absence of clinical trial evidence, the accumulation of experience as case reports can narrow the spectrum of absolute contraindications. The majority of international guidelines list HIV infection as a contraindication to AIT. Here, we describe two cases of safe, effective sublingual birch pollen AIT in HIV-positive patients undergoing concomitant antiretroviral therapy. A 32-year-old female and a 63-year-old male sensitized to tree pollen and with clinically confirmed birch pollen allergy underwent pre- and co-seasonal sublingual birch pollen AIT for three and two pollen seasons, respectively. The therapy was associated with a marked reduction in the frequency and intensity of allergic symptoms, and the reduced use of (symptomatic) rescue medication. Mild, local, treatment-emergent adverse events were noted throughout the course of treatment but resolved spontaneously. No serious adverse events were reported. In particular, there were no obvious harmful effects on the patients’ immune status or viral load. Hence, sublingual birch pollen AIT proved to be effective and safe in two HIV-positive patients.
Development of PDA Nanoparticles for H9N2 Avian Influenza BPP-V/BP-IV Epitope Peptide Vaccines: Immunogenicity and Delivery Efficiency Improvement
Authors: Liu Yongqing , Wang Xiaoli , Zhou Jiangfei , Shi Shuaibing , Shen Tengfei , Chen Liangliang , Zhang Min , Liao Chengshui , Wang Chen
Published: July 2021

The protection of current influenza vaccines is limited due to the viral antigenic shifts and antigenic drifts. The universal influenza vaccine is a new hotspot in vaccine research that aims to overcome these problems. Polydopamine (PDA), a versatile biomaterial, has the advantages of an excellent biocompatibility, controllable particle size, and distinctive drug loading approach in drug delivery systems. To enhance the immunogenicities and delivery efficiencies of H9N2 avian influenza virus (AIV) epitope peptide vaccines, PDA nanoparticles conjugated with the BPP-V and BP-IV epitope peptides were used to prepare the nano BPP-V and BP-IV epitope peptide vaccines, respectively. The characteristics of the newly developed epitope peptide vaccines were then evaluated, revealing particle sizes ranging from approximately 240 to 290 nm (PDI<0.3), indicating that the synthesized nanoparticles were stable. Simultaneously, the immunoprotective effects of nano BPP-V and BP-IV epitope peptide vaccines were assessed. The nano BPP-V and BP-IV epitope vaccines, especially nano BP-IV epitope vaccine, quickly induced anti-hemagglutinin (HA) antibody production and a sustained immune response, significantly promoted humoral and cellular immune responses, reduced viral lung damage and provided effective protection against AIV viral infection. Together, these results reveal that PDA, as a delivery carrier, can improve the immunogenicities and delivery efficiencies of H9N2 AIV nano epitope vaccines, thereby providing a theoretical basis for the design and development of PDA as a carrier of new universal influenza vaccines.
Effect of Non-thermal Atmospheric Plasma on Viability and Histamine-Producing Activity of Psychotrophic Bacteria in Mackerel Fillets
Authors: Trevisani Marcello , Cevoli Chiara , Ragni Luigi , Cecchini Matilde , Berardinelli Annachiara
Published: July 2021

Non-thermal atmospheric plasma (NTAP) has gained attention as a decontamination and shelf-life extension technology. In this study its effect on psychrotrophic histamine-producing bacteria (HPB) and histamine formation in fish stored at 0–5°C was evaluated. Mackerel filets were artificially inoculated with Morganella psychrotolerans and Photobacterium phosphoreum and exposed to NTAP to evaluate its effect on their viability and the histidine decarboxylase (HDC) activity in broth cultures and the accumulation of histamine in fish samples, stored on melting ice or at fridge temperature (5°C). NTAP treatment was made under wet conditions for 30 min, using a dielectric barrier discharge (DBD) reactor. The voltage output was characterized by a peak-to-peak value of 13.8 kV (fundamental frequency around 12.7 KHz). This treatment resulted in a significant reduction of the number of M. psychrotolerans and P. phosphoreum (≈3 log cfu/cm2) on skin samples that have been prewashed with surfactant (SDS) or SDS and lactic acid. A marked reduction of their histamine-producing potential was also observed in HDC broth incubated at either 20 or 5°C. Lower accumulation of histamine was observed in NTAP-treated mackerel filets that have been inoculated with M. psychrotolerans or P. phosphoreum and pre-washed with either normal saline or SDS solution (0.05% w/v) and stored at 5°C for 10 days. Mean histamine level in treated and control groups for the samples inoculated with either M. psychrotolerans or P. phosphoreum (≈5 log cfu/g) varied from 7 to 32 and from 49 to 66 μg/g, respectively. No synergistic effect of SDS was observed in the challenge test on meat samples. Any detectable amount of histamine was produced in the meat samples held at melting ice temperature (0–2°C) for 7 days. The effects of NTAP on the quality properties of mackerel’s filets were negligible, whereas its effect on the psychrotrophic HPB might be useful when time and environmental conditions are challenging for the cool-keeping capacity throughout the transport/storage period.
Identification and Genomic Characterization of Two Previously Unknown Magnetotactic Nitrospirae
Authors: Zhang Wensi , Wang Yinzhao , Liu Li , Pan Yongxin , Lin Wei
Published: July 2021

Magnetotactic bacteria (MTB) are a group of microbes that biomineralize membrane-bound, nanosized magnetite (Fe3O4), and/or greigite (Fe3S4) crystals in intracellular magnetic organelle magnetosomes. MTB belonging to the Nitrospirae phylum can form up to several hundreds of Fe3O4 magnetosome crystals and dozens of sulfur globules in a single cell. These MTB are widespread in aquatic environments and sometimes account for a significant proportion of microbial biomass near the oxycline, linking these lineages to the key steps of global iron and sulfur cycling. Despite their ecological and biogeochemical importance, our understanding of the diversity and ecophysiology of magnetotactic Nitrospirae is still very limited because this group of MTB remains unculturable. Here, we identify and characterize two previously unknown MTB populations within the Nitrospirae phylum through a combination of 16S rRNA gene-based and genome-resolved metagenomic analyses. These two MTB populations represent distinct morphotypes (rod-shaped and coccoid, designated as XYR, and XYC, respectively), and both form more than 100 bullet-shaped magnetosomal crystals per cell. High-quality draft genomes of XYR and XYC have been reconstructed, and they represent a novel species and a novel genus, respectively, according to their average amino-acid identity values with respect to available genomes. Accordingly, the names Candidatus Magnetobacterium cryptolimnobacter and Candidatus Magnetomicrobium cryptolimnococcus for XYR and XYC, respectively, were proposed. Further comparative genomic analyses of XYR, XYC, and previously reported magnetotactic Nitrospirae reveal the general metabolic potential of this MTB group in distinct microenvironments, including CO2 fixation, dissimilatory sulfate reduction, sulfide oxidation, nitrogen fixation, or denitrification processes. A remarkably conserved magnetosome gene cluster has been identified across Nitrospirae MTB genomes, indicating its putative important adaptive roles in these bacteria. Taken together, the present study provides novel insights into the phylogenomic diversity and ecophysiology of this intriguing, yet poorly understood MTB group.
Distribution of HCV Genotypes Among People Who Inject Drugs in Tunisia: New Evidence for Scaling Up Prevention and Treatment Toward National Elimination Goal
Authors: Chouikha Anissa , Ghrabi Amine , Ghodbane Amira , Hammemi Walid , Khedhiri Marwa , Sadraoui Amel , Touzi Henda , Hassine Hichem Ben , Maatoug Sonia , Bensaoud Chaima , Abdelhak Sonia , Bouarrouj Samir , Gdoura Mariem , Chaouachi Hedia , Triki Henda
Published: July 2021

Little is known about the distribution of hepatitis C virus (HCV) genotypes among people who inject drugs (PWID) in North African countries, including Tunisia. This study aims to describe HCV genotypes circulating among Tunisian PWID. A cross-sectional study was conducted, and 128 HCV-positive PWID were recruited between 2018 and 2019 from community-based harm reduction centers. After informed consent, sociodemographic characteristics and risk behavior data were obtained using an interviewer-administrated questionnaire. Blood samples were collected for further serological and molecular testing. Overall, five women and 123 men were included. The median age was 39.5 years. The majority of PWID (56.3%) had less than a secondary level of education, were single (57%), were unemployed (65.6%), were incarcerated at least once (93.0%), and had a history of residency in at least one foreign country (50.8%). During the previous 12 months, 82.0% reported having reused syringes at least once, 43.8% shared syringes at least once, while 56.2% had at least one unprotected sexual relation, and 28.1% had more than two different sexual partners. Tattooing was reported among 60.2%. All positive results for HCV-infection by rapid testing were confirmed by enzyme-linked immunosorbent assay (ELISA). HCV-RNA was detectable in 79.7%. Genotyping showed a predominance of genotype 1 (52%) followed by genotype 3 (34%) and genotype 4 (10%). Four patients (4%) had an intergenotype mixed infection. Subtyping showed the presence of six different HCV subtypes as follows: 1a (53.2%), 1b (6.4%), 3a (33.0%), 4a (3.2%), and 4d (4.3%). This is the first study describing circulating HCV genotypes among PWID in Tunisia. The distribution of HCV genotypes is distinct from the general population with a predominance of subtypes 1a and 3a. These findings can be used to guide national efforts aiming to optimize the access of PWID to relevant HCV prevention and treatment measures including pangenotypic regimens for patients infected with HCV genotype 3.
Understanding Beta-Lactam-Induced Lysis at the Single-Cell Level
Authors: Wong Felix , Wilson Sean , Helbig Ralf , Hegde Smitha , Aftenieva Olha , Zheng Hai , Liu Chenli , Pilizota Teuta , Garner Ethan C. , Amir Ariel , Renner Lars D.
Published: July 2021

Mechanical rupture, or lysis, of the cytoplasmic membrane is a common cell death pathway in bacteria occurring in response to β-lactam antibiotics. A better understanding of the cellular design principles governing the susceptibility and response of individual cells to lysis could indicate methods of potentiating β-lactam antibiotics and clarify relevant aspects of cellular physiology. Here, we take a single-cell approach to bacterial cell lysis to examine three cellular features—turgor pressure, mechanosensitive channels, and cell shape changes—that are expected to modulate lysis. We develop a mechanical model of bacterial cell lysis and experimentally analyze the dynamics of lysis in hundreds of single Escherichia coli cells. We find that turgor pressure is the only factor, of these three cellular features, which robustly modulates lysis. We show that mechanosensitive channels do not modulate lysis due to insufficiently fast solute outflow, and that cell shape changes result in more severe cellular lesions but do not influence the dynamics of lysis. These results inform a single-cell view of bacterial cell lysis and underscore approaches of combatting antibiotic tolerance to β-lactams aimed at targeting cellular turgor.
Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
Authors: Li Keqin , Shao Shuai , Ji Tongjie , Liu Min , Wang Lufeng , Pang Ying , Chen Mu , Xu Siyi , Zhang Kuiming , Wang Qi , Zhuang Zhongwei , Wei Liang , Zhang Yanfei , Chen Yanlin , Wang Yang , Zhang Jing , Chen Kui , Lian Hao , Zhong Chunlong
Published: July 2021

Capicua (Cic), a transcriptional repressor frequently mutated in brain cancer oligodendroglioma, is highly expressed in adult neurons. However, its function in the dendritic growth of neurons in the hippocampus remains poorly understood. Here, we confirmed that Cic was expressed in hippocampal neurons during the main period of dendritogenesis, suggesting that Cic has a function in dendrite growth. Loss-of-function and gain-of function assays indicated that Cic plays a central role in the inhibition of dendritic morphogenesis and dendritic spinesin vitro. Further studies showed that overexpression of Cic reduced the expression of Ets in HT22 cells, whilein vitroknockdown of Cic in hippocampal neurons significantly elevated the expression of Ets. These results suggest that Cic may negatively control dendrite growth through Ets, which was confirmed by ShRNA knockdown of either Etv4 or Etv5 abolishing the phenotype of Cic knockdown in cultured neurons. Taken together, our results suggest that Cic inhibits dendritic morphogenesis and the growth of dendritic spines through Ets.
Suicidal Ideations and Behavior in Patients With Young and Late Onset Dementia
Authors: Ortner Marion , Riedl Lina , Jox Ralf J. , Hartmann Julia , Roßmeier Carola , Dorn Bianca , Kehl Victoria , Egert-Schwender Silvia , Fischer Julia , Diehl-Schmid Janine
Published: July 2021

Background and Objectives: Data on suicidal ideation, behavior and the risk factors in patients with dementia is scarce. To evaluate the prevalence of death wishes, suicidal ideation, and suicidal behavior of young (YOD) and late onset dementia (LOD) and to identify risk factors for suicidal ideation and behavior.

Methods: We interviewed 157 family caregivers of patients with advanced dementia using questions from the Columbia-Suicide Severity Rating Scale to gather information about suicidal ideation and behavior before the onset of symptoms of dementia, after the onset of dementia and within 30 days prior to the interview. At the time of the interview, we also assessed disease severity, cognitive function, and other psychological, behavioral and physical symptoms of the patients as well as the caregivers' psychological well-being.

Results: Forty four (28%) of the patients expressed suicidal ideation or behavior at some time after the onset of symptoms, and 14 (9%) of these within the month prior to the assessment. Two patients had attempted suicide after the onset of dementia. There were no statistically significant differences between patients with and without suicidal ideations or behavior with regards to demographics or age at onset of dementia. In patients with advanced dementia, Alzheimer's disease (rather than frontotemporal lobar degeneration), better cognitive function, more severe psychological, behavioral, and physical symptoms, and a reduced quality of life were associated with the expression of suicidal ideation.

Conclusions: According to caregivers' reports, majority of patients with dementia did not express suicidal ideation or show suicidal behavior. Patients who expressed suicidal ideation during early stages of dementia often stopped expressing them in advanced stages. It remains unclear if this was due to reduced communication abilities, a reduction of disease awareness, and/ or an adjustment to their situation.
Clinical Utility of the 6-Item CTS, Boston-CTS, and Hand-Diagram for Carpal Tunnel Syndrome
Authors: Schulze Daniel Gregor , Nilsen Kristian Bernhard , Killingmo Rikke Munk , Zwart John Anker , Grotle Margreth
Published: July 2021

Background: Self-reported measures are often used in research and clinical practice to diagnose carpal tunnel syndrome (CTS) and guide therapeutic choices. We aimed to assess the clinical utility of the Norwegian versions of two self-reported outcome measures for symptom severity assessment, the 6-item CTS (CTS-6), and Boston-CTS (BCTQ), and of one diagnostic measure, the hand-diagram, by evaluating measurement properties including discriminative ability for severity assessment (CTS-6, BCTQ), and diagnosis of CTS (hand-diagram).

Methods: We performed forward and backward translation and cultural adaptation of the Norwegian CTS-6 and BCTQ. Following COSMIN guidelines, we investigated internal consistency, reliability, construct validity, and discriminative ability for distinguishing between severity levels of CTS in patients with confirmed CTS for the CTS-6 and BCTQ and reliability and discriminative ability for diagnosing CTS for the hand-diagram.

Results: Two hundred and fifty-one patients referred for diagnostic work-up for CTS with nerve conduction studies (NCS) participated. The CTS-6 and BCTQ had acceptable internal consistency (Crohnbach's α = 0.82 and 0.86, respectively), reliability (ICC = 0.86 and 0.90; SEM = 0.24 and 0.20; SDC95% = 0.68 and 0.55, respectively), construct validity (all eight pre-defined hypotheses confirmed) and discriminative ability to distinguish between severity levels of CTS [Area under the curve (AUC) = 0.75, 95% CI 0.64–0.85]. The hand-diagram had acceptable reliability (Cohen's kappa = 0.69) and discriminative ability to diagnose CTS (sensitivity = 0.72, specificity = 0.90).

Conclusion: Our findings support the clinical utility of the CTS-6 and BCTQ for symptom severity assessment and of the hand-diagram for diagnostic screening.
Cardiac Involvement in Women With Pathogenic Dystrophin Gene Variants
Authors: Solheim Tuva Å. , Fornander Freja , Raja Anna A. , Møgelvang Rasmus , Poulsen Nanna S. , Dunø Morten , Bundgaard Henning , Vissing John
Published: July 2021

Objective: To determine the frequency and extent of cardiac involvement in female carriers of pathogenic variants in DMD, 53 women were examined through an observational, cross-sectional study.

Methods: Genetically verified female carriers of pathogenic DMD variants were examined by cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement, echocardiography, 24-h Holter monitoring, ECG, and blood concentrations of skeletal and cardiac muscle biomarkers.

Results: Fifty-three female carriers of pathogenic DMD variants (mean age 49.6 years, 33 associated with DMD, and 20 with BMD) were included in the study. Sixty-two percent had cardiac dysfunction on echocardiography. On CMR, 49% had myocardial fibrosis, 35% had dilated left ventricles, and 10% had left ventricular hypertrophy. ECGs were abnormal in 72%, and abnormal Holter monitoring was found in 43%. Age did not correlate with myocardial fibrosis or cardiac dysfunction. Myocardial fibrosis was more frequent in carriers of pathogenic variants associated with DMD vs. BMD (61 vs. 28%, p = 0.02).

Conclusion: This study shows that cardiac involvement, affecting both structure and function of the heart, is found in over 2/3 of women with a pathogenic DMD variant. The study supports early cardiac screening, including ECG, Holter, and cardiac imaging, in this group of carriers, so that symptoms related to pathogenic variants in DMD can be recognized, and relevant treatment can be initiated. Longitudinal studies are needed to assess morbidity and mortality related to single, pathogenic DMD variants in women.
Associations Among Parental Caregiving Quality, Cannabinoid Receptor 1 Expression-Based Polygenic Scores, and Infant-Parent Attachment: Evidence for Differential Genetic Susceptibility?
Authors: Potter-Dickey Amelia , Letourneau Nicole , Silveira Patricia P. , Ntanda Henry , Giesbrecht Gerald F. , Hart Martha , Dewell Sarah , de Koning A. P. Jason
Published: July 2021

Attachment is a biological evolutionary system contributing to infant survival. When primary caregivers/parents are sensitive and responsive to their infants’ needs, infants develop a sense of security. Secure infant attachment has been linked to healthy brain and organ-system development. Belsky and colleagues proposed the term differential susceptibility to describe context-dependent associations between genetic variations and behavioral outcomes as a function of parenting environments. Variations in the Cannabinoid Receptor Gene 1 (CNR1) are associated with memory, mood, and reward and connote differential susceptibility to more and less optimal parental caregiving quality in predicting children’s behavioral problems.

Aim

To determine if parental caregiving quality interacts with children’s expression-based polygenic risk score (ePRS) for the CNR1 gene networks in the prefrontal cortex, striatum, and hippocampus in predicting the probability of attachment security and disorganized attachment.

Design

Prospective correlational methods examined maternal-infant pairs (n = 142) from which infants provided DNA samples at 3 months. Parental caregiving quality was assessed via the Child Adult Relationship Experiment (CARE)-index at 6 months, and attachment security via the Strange Situation Procedure at a mean age of 22 months. The CNR1 ePRSs include genes co-expressed with the CNR1 genes in the prefrontal cortex, striatum, or hippocampus, and were calculated using the effect size of the association between the individual single nucleotide polymorphisms from those genes and region-specific gene expression (GTEx). Logistic regression was employed (alpha < 0.05, two-tailed) to examine the main and interaction effects between parental caregiving quality and ePRSs in predicting attachment patterns. Interpretation of results was aided by analyses that distinguished between differential susceptibility and diathesis-stress.

Results

Significant interactions were observed between (1) maternal sensitivity and ePRS in the striatum in predicting attachment security, (2) maternal unresponsiveness with the ePRS in the hippocampus in predicting disorganization, and (3) maternal controlling with the ePRS in the hippocampus in predicting disorganization.

Conclusion

These findings offer support for genetic differential susceptibility to the quality of maternal sensitivity in the context of the ePRS in the striatum. However, the significant interactions between hippocampal ePRS and maternal unresponsiveness and controlling in predicting the probability of disorganization were more suggestive of the diathesis-stress model.
Case Report: Probable Cerebral Amyloid Angiopathy-Related Inflammation During Bevacizumab Treatment for Metastatic Cervical Cancer
Authors: Koudriavtseva Tatiana , Lorenzano Svetlana , Anelli Vincenzo , Sergi Domenico , Stefanile Annunziata , Di Domenico Enea Gino , Maschio Marta , Galiè Edvina , Piantadosi Carlo
Published: July 2021

Bevacizumab is an anti-angiogenic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF) that induces the proliferation and migration of vascular endothelial cells thus, promoting vasculogenesis. Bevacizumab inhibits cancer angiogenesis, which is fundamental for either tumor development, exponential growth, or metastatic spread by supplying nutrients and oxygen. We report a new possible adverse event of bevacizumab, a Cerebral Amyloid Angiopathy-Related Inflammation (CAARI), in a 72-year-old woman with metastatic cervical cancer. After six cycles every three weeks of chemotherapy (cisplatin, paclitaxel, bevacizumab) and following two maintenance bevacizumab administrations, the patient presented a worsening confusional state. The MRI scan showed bilateral asymmetric temporo-parieto-occipital hyperintensity with numerous cortical microbleeds indicative of a CAARI. After stopping bevacizumab treatment, steroid therapy was administered resulting in rapid clinical improvement. The subsequent neurological and oncological follow-up was negative for recurrence. The patient was a heterozygote carrier for apolipoprotein-E ε4 that increases the risk of sporadic Cerebral Amyloid Angiopathy (CAA), which is characterized by beta-amyloid accumulation and fibrinoid necrosis in cerebral vasculature leading to micro/macrohemorrhages and dementia. Moreover, CAA is present in 30% of people aged over 60 years without dementia. In the brains of CAA patients, there is a proinflammatory state with cerebrovascular endothelial cell alteration and elevated levels of either adhesion molecules or inflammatory interleukins that increase the blood–brain barrier permeability. Moreover, CAARI is an inflammatory form of CAA. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival effects on endothelial cells, impairs their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, bevacizumab administration may have further increased permeability of cerebral microvasculature likely impaired by an underlying, asymptomatic CAA. To our knowledge, this is the first case reporting on the development of probable CAARI during bevacizumab treatment, which should alert the clinicians in case of neurological symptom onset in older patients under anti-angiogenic therapy.
Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis
Authors: Wu Xiaodan , Fan Yihui , Liu Yupeng , Shen Biao , Lu Haimin , Ma Haitao
Published: July 2021

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.
Identification of a Four Hypoxia-Associated Long Non-Coding RNA Signature and Establishment of a Nomogram Predicting Prognosis of Clear Cell Renal Cell Carcinoma
Authors: Chen Hualin , Pan Yang , Jin Xiaoxiang , Chen Gang
Published: July 2021

To identify novel hypoxia-associated long non-coding RNAs (lncRNAs) as potential biomarkers, we developed a risk stratification signature and constructed a prognosis prediction nomogram of clear cell renal cell carcinoma (ccRCC). Hypoxia-related lncRNAs were identified through Pearson correlation analysis between the expression profiles of hypoxia-related differentially expressed genes and lncRNAs from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset. Then, a signature of four key lncRNAs (COMETT, EMX2OS, AC026462.3, and HAGLR) was developed. The four lncRNAs were downregulated in high-grade, advanced stage, and high-risk ccRCC. The signature had an independent and long-standing prognosis prediction ability up to a 10-year follow-up. Notably, the risk score was significantly positively correlated with the infiltration abundances of six immune cells from the Tumor IMmune Estimation Resource (TIMER). The gene set enrichment analysis (GSEA) also suggested that the signature was involved in metabolism and tumorigenesis, which were closely related to the hypoxic tumor microenvironment. Ultimately, a nomogram of signature, age, stage, and grade, was built to predict the individual long-term survival possibility. Finally, the expressions of four lncRNAs were validated by quantitative real-time PCR (qRT-PCR). Our study identified a four-lncRNA signature and established a prognostic nomogram that reliably predicts survival in ccRCC. The findings may be beneficial to therapeutic customization and medical decision-making.
Hybrid Procedures. Opening Doors for Surgeon and Cardiologist Close Collaboration
Authors: Gil-Jaurena Juan-Miguel , Zunzunegui José-Luis , Pérez-Caballero Ramón , Pita Ana , Pardo Carlos , Calle Corazón , Murgoitio Uxue , Ballesteros Fernando , Rodríguez Alejandro , Medrano Constancio
Published: July 2021

Background: Collaboration between cardiac surgeons and cardiologists can offer interventions that each specialist may not be able to offer on their own. This type of collaboration has been demonstrated with the hybrid Stage I in patients with hypoplastic heart syndrome. Since that time, a hybrid approach to cardiac interventions has been expanded to an incredible variety of potential indications.

Methods: Seventy-one patients were scheduled for a hybrid procedure along 8 years. This was defined as close collaboration between surgeon and cardiologist working together in the same room, either cath-lab (27 patients) or theater (44 patients).

Results: Six groups were arbitrarily defined. A: vascular cut-down in the cath-lab (27 neonates); B: bilateral banding (plus ductal stent) in hypoplastic left heart syndrome or alike (15 children); C: perventricular closure of muscular ventricular septal defect (10 cases); D: balloon/stenting of pulmonary branches along with major surgical procedure (12 kids); E: surgical implantation of Melody valve (six patients) and others (F, one case). Two complications were recorded: left ventricular free wall puncture and previous conduit tearing. Both drawbacks were successfully sort out under cardiopulmonary by-pass.

Conclusion: Surgeon and cardiologist partnership can succeed where their isolated endeavors are not enough. Hybrid procedures keep on spreading, overcoming initial expectations. As a bridge to biventricular repair or transplant, bilateral banding plus ductal stent sounds interesting. Novel indications can be classified into different groups. Hybrid procedures are not complication-free.
Functional Characterization of Olfactory Receptors in the Thyroid Gland
Authors: Weidinger Daniel , Jovancevic Nikolina , Zwanziger Denise , Theurer Sarah , Hönes Judith , Führer Dagmar , Hatt Hanns
Published: July 2021

Olfactory receptors (ORs) are almost ubiquitously expressed in the human body. However, information about their functions in these tissues is lacking. To date, no functional characterization of expressed ORs in the human thyroid has been performed. In this study, we detected and compared the expression of OR2H2 and OR2W3 in healthy and malignant cell lines and their corresponding tissues, respectively. We demonstrated that stimulation of ORs by their specific ligand resulted in a transient increase in intracellular calcium and cAMP concentrations. In the case of OR2H2, the downstream signaling cascade analysis revealed that adenylate cyclase (AC) and phosphoinositide phospholipase C (PLC) were involved. Furthermore, OR2H2 and OR2W3 activation affected migration, proliferation, and invasion. These are the first insights that ORs influence physiology-relevant processes in the healthy and malignant thyroid.
Autogenic Training Improves the Subjective Perception of Physical and Psychological Health and of Interpersonal Relational Abilities: An Electronic Field Survey During the COVID-19 Crisis in Spain
Authors: de Rivera Luis , Ozamiz-Etxebarria Naiara , Dosil-Santamaría María , de Rivera-Monterrey Leonor
Published: July 2021

Currently, humanity is facing one of the most critical situations of this century, the COVID-19. The adverse effects of the pandemic on the mental health of the population are well known. Fear of illness, confinement, lack of financial resources, or poor social support can influence people’s mental state. Despite these risks, several psychological resources may help address this situation. The present study investigated the effectiveness of a self-relaxation techniques known as autogenic training. Autogenic training is a well-known method in Europe for the treatment of anxiety and stress disorders. The practice of autogenic training is also reported to improve neurovegetative and immune regulation. This study focuses on describing how autogenic training is helping its practitioners to cope with the pandemic. Specifically, they report strong beneficial effects on their physical, psychological, and relational health. In total, 75 autogenic training practitioners (41 women), age 22–71, participated in the survey. An ad-hoc questionnaire was developed to collect information on sociodemographic variables, health status during the pandemic, characteristics of their AT practice, and response to the pandemic as outcome variables. The questionnaire was distributed through Google Forms in the first week of September 2020. The results show that there was an increase in the practice of autogenic therapy during the pandemic, especially among women. In addition, the majority of participants (88%) remained healthy during the pandemic. Furthermore, the results show that autogenic training is very useful for physical and psychological health and for a better understanding of others. Therefore, the practice of autogenic training is recommended to people who live moments of anxiety, are afraid of illness, or feel that they have to improve the quality of relationships with others.
Leader–Follower Congruence in Work Engagement and Leader–Member Exchange: The Moderating Role of Conscientiousness of Followers
Authors: Ye Yanhua , Wang Ziwen , Lu Xiaowei
Published: July 2021

Extant research has investigated the relationship between work engagement and various outcomes, such as job performance and organizational commitment, neglecting the effect of work engagement on social relationships at work. Drawing upon person-environment fit theory and LMX theory, the present study aims to examine the effect of (in)congruence between leader and follower work engagement on leader–member exchange (LMX) and the moderating effect of conscientiousness. About 273 employees and 72 leaders participated in this study and completed the measurements of work engagement, conscientiousness, and LMX at two time points. Using cross-level polynomial regressions, we found that, compared with incongruent work engagement, employees perceived high levels of LMX quality when their work engagement was aligned with that of their leaders. Regarding the congruence, the employees reported higher levels of LMX when congruence in work engagement was at higher rather than lower levels. Regarding the incongruence, when the employees engaged less in their work tasks than their leaders, they were more likely to experience lower LMX. Moreover, the negative relationship between incongruence in leader and follower work engagement and LMX was mitigated when followers were more conscientious. All our hypotheses were supported. Both theoretical and practical implications for work engagement as well as future directions are discussed.
Critical Analysis of the Risks in the Use of the Internet and Social Networks in Childhood and Adolescence
Authors: Núñez-Gómez Patricia , Larrañaga Kepa Paul , Rangel Celia , Ortega-Mohedano Félix
Published: July 2021

Kids are people who consume content on the Internet very frequently and actively participate in social networks, so it is necessary to know the risks of their use by children and adolescents, in order to propose a critical analysis of them. This work is the result of two research studies: a qualitative and a quantitative analysis of 1,350 children and adolescents between 6 and 12 years old living in Spain. The objectives of this paper are analysing the attitudes of children and adolescents about the safe use of the Internet and social networks, studying the differences in the discourse of children and adults about the risks of their use, as well as defining areas for improvement to promote the safe use of the Internet and social networks. The main findings include intergenerational tensions between adults and children in the use of the Internet, the difficulty of reaching consensus and quality support when using the Internet. Children have transcended the physical and digital space considering it, so they must be given the tools, competences and security to fully develop their digital identity.