bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct and Indirect Effects of Sex Steroids on Gonadotrope Cell Plasticity in the Teleost Fish Pituitary
Authors: Fontaine Romain , Royan Muhammad Rahmad , von Krogh Kristine , Weltzien Finn-Arne , Baker Dianne M.
Published: December 2020

The pituitary gland controls many important physiological processes in vertebrates, including growth, homeostasis, and reproduction. As in mammals, the teleost pituitary exhibits a high degree of plasticity. This plasticity permits changes in hormone production and secretion necessary to meet the fluctuating demands over the life of an animal. Pituitary plasticity is achieved at both cellular and population levels. At the cellular level, hormone synthesis and release can be regulated via changes in cell composition to modulate both sensitivity and response to different signals. At the cell population level, the number of cells producing a given hormone can change due to proliferation, differentiation of progenitor cells, or transdifferentiation of specific cell types. Gonadotropes, which play an important role in the control of reproduction, have been intensively investigated during the last decades and found to display plasticity. To ensure appropriate endocrine function, gonadotropes rely on external and internal signals integrated at the brain level or by the gonadotropes themselves. One important group of internal signals is the sex steroids, produced mainly by the gonadal steroidogenic cells. Sex steroids have been shown to exert complex effects on the teleost pituitary, with differential effects depending on the species investigated, physiological status or sex of the animal, and dose or method of administration. This review summarizes current knowledge of the effects of sex steroids (androgens and estrogens) on gonadotrope cell plasticity in teleost anterior pituitary, discriminating direct from indirect effects.
Numerical Study on the Thermal Hydraulic Characteristics in a Wire-Wrapped Assembly of LFRs
Authors: Li Jun , Fang Di , Guo Chao , Wang Mingjun , Deng Jian , Tian Wenxi , Qiu Suizheng , Su G. H.
Published: December 2020

The concept of wire-wrapped assembly has been widely adopted in liquid metal-cooled reactors to enhance the capability of flow and heat transfer. The detailed 3D thermal hydraulic behaviors of liquid metal in the wire-wrapped assembly directly affect the safety of the reactor. In the present work, a numerical study on a 19-pin wire-wrapped assembly cooled by a lead-bismuth eutectic was carried out using the CFD method. The geometrical model is referred to in the test section in KIT’s 19-pin experiments, which is a scaled test assembly based on the MYRRHA reactor. The established CFD model was validated against experimental data and results showed that the SST k-ω model accompanied with the modified Prt was appropriate for the current problem. Then the numerical models were extensively used in the modeling of the blocked assembly flow with a cylindrical blockage. Also, the influences of blockage longitude, position, and porosity on the thermal hydraulic characteristics in the assembly were evaluated in detail. This work is meaningful for the deep understanding of safety features under the condition of assembly blockage operation in LFRs.
Environmental DNA (eDNA) Monitoring of Noble Crayfish Astacus astacus in Lentic Environments Offers Reliable Presence-Absence Surveillance – But Fails to Predict Population Density
Authors: Johnsen Stein I. , Strand David A. , Rusch Johannes C. , Vrålstad Trude
Published: December 2020

Noble crayfish is the most widespread native freshwater crayfish species in Europe. It is threatened in its entire distribution range and listed on the International Union for Concervation Nature- and national red lists. Reliable monitoring data is a prerequisite for implementing conservation measures, and population trends are traditionally obtained from catch per unit effort (CPUE) data. Recently developed environmental DNA (eDNA) tools can potentially improve the effort. In the past decade, eDNA monitoring has emerged as a promising tool for species surveillance, and some studies have established that eDNA methods yield adequate presence-absence data for crayfish. There are also high expectations that eDNA concentrations in the water can predict biomass or relative density. However, eDNA studies for crayfish have not yet been able to establish a convincing relationship between eDNA concentrations and crayfish density. This study compared eDNA and CPUE data obtained the same day and with high sampling effort, and evaluated whether eDNA concentrations can predict relative density of crayfish. We also compared two analytical methods [Quantitative real-time PCR (qPCR) and digital droplet PCR (ddPCR)], and estimated the detection probability for eDNA monitoring compared to trapping using occupancy modeling. In all lakes investigated, we detected eDNA from noble crayfish, even in lakes with very low densities. The eDNA method is reliable for presence-absence monitoring of noble crayfish, and the probability of detecting noble crayfish from eDNA samples increased with increasing relative crayfish densities. However, the crayfish eDNA concentrations were consistently low and mostly below the limit of quantification, even in lakes with very high crayfish densities. The hypothesis that eDNA concentrations can predict relative crayfish density was consequently not supported. Our study underlines the importance of intensified sampling effort for successful detection of very low-density populations, and for substantiating presumed absence, inferred from negative results. Surprisingly, we found a higher likelihood of eDNA detection using qPCR compared to ddPCR. We conclude that eDNA monitoring cannot substitute CPUE data, but is a reliable supplement for rapid presence-absence overviews. Combined with eDNA analyses of alien crayfish species and diseases such as crayfish plague, this is a cost-efficient supplement offering a more holistic monitoring approach for aquatic environments and native crayfish conservation.
Predictions of Disease Risk in Space and Time Based on the Thermal Physiology of an Amphibian Host-Pathogen Interaction
Authors: Sonn Julia M. , Porter Warren P. , Mathewson Paul D. , Richards-Zawacki Corinne L.
Published: December 2020

Emerging infectious diseases have been responsible for declines and extinctions in a growing number of species. Predicting disease variables like infection prevalence and mortality and how they vary in space and time will be critical to understanding how host-pathogen dynamics play out in natural environments and will help to inform management actions. The pandemic disease chytridiomycosis, caused by the fungal pathogen, Batrachochytrium dendrobatidis (Bd), has been implicated in declines in hundreds of amphibian species worldwide. We used field-collected measurements of host body temperatures and other physiological parameters to develop a mechanistic model of disease risk in a declining amphibian, the Northern cricket frog (Acris crepitans). We first used a biophysical model to predict host body temperatures across the species range in the eastern United States. We then used empirically derived relationships between host body temperature, infection prevalence and survival to predict where and when the risk of Bd-related declines is greatest. Our model predicts that pathogen prevalence is greatest, and survival of infected A. crepitans frogs is lowest, just prior to breeding when host body temperatures are low. Taken together, these results suggest that Bd poses the greatest threat to short-lived A. crepitans populations in the northern part of this host’s range and that disease-related recruitment failure may be common. Furthermore, our study demonstrates the utility of mechanistic modeling approaches for predicting disease outbreaks and dynamics in animal hosts.
Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma
Authors: Xia Qi , Shu Zheyue , Ye Ting , Zhang Min
Published: December 2020

As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is the fifth major cause of cancer-associated mortality worldwide. In 90% of cases, HCC develops in the context of liver cirrhosis and chronic hepatitis B virus (HBV) infection is an important etiology for cirrhosis and HCC, accounting for 53% of all HCC cases. To understand the underlying mechanisms of the dynamic chain reactions from normal to HBV infection, from HBV infection to liver cirrhosis, from liver cirrhosis to HCC, we analyzed the blood lncRNA expression profiles from 38 healthy control samples, 45 chronic hepatitis B patients, 46 liver cirrhosis patients, and 46 HCC patients. Advanced machine-learning methods including Monte Carlo feature selection, incremental feature selection (IFS), and support vector machine (SVM) were applied to discover the signature associated with HCC progression and construct the prediction model. One hundred seventy-one key HCC progression-associated lncRNAs were identified and their overall accuracy was 0.823 as evaluated with leave-one-out cross validation (LOOCV). The accuracies of the lncRNA signature for healthy control, chronic hepatitis B, liver cirrhosis, and HCC were 0.895, 0.711, 0.870, and 0.826, respectively. The 171-lncRNA signature is not only useful for early detection and intervention of HCC, but also helpful for understanding the multistage tumorigenic processes of HCC.
Detection of Citrullinated Fibrin in Plasma Clots of Rheumatoid Arthritis Patients and Its Relation to Altered Structural Clot Properties, Disease-Related Inflammation and Prothrombotic Tendency
Authors: Bezuidenhout Johannes A. , Venter Chantelle , Roberts Timothy J. , Tarr Gareth , Kell Douglas B. , Pretorius Etheresia
Published: December 2020

Aims

The risk of cardiovascular events in patients with Rheumatoid Arthritis (RA) is disproportionately heightened as a result of systemic inflammation. The relative effect of autoimmune-associated citrullination on the structure and thrombotic potential of fibrin(ogen) remains unknown. We therefore compared indices of vascular function, inflammation, coagulation and fibrin clot composition in RA patients with healthy controls and evaluated parameter association with disease presence.

Methods

Blood samples were collected from 30 RA patients and 30 age- and gender-matched healthy volunteers. Levels of serum amyloid A (SAA), c-reactive protein (CRP), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) was measured using a sandwich immunoassay. Whole blood coagulation was assessed using Thromboelastography (TEG®). Fibrin clot networks and fiber structure was investigated using Scanning Electron Microscopy. The detection and quantification of citrullination in formed fibrin clots was performed using a fluorescently labeled Citrulline monoclonal antibody with Fluorescence Wide Field Microscopy.

Results

Concentrations of SAA, CRP and ICAM-1 were significantly elevated in RA patients compared to controls. TEG parameters relating to coagulation initiation, rate of fibrin cross-linking, and time to reach maximum thrombus generation were attenuated in RA patients. Microscopic analysis revealed denser networks of thicker fibrin fibers in RA patients compared to controls and multiple citrullinated regions within fibrin clot structures in RA patients were present.

Conclusion

Our findings provide novel evidence for the citrullination of fibrin within vasculature is more prominent in RA plasma compared to control plasma and plasma is more accessible than synovial fluid. Citrullinated fibrinogen could play a role as a determinant of thrombotic risk in RA patients.
Essentially Leading Antibody Production: An Investigation of Amino Acids, Myeloma, and Natural V-Region Signal Peptides in Producing Pertuzumab and Trastuzumab Variants
Authors: Ling Wei-Li , Su Chinh Tran-To , Lua Wai-Heng , Poh Jun-Jie , Ng Yuen-Ling , Wipat Anil , Gan Samuel Ken-En
Published: December 2020

Boosting the production of recombinant therapeutic antibodies is crucial in both academic and industry settings. In this work, we investigated the usage of varying signal peptides by antibody V-genes and their roles in recombinant transient production, systematically comparing myeloma and the native signal peptides of both heavy and light chains in 168 antibody permutation variants. We found that amino acids count and types (essential or non-essential) were important factors in a logistic regression equation model for predicting transient co-transfection protein production rates. Deeper analysis revealed that the culture media were often incomplete and that the supplementation of essential amino acids can improve the recombinant protein yield. While these findings are derived from transient HEK293 expression, they also provide insights to the usage of the large repertoire of antibody signal peptides, where by varying the number of specific amino acids in the signal peptides attached to the variable regions, bottlenecks in amino acid availability can be mitigated.
Electric Vehicle Battery Disassembly Sequence Planning Based on Frame-Subgroup Structure Combined with Genetic Algorithm
Authors: Ke Qingdi , Zhang Peng , Zhang Lei , Song Shouxu
Published: December 2020

Since the electric vehicle battery (EVB) is wildly recycled in industry, the disassembly procedures of variable EVBs is so important that can influence the efficiency and environmental impacts in remanufacturing. To improve disassembly efficiency in EVB remanufacturing, a disassembly sequence planning method based on frame-subgroup structure is proposed in this paper. Firstly, the improved disassembly relation hybrid graph and disassembly relation matrix are proposed to identify the disassembly precedence relationship and connection relationship between the components in EVB. Secondly, the frame - subgroup structure is given, and the method for solving disassembly sequence planning with frame-subgroup structure and genetic algorithm is introduced. In this method, to simplify the series of processes such as encoding, decoding, crossover and mutation, the solution space composed of all disassembly sequences is transformed into the positive integer sequence for the disassembly efficiency in battery remanufacturing. Finally, the case study of EVB disassembly sequence planning is presented to validate the feasibility of this proposed method. Comparing with other traditional methods, the advantage and application of this proposed method are introduced.
Correlation Between the COVID-19 Respiratory Triage Score and SARS-COV-2 PCR Test
Authors: Aldobyany Ahmad , Touman Abdelfattah , Ghaleb Nabil , Alsaggaf Rajaa , Murtaza Noureen , Hamada Adel , Alknawy Moataz , Albanna Amr S. , Alqurashi Eid
Published: December 2020

Background: COVID-19 clinical presentation is usually non-specific and includes commonly encountered symptoms like fever, cough, nausea, and vomiting. It has been reported that COVID-19 patients can potentially transmit the disease to others before developing symptoms. Thus, extensive surveillance and screening of individuals at risk of the disease is required to limit SARS-COV-2 spread. The COVID-19 respiratory triage score has been used for patient screening. We aimed to determine its diagnostic performance characteristics, which have not been adequately studied before.

Methodology: This is a retrospective observational study involving all patients screened for COVID-19 at a tertiary care facility. Patients were tested using nasopharyngeal swab for SARS-COV-2 PCR. The Saudi CDC COVID-19 respiratory triage score was measured for all subjects. The sensitivity, specificity, positive predictive value, and negative predicted value of COVID-19 respiratory triage score were measured with reference to SARS-COV-2 PCR test. Multivariate regression analysis was done to identify factors that can predict a positive SARS-COV-2 PCR test.

Result: A total of 1,435 subjects were included. The COVID-19 respiratory triage score provided a marginal diagnostic performance with a receiver-operating characteristics (ROC) area under the curve value of 0.60 (95% CI: 0.57–0.64). A triage score of 5 provided the best cut-off value for the combined sensitivity and specificity. Clinical characteristics that independently predicted positive COVID-19 PCR test include male sex (adjusted OR: 1.47; p = 0.034), healthcare workers and their family members (adjusted OR: 1.99; 95%; p = 0.016), fever (adjusted OR: 2.98; p < 0.001), and moderate disease severity (adjusted OR: 5; p < 0.001).

Conclusion: The current COVID-19 respiratory triage score has marginal diagnostic performance characteristics. Its performance can improve by including additional predictors to the respiratory symptoms in order to avoid missing COVID-19 patients with atypical presentation and to limit unnecessary SARS-COV-2 PCR testing.
Association of Cigarette Smoking, COPD, and Lung Cancer With Expression of SARS-CoV-2 Entry Genes in Human Airway Epithelial Cells
Authors: Yin Junping , Kasper Brigitte , Petersen Frank , Yu Xinhua
Published: December 2020

SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.
Whole Transcriptome Analysis Provides Insights Into the Molecular Mechanisms of Chlamydospore-Like Cell Formation in Phanerochaete chrysosporium
Authors: Liu Lei , Li Huihui , Liu Yanyan , Li Yi , Wang Hailei
Published: December 2020

Phanerochaete chrysosporium is a white rot fungus naturally isolated from hardwoods and widely used in environmental pollution control because it produces extracellular peroxidases. It forms chlamydospores during nitrogen starvation, which naturally occurs in the habitat of P. chrysosporium. Chlamydospores protect fungi against many stresses; the molecular basis underlying chlamydospore formation in basidiomycetes is poorly explored. Chlamydospores in P. chrysosporium have a different cell wall compared with hyphae, as confirmed by cell wall digestion and microscopy. Furthermore, this study investigated the transcriptome of P. chrysosporium in different life stages, including conidium, hypha, and chlamydospore formation, through RNA sequencing. A total of 2215 differentially expressed genes were identified during these processes. The expression patterns of genes involved in several molecular events critical for chlamydospore formation, including starch and sucrose metabolism, phosphatase and kinase, and transcription factors, were determined. This study serves as a basis for further investigating the function of chlamydospore formation in the biotechnologically relevant fungus P. chrysosporium.
Predicting Metabolite-Disease Associations Based on Spy Strategy and ABC Algorithm
Authors: Lei Xiujuan , Zhang Cheng , Wang Yueyue
Published: December 2020

In recent years, latent metabolite-disease associations have been a significant focus in the biomedical domain. And more and more experimental evidence has been adduced that metabolites correlate with the diagnosis of complex human diseases. Several computational methods have been developed to detect potential metabolite-disease associations. In this article, we propose a novel method based on the spy strategy and an artificial bee colony (ABC) algorithm for metabolite-disease association prediction (SSABCMDA). Due to the fact that there are large parts of missing associations in unconfirmed metabolite-disease pairs, spy strategy is adopted to extract reliable negative samples from unconfirmed pairs. Considering the effects of parameters, the ABC algorithm is utilized to optimize parameters. In relevant cross-validation experiments, our method achieves excellent predictive performance. Moreover, three types of case studies are conducted on three common diseases to demonstrate the validity and utility of SSABCMDA method. Relevant experimental results indicate that our method can predict potential associations between metabolites and diseases effectively.
A Systematic Review of Training Methods That May Improve Selective Voluntary Motor Control in Children With Spastic Cerebral Palsy
Authors: Fahr Annina , Keller Jeffrey W. , van Hedel Hubertus J. A.
Published: December 2020

Background: Impaired selective voluntary motor control is defined as “the reduced ability to isolate the activation of muscles in response to demands of a voluntary posture or movement.” It is a negative motor sign of an upper motor neuron lesion.

Objective: This paper reviews interventions that may improve selective motor control in children and youths with spastic cerebral palsy. The aim was to systematically evaluate the methodological quality and formulate the level of evidence from controlled studies.

Methods: Six databases (Scopus, Web of Science, PubMed, Embase, MEDLINE, and CINAHL) were searched with predefined search terms for population, interventions, and outcomes. Two reviewers independently completed study selection and ratings of methodological quality and risk of bias. Evidence was summarized in a best evidence synthesis.

Results: Twenty-three studies from initially 2,634 papers were included. The interventions showed a wide variety of approaches, such as constraint-induced movement therapy (CIMT), electrical stimulation, robot-assisted therapy, and functional training. The evidence synthesis revealed conflicting evidence for CIMT, robot-assisted rehabilitation and mirror therapy for the upper extremities in children with cerebral palsy.

Conclusions: Final recommendations are difficult due to heterogeneity of the reviewed studies. Studies that include both an intervention and an outcome that specifically focus on selective voluntary motor control are needed to determine the most effective therapy.
Shared Characteristics of Intrinsic Connectivity Networks Underlying Interoceptive Awareness and Empathy
Authors: Stoica Teodora , Depue Brendan
Published: December 2020

Awareness of internal bodily sensations (interoceptive awareness; IA) and its connection to complex socioemotional abilities like empathy has been postulated, yet the functional neural circuitry they share remains poorly understood. The present fMRI study employs independent component analysis (ICA) to investigate which empathy facet (Cognitive or Affective) shares resting-state functional connectivity (rsFC) and/or BOLD variability (rsBOLD) with IA. Healthy participants viewed an abstract nonsocial movie demonstrated to evoke strong rsFC in brain networks resembling rest (InScapes), and resultant rsFC and rsBOLD data were correlated with self-reported empathy and IA questionnaires. We demonstrate a bidirectional behavioral and neurobiological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA share both rsFC and rsBOLD, while Cognitive empathy and IA only share rsBOLD. Specifically, increased rsFC in the right inferior frontal operculum (rIFO) of a larger attention network was associated with increased vicarious experience but decreased awareness of inner body sensations. Furthermore, increased rsBOLD between brain regions of an interoceptive network was related to increased sensitivity to internal sensations along with decreased Affective empathy. Finally, increased rsBOLD between brain regions subserving a mentalizing network related to not only an improved ability to take someone’s perspective, but also a better sense of mind-body interconnectedness. Overall, these findings suggest that the awareness of one’s own internal body changes (IA) is related to the socioemotional ability of feeling and understanding another’s emotional state (empathy) and critically, that this relationship is reflected in the brain’s resting state neuroarchitecture. Methodologically, this work highlights the importance of utilizing rsBOLD as a complementary window alongside rsFC to better understand neurological phenomena. Our results may be beneficial in aiding diagnosis in clinical populations such as autism spectrum disorder (ASD), where participants may be unable to complete tasks or questionnaires due to the severity of their symptoms.
A Geometric Theory Integrating Human Binocular Vision With Eye Movement
Authors: Turski Jacek
Published: December 2020

A theory of the binocular system with asymmetric eyes (AEs) is developed in the framework of bicentric perspective projections. The AE accounts for the eyeball's global asymmetry produced by the foveal displacement from the posterior pole, the main source of the eye's optical aberrations, and the crystalline lens' tilt countering some of these aberrations. In this theory, the horopter curves, which specify retinal correspondence of binocular single vision, are conic sections resembling empirical horopters. This advances the classic model of empirical horopters as conic sections introduced in an ad hoc way by Ogle in 1932. In contrast to Ogle's theory, here, anatomically supported horopteric conics vary with the AEs' position in the visual plane of bifoveal fixations and their transformations are visualized in a computer simulation. Integrating horopteric conics with eye movements can help design algorithms for maintaining a stable perceptual world from visual information captured by a mobile robot's camera head. Further, this paper proposes a neurophysiologically meaningful definition for the eyes' primary position, a concept which has remained elusive despite its theoretical importance to oculomotor research. Finally, because the horopteric conic's shape is dependent on the AE's parameters, this theory allows for changes in retinal correspondence, which is usually considered preformed and stable.
Time-Dependent Effects of Acute Handling on the Brain Monoamine System of the Salmonid Coregonus maraena
Authors: Martorell-Ribera Joan , Venuto Marzia Tindara , Otten Winfried , Brunner Ronald M. , Goldammer Tom , Rebl Alexander , Gimsa Ulrike
Published: December 2020

The immediate stress response involves the activation of the monoaminergic neurotransmitter systems including serotonin, dopamine and noradrenaline in particular areas of the fish brain. We chose maraena whitefish as a stress-sensitive salmonid species to investigate the influence of acute and chronic handling on the neurochemistry of monoamines in the brain. Plasma cortisol was quantified to assess the activation of the stress axis. In addition, we analyzed the expression of 37 genes related to the monoamine system to identify genes that could be used as markers of neurophysiological stress effects. Brain neurochemistry responded to a single handling (1 min netting and chasing) with increased serotonergic activity 3 h post-challenge. This was accompanied by a modulated expression of monoaminergic receptor genes in the hindbrain and a significant increase of plasma cortisol. The initial response was compensated by an increased monoamine synthesis at 24 h post-challenge, combined with the modulated expression of serotonin-receptor genes and plasma cortisol concentrations returning to control levels. After 10 days of repeated handling (1 min per day), we detected a slightly increased noradrenaline synthesis and a down-regulated expression of dopamine-receptor genes without effect on plasma cortisol levels. In conclusion, the changes in serotonergic neurochemistry and selected gene-expression profiles, together with the initial plasma cortisol variation, indicate an acute response and a subsequent recovery phase with signs of habituation after 10 days of daily exposure to handling. Based on the basal expression patterns of particular genes and their significant regulation upon handling conditions, we suggest a group of genes as potential biomarkers that indicate handling stress on the brain monoamine systems.
Vitamin A Deficiency in the Early-Life Periods Alters a Diversity of the Colonic Mucosal Microbiota in Rats
Authors: Chen Baolin , Liu Shu , Feng Di , Xiao Lu , Yang Ting , Li Tingyu , Sun Wuqing , Chen Jie
Published: December 2020

Vitamin A deficiency (VAD) remains a public health issue worldwide, affecting pregnant women and children. The early-life microbiota is a potentially effective intervention target for modulating immune and metabolic development of the host. This paper investigates the effects of VAD during different life periods on the structure of the colonic mucosa microbiota in adolescent rats. The results showed that the concentrations of serum retinol were > ~1.05 μmol/L in maternal VA normal (VAN)rats and < 0.7 μmol/L in maternal VAD rats, while the serum retinol levels were higher than 0.7 μmol/L in the pups of the VAN group and below 0.5 μmol/L in the pups of the VAD group. Compared to the offspring persistent with VAN from embryonic stage (group A), all the remaining groups exhibited an increased ratio of Firmicutes/Bacteroidetes abundance. A metagenome analysis (LEfSe) and a differentially abundant features approach using Metastats for genus abundances revealed that Diaphorobacter and Psychrobacter were increased in the offspring persistent with VAD from embryonic stage (group B);Bifidobacterium was decreased and Staphylococcus was increased in the offspring with VAD after weaning (group C); Propionibacterium and Enterobacter were increased significantly in the offspring with VAD during gestation(group E); and Ochrobactrum was increased in group B and the offspring with VAD during gestation and lactation(group D). Faecalibacterium abundance was significantly and positively related to serum retinol levels, while that of Staphylococcus was significantly and negatively correlated with serum retinol levels. VAD in different life periods can alter the gut microbiome in rats, but VAD in the early-life periods (especially gestation and/or lactation) leads to a diversity of the colonic mucosal microbiota in adolescent rats as well as an imbalance of the ratio between Firmicutes and Bacteroidetes. The early-life period may become a time window of VA intervention to improve intestinal microbiota caused by VA deficiency, but the specific mechanism requires more in-depth research.
PD-L1 Expression in Muscle-Invasive Urinary Bladder Urothelial Carcinoma According to Basal/Squamous-Like Phenotype
Authors: Kim Bohyun , Lee Cheol , Kim Young A. , Moon Kyung Chul
Published: December 2020

Urothelial carcinoma (UC) is the most common histologic type of urinary bladder cancer, and muscle-invasive UC shows aggressive behaviors. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockades have been approved as standard treatments for patients with advanced stage UC. A total of 166 muscle-invasive urinary bladder cancer (MIBC) patients, who underwent transurethral resection of the bladder or cystectomy from 2004 to 2010 were included. We evaluated PD-L1 expression by the SP142 and SP263 assays and classified the cases “positive” or “negative” according to the manufacturer’s recommendations. We performed immunohistochemistry (IHC) for cytokeratin (CK) 5/6, CK14, GATA3, FOXA1, and CK20 and classified samples as Basal-Squamous-like (BASQ) or non-BASQ subtype. The overall concordance rate for PD-L1 expression is 91.6% (152/166) (kappa = 0.732). The SP142 assay showed 15.1% positivity; the SP263 assay showed 23.5%. The high positivity in the SP142 and SP263 assay was significantly correlated with positive CK5/6, CK14 expression, negative GATA3, FOXA1, and CK20 expression. Classification according to IHC expression resulted in 12.0% (20/166) of samples being classified as BASQ subtype and 88.0% (146/166) of samples being classified as non-BASQ subtype. High positivity in the SP142 and SP263 assay was significantly correlated with the BASQ subtype (p < 0.001, both). Our study is the first to analyze the association of immunohistochemically defined BASQ and non-BASQ subtypes with two PD-L1 assays in MIBC. In conclusion, we revealed that a high PD-L1 positive rate in all PD-L1 assays was significantly associated with the BASQ-subtype, and these results suggest that the BASQ classification may be important to apply the PD-1/PD-L1 blockades in MIBC.
Predictive Value of Occult Metastasis and Survival Significance of Metabolic Tumor Volume Determined by PET-CT in cT1-2N0 Squamous Cell Carcinoma of the Tongue
Authors: Yang Lijie , Liu Fei , Wu Yao , Fang Qigen , Zhang Xiaojun , Du Wei , Zhang Xu , Chen Defeng , Luo Ruihua
Published: December 2020

Objectives

Our goal was to analyze the possibility of using metabolic tumor volume (MTV) to predict occult cervical metastasis and survival in cT1-2N0 squamous cell carcinoma (SCC) of the tongue.

Methods

Data on the primary tumor MTV and cervical node status as determined by the maximum standardized uptake value were retrieved. The sensitivity and specificity in predicting occult metastasis were calculated with a fourfold table. Associations between occult metastasis and clinicopathological variables were evaluated by univariate and multivariate analyses. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS).

Results

A total of 24 (20.3%) of 118 patients had occult metastasis. An MTV cutoff value of 4.3 cm3 showed a sensitivity of 50.0% and a specificity of 76.6% in predicting occult metastasis. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT1 tumors were 66.6 and 89.8%, respectively, with values of 83.3 and 67.3%, respectively, when combined with the MTV. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT2 tumors were 72.2 and 82.2%, respectively, with values of 88.9 and 57.8%, respectively, when combined with the MTV. Patients with MTV ≥4.3 cm3 had a higher occult metastasis rate than patients with MTV <4.3 cm3. The 5-year LRC and DSS rates were 86 and 94%, respectively, in patients with MTV <4.3 cm3 and 54 and 72%, respectively, in patients with MTV ≥4.3 cm3. Both differences were found to be significant in univariate and multivariate analyses.

Conclusions

MTV ≥4.3 cm3 was associated with an increased probability of occult metastasis and lower LRC and DSS rates in early-stage SCC of the tongue.
Thrombospondin-1 Receptor CD47 Overexpression Contributes to P-Glycoprotein-Mediated Multidrug Resistance Against Doxorubicin in Thyroid Carcinoma FTC-133 Cells
Authors: Courageot Marie-Pierre , Duca Laurent , Martiny Laurent , Devarenne-Charpentier Emmanuelle , Morjani Hamid , El Btaouri Hassan
Published: December 2020

It is now admitted that in addition to acquired resistance, the tumor microenvironment contributes to the development of chemo-resistance and malignant progression. In a previous study, we showed that Dox induced apoptosis in FTC-133 cells by trigging JNK pathway. This process was accompanied by a decrease of thrombospondin-1 (TSP-1) expression. Moreover, exogenous TSP-1 or its C-terminal-derived peptide interact with receptor CD47 and are able to protect FTC-133 cells against Dox-induced apoptosis. Here, we investigated the involvement of TSP-1/CD47 interaction in a context of acquired multidrug resistance in FTC-133 cells. To that end, we established a Dox-resistant cell line (FTC-133R cells) which developed a resistance against Dox-induced apoptosis. Cell viability was evaluated by Uptiblue assay, nuclear Dox was measured by microspectrofluorimetry, caspase activity was measured by fluorescence of cleaved caspase-3 substrate, gene expression was evaluated by RT-PCR and protein expression was examined by western-blot. Our results showed that FTC-133R overexpressed the P-gp and were 15-fold resistant to Dox. JNK phosphorylation and Dox-induced apoptosis were reduced in FTC-133R cells. Expression of CD47 was increased in FTC-133R cells but TSP-1 expression presented similar levels in two cell lines. VPL restored Dox nuclear uptake and FTC-133R cell sensitivity to apoptosis and induced a decrease in CD47 mRNA expression. Moreover, knockdown of CD47 in FTC-133R cells induced an increase in JNK activation and sensitized FTC-133R cells to Dox. Our data suggest that CD47 is able to contribute to the protection of FTC-133R cells against Dox-induced apoptosis and/or to potentiate the acquired Dox resistance.
Potential Role of Adjuvant Lenvatinib in Improving Disease-Free Survival for Patients With High-Risk Hepatitis B Virus-Related Hepatocellular Carcinoma Following Liver Transplantation: A Retrospective, Case Control Study
Authors: Han Bing , Ding Han , Zhao Shuai , Zhang Yichi , Wang Jian , Zhang Yue , Gu Jinyang
Published: December 2020

Background and Aim

Although liver transplantation (LT) is one of the most effective treatments for the patients with hepatocellular carcinoma (HCC), the high-risk patients suffer from a high ratio of tumor recurrence after LT. Lenvatinib, as a novel targeted drug, has shown an excellent effect in the treatment of advanced HCC, but there is no study on its effect in preventing HCC recurrence in the patients undergoing transplantation. Therefore, this study was designed to evaluate the role of adjuvant lenvatinib in preventing recurrence of high-risk LT recipients with HBV-related HCC.

Methods

We retrospectively analyzed 23 high-risk patients consisting of lenvatinib group (n=14) and control group (n=9) with HBV-related HCC who underwent LT in our center. Disease-free survival (DFS) and HCC recurrence of the two groups were compared. The adverse events (AEs) and drug tolerance of lenvatinib were evaluated.

Results

The median DFS in lenvatinib group was 291 (95%CI 204–516) days, significantly longer than 182 (95%CI 56–537) days in control group (P=0.04). Three patients in lenvatinib group (21.4%) and five patients in control group (55.6%) had short-term HCC recurrence (P=0.11). All patients in lenvatinib group could tolerate oral lenvatinib for at least three cycles except six cases (42.9%) of dose reduction and 1 case of interruption (14.3%). Thirteen patients (92.9%) taking lenvatinib experienced AEs. The most common AEs were hypertension (64.3%) and proteinuria (42.9%), and the most serious AEs were Grade 3 for 4 cases (28.5%) according to common terminology criteria for adverse events (CTCAE) version 5.0. Additionally, no influence of lenvatinib on the dosage and blood concentration of FK506 was observed.

Conclusions

Adjuvant lenvatinib had a potential benefit on prolonging the DFS and reducing the recurrence of high-risk HBV-related HCC patients following liver transplantation with an acceptable drug safety and patient tolerance.
A Review on Anti-Tumor Mechanisms of Coumarins
Authors: Wu Yi , Xu Jing , Liu Yiting , Zeng Yiyu , Wu Guojun
Published: December 2020

Coumarins are a class of compound with benzopyrone as their basic structure. Due to abundant sources, easy synthesis, and various pharmacological activities, coumarins have attracted extensive attention from researchers. In particular, coumarins have very significant anti-tumor abilities and a variety of anti-tumor mechanisms, including inhibition of carbonic anhydrase, targeting PI3K/Akt/mTOR signaling pathways, inducing cell apoptosis protein activation, inhibition of tumor multidrug resistance, inhibition of microtubule polymerization, regulating the reactive oxygen species, and inhibition of tumor angiogenesis, etc. This review focuses on the mechanisms and the research progress of coumarins against cancers in recent years.
Analysis of Prognostic Factors of World Health Organization Grade Ⅲ Meningiomas
Authors: Tian Weidong , Liu Jingdian , Zhao Kai , Wang Junwen , Jiang Wei , Shu Kai , Lei Ting
Published: December 2020

Objective

WHO grade III meningiomas are highly aggressive and lethal. However, there is a paucity of clinical information because of a low incidence rate, and little is known for prognostic factors. The aim of this work is to analyze clinical characteristics and prognosis in patients diagnosed as WHO grade III meningiomas.

Methods

36 patients with WHO grade III meningiomas were enrolled in this study. Data on gender, age, clinical presentation, preoperative Karnofsky Performance Status (KPS), histopathologic features, tumor size, location, radiologic findings, postoperative radiotherapy (RT), surgical treatment, and prognosis were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted by the Cox regression model.

Results

Median PFS is 20 months and median OS is 36 months in 36 patients with WHO grade III meningiomas. Patients with secondary tumors which transformed from low grade meningomas had lower PFS (p=0.0014) compared with primary group. Multivariate analysis revealed that tumors location (PFS, p=0.016; OS, p=0.013), Ki-67 index (PFS, p=0.004; OS, p<0.001) and postoperative radiotherapy (PFS, p=0.006; OS, p<0.001) were associated with prognosis.

Conclusion

WHO grade III meningiomas which progressed from low grade meningiomas were more prone to have recurrences or progression. Tumors location and Ki-67 index can be employed to predict patient outcomes. Adjuvant radiotherapy after surgery can significantly improve patient prognosis.
First-Line Durvalumab Plus Platinum-Etoposide Versus Platinum-Etoposide for Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis
Authors: Zhang Longfeng , Hang Yongfu , Liu Maobai , Li Na , Cai Hongfu
Published: December 2020

Background

The aim of the present study was to evaluate the cost-effectiveness of durvalumab plus platinum–etoposide versus platinum–etoposide as first-line treatments for small-cell lung cancer from the perspective of the US payer.

Methods

This study established a partition survival model for three health states, metastasis probability, and safety data based on the CASPIAN clinical trial. The health utility value was mainly derived from the published literature. Only direct medical costs were considered. Sensitivity analyses were conducted to assess the robustness of the incremental cost per quality-adjusted life year (QALY).

Results

Durvalumab plus platinum–etoposide increased QALY by 0.220 compared to that observed with platinum–etoposide only. The cost increased by $78,198.75 and the incremental cost per QALY increased by $355,448.86. One-way and probability sensitivity analyses indicated that the model parameters varied within a limited range and had no significant effect on the results.

Conclusions

Although durvalumab plus platinum–etoposide can improve quality of life, it also substantially increases the cost of medical treatment. Under a willingness-to-pay threshold of $100,000, durvalumab does not have a cost-effective comparative advantage.
Metabolism-Associated Molecular Classification of Colorectal Cancer
Authors: Zhang Meng , Wang Hai-zhou , Peng Ru-yi , Xu Fei , Wang Fan , Zhao Qiu
Published: December 2020

The high heterogeneity of colorectal cancer (CRC) is the main clinical challenge for individualized therapies. Molecular classification will contribute to drug discovery and personalized management optimizing. Here, we aimed to characterize the molecular features of CRC by a classification system based on metabolic gene expression profiles. 435 CRC samples from the Genomic Data Commons data portal were chosen as training set while 566 sample in GSE39582 were selected as testing set. Then, a non-negative matrix factorization clustering was performed, and three subclasses of CRC (C1, C2, and C3) were identified in both training set and testing set. Results showed that subclass C1 displayed high metabolic activity and good prognosis. Subclass C2 was associated with low metabolic activities and displayed high immune signatures as well as high expression of immune checkpoint genes. C2 had the worst prognosis among the three subtypes. Subclass C3 displayed intermediate metabolic activity, high gene mutation numbers and good prognosis. Finally, a 27-gene metabolism-related signature was identified for prognosis prediction. Our works deepened the understanding of metabolic hallmarks of CRC, and provided valuable information for “multi-molecular” based personalized therapies.
Gut Microbiota of Young Children Living in Four Brazilian Cities
Authors: Chew Charmaine , Barros Karina Vieira , Weffort Virginia Resende Silva , Maranhão Hélcio de Sousa , Laranjeira Marisa , Knol Jan , Roeselers Guus , de Morais Mauro Batista
Published: December 2020

Recent studies have demonstrated that gut microbiota development is influenced by human biogeographic factors such as race, ethnicity, diet, lifestyle or culture-specific variations, and other environmental influences. However, biogeographic variation in gut microbiota assembly remains largely unexplored in Latin America. In this paper, we compared food recall information and microbiota composition of toddlers living in geographically separated urban populations within four states of Brazil. 16S RNA gene sequencing revealed that alpha diversity was similar between the four different populations. Gut microbiota compositions were dominated by members of the phyla Firmicutes and Bacteroidetes, resembling a more adult-like microbiota as compared with those of Western European toddlers of similar age. These findings suggest that inter-individual and nutrition-induced differences were apparent in the fecal microbiota. We conclude that urban dietary pattern plays a larger role in influencing the gut microbiota composition than do biogeographic factors.
Brainstem Auditory Evoked Potentials and Visual Potentials in Kawasaki Disease: An Observational Monocentric Study
Authors: Maggio Maria Cristina , Corsello Giovanni , Salvo Giuseppe , Puma Domenico Giuseppe , Cimaz Rolando
Published: December 2020

Background: Kawasaki Disease is a systemic vasculitis, particularly involving coronary arteries. Rare involvement of other vascular districts is described, as central nervous system arteries, leading to a vasculitic neuropathy. Sensorineural hearing loss and alterations of evoked potentials are uncommonly reported complications.

Methods: In an observational monocentric study, 59 children (37 males; 22 females; mean age: 2.7 ± 2.2 years) with documented Kawasaki Disease were enrolled. No risk factors for hearing loss and/or neurological impairment were identified in the cohort. Brainstem auditory evoked potentials and visual evoked potentials were correlated with clinical, hamatological and radiological data, evaluated in the acute phase of the Kawasaki Disease, and during the follow-up.

Results: Evoked potentials were altered in 39/59 patients (66%): of these, 27/39 (69%) showed altered IV and V waves and/or III-V interwave latencies of brainstem auditory evoked potentials; 4/39 (10%) showed pathological visual evoked potentials; 8/39 (21%) had abnormalities of both brainstem auditory evoked potentials and visual evoked potentials. No permanent deafness was reported.

Conclusion: Abnormalities in visual evoked potentials were not significantly correlated with coronary artery lesions; however, the presence of abnormalities of brainstem auditory evoked potentials were associated with the risk of coronary artery lesions.