bluuebunny/crossref_metadata_2025 huggingface dataset:
E2F1 and epigenetic modifiers orchestrate breast cancer progression by regulating oxygen-dependent ESRP1 expression
Authors: Ashok Cheemala , Ahuja Neha , Natua Subhashis , Mishra Jharna , Samaiya Atul , Shukla Sanjeev
Published: August 2021

Epithelial splicing regulatory protein 1 (ESRP1) is an RNA binding protein that governs the alternative splicing events related to epithelial phenotypes. ESRP1 contributes significantly at different stages of cancer progression. ESRP1 expression is substantially elevated in carcinoma in situ compared to the normal epithelium, whereas it is drastically ablated in cancer cells within hypoxic niches, which promotes epithelial to mesenchymal transition (EMT). Although a considerable body of research sought to understand the EMT-associated ESRP1 downregulation, the regulatory mechanisms underlying ESRP1 upregulation in primary tumors remained largely uncharted. This study seeks to unveil the regulatory mechanisms that spatiotemporally fine-tune the ESRP1 expression during breast carcinogenesis. Our results reveal that an elevated expression of transcription factor E2F1 and increased CpG hydroxymethylation of the E2F1 binding motif conjointly induce ESRP1 expression in breast carcinoma. However, E2F1 fails to upregulate ESRP1 despite its abundance in oxygen-deprived breast cancer cells. Mechanistically, impelled by the hypoxia-driven reduction of tet methylcytosine dioxygenase 3 (TET3) activity, CpG sites across the E2F1 binding motif lose the hydroxymethylation marks while gaining the de novo methyltransferase-elicited methylation marks. These two oxygen-sensitive epigenetic events work in concert to repel E2F1 from the ESRP1 promoter, thereby diminishing ESRP1 expression under hypoxia. Furthermore, E2F1 skews the cancer spliceome by upregulating splicing factor SRSF7 in hypoxic breast cancer cells. Our findings provide previously unreported mechanistic insights into the plastic nature of ESRP1 expression and insinuate important implications in therapeutics targeting breast cancer progression.
Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study
Authors: Iob Eleonora , Baldwin Jessie R. , Plomin Robert , Steptoe Andrew
Published: August 2021

Dysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.
Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis
Authors: Smith Caren E. , Parnell Laurence D. , Lai Chao-Qiang , Rush John E. , Freeman Lisa M.
Published: August 2021

Dilated cardiomyopathy (DCM) is a disease of the heart muscle that affects both humans and dogs. Certain canine diets have been associated with DCM, but the diet-disease link is unexplained, and novel methods are needed to elucidate mechanisms. We conducted metabolomic profiling of 9 diets associated with canine DCM, containing ≥ 3 pulses, potatoes, or sweet potatoes as main ingredients, and in the top 16 dog diet brands most frequently associated with canine DCM cases reported to the FDA (3P/FDA diets), and 9 non-3P/FDA diets. We identified 88 named biochemical compounds that were higher in 3P/FDA diets and 23 named compounds that were lower in 3P/FDA diets. Amino acids, amino acid-derived compounds, and xenobiotics/plant compounds were the largest categories of biochemicals that were higher in 3P/FDA diets. Random forest analyses identified the top 30 compounds that distinguished the two diet groups with 100% predictive accuracy. Four diet ingredients distinguished the two diet groups (peas, lentils, chicken/turkey, and rice). Of these ingredients, peas showed the greatest association with higher concentrations of compounds in 3P/FDA diets. Moreover, the current foodomics analyses highlight relationships between diet and DCM in dogs that can identify possible etiologies for understanding diet-disease relationships in dogs and humans.
Evaluation of a high-throughput, cost-effective Illumina library preparation kit
Authors: Tvedte Eric S. , Michalski Jane , Cheng Shaoji , Patkus Rayanna S. , Tallon Luke J. , Sadzewicz Lisa , Bruno Vincent M. , Silva Joana C. , Rasko David A. , Dunning Hotopp Julie C.
Published: August 2021

Library preparation for high-throughput sequencing applications is a critical step in producing representative, unbiased sequencing data. The iGenomX Riptide High Throughput Rapid Library Prep Kit purports to provide high-quality sequencing data with lower costs compared to other Illumina library kits. To test these claims, we compared sequence data quality of Riptide libraries to libraries constructed with KAPA Hyper and NEBNext Ultra. Across several single-source genome samples, mapping performance and de novo assembly of Riptide libraries were similar to conventional libraries prepared with the same DNA. Poor performance of some libraries resulted in low sequencing depth. In particular, degraded DNA samples may be challenging to sequence with Riptide. There was little cross-well plate contamination with the overwhelming majority of reads belong to the proper source genomes. The sequencing of metagenome samples using different Riptide primer sets resulted in variable taxonomic assignment of reads. Increased adoption of the Riptide kit will decrease library preparation costs. However, this method might not be suitable for degraded DNA.
A computational framework to establish data-driven constitutive models for time- or path-dependent heterogeneous solids
Authors: Ge Weijian , Tagarielli Vito L.
Published: August 2021

We propose and implement a computational procedure to establish data-driven surrogate constitutive models for heterogeneous materials. We study the multiaxial response of non-linear n-phase composites via Finite Element (FE) simulations and computational homogenisation. Pseudo-random, multiaxial, non-proportional histories of macroscopic strain are imposed on volume elements of n-phase composites, subject to periodic boundary conditions, and the corresponding histories of macroscopic stresses and plastically dissipated energy are recorded. The recorded data is used to train surrogate, phenomenological constitutive models based on neural networks (NNs), and the accuracy of these models is assessed and discussed. We analyse heterogeneous composites with hyperelastic, viscoelastic or elastic–plastic local constitutive descriptions. In each of these three cases, we propose and assess optimal choices of inputs and outputs for the surrogate models and strategies for their training. We find that the proposed computational procedure can capture accurately and effectively the response of non-linear n-phase composites subject to arbitrary mechanical loading.
Prevalence and genetic characteristics of Blastocystis hominis and Cystoisospora belli in HIV/AIDS patients in Guangxi Zhuang Autonomous Region, China
Authors: Xu Ning , Jiang Zhihua , Liu Hua , Jiang Yanyan , Wang Zunfu , Zhou Dongsheng , Shen Yujuan , Cao Jianping
Published: August 2021

Blastocystis hominis and Cystoisospora belli are considered to be common opportunistic intestinal protozoa in HIV/AIDS patients. In order to investigate the prevalence and genetic characteristics of B. hominis and C. belli in HIV/AIDS patients, a total of 285 faecal samples were individually collected from HIV/AIDS patients in Guangxi, China. B. hominis and C. belli were investigated by amplifying the barcode region of the SSU rRNA gene and the internal transcribed spacer 1 (ITS-1) region of the rRNA gene, respectively. Chi-square test or Fisher’s exact test were conducted to assess the risk factors related to B. hominis and C. belli infection. The prevalence of B. hominis and C. belli was 6.0% (17/285) and 1.1% (3/285) respectively. Four genotypes of B. hominis were detected, with ST3 (n = 8) and ST1 (n = 6) being predominant, followed by ST6 (n = 2) and ST7 (n = 1). Females had a statistically higher prevalence of B. hominis (11.6%) than males (4.2%). The statistical analysis also showed that the prevalence of B. hominis was significantly associated with age group and educational level. Our study provides convincing evidence for the genetic diversity of B. hominis, which indicates its potential zoonotic transmission and is the first report on the molecular characteristics of C. belli in HIV/AIDS patients in China.
A novel murine in vivo model for acute hereditary angioedema attacks
Authors: Bupp Sujata , Whittaker Matthew , Lehtimaki Mari , Park JuMe , Dement-Brown Jessica , Zhou Zhao-Hua , Kozlowski Steven
Published: August 2021

Hereditary Angioedema (HAE) is a rare genetic disease generally caused by deficiency or mutations in the C1-inhibitor gene, SERPING1, a member of the Serpin family. HAE results in acute attacks of edema, vasodilation, GI pain and hypotension. C1INH is a key inhibitor of enzymes controlling complement activation, fibrinolysis and the contact system. In HAE patients, contact system activation leads to uncontrolled production of bradykinin, the vasodilator responsible for the characteristic symptoms of HAE. In this study, we present the first physiological in vivo model to mimic acute HAE attacks. We evaluate hypotension, one of the many hallmark symptoms of acute HAE attacks using Serping1 deficient mice (serping1−/−) and implanted telemetry. Attacks were induced by IV injection of a silica nanoparticle (SiNP) suspension. Blood pressure was measured in real time, in conscious and untethered mice using implanted telemetry.SiNP injection induced a rapid, reversible decrease in blood pressure, in the presence of angiotensin converting enzyme (ACE) inhibition. We also demonstrate that an HAE therapeutic, ecallantide, can prevent HAE attacks in this model. The in vivo murine model described here can facilitate the understanding of acute HAE attacks, support drug development and ultimately contribute to improved patient care.
Comparative effectiveness of pneumococcal vaccination with PPV23 and PCV13 in COPD patients over a 5-year follow-up cohort study
Authors: Ignatova Galina L. , Avdeev Sergey N. , Antonov Vladimir N.
Published: August 2021

Vaccination against Streptococcus pneumoniae is among the most effective measures for preventing pneumonia and reducing the rate of chronic obstructive pulmonary disease (COPD) exacerbations. The objective of this work was to evaluate the long-term effectiveness of PCV13 and PPV23 for preventing pneumonia and COPD exacerbations. The open-label, prospective, observational cohort study involved 302 male patients aged ≥ 45 years: PCV13 group (n = 123); PPV23 group (n = 32); and vaccine-naïve group (n = 147). The primary endpoint included the frequency of pneumonia episodes and COPD exacerbations per year over a 5-year follow-up period. The secondary endpoints included the dynamics of dyspnea severity (MMRC), the BODE index, FEV1, the CAT index, the SGRQ score, and the results of 6-min walk test. Vaccination with PCV13 and PPV23 significantly reduces the total rate of pneumonia during the first year after vaccination. Starting with the second year, clinical effectiveness in PPV23 group decreases compared with both PCV13 group and vaccine-naïve patients. Pneumonia by year 5 after vaccination was registered in 47% of patients in the PPV23 group, versus 3.3% of patients in the PCV13 group (p < 0.001); COPD exacerbations—in 81.3% versus 23.6%, respectively (p < 0.001). Vaccination with PCV13 significantly reduced and maintained the BODE index over the 5-year follow-up period. Although both vaccines have comparable clinical effects during the first year after vaccination, only PCV13 is characterized by persistent clinical effectiveness during the 5-year follow-up period. Patients older than 55 years who received PPV23 have significantly higher risks of having pneumonia episodes more frequently during the long-term follow-up.
Identification of de novo EP300 and PLAU variants in a patient with Rubinstein–Taybi syndrome-related arterial vasculopathy and skeletal anomaly
Authors: Park Jong Eun , Kim Eunmi , Lee Dong-Won , Park Taek Kyu , Kim Min Sun , Jang Shin Yi , Ahn Jaemyung , Park Kwang Bo , Kim Keon-Ha , Park Hae-Chul , Ki Chang-Seok , Kim Duk-Kyung
Published: August 2021

Rubinstein–Taybi syndrome (RSTS) is a human genetic disorder characterized by distinctive craniofacial features, broad thumbs and halluces, and intellectual disability. Mutations in the CREB binding protein (CREBBP) and E1A binding protein p300 (EP300) are the known causes of RSTS disease. EP300 regulates transcription via chromatin remodeling and plays an important role in cell proliferation and differentiation. Plasminogen activator, urokinase (PLAU) encodes a serine protease that converts plasminogen to plasmin and is involved in several biological processes such as the proteolysis of extracellular matrix-remodeling proteins and the promotion of vascular permeability and angiogenesis. Recently, we discovered a patient who presented with RSTS-related skeletal anomaly and peripheral arterial vasculopathy. To investigate the genetic cause of the disease, we performed trio whole genome sequencing of the genomic DNA from the proband and the proband’s parents. We identified two de novo variants coined c.1760T>G (p.Leu587Arg) and c.664G>A (p.Ala222Thr) in EP300 and PLAU, respectively. Furthermore, functional loss of EP300a and PLAUb in zebrafish synergistically affected the intersegmental vessel formation and resulted in the vascular occlusion phenotype. Therefore, we hypothesize that the de novo EP300 variant may have caused RSTS, while both the identified EP300 and PLAU variants may have contributed to the patient’s vascular phenotype.
DNA barcodes enable higher taxonomic assignments in the Acari
Authors: Young Monica R. , deWaard Jeremy R. , Hebert Paul D. N.
Published: August 2021

Although mites (Acari) are abundant in many terrestrial and freshwater ecosystems, their diversity is poorly understood. Since most mite species can be distinguished by variation in the DNA barcode region of cytochromecoxidase I, the Barcode Index Number (BIN) system provides a reliable species proxy that facilitates large-scale surveys. Such analysis reveals many new BINs that can only be identified as Acari until they are examined by a taxonomic specialist. This study demonstrates that the Barcode of Life Datasystem’s identification engine (BOLD ID) generally delivers correct ordinal and family assignments from both full-length DNA barcodes and their truncated versions gathered in metabarcoding studies. This result was demonstrated by examining BOLD ID’s capacity to assign 7021 mite BINs to their correct order (4) and family (189). Identification success improved with sequence length and taxon coverage but varied among orders indicating the need for lineage-specific thresholds. A strict sequence similarity threshold (86.6%) prevented all ordinal misassignments and allowed the identification of 78.6% of the 7021 BINs. However, higher thresholds were required to eliminate family misassignments for Sarcoptiformes (89.9%), and Trombidiformes (91.4%), consequently reducing the proportion of BINs identified to 68.6%. Lineages with low barcode coverage in the reference library should be prioritized for barcode library expansion to improve assignment success.
Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
Authors: Alfardus Huda , de los Angeles Estevez-Cebrero Maria , Rowlinson Jonathan , Aboalmaaly Amna , Lourdusamy Anbarasu , Abdelrazig Salah , Ortori Catherine , Grundy Richard , Kim Dong-Hyun , McIntyre Alan , Smith Stuart
Published: August 2021

While specific microRNA (miRNA) signatures have been identified in glioblastoma (GBM), the intratumour heterogeneity in miRNA expression has not yet been characterised. In this study, we reveal significant alterations in miRNA expression across three GBM tumour regions: the core, rim, and invasive margin. Our miRNA profiling analysis showed that miR-330-5p and miR-215-5p were upregulated in the invasive margin relative to the core and the rim regions, while miR-619-5p, miR-4440 and miR-4793-3p were downregulated. Functional analysis of newly identified miRNAs suggests their involvement in regulating lipid metabolic pathways. Subsequent liquid chromatography–mass spectrometry (LC–MS) and tandem mass spectroscopy (LC–MS/MS) profiling of the intracellular metabolome and the lipidome of GBM cells with dysregulated miRNA expression confirmed the alteration in the metabolite levels associated with lipid metabolism. The identification of regional miRNA expression signatures may underlie the metabolic heterogeneity within the GBM tumour and understanding this relationship may open new avenues for the GBM treatment.
“Guilt by association” is not competitive with genetic association for identifying autism risk genes
Authors: Gunning Margot , Pavlidis Paul
Published: August 2021

Discovering genes involved in complex human genetic disorders is a major challenge. Many have suggested that machine learning (ML) algorithms using gene networks can be used to supplement traditional genetic association-based approaches to predict or prioritize disease genes. However, questions have been raised about the utility of ML methods for this type of task due to biases within the data, and poor real-world performance. Using autism spectrum disorder (ASD) as a test case, we sought to investigate the question: can machine learning aid in the discovery of disease genes? We collected 13 published ASD gene prioritization studies and evaluated their performance using known and novel high-confidence ASD genes. We also investigated their biases towards generic gene annotations, like number of association publications. We found that ML methods which do not incorporate genetics information have limited utility for prioritization of ASD risk genes. These studies perform at a comparable level to generic measures of likelihood for the involvement of genes in any condition, and do not out-perform genetic association studies. Future efforts to discover disease genes should be focused on developing and validating statistical models for genetic association, specifically for association between rare variants and disease, rather than developing complex machine learning methods using complex heterogeneous biological data with unknown reliability.
Increased biological antioxidant potential in the cerebrospinal fluid of transient global amnesia patients
Authors: Kawai Takayuki , Sakakibara Ryuji , Aiba Yosuke , Tateno Fuyuki , Ogata Tsuyoshi , Sawai Setsu
Published: August 2021

Oxidative stress may accompany the pathological process in transient global amnesia (TGA). We measured the biological antioxidant potential (BAP) in the cerebrospinal fluid (CSF) of TGA patients. We enrolled 13 TGA patients (7 men, 6 women; mean age 65.0 years [48–70 years]) and 24 control subjects (12 men, 12 women; mean age 38.2 years [17–65 years]; age did not correlate with csfBAP in this group). We performed brain MRI in all TGA patients, and CA1 lesions were noted by MRI in 5 subjects. We measured csfBAP, total antioxidant properties, in all TGA patients and controls. csfBAP levels were higher in TGA patients than in controls (p = 0.024, 0.028). csfBAP levels in TGA patients did not differ between MRI-positive and -negative subgroups. Elevated csfBAP levels were observed in TGA patients, suggesting that oxidative stress may have a role in the pathogenesis of TGA.
Recombinase polymerase amplification (RPA) with lateral flow detection for three Anaplasma species of importance to livestock health
Authors: Salazar Andrea , Ochoa-Corona Francisco M. , Talley Justin L. , Noden Bruce H.
Published: August 2021

Anaplasma marginale, A. ovis, and A. phagocytophilum are the causative agents of bovine anaplasmosis, ovine anaplasmosis, and granulocytic anaplasmosis, respectively. The gold standard for diagnosis of post-acute and long-term persistent infections is the serological cELISA, which does not discriminate between Anaplasma species and requires highly equipped laboratories and trained personnel. This study addresses the development of a rapid, isothermal, sensitive, species-specific RPA assays to detect three Anaplasma species in blood and cELISA A. marginale-positive serum samples. Three RPA primer and probe sets were designed targeting msp4 genes of each Anaplasma species and the internal control (GAPDH gene) for each assay. The limit of detection of gel-based or RPA-basic assays is 8.99 × 104 copies/µl = A. marginale, 5.04 × 106 copies/µl = A. ovis, and 4.58 × 103 copies/µl = A. phagocytophilum, and for each multiplex lateral flow or RPA-nfo assays is 8.99 × 103 copies/µl of A. marginale, 5.04 × 103 copies/µl of A. ovis, 4.58 × 103 copies/µl of A. phagocytophilum, and 5.51 × 103 copies/µl of internal control (GAPDH). Although none of the 80 blood samples collected from Oklahoma cattle were positive, the RPA-nfo assays detected all A. marginale cattle blood samples with varying prevalence rates of infection, 83% of the 24 cELISA A. marginale-positive serum samples, and all A. phagocytophilum cell culture samples. Overall, although early detection of three Anaplasma species was not specifically addressed, the described RPA technique represents an improvement for detection of three Anaplasma in regions where access to laboratory equipment is limited.
Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with minor sex-specific effects
Authors: Laube Mandy , Dornis Diana , Wenzel Fine , Thome Ulrich H.
Published: August 2021

Male sex remains an independent risk factor for respiratory distress syndrome (RDS) in preterm infants. Insufficient Na+ transport-mediated alveolar fluid clearance contributes to RDS development and we previously demonstrated sex-specific differences in Na+ transport. The epidermal growth factor (EGF) is important during fetal lung development with possible influence on Na+ transport. Sex-specific effects of EGF during surfactant synthesis were shown. We thus determined whether EGF exerts sex-specific effects on Na+ transport in fetal alveolar cells. We analyzed sex-specific fetal distal lung epithelial (FDLE) cells exposed to EGF and related ligands with Ussing chambers, RT-qPCR and Western blots. EGF strongly reduced the epithelial Na+ channel (ENaC) mRNA levels in both male and female FDLE cells. This was corroborated by a markedly reduced ENaC activity, while amiloride-insensitive pathways as well as barrier function were raised by EGF. In contrast to chronic effects, acute effects of EGF were sex-specific, because Na+ transport was reduced only in males. AKT phosphorylation was elevated only in female cells, while pERK1/2 was increased in both male and female cells. EGF showed certain sex- and time-dependent effects in FDLE cells. Nevertheless, the results suggest that EGF is an unlikely cause for the sex-specific differences in Na+ transport.
Effect of graphene oxide flakes size and number of layers on photocatalytic hydrogen production
Authors: Gacka Ewelina , Majchrzycki Łukasz , Marciniak Bronisław , Lewandowska-Andralojc Anna
Published: August 2021

The present study explored the correlation between the photocatalytic activity toward hydrogen production of the graphene-based materials and graphene oxide (GO) morphology. In this work we applied the technique based on the combination of time-dependent sonication and iterative centrifugation cascades, which were designed to achieve nanosheets size and the number of layers selection. First such obtained GO dispersions were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and optical spectroscopy. Those combined measurements showed that the intensity of the π-π peak at 230 nm seems to be very sensitive to the number of layers of nanosheets. Next, GO dispersions were used to establish influence of the size and the number of layers of GO flakes on the photocatalytic hydrogen production in the photocatalytic system, containing eosin Y as a sensitizer, triethanolamine as a sacrificial electron donor, and CoSO4 as precatalyst. The H2 production efficiency varied by a factor of 3.7 for GO dispersions sonicated for various amount of time. Interestingly it was found that too long ultrasound treatment had negative impact on the GO enhancement of hydrogen production which was related to the fragmentation of GO flakes. The photocatalytic system produced the highest amount of H2 when graphene oxide occurs as monolayers and efficiency becomes lower with the decrease of GO sheets size. Our results demonstrate the importance of optimizing the size and the number of layers of the GO flakes prior to preparation of GO-based materials.
Research on the method of designing cap lens using ant colony algorithm
Authors: Liu Wenlin , Qin Hua , Lv Zhiwei , Feng Yanze , Shi Yuetong , Liu Zixiang , Bai Chenghao
Published: August 2021

It is necessary to select the appropriate parameters defining a aspheric lens for coupling the light from a laser diode into the optical fiber by cap aspheric lenses. In this paper, the ant colony optimization algorithm is applied to the optimization of structural parameters of the cap aspheric lens, and the merit function defining the optimization problem and detailed design steps are given. A cap aspheric lens with center thickness of 1.1019 mm and effective focal length of 1.10331 mm is designed using a self-made MATLAB program of ant colony optimization algorithm, which can couple the light emitting from a laser diode into a single mode fiber with a diameter of 9 um, the light-emitting surface of the LD is 3 µm × 2 µm, and beam-divergence angle in the X and Y directions are ± 35° and ± 23.58°, respectively. The theoretical coupling efficiency is 89.8%, and the experiment shows that the maximum coupling efficiency and average coupling efficiency are 88.63% and 79.39%, respectively. Design and experimental results prove that the design method in this paper is feasible and effective.
Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range
Authors: Winkley Konner , Banerjee Dithi , Bradley Todd , Koseva Boryana , Cheung Warren A. , Selvarangan Rangaraj , Pastinen Tomi , Grundberg Elin
Published: August 2021

Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2. However, it is unclear if this reflects increased immune activation or increased immune residence in the nasal mucosa. We hypothesized that immune residency in the nasal mucosa of healthy individuals may differ across the age range. We applied single-cell RNA-sequencing and measured the cellular composition and transcriptional profile of the nasal mucosa in 35 SARS-CoV-2 negative children and adults, ranging in age from 4 months to 65 years. We analyzed in total of ~ 30,000 immune and epithelial cells and found that age and immune cell proportion in the nasal mucosa are inversely correlated, with little evidence for structural changes in the transcriptional state of a given cell type across the age range. Orthogonal validation by epigenome sequencing indicate that it is especially cells of the innate immune system that underlie the age-association. Additionally, we characterize the predominate immune cell type in the nasal mucosa: a resident T cell like population with potent antiviral properties. These results demonstrate fundamental changes in the immune cell makeup of the uninfected nasal mucosa over the lifespan. The resource we generate here is an asset for future studies focusing on respiratory infection and immunization strategies.
Allergic diseases attributable to atopy in a population sample of Asian children
Authors: Wu Chao-Yi , Huang Hsin-Yi , Pan Wen-Chi , Liao Sui-Ling , Hua Man-Chin , Tsai Ming-Han , Lai Shen-Hao , Yeh Kuo-Wei , Chen Li-Chen , Huang Jing-Long , Yao Tsung-Chieh
Published: August 2021

The proportion of allergic diseases attributable to atopy remains a subject of controversy. This study aimed to estimate the population risk of physician-diagnosed asthma, rhinitis and eczema attributed to atopy among a population sample of Asian school-age children. Asian children aged 5–18 years (n = 1321) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were tested for serum allergen-specific immunoglobulin E. Physician-diagnosed asthma, rhinitis and eczema were assessed by a modified International Study of Asthma and Allergies in Childhood questionnaire. Atopy was defined as the presence of serum allergen-specific immunoglobulin E. In this population-based study, 50.4% of the subjects with asthma, 46.3% with rhinitis, and 46.7% with eczema were attributable to atopy. The population attributable risk (PAR) of atopy for three allergic diseases was higher in adolescents (asthma, 54.4%; rhinitis, 59.6%; eczema, 49.5%) than younger children aged less than 10 years (asthma, 46.9%; rhinitis, 39.5%; eczema, 41.9%). Among the seven allergen categories, sensitization to mites had the highest PARs for all three allergic diseases (51.3 to 64.1%), followed by sensitization to foods (asthma, 7.1%; rhinitis, 10.4%; eczema 27.7%). In conclusion, approximately half (46.3 to 50.4%) of Asian children in Taiwan with allergic diseases are attributable to atopy.
Fluorescence/photoacoustic imaging-guided nanomaterials for highly efficient cancer theragnostic agent
Authors: Doan Vu Hoang Minh , Nguyen Van Tu , Mondal Sudip , Vo Thi Mai Thien , Ly Cao Duong , Vu Dinh Dat , Ataklti Gebremedhin Yonatan , Park Sumin , Choi Jaeyeop , Oh Junghwan
Published: August 2021

Imaging modalities combined with a multimodal nanocomposite contrast agent hold great potential for significant contributions in the biomedical field. Among modern imaging techniques, photoacoustic (PA) and fluorescence (FL) imaging gained much attention due to their non-invasive feature and the mutually supportive characteristic in terms of spatial resolution, penetration depth, imaging sensitivity, and speed. In this present study, we synthesized IR783 conjugated chitosan–polypyrrole nanocomposites (IR-CS–PPy NCs) as a theragnostic agent used for FL/PA dual-modal imaging. A customized FL and photoacoustic imaging system was constructed to perform required imaging experiments and create high-contrast images. The proposed nanocomposites were confirmed to have great biosafety, essentially a near-infrared (NIR) absorbance property with enhanced photostability. The in vitro photothermal results indicate the high-efficiency MDA-MB-231 breast cancer cell ablation ability of IR-CS–PPy NCs under 808 nm NIR laser irradiation. The in vivo PTT study revealed the complete destruction of the tumor tissues with IR-CS–PPy NCs without further recurrence. The in vitro and in vivo results suggest that the demonstrated nanocomposites, together with the proposed imaging systems could be an effective theragnostic agent for imaging-guided cancer treatment.
Evidence for a thromboembolic pathogenesis of lung cavitations in severely ill COVID-19 patients
Authors: Kruse Jan Matthias , Zickler Daniel , Lüdemann Willie M. , Piper Sophie K. , Gotthardt Inka , Ihlow Jana , Greuel Selina , Horst David , Kahl Andreas , Eckardt Kai-Uwe , Elezkurtaj Sefer
Published: August 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25–17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35–58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.
Chitosan-derived nanoparticles impede signal transduction in T790M lung cancer therapy
Authors: Huang Guojun , Chen Qi , Hu Jiawei , Mao Jianming , He Yunhong , Bai Hongzhen , Tang Guping
Published: August 2021

Chitosan-derived nanomedicine (DGA) to impede signal transduction and induce synergistic curative effect for T790M lung cancer therapy, by a combination with persuading mitochondrial dysfunction and inhibiting miRNA expression.
Borate and phosphite treatments of potato plants (Solanum tuberosum L.) as a proof of concept to reinforce the cell wall structure and reduce starch digestibility
Authors: Fiorillo Anna , Fogliano Vincenzo , Marra Mauro , Camoni Lorenzo
Published: August 2021

Potatoes are one of the main sources of carbohydrates in human diet, however they have a high glycaemic index (GI).
Highly diastereoselective entry to chiral oxindole-based β-amino boronic acids and spiro derivatives
Authors: Manenti Marco , Gazzotti Stefano , Lo Presti Leonardo , Molteni Giorgio , Silvani Alessandra
Published: August 2021

The Cu-catalysed addition of 1,1-diborylmethane to isatin ketimines, coupled with the application of Ellman's chiral auxiliary strategy, provides easy access to various boron-containing peptidomimetic derivatives and spirocyclic hemiboronic esters.
Microstructure and properties of SiC ceramic brazed with Zr–Cu composite filler metal
Authors: Zhou Bofang , Li Taohua , Zhang Hongxia , Hou Junliang
Published: August 2021

The microstructure and properties of SiC ceramic brazed with Zr–Cu composite filler metal were investigated.
Phosphorus speciation analysis of fatty-acid-based feedstocks and fast pyrolysis biocrudes via gel permeation chromatography inductively coupled plasma high-resolution mass spectrometry
Authors: Garcia-Montoto Victor , Verdier Sylvain , Dayton David C. , Mante Ofei , Arnaudguilhem Carine , Christensen Jan H. , Bouyssiere Brice
Published: August 2021

Renewable feedstocks, such as lignocelulosic fast pyrolysis oils and both vegetable oil and animal fats, are becoming a viable alternative to petroleum for producing high-quality renewable transportation fuels.
Pentafluoropyridine functionalized novel heteroatom-doped with hierarchical porous 3D cross-linked graphene for supercapacitor applications
Authors: Kumar Amit , Tan Chih-Shan , Kumar Nagesh , Singh Pragya , Sharma Yogesh , Leu Jihperng , Huang E.-Wen , Winie Tan , Wei Kung-Hwa , Tseng Tseung Yuen
Published: August 2021

Demonstration of the effect of Gibbs free energy (GT = −643.26 eV) on N, P, F co-doped graphene, simulated via density functional theory (DFT).
Preparation of solution processed photodetectors comprised of two-dimensional tin(ii) sulfide nanosheet thin films assembled via the Langmuir–Blodgett method
Authors: Norton Kane , Jacobs Janet , Neilson Joseph , Hopkinson David , Mokhtar Mohammad Z. , Curry Richard J. , Lewis David J.
Published: August 2021

Norton et al. report the manufacture of fully solution processed photodetectors based on two-dimensional tin(ii) sulfide assembled via the Langmuir–Blodgett method.
Effect of anisotropic conductivity of Ag2S-modified ZnmIn2S3+m (m = 1, 5) on the photocatalytic properties in solar hydrogen evolution
Authors: Liu Jingyuan , Xue Xinyi , Zhou Xin , Chen Gang , Liu Wei
Published: August 2021

The anisotropic carrier transport property of Ag2S/Zn5In2S8 is substantially stronger than that of Ag2S/ZnIn2S4, resulting in higher bulk carrier separation rate and photocatalytic hydrogen evolution performance of Ag2S/Zn5In2S8.
Surface-modified boron nitride as a filler to achieve high thermal stability of polymer solid-state lithium-metal batteries
Authors: Zhang XinLong , Guo WenYao , Zhou Luozeng , Xu Qunjie , Min Yulin
Published: August 2021

A polyethylene oxide composite polymer electrolyte with high thermal stability and mechanical strength was prepared via the modification of boron nitride. The modification was beneficial for the thermal conductivity, enhancing the thermal stability of the battery.
Colloidal synthesis of lead-free Cs2TiBr6−xIxperovskite nanocrystals
Authors: Liga Shanti Maria , Konstantatos Gerasimos
Published: August 2021

First colloidal synthesis of pure and mixed bromide–iodide cesium titanium perovskite nanocrystals. By adjusting the halide precursors’ ratio, the bandgap can be tuned from 2.3 eV to 1.2 eV.
Colorimetric metasurfaces shed light on fibrous biological tissue
Authors: Haddadin Zaid , Pike Trinity , Moses Jebin J. , Poulikakos Lisa V.
Published: August 2021

Fibrotic diseases affect all human organs (left), yet the selective visualization of tissue microstructure remains challenging in clinical and industrial settings. Colorimetric metasurfaces (right) address this challenge with an on-chip platform.
The Contribution of Vocabulary, Grammar, and Phonological Awareness Across a Continuum of Narrative Ability Levels in Young Children
Authors: Khan Kiren S. , Logan Jessica , Justice Laura M. , Bowles Ryan P. , Piasta Shayne B.
Published: August 2021

Purpose

Narrative skill represents a higher-level linguistic skill that shows incremental development in the preschool years. During these years, there are considerable individual differences in this skill, with some children being highly skilled narrators (i.e., precocious) relative to peers of their age. In this study, we explored the contribution of three lower-level language skills to a range of narrative abilities, from children performing below expected levels for their age to those performing much higher than the expected levels for their age. We speculated that individual differences in lower-level skills would contribute meaningfully to variability in narrative skills.

Method

Using a sample of 336 children between 3 and 6 years of age (M= 4.27 years,SD= 0.65), both multiple regression and quantile regression approaches were used to explore how vocabulary, grammar, and phonological awareness account for variance in children's “narrative ability index” (NAI), an index of how children scored on the Narrative Assessment Protocol–Second Edition relative to the expected performance for their age.

Results

Multiple regression results indicated that lower-level language skills explained a significant amount of variance (approximately 13%) in children's NAI scores. Quantile regression results indicated that phonological awareness and vocabulary accounted for significant variance in children's NAI scores at lower quantiles. At the median quantile, vocabulary and grammar accounted for significant variance in children's NAI scores. For precocious narrators, only vocabulary accounted for a significant amount of variance in children's NAI scores.

Conclusion

Results indicate that lower-level language skills work in conjunction to support narrative skills at different ability levels, improving understanding of how lower-level language skills contribute across a spectrum of higher-level linguistic abilities.
Speech-Language Therapy Clinical Services, Student Education, and Practical Training in the Time of COVID-19: The Rise of Telepractice, Telesupervision, and Distance Learning in Cyprus
Authors: Voniati Louiza , Kilili-Lesta Margarita , Christopoulou Maria C.
Published: August 2021

Purpose

This study aimed to outline the changing forms of speech-language pathology practices, for both clinical services, as well as the profession's education and practicum training in the time of COVID-19 at the European University Cyprus (EUC). This study also aimed to document the steps taken to continue service delivery safely and effectively for both the EUC's Speech, Language and Hearing Clinic's clients and the speech-language therapy students completing their practicum.

Method

The steps for the access to and continuity of speech-language therapy services and education/training are outlined chronologically, throughout the different phases of the COVID-19 pandemic status in the country. The rise of telepractice, telesupervision, and distance learning, adapted as solutions to the obstacles caused by the pandemic, are explained in detail, while the benefits and limitations are discussed at each step. The professional development that had to take place before this rise is also described.

Conclusions

The utilization of online/telecommunication technology for education, practical training, and speech-language pathologist service delivery during the time of COVID-19 in Cyprus is here to stay and will probably affect the future of the profession's clinical practice, and consequently, training programs in Cyprus in the years to come. It is uncertain if the effects of such adaptations can generalize in other populations or countries, especially where regulations and policies are already in place, or where the technological foundation is not similar. Through the benefits and limitations presented, conclusions are drawn for the future applications of telepractice, telesupervision, and distance learning post–COVID-19. Suggestions are made for the possible areas of future research, concerning clinical practice and clinical practicum training, as well as for the need to define regulations and establish these types of services in the country.

Supplemental Material

https://doi.org/10.23641/asha.15057396
Infrasound signals of fireballs detected by the Geostationary Lightning Mapper
Authors: Ott T. , Drolshagen E. , Koschny D. , Drolshagen G. , Pilger C. , Gaebler P. , Hupe P. , Mialle P. , Vaubaillon J. , Poppe B.
Published: August 2021

Context. Fireballs are particularly bright meteors produced by large meteoroids or small asteroids that enter the Earth’s atmosphere. These objects, of sizes from some tens of centimetres to a few metres, are difficult to record with typical meteor detection methods. Therefore, their characteristics and fluxes are still not well known. Infrasound signals can travel particularly well through the atmosphere over large distances. Impacting meteoroids and asteroids can produce those signals, as well as space-detectable optical signatures.

Aims. This paper aims to study and compare fireball data from the Geostationary Lightning Mappers (GLMs) on board the two Geostationary Observational Environmental Satellites (GOES-16 and GOES-17) and the data from the infrasound stations of the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organisation (Vienna, Austria). The overall goal is a more accurate energy estimation of meteoroids and asteroids as well as a better understanding of both methods.

Methods. The data consist of the brightest 50 events in the GLM database, as identified by recorded peak energy. For 24 of those fireballs, a significant signature could be identified in infrasound data. The data are supplemented by, if available, optical fireball data based on US government sensors on satellites provided by NASA’s Center for Near-Earth Object Studies (CNEOS).

Results. The energies as computed from the GLM data range from 3.17 × 107 J up to 1.32 × 1012 J with a mean of 1.65 × 1011 J. The smallest meteoroid recorded by infrasound had an energy of about 1.8 × 109 J, the largest one of about 9.6 × 1013 J, and the mean energy is 5.2 × 1012 J. For 19 events, data were simultaneously available from all three data sources. A comparison between the energy values for the same event as determined from the different data sources indicates that CNEOS tends to give the lowest energy estimations. Analysis of infrasound data results in the largest derived energies.

Conclusions. The energies derived using the three methods often deviate from one another by as much as an order of magnitude. This indicates a potential observational bias and highlights uncertainties in fireball energy estimation. By determining the fireball energy with another independent method, this study can help to better quantify and address this range of uncertainty.