bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation Method and Characterization of Outer Membranes Vesicles of Helicobacter pylori Grown in a Chemically Defined Medium
Authors: Melo Joana , Pinto Vanessa , Fernandes Tânia , Malheiro Ana R. , Osório Hugo , Figueiredo Ceu , Leite Marina
Published: June 2021

Outer membrane vesicles (OMVs) are small vesicles constitutively shed by all Gram-negative bacterium, which have been proposed to play a role in Helicobacter pylori persistence and pathogenesis. The methods currently available for the isolation of H. pylori OMVs are diverse and time-consuming, raising the need for a protocol standardization, which was the main aim of this study. Here, we showed that the chemically defined F12 medium, supplemented with cholesterol, nutritionally supports bacterial growth and maintains H. pylori viability for at least 72 h. Additionally, we developed an abridged protocol for isolation of OMVs from these bacterial cultures, which comprises a low-speed centrifugation, supernatant filtration through a 0.45 μm pore, and two ultracentrifugations for OMVs’ recovery and washing. Using this approach, a good yield of highly pure bona fide OMVs was recovered from cultures of different H. pylori strains and in different periods of bacterial growth, as assessed by nanoparticle tracking analysis, transmission electron microscopy (TEM), and proteomic analyses, confirming the reliability of the protocol. Analysis of the proteome of OMVs isolated from H. pylori F12-cholesterol cultures at different time points of bacterial growth revealed differentially expressed proteins, including the vacuolating cytotoxin VacA. In conclusion, this work proposes a time- and cost-efficient protocol for the isolation of H. pylori OMVs from a chemically defined culture medium that is suitable for implementation in research and in the biopharmaceutical field.
Three New Quinazoline-Containing Indole Alkaloids From the Marine-Derived Fungus Aspergillus sp. HNMF114
Authors: Liu Sha-Sha , Yang Li , Kong Fan-Dong , Zhao Jia-Hui , Yao Li , Yuchi Zhi-Guang , Ma Qing-Yun , Xie Qing-Yi , Zhou Li-Man , Guo Meng-Fei , Dai Hao-Fu , Zhao You-Xing , Luo Du-Qiang
Published: June 2021

By feeding tryptophan to the marine-derived fungus Aspergillus sp. HNMF114 from the bivalve mollusk Sanguinolaria chinensis, 3 new quinazoline-containing indole alkaloids, named aspertoryadins H–J (1–3), along with 16 known ones (4–19), were obtained. The structures of the new compounds were elucidated by the analysis of spectroscopic data combined with quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts and electron capture detector (ECD) spectra. Structurally, compound 3 represents the first example of this type of compound, bearing an amide group at C-3. Compounds 10 and 16 showed potent α-glucosidase inhibitory activity with IC50 values of 7.18 and 5.29 μM, and compounds 13 and 14 showed a clear activation effect on the ryanodine receptor from Spodoptera frugiperda (sfRyR), which reduced the [Ca2+]ER by 37.1 and 36.2%, respectively.
Systematic Review of Studies on Subliminal Exposure to Phobic Stimuli: Integrating Therapeutic Models for Specific Phobias
Authors: Frumento Sergio , Menicucci Danilo , Hitchcott Paul Kenneth , Zaccaro Andrea , Gemignani Angelo
Published: June 2021

We systematically review 26 papers investigating subjective, behavioral, and psychophysiological correlates of subliminal exposure to phobic stimuli in phobic patients. Stimulations were found to elicit: (1) cardiac defense responses, (2) specific brain activations of both subcortical (e.g., amygdala) and cortical structures, (3) skin conductance reactions, only when stimuli lasted >20 ms and were administered with intertrial interval >20 s. While not inducing the distress caused by current (supraliminal) exposure therapies, exposure to subliminal phobic stimuli still results in successful extinction of both psychophysiological and behavioral correlates: however, it hardly improves subjective fear. We integrate those results with recent bifactorial models of emotional regulation, proposing a new form of exposure therapy whose effectiveness and acceptability should be maximized by a preliminary subliminal stimulation. Systematic Review Registration: identifier [CRD42021129234].
Diet and Lifestyle Changes During the COVID-19 Pandemic in Ibero-American Countries: Argentina, Brazil, Mexico, Peru, and Spain
Authors: Enriquez-Martinez Oscar G. , Martins Marcia C. T. , Pereira Taisa S. S. , Pacheco Sandaly O. S. , Pacheco Fabio J. , Lopez Karen V. , Huancahuire-Vega Salomon , Silva Daniela A. , Mora-Urda Ana I. , Rodriguez-Vásquez Mery , Montero López M. Pilar , Molina Maria C. B.
Published: June 2021

This study aimed to evaluate changes in dietary and lifestyle habits during the period of confinement due to the first wave of the COVID-19 pandemic in Ibero-American countries. A cross-sectional investigation was conducted with 6,325 participants of both genders (68% women), over 18 years of age and from five countries: Brazil (N = 2,171), Argentina (N = 1,111), Peru (N = 1,174), Mexico (N = 686), and Spain (N = 1,183). Data were collected during the year 2020, between April 01 and June 30 in Spain and between July 13 and September 26, in the other countries studied using a self-administered online survey designed for the assessment of sociodemographic, employment, physical activity, health status, and dietary habits changes. Most participants (61.6%), mainly those from Spain, remained constant, without improving or worsening their pattern of food consumption. Among those who changed, a pattern of better eating choices prevailed (22.7%) in comparison with those who changed toward less healthy choices (15.7%). Argentina and Brazil showed the highest proportion of changes toward a healthier pattern of food consumption. Peruvians and Mexicans were less likely to make healthy changes in food consumption (OR: 0.51; 95% CI: 0.4–0.6 and OR: 0.69; 95% CI: 0.4–0.8, respectively), when compared to Argentinians. Most respondents did not change their pattern of meal consumption, but those who did reduced their consumption of main meals and increased intake of small meals and snacks. Although most participants affirmed to be doing physical activity at home, about one-half reported perception of weight gain. Individuals with alterations in sleep pattern (either by increasing or decreasing sleep time) were more likely to change their diets to a healthier pattern. In contrast, individuals with confirmed diagnosis of COVID-19 and those who reported feeling anxious were more likely to perform changes to a less healthy eating pattern (OR: 1.72; 95% CI: 1.2–2.3 and OR: 1.21; 95% CI: 1.1–1.4, respectively). In conclusion, although most participants remained constant in their eating habits, lifestyle changes and anxiety feelings were reported. Among those who changed patterns of food consumption, healthier choices prevailed, with differences between countries. However, there were alterations in the distribution of meals, with higher consumption of snacks and small meals. These results can be used to guide policies to prevent deleterious consequences that may affect the incidence of chronic diseases.
High Expression of Cancer-IgG Is Associated With Poor Prognosis and Radioresistance via PI3K/AKT/DNA-PKcs Pathway Regulation in Lung Adenocarcinoma
Authors: Yang Xiongtao , Wang Guohui , You Jing , Gu Runchuan , Xu Xiaohong , Xu Changdan , Wang Hao , Zhao Ruisong , Qiu Xiaoyan , Zhu Guangying
Published: June 2021

Background

Lung adenocarcinoma (LUAD) is the dominant type of lung neoplasms, and radiotherapy is its mainstay treatment, yet poor prognosis caused by radioresistance remains problematic. Cancer-derived immunoglobulin G (cancer-IgG) has been detected in multiple cancers and plays important roles in carcinogenesis. This study aimed to demonstrate that cancer-IgG is associated with poor prognosis of LUAD and to identify its role in radioresistance.

Methods

Cancer-IgG expression was detected by immunohistochemistry from 56 patients with stage III LUAD and by western blot and immunofluorescence in LUAD cell lines and in a human bronchial epithelial cell line. The effects of cancer-IgG silencing on the proliferation and apoptosis of PC9 and H292 cells were evaluated by plate cloning and apoptosis assay; the effects of cancer-IgG silencing on DNA damage repair ability and radiosensitivity were evaluated by colony-forming assay, γH2AX immunofluorescence, and neutral comet assay. Finally, we used the protein phosphorylation microarray and western blot to explore mechanisms involving cancer-IgG that increased radioresistance.

Results

Cancer-IgG is widely expressed in stage III LUAD, and the overall survival and disease-free survival of patients with positive expression are notably lower than those of patients with negative expression, indicating the associations between cancer-IgG and poor prognosis as well as radioresistance. The expression of cancer-IgG in the four LUAD cell lines was located mainly on the cell membrane and cytoplasm and not in the normal lung epithelial cell. Knockdown of cancer-IgG in PC9 and H292 cells resulted in increased apoptosis and negatively affected cancer cell proliferation. After irradiation, silencing of cancer-IgG showed a decrease in colonies as well as increases in the Olive tail moment and γH2AX foci in nucleus, indicating that the knockdown of cancer-IgG resulted in a decrease in the damage repair ability of DNA double-strand breaks in LUAD cells and an enhanced radiosensitivity. The expression of p-AKT, p-GSK3β, and p-DNA-PKcs decreased in the knockdown group after radiotherapy, suggesting that cancer-IgG could affect radiotherapy resistance by mediating double-strand breaks damage repair in LUAD cells through the PI3K/AKT/DNA-PKcs pathway.

Conclusions

This study revealed that cancer-IgG regulates PI3K/AKT/DNA-PKcs signaling pathways to affect radioresistance of LUAD and associated with poor prognosis.
Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia
Authors: Simonetti Giorgia , Angeli Davide , Petracci Elisabetta , Fonzi Eugenio , Vedovato Susanna , Sperotto Alessandra , Padella Antonella , Ghetti Martina , Ferrari Anna , Robustelli Valentina , Di Liddo Rosa , Conconi Maria Teresa , Papayannidis Cristina , Cerchione Claudio , Rondoni Michela , Astolfi Annalisa , Ottaviani Emanuela , Martinelli Giovanni , Gottardi Michele
Published: June 2021

Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related peptide family. It is secreted in vitro by endothelial cells and vascular smooth muscle cells, and is significantly upregulated by a number of stimuli. Moreover, ADM participates in the regulation of hematopoietic compartment, solid tumors and leukemias, such as acute myeloid leukemia (AML). To better characterize ADM involvement in AML pathogenesis, we investigated its expression during human hematopoiesis and in leukemic subsets, based on a morphological, cytogenetic and molecular characterization and in T cells from AML patients. In hematopoietic stem/progenitor cells and T lymphocytes from healthy subjects, ADM transcript was barely detectable. It was expressed at low levels by megakaryocytes and erythroblasts, while higher levels were measured in neutrophils, monocytes and plasma cells. Moreover, cells populating the hematopoietic niche, including mesenchymal stem cells, showed to express ADM. ADM was overexpressed in AML cells versus normal CD34+ cells and in the subset of leukemia compared with hematopoietic stem cells. In parallel, we detected a significant variation of ADM expression among cytogenetic subgroups, measuring the highest levels in inv(16)/t(16;16) or complex karyotype AML. According to the mutational status of AML-related genes, the analysis showed a lower expression of ADM in FLT3-ITD, NPM1-mutated AML and FLT3-ITD/NPM1-mutated cases compared with wild-type ones. Moreover, ADM expression had a negative impact on overall survival within the favorable risk class, while showing a potential positive impact within the subgroup receiving a not-intensive treatment. The expression of 135 genes involved in leukemogenesis, regulation of cell proliferation, ferroptosis, protection from apoptosis, HIF-1α signaling, JAK-STAT pathway, immune and inflammatory responses was correlated with ADM levels in the bone marrow cells of at least two AML cohorts. Moreover, ADM was upregulated in CD4+ T and CD8+ T cells from AML patients compared with healthy controls and some ADM co-expressed genes participate in a signature of immune tolerance that characterizes CD4+ T cells from leukemic patients. Overall, our study shows that ADM expression in AML associates with a stem cell phenotype, inflammatory signatures and genes related to immunosuppression, all factors that contribute to therapy resistance and disease relapse.
Pharmacokinetics, Immunogenicity and Safety Study for SHR-1309 Injection and Perjeta® in Healthy Chinese Male Volunteers
Authors: Cui Yingzi , Cui Dongyang , Ren Xinran , Chen Xuesong , Liu Guangwen , Liu Zhengzhi , Wang Yanli , Qu Xinyao , Zhao Yicheng , Yang Haimiao
Published: June 2021

Objectives: Pertuzumab is a monoclonal antibody for the treatment of breast cancer. The aim of this study was to compare the pharmacokinetics, immunogenicity and safety of the test preparation SHR-1309 injecta and the reference preparation Perjeta® in healthy Chinese male subjects.

Methods: In this randomized, double-blind, single dose, two-way, parallel bioequivalence trial, a total of 80 qualified Chinese male subjects were selected and randomly divided into two groups. Each subject was intravenously injected with SHR-1309 or Perjeta®. Blood samples were collected at 21 different time points for pharmacokinetic analysis. In addition, immunogenicity was assessed at five different time points. The safety of the medication was monitored throughout the whole trial.

Results: Cmax and AUC0-t were the primary pharmacokinetic parameters. Under a 90% confidence interval, their geometric mean ratios were 98.30 and 88.41% for SHR-1309 injection and Perjeta®, respectively. The geometric mean ratio of secondary pharmacokinetic parameters AUC0-∞ was 88.58%. These evaluation indexes are in the standard range of 80–125%, so SHR-1309 can be considered bioequivalent to Perjeta®. After 1,680 h (day 70) of administration, the two groups had 12 and 13 subjects who produced antidrug antibody (ADA), respectively. The occurrence time and proportion of ADA in SHR-1309 and Perjeta® were similar between subjects, and they had similar immunogenicity. During the entire trial period, there were 71 drug-related adverse reactions in 29 subjects who received SHR-1309 and 61 drug-related adverse reactions in 32 subjects who received Perjeta®. The incidence of adverse reactions between the two drugs was similar.

Conclusion: The pharmacokinetic parameters, immunogenicity and safety of the biosimilar SHR-1309 injection produced by Shanghai Hengrui Pharmaceutical Co. Ltd. were similar to the original drug Perjeta® produced by Roche Pharma AG. The two drugs met the bioequivalence evaluation criteria. Therefore, SHR-1309 is bioequivalent to Perjeta®. Clinical trial registration: CTR20200,738.
Nano and Microparticles as Potential Oral Vaccine Carriers and Adjuvants Against Infectious Diseases
Authors: Jazayeri Seyed Davoud , Lim Hui Xuan , Shameli Kamyar , Yeap Swee Keong , Poh Chit Laa
Published: June 2021

Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.
Elucidation of Novel cis-Regulatory Elements and Promoter Structures Involved in Iron Excess Response Mechanisms in Rice Using a Bioinformatics Approach
Authors: Kakei Yusuke , Masuda Hiroshi , Nishizawa Naoko K. , Hattori Hiroyuki , Aung May Sann
Published: June 2021

Iron (Fe) excess is a major constraint on crop production in flooded acidic soils, particularly in rice cultivation. Under Fe excess, plants activate a complex mechanism and network regulating Fe exclusion by roots and isolation in various tissues. In rice, the transcription factors and cis-regulatory elements (CREs) that regulate Fe excess response mechanisms remain largely elusive. We previously reported comprehensive microarray analyses of several rice tissues in response to various levels of Fe excess stress. In this study, we further explored novel CREs and promoter structures in rice using bioinformatics approaches with this microarray data. We first performed network analyses to predict Fe excess-related CREs through the categorization of the gene expression patterns of Fe excess-responsive transcriptional regulons, and found four major expression clusters: Fe storage type, Fe chelator type, Fe uptake type, and WRKY and other co-expression type. Next, we explored CREs within these four clusters of gene expression types using a machine-learning method called microarray-associated motif analyzer (MAMA), which we previously established. Through a comprehensive bioinformatics approach, we identified a total of 560 CRE candidates extracted by MAMA analyses and 42 important conserved sequences of CREs directly related to the Fe excess response in various rice tissues. We explored several novel cis-elements as candidate Fe excess CREs including GCWGCWGC, CGACACGC, and Myb binding-like motifs. Based on the presence or absence of candidate CREs using MAMA and known PLACE CREs, we found that the Boruta-XGBoost model explained expression patterns with high accuracy of about 83%. Enriched sequences of both novel MAMA CREs and known PLACE CREs led to high accuracy expression patterns. We also found new roles of known CREs in the Fe excess response, including the DCEp2 motif, IDEF1-, Zinc Finger-, WRKY-, Myb-, AP2/ERF-, MADS- box-, bZIP and bHLH- binding sequence-containing motifs among Fe excess-responsive genes. In addition, we built a molecular model and promoter structures regulating Fe excess-responsive genes based on new finding CREs. Together, our findings about Fe excess-related CREs and conserved sequences will provide a comprehensive resource for discovery of genes and transcription factors involved in Fe excess-responsive pathways, clarification of the Fe excess response mechanism in rice, and future application of the promoter sequences to produce genotypes tolerant of Fe excess.
Deceleration Assistance Mitigated the Trade-off Between Sense of Agency and Driving Performance
Authors: Wen Wen , Yun Sonmin , Yamashita Atsushi , Northcutt Brandon D. , Asama Hajime
Published: June 2021

Driving assistance technology has gained traction in recent years and is becoming more widely used in vehicles. However, drivers usually experience a reduced sense of agency when driving assistance is active even though automated assistance improves driving performance by reducing human error and ensuring quick reactions. The present study examined whether driving assistance can maintain human sense of agency during early deceleration in the face of collision risk, compared with manual deceleration. In the experimental task, participants decelerate their vehicle in a driving simulator to avoid collision with a vehicle that suddenly cut in front of them and decelerated. In the assisted condition, the system performed deceleration 100 ms after the cut-in. Participants were instructed to decelerate their vehicle and follow the vehicle that cut-in. This design ensured that the deceleration assistance applied a similar control to the vehicle as the drivers intended to, only faster and smoother. Participants rated their sense of agency and their driving performance. The results showed that drivers maintained their sense of agency and improved driving performance under driving assistance. The findings provided insights into designing driving assistance that can maintain drivers’ sense of agency while improving future driving performance. It is important to establish a mode of joint-control in which the system shares the intention of human drivers and provides improved execution of control.
Differences in Food Craving in Individuals With Obesity With and Without Binge Eating Disorder
Authors: Reents Janina , Pedersen Anya
Published: June 2021

Overeating behavior is supposedly a major contributing factor to weight gain and obesity. Binge eating disorder (BED) with reoccurring episodes of excessive overeating is strongly associated with obesity. Learning models of overeating behavior and BED assume that mere confrontation with food leads to a conditioned response that is experienced as food craving. Accordingly, individuals with obesity and BED were shown to have high trait food cravings. To date, little is known about differences in state food cravings and cue reactivity at the sight of palatable food in individuals with obesity and BED compared to individuals with obesity without BED. Therefore, the aim of our study was to examine differences in cue-induced, state and trait food cravings in people with obesity with and without BED. We found that all aspects of food cravings were more prevalent in individuals with obesity and BED than in individuals without BED. By implementing a food cue reactivity paradigm, our results show that individuals with obesity with BED have more cue-induced cravings than individuals with obesity without BED. Moreover, these cue-induced cravings in individuals with obesity and BED were highest for high-fat and high-sugar foods as opposed to low-calorie foods. Thus, our results emphasize the role of increased cue reactivity and craving at the sight of palatable foods in individuals with obesity and BED. Hence, our findings support etiological models of conditioned binge eating and are in line with interventions targeting cue reactivity in BED.
Paint It Red - A Multimethod Study of the Nudging Effect of Coloured Cycle Lanes
Authors: Fyhri Aslak , Karlsen Katrine , Sundfør Hanne B.
Published: June 2021

Many countries colour their cycle lanes, but there is still a lack of research into the impact of this policy. Rather than constraining or regulating movement, coloured asphalt conveys information, and can serve as a good example of a “nudge”. In transport, there are few good examples of effective nudges for improved safety or sustainability. We used a multi-method approach to study the behaviour and experiences of cyclists before and after cycle lanes were coloured using red asphalt. Video data were collected and analysed to measure the extent to which motorists stopped in the cycle lane; motorist distance from the cycle lane on passing; and bicycle placement in the cycle lane. Cyclists (n = 1583) were asked how they experienced the cycle lane in field surveys. GPS data from cyclists (n = 2448) was used to measure whether colouring the cycle lanes resulted in a change of cyclists’ route choice. Video data showed no significant decrease in the share of passing motorists who stopped in the cycle lane. However, there was a significant decrease in the share of motorists stopping in the cycle lane rather than in the car lane or on the pavement. After recoating, motorists also kept a greater distance from the cycle lane; a greater share of cyclists chose to cycle in the cycle lane and a lower share cycled on the pavement. Analysis of survey data showed that visibility, perceived safety and ease of visualisation improved more in the recoated streets than in control streets. Analysis of the GPS data revealed a significant increase in cycling in the first streets to get red asphalt, with mixed results for the later streets. We discuss possible mechanisms behind the effects observed, and whether coloured cycle lanes can be considered as a form of nudging.
Developmental Features of Lexical Richness in English Writings by Chinese Beginner Learners
Authors: Zhang Huiping , Chen Ming , Li Xuelan
Published: June 2021

This paper reports a cross-sectional study that investigates the developmental features in second language writings by Chinese beginner learners of English by using four lexical richness measures—lexical sophistication, lexical variation, lexical density, and lexical errors—from the perspective of the language exposure hypothesis. Specifically, the study compares English compositions written by Chinese students of grade 7, grade 8, and grade 9 in terms of lexical sophistication, lexical variation, lexical density, and lexical errors. The English compositions were sampled from the Writing Corpus of Chinese Beginner Learners of English, and the sample size of the three grades remained almost the same. The analysis revealed that lexical richness in the writing samples of beginner learners is comparatively low, with beginner learners transferring lexical features of the oral register to their second language writings; furthermore, all four measures yielded significant, albeit non-linear and unevenly paced, developments across grade levels. Based on the findings, several suggestions for vocabulary teaching are provided.
The Association Between the 5Cs and Anxiety—Insights From Three Countries: Portugal, Slovenia, and Spain
Authors: Kozina Ana , Gomez-Baya Diego , Gaspar de Matos Margarida , Tome Gina , Wiium Nora
Published: June 2021

Several of the most frequent psychological difficulties in childhood and adolescence are related to anxiety and lead to numerous short- and long-term negative outcomes in emotional, social, and academic domains. Empirical evidence consistently shows that the 5Cs (competence, caring, confidence, connection, and character) of Positive Youth Development (PYD) are positively related to adolescents’ contribution to self, family, and society as well as negatively related to risky behaviors and emotional difficulties, such as anxiety. Thus, the PYD can be one of the models that informs prevention programs. To provide contextualized, data-driven support for prevention efforts, we have analyzed the predictive value of the 5Cs for anxiety and anxiety dimensions using three different convenience youth samples from Portugal (N= 384, 46.6% female), Slovenia (N= 449, 69% females), and Spain (N= 768; 60.5% females). To assess the 5Cs, we used the same short form of the PYD scale in all samples (Geldhof et al., 2013) and different anxiety measures across samples: the Multidimensional Anxiety Scale for Children (MASC) in Portugal, the Lestvica anksioznosti za otroke in mladostnike anxiety scale (LAOM) in Slovenia and the Generalized Anxiety Disorder-7 (GAD-7) in Spain. The findings show significant associations of PYD and anxiety across all three contexts with all three different anxiety measures used. The associations vary across countries emphasizing the need to further research the role of contexts in anxiety prevention. Despite variations the results do indicate that connection is negatively associated with anxiety in all three contexts using the three anxiety measures, while confidence is a negative predictor and caring is a positive predictor of anxiety in Slovenia and Spain. Implications for practice within an educational framework for adolescents and youth are discussed, together with public policy recommendations.
A Return-to-Work Intervention for Prematurely Retired Depression or Anxiety Disorder Patients
Authors: Behrens-Wittenberg Eva , Wedegaertner Felix
Published: June 2021

Background: Depression and anxiety disorders are the most common cause for premature retirement of people of middle age. These people are expelled from the workforce. The following social disintegration can have an additional detrimental effect on subjects' psychological well-being which further reduces the chance to re-enter the workforce. Depression and anxiety in general need not be regarded as irreversible causes of disability. Therefore, long-term disability should be avoidable in many cases. This two-arm prospective controlled study tests a novel approach for those who have become economically inactive due to their illness with the goal to improve psychological well-being and return to work. Forty-one subjects were followed-up on over a period of 12 months and compared to 41 control cases. ANOVA for repeated measures showed that experimental subjects' psychological well-being and work ability was much better after the intervention than in the control group. These findings show that an individually tailored return-to-work intervention can be a useful therapeutic tool even after retirement.
TAPAS: An Open-Source Software Package for Translational Neuromodeling and Computational Psychiatry
Authors: Frässle Stefan , Aponte Eduardo A. , Bollmann Saskia , Brodersen Kay H. , Do Cao T. , Harrison Olivia K. , Harrison Samuel J. , Heinzle Jakob , Iglesias Sandra , Kasper Lars , Lomakina Ekaterina I. , Mathys Christoph , Müller-Schrader Matthias , Pereira Inês , Petzschner Frederike H. , Raman Sudhir , Schöbi Dario , Toussaint Birte , Weber Lilian A. , Yao Yu , Stephan Klaas E.
Published: June 2021

Psychiatry faces fundamental challenges with regard to mechanistically guided differential diagnosis, as well as prediction of clinical trajectories and treatment response of individual patients. This has motivated the genesis of two closely intertwined fields: (i) Translational Neuromodeling (TN), which develops “computational assays” for inferring patient-specific disease processes from neuroimaging, electrophysiological, and behavioral data; and (ii) Computational Psychiatry (CP), with the goal of incorporating computational assays into clinical decision making in everyday practice. In order to serve as objective and reliable tools for clinical routine, computational assays require end-to-end pipelines from raw data (input) to clinically useful information (output). While these are yet to be established in clinical practice, individual components of this general end-to-end pipeline are being developed and made openly available for community use. In this paper, we present the Translational Algorithms for Psychiatry-Advancing Science (TAPAS) software package, an open-source collection of building blocks for computational assays in psychiatry. Collectively, the tools in TAPAS presently cover several important aspects of the desired end-to-end pipeline, including: (i) tailored experimental designs and optimization of measurement strategy prior to data acquisition, (ii) quality control during data acquisition, and (iii) artifact correction, statistical inference, and clinical application after data acquisition. Here, we review the different tools within TAPAS and illustrate how these may help provide a deeper understanding of neural and cognitive mechanisms of disease, with the ultimate goal of establishing automatized pipelines for predictions about individual patients. We hope that the openly available tools in TAPAS will contribute to the further development of TN/CP and facilitate the translation of advances in computational neuroscience into clinically relevant computational assays.
Retrospective Evaluation of Claw Lesions, Inflammatory Markers, and Outcome after Abomasal Rolling in Cattle with Left Displacement of the Abomasum
Authors: Tschoner Theresa , Zablotski Yury , Feist Melanie
Published: June 2021

Lameness is often diagnosed in cattle with left displacement of the abomasum (LDA). Laterality of lying has an effect on the etiology of LDA, and lame cows prefer to lie on the affected limb. The objective of this study was to investigate the possible association between laterality of claw lesion and presence of LDA. The medical records of 252 cattle presented with a diagnosis of LDA and subjected to a diagnostic examination of claw lesions over a period of 11 years (2009–2019), were analyzed retrospectively. Data were evaluated for presence and localization of claw lesion, concentrations of inflammatory markers, and abomasal rolling as therapy. At least one claw lesion was diagnosed in 46.4% of cattle. There was no association between laterality of claw lesion and LDA. Presence of claw lesion or oral drench and/or analgesic treatment did not have an effect on occurrence of relapse. A high number of cattle was diagnosed with both LDA and claw lesions. Focus should lie on preventing painful claw lesions in the dry and the early post-partum period. The high recurrence rate after abomasal rolling suggests that abomasal rolling should only be considered as a therapy for temporary relief, and surgical procedures should be discussed with farmers.
Solid State Fermentation as a Tool to Stabilize and Improve Nutritive Value of Fruit and Vegetable Discards: Effect on Nutritional Composition, In Vitro Ruminal Fermentation and Organic Matter Digestibility
Authors: Ibarruri Jone , Goiri Idoia , Cebrián Marta , García-Rodríguez Aser
Published: June 2021

This research aimed to evaluate in vitro organic matter digestibility, fermentation characteristics and methane production of fruit and vegetable discards processed by solid state fermentation (SSF) by Rhizopus sp. Mixtures were composed of approximately 28% citric fruits, 35% other fruits and 37% vegetables. Fruit and vegetables were processed and fermented to obtain a stabilized product. Nutritional characterization and in vitro ruminal fermentation tests were performed to determine the effect of fungal bioconversion on digestibility, end products and gas production kinetics. Results indicate that SSF reduced organic matter and reducing sugars, while it increased crude protein and neutral detergent fiber, acid detergent fiber and neutral detergent insoluble protein. The in vitro gas production showed that SSF led to a reduction of the organic matter digestibility (p < 0.001), short chain fatty acids (SCFA; p = 0.003) and CH4 (p = 0.002). SSF reduced the gas production from the insoluble fraction (p = 0.001), without modifying the production rate (p = 0.676) or the lag time (p = 0.574). Regarding SCFA profile, SSF increased acetic (p = 0.020) and decreased propionic (p = 0.004) and butyric (p = 0.006) acids proportions, increasing acetic to propionic (p = 0.008) and acetic plus butyric to propionic (p = 0.011) ratios. SSF succeeded in obtaining a stabilized material enriched in protein, but at the expense of a reduction of protein availability and organic matter digestibility. These changes should be considered before including them in a ruminant’s rations.
Effects of Dietary Paper Mulberry (Broussonetia papyrifera) on Growth Performance and Muscle Quality of Grass Carp (Ctenopharyngodon idella)
Authors: Tang Tao , Bai Jinhai , Ao Zhipeng , Wei Zehong , Hu Yi , Liu Shaojun
Published: June 2021

The present study investigated the effects of dietary paper mulberry (Broussonetia Papyrifera, BP) on growth performance, muscle quality and muscle growth-related mRNA expressions of grass carp. Fish (initial weight: 50.0 ± 0.5 g) were fed diets supplemented with 0% (control diet), 5%, 10%, 15% and 20% BP for 8 weeks. The results showed that increasing levels of paper mulberry linearly and quadratically decreased the special gain rate (SGR) and increased the feed conversion rate (FCR) of grass carp (p < 0.05). Significantly positive quadratic trends were found between paper mulberry levels and muscle crude fat or crude protein of grass carp (p < 0.05). In comparison to the control diet, the 10%BP and 15%BP groups had significantly decreased muscle crude fat and increased crude protein (p < 0.05). The levels of paper mulberry resulted in a linear and quadratic increase in water loss of grass carp muscle (p < 0.05), and all groups with paper mulberry supplementation were significantly higher than the control group (p < 0.05). Significant positive linear and quadratic trends were found between the paper mulberry levels and muscle fiber diameter or density of grass carp (p < 0.05). In comparison to the control diet, the significant differences were found in the 15%BP and 20%BP groups (p < 0.05). The muscle adhesiveness and hardness linearly and quadratically increased with the increasing levels of paper mulberry (p < 0.05), and both of which increased significantly when the level of paper mulberry reached 10% (p < 0.05). In addition, the increase in paper mulberry linearly and quadratically improved the expressions of myoblast determination protein (MyoD), myogenin (MyoG), paired box protein 7 (Pax7) and myostatin 1 (MSTN1) (p < 0.05). When the supplementation of paper mulberry reached 15%, the expressions of all these mRNAs were significantly higher than those of the control group (p < 0.05). In summary, adding 5% paper mulberry did not affect the growth of grass carp. However, the supplementation of 10% paper mulberry could improve muscle quality through improving muscle hardness, reducing fat accumulation and muscle fiber diameter, at the cost of reducing growth performance.
Effect of the Spatial Distribution of the Temperature and Humidity Index in a New Zealand White Rabbit House on Respiratory Frequency and Ear Surface Temperature
Authors: Silva Maria Alice Junqueira Gouvêa , Ferraz Patrícia Ferreira Ponciano , Santos Luana Mendes dos , Ferraz Gabriel Araújo e Silva , Rossi Giuseppe , Barbari Matteo
Published: June 2021

The objective of this study was to characterize and evaluate the temperature and humidity index (THI) of New Zealand white (NZW) rabbits kept in a rabbit house using geostatistical techniques. Furthermore, we sought to evaluate its relationship with respiratory frequency (RF) and ear surface temperature (EST). The experiment was conducted at the Federal University of Lavras, Brazil. A total of 52 NZW rabbits were used. For the characterization of the thermal environment, the dry bulb temperature (tdb, °C), relative humidity (RH, %), and dew point temperature (tdp, °C) were collected at 48 points in the rabbit house at 6:00 a.m., 12:00 p.m., and 6:00 p.m. for seven days. The RF and EST of the animals was monitored. Subsequently, the THI was calculated and the data were analyzed using geostatistical tools and kriging interpolation. In addition, the RF and EST data were superimposed on the rabbit house’s THI data maps. The magnitude of the variability and structure of the THI inside the rabbit house were characterized and the heterogeneity was visualized. Critical THI points inside the rabbit house and in locations where animals with high RF and ESTs were housed were identified, thus providing information about improving the production environment.
Induced Mitochondrial Alteration and DNA Damage via IFNGR-JAK2-STAT1-PARP1 Pathway Facilitates Viral Hepatitis Associated Hepatocellular Carcinoma Aggressiveness and Stemness
Authors: Cherng Yih-Giun , Chu Yi Cheng , Yadav Vijesh Kumar , Huang Ting-Yi , Hsieh Ming-Shou , Lee Kwai-Fong , Lee Wei-Hwa , Yeh Chi-Tai , Ong Jiann Ruey
Published: June 2021

Background: Hepatitis virus is a major risk factor for liver cancer. The mitochondrial dysfunction IFN gamma-related pathways are activated after virus infection. Jak family-related protein is involved in the downstream of IFN gamma-related pathways. However, the effect of the IFNGR-JAK-STAT pathway acting as functional regulators of their related protein expression on virus infection and hepatocellular carcinoma (HCC) remains unclear. Interestingly, the role of the DNA repair gene (PARP1) in therapy resistant cancers also has not been studied and explored well. In this study, we hypothesized that momelotinib could suppress the progression of HCC by targeting Jak family related and PARP1 DNA repair protein. Based on this observation, we link the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors. Methods: We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation assay, cell invasion, migration, and tumorsphere-formation assay were used for drug cytotoxicity, cell viability, and possible molecular mechanism. Result: We first demonstrated that the expression of Jak1 and 2 is significantly upregulated in vHCC than in nvHCC/normal liver tissues. In addition, the gene expression of IFN gamma-related pathways is activated after virus infection. Additionally, we found that momelotinib significantly inhibited the growth of HCC cells and reduces the expression of Jak2, which showed the importance of momelotinib in targeting Jak2 and reducing tumorigenesis in HCC. Meanwhile, momelotinib effectively inhibited the IFNGR-JAK-STAT pathway and reduced the migratory/invasive ability of vHCC cells through down-regulating EMT biomarkers (E-cadherin and vimentin), transcription factor (Slug), and significantly inhibits the DNA damage repair enzyme PARP1. It also induced cell apoptosis of vHCC cells. Furthermore, the combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden. Conclusions: Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.
Association of Circadian Clock Gene Expression with Glioma Tumor Microenvironment and Patient Survival
Authors: De La Cruz Minyety Julianie , Shuboni-Mulligan Dorela D. , Briceno Nicole , Young Demarrius , Gilbert Mark R. , Celiku Orieta , Armstrong Terri S.
Published: June 2021

Circadian clock genes have been linked to clinical outcomes in cancer, including gliomas. However, these studies have not accounted for established markers that predict the prognosis, including mutations in Isocitrate Dehydrogenase (IDH), which characterize the majority of lower-grade gliomas and secondary high-grade gliomas. To demonstrate the connection between circadian clock genes and glioma outcomes while accounting for the IDH mutational status, we analyzed multiple publicly available gene expression datasets. The unsupervised clustering of 13 clock gene transcriptomic signatures from The Cancer Genome Atlas showed distinct molecular subtypes representing different disease states and showed the differential prognosis of these groups by a Kaplan–Meier analysis. Further analyses of these groups showed that a low period (PER) gene expression was associated with the negative prognosis and enrichment of the immune signaling pathways. These findings prompted the exploration of the relationship between the microenvironment and clock genes in additional datasets. Circadian clock gene expression was found to be differentially expressed across the anatomical tumor location and cell type. Thus, the circadian clock expression is a potential predictive biomarker in glioma, and further mechanistic studies to elucidate the connections between the circadian clock and microenvironment are warranted.
Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions
Authors: Gómez Antonio , Pato Miguel L. , Bujanda Luis , Sala Núria , Companioni Osmel , Cosme Ángel , Tufano Martina , Hanly David J. , García Nadia , Sanz-Anquela José Miguel , Gisbert Javier P. , López Consuelo , Elizalde José Ignacio , Cuatrecasas Miriam , Andreu Victoria , Paules María José , Martín-Arranz María Dolores , Ortega Luis , Poves Elvira , Barrio Jesús , Torres María Ángeles , Muñoz Guillermo , Ferrández Ángel , Ramírez-Lázaro María José , Lario Sergio , González Carlos A , Esteller Manel , Berdasco María
Published: June 2021

To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.
A Review of Computer-Aided Expert Systems for Breast Cancer Diagnosis
Authors: Liew Xin Yu , Hameed Nazia , Clos Jeremie
Published: June 2021

A computer-aided diagnosis (CAD) expert system is a powerful tool to efficiently assist a pathologist in achieving an early diagnosis of breast cancer. This process identifies the presence of cancer in breast tissue samples and the distinct type of cancer stages. In a standard CAD system, the main process involves image pre-processing, segmentation, feature extraction, feature selection, classification, and performance evaluation. In this review paper, we reviewed the existing state-of-the-art machine learning approaches applied at each stage involving conventional methods and deep learning methods, the comparisons within methods, and we provide technical details with advantages and disadvantages. The aims are to investigate the impact of CAD systems using histopathology images, investigate deep learning methods that outperform conventional methods, and provide a summary for future researchers to analyse and improve the existing techniques used. Lastly, we will discuss the research gaps of existing machine learning approaches for implementation and propose future direction guidelines for upcoming researchers.