bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the Signatures and Rules of Circulating Extracellular MicroRNA for Distinguishing Cancer Subtypes
Authors: Yuan Fei , Li Zhandong , Chen Lei , Zeng Tao , Zhang Yu-Hang , Ding Shijian , Huang Tao , Cai Yu-Dong
Published: March 2021

Cancer is one of the most threatening diseases to humans. It can invade multiple significant organs, including lung, liver, stomach, pancreas, and even brain. The identification of cancer biomarkers is one of the most significant components of cancer studies as the foundation of clinical cancer diagnosis and related drug development. During the large-scale screening for cancer prevention and early diagnosis, obtaining cancer-related tissues is impossible. Thus, the identification of cancer-associated circulating biomarkers from liquid biopsy targeting has been proposed and has become the most important direction for research on clinical cancer diagnosis. Here, we analyzed pan-cancer extracellular microRNA profiles by using multiple machine-learning models. The extracellular microRNA profiles on 11 cancer types and non-cancer were first analyzed by Boruta to extract important microRNAs. Selected microRNAs were then evaluated by the Max-Relevance and Min-Redundancy feature selection method, resulting in a feature list, which were fed into the incremental feature selection method to identify candidate circulating extracellular microRNA for cancer recognition and classification. A series of quantitative classification rules was also established for such cancer classification, thereby providing a solid research foundation for further biomarker exploration and functional analyses of tumorigenesis at the level of circulating extracellular microRNA.
Current Immunotherapies for Glioblastoma Multiforme
Authors: Huang Boyuan , Li Xuesong , Li Yuntao , Zhang Jin , Zong Zhitao , Zhang Hongbo
Published: March 2021

Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.
Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
Authors: Lykowska-Szuber Liliana , Walczak Michal , Skrzypczak-Zielinska Marzena , Suszynska-Zajczyk Joanna , Stawczyk-Eder Kamila , Waszak Katarzyna , Eder Piotr , Wozniak Anna , Krela-Kazmierczak Iwona , Slomski Ryszard , Dobrowolska Agnieszka
Published: March 2021

Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested that specific loci polymorphism of the TNFRSF1B, FCGR3A, IL1R, IL1B, and FAS genes could be a predictor of the primary non-response to anti-TNF therapy in CD patients. In this work, we propose to explain this hypothesis by functional analysis in colon biopsies and in a cell culture model. Using the RT-qPCR analysis, we estimated the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes mRNA level in colon biopsies material from inflamed and non-inflamed tissue from 21 CD patients (14 responders and 7 non-responders to anti-TNF therapy) and 6 controls, as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from 14 CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls cultured for 72 h with 10 μg/ml of anti-TNF antibody. Our findings demonstrated a significant down-regulation of TNFRSF1B gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the FCGR3A and IL1B genes was significantly up-regulated in non-responders in the inflamed colon region. In vitro research results indicate that the anti-TNF drug induced a significant decrease in TNFRSF1B, FCGR3A, and FAS gene expression in non-responders. These results show that altered TNFRSF1B, FCGR3A, and IL1B genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients.
Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression
Authors: Li Qian , Hu Liang , Li Juan , Yu Pan , Hu Fan , Wan Bing , Xu Miaomiao , Cheng Huixian , Yu Wanyou , Jiang Liping , Shi Yadan , Li Jincan , Duan Manlin , Long Yun , Liu Wen-Tao
Published: March 2021

Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured in vitro. The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells in vitro and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.
A Detailed Analysis of Parameters Supporting the Engraftment and Growth of Chronic Lymphocytic Leukemia Cells in Immune-Deficient Mice
Authors: Patten Piers E. M. , Ferrer Gerardo , Chen Shih-Shih , Kolitz Jonathan E. , Rai Kanti R. , Allen Steven L. , Barrientos Jacqueline C. , Ioannou Nikolaos , Ramsay Alan G. , Chiorazzi Nicholas
Published: March 2021

Patient-derived xenograft models of chronic lymphocytic leukemia (CLL) can be created using highly immunodeficient animals, allowing analysis of primary tumor cells in an in vivo setting. However, unlike many other tumors, CLL B lymphocytes do not reproducibly grow in xenografts without manipulation, proliferating only when there is concomitant expansion of T cells. Here we show that in vitro pre-activation of CLL-derived T lymphocytes allows for a reliable and robust system for primary CLL cell growth within a fully autologous system that uses small numbers of cells and does not require pre-conditioning. In this system, growth of normal T and leukemic B cells follows four distinct temporal phases, each with characteristic blood and tissue findings. Phase 1 constitutes a period during which resting CLL B cells predominate, with cells aggregating at perivascular areas most often in the spleen. In Phase 2, T cells expand and provide T-cell help to promote B-cell division and expansion. Growth of CLL B and T cells persists in Phase 3, although some leukemic B cells undergo differentiation to more mature B-lineage cells (plasmablasts and plasma cells). By Phase 4, CLL B cells are for the most part lost with only T cells remaining. The required B-T cell interactions are not dependent on other human hematopoietic cells nor on murine macrophages or follicular dendritic cells, which appear to be relatively excluded from the perivascular lymphoid aggregates. Notably, the growth kinetics and degree of anatomic localization of CLL B and T cells is significantly influenced by intravenous versus intraperitoneal administration. Importantly, B cells delivered intraperitoneally either remain within the peritoneal cavity in a quiescent state, despite the presence of dividing T cells, or migrate to lymphoid tissues where they actively divide; this dichotomy mimics the human condition in that cells in primary lymphoid tissues and the blood are predominately resting, whereas those in secondary lymphoid tissues proliferate. Finally, the utility of this approach is illustrated by documenting the effects of a bispecific antibody reactive with B and T cells. Collectively, this model represents a powerful tool to evaluate CLL biology and novel therapeutics in vivo.
The Local and Systemic Humoral Immune Response Against Homologous and Heterologous Strains of the Type 2 Porcine Reproductive and Respiratory Syndrome Virus
Authors: Kick Andrew R. , Amaral Amanda F. , Frias-De-Diego Alba , Cortes Lizette M. , Fogle Jonathan E. , Crisci Elisa , Almond Glen W. , Käser Tobias
Published: March 2021

The humoral immune response plays a crucial role in the combat and protection against many pathogens including the economically most important, highly prevalent, and diverse pig pathogen PRRSV – the Porcine Reproductive and Respiratory Syndrome Virus. In addition to viremia and viral shedding analyses, this study followed the local and systemic humoral immune response of pigs for 63 days upon inoculation with one of three types of Type-2 PRRSV (PRRSV-2) strains – one modified live virus (MLV) vaccine strain, and two lineage 1 PRRSV-2 strains, NC134 and NC174. The local response was analyzed by quantifying immunoglobulin (Ig)A in nasal swabs. The systemic response was studied by the quantification of IgG with ELISA and homo- and heterologous neutralizing antibodies (NAs) utilizing a novel method of flow cytometry. In all PRRSV-2 inoculated groups, viral nasal shedding started at 3 dpi, peaked between 3 and 7 days post inoculation, and was cleared at 28–35 dpi with sporadic rebounds thereafter. The local IgA response started 4–7 days after viral shedding occurred and showed a bi-phasic course with peaks at 14 dpi and at 28–35 dpi. Of note, the NC134 and NC174 strains induced a much stronger local IgA response. As reported earlier, main viremia lasted from 7 dpi to 28 dpi (NC174), 42 dpi (NC134) or until the end of the study (MLV). Similar to the local IgA response, the systemic IgG response started 4–7 days after viremia; but in contrast to viremia, serum IgG levels stayed high for all PRRSV-2 inoculated groups until the end of the study. A significant finding was that while the serum NA response in the MLV group was delayed by 28 days, serum NAs in pigs infected with our two NC134 and NC174 strains could be detected as early as 7 dpi (NC134) and 14 dpi (NC174). Compared to homologous NA responses, the NA responses against heterologous strains was strong but slightly delayed between our lineage 1 one strains or non-existent between the MLV and lineage 1 strains. This study improves our understanding of the relationship between local and systemic infections and the humoral immune response induced by PRRSV-2 infection or MLV vaccination. Our data also provide novel insights into the timeline of the development of homologous and heterologous NA levels – by both MLV vaccination or infection with two strains from the currently prevalent PRRSV-2 lineage 1.
Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients
Authors: Contoli Marco , Papi Alberto , Tomassetti Luca , Rizzo Paola , Vieceli Dalla Sega Francesco , Fortini Francesca , Torsani Francesca , Morandi Luca , Ronzoni Luca , Zucchetti Ottavio , Pavasini Rita , Fogagnolo Alberto , Volta Carlo Alberto , Bartlett Nathan W. , Johnston Sebastian L. , Spadaro Savino , Campo Gianluca
Published: March 2021

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19.

Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile.

Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay.

Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels.

Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention.

Clinical Trial Registration:ClinicalTrials.gov identifier NCT04343053.
Remote Predictions of Mahi-Mahi (Coryphaena hippurus) Spawning in the Open Ocean Using Summarized Accelerometry Data
Authors: Schlenker Lela S. , Faillettaz Robin , Stieglitz John D. , Lam Chi Hin , Hoenig Ronald H. , Cox Georgina K. , Heuer Rachael M. , Pasparakis Christina , Benetti Daniel D. , Paris Claire B. , Grosell Martin
Published: March 2021

Identifying complex behaviors such as spawning and fine-scale activity is extremely challenging in highly migratory fish species and is becoming increasingly critical knowledge for fisheries management in a warming ocean. Habitat use and migratory pathways have been extensively studied in marine animals using pop-up satellite archival tags (PSATs), but high-frequency data collected on the reproductive and swimming behaviors of marine fishes has been limited by the inability to remotely transmit these large datasets. Here, we present the first application of remotely transmitted acceleration data to predict spawning and discover drivers of high activity in a wild and highly migratory pelagic fish, the mahi-mahi (Coryphaena hippurus). Spawning events were predicted to occur at nighttime, at a depth distinct from non-spawning periods, primarily between 27.5 and 30°C, and chiefly at the new moon phase in the lunar cycle. Moreover, throughout their large-scale migrations, mahi-mahi exhibited behavioral thermoregulation to remain largely between 27 and 28°C and reduced their relative activity at higher temperatures. These results show that unveiling fine-scale activity patterns are necessary to grasp the ecology of highly mobile species. Further, our study demonstrates that critical, and new, ecological information can be extracted from PSATs, greatly expanding their potential to study the reproductive behavior and population connectivity in highly migratory fishes.
D-Limonene Is a Potential Monoterpene to Inhibit PI3K/Akt/IKK-α/NF-κB p65 Signaling Pathway in Coronavirus Disease 2019 Pulmonary Fibrosis
Authors: Yang Fan , Chen Ru , Li Wan-yang , Zhu Hao-yue , Chen Xiao-xuan , Hou Zhen-feng , Cao Ren-shuang , Zang GuoDong , Li Yu-xuan , Zhang Wei
Published: March 2021

At the time of the prevalence of coronavirus disease 2019 (COVID-19), pulmonary fibrosis (PF) related to COVID-19 has become the main sequela. However, the mechanism of PF related to COVID (COVID-PF) is unknown. This study aimed to explore the key targets in the development of COVID-PF and the mechanism of d-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. d-Limonene was molecularly docked with related proteins to screen its pharmacological targets, and a rat lung fibrosis model was established to verify d-limonene's effect on COVID-PF-related targets. The results showed that the imbalance between collagen breakdown and metabolism, inflammatory response, and angiogenesis are the core processes of COVID-PF; and PI3K/AKT signaling pathways are the key targets of the treatment of COVID-PF. The ability of d-limonene to protect against PF induced by bleomycin in rats was reported. The mechanism is related to the binding of PI3K and NF-κB p65, and the inhibition of PI3K/Akt/IKK-α/NF-κB p65 signaling pathway expression and phosphorylation. These results confirmed the relationship between the PI3K–Akt signaling pathway and COVID-PF, showing that d-limonene has a potential therapeutic value for COVID-PF.
Patient Preferences to Assess Value IN Gene Therapies: Protocol Development for the PAVING Study in Hemophilia
Authors: van Overbeeke Eline , Hauber Brett , Michelsen Sissel , Goldman Michel , Simoens Steven , Huys Isabelle
Published: March 2021

Introduction: Gene therapies are innovative therapies that are increasingly being developed. However, health technology assessment (HTA) and payer decision making on these therapies is impeded by uncertainties, especially regarding long-term outcomes. Through measuring patient preferences regarding gene therapies, the importance of unique elements that go beyond health gain can be quantified and inform value assessments. We designed a study, namely the Patient preferences to Assess Value IN Gene therapies (PAVING) study, that can inform HTA and payers by investigating trade-offs that adult Belgian hemophilia A and B patients are willing to make when asked to choose between a standard of care and gene therapy.

Methods and Analysis: An eight-step approach was taken to establish the protocol for this study: (1) stated preference method selection, (2) initial attributes identification, (3) stakeholder (HTA and payer) needs identification, (4) patient relevant attributes and information needs identification, (5) level identification and choice task construction, (6) educational tool design, (7) survey integration, and (8) piloting and pretesting. In the end, a threshold technique survey was designed using the attributes “Annual bleeding rate,” “Chance to stop prophylaxis,” “Time that side effects have been studied,” and “Quality of Life.”

Ethics and Dissemination: The Medical Ethics Committee of UZ KU Leuven/Research approved the study. Results from the study will be presented to stakeholders and patients at conferences and in peer-reviewed journals. We hope that results from the PAVING study can inform decision makers on the acceptability of uncertainties and the value of gene therapies to patients.
Application of Machine Learning Algorithms to Predict Central Lymph Node Metastasis in T1-T2, Non-invasive, and Clinically Node Negative Papillary Thyroid Carcinoma
Authors: Zhu Jiang , Zheng Jinxin , Li Longfei , Huang Rui , Ren Haoyu , Wang Denghui , Dai Zhijun , Su Xinliang
Published: March 2021

Purpose: While there are no clear indications of whether central lymph node dissection is necessary in patients with T1-T2, non-invasive, clinically uninvolved central neck lymph nodes papillary thyroid carcinoma (PTC), this study seeks to develop and validate models for predicting the risk of central lymph node metastasis (CLNM) in these patients based on machine learning algorithms.

Methods: This is a retrospective study comprising 1,271 patients with T1-T2 stage, non-invasive, and clinically node negative (cN0) PTC who underwent surgery at the Department of Endocrine and Breast Surgery of The First Affiliated Hospital of Chongqing Medical University from February 1, 2016, to December 31, 2018. We applied six machine learning (ML) algorithms, including Logistic Regression (LR), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Decision Tree (DT), and Neural Network (NNET), coupled with preoperative clinical characteristics and intraoperative information to develop prediction models for CLNM. Among all the samples, 70% were randomly selected to train the models while the remaining 30% were used for validation. Indices like the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and accuracy were calculated to test the models' performance.

Results: The results showed that ~51.3% (652 out of 1,271) of the patients had pN1 disease. In multivariate logistic regression analyses, gender, tumor size and location, multifocality, age, and Delphian lymph node status were all independent predictors of CLNM. In predicting CLNM, six ML algorithms posted AUROC of 0.70–0.75, with the extreme gradient boosting (XGBoost) model standing out, registering 0.75. Thus, we employed the best-performing ML algorithm model and uploaded the results to a self-made online risk calculator to estimate an individual's probability of CLNM (https://jin63.shinyapps.io/ML_CLNM/).

Conclusions: With the incorporation of preoperative and intraoperative risk factors, ML algorithms can achieve acceptable prediction of CLNM with Xgboost model performing the best. Our online risk calculator based on ML algorithm may help determine the optimal extent of initial surgical treatment for patients with T1-T2 stage, non-invasive, and clinically node negative PTC.
Cholestasis-Associated Pruritus and Its Pruritogens
Authors: Langedijk Jacqueline A. G. M. , Beuers Ulrich H. , Oude Elferink Ronald P. J.
Published: March 2021

Pruritus is a debilitating symptom of various cholestatic disorders, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and inherited progressive familial intrahepatic cholestasis (PFIC). The molecular mechanisms leading to cholestasis-associated pruritus are still unresolved and the involved pruritogens are indecisive. As a consequence of pruritus, patients suffer from sleep deprivation, loss of daytime concentration, auto-mutilation and sometimes even suicidal ideations. Current guideline-approved therapy of cholestasis-associated pruritus includes stepwise administration of several medications, which may alleviate complaints in some, but not all affected patients. Therefore, also experimental therapeutic approaches are required to improve patients' quality of life. This article reviews the current state of research on pruritogens and their receptors, and shortly discusses the most recent experimental therapies.
Microbial Community Field Surveys Reveal Abundant Pseudomonas Population in Sorghum Rhizosphere Composed of Many Closely Related Phylotypes
Authors: Chiniquy Dawn , Barnes Elle M. , Zhou Jinglie , Hartman Kyle , Li Xiaohui , Sheflin Amy , Pella Allyn , Marsh Ellen , Prenni Jessica , Deutschbauer Adam M. , Schachtman Daniel P. , Tringe Susannah G.
Published: March 2021

While the root-associated microbiome is typically less diverse than the surrounding soil due to both plant selection and microbial competition for plant derived resources, it typically retains considerable complexity, harboring many hundreds of distinct bacterial species. Here, we report a time-dependent deviation from this trend in the rhizospheres of field grown sorghum. In this study, 16S rRNA amplicon sequencing was used to determine the impact of nitrogen fertilization on the development of the root-associated microbiomes of 10 sorghum genotypes grown in eastern Nebraska. We observed that early rhizosphere samples exhibit a significant reduction in overall diversity due to a high abundance of the bacterial genus Pseudomonas that occurred independent of host genotype in both high and low nitrogen fields and was not observed in the surrounding soil or associated root endosphere samples. When clustered at 97% identity, nearly all the Pseudomonas reads in this dataset were assigned to a single operational taxonomic unit (OTU); however, exact sequence variant (ESV)-level resolution demonstrated that this population comprised a large number of distinct Pseudomonas lineages. Furthermore, single-molecule long-read sequencing enabled high-resolution taxonomic profiling revealing further heterogeneity in the Pseudomonas lineages that was further confirmed using shotgun metagenomic sequencing. Finally, field soil enriched with specific carbon compounds recapitulated the increase in Pseudomonas, suggesting a possible connection between the enrichment of these Pseudomonas species and a plant-driven exudate profile.
Rapid Changes in the Phytoplankton Community of a Subtropical, Shallow, Hypereutrophic Lake During the Rainy Season
Authors: Díaz-Torres Osiris , de Anda José , Lugo-Melchor Ofelia Yadira , Pacheco Adriana , Orozco-Nunnelly Danielle A. , Shear Harvey , Senés-Guerrero Carolina , Gradilla-Hernández Misael Sebastián
Published: March 2021

Lake Cajititlán is a small, shallow, subtropical lake located in an endorheic basin in western Mexico. It is characterized by a strong seasonality of climate with pronounced wet and dry seasons and has been classified as a hypereutrophic lake. This eutrophication was driven by improperly treated sewage discharges from four municipal wastewater treatment plants (WWTPs) and by excessive agricultural activities, including the overuse of fertilizers that reach the lake through surface runoff during the rainy season. This nutrient rich runoff has caused algal blooms, which have led to anoxic or hypoxic conditions, resulting in large-scale fish deaths that have occurred during or immediately after the rainy season. This study investigated the changes in the phytoplankton community in Lake Cajititlán during the rainy season and the association between these changes and the physicochemical water quality and environmental parameters measured in the lake’s basin.PlanktothrixandCylindrospermopsiswere the dominant genera of the cyanobacterial community, while the Chlorophyceae, Chrysophyceae, and Trebouxiophyceae classes dominated the microalgae community. However, the results showed a significant temporal shift in the phytoplankton communities in Lake Cajititlán induced by the rainy season. The findings of this study suggest that significant climatic variations cause high seasonal surface runoff and rapid changes in the water quality (Chlorophyll-a, DO, NH4+, and NO3–) and in variations in the composition of the phytoplankton community. Finally, an alternation between phosphorus and nitrogen limitation was observed in Lake Cajititlán during the rainy season, clearly correlating to the presence ofPlanktothrixwhen the lake was limited by phosphorus and to the presence ofCylindrospermopsiswhen the lake was limited by nitrogen. The evidence presented in this study supports the idea that the death of fish in Lake Cajititlán could be mainly caused by anoxia, caused by rapid changes in water quality during the rainy season. Based on our review of the literature, this is the first study on the phytoplankton community in a subtropical lake during the rainy season using high throughput 16S rRNA and 18S rRNA amplicon sequencing.
Structural, Metabolic and Evolutionary Comparison of Bacterial Endospore and Exospore Formation
Authors: Beskrovnaya Polina , Sexton Danielle L. , Golmohammadzadeh Mona , Hashimi Ameena , Tocheva Elitza I.
Published: March 2021

Sporulation is a specialized developmental program employed by a diverse set of bacteria which culminates in the formation of dormant cells displaying increased resilience to stressors. This represents a major survival strategy for bacteria facing harsh environmental conditions, including nutrient limitation, heat, desiccation, and exposure to antimicrobial compounds. Through dispersal to new environments via biotic or abiotic factors, sporulation provides a means for disseminating genetic material and promotes encounters with preferable environments thus promoting environmental selection. Several types of bacterial sporulation have been characterized, each involving numerous morphological changes regulated and performed by non-homologous pathways. Despite their likely independent evolutionary origins, all known modes of sporulation are typically triggered by limited nutrients and require extensive membrane and peptidoglycan remodeling. While distinct modes of sporulation have been observed in diverse species, two major types are at the forefront of understanding the role of sporulation in human health, and microbial population dynamics and survival. Here, we outline endospore and exospore formation by members of the phyla Firmicutes and Actinobacteria, respectively. Using recent advances in molecular and structural biology, we point to the regulatory, genetic, and morphological differences unique to endo- and exospore formation, discuss shared characteristics that contribute to the enhanced environmental survival of spores and, finally, cover the evolutionary aspects of sporulation that contribute to bacterial species diversification.
Untargeted Metabolomics Reveals Alterations in the Primary Metabolites and Potential Pathways in the Vegetative Growth of Morchella sextelata
Authors: Deng Kejun , Lan Xiuhua , Fang Qing , Li Mengke , Xie Guangbo , Xie Liyuan
Published: March 2021

Morchella sextelata, one of the true morels, has recently been artificially cultivated with stable production in China. Analysis of the variations in primary metabolites during the vegetative stages of M. sextelata is critical for understanding the metabolic process. In this study, three developmental stages were categorized based on morphological and developmental changes, including the young mushroom period, marketable mature period, and physiological maturity period. Untargeted metabolomics-based mass spectrometry was used to analyze the change of metabolites during the growth stages of M. sextelata. The result showed that the metabolites’ content at the different growth stages were significantly different. The relative contents of linoleic acid, mannitol, oleamide, and betaine were higher at each growth stage. Flavor substances were significantly metabolizable during commodity maturity, while amino acids, organic acids, and lipids were significantly metabolizing at physiological maturity. Pathway analysis of the most significant changes involved Pyrimidine metabolism, Vitamin B6 metabolism, Arginine biosynthesis, Lysine biosynthesis, and Lysine degradation. The results can provide a theoretical basis for further clarifying the metabolic regulation mechanism and lay the foundation for optimizing the cultivation process of M. sextelata.
Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease
Authors: Shi Deling , Sheng Anran , Chi Lianli
Published: March 2021

Glycosaminoglycans (GAGs) are a family of linear and negatively charged polysaccharides that exist ubiquitously on the human cell surface as well as in the extracellular matrix. GAGs interact with a wide range of proteins, including proteases, growth factors, cytokines, chemokines and adhesion molecules, enabling them to mediate many physiological processes, such as protein function, cellular adhesion and signaling. GAG-protein interactions participate in and intervene in a variety of human diseases, including cardiovascular disease, infectious disease, neurodegenerative diseases and tumors. The breakthrough in analytical tools and approaches during the last two decades has facilitated a greater understanding of the importance of GAG-protein interactions and their roles in human diseases. This review focuses on aspects of the molecular basis and mechanisms of GAG-protein interactions involved in human disease. The most recent advances in analytical tools, especially mass spectrometry-based GAG sequencing and binding motif characterization methods, are introduced. An update of selected families of GAG binding proteins is presented. Perspectives on development of novel therapeutics targeting specific GAG-protein interactions are also covered in this review.
Adaptive Balance in Posterior Cerebellum
Authors: Barmack Neal H. , Pettorossi Vito Enrico
Published: March 2021

Vestibular and optokinetic space is represented in three-dimensions in vermal lobules IX-X (uvula, nodulus) and hemisphere lobule X (flocculus) of the cerebellum. Vermal lobules IX-X encodes gravity and head movement using the utricular otolith and the two vertical semicircular canals. Hemispheric lobule X encodes self-motion using optokinetic feedback about the three axes of the semicircular canals. Vestibular and visual adaptation of this circuitry is needed to maintain balance during perturbations of self-induced motion. Vestibular and optokinetic (self-motion detection) stimulation is encoded by cerebellar climbing and mossy fibers. These two afferent pathways excite the discharge of Purkinje cells directly. Climbing fibers preferentially decrease the discharge of Purkinje cells by exciting stellate cell inhibitory interneurons. We describe instances adaptive balance at a behavioral level in which prolonged vestibular or optokinetic stimulation evokes reflexive eye movements that persist when the stimulation that initially evoked them stops. Adaptation to prolonged optokinetic stimulation also can be detected at cellular and subcellular levels. The transcription and expression of a neuropeptide, corticotropin releasing factor (CRF), is influenced by optokinetically-evoked olivary discharge and may contribute to optokinetic adaptation. The transcription and expression of microRNAs in floccular Purkinje cells evoked by long-term optokinetic stimulation may provide one of the subcellular mechanisms by which the membrane insertion of the GABAA receptors is regulated. The neurosteroids, estradiol (E2) and dihydrotestosterone (DHT), influence adaptation of vestibular nuclear neurons to electrically-induced potentiation and depression. In each section of this review, we discuss how adaptive changes in the vestibular and optokinetic subsystems of lobule X, inferior olivary nuclei and vestibular nuclei may contribute to the control of balance.
Ototoxicity of Non-aminoglycoside Antibiotics
Authors: Rybak Leonard P. , Ramkumar Vickram , Mukherjea Debashree
Published: March 2021

It is well-known that aminoglycoside antibiotics can cause significant hearing loss and vestibular deficits that have been described in animal studies and in clinical reports. The purpose of this review is to summarize relevant preclinical and clinical publications that discuss the ototoxicity of non-aminoglycoside antibiotics. The major classes of antibiotics other than aminoglycosides that have been associated with hearing loss in animal studies and in patients are discussed in this report. These antibiotics include: capreomycin, a polypeptide antibiotic that has been used to treat patients with drug-resistant tuberculosis, particularly in developing nations; the macrolides, including erythromycin, azithromycin and clarithromycin; and vancomycin. These antibiotics have been associated with ototoxicity, particularly in neonates. It is critical to be aware of the ototoxic potential of these antibiotics since so much attention has been given to the ototoxicity of aminoglycoside antibiotics in the literature.
Transcranial Magnetic Stimulation in Psychiatry: Is There a Need for Electric Field Standardization?
Authors: Turi Zsolt , Normann Claus , Domschke Katharina , Vlachos Andreas
Published: March 2021

Single-pulse and repetitive transcranial magnetic stimulation (rTMS) are used in clinical practice for diagnostic and therapeutic purposes. However, rTMS-based therapies that lead to a significant and sustained reduction in neuropsychiatric symptoms remain scarce. While it is generally accepted that the stimulation frequency plays a crucial role in producing the therapeutic effects of rTMS, less attention has been dedicated to determining the role of the electric field strength. Conventional threshold-based intensity selection approaches, such as the resting motor threshold, produce variable stimulation intensities and electric fields across participants and cortical regions. Insufficient standardization of electric field strength may contribute to the variability of rTMS effects and thus therapeutic success. Computational approaches that can prospectively optimize the electric field and standardize it across patients and cortical targets may overcome some of these limitations. Here, we discuss these approaches and propose that electric field standardization will be instrumental for translational science frameworks (e.g., multiscale modeling and basic science approaches) aimed at deciphering the subcellular, cellular, and network mechanisms of rTMS. Advances in understanding these mechanisms will be important for optimizing rTMS-based therapies in psychiatry.
The Curve Visible on the Campbell-Robson Chart Is Not the Contrast Sensitivity Function
Authors: Tardif Jessica , Watson Marcus R. , Giaschi Deborah , Gosselin Frédéric
Published: March 2021

The Campbell-Robson chart is a highly popular figure used in psychophysics and visual perception textbooks to illustrate the Contrast Sensitivity Function (CSF). The chart depicts a grating which varies logarithmically in spatial frequency (SF) from left to right and in contrast from bottom to top. Campbell and Robson’s (1964) intuition was that the boundary between the grating and the homogeneous gray area (below threshold) would trace the shape of the observer’s own CSF. In this paper, we tested this intuition. A total of 170 participants (96 adults and 74 children) adjusted the four parameters of a truncated log-parabola directly onto a Campbell-Robson chart rendition and completed a gold-standard CSF evaluation. We hoped that this procedure which requires a mere three clicks on the computer mouse, would speed up the measurement of the CSF to under a minute. Unfortunately, the only parameter of the truncated log-parabola fitted to the gold-standard CSF data that could be predicted from the Campbell-Robson chart data was the peak sensitivity for the adult participants. We conclude that the curve visible on the Campbell-Robson chart cannot be used practically to measure the CSF.
Neurons in the Locus Coeruleus Modulate the Hedonic Effects of Sub-Anesthetic Dose of Propofol
Authors: Chen Hui , Xu Dan , Zhang Yu , Yan Yan , Liu JunXiao , Liu ChengXi , Shen Wei , Yu Tian , Liu Jin
Published: March 2021

Propofol is a worldwide-used intravenous general anesthetic with ideal effects, but hedonic effects of propofol have been reported and cause addictive issue. There is little known about the neurobiological mechanism of hedonic effects of propofol. Increasing researches have shown that the dopaminergic nervous system of the ventral tegmental area (VTA) and the noradrenergic system of locus coeruleus (LC) play a crucial role in hedonic experiences, which are putative sites for mediating the hedonic effects of propofol. In the present study, rat hedonic response scale and place conditioning paradigm were employed to examine the euphoric effects of propofol. In vivo GCaMP-based (AVV-hSyn-GCaMP6s) fiber photometry calcium imaging was used to monitor the real-time neuronal activity in VTA and LC area in rats exhibiting propofol-induced euphoric behaviors. Then DREADDs (designer receptors exclusively activated by designer drugs) modulation using rAAV-hSyn-hM4D(Gi)-EGFP was performed to confirm the neuronal substrate that mediates the euphoric effects of propofol. The score of hedonic facial responses was significantly increased in the 4 mg/kg group compared with that of the 0 mg/kg group. The locomotor activity in the propofol-paired compartment was significantly increased at the 4 mg/kg dose compared with that of the saline-paired group. When compared with the 0 mg/kg group, the place preference increased in the 4 mg/kg group. Administration of 4 mg/kg of propofol triggers reliable increases in GcaMP fluorescence. However, in the VTA GcaMP-expressing rats, administration of 4 mg/kg of propofol did not induce any change of GcaMP signals. The facial score and the place preference, which increased by 4 mg/kg propofol were abolished by chemogenetic inhibition of the neuronal activity in the LC area. Our results suggest that LC noradrenergic neurons, not VTA dopaminergic neurons, are directly involved in the hedonic effects of sub-anesthetic dose of propofol.
Wnt7a Promotes the Occurrence and Development of Colorectal Adenocarcinoma
Authors: Li Congcong , Dou Xiaowei , Sun Jiahuan , Xie Min , Li Hongli , Cui Peilin
Published: March 2021

Objective

The expression of Wnt7a in colorectal cancer tissues and cell lines was analyzed, and the effect of Wnt7a on the proliferation of colorectal cancer cells was studied, so as to confirm the relationship between Wnt7a and the occurrence and development of colorectal cancer.

Methods

(1) Immunohistochemical method was used to compare the expression of Wnt7a in different tissues and its relationship with the clinicopathology of colorectal adenocarcinoma. (2) The expression levels of Wnt7a in colorectal cancer cell lines HT-29 and HCT 116 were detected by qRT-PCR. (3) The down-regulated Wnt7A expression vector was constructed, and the down-regulated Wnt7A expression cell line was established. The regeneration ability of cancer cells was detected by stem cell ball formation assay, and the influence of plate cloning assay on the proliferation ability of colorectal cancer cells was detected.

Results

(1) The positive rates of Wnt7a in normal colorectal mucosa, colorectal adenoma and colorectal adenocarcinoma tissues gradually increased,Wnt7a are closely related to the degree of colorectal adenocarcinoma differentiation, lymph node metastasis and Duke stage. (2) The expression level of Wnt7a in colorectal cancer cells was higher than that in normal colorectal epithelial cells. (3) The down-regulation of Wnt7A reduced the proliferation ability of colorectal cancer cells.

Conclusions

Wnt7a promotes the occurrence and development of colorectal adenocarcinoma.
Overexpression of RhoV Promotes the Progression and EGFR-TKI Resistance of Lung Adenocarcinoma
Authors: Chen Hongjin , Xia Ruixue , Jiang Long , Zhou Yong , Xu Haojun , Peng Weiwei , Yao Chengyun , Zhou Guoren , Zhang Yijie , Xia Hongping , Wang Yongsheng
Published: March 2021

Background

The Rho GTPase family with ~20 member genes play central roles in a wide variety of cellular processes and tumor cell migration and metastasis. Different Rho GTPase may play different roles in the progression of lung adenocarcinoma.

Methods

We comprehensively examined the expression of all Rho GTPase family member genes in a panel of lung adenocarcinoma patient’s tumors and matched normal tissues. We next investigated the critical role of RhoV in different lung adenocarcinoma cells and animal models.

Results

RhoV was identified as one of the most significantly overexpressed Rho GTPases in lung adenocarcinoma and associated with patients’ survival. Silencing RhoV expression inhibits proliferation, migration and invasion, and tumorigenicity capacities of lung adenocarcinoma cells. Moreover, knockdown RhoV promoted the sensitivity of EGFR-TKI in the gefitinib resistant PC9 cells (PC9-GR) and aggravated gefitinib-induced lung cancer cell apoptosis both in PC9 and PC9-GR cells. Our data also indicated that RhoV induced progression and EGFR-TKI resistance of lung adenocarcinoma may be related to the activation of the AKT/ERK pathway.

Conclusion

Overexpression of RhoV in lung adenocarcinoma promotes the progression and EGFR-TKI resistance, suggesting RhoV is a promising prognosis and therapeutic target of lung adenocarcinoma.
Hepatic Steatosis Predicts Higher Incidence of Recurrence in Colorectal Cancer Liver Metastasis Patients
Authors: Chen Haiyan , Dai Siqi , Fang Yimin , Chen Liubo , Jiang Kai , Wei Qichun , Ding Kefeng
Published: March 2021

Purpose: Colorectal liver metastasis (CRLM) is the major cause of death due to colorectal cancer. Although great efforts have been made in treatment of CRLM, about 60–70% of patients will develop hepatic recurrence. Hepatic steatosis was reported to provide fertile soil for metastasis. However, whether hepatic steatosis predicts higher incidence of CRLM recurrence is not clear. Therefore, we aimed to determine the role of hepatic steatosis in CRLM recurrence in the present study.

Methods: Consecutive CRLM patients undergoing curative treatment were retrospectively enrolled and CT liver-spleen attenuation ratio was used to detect the presence of hepatic steatosis. In patients with hepatic steatosis, we also detected the presence of fibrosis. Besides, a systematic literature search was performed to do meta-analysis to further analyze the association between hepatic steatosis and CRLM recurrence.

Results: A total of 195 eligible patients were included in our center. Patients with hepatic steatosis had a significantly worse overall (P = 0.0049) and hepatic recurrence-free survival (RFS) (P = 0.0012). Univariate and multivariate analysis confirmed its essential role in prediction of RFS. Besides, hepatic fibrosis is associated with worse overall RFS (P = 0.039) and hepatic RFS (P = 0.048). In meta-analysis, we included other four studies, with a total of 1,370 patients in the case group, and 3,735 patients in the control group. The odds ratio was 1.98 (95% CI: 1.25–3.14, P = 0.004), indicating that patients with steatosis had a significantly higher incidence of CRLM recurrence.

Conclusion: In summary, patients with hepatic steatosis had a significantly worse overall and hepatic RFS and it's associated with higher incidence of CRLM recurrence.
Peritumoral Edema Is Associated With Postoperative Hemorrhage and Reoperation Following Vestibular Schwannoma Surgery
Authors: Guo Xiaoming , Zhu Yueli , Wang Xiaoyu , Xu Ke , Hong Yuan
Published: March 2021

Background: Postoperative hemorrhage (POH) is a severe complication following vestibular schwannoma surgery that may require surgical treatment. The purpose of our study is to identify risk factors associated with POH and reoperation following the resection of vestibular schwannoma.

Methods: We retrospectively recruited 452 vestibular schwannoma patients treated with retrosigmoid approach. The primary outcome was POH, and the secondary outcome was reoperation for POH. Clinical and radiographic data were compared by performing univariate analysis and logistic regression analysis.

Results: Among the 452 patients, 37 patients (8.2%) presented with POH and14 patients (3.1%) required reoperation within a 30-day hospitalization period. The univariate analysis showed that peritumoral edema, tumor diameter >30 mm, severe postoperative hypertension, and length of hospital stay were associated with POH and reoperation for POH. Logistic regression analysis showed that peritumoral edema [odds ratio (OR) 4.042, 95% confident interval (CI) 1.830–8.926, P = 0.001] and tumor diameter >30 mm (OR 3.192, 95% CI 1.421–7.168, P = 0.005) were independent predictive factors for POH. Peritumoral edema (OR 7.071, 95% CI 2.342–21.356, P = 0.001) was an independent predictive factor for reoperation by using logistic regression analysis. Further analysis revealed that larger tumor and incomplete tumor resection were both associated with a higher incidence of peritumoral edema.

Conclusion: Peritumoral edema and tumor size are independent risk factors for POH following vestibular schwannoma surgery. And larger hematoma occurs more commonly in tumors with peritumoral edema which may require reoperation. Tumor size and extent of tumor resection are associated with peritumoral edema. Close attention should be paid to high-risk patients especially for those who presented with severe postoperative hypertension.