bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life
Authors: Odumade Oludare A. , Plotkin Alec L. , Pak Jensen , Idoko Olubukola T. , Pettengill Matthew A. , Kollmann Tobias R. , Ozonoff Al , Kampmann Beate , Levy Ofer , Smolen Kinga K.
Published: May 2021

Background

Human adenosine deaminases (ADAs) modulate the immune response: ADA1viametabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults. Despite the growing recognition of the role of ADAs in immune regulation, little is known about the ontogeny of ADA concentrations.

Methods

In a subgroup of the EPIC002-study, clinical data and plasma samples were collected from 540 Gambian infants at four time-points: day of birth; first week of life; one month of age; and four months of age. Concentrations of total extracellular ADA, ADA1, and ADA2 were measured by chromogenic assay and evaluated in relation to clinical data. Plasma cytokines/chemokine were measured across the first week of life and correlated to ADA concentrations.

Results

ADA2 demonstrated a steady rise across the first months of life, while ADA1 concentration significantly decreased 0.79-fold across the first week then increased 1.4-fold by four months of life. Males demonstrated significantly higher concentrations of ADA2 (1.1-fold) than females at four months; newborns with early-term (37 to <39 weeks) and late-term (≥41 weeks) gestational age demonstrated significantly higher ADA1 at birth (1.1-fold), and those born to mothers with advanced maternal age (≥35 years) had lower plasma concentrations of ADA2 at one month (0.93-fold). Plasma ADA1 concentrations were positively correlated with plasma CXCL8 during the first week of life, while ADA2 concentrations correlated positively with TNFα, IFNγ and CXCL10, and negatively with IL-6 and CXCL8.

Conclusions

The ratio of plasma ADA2/ADA1 concentration increased during the first week of life, after which both ADA1 and ADA2 increased across the first four months of life suggesting a gradual development of Th1/Th2 balanced immunity. Furthermore, ADA1 and ADA2 were positively correlated with cytokines/chemokines during the first week of life. Overall, ADA isoforms demonstrate robust ontogeny in newborns and infants but further mechanistic studies are needed to clarify their roles in early life immune development and the correlations with sex, gestational age, and maternal age that were observed.
The Diagnostic and Prognostic Potential of the B-Cell Repertoire in Membranous Nephropathy
Authors: Su Zuhui , Jin Yabin , Zhang Yu , Guan Zhanwen , Li Huishi , Chen Xiangping , Xie Chao , Zhang Chuling , Liu Xiaofen , Li Peixian , Ye Peiyi , Zhang Lifang , Kong Yaozhong , Luo Wei
Published: May 2021

Membranous nephropathy (MN), an autoimmune glomerular disease, is one of the most common causes of nephrotic syndrome in adults. In current clinical practice, the diagnosis is dependent on renal tissue biopsy. A new method for diagnosis and prognosis surveillance is urgently needed for patients. In the present study, we recruited 66 MN patients before any treatment and 11 healthy control (HC) and analyzed multiple aspects of the immunoglobulin heavy chain (IGH) repertoire of these samples using high-throughput sequencing. We found that the abnormalities of CDR-H3 length, hydrophobicity, somatic hypermutation (SHM), and germ line index were progressively more prominent in patients with MN, and the frequency of IGHV3-66 in post-therapy patients was significantly lower than that in pre-therapy patients. Moreover, we found that the IGHV3-38 gene was significantly related to PLA2R, which is the most commonly used biomarker. The most important discovery was that several IGHV, IGHD transcripts, CDR-H3 length, and SHM rate in pre-therapy patients had the potential to predict the therapeutic effect. Our study further demonstrated that the IGH repertoire could be a potential biomarker for prognosis prediction of MN. The landscape of circulating B-lymphocyte repertoires sheds new light on the detection and surveillance of MN.
Association of Circulating Vascular Endothelial Growth Factor Levels With Autoimmune Diseases: A Systematic Review and Meta-Analysis
Authors: Zhan Haoting , Li Haolong , Liu Chenxi , Cheng Linlin , Yan Songxin , Li Yongzhe
Published: May 2021

Background

Autoimmune diseases (ADs) are characterized by immune-mediated tissue damage, in which angiogenesis is a prominent pathogenic mechanism. Vascular endothelial growth factor (VEGF), an angiogenesis modulator, is significantly elevated in several ADs including rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). We determined whether circulating VEGF levels were associated with ADs based on pooled evidence.

Methods

The analyses included 165 studies from the PubMed, EMBASE, Cochrane Library, and Web of Science databases and fulfilled the study criteria. Comparisons of circulating VEGF levels between patients with ADs and healthy controls were performed by determining pooled standard mean differences (SMDs) with 95% confidence intervals (CIs) in a random-effect model using STATA 16.0. Subgroup, sensitivity, and meta-regression analyses were performed to determine heterogeneity and to test robustness.

Results

Compared with healthy subjects, circulating VEGF levels were significantly higher in patients with SLE (SMD 0.84, 95% CI 0.25–1.44, P = 0.0056), RA (SMD 1.48, 95% CI 0.82–2.15, P <0.0001), SSc (SMD 0.56, 95% CI 0.36–0.75, P <0.0001), Behcet’s disease (SMD 1.65, 95% CI 0.88–2.41, P <0.0001), Kawasaki disease (SMD 2.41, 95% CI 0.10–4.72, P = 0.0406), ankylosing spondylitis (SMD 0.78, 95% CI 0.23–1.33, P = 0.0052), inflammatory bowel disease (SMD 0.57, 95% CI 0.43–0.71, P <0.0001), psoriasis (SMD 0.98, 95% CI 0.62–1.34, P <0.0001), and Graves’ disease (SMD 0.69, 95% CI 0.20–1.19, P = 0.0056). Circulating VEGF levels correlated with disease activity and hematological parameters in ADs.

Conclusion

Circulating VEGF levels were associated with ADs and could predict disease manifestations, severity and activity in patients with ADs.

Systematic Review Registration

PROSPERO, identifier CRD42021227843.
Therapeutic Induction of Tertiary Lymphoid Structures in Cancer Through Stromal Remodeling
Authors: Johansson-Percival Anna , Ganss Ruth
Published: May 2021

Improving the effectiveness of anti-cancer immunotherapy remains a major clinical challenge. Cytotoxic T cell infiltration is crucial for immune-mediated tumor rejection, however, the suppressive tumor microenvironment impedes their recruitment, activation, maturation and function. Nevertheless, solid tumors can harbor specialized lymph node vasculature and immune cell clusters that are organized into tertiary lymphoid structures (TLS). These TLS support naïve T cell infiltration and intratumoral priming. In many human cancers, their presence is a positive prognostic factor, and importantly, predictive for responsiveness to immune checkpoint blockade. Thus, therapeutic induction of TLS is an attractive concept to boost anti-cancer immunotherapy. However, our understanding of how cancer-associated TLS could be initiated is rudimentary. Exciting new reagents which induce TLS in preclinical cancer models provide mechanistic insights into the exquisite stromal orchestration of TLS formation, a process often associated with a more functional or “normalized” tumor vasculature and fueled by LIGHT/LTα/LTβ, TNFα and CC/CXC chemokine signaling. These emerging insights provide innovative opportunities to induce and shape TLS in the tumor microenvironment to improve immunotherapies.
A Patient-Controlled Intravenous Analgesia With Tramadol Ameliorates Postpartum Depression in High-Risk Woman After Cesarean Section: A Randomized Controlled Trial
Authors: Wu Zhuoxi , Zhao Peng , Peng Jing , Fang Liang , Ding Jinping , Yan Guangming , Wang Yang , Zhu Jing , Wang Dongting , Li Yang , Chen Zhengqiong , Zhang Qingling , Deng Qiangting , Duan Guangyou , Zuo Zhiyi , Li Hong
Published: May 2021

Background: Postpartum depression (PPD) is a severe psychiatric disorder. Its risk is associated with the cesarean section (CS). Currently, there are few early intervention strategies for these women with PPD who underwent CS.

Methods: This was a parallel-group randomized controlled trial of singleton pregnant women who underwent elective CS in a tertiary referral hospital in China from October, 2017 to September, 2019. After operation, patients received randomly tramadol patient-controlled intravenous analgesia (PCIA; 4 mg/ml; TRA group), hydromorphone PCIA (0.04 mg/ml; HYD group), or ropivacaine patient-controlled epidural analgesia (PCEA; 1.5 mg/ml; ROP group) for 48 h in a 1:1:1 ratio. Total blinding during hospitalization was not feasible due to differences between the PCEA and PCIA treatments. All investigators who performed the follow-up were blinded to the group assignment.

Outcomes: A total of 1,230 patients were enrolled for eligibility. Intention-to-treat analysis showed reduced incidence of PPD in the TRA group (n = 27 [6.6%]) than that in the HYD (10.2%, OR 1.62, 95% CI 0.98~2.68; p = 0.059) and ROP groups (10.5%, OR 1.66, 95% CI 1.01~2.75; p = 0.046) at 4 weeks post-operation, however, the difference was not statistically significant (Bonferroni corrected p = 0.118, p = 0.098, respectively). Subgroup analysis in high-risk women (preoperative Edinburgh Postpartum Depression Scale [EPDS] ≥10) showed a significantly lower incidence of PPD in the TRA group (16.5%) than in the HYD (32.6%) and ROP groups (30.9%) (Bonferroni corrected p = 0.022 and p = 0.038, respectively). The per-protocol analysis yielded similar results. Reported adverse events (AEs) were mostly mild. None of the women or infant discontinued treatment due to AEs.

Conclusions: Tramadol PCIA after CS in high-risk women can help to reduce the risk of PPD at 4 weeks after elective CS.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03309163?term=ETPPD&draw=2&rank=1; ClinicalTrials.gov (NCT03309163).
Blood Microsampling to Monitor Metabolic Profiles During Physical Exercise
Authors: Nix Cindy , Hemmati Maryam , Cobraiville Gaël , Servais Anne-Catherine , Fillet Marianne
Published: May 2021

Monitoring approaches and technical improvements are key factors to improve a sportsman’s health, training, and recovery after an injury. In this study, a targeted metabolomics approach using microsampling with hemaPEN® was developed to measure changes in blood concentrations of nine amino acids and four organic acids before, during, and after exercise. The aim of this research project was to investigate if a reliable monitoring of metabolite levels during sports activity can be achieved by collecting one drop of whole blood at different time points. A hemaPEN device is an easy-to-use and noninvasive microsampling technique designed to collect four accurate and precise blood volumes simultaneously (10.96 µl). Twenty healthy volunteers between 19 and 30 years of age were included in this study. Physical activity consisted in running as fast as possible 1,600 m after 400 m warm-up. One drop of blood was collected at five time points: before exercise, after 800-m running, after 1,600 m, and 30 min and 60 min after finishing the exercise. The influence of physical activity on metabolite levels was evaluated using two ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) methods. Analytical performance criteria such as metabolite stability, method precision, trueness, and accuracy were found to be satisfactory. Expected significant metabolic changes were identified for lactic acid, main TCA cycle intermediates, and some amino acids (e.g., creatinine, choline, and taurine). This preliminary study performed on a small cohort demonstrated a high interest of using microsampling for fluxomics analysis, not only to collect quickly and easily biological samples during sports events but also because it is much easier to store and to process the samples than classical plasma/serum samples obtained by venipuncture. The present results open new avenue for fluxomics analysis in the context of health care.
A Combined Long Noncoding RNA Signature as a Candidate Prognostic Biomarker for Ovarian Cancer
Authors: Li Hui , Wang Shuoer , Yao Qianlan , Liu Yan , Yang Jing , Xu Lun , Yang Gong
Published: May 2021

Aims

Dysregulated long noncoding RNAs (lncRNAs) contributing to ovarian cancer (OC) development may serve as prognostic biomarker. We aimed to explore a lncRNA signature to serve as prognostic biomarker of OC.

Methods

Univariate Cox regression was conducted on the lncRNA expression dataset from the TCGA cohort, and 246 genes significantly associated with survival were retained for building a model. A random forest survival model was carried out, and a model was developed using 6 genes with the highest frequency. The selected genes were applied in a Cox multivariate regression model for prognostic prediction by calculating the risk score. We also used CCK-8, EdU, and colony formation assays to validate the function of these lncRNAs in OC cells.

Results

This study confirmed that the 6-lncRNA combined signature was related to OC prognosis. Systematic analysis demonstrated that lncRNA-associated genes were enriched in oncogenic signalling pathways. Five out of the 6 lncRNAs participated in OC proliferation.

Conclusion

We established a 6-lncRNA combined signature for OC prognosis, which may serve as powerful prognostic biomarker for OC after further validation.
Risk Factors, Patterns, and Long-Term Survival of Recurrence After Radiofrequency Ablation With or Without Transarterial Chemoembolization for Hepatocellular Carcinoma
Authors: Huang Jingjun , Huang Wensou , Guo Yongjian , Cai Mingyue , Zhou Jingwen , Lin Liteng , Zhu Kangshun
Published: May 2021

Objectives

To classify hepatocellular carcinoma (HCC) recurrence patterns after radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) combined with RFA (TACE-RFA) and analyze their risk factors and impacts on survival.

Methods

We retrospectively evaluated the medical records of HCC patients who underwent RFA or TACE-RFA from January 2006 to December 2016. HCC recurrences were classified into four patterns: local tumor progression (LTP), intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence. Risk factors, overall survival (OS), and post-recurrence survival of each pattern were evaluated.

Results

A total of 249 patients with a single, hepatitis-B virus (HBV)-related HCC ≤ 5.0 cm who underwent RFA (HCC ≤ 3.0 cm) or TACE-RFA (HCC of 3.1-5.0 cm) were included. During follow-up (median, 53 months), 163 patients experienced HCC recurrence: 40, 43, 62 and 18 patients developed LTP, intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence, respectively; the median post-recurrence survival was 49, 37, 25 and 15 months, respectively (P < .001); the median OS was 65, 56, 58 and 28 months, respectively (P < .001). Independent risk factors for each pattern were as follows: tumor sized 2.1-3.0 cm undergoing RFA alone and insufficient ablative margin for LTP, periportal tumor and non-smooth tumor margin for intra-segmental recurrence, HBV-DNA ≥ 2000 IU/mL for extra-segmental recurrence, and periportal tumor and α-fetoprotein ≥ 100 ng/mL for aggressive recurrence. Recurrence pattern (P < .001) and Child-Pugh class B (P = .025) were independent predictors for OS.

Conclusions

Based on our classification, each recurrence pattern had different recurrence risk factors, OS, and post-recurrence survival.
Risk of Cardiac Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-Analysis
Authors: Hu Jiexuan , Tian Ruyue , Ma Yingjie , Zhen Hongchao , Ma Xiao , Su Qiang , Cao Bangwei
Published: May 2021

Background

We performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy.

Methods

Eligible studies were selected through the following databases: PubMed, Embase and clinical trials (https://clinicaltrials.gov.) and included phase III/IV randomized controlled trials (RCTs) involving patients with the solid tumor treated with ICIs. The data was analyzed by using Review Manager (version5.3), Stata (version 15.1).

Results

Among 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08–14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1–5 myocardial disease (OR 5.09, 95% CI: 1.11–23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1–5 arrhythmology (OR 2.49, 95% CI: 1.30–4.78, p = 0.289).

Conclusions

Our meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.
Prediction of Immune-Checkpoint Blockade Monotherapy Response in Patients With Melanoma Based on Easily Accessible Clinical Indicators
Authors: Byun Hwa Kyung , Chang Jee Suk , Jung Minkyu , Koom Woong Sub , Chung Kee Yang , Oh Byung Ho , Roh Mi Ryung , Kim Kyung Hwan , Lee Choong-Kun , Shin Sang Joon
Published: May 2021

Background

Immune checkpoint blocker (ICB) has shown significant clinical activity in melanoma. However, there are no clinically approved biomarkers to aid patient selection. We aimed to identify patients with advanced or metastatic melanoma who are likely to benefit from ICB monotherapy using easily accessible clinical indicators.

Materials and Methods

We retrospectively reviewed the records of 134 patients with advanced or metastatic melanoma who received ICB monotherapy between 2014 and 2018. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were determined using Cox regression analysis.

Results

During the median follow-up of 13.7 months, the median OS and PFS were 18.4 and 3.4 months, respectively. Visceral/central nervous system (CNS) metastasis (OS: adjusted hazards ratio [HR], 1.82; p=.014; PFS: HR, 1.59; p=.024), lymphopenia (<1000 cells/µL) within 3 months (OS: HR, 1.89, p=.006; PFS: HR, 1.70; p=.010), and elevated baseline lactate dehydrogenase (LDH) level (OS: HR, 2.61; p<.001; PFS: HR, 2.66; p<.001) were independent prognostic factors for both poor OS and PFS. Development of immune-related adverse events (irAE; e.g., hypothyroidism or vitiligo) within 6 months showed a trend toward better OS in multivariable analysis (HR, 0.37; p=.058). Patients with normal LDH levels and no visceral/CNS metastasis had a substantially better OS than the others (median, 40.4 vs. 13.6 months; p<.001). Among others, patients who developed irAE within 6 months achieved long-term OS (median, 43.6 vs. 13.1 months; p=.008). A decision tree was suggested using four risk factors, and the risk stratification provided significant distinction between the survival curves.

Conclusion

The four easily accessible clinical indicators associated with better treatment outcomes after ICB monotherapy in patients with advanced or metastatic melanoma were LDH level, the extent of disease, lymphopenia, and irAE. The combined use of these indicators can be clinically useful in improving risk stratification of patients treated with ICB monotherapy.
Treating Bladder Cancer: Engineering of Current and Next Generation Antibody-, Fusion Protein-, mRNA-, Cell- and Viral-Based Therapeutics
Authors: Bogen Jan P. , Grzeschik Julius , Jakobsen Joern , Bähre Alexandra , Hock Björn , Kolmar Harald
Published: May 2021

Bladder cancer is a frequent malignancy and has a clinical need for new therapeutic approaches. Antibody and protein technologies came a long way in recent years and new engineering approaches were applied to generate innovative therapeutic entities with novel mechanisms of action. Furthermore, mRNA-based pharmaceuticals recently reached the market and CAR-T cells and viral-based gene therapy remain a major focus of biomedical research. This review focuses on the engineering of biologics, particularly therapeutic antibodies and their application in preclinical development and clinical trials, as well as approved monoclonal antibodies for the treatment of bladder cancer. Besides, newly emerging entities in the realm of bladder cancer like mRNA, gene therapy or cell-based therapeutics are discussed and evaluated. As many discussed molecules exhibit unique mechanisms of action based on innovative protein engineering, they reflect the next generation of cancer drugs. This review will shed light on the engineering strategies applied to develop these next generation treatments and provides deeper insights into their preclinical profiles, clinical stages, and ongoing trials. Furthermore, the distribution and expression of the targeted antigens and the intended mechanisms of action are elucidated.
10 nm SiO2 TM Slot Mode in Laterally Mismatched Asymmetric Fin-Waveguides
Authors: Byers James , Debnath Kapil , Arimoto Hideo , Husain Muhammad K. , Sotto Moïse , Hillier Joseph , Kiang Kian , Thomson David J. , Reed Graham T. , Charlton Martin , Saito Shinichi
Published: May 2021

In this paper we demonstrate that by breaking the left/right symmetry in a bi-planar double-silicon on insulator (SOI) photonic crystal (PhC) fin-waveguide, we can couple the conventionally used transverse-electric (TE) polarized mode to the transverse-magnetic (TM) polarization slot-mode. Finite difference time domain (FDTD) simulations indicate that the TE mode couples to the robust TM mode inside the Brillouin zone. Broadband transmission data shows propagation identified with horizontal-slot TM mode within the TE bandgap for fully mismatched fabricated devices. This simultaneously demonstrates TE to TM mode conversion, and the narrowest Si photonics SiO2 slot-mode propagation reported in the literature (10 nm wide slot), which both have many potential telecommunication applications.
Speeding Up the Heart? Traditional and New Perspectives on HCN4 Function
Authors: Hennis Konstantin , Rötzer René D. , Piantoni Chiara , Biel Martin , Wahl-Schott Christian , Fenske Stefanie
Published: May 2021

The sinoatrial node (SAN) is the primary pacemaker of the heart and is responsible for generating the intrinsic heartbeat. Within the SAN, spontaneously active pacemaker cells initiate the electrical activity that causes the contraction of all cardiomyocytes. The firing rate of pacemaker cells depends on the slow diastolic depolarization (SDD) and determines the intrinsic heart rate (HR). To adapt cardiac output to varying physical demands, HR is regulated by the autonomic nervous system (ANS). The sympathetic and parasympathetic branches of the ANS innervate the SAN and regulate the firing rate of pacemaker cells by accelerating or decelerating SDD–a process well-known as the chronotropic effect. Although this process is of fundamental physiological relevance, it is still incompletely understood how it is mediated at the subcellular level. Over the past 20 years, most of the work to resolve the underlying cellular mechanisms has made use of genetically engineered mouse models. In this review, we focus on the findings from these mouse studies regarding the cellular mechanisms involved in the generation and regulation of the heartbeat, with particular focus on the highly debated role of the hyperpolarization-activated cyclic nucleotide-gated cation channel HCN4 in mediating the chronotropic effect. By focusing on experimental data obtained in mice and humans, but not in other species, we outline how findings obtained in mice relate to human physiology and pathophysiology and provide specific information on how dysfunction or loss of HCN4 channels leads to human SAN disease.
Industry 4.0 Readiness of Technology Companies: A Pilot Study from Malaysia
Authors: Soomro Mansoor Ahmed , Hizam-Hanafiah Mohd , Abdullah Nor Liza , Ali Mohd Helmi , Jusoh Muhammad Shahar
Published: May 2021

Industry 4.0 has the potential to cause both evolutionary (operational) and revolutionary (strategic) changes, but assessing the readiness of companies towards Industry 4.0 has largely been a challenge. Industry 4.0 readiness is also important as it is the first step for companies that want to adopt Industry 4.0 technologies. This paper pilot surveys 100 technology companies in Malaysia to understand their overall readiness towards Industry 4.0. In particular, this research paper contributes to the assessment of Industry 4.0 readiness in terms of seven key areas: (i) Market pressure, (ii) risk-taking, (iii) knowledge, (iv) management support, (v) competencies, (vi) motivation and (vii) freedom. These findings can act as stepping stones for managers and companies that are aiming towards the implementation of Industry 4.0 readiness.
Numerical Investigation on the Thermal Behaviour of a LOx/LCH4 Demonstrator Cooling System
Authors: Ricci Daniele , Battista Francesco , Fragiacomo Manrico
Published: May 2021

Reliability of liquid rocket engines is strictly connected with the successful operation of cooling jackets, able to sustain the impressive operative conditions in terms of huge thermal and mechanical loads, generated in thrust chambers. Cryogenic fuels, like methane or hydrogen, are often used as coolants and they may behave as transcritical fluids flowing in the jackets: after injection in a liquid state, a phase pseudo-change occurs along the chamber because of the heat released by combustion gases and coolants exiting as a vapour. Thus, in the development of such subsystems, important issues are focused on numerical methodologies adopted to simulate the fluid thermal behaviour inside the jackets, design procedures as well as manufacturing and technological process topics. The present paper includes the numerical thermal analyses regarding the cooling jacket belonging to the liquid oxygen/liquid methane demonstrator, realized in the framework of the HYPROB (HYdrocarbon PROpulsion test Bench) program. Numerical results considering the nominal operating conditions of cooling jackets in the methane-fuelled mode and the water-fed one are included in the case of the application of electrodeposition process for manufacturing. A comparison with a similar cooling jacket, realized through the conventional brazing process, is addressed to underline the benefits of the application of electrodeposition technology.
Compost as an Option for Sustainable Crop Production at Low Stocking Rates in Organic Farming
Authors: Brock Christopher , Oltmanns Meike , Matthes Christoph , Schmehe Ben , Schaaf Harald , Burghardt Detlef , Horst Hartmut , Spieß Hartmut
Published: May 2021

Mixed-crop-livestock farms offer the best conditions for sustainable nutrient management in organic farming. However, if stocking rates are too low, sustainability might be threatened. Therefore, we studied the development of soil organic matter and nutrients as well as crop yields over the first course of a new long-term field experiment with a mimicked cattle stocking rate of 0.6 LU ha−1, which is the actual average stocking rate for organic farms in Germany. In the experiment, we tested the effects of additional compost application to improve organic matter supply to soils, and further, potassium sulfate fertilization for an improved nutrition of fodder legumes. Compost was made from internal resources of the farm (woody material from hedge-cutting). Soil organic matter and nutrient stocks decreased in the control treatment, even though yield levels, and thus nutrient exports, were comparably low. With compost application, soil organic matter and nutrient exports could be compensated for. At the same time, the yields increased but stayed at a moderate level. Potassium sulfate fertilization further improved N yields. We conclude that compost from internal resources is a viable solution to facilitate sustainable organic crop production at low stocking rates. However, we are aware that this option does not solve the basic problem of open nutrient cycles on the farm gate level.
Effect of Exogenously Applied Methyl Jasmonate on Yield and Quality of Salt-Stressed Hydroponically Grown Sea Fennel (Crithmum maritimum L.)
Authors: Labiad M. Hatim , Giménez Almudena , Varol Hafise , Tüzel Yüksel , Egea-Gilabert Catalina , Fernández Juan A. , Martínez-Ballesta María del Carmen
Published: May 2021

Salt stress is one of the main limiting factors for plant growth and crop yield. Halophytes have been postulated as a new food source since they are able to grow under saline environments and have suitable minerals and bioactive compounds. See fennel Crithmum maritimum L. is a facultative halophyte moderately tolerant to salinity. This study was carried out in order to determine the effect spraying methyl jasmonate (MeJa) on the leaves had on the growth and nutritional quality of NaCl-treated sea fennel plants grown in a hydroponic system. For that, the seedlings were treated with (a) 0.5 mM MeJa, (b) 150 mM NaCl, and (c) 0.5 mM MeJa + 150 mM NaCl. The results showed that NaCl reduced the shoot biomass of baby leaf plants, but the addition of MeJa enabled partial recovery. At the same time, when compared with the plants treated only with NaCl, MeJa favoured the Ca and K uptake and translocation to the leaves of saline-treated plants. However, MeJa did not reduce Na levels. In all treatments, nitrate and nitrite ions were in the range of the acceptable daily intake (ADI) and essential fatty acid content was elevated, although the addition of MeJa to NaCl-treated plants reduced linolenic and linoleic acid contents as compared to the plants treated only with NaCl. Total phenolic compounds were not recovered by MeJa after their decrease by salinity and no differences in antioxidant activity was found between treatments. However, all the plants maintained their antioxidant nutritional properties and increased total flavonoids after MeJa spraying to NaCl-treated plants. These results showed that MeJa spraying alleviated the negative effects of salt stress in C. maritimum grown in floating systems, improving the growth of their edible parts and increasing the total flavonoid and mineral content without affecting the total antioxidant capacity of the plant.
Intercultivar Diversity of Sour Orange (Citrus aurantium L.) Based on Genetic Markers, Phenotypic Characteristics, Aromatic Compounds and Sensorial Analysis
Authors: Ferrer Vincent , Costantino Gilles , Paoli Mathieu , Paymal Noémie , Quinton Carole , Ollitrault Patrick , Tomi Félix , Luro François
Published: May 2021

Sour oranges (Citrus aurantium L.) are well known in the processing and cosmetics industries for the aromatic properties of their essential oils. Intercultivar genetic and aromatic diversity is not well documented. The objective of this study was to evaluate the impact of morphological selection and genetic mechanisms of varietal diversification (mutation or hybridization) on the aromatic and odor variability of sour orange essential oils. Forty-five sour orange accessions from INRAE-CIRAD citrus Biological Resources Center (France) were assessed for ten simple sequence repeat (SSR) and 54 single nucleotide polymorphism (SNP) markers, nine morphochemical fruit traits and with the aromatic components of leaf and peel essential oils. Thirty-nine sour oranges displayed no intercultivar molecular polymorphism and six genotypes originated from interspecific hybridizations involving sour orange, citron, pummelo or mandarin. The peel essential oil (PEO) diversity was low, in accordance with the genetic diversity. The predominance of limonene (>90%) prevents any possible correlation to be made between the composition and the variation in sensory profiles detected by panelists. Few compounds in the leaf essential oil (LEO), such as linalool, linalyl acetate, α-terpineol and geraniol were significantly different across sour oranges varieties. The morphological fruit attributes mainly used in varietal selection differed highly across the main genetically identical group of sour orange accessions. These results confirm that mutation can generate variability in aromatic compounds and aromas and that their exploitation requires an improvement in characterization processes.
Application of Pollen Germination Media on Stigmas during Pollination Increases Seed Set in East African Highland Cooking Bananas (Musa spp.)
Authors: Waniale Allan , Swennen Rony , Mukasa Settumba B. , Tugume Arthur K. , Kubiriba Jerome , Tushemereirwe Wilberforce K. , Amah Delphine , Tumuhimbise Robooni
Published: May 2021

Seed set in East African Highland Cooking bananas (EAHBs) is extremely low and therefore hampers breeding. Pollen–pistil interaction is a key contributing factor. We assessed the effect of pollen germination media (PGM) on seed set in EAHBs. Five EAHB cultivars were pollinated with pollen from the wild banana ‘Calcutta 4’. Glucose-based PGM sprayed on freshly emerged stigmas significantly increased seed set per 100 fruits per bunch. Increases were 73.5% in ‘Enzirabahima’, 39.9% in ‘Mshale’, and 302.4% in ‘Nshonowa’. However, PGM did not increase seed set in the female sterile ‘Mlelembo’ and ‘Nakitembe’. As larger bunches were more fertile, good field management practices are also recommended to get more seed to improve breeding efficiency.
Arundo donax L.: How High Photosynthetic Capacity Is Maintained under Water Scarcity Conditions
Authors: Sánchez Elena , Rivera-Vargas Pablo , Serrat Xavier , Nogués Salvador
Published: May 2021

Arundo donax L. (giant reed) is a perennial rhizomatous grass and has been identified as an important non-food biomass crop with capacity for cultivation in marginal and degraded lands where water scarcity conditions frequently occur due to climate change. This review analyzes the effect of water stress on photosynthetic capacity and biomass production in multiple giant reed ecotypes grown in different regions around the world. Furthermore, this review will attempt to explain the reason for the high photosynthetic capacity of giant reed even under changing environmental conditions as well as indicate other morphological reasons that could contribute to maintaining this high photosynthetic rate. Finally, future research in favor of selecting ecotypes with drought tolerance is proposed.
Application of Genomic Data for Reliability Improvement of Pig Breeding Value Estimates
Authors: Melnikova Ekaterina , Kabanov Artem , Nikitin Sergey , Somova Maria , Kharitonov Sergey , Otradnov Petr , Kostyunina Olga , Karpushkina Tatiana , Martynova Elena , Sermyagin Aleksander , Zinovieva Natalia
Published: May 2021

Replacement pigs’ genomic prediction for reproduction (total number and born alive piglets in the first parity), meat, fatness and growth traits (muscle depth, days to 100 kg and backfat thickness over 6–7 rib) was tested using single-step genomic best linear unbiased prediction ssGBLUP methodology. These traits were selected as the most economically significant and different in terms of heritability. The heritability for meat, fatness and growth traits varied from 0.17 to 0.39 and for reproduction traits from 0.12 to 0.14. We confirm from our data that ssGBLUP is the most appropriate method of genomic evaluation. The validation of genomic predictions was performed by calculating the correlation between preliminary GEBV (based on pedigree and genomic data only) with high reliable conventional estimates (EBV) (based on pedigree, own phenotype and offspring records) of validating animals. Validation datasets include 151 and 110 individuals for reproduction, meat and fattening traits, respectively. The level of correlation (r) between EBV and GEBV scores varied from +0.44 to +0.55 for meat and fatness traits, and from +0.75 to +0.77 for reproduction traits. Average breeding value (EBV) of group selected on genomic evaluation basis exceeded the group selected on parental average estimates by 22, 24 and 66% for muscle depth, days to 100 kg and backfat thickness over 6–7 rib, respectively. Prediction based on SNP markers data and parental estimates showed a significant increase in the reliability of low heritable reproduction traits (about 40%), which is equivalent to including information about 10 additional descendants for sows and 20 additional descendants for boars in the evaluation dataset.
Ruminal Protozoal Populations of Angus Steers Differing in Feed Efficiency
Authors: Clemmons Brooke A. , Shin Sung B. , Smith Timothy P. L. , Embree Mallory M. , Voy Brynn H. , Schneider Liesel G. , Donohoe Dallas R. , McLean Kyle J. , Myer Phillip R.
Published: May 2021

Feed accounts for as much as 70% of beef production costs, and improvement of the efficiency with which animals convert feed to product has the potential to have substantial financial impact on the beef industry. The rumen microbiome plays a key role in determining feed efficiency; however, previous studies of rumen microbiota have not focused on protozoal communities despite the estimation that these organisms represent approximately 50% of rumen content biomass. Protozoal communities participate in the regulation of bacterial populations and nitrogen cycling—key aspects of microbiome dynamics. The present study focused on identifying potential associations of protozoal community profiles with feed efficiency. Weaned steers (n = 50) 7 months of age weighing approximately 260 kg were adapted to a growing ration and GrowSafe for 2 weeks prior to a 70-day feed efficiency trial. The GrowSafe system is a feeding system that monitors feed intake in real time. Body weights were collected on the first day and then every 7 days of the feed efficiency trial, and on the final day, approximately 50 mL of rumen content were collected via orogastric tubing and frozen at −80 °C. Body weight and feed intake were used to calculate residual feed intake (RFI) as a measure of feed efficiency, and steers were categorized as high (n = 14) or low (n = 10) RFI based on ±0.5 standard deviations about the mean RFI. Microbial DNA was extracted, and the eukaryotic component profiled by amplification and sequencing of 18S genes using degenerate primers that can amplify this locus across a range of protists. The taxonomy of protozoal sequences was assigned using QIIME 1.9 and analyzed using QIIME and SAS 9.4 with significance determined at α ≤ 0.05. Greater abundances of unassigned taxa were associated with high-RFI steers (p = 0.03), indicating a need for further study to identify component protozoal species. Differences were observed between low- and high-RFI steers in protozoal community phylogenetic diversity, including weighted beta-diversity (p = 0.04), Faith’s phylogenetic diversity (p = 0.03), and observed Operational taxonomic unit (OTU) (p = 0.03). The unassigned taxa and differences in phylogenetic diversity of protozoal communities may contribute to divergences observed in feed efficiency phenotypes in beef steers.
Therapeutics of Twin Pregnancies in Dairy Cattle
Authors: Ispierto Irina Garcia
Published: May 2021

The series of eight articles (three original articles, three reviews and two com-ments) is presented by international leaders in the subject of twin pregnancies in dairy cattle [...]
Early Nutrition with Different Diets Composition versus Fasting on Immunity-Related Gene Expression and Histomorphology of Digestive and Lymphoid Organs of Layer-Type Chicks
Authors: Selim Shaimaa , Abdel-Megeid Nazema S. , Abou-Elnaga Manal K. , Mahmoud Samy F.
Published: May 2021

Early feeding post-hatching (EFPH) can impact the immune response and modify the immunity-related gene expression. Therefore, we aimed to examine the effects of EFPH with different diets composition versus fasting during the first 72 h of chick’s life on the histomorphological structures of the liver, proventriculus, central and peripheral lymphoid organs, and immunity-related genes in layer-type chicks during the brooding period. A total of 400 chicks were randomly allotted into 4 groups with 4 replicates each. The experimental groups during the first 72 h of life were: feed and water deprivation (control, T1), feeding a starter layer diet (20% CP and 11.84 MJ/kg ME, T2), feeding a starter layer diet contained 3% molasses in its composition (20% CP and 11.81 MJ/kg ME; T3), and feeding a starter broiler diet (23% CP and 12.68 MJ/kg ME, T4). After the first 72 h of chick’s life, all chicks were fed ad libitum the T2 diet. EFPH had no negative effect on the development of the lymphoid or digestive organs in chicks. Greater relative weights of the spleen and bursa of Fabricius (p < 0.05) were observed in the early fed chicks compared to control at day 14 of age. Histomorphological examination revealed an increase (p < 0.05) in thymus cortex and cortex:medulla in the T3 and T4 groups compared to the fasted ones at day 28 of age. Pelicae height, follicular width, cortex, and cortex:medulla of bursa were improved (p < 0.01) in the fed groups compared to fasted chicks, with resultant influences on the primary lymphoid organs. Compared to control, higher germinal center areas and white pulp of the spleen (p < 0.05) were recorded in the early fed chicks, implying augmented proliferation and maturation of B cells in the secondary lymphoid organs. In the liver, a strong positive reaction to Best’s carmine stain in the early fed groups, indicating that the liver of these chicks had numerous glycogen granules or greater glycogen density in the cytoplasm of hepatocytes. There was a significant enhancement in the proventriculus mucosal and gland thickness, as well as fold height (p < 0.05) in the early fed chicks. The expression levels of splenic Toll-like receptor 2, interleukin 4, tumor necrosis factor α, and interferon gamma were up-regulated (p < 0.01) in most of the early fed chicks (T2, T3, and T4) compared to fasted ones at 14 day of age. In conclusion, EFPH could modify the splenic-immunity related genes and modulate the histomorphology of the digestive (liver and proventriculus) and lymphoid organs in layer-type chicks during the brooding period.
DNA Protection by an Aronia Juice-Based Food Supplement
Authors: Bakuradze Tamara , Meiser Peter , Galan Jens , Richling Elke
Published: May 2021

Background: This study investigated the effects of an aronia juice-based food supplement on background and total DNA strand breaks in whole blood, and on H2O2-induced DNA strand breaks in isolated peripheral blood lymphocytes. Methods: Ninety-one healthy volunteers were randomly selected to consume either the food supplement (2 × 25 mL drinking ampules, n = 45) or no supplement (n = 46) daily for eight weeks. Results: Background DNA strand breaks decreased significantly after four and eight weeks of supplement consumption, compared to baseline (p < 0.05), but the overall effect was low, and neither group showed a decrease in total DNA strand breaks. Conversely, supplement consumption clearly reduced H2O2-induced DNA strand breaks ex vivo (p < 0.001), with statistically significant reductions after four and eight weeks, compared to the control group (p < 0.05). Conclusions: Thus, although consuming antioxidant supplements might produce only marginal immediate benefits under healthy conditions, potential preventive effects warrant further investigation.
Multi-Sensor Fusion Positioning Method Based on Batch Inverse Covariance Intersection and IMM
Authors: Liu Yanxu , Deng Zhongliang , Hu Enwen
Published: May 2021

For mass application positioning demands, the current single positioning sensor cannot provide reliable and accurate positioning. Herein, we present batch inverse covariance intersection (BICI) and BICI with interacting multiple model (BICI-IMM) multi-sensor fusion positioning methods, which are based on the batch form of the sequential inverse covariance intersection (SICI) fusion method. Meanwhile, it is proved that the BICI is robust. Compared with SICI, BICI-IMM reduces estimation error variance of the motion model and has less conservativeness. The BICI-IMM algorithm improves the accuracy of local filtering by interacting with multiple models and realizes global fusion estimation based on BICI. The validity of the BICI and BICI-IMM algorithm are demonstrated by two simulations and experiments in the open and semi-open scenes, and its positioning accuracy relations are shown. In addition, it is demonstrated that the BICI-IMM algorithm can improve the positioning accuracy in the actual scenes.
Dynamic Modeling and Control of a Parallel Mechanism Used in the Propulsion System of a Biomimetic Underwater Vehicle
Authors: Algarín-Pinto Juan Antonio , Garza-Castañón Luis E. , Vargas-Martínez Adriana , Minchala-Ávila Luis I.
Published: May 2021

Incorporation of parallel mechanisms inside propulsion systems in biomimetic autonomous underwater vehicles (BAUVs) is a novel approach for motion generation. The vehicle to which the studied propulsion system is implemented presents thunniform locomotion, and its thrust depends mainly on the oscillation from its caudal fin. This paper describes the kinematic and dynamic modeling of a 3-DOF spherical 3UCU-1S parallel robotic system to which the caudal fin of a BAUV is attached. Lagrange formalism was employed for inverse dynamic modeling, and its derivation is detailed throughout this paper. Additionally, the implementation of control strategies to compute forces required to actuate limbs to change platform’s flapping frequencies was developed. Four controllers: classic PD, a feedforward plus feedback PD, an adaptive Fuzzy-PD, and a feedforward plus Fuzzy-PD were compared in different simulations. Results showed that augmenting oscillating frequencies (from 0.5 to 5 Hz) increased the complexity of the path tracking task, where the classic control strategy (i.e., PD) was not sufficient, reaching percentage errors above 9%. Control strategies using feedforward terms combined with adaptive feedback techniques reduced tracking error below 2% even during the presence of external disturbances.