bluuebunny/crossref_metadata_2025 huggingface dataset:
A General Framework for Spatio-Temporal Modeling of Epidemics With Multiple Epicenters: Application to an Aerially Dispersed Plant Pathogen
Authors: Ojwang' Awino M. E. , Ruiz Trevor , Bhattacharyya Sharmodeep , Chatterjee Shirshendu , Ojiambo Peter S. , Gent David H.
Published: November 2021

The spread dynamics of long-distance-dispersed pathogens are influenced by the dispersal characteristics of a pathogen, anisotropy due to multiple factors, and the presence of multiple sources of inoculum. In this research, we developed a flexible class of phenomenological spatio-temporal models that extend a modeling framework used in plant pathology applications to account for the presence of multiple sources and anisotropy of biological species that can govern disease gradients and spatial spread in time. We use the cucurbit downy mildew pathosystem (caused by Pseudoperonospora cubensis) to formulate a data-driven procedure based on the 2008 to 2010 historical occurrence of the disease in the U.S. available from standardized sentinel plots deployed as part of the Cucurbit Downy Mildew ipmPIPE program. This pathosystem is characterized by annual recolonization and extinction cycles, generating annual disease invasions at the continental scale. This data-driven procedure is amenable to fitting models of disease spread from one or multiple sources of primary inoculum and can be specified to provide estimates of the parameters by regression methods conditional on a function that can accommodate anisotropy in disease occurrence data. Applying this modeling framework to the cucurbit downy mildew data sets, we found a small but consistent reduction in temporal prediction errors by incorporating anisotropy in disease spread. Further, we did not find evidence of an annually occurring, alternative source of P. cubensis in northern latitudes. However, we found a signal indicating an alternative inoculum source on the western edge of the Gulf of Mexico. This modeling framework is tractable for estimating the generalized location and velocity of a disease front from sparsely sampled data with minimal data acquisition costs. These attributes make this framework applicable and useful for a broad range of ecological data sets where multiple sources of disease may exist and whose subsequent spread is directional.
Single-Cell RNA Sequencing Defines the Regulation of Spermatogenesis by Sertoli-Cell Androgen Signaling
Authors: Cao Congcong , Ma Qian , Mo Shaomei , Shu Ge , Liu Qunlong , Ye Jing , Gui Yaoting
Published: November 2021

Androgen receptor (AR) signaling is essential for maintaining spermatogenesis and male fertility. However, the molecular mechanisms by which AR acts between male germ cells and somatic cells during spermatogenesis have not begun to be revealed until recently. With the advances obtained from the use of transgenic mice lacking AR in Sertoli cells (SCARKO) and single-cell transcriptomic sequencing (scRNA-seq), the cell specific targets of AR action as well as the genes and signaling pathways that are regulated by AR are being identified. In this study, we collected scRNA-seq data from wild-type (WT) and SCARKO mice testes at p20 and identified four somatic cell populations and two male germ cell populations. Further analysis identified that the distribution of Sertoli cells was completely different and uncovered the cellular heterogeneity and transcriptional changes between WT and SCARKO Sertoli cells. In addition, several differentially expressed genes (DEGs) in SCARKO Sertoli cells, many of which have been previously implicated in cell cycle, apoptosis and male infertility, have also been identified. Together, our research explores a novel perspective on the changes in the transcription level of various cell types between WT and SCARKO mice testes, providing new insights for the investigations of the molecular and cellular processes regulated by AR signaling in Sertoli cells.
Shelf-Life Extension of Fc-Fused Single Chain Fragment Variable Antibodies by Lyophilization
Authors: Schneider Kai-Thomas , Kirmann Toni , Wenzel Esther Veronika , Grosch Jan-Hendrik , Polten Saskia , Meier Doris , Becker Marlies , Matejtschuk Paul , Hust Michael , Russo Giulio , Dübel Stefan
Published: November 2021

Generation of sequence defined antibodies from universal libraries by phage display has been established over the past three decades as a robust method to cope with the increasing market demand in therapy, diagnostics and research. For applications requiring the bivalent antigen binding and an Fc part for detection, phage display generated single chain Fv (scFv) antibody fragments can rapidly be genetically fused to the Fc moiety of an IgG for the production in eukaryotic cells of antibodies with IgG-like properties. In contrast to conversion of scFv into IgG format, the conversion to scFv-Fc requires only a single cloning step, and provides significantly higher yields in transient cell culture production than IgG. ScFv-Fcs can be effective as neutralizing antibodiesin vivoagainst a panel of pathogens and toxins. However, different scFv fragments are more heterologous in respect of stability than Fab fragments. While some scFv fragments can be made extremely stable, this may change due to few mutations, and is not predictable from the sequence of a newly selected antibody. To mitigate the necessity to assess the stability for every scFv-Fc antibody, we developed a generic lyophilization protocol to improve their shelf life. We compared long-term stability and binding activity of phage display-derived antibodies in the scFv-Fc and IgG format, either stored in liquid or lyophilized state. Conversion of scFv-Fcs into the full IgG format reduced protein degradation and aggregation, but in some cases compromised binding activity. Comparably to IgG conversion, lyophilization of scFv-Fc resulted in the preservation of the antibodies’ initial properties after storage, without any drop in affinity for any of the tested antibody clones.
Development and Validation of a Prediction Model for Acute Kidney Injury Among Patients With Acute Decompensated Heart Failure
Authors: Wang Lei , Zhao Yun-Tao
Published: November 2021

Background: Acute kidney injury is an adverse event that carries significant morbidity among patients with acute decompensated heart failure (ADHF). We planned to develop a parsimonious model that is simple enough to use in clinical practice to predict the risk of acute kidney injury (AKI) occurrence.

Methods: Six hundred and fifty patients with ADHF were enrolled in this study. Data for each patient were collected from medical records. We took three different approaches of variable selection to derive four multivariable logistic regression model. We selected six candidate predictors that led to a relatively stable outcome in different models to derive the final prediction model. The prediction model was verified through the use of the C-Statistics and calibration curve.

Results: Acute kidney injury occurred in 42.8% of the patients. Advanced age, diabetes, previous renal dysfunction, high baseline creatinine, high B-type natriuretic peptide, and hypoalbuminemia were the strongest predictors for AKI. The prediction model showed moderate discrimination C-Statistics: 0.766 (95% CI, 0.729–0.803) and good identical calibration.

Conclusion: In this study, we developed a prediction model and nomogram to estimate the risk of AKI among patients with ADHF. It may help clinical physicians detect AKI and manage it promptly.
Research on the National New Energy Strategy From the Perspective of Political Economics
Authors: Pan Hao , Xu Shichang , Wang Zidi , Liang Zijian , Zeng Lingdong
Published: November 2021

Based on the perspective of political economics analysis, this article conducts research on the national new energy strategy as the economic situation changes differently from the past. Under the socialist market economy system with Chinese characteristics, the new energy strategy is not only an inevitable choice for China as a responsible major country, but also a key measure to promoting high-quality economic development. Through the analysis of the main dilemmas faced by China’s implementation of new energy strategy, this article proposes to design policies in terms of core technology research, innovative industry financing, cultivating professional talents, and continuous expansion of opening up, to originate a high-quality development path for China.
The Genetic Architecture of Grain Yield in Spring Wheat Based on Genome-Wide Association Study
Authors: Li Yuyao , Tang Jingquan , Liu Wenlin , Yan Wenyi , Sun Yan , Che Jingyu , Tian Chao , Zhang Hongji , Yu Lihe
Published: November 2021

Uncovering the genetic architecture for grain yield (GY)–related traits is important for wheat breeding. To detect stable loci for GY-related traits, a genome-wide association study (GWAS) was conducted in a diverse panel, which included 251 elite spring wheat accessions mainly from the Northeast of China. In total, 52,503 single nucleotide polymorphisms (SNPs) from the wheat 55 K SNP arrays were used. Thirty-eight loci for GY-related traits were detected and each explained 6.5–16.7% of the phenotypic variations among which 12 are at similar locations with the known genes or quantitative trait loci and 26 are likely to be new. Furthermore, six genes possibly involved in cell division, signal transduction, and plant development are candidate genes for GY-related traits. This study provides new insights into the genetic architecture of GY and the significantly associated SNPs and accessions with a larger number of favorable alleles could be used to further enhance GY in breeding.
Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome
Authors: Ruiz-Pablos Manuel , Paiva Bruno , Montero-Mateo Rosario , Garcia Nicolas , Zabaleta Aintzane
Published: November 2021

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin. Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection. Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance. Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals. Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency. Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients.
IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice
Authors: Jiang Jinqiu , Qin Tao , Zhang Liang , Liu Qiao , Wu Jiabin , Dai Rongxin , Zhou Lina , Zhao Qin , Luo Xiaoyan , Wang Hua , Zhao Xiaodong
Published: November 2021

Mutations in human DOCK8 cause a combined immunodeficiency syndrome characterized by allergic diseases such as asthma and food allergy. However, the underlying mechanism is unclear. Regulatory B (Breg) cells that produce IL-10 exert potent immunosuppressive functions in patients with allergic and autoimmune disorders. DOCK8-deficient B cells show diminished responses to TLR9 signaling, suggesting a possible defect in IL-10-producing Breg cells in those with DOCK8 deficiency, which may contribute to allergies. Here, we isolated peripheral blood mononuclear cells from DOCK8-deficient patients and generated a Dock8 KO mouse model to study the effect of DOCK8 deficiency on Breg cells. DOCK8-deficient patients and Dock8 KO mice harbored quantitative and qualitative defects in IL-10-producing Breg cells; these defects were caused by abnormal Dock8-/- CD4+ T cells. We found that recombinant murine (rm)IL-21 restored the function of Bregs both in vitro and in Dock8 KO mice, leading to reduced inflammatory cell infiltration of the lungs in a murine asthma model. Overall, the results provide new insight into the potential design of Breg-based or IL-21-based therapeutic strategies for allergic diseases, including asthma associated with DOCK8 deficiency.
Obesity Prolongs the Inflammatory Response in Mice After Severe Trauma and Attenuates the Splenic Response to the Inflammatory Reflex
Authors: Gärtner Fabian , Gihring Adrian , Roth Aileen , Bischof Joachim , Xu Pengfei , Elad Leonard , Wabitsch Martin , Burster Timo , Knippschild Uwe
Published: November 2021

Thoracic traumas with extra-thoracic injuries result in an immediate, complex host response. The immune response requires tight regulation and can be influenced by additional risk factors such as obesity, which is considered a state of chronic inflammation. Utilizing high-dimensional mass and regular flow cytometry, we define key signatures of obesity-related alterations of the immune system during the response to the trauma. In this context, we report a modification in important components of the splenic response to the inflammatory reflex in obese mice. Furthermore, during the response to trauma, obese mice exhibit a prolonged increase of neutrophils and an early accumulation of inflammation associated CCR2+CD62L+Ly6Chimonocytes in the blood, contributing to a persistent inflammatory phase. Moreover, these mice exhibit differences in migration patterns of monocytes to the traumatized lung, resulting in decreased numbers of regenerative macrophages and an impaired M1/M2 switch in traumatized lungs. The findings presented in this study reveal an attenuation of the inflammatory reflex in obese mice, as well as a disturbance of the monocytic compartment contributing to a prolonged inflammation phase resulting in fewer phenotypically regenerative macrophages in the lung of obese mice.
Molecular Tuning of Actin Dynamics in Leukocyte Migration as Revealed by Immune-Related Actinopathies
Authors: Kamnev Anton , Lacouture Claire , Fusaro Mathieu , Dupré Loïc
Published: November 2021

Motility is a crucial activity of immune cells allowing them to patrol tissues as they differentiate, sample or exchange information, and execute their effector functions. Although all immune cells are highly migratory, each subset is endowed with very distinct motility patterns in accordance with functional specification. Furthermore individual immune cell subsets adapt their motility behaviour to the surrounding tissue environment. This review focuses on how the generation and adaptation of diversified motility patterns in immune cells is sustained by actin cytoskeleton dynamics. In particular, we review the knowledge gained through the study of inborn errors of immunity (IEI) related to actin defects. Such pathologies are unique models that help us to uncover the contribution of individual actin regulators to the migration of immune cells in the context of their development and function.
A New Murine Model of Primary Autoimmune Hemolytic Anemia (AIHA)
Authors: Dei Zotti Flavia , Qiu Annie , La Carpia Francesca , Moriconi Chiara , Hudson Krystalyn E.
Published: November 2021

Loss of humoral tolerance to red blood cells (RBCs) can lead to autoimmune hemolytic anemia (AIHA), a severe, and sometimes fatal disease. Patients with AIHA present with pallor, fatigue, decreased hematocrit, and splenomegaly. While secondary AIHA is associated with lymphoproliferative disorders, infections, and more recently, as an adverse event secondary to cancer immunotherapy, the etiology of primary AIHA is unknown. Several therapeutic strategies are available; however, there are currently no licensed treatments for AIHA and few therapeutics offer treatment-free durable remission. Moreover, supportive care with RBC transfusions can be challenging as most autoantibodies are directed against ubiquitous RBC antigens; thus, virtually all RBC donor units are incompatible. Given the severity of AIHA and the lack of treatment options, understanding the cellular and molecular mechanisms that facilitate the breakdown in tolerance would provide insight into new therapeutics. Herein, we report a new murine model of primary AIHA that reflects the biology observed in patients with primary AIHA. Production of anti-erythrocyte autoantibodies correlated with sex and age, and led to RBC antigen modulation, complement fixation, and anemia, as determined by decreased hematocrit and hemoglobin values and increased reticulocytes in peripheral blood. Moreover, autoantibody-producing animals developed splenomegaly, with altered splenic architecture characterized by expanded white pulp areas and nearly diminished red pulp areas. Additional analysis suggested that compensatory extramedullary erythropoiesis occurred as there were increased frequencies of RBC progenitors detectable in the spleen. No significant correlations between AIHA onset and inflammatory status or microbiome were observed. To our knowledge, this is the first report of a murine model that replicates observations made in humans with idiopathic AIHA. Thus, this is a tractable murine model of AIHA that can serve as a platform to identify key cellular and molecular pathways that are compromised, thereby leading to autoantibody formation, as well as testing new therapeutics and management strategies.
Radiation Augments the Local Anti-Tumor Effect of In Situ Vaccine With CpG-Oligodeoxynucleotides and Anti-OX40 in Immunologically Cold Tumor Models
Authors: Pieper Alexander A. , Zangl Luke M. , Speigelman Dan V. , Feils Arika S. , Hoefges Anna , Jagodinsky Justin C. , Felder Mildred A. , Tsarovsky Noah W. , Arthur Ian S. , Brown Ryan J. , Birstler Jen , Le Trang , Carlson Peter M. , Bates Amber M. , Hank Jacquelyn A. , Rakhmilevich Alexander L. , Erbe Amy K. , Sondel Paul M. , Patel Ravi B. , Morris Zachary S.
Published: November 2021

Introduction

Combining CpG oligodeoxynucleotides with anti-OX40 agonist antibody (CpG+OX40) is able to generate an effective in situ vaccine in some tumor models, including the A20 lymphoma model. Immunologically “cold” tumors, which are typically less responsive to immunotherapy, are characterized by few tumor infiltrating lymphocytes (TILs), low mutation burden, and limited neoantigen expression. Radiation therapy (RT) can change the tumor microenvironment (TME) of an immunologically “cold” tumor. This study investigated the effect of combining RT with the in situ vaccine CpG+OX40 in immunologically “cold” tumor models.

Methods

Mice bearing flank tumors (A20 lymphoma, B78 melanoma or 4T1 breast cancer) were treated with combinations of local RT, CpG, and/or OX40, and response to treatment was monitored. Flow cytometry and quantitative polymerase chain reaction (qPCR) experiments were conducted to study differences in the TME, secondary lymphoid organs, and immune activation after treatment.

Results

An in situ vaccine regimen of CpG+OX40, which was effective in the A20 model, did not significantly improve tumor response or survival in the “cold” B78 and 4T1 models, as tested here. In both models, treatment with RT prior to CpG+OX40 enabled a local response to this in situ vaccine, significantly improving the anti-tumor response and survival compared to RT alone or CpG+OX40 alone. RT increased OX40 expression on tumor infiltrating CD4+ non-regulatory T cells. RT+CpG+OX40 increased the ratio of tumor-infiltrating effector T cells to T regulatory cells and significantly increased CD4+ and CD8+ T cell activation in the tumor draining lymph node (TDLN) and spleen.

Conclusion

RT significantly improves the local anti-tumor effect of the in situ vaccine CpG+OX40 in immunologically “cold”, solid, murine tumor models where RT or CpG+OX40 alone fail to stimulate tumor regression.
The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous
Authors: Chen Jia-ming , Huang Qiao-yi , Zhao Yun-xia , Chen Wei-hong , Lin Shu , Shi Qi-yang
Published: November 2021

Intrauterine adhesion (IUA) is an endometrial fibrosis disease caused by repeated operations of the uterus and is a common cause of female infertility. In recent years, treatment using mesenchymal stem cells (MSCs) has been proposed by many researchers and is now widely used in clinics because of the low immunogenicity of MSCs. It is believed that allogeneic MSCs can be used to treat IUA because MSCs express only low levels of MHC class I molecules and no MHC class II or co-stimulatory molecules. However, many scholars still believe that the use of allogeneic MSCs to treat IUA may lead to immune rejection. Compared with allogeneic MSCs, autologous MSCs are safer, more ethical, and can better adapt to the body. Here, we review recently published articles on the immunomodulation of allogeneic and autologous MSCs in IUA therapy, with the aim of proving that the use of autologous MSCs can reduce the possibility of immune rejection in the treatment of IUAs.
Water-Soluble Ruthenium (II) Complex Derived From Optically Pure Limonene and Its Microencapsulation Are Efficient Tools Against Bacterial Food Pathogen Biofilms: Escherichia coli, Staphylococcus aureus, Enteroccocus faecalis, and Listeria monocytogenes
Authors: Khelissa Simon , El Fannassi Yousra , Mechmechani Samah , Alhuthali Sakhr , El Amrani Mohamed Amin , Gharsallaoui Adem , Barras Alexandre , Chihib Nour-Eddine
Published: November 2021

Bioactive aminooxime ligands based on optically pure (R)-limonene have been synthesized in two steps. Their ruthenium (II) cationic water-soluble complex was prepared by a reaction between dichloro (para-cymene) ruthenium (II) dimers and aminooxime ligands in a 1:2 molar ratio. Antibacterial and antibiofilm activities of the synthetized complex were assessed against Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis. The results revealed that the ruthenium (II) complex has higher antibacterial and antibiofilm activities in comparison with free ligands or the enantiopure (R)-limonene. Moreover, microencapsulation of this complex reduced its cytotoxicity and improved their minimum inhibitory concentration and antibiofilm activity toward the considered bacteria. The ruthenium (II) complex targets the bacterial cell membrane, which leads to rapid leakage of intracellular potassium. Our study suggests that the developed ruthenium (II) complexes could be useful as an alternative to conventional disinfectants.
Validation of Discrete and Regression-Based Performance and Cognitive Fatigability Normative Data for the Paced Auditory Serial Addition Test in Multiple Sclerosis
Authors: Walker Caitlin S. , Berard Jason A. , Walker Lisa A. S.
Published: November 2021

Cognitive fatigability is an objective performance decrement that occurs over time during a task requiring sustained cognitive effort. Although cognitive fatigability is a common and debilitating symptom in multiple sclerosis (MS), there is currently no standard for its quantification. The objective of this study was to validate the Paced Auditory Serial Addition Test (PASAT) discrete and regression-based normative data for quantifying performance and cognitive fatigability in an Ontario-based sample of individuals with MS. Healthy controls and individuals with MS completed the 3″ and 2″ versions of the PASAT. PASAT performance was measured with total correct, dyad, and percent dyad scores. Cognitive fatigability scores were calculated by comparing performance on the first half (or third) of the task to the last half (or third). The results revealed that the 3″ PASAT was sufficient to detect impaired performance and cognitive fatigability in individuals with MS given the increased difficulty of the 2″ version. In addition, using halves or thirds for calculating cognitive fatigability scores were equally effective methods for detecting impairment. Finally, both the discrete and regression-based norms classified a similar proportion of individuals with MS as having impaired performance and cognitive fatigability. These newly validated discrete and regression-based PASAT norms provide a new tool for clinicians to document statistically significant cognitive fatigability in their patients.
Comparison of Interleukin-6 Plasma Concentration in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Pediatric Sepsis
Authors: Diaz Franco , Bustos B Raúl , Yagnam Felipe , Karsies Todd J. , Vásquez-Hoyos Pablo , Jaramillo-Bustamante Juan-Camilo , Gonzalez-Dambrauskas Sebastián , Drago Michelle , Cruces Pablo
Published: November 2021

Importance: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy.

Objective: To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis.

Design: A retrospective cohort study from previously collected data.

Setting: Individual patient data were gathered from three different international datasets.

Participants: Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy.

Exposure: None.

Main Outcome(s) and Measure(s): The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done.

Results: We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis (p < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock.

Conclusions and Relevance: IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.
The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice
Authors: Chen Peng , Chen Fuchao , Lei Jiexin , Wang Gaohua , Zhou Benhong
Published: November 2021

Background: Despite considerable advances in pharmacotherapy, more effective therapeutic interventions for aging-related neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), remain limited. Urolithin B (UB), one of the major subcategories of urolithins (microbiota metabolites) found in various tissues after ellagitannin consumption, has been shown to possess antioxidant, anti-inflammatory, and antiapoptotic effects. However, the neuroprotective effect of UB on brain aging in mice and its potential mechanisms were still unknown.

Methods: In the current research, we first assessed the ameliorative effects of UB on oxidative injury and apoptosis induced by H2O2 in neuro-2a cells. Then a subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of UB. The capacity of memory and learning, alterations of hippocampus histology and corresponding molecular mechanisms were all evaluated.

Results: The D-gal-induced accelerated aging model in vivo demonstrated that UB could significantly ameliorate deficits in learning and memory by inhibiting the accumulation of advanced glycation end products (AGEs) and elevating the expression and activity of Cu, Zn-SOD and CAT. Furthermore, UB downregulated the c-Jun N-terminal kinase (JNK) signaling pathway and prevented cytochrome c release from isolated mitochondria, thereby inhibiting neuronal apoptosis during the aging process. More importantly, UB stimulation of aging mice activated ERK and phosphoinositide 3-kinase (PI3K), leading to neuronal survival along with Akt and p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and activation.

Conclusion: In summary, UB effectively alleviated cognitive deficits and ameliorated brain aging-related conditions and could be considered a healthcare product to prevent aging-associated NDs such as AD.
Fiber Optic Sensing in Spacecraft Engineering: An Historical Perspective From the European Space Agency
Authors: McKenzie Iain , Ibrahim Selwan , Haddad Emile , Abad Silvia , Hurni Andreas , Cheng Lun K.
Published: November 2021

For over two decades the European Space Agency has investigated the possibility of using fiber optic sensors in spacecraft engineering as tools to advance the monitoring and control of spacecraft. The applications have been diverse covering both launcher and satellite applications and encompassing environments from cryogenic to high temperature re-entry applications. The aim of this review is to capture the history and status of fiber optic sensors for space applications demonstrating the breadth of applications that have been studied and the lessons learnt along the way. Finally, it is the intention of this review to look forward, pointing to how this technology can be used in the future and identifying what are the key remaining challenges to its further successful exploitation.
Comparing the Self- and External Assessment Versions of the HCL-33 as Screening Instruments for Bipolar Disorder in Older Depressed Patients
Authors: Zhang Xinqiao , Li Wen , Zhao Na , Jin Yu , Cheung Teris , Ungvari Gabor S. , Cui Xi-Ling , Wang Gang , Xiang Yu-Tao , Angst Jules
Published: November 2021

Objectives: The misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD) is common in depressed older adults. The self-rated HCL-33 and its external assessment version (HCL-33-EA) have been developed to screen for hypomanic symptoms. This study compared the screening ability of these two instruments to discriminate BD from MDD.

Methods: A total of 215 patients (107 with BD and 108 with MDD) and their carers were recruited. Patients and their carers completed the HCL-33 and HCL-33-EA, respectively. The consistency of the total score and the positive response to each item between the two scales was calculated with the intraclass correlation coefficient (ICC) and Cohen's kappa coefficient separately. Receiver operating characteristics (ROC) curves were drawn for both instruments. The optimal cut-off points were determined according to the maximum Youden's Index. The areas under the ROC curve (AUC) of the HCL-33 and HCL-33-EA were calculated separately and compared. The sensitivity and specificity at the optimal cut-off values were also calculated separately for the HCL-33 and HCL-33-EA.

Results: The intraclass correlation coefficient (ICC) between the total scores of the HCL-33 and HCL-33-EA was 0.823 (95% CI = 0.774–0.862). The positive response rate on all items showed high agreement between the two instruments. ROC curve analysis demonstrated that the total scores of both HCL-33 and HCL-33-EA differentiated well between MDD and BD, while there was no significant difference in the AUCs between the two scales (Z = 0.422, P = 0.673). The optimal cutoff values for the HCL-33 and HCL-33-EA were 14 and 12, respectively. With the optimal cutoff value, the sensitivities of the HCL-33 and HCL-33-EA were 88.8% and 93.5%, and their specificities were 82.4% and 79.6%.

Conclusion: Both the HCL-33 and HCL-33-EA had good screening ability for discriminating BD from MDD in depressed older adults.
Why Do We Need Maths in Medicine?
Authors: Cockcroft James , Saigar Mariam , Dawkins Andrew , Rutland Catrin S.
Published: November 2021

Maths is a crucial part of medicine. All the graphs, equations, statistics, and general maths we learn at school help us to understand important aspects of human and veterinary medicine, biology, and science in general. People always think that biology and chemistry are important for doctors, nurses, midwives, scientists, and all the other people involved in medicine and healthcare-related jobs, but in fact maths is also vital. So, whether you are thinking of becoming a doctor, hoping to invent medical technologies, or just wishing to understand treatments you get as a patient, understanding the maths behind medicine is crucial. This article explores how we check whether someone has a disease such as coronavirus or heart disease, how we predict and measure how many people will be affected by various diseases, and how maths is used to treat patients and prevent the spread of contagious diseases. While people are generally aware that sciences like biology and chemistry are important for jobs in the medical field, many may not realize that maths is also vital for most of these jobs. This article looks at some of the ways we use maths in medicine. If you want to become a doctor, veterinary surgeon, nurse, midwife, medical scientist, or to have any job related to healing people and animals, or even if you just want to be an informed patient, knowledge of maths is quite important!
Outcomes of Ventriculoperitoneal Shunt in Patients With Idiopathic Normal-Pressure Hydrocephalus 2 Years After Surgery
Authors: Popal Abdul Malik , Zhu Zhoule , Guo Xinxia , Zheng Zhe , Cai Chengwei , Jiang Hongjie , Zhang Jianmin , Shao Anwen , Zhu Junming
Published: November 2021

Objective: To evaluate the outcomes and prognostic factors of ventriculoperitoneal shunts (VP-shunts) in patients with idiopathic normal-pressure hydrocephalus (iNPH) at 6 months and 2 years after surgery.

Method: We retrospectively analyzed 68 patients admitted to our institute and diagnosed with probable iNPH from January 2017 to March 2021. All patients underwent VP-shunt surgery with a programmable valve, and their outcomes were assessed via the Krauss index and modified Rankin scale (mRS) at 6 months and 2 years post-surgery. Univariate and multivariate regression analysis was performed to identify the prognostic factors.

Results: The mean age of the patients was 71.1 ± 8.4 (mean ± standard deviation) years. On the Krauss improvement index, 6-month follow-up results were available for 68 patients. Of these patients, 91.2% experienced attenuation of their preoperative symptoms, with a mean Krauss index of 0.58 ± 0.27, and 48 patients (70.6%) had a Krauss index ≥0.5. Two-year follow-up results were available for 33 patients; 90.9% of them had sustained improvement, with a Krauss index of 0.54 ± 0.31, and 21 patients (66.3%) had a Krauss index ≥0.5. Thirty-three patients (58%) were living independently after 2 years (mRS 0–2). The outcomes were worse for patients with multiple comorbidities. Neither an increased patient age nor a prolonged history of illness was statistically significant prognostic factors for adverse outcomes of VP-shunt surgery.

Conclusion: Surgical treatment was well-tolerated by patients with iNPH who received VP-shunts. Most patients experienced attenuation of their preoperative symptoms. Multiple concurrent comorbidities should be considered as adverse prognostic factors before shunt insertion in patients with iNPH.
Comparison of Protectivity and Safety of Two Vaccines against Actinobacillus pleuropneumoniae in a Field Study
Authors: Hölzen Peter , Warnck Tobias , Hoy Steffen , Schlegel Kathleen , Hennig-Pauka Isabel , Gaumann Horst
Published: November 2021

Actinobacillus pleuropneumoniae causing porcine pleuropneumoniae is responsible for lowered productivity and reduction of performance indicators such as daily weight gain and increase of losses in the swine industry worldwide. To control the disease, vaccination is used to reduce clinical signs and production losses. A randomized, blinded field trail was conducted to compare two licensed A. pleuropneumoniae vaccines in 600 finishing pigs in terms of lung lesions, mortality, medication, weight gain and safety, in a farm in northeast Germany. After weaning, pigs were allocated randomly in two groups resulting in group sizes of 300 individuals. Nursery pigs were vaccinated at the age of 7 to 10 weeks either with a A. pleuropneumoniae bacterin, containing ApxI-III toxoids (group 1), or with a subunit purified A. pleuropneumoniae toxoid vaccine (group 2). Blinded lung lesion scoring at slaughter following the Ceva Lung Program methodology revealed a significantly lower proportion of lungs affected with pleurisy in group 1 compared to group 2. Weighing of the animals did not show a significant difference (p = 0.092); however, at the end of finishing animals of group 1 showed a 1.59 kg higher weight (100.40 ± 10.15 kg) compared to animals in group 2 (98.81 kg ± 11.56 kg). Mortality and antimicrobial medication were significantly lower in group 1 compared to group 2 (13 losses and 17 antimicrobial medications in group 2, 4 losses and 1 antimicrobial medications in group 1). Injection site and systemic adverse reactions were recorded on both days of vaccination and did not differ significantly between the groups (p > 0.05). In this study, the efficacy of vaccination with a commercially available A. pleuropneumoniae bacterin containing ApxI-III toxoids was superior to that of a commercially available A. pleuropneumoniae subunit toxoid vaccine in preventing pulmonary lesions associated with A. pleuropneumoniae infection.Grzegorz Woźniakowski
Growth and Yield Responses of Pot-Grown Long Bean and Luffa to Nitrogen Rates
Authors: Wang Yanlin , Maltais-Landry Gabriel , Rathinasabapathi Bala , Sargent Steven A. , Liu Guodong
Published: November 2021

Optimizing nitrogen (N) input rates for vegetable production is crucial in Florida to reducing production costs and enhancing environmental sustainability. Asian vegetables emerging and expanding in Florida not only increase profit for growers, but also enhance food diversity for consumers. The objective of this study was to gain a better understanding of the partitioning and usage of N and carbohydrates in two Asian vegetable crops: long bean (Vigna unguiculata ssp. sesquipedalis (L.) Verdc.) and angled luffa (Luffa acutangular (L.) Roxb.). Four N rates (0, 0.91, 1.36, and 1.81 g N pot−1) were compared in a high tunnel trial to understand the influence of N fertilization on the two crops. For long bean, plant biomass was highest at the highest N input, and N-fertilized plants had significantly higher leaf greenness than the control at the flower initiation and mid-reproductive stages. However, N inputs had no apparent effect on yield, nitrogen use efficiency (NUE), blade total N concentration, roots (length, volume, dry biomass, and root-to-shoot ratio), or nodules (number plant−1 and biomass). For luffa, the highest N input had significantly greater total yield, fruit number, and leaf greenness at the flower initiation and mid-reproductive stages, although there was no significant difference in shoot biomass, blade total N content, or NUE among treatments. Within the range of these N rates, our results suggest that higher N inputs promoted vegetative growth of long bean, whereas reproductive growth was promoted in luffa. This study highlights differences in the sink–source relationship of N for long bean and luffa production in high tunnel, which can guide N input decisions for these two crops that are rapidly expanding in the USA.
Feeding Sows Lucerne, or Diets with Similar Energy and Nutritional Profiles to Lucerne, Improves the Pre-Weaning Performance of Piglets
Authors: Wijesiriwardana Udani A. , Plush Kate J. , Tritton Sally , Pluske John R. , Cottrell Jeremy J. , Dunshea Frank R.
Published: November 2021

Feeding fibre and branched-chain amino acids (BCAA) to sows during late gestation and lactation, respectively, have been shown to improve litter weights at weaning. Therefore, supplementing primiparous sow diets with lucerne chaff, a feedstuff high in fibre, BCAA and tryptophan, may improve the performance of their progeny. Experiment 1 investigated the effects of feeding primiparous sows (n = 118) either (i) a control diet (CON); (ii) CON with 1 kg of lucerne chaff (LUC); or (iii) a diet formulated to have a similar digestible energy and BCAA content as CON + LUC (SIMLUC 1) until farrowing. The LUC and SIMLUC 1 diets improved day 21 litter weight (p = 0.055). In Experiment 2 primiparous (n = 111) and multiparous sows (parities 2–5, n = 112) were fed either the CON or SIMLUC diet (SIMLUC 2) from day 110 of gestation to farrowing (PreF), or to day 10 post-farrowing (PreF + PostF). The SIMLUC 2 diet tended to be more beneficial to primiparous compared to multiparous sows when fed PreF, as indicated by an interaction between diet and parity on day 21 average piglet weights (p = 0.078). Overall, SIMLUC is most effective in improving primiparous progeny performance as evidenced by their D21 weights.
SNPs, InDels, and Microsatellites within and Near to Rice NBS-LRR Resistance Gene Candidates
Authors: Quinton-Tulloch Mark J. , Steele Katherine A.
Published: November 2021

Plant resistance genes (R-genes) drive the immune responses of crops against specific pathotypes of disease-causing organisms. Over time, genetic diversity in R-genes and R-pseudogenes has arisen among different rice varieties. This bioinformatics study was carried out to (i) predict the full sets of candidate nucleotide-binding site leucine-rich repeat (NLR) R-genes present in six rice genomes; (ii) detect variation within candidate R-genes; (iii) identify potential selectable markers within and near to LRR genes among 75 diverse indica rice genomes. Four high quality indica genomes, plus the standard japonica and indica reference genomes, were analysed with widely available bioinformatic tools to identify candidate R-genes and R-pseudogenes. They were detected in clusters, consistent with previous studies. BLAST analysis of cloned protein sequences of 31 R-gene loci gave confidence in this approach for detection of cloned NLR R-genes. Approximately 10% of candidate R-genes were located within 1 kb of a microsatellite (SSR) marker. Sequence comparisons among indica rice genomes detected SNPs or InDels in 334 candidate rice R-genes. There were significantly more SNPs and InDels within the identified NLR R-gene candidates than in other types of gene. The genome-wide locations of candidate R-genes and their associated markers are presented here for the potential future development of improved disease-resistant varieties. Limitations of in silico approaches used for R-gene discovery are discussed.
A Comprehensive Plant microRNA Simple Sequence Repeat Marker Database to Accelerate Genetic Improvements in Crops
Authors: Biswas Manosh Kumar , Biswas Dhiman , Bagchi Mita , Yi Ganjun , Deng Guiming
Published: November 2021

Microsatellites, or simple sequences repeat (SSRs), are distributed in genes, intergenic regions and transposable elements in the genome. SSRs were identified for developing markers from draft genome assemblies, transcriptome sequences and genome survey sequences in plant and animals. The identification, distribution, and density of microsatellites in pre-microRNAs (miRNAs) are not well documented in plants. In this study, SSRs were identified in 16,892 pre-miRNA sequences from 292 plant species in six taxonomic groups (algae to dicots). Fifty-one percent of pre-miRNA sequences contained SSRs. Mononucleotide repeats were the most abundant, followed by di- and trinucleotide repeats. Tetra-, penta-, and hexarepeats were rare. A total of 9,498 (57.46%) microsatellite loci had potential as pre-miRNA SSR markers. Of the markers, 3,573 (37.62%) were non-redundant, and 2,341 (65.51%) primer pairs could be transferred to at least one of the plant taxonomic groups. All data and primer pairs were deposited in a user-friendly, freely accessible plant miRNA SSR marker database. The data presented in this study, accelerate the understanding of pre-miRNA evolution and serve as valuable genomic treasure for genetic improvements in a wide range of crops, including legumes, cereals, and cruciferous crops.
Field Crop Responses and Management Strategies to Mitigate Soil Salinity in Modern Agriculture: A Review
Authors: Alkharabsheh Hiba M. , Seleiman Mahmoud F. , Hewedy Omar A. , Battaglia Martin L. , Jalal Rewaa S. , Alhammad Bushra A. , Schillaci Calogero , Ali Nawab , Al-Doss Abdullah
Published: November 2021

The productivity of cereal crops under salt stress limits sustainable food production and food security. Barley followed by sorghum better adapts to salinity stress, while wheat and maize are moderately adapted. However, rice is a salt-sensitive crop, and its growth and grain yield are significantly impacted by salinity stress. High soil salinity can reduce water uptake, create osmotic stress in plants and, consequently, oxidative stress. Crops have evolved different tolerance mechanisms, particularly cereals, to mitigate the stressful conditions, i.e., effluxing excessive sodium (Na+) or compartmentalizing Na+ to vacuoles. Likewise, plants activate an antioxidant defense system to detoxify apoplastic cell wall acidification and reactive oxygen species (ROS). Understanding the response of field crops to salinity stress, including their resistance mechanisms, can help breed adapted varieties with high productivity under unfavourable environmental factors. In contrast, the primary stages of seed germination are more critical to osmotic stress than the vegetative stages. However, salinity stress at the reproductive stage can also decrease crop productivity. Biotechnology approaches are being used to accelerate the development of salt-adapted crops. In addition, hormones and osmolytes application can mitigate the toxicity impact of salts in cereal crops. Therefore, we review the salinity on cereal crops physiology and production, the management strategies to cope with the harmful negative effect on cereal crops physiology and production of salt stress.