bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pathogenic Missense Variant in NFKB1 Causes Common Variable Immunodeficiency Due to Detrimental Protein Damage
Authors: Fliegauf Manfred , Krüger Renate , Steiner Sophie , Hanitsch Leif Gunnar , Büchel Sarah , Wahn Volker , von Bernuth Horst , Grimbacher Bodo
Published: April 2021

In common variable immunodeficiency (CVID), heterozygous damaging NFKB1 variants represent the most frequent monogenic cause. NFKB1 encodes the precursor p105, which undergoes proteasomal processing to generate the mature NF-κB transcription factor subunit p50. The majority of NFKB1 sequence changes comprises missense variants of uncertain significance (VUS), each requiring functional evaluation to assess causality, particularly in families with multiple affected members presenting with different phenotypes. In four affected members of a German family, all diagnosed with CVID, we identified a previously uncharacterized heterozygous NFKB1 missense variant (c.1049A>G; p.Tyr350Cys). The clinical phenotypes varied markedly regarding onset, frequency and severity of infections. Consistent immunologic findings were hypogammaglobulinemia with normal specific antibody response to protein- and polysaccharide-based vaccinations, reduced switched memory B cells and decreased lymphocyte proliferation upon stimulation with the B cell mitogen SAC. To assess the pathogenicity of the NFKB1 missense variant, we employed immunophenotyping and functional analyses in a routine in vitro cell culture model. Following site-directed mutagenesis to introduce the variant into overexpression vectors encoding EGFP-fused p105 or p50, we analyzed transiently transfected HEK293T cells by confocal imaging and Western blotting. The cytoplasmic p105-Tyr350Cys precursor gained only weak expression levels indicating accelerated decay. The missense change disabled processing of the precursor to prevent the generation of mutant p50. Unlike the wildtype p50, the overexpressed mutant p50-Tyr350Cys was also not sustainable and showed a conspicuous subnuclear mislocalization with accumulation in dense aggregates instead of a homogenous distribution. Electrophoretic mobility shift assays, fluorescence-based reporter gene analyses and co-transfection experiments however demonstrated, that the DNA-binding activity of p50-Tyr350Cys and the interaction with RelA(p65), IκBα and wildtype p50 were preserved. Mutation carriers had reduced p105 and p50 levels, indicating insufficient protein amounts as the most likely primary defect. In conclusion, the missense variant c.1049A>G caused a detrimental defect, preventing the persistent expression of both, the p105-Tyr350Cys precursor and the mature p50-Tyr350Cys. The variable clinical phenotypes among affected family members sharing an identical pathogenic NFKB1 variant support a disease mechanism provoked by a p105/p50 (haplo)insufficient condition.
Real-World Experiences With Facilitated Subcutaneous Immunoglobulin Substitution in Patients With Hypogammaglobulinemia, Using a Three-Step Ramp-Up Schedule
Authors: Hustad Nina B. , Degerud Hanna M. , Hjelmerud Ingrid , Fraz Mai S. A. , Nordøy Ingvild , Trøseid Marius , Fevang Børre , Aukrust Pål , Jørgensen Silje F.
Published: April 2021

Immunoglobulin replacement therapy with facilitated subcutaneous immunoglobulin (fSCIg) can be self-administrated at home and given at longer intervals compared to subcutaneous immunoglobulin (SCIg) therapy, but real-word experience of home-based fSCIg therapy is limited. Herein we present our real-word clinical experiences with home-based fSCIg therapy using a three-step ramp-up schedule. We registered data from all patients with immunodeficiency starting fSCIg from 01.01.2017 to 31.12.2019. For comparison we also included patients starting conventional SCIg training. Fifty-four patients followed for a median of 18 months (IQR 12, range 0–40), received fSCIg training, and 84 patients received conventional SCIg training. Out of 54 patients starting with fSCIg, 41 patients had previous experience with conventional SCIg therapy, and the main reason for starting fSCIg was ‘longer intervals between therapies’ (n=48). We found an increase in training requirement for fSCIg (3 ± 1 [2-9] days) compared to conventional SCIg (2 ± 0 [1-7] days), P< 0.001 (median ± IQR, [range]). For fSCIg training, IgG levels were stable from baseline (8.9 ± 2.3 g/L), 3-6 months (10.2 ± 2.2 g/L) and 9-12 months (9.9 ± 2.3 g/L), P= 0.11 (mean ± SD). The most common side-effect was: ‘rubor around injection site’ (n=48, 89%). No patients experienced severe adverse events (grade 3-4). Thirteen patients (24%) discontinued fSCIg therapy due to local adverse events (n=9), cognitive/psychological difficulties (n=6) and/or systemic adverse events (n=3). In conclusion, fSCIg training using a three-step ramp-up schedule is safe and well tolerated by the majority of patients, but requires longer training time compared to conventional SCIg.
Palm Oil-Based Enriched Diets for the Rotifer, Brachionus plicatilis, Improved the Growth of Asian Seabass (Lates calcarifer) Larvae
Authors: Safiin Nik Siti Zaimah , Mustafa Saleem , Ching Fui Fui , Shapawi Rossita
Published: April 2021

Different types and inclusion levels of palm oil were incorporated in the enriched diets of L-type rotifer, Brachionus plicatilis, and fed to Asian seabass (Lates calcarifer) larvae. The dietary fish oil was replaced with either 50 or 75% of crude palm oil, CPO (CPO50, CPO75) and refined bleached deodorized palm olein, RPO (RPO50, RPO75). The enriched diet containing 100% fish oil (FO100) was used as the experimental control. Triplicate groups of the fish larvae of initial length 2.72 ± 0.14 mm were fed with enriched rotifer for 15 days. In general, palm oil-based enriched diets performed better than the control diet (FO100). Specifically, final mean body weight (31.3 ± 9.2 mg), final mean total length (11.5 ± 1.6 mm), SGR (29.0 ± 1.4%/day) and WG (7,769.4 ± 1,510.8%) of Asian seabass larvae fed RPO75 were significantly higher (P < 0.05) compared to those fed the other palm oil-based diet and FO100. The rotifer enriched with palm oil significantly affected the body proximate composition and fatty acid profiles of the fed larvae. The present study suggests that RPO and CPO can be considered as a good alternative dietary lipid for enrichment of rotifer to positively influence the nutritional requirements of the Asian seabass larvae and support their survival and growth.
Traceability Approaches for Marine Genetic Resources Under the Proposed Ocean (BBNJ) Treaty
Authors: Humphries Fran , Rabone Muriel , Jaspars Marcel
Published: April 2021

Negotiations are underway for a new treaty for the conservation and sustainable use of biodiversity of areas beyond national jurisdiction under the United Nations Convention on the Law of the Sea. Points of contention in the negotiation concern marine genetic resources and questions of monetary and/or non-monetary benefit sharing arising from their use. Tracing the origin of marine genetic resources used in scientific research, development and commercialization may offer the evidence needed to prove they came from areas beyond national jurisdiction and that benefit sharing is owed. Traceability is complex and multidisciplinary: involving legal, scientific and informatics considerations. We look at different traceability approaches within national jurisdictions and how these might provide lessons for the proposed treaty, using one of the few case studies available to trace the commercial development of a marine genetic resource from areas beyond national jurisdiction. We discuss this case study in relation to existing legal frameworks including the Nagoya Protocol and other systems based on open sharing of information and materials, including existing scientific practice. We conclude that a well-designed traceability system tailored to the unique geographical, political and jurisdictional characteristics of areas beyond national jurisdiction could lead to more equitable outcomes for the sharing of benefits from the use of marine genetic resources. Our key recommendations are that any traceability mechanism needs to be light touch, integrated with existing systems such as bioinformatics databases and not impose additional burdens on scientific users. Systems should be designed to improve scientific knowledge of ocean biodiversity to allow better conservation measures to be developed. If treaty negotiators engage commercial sectors to find workable policy solutions for the draft treaty that promote greater transparency and data sharing from these sectors, there may be a greater chance for traceability mechanisms to support benefit sharing.
Reconstruction and Analysis of the Immune-Related LINC00987/A2M Axis in Lung Adenocarcinoma
Authors: Ma Jiakang , Lin Xiaoyan , Wang Xueting , Min Qingqing , Wang Tonglian , Tang Chaozhi
Published: April 2021

Enhancer RNAs (eRNAs) participate in tumor growth and immune regulation through complex signaling pathways. However, the immune-related function of the eRNA-mRNA axis in lung adenocarcinoma (LUAD) is unclear. Data on the expression of eRNAs and mRNAs were downloaded from The Cancer Genome Atlas, GEO, and UCSC Xena, including LUAD, and pan-cancer clinical data and mutational information. Immune gene files were obtained from ImmLnc and ImmPort databases. Survival indices, including relapse-free and overall survival, were analyzed using the Kaplan–Meier and log-rank methods. The level of immune cell infiltration, degree of tumor hypoxia, and tumor cell stemness characteristics were quantified using the single-sample gene set enrichment analysis algorithm. The immune infiltration score and infiltration degree were evaluated using the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden and microsatellite instability were examined using the Spearman test. The LUAD-associated immune-related LINC00987/A2M axis was down-regulated in most cancer types, indicating poor survival and cancer progression. Immune cell infiltration was closely related to abnormal expression of the LINC00987/A2M axis, linking its expression to a possible evaluation of sensitivity to checkpoint inhibitors and response to chemotherapy. Abnormal expression of the LINC00987/A2M axis was characterized by heterogeneity in the degree of tumor hypoxia and stemness characteristics. The abnormal distribution of immune cells in LUAD was also verified through pan-cancer analysis. Comprehensive bioinformatic analysis showed that the LINC00987/A2M axis is a functional and effective tumor suppressor and biomarker for assessing the immune microenvironment and prognostic and therapeutic evaluations of LUAD.
Vestibular Preservation After Cochlear Implantation Using the Round Window Approach
Authors: Tsukada Keita , Usami Shin-ichi
Published: April 2021

Background: The development of less traumatic surgical techniques, such as the round window approach (RWA), as well as the use of flexible electrodes and post-operative steroid administration have enabled the preservation of residual hearing after cochlear implantation (CI) surgery. However, consideration must still be given to the complications that can accompany CI. One such potential complication is the impairment of vestibular function with resulting vertigo symptoms. The aim of our current study was to examine the changes in vestibular function after implantation in patients who received CI using less traumatic surgery, particularly the RWA technique.

Methods: Sixty-six patients who received CI in our center were examined by caloric testing, cervical vestibular evoked myogenic potential (cVEMP) and ocular VEMP (oVEMP) before or after implantation, or both, to obtain data on semicircular canal, saccular and utricular function, respectively. Less traumatic CI surgery was performed by the use of the RWA and insertion of flexible electrodes such as MED-EL FLEX soft, FLEX 28, and FLEX 24 (Innsbruck, Austria).

Results: Caloric response and the asymmetry ratio of cVEMP and oVEMP were examined before and after implantation using less traumatic surgical techniques. Compared with before implantation, 93.9, 82.4, and 92.5% of the patients showed preserved vestibular function after implantation based on caloric testing, cVEMP and oVEMP results, respectively. We also examined the results for vestibular function by a comparison of the 66 patients using the RWA and flexible electrodes, and 17 patients who underwent cochleostomy and insertion of conventional or hard electrodes. We measured responses using caloric testing, cVEMP and oVEMP in patients after CI. There were no differences in the frequencies of abnormal caloric and oVEMP results in the implanted ears between the RWA and cochleostomy. On the other hand, the frequency of abnormal cVEMP responses in the implanted ears in the patients who received implantation by cochleostomy was significantly higher than that in the patients undergoing surgery using the RWA.

Conclusion: Patients receiving CI using less traumatic surgical techniques such as RWA and flexible electrodes have reduced risk of damage to vestibular function.
Prognostic Factors and Models for Changes in Cognitive Performance After Multi-Domain Cognitive Training in Healthy Older Adults: A Systematic Review
Authors: Roheger Mandy , Liebermann-Jordanidis Hannah , Krohm Fabian , Adams Anne , Kalbe Elke
Published: April 2021

Background: Cognitive Training (CT) may contribute to the maintenance and even enhancement of cognitive functions in healthy older adults. However, the question who benefits most from multi-domain CTs is still highly under-investigated.

Objective: The goal is to investigate prognostic factors and models for changes in cognitive test performance in healthy older adults after a multi-domain CT.

Methods: The data bases MEDLINE, Web of Science Core Collection, CENTRAL, and PsycInfo were searched up to July 2019. Studies investigating prognostic factors and/or models on cognitive outcomes (global cognition, memory, attention, executive functions, language, visuo-spatial abilities) after conducting a multi-domain CT in healthy older adults were included. Risk of Bias was assessed using the QUIPS and the PROBAST tool.

Results: 23 prognostic factor and model studies were included. Results indicate a high heterogeneity regarding the conducted multi-domain CTs, the investigated prognostic factors, the investigated outcomes, and the used statistical approaches. Age and neuropsychological performance at study entry were the most investigated predictors, yet they show inconsistent results.

Conclusion: Data on prognostic factors and models of changes after multi-domain CT are still too rare and inconsistent to draw clear conclusions due to statistical shortcomings and low reporting quality. Approaches for future research are outlined.

Registration:https://www.crd.york.ac.uk/prospero/, ID: CRD42020147531
Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene
Authors: Ma Suk-Ling , Chen Lu Hua , Lee Chi-Chiu , Lai Kelly Y. C. , Hung Se-Fong , Tang Chun-Pan , Ho Ting-Pong , Shea Caroline , Mo Flora , Mak Timothy S. H. , Sham Pak-Chung , Leung Patrick W. L.
Published: April 2021

Background: Recent findings indicated a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), as well as shared genetic influences on them. The latter might contribute at least partly to the former clinical scenario. This study aimed at investigating whether SHANK genes were potential pleiotropic genes to the two said disorders, underlying their genetic overlap.

Methods: This study recruited 298 boys with ADHD (including 256 family trios of 1 ADHD boy and his 2 biological parents), 134 boys with ASD, 109 boys with both ADHD and ASD, and 232 typically developing boys as community controls. They were aged between 6 and 11 years old.

Results: There was no significant difference in allele frequency of a number of single nucleotide polymorphisms (SNPs) in SHANK2/SHANK3 between the three clinical groups (ADHD, ASD, and ADHD + ASD) and between the two control groups (community controls and pseudo-controls), respectively. The three clinical groups and the two control groups were thus, respectively, combined. A comparison between the two aggregated samples identified significant evidence of disease association for three SHANK2 SNPs with both ADHD and ASD, even after multiple testing correction: rs11236616 (OR = 0.762, permuted p = 0.0376), rs7106631 (OR = 0.720, permuted p = 0.0034), and rs9888288 (OR = 0.770, permuted p = 0.0407). Comparisons among individual groups pointed to a similar trend of findings.

Conclusion:SHANK2 could be considered a potential pleiotropic gene underlying the genetic overlap between ADHD and ASD. This might contribute partly to their high comorbidity in the afflicted children.
Patterns of Nutrient Intake in Relation to Sarcopenia and Its Components
Authors: Bagheri Amir , Hashemi Rezvan , Heshmat Ramin , Motlagh Ahmadreza Dorosty , Esmaillzadeh Ahmad
Published: April 2021

Background: Despite the associations between individual nutrients and sarcopenia, we are aware of no information about the link between patterns of nutrient intake and odds of sarcopenia and its components. The present study aimed to examine the association between nutrient-based dietary patterns and sarcopenia and its components among the Iranian adult population.

Methods: In this population-based, cross-sectional study, we enrolled 300 elderly adults (150 men and 150 women) aged ≥55 years by using a cluster random sampling method. Dietary intakes of the study population were assessed using a validated food frequency questionnaire. Principal component analysis was conducted to derive nutrient patterns based on a daily intake of 33 nutrients. Muscle mass, muscle strength, and gait speed were measured according to standard methods. Sarcopenia and its components were defined based on the European Working Group on Sarcopenia.

Results: Three major nutrient-based dietary patterns were identified: (1) the “pro-vit pattern” that was high in pantothenic (B5), cobalamin (B12), calcium, protein, phosphor, riboflavin (B2), zinc, cholesterol, saturated fat, folate, niacin (B3), selenium, vitamin D, vitamin K, and vitamin A; (2) the “anti-inflammatory” pattern, which was rich in polyunsaturated fat, monounsaturated fat, copper, vitamin E, omega-3, magnesium, iron, pyridoxine (B6), sodium, and caffeine; and (3) the “carbo-vit” patternm which is characterized by high intake of fructose, glucose, dietary fiber, biotin, potassium, thiamin (B1), vitamin C, and chromium. After adjusting for confounders, subjects in the top tertile of the anti-inflammatory pattern had lower odds of sarcopenia (OR 0.25; 95% CI 0.10–0.63) and low muscle strength (OR: 0.46; 95% CI: 0.22–0.96) than those in the bottom tertile. Greater adherence to the carbo-vit pattern was inversely associated with the odds of low gait speed (OR: 0.46; 95% CI: 0.235–0.93).

Conclusion: Major nutrient-based dietary patterns were significantly associated with sarcopenia and its components. Further studies are required to confirm our findings.
Identification and Validation of SNP-Containing Genes With Prognostic Value in Gastric Cancer via Integrated Bioinformatics Analysis
Authors: Li Hui , Guo Jing , Cheng Guang , Wei Yucheng , Liu Shihai , Qi Yaoyue , Wang Gongjun , Xiao Ruoxi , Qi Weiwei , Qiu Wensheng
Published: April 2021

Background

Gastric cancer is one of the most common malignancies worldwide. Although the diagnosis and treatment of this disease have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer.

Methods

SNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using DAVID software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR and Western blotting were used to verify the expression of the hub genes in gastric cancer cells.

Results

From the database, 945 genes with mutations in more than 25 samples were identified. The PPI network had 360 nodes and 1616 edges. Finally, cytoHubba identified six key genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients.

Conclusion

Our results indicate that TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4 may be key genes for the development and prognosis of gastric cancer. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients.
Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer
Authors: Huang Haiming , Du Jialin , Jin Bo , Pang Lu , Duan Nan , Huang Chenwei , Hou Jiayin , Yu Wei , Hao Han , Li Haixia
Published: April 2021

Background

The recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.

Methods

RNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.

Results

RNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.

Conclusions

These findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.
Relationship Between National Economic Development and Body Mass Index in Chinese Children and Adolescents Aged 5–19 From 1986 to 2019
Authors: Bu Te , Popovic Stevo , Huang Huiqing , Fu Tao , Gardasevic Jovan
Published: April 2021

Obesity represents a major risk factor for population health. No studies have evaluated how economic expansion impacts the prevalence of obesity. The purpose of this study was to assess the relationship between national economic development and body mass index (BMI) in Chinese children and adolescents. Data of mean BMI in children and adolescents aged 5–19 from 1986 to 2019 were extracted from an international database of cardiometabolic risk factors. Chinese economic development was quantified by the gross domestic product (GDP), which was extracted from the International Monetary Fund. The relationships between GDP and BMI were assessed in 1-year age groups for ages 5–19 years. In addition, the linear regression from the main data and estimated GDP growth allowed the projections of mean BMI for each age group between 2020 and 2025. The results suggest there was a linear increase in BMI over years, which means that there has been a steady increase in BMI over the economic expansion. Overall, 97% of the variance (Pearson correlation coefficient) of BMI in boys can be explained by the GDP expansion, and the same pattern (98% of the variance) occurred in girls. Projected mean BMI were provided for constructing future national strategies to prevent overweight and obesity in youth. In conclusion, BMI in children and adolescents aged 5–19 trended upwards between 1986 and 2019. Our analyses for the first time suggest that globalization has a major impact on BMI in China. Economic expansion was highly predictive of BMI increases.
Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms
Authors: Belluardo Natale , Mudò Giuseppa , Di Liberto Valentina , Frinchi Monica , Condorelli Daniele F. , Traversa Ugo , Ciruela Francisco , Ciccarelli Renata , Di Iorio Patrizia , Giuliani Patricia
Published: April 2021

Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated.
Designing Phononic Band Gaps With Sticky Potentials
Authors: Zheng Yuanjian , Mahajan Shivam , Chattoraj Joyjit , Pica Ciamarra Massimo
Published: April 2021

Spectral gaps in the vibrational modes of disordered solids are key design elements in the synthesis and control of phononic meta-materials that exhibit a plethora of novel elastic and mechanical properties. However, reliably producing these gaps often require a high degree of network specificity through complex control optimization procedures. In this work, we present as an additional tool to the existing repertoire, a numerical scheme that rapidly generates sizeable spectral gaps in absence of any fine tuning of the network structure or elastic parameters. These gaps occur even in disordered polydisperse systems consisting of relatively few particles (N ~ 102 − 103). Our proposed procedure exploits sticky potentials that have recently been shown to suppress the formation of soft modes, thus effectively recovering the linear elastic regime where band structures appear, at much shorter length scales than in conventional models of disordered solids. Our approach is relevant to design and realization of gapped spectra in a variety of physical setups ranging from colloidal suspensions to 3D-printed elastic networks.
Effects of Heat Waves During Post-natal Development on Mitochondrial and Whole Body Physiology: An Experimental Study in Zebra Finches
Authors: Ton Riccardo , Stier Antoine , Cooper Christine E. , Griffith Simon C.
Published: April 2021

Human-induced climate change is increasing the frequency, duration, and intensity of heat waves and exposure to these extreme temperatures impacts individual physiology and performance (e.g., metabolism, water balance, and growth). These traits may be susceptible to thermal conditions experienced during embryonic development, but experiments focusing on post-natal development are scant. Documented effects of heat waves on whole-body metabolism may reflect changes in mitochondrial function, but most studies do not measure physiological traits at both the cellular and whole organism levels. Here, we exposed nests of zebra finches to experimentally simulated heat waves for 18 days after hatching and measured body mass, growth rate, whole-body metabolic rate, body temperature, wet thermal conductance, evaporative water loss, and relative water economy of chicks at three ages corresponding to ectothermic (day 5), poikilothermic (day 12), and homoeothermic (day 50) stages. Additionally, we measured mitochondrial bioenergetics of blood cells 80 days post-hatch. While early-life exposure to heat wave conditions did not impact whole body metabolic and hygric physiology, body temperature was lower for birds from heated compared with control nests at both 12 and 50 days of age. There was also an effect of nest heating at the cellular level, with mitochondria from heated birds having higher endogenous and proton-leak related respiration, although oxidative phosphorylation, maximum respiratory capacity, and coupling efficiency were not impacted. Our results suggest that early-life exposure to high ambient temperature induces programming effects on cellular-level and thermal physiology that may not be apparent for whole-animal metabolism.
Senescence-Specific Expression of RAmy1A Accelerates Non-structural Carbohydrate Remobilization and Grain Filling in Rice (Oryza sativa L.)
Authors: Ouyang Ning , Sun Xuewu , Tan Yanning , Sun Zhizhong , Yu Dong , Liu Hai , Liu Citao , Liu Ling , Jin Lu , Zhao Bingran , Yuan Dingyang , Duan Meijuan
Published: April 2021

Remobilization of pre-anthesis NSCs (non-structural carbohydrates) is significant for effective grain filling in rice (Oryza sativa L.). However, abundant starch particles as an important component of NSCs are still present in the leaf sheath and stem at the late stage of grain filling. There are no studies on how bioengineering techniques can be used to improve the efficiency of NSC remobilization. In this study, RAmy1A was expressed under the senescence-specific promoter of SAG12, which was designed to degrade starch in the leaf sheath and stem during grain filling. RAmy1A mRNA successfully accumulated in the leaf, stem, and sheath of transgenic plants after anthesis. At the same time, the starch and total soluble sugar content in the leaf, stem, and leaf sheath were obviously decreased during the grain-filling period. The photosynthetic rate of transgenic lines was higher than that of the wild types by an average of 4.0 and 9.9%, at 5 and 10 days after flowering, respectively. In addition, the grain-filling rate of transgenic lines was faster than that of the wild types by an average of 26.09%. These results indicate an enhanced transport efficiency of NSCs from source tissues in transgenic rice. Transgenic rice also displayed accelerated leaf senescence, which was hypothesized to contribute to decreased grain weight.
Stop Blaming me for What Others Did to you: New Alternative Masculinity’s Communicative Acts Against Blaming Discourses
Authors: Schubert Tinka , Aguilar Consol , Kim Kyung Hi , Gómez Aitor
Published: April 2021

Some feminist discourses blame some men for gender inequality, gender domination, and gender-based violence. Some women use such discourse as a perfect scenario to criticize some men’s behavior. Indeed, they usually do so with Oppressed Traditional Masculinities (OTM) but not with Dominant Traditional Masculinities (DTM), who are the men who were violent with those women and with whom some of those women chose to have relationships. However, there have always been men who have been on the side of women and have never committed violence against them. Therefore, New Alternative Masculinities (NAM) reject being indicated as guilty of the violence committed against women by DTM. Through a communicative approach, applying six semi-structured interviews with a communicative orientation and a communicative data analysis of all information, this article explores both women’s communicative acts that blame OTM for what DTM have done to women and NAM’s reactions to these accusations to stop such blaming to make it possible to overcome hegemonic discourses.
What's Happened to Italian Adolescents During the COVID-19 Pandemic? A Preliminary Study on Symptoms, Problematic Social Media Usage, and Attachment: Relationships and Differences With Pre-pandemic Peers
Authors: Muzi Stefania , Sansò Alessandra , Pace Cecilia Serena
Published: April 2021

Italian adolescents were confined at home for 3 months due to the COVID-19 pandemic, which exposed them to feelings of fear, uncertainty, and loneliness that may have increased their vulnerability to emotional-behavioral symptoms (e.g., anxiety) and binge-eating attitudes. Potential risk factors for these psychopathological symptoms are problematic social media usage and attachment insecurity. Therefore, this study aimed: (1) to assess emotional-behavioral symptoms, binge eating, problematic social media usage, and attachment representations of adolescents during the pandemic, comparing them with prepandemic similar samples; (2) to investigate relationships among variables, exploring the role of problematic social media usage and insecure attachment as risk factors for more psychopathological symptoms. Participants were 62 community adolescents aged 12–17 years, enrolled through schools, and assessed online through the following measures: Youth Self-Report for emotional-behavioral problems, Binge-Eating Scale for binge eating, Social Media Disorder Scale for problematic social media usage, and the Friends and Family Interview for attachment. The main results were: (1) 9.4% of adolescents showed clinical rates of emotional-behavioral symptoms and 4.8% of binge eating attitudes. The comparison with pre-pandemic samples revealed that pandemic teenagers showed lower internalizing, but higher other problems (e.g., binge drinking, self-destructive behaviors) and more problematic social media usage than pre-pandemic peers. No differences in binge-eating attitudes and attachment were revealed (76% secure classifications). (2) Problematic social media usage was related to more binge eating and emotional-behavioral problems, predicting 5.4% of both delinquent and attention problems. Attachment disorganization predicted 16.5% of internalizing problems, somatic complaints, and social and identity-related problems. In conclusion, confinement did not increase adolescents' internalizing symptoms -i.e., vulnerability to mood disorders of an anxious-depressive type- which even decreased. However, teenagers may have expressed their discomfort through other problems and symptoms of social media disorder. Further studies should explore the role of adolescents' problematic social media usage and attachment insecurity as risk factors for additional psychopathological symptoms.
Temporal Changes in Reverse Torque of Locking-Head Screws Used in the Locking Plate in Segmental Tibial Defect in Goat Model
Authors: Grzeskowiak Remigiusz M. , Rifkin Rebecca E. , Croy Elizabeth G. , Steiner Richard C. , Seddighi Reza , Mulon Pierre-Yves , Adair Henry S. , Anderson David E.
Published: April 2021

The objective of this study was to evaluate changes in peak reverse torque (PRT) of the locking head screws that occur over time. A locking plate construct, consisting of an 8-hole locking plate and 8 locking screws, was used to stabilize a tibia segmental bone defect in a goat model. PRT was measured after periods of 3, 6, 9, and 12 months of ambulation. PRT for each screw was determined during plate removal. Statistical analysis revealed that after 6 months of loading, locking screws placed in position no. 4 had significantly less PRT as compared with screws placed in position no. 5 (p < 0.05). There were no statistically significant differences in PRT between groups as a factor of time (p > 0.05). Intracortical fractures occurred during the placement of 151 out of 664 screws (22.7%) and were significantly more common in the screw positions closest to the osteotomy (positions 4 and 5, p < 0.05). Periosteal and endosteal bone reactions and locking screw backout occurred significantly more often in the proximal bone segments (p < 0.05). Screw backout significantly, negatively influenced the PRT of the screws placed in positions no. 3, 4, and 5 (p < 0.05). The locking plate-screw constructs provided stable fixation of 2.5-cm segmental tibia defects in a goat animal model for up to 12 months.
Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED)
Authors: Huenerfauth Enrice , Nessler Jasmin , Erath Johannes , Tipold Andrea
Published: April 2021

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.
Editorial for the Special Issue on “Bayesian Networks: Inference Algorithms, Applications, and Software Tools”
Authors: Codetta-Raiteri Daniele
Published: April 2021

In the field of Artificial Intelligence, Bayesian Networks (BN) [...]
Adaptive Cruise Control System Evaluation According to Human Driving Behavior Characteristics
Authors: Liu Lin , Zhang Qiang , Liu Rui , Zhu Xichan , Ma Zhixiong
Published: April 2021

With the rapid and wide implementation of adaptive cruise control system (ACC), the testing and evaluation method becomes an important question. Based on the human driver behavior characteristics extracted from naturalistic driving studies (NDS), this paper proposed the testing and evaluation method for ACC systems, which considers safety and human-like at the same time. Firstly, usage scenarios of ACC systems are defined and test scenarios are extracted and categorized as safety test scenarios and human-like test scenarios according to the collision likelihood. Then, the characteristic of human driving behavior is analyzed in terms of time to collision and acceleration distribution extracted from NDS. According to the dynamic parameters distribution probability, the driving behavior is divided into safe, critical, and dangerous behavior regarding safety and aggressive and normal behavior regarding human-like according to different quantiles. Then, the baselines for evaluation are designed and the weights of different scenarios are determined according to exposure frequency, resulting in a comprehensive evaluation method. Finally, an ACC system is tested in the selected test scenarios and evaluated with the proposed method. The tested vehicle finally got a safety score of 0.9496 (full score: 1) and a human-like score as fail. The results revealed the tested vehicle has a remarkably different driving pattern to human drivers, which may lead to uncomfortable ride experience and user-distrust of the system.
Prevalence of Antibiotic-Resistant Bacteria ESKAPE among Healthy People Estimated by Monitoring of Municipal Wastewater
Authors: Nishiyama Masateru , Praise Susan , Tsurumaki Keiichi , Baba Hiroaki , Kanamori Hajime , Watanabe Toru
Published: April 2021

There is increasing attention toward factors that potentially contribute to antibiotic resistance (AR), as well as an interest in exploring the emergence and occurrence of antibiotic resistance bacteria (ARB). We monitored six ARBs that cause hospital outbreaks in wastewater influent to highlight the presence of these ARBs in the general population. We analyzed wastewater samples from a municipal wastewater treatment plant (MWWTP) and hospital wastewater (HW) for six species of ARB: Carbapenem-resistant Enterobacteria (CARBA), extended-spectrum β-lactamase producing Enterobacteria (ESBL), multidrug-resistant Acinetobacter (MDRA), multidrug-resistant Pseudomonas aeruginosa (MDRP), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). We registered a high percentage of ARBs in MWWTP samples (>66%) for all ARBs except for MDRP, indicating a high prevalence in the population. Percentages in HW samples were low (<78%), and no VRE was detected throughout the study. CARBA and ESBL were detected in all wastewater samples, whereas MDRA and MRSA had a high abundance. This result demonstrated the functionality of using raw wastewater at MWWTP to monitor the presence and extent of ARB in healthy populations. This kind of surveillance will contribute to strengthening the efforts toward reducing ARBs through the detection of ARBs to which the general population is exposed.
The General Population’s Inappropriate Behaviors and Misunderstanding of Antibiotic Use in China: A Systematic Review and Meta-Analysis
Authors: Duan Lixia , Liu Chenxi , Wang Dan
Published: April 2021

The general population has increasingly become the key contributor to irrational antibiotic use in China, which fuels the emergence of antibiotic resistance. This study aimed to estimate the prevalence of the general population’s irrational use behaviors of antibiotics and identify the potential reasons behind them. A systematic review and meta-analysis were performed concerning four main behaviors relevant to easy access and irrational use of antibiotics and common misunderstandings among the population about antibiotics. Four databases were searched, and studies published before 28 February 2021 were retrieved. Medium and high-level quality studies were included. Random effects meta-analysis was performed to calculate the prevalence of the general population’s irrational behaviors and misunderstandings relevant to antibiotic use. A total of 8468 studies were retrieved and 78 met the criteria and were included. The synthesis showed the public can easily obtain unnecessary antibiotics, with an estimated 37% (95% CI: 29–46) of the population demanding antibiotics from physicians and 47% (95% CI: 38–57) purchasing non-prescription antibiotics from pharmacies. This situation is severe in the western area of China. People also commonly inappropriately use antibiotics by not following antibiotic prescriptions (pooled estimate: 48%, 95% CI: 41–55) and preventatively use antibiotics for non-indicated diseases (pooled estimate: 35%, 95% CI: 29–42). Misunderstanding of antibiotic use was also popular among people, including incorrect antibiotic recognition, wrong antibiotic use indication, inappropriate usage, and ignorance of potential adverse outcomes. Over-and inappropriate use of antibiotics is evident in China and a multifaceted antibiotic strategy targeted at the general population is urgently required.
Current Perspective of Hydrogen Sulfide as a Novel Gaseous Modulator of Oxidative Stress in Glaucoma
Authors: Feng Yuan , Prokosch Verena , Liu Hanhan
Published: April 2021

Glaucoma is a group of diseases characterized by the progressive loss of retinal ganglion cells and their axons. Elevated intraocular pressure (IOP) is the main clinical manifestation of glaucoma. Despite being in the focus of the studies for decades, the characteristic and the exact pathology of neurodegeneration in glaucoma remains unclear. Oxidative stress is believed to be one of the main risk factors in neurodegeneration, especially its damage to the retinal ganglion cells. Hydrogen sulfide (H2S), the recently recognized gas signaling molecule, plays a pivotal role in the nervous system, vascular system, and immune system. It has also shown properties in regulating oxidative stress through different pathways in vivo. In this review, we summarize the distribution and the properties of H2S within the eye with an emphasis on its role in modulating oxidative stress in glaucoma.
Broa, an Ethnic Maize Bread, as a Source of Phenolic Compounds
Authors: Bento-Silva Andreia , Duarte Noélia , Mecha Elsa , Belo Maria , Serra Ana Teresa , Vaz Patto Maria Carlota , Bronze Maria Rosário
Published: April 2021

Maize is an important source of phenolic compounds, specially hydroxycinnamic acids, which are widely known for their antioxidant activity and associated health benefits. However, these effects depend on their bioaccessibility, which is influenced by the different techniques used for food processing. Several traditional products can be obtained from maize and, in Portugal, it is used for the production of an ethnic bread called broa. In order to evaluate the effect of processing on maize phenolic composition, one commercial hybrid and five open-pollinated maize flours and broas were studied. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteu and ORAC assays, respectively. The major phenolics, namely ferulic and p-coumaric acids (in their soluble-free, soluble-conjugated and insoluble forms), insoluble ferulic acid dimers and soluble hydroxycinnamic acid amides were quantitated. Results show that the total phenolic content, antioxidant activity and hydroxycinnamic acids resisted traditional processing conditions used in the production of broas. The content in soluble-free phenolics increased after processing, meaning that their bioaccessibility improved. Portuguese traditional broas, produced with open-pollinated maize varieties, can be considered an interesting dietary source of antioxidant compounds due to the higher content in hydroxycinnamic acids and derivatives.
Oxidative Stress in Vascular Pathophysiology: Still Much to Learn
Authors: Zalba Guillermo
Published: April 2021

Low concentration of reactive oxygen species (ROS) is essential for physiological cellular processes [...]