bluuebunny/crossref_metadata_2025 huggingface dataset:
Motives for Texting During Early Adolescence
Authors: Yau Joanna C. , McPartlan Peter , Reich Stephanie M.
Published: June 2021

Research on adolescent texting has largely focused on whether the frequency of texting is associated with well-being. Whether the motives for texting is associated with well-being is not well known. We surveyed 130 young adolescents (Mage = 12.41 years) and identified user-clusters based on their motives for texting. We then examined whether the clusters were associated with phone habits that may affect health and learning (e.g., phone placement when sleeping). Participants were asked how often they texted someone when they were excited, proud, frustrated, angry, anxious, sad, needed help with homework, wanted to make plans, and needed advice [0 (never) to 4 (always)]. Using k-means clustering, we identified six clusters. On one end of the continuum were Frequent-Texters and Positive-Frequent-Texters. Frequent-Texters texted often for all purposes and Positive-Frequent-Texters frequently texted for all purposes except expressing negative emotions. On the other end of the continuum were Selective-Texters and Positive-Selective-Texters. Selective-Texters rarely texted for any reason and Positive-Selective-Texters rarely texted except for expressing positive emotions. In between were the Moderate-Texters and the Positive-Practical-Moderate-Texters. Moderate-Texters texted less frequently than Frequent-Texters and more frequently than Selective-Texters for all purposes. Positive-Practical-Moderate-Texters texted more frequently than Moderate-Texters for positive emotions and for practical reasons. Clusters differed by gender, texting experience, and Fear of Missing Out (FOMO). Frequent-Texters started texting at a marginally younger age than Selective-Texters, had high FOMO scores, and were all girls. Clusters also differed in their phone habits. For instance, when sleeping, Frequent-Texters were more likely than other groups to have their phones on or next to the bed. When doing homework, Selective-Texters were less likely to keep their phones on or near them. Interestingly, Positive-Frequent-Texters were more likely to have the ringer on or to have their phone on vibrate while doing homework, but not more likely to keep their phones nearby. Given that texting is a common communication method, it is important to understand the heterogeneity of reasons why youth text and how those reasons relate to phone habits.
Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency
Authors: Ferrua Francesca , Bortolomai Ileana , Fontana Elena , Di Silvestre Dario , Rigoni Rosita , Marcovecchio Genni Enza , Draghici Elena , Brambilla Francesca , Castiello Maria Carmina , Delfanti Gloria , Moshous Despina , Picard Capucine , Taghon Tom , Bordon Victoria , Schulz Ansgar S. , Schuetz Catharina , Giliani Silvia , Soresina Annarosa , Gennery Andrew R. , Signa Sara , Dávila Saldaña Blachy J. , Delmonte Ottavia M. , Notarangelo Luigi D. , Roifman Chaim M. , Poliani Pietro Luigi , Uva Paolo , Mauri Pier Luigi , Villa Anna , Bosticardo Marita
Published: June 2021

Major Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC). However, the contribution of TEC alterations to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC in this disease. We observed an overall perturbation of thymic structure and function in both MHCII−/−mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, we demonstrated that impairment of lymphostromal cross-talk in the thymus of MHCII−/−mice affects mTEC maturation and promiscuous gene expression and causes defects of central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential benefits of hematopoietic stem cell transplantation in MHCII deficiency.
Synovial Macrophages in Osteoarthritis: The Key to Understanding Pathogenesis?
Authors: Thomson Amanda , Hilkens Catharien M. U.
Published: June 2021

Effective treatment of osteoarthritis (OA) remains a huge clinical challenge despite major research efforts. Different tissues and cell-types within the joint contribute to disease pathogenesis, and there is great heterogeneity between patients in terms of clinical features, genetic characteristics and responses to treatment. Inflammation and the most abundant immune cell type within the joint, macrophages, have now been recognised as possible players in disease development and progression. Here we discuss recent findings on the involvement of synovial inflammation and particularly the role of synovial macrophages in OA pathogenesis. Understanding macrophage involvement may hold the key for improved OA treatments.
Transcriptomic Analysis and C-Terminal Epitope Tagging Reveal Differential Processing and Signaling of Endogenous TLR3 and TLR7
Authors: Chen Chiung-Ya , Hung Yun-Fen , Tsai Ching-Yen , Shih Yi-Chun , Chou Ting-Fang , Lai Ming-Zong , Wang Ting-Fang , Hsueh Yi-Ping
Published: June 2021

Toll-like receptor (TLR) signaling is critical for defense against pathogenic infection, as well as for modulating tissue development. Activation of different TLRs triggers common inflammatory responses such as cytokine induction. Here, we reveal differential impacts of TLR3 and TLR7 signaling on transcriptomic profiles in bone marrow-derived macrophages (BMDMs). Apart from self-regulation, TLR3, but not TLR7, induced expression of other TLRs, suggesting that TLR3 activation globally enhances innate immunity. Moreover, we observed diverse influences of TLR3 and TLR7 signaling on genes involved in methylation, caspase and autophagy pathways. We compared endogenous TLR3 and TLR7 by using CRISPR/Cas9 technology to knock in a dual Myc-HA tag at the 3’ ends of mouse Tlr3 and Tlr7. Using anti-HA antibodies to detect endogenous tagged TLR3 and TLR7, we found that both TLRs display differential tissue expression and posttranslational modifications. C-terminal tagging did not impair TLR3 activity. However, it disrupted the interaction between TLR7 and myeloid differentiation primary response 88 (MYD88), the Tir domain-containing adaptor of TLR7, which blocked its downstream signaling necessary to trigger cytokine and chemokine expression. Our study demonstrates different properties for TLR3 and TLR7, and also provides useful mouse models for further investigation of these two RNA-sensing TLRs.
A Fish Chorus on the Margin of New Jersey Atlantic Continental Shelf
Authors: Zhang Qianchu , Katsnelson Boris
Published: June 2021

We report herein an underwater biological chorus coming from the margin of the New Jersey Atlantic continental shelf that we tentatively attribute to a species of fish. The chorus occurred every night for over a month during the Shallow Water 2006 experiment and covers the frequency band 150–4,800 Hz, with maximum intensity in the band from 1450 to 2,000 Hz. Remarkable intensity peaks occurred at 500, 725, 960, 1,215, 1,465, 1,700, and 1,920 Hz, rising to as much as 20 dB above the background noise without the chorus. The chorus begins at sunset and reaches its maximum intensity within an hour, following which it weakens slightly and then gradually climbs again to a peak before sunrise, at which point it quickly weakens and disappears. Its frequency-domain characteristics and the nocturnal timing are reminiscent of sound produced by underwater animals. The intensity of the chorus weakens along the across-shelf path going shoreward, which indicates that the chorus originates from the margin of the continental shelf rather than from the coastal zone, as is generally considered. The chorus contains a single type of acoustic signal that takes the form of double-pulse bursts that last about 8.7 ms, with each pulse containing several acoustic cycles. The time interval between successive bursts varies from 1.5 to 1.9 s. Signals containing a number of bursts vary in length from tens to hundreds of seconds. Although it is impossible to determine the fish species responsible for the chorus, its characteristics, including its low frequency and intensity, its single type of short-duration sound signal, and its multiple peaks in the frequency domain, are all consistent with the general characteristics of fish sounds.
Automated Digital Quantification of Pulmonary Fibrosis in Human Histopathology Specimens
Authors: Testa Lauren C. , Jule Yvon , Lundh Linnea , Bertotti Karine , Merideth Melissa A. , O'Brien Kevin J. , Nathan Steven D. , Venuto Drew C. , El-Chemaly Souheil , Malicdan May Christine V. , Gochuico Bernadette R.
Published: June 2021

Pulmonary fibrosis is characterized by abnormal interstitial extracellular matrix and cellular accumulations. Methods quantifying fibrosis severity in lung histopathology samples are semi-quantitative, subjective, and analyze only portions of sections. We sought to determine whether automated computerized imaging analysis shown to continuously measure fibrosis in mice could also be applied in human samples. A pilot study was conducted to analyze a small number of specimens from patients with Hermansky-Pudlak syndrome pulmonary fibrosis (HPSPF) or idiopathic pulmonary fibrosis (IPF). Digital images of entire lung histological serial sections stained with picrosirius red and alcian blue or anti-CD68 antibody were analyzed using dedicated software to automatically quantify fibrosis, collagen, and macrophage content. Automated fibrosis quantification based on parenchymal tissue density and fibrosis score measurements was compared to pulmonary function values or Ashcroft score. Automated fibrosis quantification of HPSPF lung explants was significantly higher than that of IPF lung explants or biopsies and was also significantly higher in IPF lung explants than in IPF biopsies. A high correlation coefficient was found between some automated quantification measurements and lung function values for the three sample groups. Automated quantification of collagen content in lung sections used for digital image analyses was similar in the three groups. CD68 immunolabeled cell measurements were significantly higher in HPSPF explants than in IPF biopsies. In conclusion, computerized image analysis provides access to accurate, reader-independent pulmonary fibrosis quantification in human histopathology samples. Fibrosis, collagen content, and immunostained cells can be automatically and individually quantified from serial sections. Robust automated digital image analysis of human lung samples enhances the available tools to quantify and study fibrotic lung disease.
Inducible HIV-1 Reservoir Quantification: Clinical Relevance, Applications and Advancements of TILDA
Authors: Lungu Cynthia , Banga Riddhima , Gruters Rob A. , Procopio Francesco A.
Published: June 2021

The presence of a stable HIV-1 reservoir persisting over time despite effective antiretroviral suppression therapy precludes a cure for HIV-1. Characterizing and quantifying this residual reservoir is considered an essential prerequisite to develop and validate curative strategies. However, a sensitive, reproducible, cost-effective, and easily executable test is still needed. The quantitative viral outgrowth assay is considered the gold standard approach to quantify the reservoir in HIV-1-infected patients on suppressive ART, but it has several limitations. An alternative method to quantify the viral reservoir following the reactivation of latent HIV-1 provirus detects multiply-spliced tat/rev RNA (msRNA) molecules by real-time PCR [tat/rev induced limiting dilution assay (TILDA)]. This article provides a perspective overview of the clinical relevance, various applications, recent advancements of TILDA, and how the assay has contributed to our understanding of the HIV-1 reservoir.
Role of Neuron and Glia in Alzheimer’s Disease and Associated Vascular Dysfunction
Authors: Bandyopadhyay Sanghamitra
Published: June 2021

Amyloidogenicity and vascular dysfunction are the key players in the pathogenesis of Alzheimer’s disease (AD), involving dysregulated cellular interactions. An intricate balance between neurons, astrocytes, microglia, oligodendrocytes and vascular cells sustains the normal neuronal circuits. Conversely, cerebrovascular diseases overlap neuropathologically with AD, and glial dyshomeostasis promotes AD-associated neurodegenerative cascade. While pathological hallmarks of AD primarily include amyloid-β (Aβ) plaques and neurofibrillary tangles, microvascular disorders, altered cerebral blood flow (CBF), and blood-brain barrier (BBB) permeability induce neuronal loss and synaptic atrophy. Accordingly, microglia-mediated inflammation and astrogliosis disrupt the homeostasis of the neuro-vascular unit and stimulate infiltration of circulating leukocytes into the brain. Large-scale genetic and epidemiological studies demonstrate a critical role of cellular crosstalk for altered immune response, metabolism, and vasculature in AD. The glia associated genetic risk factors include APOE, TREM2, CD33, PGRN, CR1, and NLRP3, which correlate with the deposition and altered phagocytosis of Aβ. Moreover, aging-dependent downregulation of astrocyte and microglial Aβ-degrading enzymes limits the neurotrophic and neurogenic role of glial cells and inhibits lysosomal degradation and clearance of Aβ. Microglial cells secrete IGF-1, and neurons show a reduced responsiveness to the neurotrophic IGF-1R/IRS-2/PI3K signaling pathway, generating amyloidogenic and vascular dyshomeostasis in AD. Glial signals connect to neural stem cells, and a shift in glial phenotype over the AD trajectory even affects adult neurogenesis and the neurovascular niche. Overall, the current review informs about the interaction of neuronal and glial cell types in AD pathogenesis and its critical association with cerebrovascular dysfunction.
Environmental Enrichment Improves Vestibular Oculomotor Learning in Mice
Authors: van der Geest Jos N. , Spoor Marcella , Frens Maarten A.
Published: June 2021

We assessed the behavioral effects of environmental enrichment on contrast sensitivity, reflexive eye movements and on oculomotor learning in mice that were housed in an enriched environment for a period of 3 weeks. Research has shown that a larger cage and a more complex environment have positive effects on the welfare of laboratory mice and other animals held in captivity. It has also been shown that environmental enrichment affects various behavior and neuroanatomical and molecular characteristics. We found a clear effect on oculomotor learning. Animals that were housed in an enriched environment learned significantly faster than controls that were housed under standard conditions. In line with existing literature, the enriched group also outperformed the controls in behavioral tests for explorative behavior. Meanwhile, both visual and reflexive oculomotor performance in response to visual and vestibular stimuli was unaffected. This points toward an underlying mechanism that is specific for motor learning, rather than overall motor performance.
Prevention of HIV-1 TAT Protein-Induced Peripheral Neuropathy and Mitochondrial Disruption by the Antimuscarinic Pirenzepine
Authors: Han May Madi , Frizzi Katie E. , Ellis Ronald J. , Calcutt Nigel A. , Fields Jerel Adam
Published: June 2021

HIV-associated distal sensory polyneuropathy (HIV-DSP) affects about one third of people with HIV and is characterized by distal degeneration of axons. The pathogenesis of HIV-DSP is not known and there is currently no FDA-approved treatment. HIV trans-activator of transcription (TAT) is associated with mitochondrial dysfunction and neurotoxicity in the brain and may play a role in the pathogenesis of HIV-DSP. In the present study, we measured indices of peripheral neuropathy in the doxycycline (DOX)-inducible HIV-TAT (iTAT) transgenic mouse and investigated the therapeutic efficacy of a selective muscarinic subtype-1 receptor (M1R) antagonist, pirenzepine (PZ). PZ was selected as we have previously shown that it prevents and/or reverses indices of peripheral neuropathy in multiple disease models. DOX alone induced weight loss, tactile allodynia and paw thermal hypoalgesia in normal C57Bl/6J mice. Conduction velocity of large motor fibers, density of small sensory nerve fibers in the cornea and expression of mitochondria-associated proteins in sciatic nerve were unaffected by DOX in normal mice, whereas these parameters were disrupted when DOX was given to iTAT mice to induce TAT expression. Daily injection of PZ (10 mg/kg s.c.) prevented all of the disorders associated with TAT expression. These studies demonstrate that TAT expression disrupts mitochondria and induces indices of sensory and motor peripheral neuropathy and that M1R antagonism may be a viable treatment for HIV-DSP. However, some indices of neuropathy in the DOX-inducible TAT transgenic mouse model can be ascribed to DOX treatment rather than TAT expression and data obtained from animal models in which gene expression is modified by DOX should be accompanied by appropriate controls and treated with due caution.
The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer
Authors: Crombet Ramos Tania , Santos Morales Orestes , Dy Grace K. , León Monzón Kalet , Lage Dávila Agustín
Published: June 2021

Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from Neisseria meningitides, which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors’ sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.
Women’s Participation in Pap Smear Screening in a Developing Country: Evidence for Improving Health Systems
Authors: Santamaría-Ulloa Carolina , Quirós-Rojas Ileana , Montero-López Melina , Quesada-Leitón Hazel
Published: June 2021

Introduction

Every year about 83,000 women are diagnosed with cervical cancer in the Americas. Latin America and the Caribbean (LAC) has one of the highest incidence and mortality rates from cervical cancer in the world. Although incidence has decreased by half in the last 30 years, cervical cancer remains a public health concern. The detection of precursor lesions through Papanicolaou (Pap) smear remains a critical tool in the context of prevention in Costa Rica and many other LAC countries.

Objective

To determine predictors of participation in Pap smear screening among Costa Rican women, with a special focus on women who have never had a Pap smear or have had a smear 5 or more years ago.

Methods

The data source for this study is the Costa Rican Households National Survey conducted in 2014. This survey is representative at the national, urban/rural zone, and administrative region level. A subsample of women aged 20 to 69 years who responded to the survey’s Papanicolaou Module were included in this study (n = 11,709). Statistical analyses were conducted in R-Studio. Statistical significance level was set at 5%. Two multinomial regression models were estimated. The first model aimed to explain the five different categories of cytology use, which were defined according to the last time women had a Pap smear. The second model aimed to explain the five different categories of reasons why women had never had a Pap smear. Both models controlled for age, educational attainment, and marital status.

Results

Young women with high educational attainment were more likely to have never had a cytology. Women with a lower educational attainment, married, or in domestic relationship and of older age had greater odds of having had a cytology 5 or more years ago. Each year increment in age was significantly associated with an increase in the odds of never having a Pap smear because of health care access issues or because of cultural reasons as compared to not having an active sexual life.

Conclusions

Findings can inform public policy targeted to higher risk female populations where access to health services can be improved.
Transcriptome Analysis Reveals MFGE8-HAPLN3 Fusion as a Novel Biomarker in Triple-Negative Breast Cancer
Authors: Wang Meng-Yuan , Huang Man , Wang Chao-Yi , Tang Xiao-Ying , Wang Jian-Gen , Yang Yong-De , Xiong Xin , Gao Chao-Wei
Published: June 2021

Background

Triple-negative breast cancer (TNBC) is a highly aggressive cancer with poor prognosis. The lack of effective targeted therapies for TNBC remains a profound clinical challenge. Fusion transcripts play critical roles in carcinogenesis and serve as valuable diagnostic and therapeutic targets in cancer. The present study aimed to identify novel fusion transcripts in TNBC.

Methods

We analyzed the RNA sequencing data of 360 TNBC samples to identify and filter fusion candidates through SOAPfuse and ChimeraScan analysis. The characteristics, including recurrence, fusion type, chromosomal localization, TNBC subgroup distribution, and clinicopathological correlations, were analyzed in all candidates. Furthermore, we selected the promising fusion transcript and predicted its fusion type and protein coding capacity.

Results

Using the RNA sequencing data, we identified 189 fusion transcripts in TNBC, among which 22 were recurrent fusions. Compared to para-tumor tissues, TNBC tumor tissues accumulated more fusion events, especially in high-grade tumors. Interestingly, these events were enriched at specific chromosomal loci, and the distribution pattern varied in different TNBC subtypes. The vast majority of fusion partners were discovered on chromosomes 1p, 11q, 19p, and 19q. Besides, fusion events mainly clustered on chromosome 11 in the immunomodulatory subtype and chromosome 19 in the luminal androgen receptor subtype of TNBC. Considering the tumor specificity and frameshift mutation, we selected MFGE8-HAPLN3 as a novel biomarker and further validated it in TNBC samples using PCR and Sanger sequencing. Further, we successfully identified three types of MFGE8-HAPLN3 (E6-E2, E5-E3, and E6-E3) and predicted the ORF of E6-E2, which could encode a protein of 712 amino acids, suggesting its critical role in TNBC.

Conclusions

Improved bioinformatic stratification and comprehensive analysis identified the fusion transcript MFGE8-HAPLN3 as a novel biomarker with promising clinical application in the future.
Inhomogeneous Transmission and Asynchronic Mixing in the Spread of COVID-19 Epidemics
Authors: Mendoza Carlos I.
Published: June 2021

The ongoing epidemic of COVID-19 first found in China has reinforced the need to develop epidemiological models capable of describing the progression of the disease to be of use in the formulation of mitigation policies. Here, this problem is addressed using a metapopulation approach to consider the inhomogeneous transmission of the spread arising from a variety of reasons, like the distribution of local epidemic onset times or of the transmission rates. We show that these contributions can be incorporated into a susceptible-infected-recovered framework through a time-dependent transmission rate. Thus, the reproduction number decreases with time despite the population dynamics remaining uniform and the depletion of susceptible individuals is small. The obtained results are consistent with the early subexponential growth observed in the cumulated number of confirmed cases even in the absence of containment measures. We validate our model by describing the evolution of COVID-19 using real data from different countries, with an emphasis in the case of Mexico, and show that it also correctly describes the longtime dynamics of the spread. The proposed model yet simple is successful at describing the onset and progression of the outbreak, and considerably improves the accuracy of predictions over traditional compartmental models. The insights given here may prove to be useful to forecast the extent of the public health risks of the epidemics, thus improving public policy-making aimed at reducing such risks.
Red Blood Cell 2,3-Diphosphoglycerate Decreases in Response to a 30 km Time Trial Under Hypoxia in Cyclists
Authors: Płoszczyca Kamila , Czuba Miłosz , Chalimoniuk Małgorzata , Gajda Robert , Baranowski Marcin
Published: June 2021

Red blood cell 2,3-diphosphoglycerate (2,3-DPG) is one of the factors of rightward-shifted oxygen dissociation curves and decrease of Hb-O2affinity. The reduction of Hb-O2affinity is beneficial to O2unloading at the tissue level. In the current literature, there are no studies about the changes in 2,3-DPG level following acute exercise in moderate hypoxia in athletes. For this reason, the aim of this study was to analyze the effect of prolonged intense exercise under normoxic and hypoxic conditions on 2,3-DPG level in cyclists. Fourteen male trained cyclists performed a simulation of a 30 km time trial (TT) in normoxia and normobaric hypoxia (FiO2= 16.5%, ~2,000 m). During the TT, the following variables were measured: power, blood oxygen saturation (SpO2), and heart rate (HR). Before and immediately after exercise, the blood level of 2,3-DPG and acid–base equilibrium were determined. The results showed that the mean SpO2during TT in hypoxia was 8% lower than in normoxia. The reduction of SpO2in hypoxia resulted in a decrease of average power by 9.6% (p< 0.001) and an increase in the 30 km TT completion time by 3.8% (p< 0.01) compared to normoxia. The exercise in hypoxia caused a significant (p< 0.001) decrease in 2,3-DPG level by 17.6%. After exercise in normoxia, a downward trend of 2,3-DPG level was also observed, but this effect was not statistically significant. The analysis also revealed that changes of acid–base balance were significantly larger (p< 0.05) after exercise in hypoxia than in normoxia. In conclusion, intense exercise in hypoxic conditions leads to a decrease in 2,3-DPG concentration, primarily due to exercise-induced acidosis.
Variation of Morphological, Agronomic and Chemical Composition Traits of Local Hazelnuts Collected in Northern Spain
Authors: Campa Negrillo Ana , Rodríguez Madrera Roberto , Suárez Valles Belén , Ferreira Juan Jose
Published: June 2021

Hazelnut is a traditional crop in northern Spain, where it grows wild as well as being cultivated. A field collection of 41 local and 17 non-local accessions, including 15 well-known cultivars, was established at SERIDA in Villaviciosa, Spain. Here, phenotypic variation was documented for phenological and morphological traits and chemical composition. A large degree of variation for most morphological and phenological traits, except nut maturity date, was revealed. Estimates of broad-sense heritability were high (>0.75) for most of the assessed characters, except for the first male bloom date (0.65), male and female flowering periods (0.40, 0.31), kernel weight (0.69), and kernel percentage (0.33). Local accessions produced smaller nuts and kernels than well-known cultivars but with higher kernel percentage. Limited overlapping between the male and female flowering periods (dychogamy) was observed, except for ‘Forcinas 1’, ‘Forcinas 2’, and ‘Morell’. The local accessions generally exhibited significantly later male and female flowering compared with the reference cultivars. The local materials showed similar nutritional values to those reported previously for hazelnut. Moreover, the local accessions presented average values similar to the non-local accessions for total fat, ash and carbohydrate contents, as well as energy value, but their protein contents were lower. Their oils were rich in functional compounds, such as unsaturated fatty acids (average: 90.1%), tocopherols (514 mg/kg) and squalene (294.3 mg/kg). A hierarchical clustering on principal components analysis grouped the accessions and differentiated eight local accessions from the rest, including the landrace ‘Casina’. This finding provides potential new cultivars, as well as sources of desirable traits, for European hazelnut breeding programs.
Environmental Factors Associated With Nitrogen Fixation Prediction in Soybean
Authors: de Borja Reis André Froes , Moro Rosso Luiz , Purcell Larry C. , Naeve Seth , Casteel Shaun N. , Kovács Péter , Archontoulis Sotirios , Davidson Dan , Ciampitti Ignacio A.
Published: June 2021

Biological nitrogen (N)-fixation is the most important source of N for soybean [Glycine max (L.) Merr.], with considerable implications for sustainable intensification. Therefore, this study aimed to investigate the relevance of environmental factors driving N-fixation and to develop predictive models defining the role of N-fixation for improved productivity and increased seed protein concentration. Using the elastic net regularization of multiple linear regression, we analyzed 40 environmental factors related to weather, soil, and crop management. We selected the most important factors associated with the relative abundance of ureides (RAU) as an indicator of the fraction of N derived from N-fixation. The most relevant RAU predictors were N fertilization, atmospheric vapor pressure deficit (VPD) and precipitation during early reproductive growth (R1–R4 stages), sowing date, drought stress during seed filling (R5–R6), soil cation exchange capacity (CEC), and soil sulfate concentration before sowing. Soybean N-fixation ranged from 60 to 98% across locations and years (n = 95). The predictive model for RAU showed relative mean square error (RRMSE) of 4.5% and an R2 value of 0.69, estimated via cross-validation. In addition, we built similar predictive models of yield and seed protein to assess the association of RAU and these plant traits. The variable RAU was selected as a covariable for the models predicting yield and seed protein, but with a small magnitude relative to the sowing date for yield or soil sulfate for protein. The early-reproductive period VPD affected all independent variables, namely RAU, yield, and seed protein. The elastic net algorithm successfully depicted some otherwise challenging empirical relationships to assess with bivariate associations in observational data. This approach provides inference about environmental variables while predicting N-fixation. The outcomes of this study will provide a foundation for improving the understanding of N-fixation within the context of sustainable intensification of soybean production.
Natural Biostimulants Elicit Plant Immune System in an Integrated Management Strategy of the Postharvest Green Mold of Orange Fruits Incited by Penicillium digitatum
Authors: La Spada Federico , Aloi Francesco , Coniglione Maurizio , Pane Antonella , Cacciola Santa Olga
Published: June 2021

This study was aimed at testing the integrated use of a natural biostimulant based on seaweed (Ascophyllum nodosum) and plant (alfalfa and sugarcane) extracts and reduced dosages of the conventional synthetic fungicide Imazalil (IMZ) to manage postharvest rots of orange fruits. The following aspects were investigated: (i) the effectiveness of postharvest treatment with natural biostimulant alone or in mixture with IMZ at a reduced dose against green mold caused byPenicillium digitatum; (ii) the differential expression of defense genes in orange fruits treated with the natural biostimulant both alone and in combination with a reduced dose of IMZ; (iii) the persistence of the inhibitory activity of both biostimulant and the mixture biostimulant/IMZ against green mold; and (iv) the residue level of fungicide in citrus peel when applied alone or in combination with the biostimulant. Treatments with the chemical plant resistance-inducer potassium phosphite, alone or with a reduced dose of IMZ, were included for comparison. The mixture of natural biostimulant and IMZ at a low dose consistently reduced the incidence and severity of fruit green mold and induced a significant increase of the expression level of β-1,3-glucanase-, peroxidase (PEROX)-, and phenylalanine ammonia-lyase (PAL)-encoding genes in fruit peel, suggesting that the natural biostimulant elicits a long-lasting resistance of citrus fruits to infections byP. digitatum. Interestingly, the residual concentration of IMZ in fruits treated with the biostimulant/fungicide mixture was significantly lower than that of IMZ in fruits treated only with the fungicide at the same dose and by far below the threshold values set by the European Union. This study laid the foundations for (i) conceiving a practical and more eco-friendly alternative to the conventional postharvest management of green mold of citrus fruits, based almost exclusively on the use of synthetic fungicide IMZ, alone or mixed with potassium phosphite and (ii) providing a better insight into the mechanisms of disease resistance induction by biostimulants.
N-Glycosylation of the SARS-CoV-2 Receptor Binding Domain Is Important for Functional Expression in Plants
Authors: Shin Yun-Ji , König-Beihammer Julia , Vavra Ulrike , Schwestka Jennifer , Kienzl Nikolaus F. , Klausberger Miriam , Laurent Elisabeth , Grünwald-Gruber Clemens , Vierlinger Klemens , Hofner Manuela , Margolin Emmanuel , Weinhäusel Andreas , Stöger Eva , Mach Lukas , Strasser Richard
Published: June 2021

Nicotiana benthamiana is used worldwide as production host for recombinant proteins. Many recombinant proteins such as monoclonal antibodies, growth factors or viral antigens require posttranslational modifications like glycosylation for their function. Here, we transiently expressed different variants of the glycosylated receptor binding domain (RBD) from the SARS-CoV-2 spike protein in N. benthamiana. We characterized the impact of variations in RBD-length and posttranslational modifications on protein expression, yield and functionality. We found that a truncated RBD variant (RBD-215) consisting of amino acids Arg319-Leu533 can be efficiently expressed as a secreted soluble protein. Purified RBD-215 was mainly present as a monomer and showed binding to the conformation-dependent antibody CR3022, the cellular receptor angiotensin converting enzyme 2 (ACE2) and to antibodies present in convalescent sera. Expression of RBD-215 in glycoengineered ΔXT/FT plants resulted in the generation of complex N-glycans on both N-glycosylation sites. While site-directed mutagenesis showed that the N-glycans are important for proper RBD folding, differences in N-glycan processing had no effect on protein expression and function.
Psychometric Validation of the Multidimensional Scale of Perceived Social Support During Pregnancy in Rural Pakistan
Authors: Sharif Maria , Zaidi Ahmed , Waqas Ahmed , Malik Abid , Hagaman Ashley , Maselko Joanna , LeMasters Katherine , Liaqat Rakhshanda , Bilal Samina , Bibi Tayyaba , Ahmad Ikhlaq , Sikander Siham , Rahman Atif
Published: June 2021

Background: The Multidimensional Scale of Perceived Social Support (MSPSS) is a short and reliable instrument that assesses perceived social support from the social network of an individual. A previous study in Pakistan among postpartum women has demonstrated a unidimensional factor structure in contrast to the original three-factor structure. The emergence of a one-factor structure for postpartum women in Pakistan may be due to traditional postpartum practices unique to the women of the subcontinent. Building upon the previous evidence, this study aims to explore the psychometric properties of MSPSS among pregnant women in their third trimester in rural Pakistan.

Methods: A cross-sectional survey was conducted from October 2014 to February 2016, in rural Pakistan. A sample of 1,154 pregnant women (aged ≥ 18 years) in their third trimester who were registered with the local Lady Health Worker Program and were living in the north of the Punjab Province was included in this study. They were assessed using Urdu translated scales of Patient Health Questionnaire, MSPSS, Maternal Social Support Index, and Perceived Stress Scale. Principal Axis Factoring was used to assess the construct validity of the MSPSS.

Results: The MSPSS scale showed an excellent internal consistency, yielding a Cronbach's α-value of 0.933. The MSPSS scale exhibited an excellent construct validity, and confirmatory factor analysis retained three factors (family, friends, and significant others) for both the depressed and non-depressed samples. Internal reliability and construct validity were also established.

Conclusion: The psychometric findings suggest that the tridimensional structure of MSPSS is a valid and reliable measure of perceived social support among the Pakistani population with and without perinatal depression. The perceived social support is an important predictor of maternal mental well-being and psychopathologies, and the MSPSS can serve as a useful tool in mental health research in Pakistan.
Is There a “Gestalt Bias” in Indulgence? Subjectively Constructing Food Units Into Wholes (vs. Parts) Increases Desire to Eat and Actual Consumption
Authors: Joye Yannick , Bruyneel Sabrina , Fennis Bob M.
Published: June 2021

In the present work we extend research into the unit bias effect and its extension—the portion size effect—by demonstrating the existence of a “Gestalt bias.” Drawing on the tenets of Gestalt psychology, we show that a unit bias effect can be observed for food portions that are composed of identical basic units, but which are subjectively grouped into, or perceived as a Gestalt—a larger whole. In three studies, we find that such subjectively constructed food wholes constitute a new (perceptual) unit that is perceived bigger than the units it is constructed from, thereby prompting increased eating and desire to eat.
Characteristics of Publications on Occupational Stress: Contributions and Trends
Authors: Zhang Yang , Huang Lei , Wang Yongwei , Lan Yajia , Zhang Yonggang
Published: June 2021

This study aimed to analyze the bibliometric characteristics of the publications on occupational stress and highlight key research topics and future trends. The Web of Science Core Collection database was searched to collect publications on occupational stress, from inception to December 9, 2020. Two authors independently screened eligible literature and extracted the data. Bibliometric analyses were performed using VOSviewer 1.6.6 and R 3.6.3 software. Overall, 6,564 publications on occupational stress were included. “Stress,” with a total link strength of 1,252, appeared as the most co-occurrence keyword, followed by “occupational stress,” “job stress,” and “job satisfaction.” All studies were published between 1956 and 2020. Among them, 6,176 (94.35%) papers were written in English, and 4,706 (70.25%) were original articles. The top three Web of Science categories were “public environmental occupational health” (n = 1,711), “psychology, applied” (n = 846), and “psychology, multidisciplinary” (n = 650). The 100 top-cited articles were mentioned a total of 36,145 times, with a median of 361, ranging from 174 to 5,574. The United States was the most productive country, with 1,780 publications. The main partners of the United States were England and China. Three themes of occupational stress research were identified: job satisfaction, burnout, and occupational stress-related health problems. This bibliometric analysis provides a comprehensive understanding of the trends and most influential contributions to the field of occupational stress, thus promoting ideas for future research.
An NRF2 Perspective on Stem Cells and Ageing
Authors: Dodson Matthew , Anandhan Annadurai , Zhang Donna D. , Madhavan Lalitha
Published: June 2021

Redox and metabolic mechanisms lie at the heart of stem cell survival and regenerative activity. NRF2 is a major transcriptional controller of cellular redox and metabolic homeostasis, which has also been implicated in ageing and lifespan regulation. However, NRF2’s role in stem cells and their functioning with age is only just emerging. Here, focusing mainly on neural stem cells, which are core to adult brain plasticity and function, we review recent findings that identify NRF2 as a fundamental player in stem cell biology and ageing. We also discuss NRF2-based molecular programs that may govern stem cell state and function with age, and implications of this for age-related pathologies.
Using Deep Learning Neural Network in Artificial Intelligence Technology to Classify Beef Cuts
Authors: GC Sunil , Saidul Md Borhan , Zhang Yu , Reed Demetris , Ahsan Mostofa , Berg Eric , Sun Xin
Published: June 2021

The objective of this research was to evaluate the deep learning neural network in artificial intelligence (AI) technologies to rapidly classify seven different beef cuts (bone in rib eye steak, boneless rib eye steak, chuck steak, flank steak, New York strip, short rib, and tenderloin). Color images of beef samples were acquired from a laboratory-based computer vision system and collected from the Internet (Google Images) platforms. A total of 1,113 beef cut images were used as training, validation, and testing data subsets for this project. The model developed from the deep learning neural network algorithm was able to classify certain beef cuts (flank steak and tenderloin) up to 100% accuracy. Two pretrained convolution neutral network (CNN) models Visual Geometry Group (VGG16) and Inception ResNet V2 were used to train, validate, and test these models in classifying beef cut images. An image augmentation technique was incorporated in the convolution neutral network models for avoiding the overfitting problems, which demonstrated an improvement in the performance of the image classifier model. The VGG16 model outperformed the Inception ResNet V2 model. The VGG16 model coupled with data augmentation technique was able to achieve the highest accuracy of 98.6% on 116 test images, whereas Inception ResNet V2 accomplished a maximum accuracy of 95.7% on the same test images. Based on the performance metrics of both models, deep learning technology evidently showed a promising effort for beef cuts recognition in the meat science industry.
Men and Those With a History of Smoking Are Associated With the Development of Postoperative Ileus Following Elective Colorectal Cancer Resection at a Private Academic Hospital in Johannesburg, South Africa: A Retrospective Cohort Study
Authors: Watkins Estella L. , Schellack Natalie , Abraham Veena , Bebington Brendan
Published: June 2021

Introduction: A scarcity of local published data on colorectal cancer (CRC) postoperative complications, including postoperative ileus (POI), exists. POI is a temporary gastrointestinal (GI) state of absent or reduced gastric motility shown to increase patient morbidity, prolong length-of-stay (LOS), and intensify the healthcare resource burden. The pathogenesis of POI involves a neurogenic and inflammatory phase plus a pharmacological component.

Aim and Objectives: This study aimed to determine centre-specific preoperative risk factors associated with the development of ileus post elective therapeutic CRC resection. The objectives were to determine whether patient demographics; functional status; comorbidities; GI history; pharmacotherapy (including neoadjuvant chemotherapy); and lastly neoadjuvant radiation and chemoradiation were associated with the development of POI.

Method: Patients who underwent CRC resection between January 2016 and May 2019 were retrospectively identified from an existing database. Urgent—or non-therapeutic surgeries; surgeries with the complication anastomotic leak or GI obstruction; patients under 18 at the time of surgery or surgeries preceded by preoperative parenteral nutrition were excluded. A comparison was done of the incidence of exposure in the study cohort to investigated variables as potential risk factors for the complication POI.

Results: A total of 155 patient cases were included, and 56 (36%) of them developed POI. Univariate comparison of patients who developed POI with demographic characteristics of patients who did not suggested that women were at lower risk to develop POI compared to men (p = 0,013; RR 0,56; 95% CI 0,36–0,89). Functional status suggested that all previous smokers were at a higher risk to develop POI compared to lifetime non-smokers (p = 0,0069; RR 1,78; 95% CI 1,17–2,70). Multivariable comparison of ≤ 5 qualifying parameters showed no significance.

Conclusion: The high local incidence of POI in this patient population shows that intervention is required to reduce the POI rate and improve postoperative outcomes. This study suggests that for men and all patients with a history of smoking both, CRC resection preoperative recommendations with the intention to prevent POI should include instructions initiating the activation of preventive strategies like the Enhanced Recovery After Surgery (ERAS) programme. More studies are needed to adequately determine local perioperative risk factors for POI.
Concurrent Evaluation of Mortality and Behavioral Responses: A Fast and Efficient Testing Approach for High-Throughput Chemical Hazard Identification
Authors: Thunga Preethi , Truong Lisa , Tanguay Robyn L. , Reif David M.
Published: June 2021

The continual introduction of new chemicals into the market necessitates fast, efficient testing strategies for evaluating their toxicity. Ideally, these high-throughput screening (HTS) methods should capture the entirety of biological complexity while minimizing reliance on expensive resources that are required to assess diverse phenotypic endpoints. In recent years, the zebrafish (Danio rerio) has become a preferred vertebrate model to conduct rapid in vivo toxicity tests. Previously, using HTS data on 1060 chemicals tested as part of the ToxCast program, we showed that early, 24 h post-fertilization (hpf), behavioral responses of zebrafish embryos are predictive of later, 120 h post-fertilization, adverse developmental endpoints—indicating that embryonic behavior is a useful endpoint related to observable morphological effects. Here, our goal was to assess the contributions (i.e., information gain) from multiple phenotypic data streams and propose a framework for efficient identification of chemical hazards. We systematically swept through analysis parameters for data on 24 hpf behavior, 120 hpf behavior, and 120 hpf morphology to optimize settings for each of these assays. We evaluated the concordance of data from behavioral assays with that from morphology. We found that combining information from behavioral and mortality assessments captures early signals of potential chemical hazards, obviating the need to evaluate a comprehensive suite of morphological endpoints in initial screens for toxicity. We have demonstrated that such a screening strategy is useful for detecting compounds that elicit adverse morphological responses, in addition to identifying hazardous compounds that do not disrupt the underlying morphology. The application of this design for rapid preliminary toxicity screening will accelerate chemical testing and aid in prioritizing chemicals for risk assessment.