bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Genome DNA Methylation at Inherited Coat Color Dilutions of Rex Rabbits
Authors: Chen Yang , Hu Shuaishuai , Liu Ming , Zhao Bohao , Yang Naisu , Li Jiali , Chen Qiuran , Zhou Juan , Bao Guolian , Wu Xinsheng
Published: January 2021

Background:The dilution of color in rabbits is associated with many different genetic mechanisms that form different color groups. A number of previous studies have revealed potential regulatory mechanisms by which epigenetics regulate pigmentation. However, the genome-wide DNA methylation involved in animal coat color dilution remains unknown.

Results:We compared genome-wide DNA methylation profiles in Rex rabbit hair follicles in a Chinchilla group (Ch) and a diluted Chinchilla group (DCh) through whole-genome bisulfite sequencing (WGBS). Approximately 3.5% of the cytosine sites were methylated in both groups, of which the CG methylation type was in greatest abundance. In total, we identified 126,405 differentially methylated regions (DMRs) between the two groups, corresponding to 11,459 DMR-associated genes (DMGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these DMGs were principally involved in developmental pigmentation and Wnt signaling pathways. In addition, two DMRs were randomly selected to verify that the WGBS data were reliable using bisulfite sequencing PCR, and seven DMGs were analyzed to establish the relationship between the level of DNA methylation and mRNA expression using qRT-PCR. Due to the limitation of small sample size, replication of the results with a larger sample size would be important in future studies.

Conclusion:These findings provide evidence that there is an association between inherited color dilution and DNA methylation alterations in hair follicles, greatly contributing to our understanding of the epigenetic regulation of rabbit pigmentation.
Comparative Transcriptome Analysis During the Seven Developmental Stages of Channel Catfish (Ictalurus punctatus) and Tra Catfish (Pangasianodon hypophthalmus) Provides Novel Insights for Terrestrial Adaptation
Authors: Ma Xiaoli , Shang Mei , Su Baofeng , Wiley Anne , Bangs Max , Alston Veronica , Simora Rhoda Mae , Nguyen Mai Thi , Backenstose Nathan J. C. , Moss Anthony G. , Duong Thuy-Yen , Wang Xu , Dunham Rex A.
Published: January 2021

Tra catfish (Pangasianodon hypophthalmus), also known as striped catfish, is a facultative air-breather that uses its swim bladder as an air-breathing organ (ABO). A related species in the same order (Siluriformes), channel catfish (Ictalurus punctatus), does not possess an ABO and thus cannot breathe in the air. Tra and channel catfish serve as great comparative models for investigating possible genetic underpinnings of aquatic to land transitions, as well as for understanding genes that are crucial for the development of the swim bladder and the function of air-breathing in tra catfish. In this study, hypoxia challenge and microtomy experiments collectively revealed critical time points for the development of the air-breathing function and swim bladder in tra catfish. Seven developmental stages in tra catfish were selected for RNA-seq analysis based on their transition to a stage that could live at 0 ppm oxygen. More than 587 million sequencing clean reads were generated, and a total of 21,448 unique genes were detected. A comparative genomic analysis between channel catfish and tra catfish revealed 76 genes that were present in tra catfish, but absent from channel catfish. In order to further narrow down the list of these candidate genes, gene expression analysis was performed for these tra catfish-specific genes. Fourteen genes were inferred to be important for air-breathing. Of these,HRG,GRP, andCX3CL1were identified to be the most likely genes related to air-breathing ability in tra catfish. This study provides a foundational data resource for functional genomic studies in air-breathing function in tra catfish and sheds light on the adaptation of aquatic organisms to the terrestrial environment.
Investigation on Potential Correlation Between Small Nuclear Ribonucleoprotein Polypeptide A and Lung Cancer
Authors: Yuan Maoxi , Yu Chunmei , Chen Xin , Wu Yubing
Published: January 2021

SNRPA (small nuclear ribonucleoprotein polypeptide A) gene is essential for the pre-mRNA splicing process. Using the available datasets of TCGA or GEO, we aimed at exploring the potential association between the SNRPA gene and lung cancer by several online tools (such as GEIPA2, MEXPRESS, Oncomine) and bioinformatics analysis software (R or GSEA). SNRPA was highly expressed in the tissues of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma tissue (LUSC), compared with control tissues. The high SNRPA expression was associated with a poor survival prognosis of LUAD cases, while the genetic alteration within SNRPA was linked to the overall survival prognosis of LUSC cases. There was a potential correlation between promoter methylation and the expression of SNRPA for LUAD. Compared with normal tissues, we observed a higher phosphorylation level at the S115 site of SNRPA protein (NP_004587.1) (p = 0.002) in the primary LUAD tissues. The potential ATR kinase of the S115 site was predicted. Besides, SNRPA expression in lung cancer was negatively correlated with the infiltration level of M2 macrophage but positively correlated with that of Follicular B helper T cells, in both LUAD and LUSC. The enrichment analysis of SNRPA-correlated genes showed that cell cycle and ubiquitin mechanism-related issues were mainly observed for LUAD; however, RNA splicing-related cellular issues were mainly for LUSC. In summary, the SNRPA gene was identified as a potential prognosis biomarker of lung cancer, especially lung adenocarcinoma, which sheds new light on the association between the spliceosomal complex component and tumorigenesis.
Research on Components Assembly Platform of Biological Sequences Alignment Algorithm
Authors: Shi Haihe , Wu Gang , Zhang Xuchu , Wang Jun , Shi Haipeng , Xu Shenghua
Published: January 2021

After years of development, the complexity of the biological sequence alignment algorithm is gradually increasing, and the lack of high abstract level domain research leads to the complexity of its algorithm development and improvement. By applying the idea of software components to the design and development of algorithms, the development efficiency and reliability of biological sequence alignment algorithms can be effectively improved. The component assembly platform applies related assembly technology, which simplifies the operation difficulty of component assembly and facilitates the maintenance and optimization of the algorithm. At the same time, a friendly visual interface is used to intuitively complete the assembly of algorithm components, and an executable sequence alignment algorithm program is obtained, which can directly carry out alignment computing.
Research Status and Molecular Mechanism of the Traditional Chinese Medicine and Antitumor Therapy Combined Strategy Based on Tumor Microenvironment
Authors: Zhang Yang , Lou Yanni , Wang Jingbin , Yu Cunguo , Shen Wenjuan
Published: January 2021

Treatment of malignant tumors encompasses multidisciplinary comprehensive diagnosis and treatment and reasonable combination and arrangement of multidisciplinary treatment, which is not a simple superimposition of multiple treatment methods, but a comprehensive consideration of the characteristics and specific conditions of the patients and the tumor. The mechanism of tumor elimination by restoring the body’s immune ability is consistent with the concept of “nourishing positive accumulation and eliminating cancer by itself” in traditional Chinese medicine (TCM). The formation and dynamic changes in the tumor microenvironment (TME) involve many different types of cells and multiple signaling pathways. Those changes are similar to the multitarget and bidirectional regulation of immunity by TCM. Discussing the relationship and mutual influence of TCM and antitumor therapy on the TME is a current research hotspot. TCM has been applied in the treatment of more than 70% of cancer patients in China. Data have shown that TCM can significantly enhance the sensitivity to chemotherapeutic drugs, enhance tumor-suppressing effects, and significantly improve cancer-related fatigue, bone marrow suppression, and other adverse reactions. TCM treatments include the application of Chinese medicine monomers, extracts, classic traditional compound prescriptions, listed compound drugs, self-made compound prescriptions, as well as acupuncture and moxibustion. Studies have shown that the TCM functional mechanism related to the positive regulation of cytotoxic T cells, natural killer cells, dendritic cells, and interleukin-12, while negatively regulating of regulatory T cells, tumor-associated macrophages, myeloid-derived suppressive cells, PD-1/PD-L1, and other immune regulatory factors. However, the application of TCM in cancer therapy needs further study and confirmation. This article summarizes the existing research on the molecular mechanism of TCM regulation of the TME and provides a theoretical basis for further screening of the predominant population. Moreover, it predicts the effects of the combination of TCM and antitumor therapy and proposes further developments in clinical practice to optimize the combined strategy.
Massive Aggregations of Serpulidae Associated With Eutrophication of the Mar Menor, Southeast Iberian Peninsula
Authors: Sandonnini Jessica , Del Pilar Ruso Yoana , Cortés Melendreras Emilio , Giménez Casalduero Francisca
Published: January 2021

For decades, inputs of nutrients and organic matter into the Mar Menor coastal lagoon have favored the change from an original oligotrophic to a eutrophic state. The lagoon reached a stage of severe eutrophication and “environmental collapse” during the spring of 2016. This paper describes the massive growth of Serpulidae (Annelida, Polychaeta) forming large aggregations and reef structures after the environmental collapse caused by the eutrophic crisis. Four species belonging to the genera Hydroides and Serpula were identified; the identified species are Hydroides elegans, Hydroides dianthus, Serpula concharum, and Serpula vermicularis. The presence of bi-operculate and tri-operculate specimens is also documented in this study.
Impacts of Acclimation in Warm-Low pH Conditions on the Physiology of the Sea Urchin Heliocidaris erythrogramma and Carryover Effects for Juvenile Offspring
Authors: Harianto Januar , Aldridge Joshua , Torres Gabarda Sergio A. , Grainger Richard J. , Byrne Maria
Published: January 2021

Ocean warming (OW) and acidification (OA) affects nearly all aspects of marine organism physiology and it is important to consider both stressors when predicting responses to climate change. We investigated the effects of long-term exposure to OW and OA on the physiology of adults of the sea urchin,Heliocidaris erythrogramma, a species resident in the southeast Australia warming hotspot. The urchins were slowly introduced to stressor conditions in the laboratory over a 7-week adjustment period to three temperature (ambient, +2°C, +3°C) and two pH (ambient: pHT8.0; −0.4 units: pHT7.6) treatments. They were then maintained in a natural pattern of seasonal temperature and photoperiod change, and fixed pH, for 22 weeks. Survival was monitored through week 22 and metabolic rate was measured at 4 and 12 weeks of acclimation, feeding rate and ammonia excretion rate at 12 weeks and assimilation efficiency at 13 weeks. Acclimation to +3°C was deleterious regardless of pH. Mortality from week 6 indicated that recent marine heatwaves are likely to have been deleterious to this species. Acclimation to +2°C did not affect survival. Increased temperature decreased feeding and increased excretion rates, with no effect of acidification. While metabolic rate increased additively with temperature and low pH at week 4, there was no difference between treatments at week 12, indicating physiological acclimation in surviving urchins to stressful conditions. Regardless of treatment,H. erythrogrammahad a net positive energy budget indicating that the responses were not due to energy limitation. To test for the effect of parental acclimation on offspring responses, the offspring of acclimated urchins were reared to the juvenile stage in OW and OA conditions. Parental acclimation to warming, but not acidification altered juvenile physiology with an increase in metabolic rate. Our results show that incorporation of gradual seasonal environmental change in long-term acclimation can influence outcomes, an important consideration in predicting the consequences of changing climate for marine species.
Short-Term Exposure to Sterile Seawater Reduces Bacterial Community Diversity in the Sea Anemone, Exaiptasia diaphana
Authors: Dungan Ashley M. , van Oppen Madeleine J. H. , Blackall Linda L.
Published: January 2021

The global decline of coral reefs heightens the need to understand how corals may persist under changing environmental conditions. Restructuring of the coral-associated bacterial community, either through natural or assisted strategies, has been suggested as a means of adaptation to climate change. A low complexity microbial system would facilitate testing the efficacy of microbial restructuring strategies. We used the model organism for corals,Exaiptasia diaphana, and determined that short-term (3 weeks) exposure to filter-sterilized seawater conditions alone reduced the complexity of the microbiome. Metabarcoding of the V5–V6 region of the bacterial 16S rRNA gene revealed that alpha diversity was approximately halved in anemones reared in filter-sterilized seawater compared to controls reared in unfiltered seawater and that the composition (beta diversity) differed significantly between the two. By reducing the complexity of theE. diaphanamicrobiome, the development of a system for testing assisted strategies such as probiotics, is more feasible.
Case Report: Diagnosis of Primary Cutaneous Amyloidosis Using Dermoscopy and Reflectance Confocal Microscopy
Authors: Wang Xiuli , Wang Hui , Zhong Zhenyu , Zheng Liyun , Wang Yifan , Guo Ze , Li Hui , Gao Min
Published: January 2021

The dermoscopy and reflectance confocal microscopy (RCM) can provide new insights for diagnosis disease as non-invasive and easy-to-use tool. We described the dermoscopy and RCM characteristics of two patients with primary cutaneous amyloidosis (PCA) respectively. The dermoscopy characteristics were as follows: brownish macules with brown or white centers surrounded by hyperpigmented blotches, and a whitish scar-like center encircled by irregular brownish hyperpigmented spots or patches. The RCM features were increased melanin deposition in the basal layer, highly refractive structures with various shapes in the enlarged papillary dermis, and the increased pleomorphic structure of the dermal papillary ring. This is the first report the dermoscopy and RCM characteristics of PCA. We hope the characteristic dermoscopy and RCM appearances would provide a basis for doctors to diagnose and intervene earlier.
MiR-21 Is Remotely Governed by the Commensal Bacteria and Impairs Anti-TB Immunity by Down-Regulating IFN-γ
Authors: Yang Fang , Yang Yi , Chen Yiwei , Li Guobao , Zhang Guoliang , Chen Lingming , Zhang Zhiyi , Mai Qiongdan , Zeng Gucheng
Published: January 2021

Tuberculosis (TB), which is a frequent and important infectious disease caused by Mycobacterium tuberculosis, has resulted in an extremely high burden of morbidity and mortality. The importance of intestinal dysbacteriosis in regulating host immunity has been implicated in TB, and accumulating evidence suggests that microRNAs (miRNAs) might act as a key mediator in maintaining intestinal homeostasis through signaling networks. However, the involvement of miRNA in gut microbiota, TB and the host immune system remains unknown. Here we showed that intestinal dysbacteriosis increases the susceptibility to TB and remotely increased the expression of miR-21 in lung. Systemic antagonism of miR-21 enhanced IFN-γ production and further conferred immune protection against TB. Molecular experiments further indicated that miR-21a-3p could specifically target IFN-γ mRNA. These findings revealed regulatory pathways implicating intestinal dysbacteriosis induced-susceptibility to TB: intestinal dysbiosis→lung miRNA→targeting IFN-γ→impaired anti-TB immunity. This study also suggested that deregulated miRNAs by commensal bacteria could become promising targets as TB therapeutics.
Unravelling the Role of Rumen Microbial Communities, Genes, and Activities on Milk Fatty Acid Profile Using a Combination of Omics Approaches
Authors: Stergiadis Sokratis , Cabeza-Luna Irene , Mora-Ortiz Marina , Stewart Robert D. , Dewhurst Richard J. , Humphries David J. , Watson Mick , Roehe Rainer , Auffret Marc D.
Published: January 2021

Milk products are an important component of human diets, with beneficial effects for human health, but also one of the major sources of nutritionally undesirable saturated fatty acids (SFA). Recent discoveries showing the importance of the rumen microbiome on dairy cattle health, metabolism and performance highlight that milk composition, and potentially milk SFA content, may also be associated with microorganisms, their genes and their activities. Understanding these mechanisms can be used for the development of cost-effective strategies for the production of milk with less SFA. This work aimed to compare the rumen microbiome between cows producing milk with contrasting FA profile and identify potentially responsible metabolic-related microbial mechanisms. Forty eight Holstein dairy cows were fed the same total mixed ration under the same housing conditions. Milk and rumen fluid samples were collected from all cows for the analysis of fatty acid profiles (by gas chromatography), the abundances of rumen microbiome communities and genes (by whole-genome-shotgun metagenomics), and rumen metabolome (using 500 MHz nuclear magnetic resonance). The following groups: (i) 24 High-SFA (66.9–74.4% total FA) vs. 24 Low-SFA (60.2–66.6%% total FA) cows, and (ii) 8 extreme High-SFA (69.9–74.4% total FA) vs. 8 extreme Low-SFA (60.2–64.0% total FA) were compared. Rumen of cows producing milk with more SFA were characterized by higher abundances of the lactic acid bacteria Lactobacillus, Leuconostoc, and Weissella, the acetogenic Proteobacteria Acetobacter and Kozakia, Mycobacterium, two fungi (Cutaneotrichosporon and Cyphellophora), and at a lesser extent Methanobrevibacter and the protist Nannochloropsis. Cows carrying genes correlated with milk FA also had higher concentrations of butyrate, propionate and tyrosine and lower concentrations of xanthine and hypoxanthine in the rumen. Abundances of rumen microbial genes were able to explain between 76 and 94% on the variation of the most abundant milk FA. Metagenomics and metabolomics analyses highlighted that cows producing milk with contrasting FA profile under the same diet, also differ in their rumen metabolic activities in relation to adaptation to reduced rumen pH, carbohydrate fermentation, and protein synthesis and metabolism.
An Optimized Bacteriophage Cocktail Can Effectively Control Salmonella in vitro and in Galleria mellonella
Authors: Nale Janet Y. , Vinner Gurinder K. , Lopez Viviana C. , Thanki Anisha M. , Phothaworn Preeda , Thiennimitr Parameth , Garcia Angela , AbuOun Manal , Anjum Muna F. , Korbsrisate Sunee , Galyov Edouard E. , Malik Danish J. , Clokie Martha R. J.
Published: January 2021

Salmonella spp. is a leading cause of gastrointestinal enteritis in humans where it is largely contracted via contaminated poultry and pork. Phages can be used to control Salmonella infection in the animals, which could break the cycle of infection before the products are accessible for consumption. Here, the potential of 21 myoviruses and a siphovirus to eliminate Salmonella in vitro and in vivo was examined with the aim of developing a biocontrol strategy to curtail the infection in poultry and swine. Together, the phages targeted the twenty-three poultry and ten swine prevalent Salmonella serotype isolates tested. Although individual phages significantly reduced bacterial growth of representative isolates within 6 h post-infection, bacterial regrowth occurred 1 h later, indicating proliferation of resistant strains. To curtail bacteriophage resistance, a novel three-phage cocktail was developed in vitro, and further investigated in an optimized Galleria mellonella larva Salmonella infection model colonized with representative swine, chicken and laboratory strains. For all the strains examined, G. mellonella larvae given phages 2 h prior to bacterial exposure (prophylactic regimen) survived and Salmonella was undetectable 24 h post-phage treatment and throughout the experimental time (72 h). Administering phages with bacteria (co-infection), or 2 h post-bacterial exposure (remedial regimen) also improved survival (73–100% and 15–88%, respectively), but was less effective than prophylaxis application. These pre-livestock data support the future application of this cocktail for further development to effectively treat Salmonella infection in poultry and pigs. Future work will focus on cocktail formulation to ensure stability and incorporation into feeds and used to treat the infection in target animals.
Development and External Validation of a Novel Immune Checkpoint–Related Gene Signature for Prediction of Overall Survival in Hepatocellular Carcinoma
Authors: Zhao Enfa , Chen Shimin , Dang Ying
Published: January 2021

Objective: The purpose of this study was to develop and validate a novel immune checkpoint–related gene signature for prediction of overall survival (OS) in hepatocellular carcinoma (HCC).

Methods: mRNA expression profiles and clinical follow-up information were obtained in the International Cancer Genome Consortium database. An external dataset from The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma database was used to validate the results. The univariate and multivariate Cox regression analyses were performed based on the differentially expressed genes. We generated a four-mRNA signature to predict patient survival. Furthermore, the reliability and validity were validated in TCGA cohort. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value.

Results: A four-gene (epidermal growth factor, mutated in colorectal cancer, mitogen-activated protein kinase kinase 2, and NRAS proto-oncogene, GTPase) signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all P < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Furthermore, the signature presented an excellent diagnostic power in differentiating HCC and adjacent tissues. Immune cell infiltration analysis revealed that the signature was associated with a number of immune cell subtypes.

Conclusion: We identified a four–immune checkpoint–related gene signature as a robust biomarker with great potential for clinical application in risk stratification and OS prediction in HCC patients and could be a potential indicator of immunotherapy in HCC. The diagnostic signature had been validated to accurately distinguish HCC from adjacent tissues.
Estimating Burden of Disease Among Blind Individuals With Non-24-Hour Sleep-Wake Disorder
Authors: Van Draanen Lauren , Xiao Changfu , Polymeropoulos Mihael H.
Published: January 2021

Purpose: To quantify the burden of disease in blind patients with Non-24-H Sleep- Wake Disorder (N24HSWD), utilizing longitudinal sleep diary data. N24HSWD is a circadian disorder characterized by a cyclical pattern of aberrant circadian and sleep-wake cycles that are associated with increased frequency of sleep episodes during the school/work day hours. Daytime sleep episodes would be predicted to decrease the opportunity for school/work participation, significantly impacting the quality of life of the patient.

Methods: We used the sleep diary data of daytime sleep from a period of ~90 days in blind individuals that presented with a sleep complaint. These subjects were identified from a group of blind individuals with N24HSWD (n = 121) and a control group of blind individuals without N24HSWD (n = 57).

Results: N24HSWD patients had more frequent and longer episodes of daytime sleep as compared to a control group. Using duration of daytime sleep as a surrogate for defining a healthy or unhealthy day, N24HSWD patients also had significantly fewer healthy days, defined by daytime sleep free days (DSFD), days without a sleep episode between 9:00 a.m. and 5:00 p.m, as compared to the control group.

Conclusion: Daytime sleep free day (DSFD) is a useful and specific measure of disease burden in patients with N24HSWD and it is predicted to be correlated with the standardized HRQOL-4, Healthy Days measurement.
Should We Use Clinical Tools to Identify Disease Progression?
Authors: Inojosa Hernan , Proschmann Undine , Akgün Katja , Ziemssen Tjalf
Published: January 2021

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients in the course of their disease. The transition from relapsing remitting (RRMS) to secondary progressive forms of the disease (SPMS) represents a significant change in their quality of life and perception of the disease. It could also be a therapeutic key for opportunities, where approaches different from those in the initial phases of the disease can be adopted. The characterization of structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed to differentiate between both phenotypes. However, there is no definite threshold between them. Whether the risk of clinical progression can be predicted by structural markers at early disease phases is still a focus of clinical research. However, several theories and pathological evidence suggest that both disease phenotypes are part of a continuum with common pathophysiological mechanisms. In this case, the clinical evaluation of the patients would play a preponderant role above destruction biomarkers for the early identification of disability progression and SPMS. For this purpose, the use of clinical tools beyond the Expanded Disability Status Scale (EDSS) should be considered. Besides established functional tests such as the Multiple Sclerosis Functional Composite (MSFC), patient's neurological history or digital resources may help neurologists in the decision-taking. In this article, we discuss arguments for the use of clinical markers in the detection of secondary progressive MS and the characterization of progressive disease activity.
Resting State Functional Connectivity of Brain With Electroconvulsive Therapy in Depression: Meta-Analysis to Understand Its Mechanisms
Authors: Sinha Preeti , Joshi Himanshu , Ithal Dhruva
Published: January 2021

Introduction: Electroconvulsive therapy (ECT) is a commonly used brain stimulation treatment for treatment-resistant or severe depression. This study was planned to find the effects of ECT on brain connectivity by conducting a systematic review and coordinate-based meta-analysis of the studies performing resting state fMRI (rsfMRI) in patients with depression receiving ECT.

Methods: We systematically searched the databases published up to July 31, 2020, for studies in patients having depression that compared resting-state functional connectivity (rsFC) before and after a course of pulse wave ECT. Meta-analysis was performed using the activation likelihood estimation method after extracting details about coordinates, voxel size, and method for correction of multiple comparisons corresponding to the significant clusters and the respective rsFC analysis measure with its method of extraction.

Results: Among 41 articles selected for full-text review, 31 articles were included in the systematic review. Among them, 13 articles were included in the meta-analysis, and a total of 73 foci of 21 experiments were examined using activation likelihood estimation in 10 sets. Using the cluster-level interference method, one voxel-wise analysis with the measure of amplitude of low frequency fluctuations and one seed-voxel analysis with the right hippocampus showed a significant reduction (p < 0.0001) in the left cingulate gyrus (dorsal anterior cingulate cortex) and a significant increase (p < 0.0001) in the right hippocampus with the right parahippocampal gyrus, respectively. Another analysis with the studies implementing network-wise (posterior default mode network: dorsomedial prefrontal cortex) resting state functional connectivity showed a significant increase (p < 0.001) in bilateral posterior cingulate cortex. There was considerable variability as well as a few key deficits in the preprocessing and analysis of the neuroimages and the reporting of results in the included studies. Due to lesser studies, we could not do further analysis to address the neuroimaging variability and subject-related differences.

Conclusion: The brain regions noted in this meta-analysis are reasonably specific and distinguished, and they had significant changes in resting state functional connectivity after a course of ECT for depression. More studies with better neuroimaging standards should be conducted in the future to confirm these results in different subgroups of depression and with varied aspects of ECT.
Gender-Specific Inverse Associations Between Beans Intake, Serum Urate Levels, and Hyperuricemia: A Cross-Sectional Analysis Based on the Henan Rural Cohort Study
Authors: Cui Ningning , Dong Xiaokang , Xue Yuan , Liao Wei , Liu Xiaotian , Li Yuqian , Hou Jian , Huo Wenqian , Li Linlin , Mao Zhenxing , Zheng Zhaohui , Wang Chongjian
Published: January 2021

Background and Aims: Beans are rich in purines, which are important substances that lead to elevated serum urate, especially exogenous purines. Few studies were conducted to assess the relationship between beans intake and serum urate or hyperuricemia, especially in rural people. The purpose of this study was to validate the association by gender in the rural Chinese population.

Methods: A total of 38,855 participants aged 18–79 years old were enrolled from the Henan Rural Cohort Study (Registration number: ChiCTR-OOC-15006699). Dietary data were collected using a validated food frequency questionnaire (FFQ). Linear regression models and logistic regression models were used to examine the associations between beans intake and serum urate levels or hyperuricemia. Restricted cubic spline regression was performed to display the dose–response relationship.

Results: In multivariate-adjusted linear regression, an inverse correlation was found between beans intake and serum urate level (the highest quartile Q4 vs. the bottom quartile Q1) in both men (P = 0.008) and women (P < 0.001). Per 10-g increment in beans intake was associated with 0.30 μmol/L decreased concentration of serum urate in men and 0.71 μmol/L in women. The multivariate-adjusted odds ratios (ORs) of hyperuricemia were 0.83 (0.71, 0.97) in men and 0.73 (0.63, 0.84) in women (Q4 vs. Q1). Per 10-g increment in beans intake created a 1% decreased risk of hyperuricemia in men and 3% in women. The cubic spline suggested a risk reduction for hyperuricemia with increasing intake of beans.

Conclusion: A higher beans intake was associated with a lower serum urate level and a reduced risk of hyperuricemia in both sexes, and the association was more pronounced in women.
Radiation-Induced Sarcoma of the Head and Neck Following Radiotherapy for Nasopharyngeal Carcinoma: A Single Institutional Experience and Literature Review
Authors: Lou Jianlin , Jiang Lin , Dai Xinshen , Wang Huanhuan , Yang Jia , Guo Liang , Fang Meiyu , Wang Shengye
Published: January 2021

Background and Objective

Radiotherapy (RT) is the primary treatment option for nasopharyngeal carcinoma (NPC), but it is associated with radiation-induced sarcomas (RISs). This study aims to investigate clinicopathological features and head and neck RIS prognosis after NPC RT.

Methods

The medical and radiological records of the NPC patients (n =14,074) referred to Zhejiang Cancer Hospital, Hang Zhou, China between January 1995 and December 2018 were retrospectively reviewed. Among them, 22 patients were determined to have RIS after RT for NPC. The clinicopathological data, diagnosis, treatment, and follow-up results of 22 patients with RIS were analyzed in this retrospective research. All 22 patients underwent surgery as the main treatment. The levels of Overall Survival (OS) were determined through the Log-rank test and Kaplan–Meier method.

Results

Among these patients, 13 were males and nine females with the male/female ratio of 1.44:1. The age during the primary RT of NPC ranged from 25 to 61 years old (median age: 37 years old). Patients’ ages ranged from 33 to 73 years old (median age: 52.5 years old) when diagnosed with RIS. The latency period for development of the RIS was between 3 and 36 years (median: 8.5 years) after RT. In this cohort, R0 resection was achieved in 13 cases, R1 resection in five cases, and R2 resection in four cases. During the follow-up period ranged from 2 to 102 months (median 14 months), 15 patients had died of the disease. Kaplan–Meier method showed that the 2-year, 3-year, and the 5-year cumulative OS rate was 50.3, 43.2, and 14.4%, respectively. The median survival time was 34 months. Surgical resection with R0 resection achieves a significantly better prognosis (P = 0.012). Patients under the age of 37 years old at the time of initial RT had a relatively better prognosis (P = 0.035).

Conclusions

Although the incidence of RIS after RT of NPC is generally low, the treatment of RIS is very difficult. The RISs are associated with poor overall prognosis. R0 resection can improve the prognosis thus it should be considered as the primary and optimal choice for the treatment of RIS.
Preoperative Serum Sodium Level as a Prognostic and Predictive Biomarker for Adjuvant Therapy in Esophageal Cancer
Authors: Wang Qifeng , Peng Lin , Han Yongtao , Li Tao , Dai Wei , Wang Yi , Wu Lei , Wei Yang , Xie Tianpeng , Fang Qiang , Li Qiang , Lang Jinyi , Cao Bangrong
Published: January 2021

Background

Low serum sodium has been associated with unfavorable outcome in several cancers. The prognostic value of serum sodium in esophageal carcinoma (EC) remains unclear. This study aimed to investigate preoperative serum sodium in association with outcome and survival benefit of adjuvant therapy for patients with EC.

Methods

Preoperative serum sodium and clinicopathological indexes were retrospectively analyzed in 2155 patients who underwent esophagectomy at Sichuan cancer hospital. Overall survival (OS) and disease-free survival (DFS) were analyzed by using Kaplan-Meier method and Cox regression. Benefit of adjuvant therapy was estimated by using Propensity Score Matching.

Results

The incidence of hyponatremia and hypernatremia were 2% (43/2155) and 3.5% (76/2155) in treatment-naive patients. Both sodium disorders indicated unfavorable OS (hyponatremia, adjusted HR[95% CI] = 1.78[1.2–2.62]; hypernatremia, adjusted HR = 1.52[1.1–2.11]) and DFS (hyponatremia, adjusted HR[95% CI] = 1.52[1.03–2.23]; hypernatremia, adjusted HR = 1.45[1.06–1.99]). Decreased sodium concentrations within the normal range were associated with poor OS and DFS. Postoperative adjuvant therapy was associated with improved three-year OS (56.6 vs. 40%; adjusted HR = 0.55 [95% CI, 0.41–0.73]) and DFS (51.9 vs. 36.2%; adjusted HR = 0.63 [95% CI, 0.48–0.83]) versus surgery alone in patients with low serum sodium (Na < 139.6 mmol/liter), but not in other sodium subgroups. Meanwhile, serum sodium was inversely correlated with cell counts of leukocytes, neutrophils, monocytes and C-reactive protein levels.

Conclusions

These results suggested that low preoperative serum sodium is associated with poor outcome in EC patients, and may predict survival benefit of adjuvant therapy.
Brain Tumor Microenvironment and Angiogenesis in Melanoma Brain Metastases
Authors: Trembath Dimitri G. , Davis Eric S. , Rao Shanti , Bradler Evan , Saada Angelica F. , Midkiff Bentley R. , Snavely Anna C. , Ewend Matthew G. , Collichio Frances A. , Lee Carrie B. , Karachaliou Georgia-Sofia , Ayvali Fatih , Ollila David W. , Krauze Michal T. , Kirkwood John M. , Vincent Benjamin G. , Nikolaishvilli-Feinberg Nana , Moschos Stergios J.
Published: January 2021

Background

High tumor-infiltrating lymphocytes (TILs) and hemorrhage are important prognostic factors in patients who have undergone craniotomy for melanoma brain metastases (MBM) before 2011 at the University of Pittsburgh Medical Center (UPMC). We have investigated the prognostic or predictive role of these histopathologic factors in a more contemporary craniotomy cohort from the University of North Carolina at Chapel Hill (UNC-CH). We have also sought to understand better how various immune cell subsets, angiogenic factors, and blood vessels may be associated with clinical and radiographic features in MBM.

Methods

Brain tumors from the UPMC and UNC-CH patient cohorts were (re)analyzed by standard histopathology, tumor tissue imaging, and gene expression profiling. Variables were associated with overall survival (OS) and radiographic features.

Results

The patient subgroup with high TILs in craniotomy specimens and subsequent treatment with immune checkpoint inhibitors (ICIs, n=7) trended to have longer OS compared to the subgroup with high TILs and no treatment with ICIs (n=11, p=0.059). Bleeding was significantly associated with tumor volume before craniotomy, high melanoma-specific expression of basic fibroblast growth factor (bFGF), and high density of CD31+αSMA- blood vessels. Brain tumors with high versus low peritumoral edema before craniotomy had low (17%) versus high (41%) incidence of brisk TILs. Melanoma-specific expression of the vascular endothelial growth factor (VEGF) was comparable to VEGF expression by TILs and was not associated with any particular prognostic, radiographic, or histopathologic features. A gene signature associated with gamma delta (gd) T cells was significantly higher in intracranial than same-patient extracranial metastases and primary melanoma. However, gdT cell density in MBM was not prognostic.

Conclusions

ICIs may provide greater clinical benefit in patients with brisk TILs in MBM. Intratumoral hemorrhage in brain metastases, a significant clinical problem, is not merely associated with tumor volume but also with underlying biology. bFGF may be an essential pathway to target. VEGF, a factor principally associated with peritumoral edema, is not only produced by melanoma cells but also by TILs. Therefore, suppressing low-grade peritumoral edema using corticosteroids may harm TIL function in 41% of cases. Ongoing clinical trials targeting VEGF in MBM may predict a lack of unfavorable impacts on TIL density and/or intratumoral hemorrhage.
LETM1 Knockdown Promotes Autophagy and Apoptosis Through AMP-Activated Protein Kinase Phosphorylation-Mediated Beclin-1/Bcl-2 Complex Dissociation in Hepatocellular Carcinoma
Authors: Zhou Baoyong , Yang Changhong , Yan Xiong , Shi Zhengrong , Xiao Heng , Wei Xufu , Jiang Ning , Wu Zhongjun
Published: January 2021

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is an inner mitochondrial membrane protein that has been reported to be involved in many primary tumors and may regulate many biological processes. However, the biological role and molecular mechanism of LETM1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that LETM1 was highly expressed in HCC tissues and cell lines and that higher LETM1 expression was associated with a lower overall survival rate in HCC patients. In addition, knockdown of LETM1 inhibited proliferation and enhanced apoptosis and autophagy in the Huh 7 and QGY-7701 liver cancer cell lines. Mechanistically, knockdown of LETM1 dissociated the Beclin-1/Bcl-2 complex through phosphorylation of AMPK and Bcl-2. These results demonstrated that LETM1 is involved in the development of HCC and could be a novel therapeutic target in HCC.
Narrow-Margin Hepatectomy Resulted in Higher Recurrence and Lower Overall Survival for R0 Resection Hepatocellular Carcinoma
Authors: Liu Lihong , Shui Yongjie , Yu Qianqian , Guo Yinglu , Zhang Lili , Zhou Xiaofeng , Yu Risheng , Lou Jianying , Wei Shumei , Wei Qichun
Published: January 2021

Purpose

To evaluate the impact of resection margin on recurrence pattern and survival for hepatocellular carcinoma (HCC) with narrow margin resection, with the aim to guide postoperative treatment.

Materials and Methods

Two hundred forty HCC patients after curative hepatectomy between 2014 and 2016 were reviewed retrospectively. The cases were divided into narrow-margin (width of resection margin <1cm, n=106) and wide-margin (width of resection margin ≥1cm, n=134) groups based on the width of resection margin. Recurrence pattern, recurrence-free survival (RFS), and overall survival (OS) were compared between the above two groups. An additional cohort of nine cases with positive margin plus post-operative stereotactic body radiotherapy (SBRT) was also analyzed for the recurrence pattern.

Results

Postoperative recurrence was found in 128 (53.3%) patients. The recurrence rate was significantly higher in narrow-margin group than that in wide-margin group (P=0.001), especially for the pattern of marginal recurrence (20.8 vs. 4.5%, P=0.003). The 1-, 2-, 3-year RFS rates for the narrow-margin and wide-margin groups were 55.8, 43.9, 36.9, and 78.7, 67.9, 60.2%, respectively, with significant difference between the two groups (P<0.001). Patients with narrow margin showed a tendency of decreased OS than those with wide margin (P<0.001). As comparison, the nine cases with positive margin treated with postoperative SBRT showed low recurrence rate and no marginal recurrence was found.

Conclusion

Patients with narrow resection margin were associated with higher recurrence rate and worse survival than those with wide resection margin. These patients may benefit from adjuvant local treatment, such as radiotherapy.
Importance of Non-pharmacological Approaches for Treating Irritable Bowel Syndrome: Mechanisms and Clinical Relevance
Authors: Orock Albert , Yuan Tian , Greenwood-Van Meerveld Beverley
Published: January 2021

Chronic visceral pain represents a major unmet clinical need with the severity of pain ranging from mild to so severe as to prevent individuals from participating in day-to-day activities and detrimentally affecting their quality of life. Although chronic visceral pain can be multifactorial with many different biological and psychological systems contributing to the onset and severity of symptoms, one of the major triggers for visceral pain is the exposure to emotional and physical stress. Chronic visceral pain that is worsened by stress is a hallmark feature of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Current pharmacological interventions for patients with chronic visceral pain generally lack efficacy and many are fraught with unwanted side effects. Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain; however, the molecular mechanisms underlying CBT remain incompletely understood. Preclinical studies in experimental models of stress-induced visceral pain employing environmental enrichment (EE) as an animal model surrogate for CBT are unraveling the mechanism by which environmental signals can lead to long-lasting changes in gene expression and behavior. Evidence suggests that EE signaling interacts with stress and nociceptive signaling. This review will (1) critically evaluate the behavioral and molecular changes that lead to chronic pain in IBS, (2) summarize the pharmacological and non-pharmacological approaches used to treat IBS patients, and (3) provide experimental evidence supporting the potential mechanisms by which CBT ameliorates stress-induced visceral pain.
Abnormalities of Serum Fatty Acids in Children With Henoch–Schönlein Purpura by GC-MS Analysis
Authors: Wen Min , Feng Shipin , Dang Xiqiang , Ding Xuewei , Xu Zhiquan , Huang Xiaoyan , Lin Qiuyu , Xiang Wei , Li Xiaoyan , He Xiaojie
Published: January 2021

Purpose: The objectives of this work were to test the levels of serum medium- and long- chain fatty acids (MLCFAs) in children and to discover their possible relationship with Henoch-Schönlein Purpura (HSP), also known as Immunoglobulin A vasculitis.

Methods: A total of 57 children with HSP (HSP group) and 28 healthy children (CON group) were recruited for this study. Serum specimens were collected to detect the compositions and contents of MLCFAs by gas chromatography with mass spectrometry (GC-MS) analysis.

Results: The contents of all detected 37 MLCFAs in the HSP group were higher than the healthy group. Thirty-one species of MLCFAs were discovered to have a significant difference (p < 0.05) in two groups. Comparing to healthy controls, there were 31, 31, 18 fatty acids showed a statistical difference in the untreated group, regular treated group, and withdrawal group of HSP, respectively. The trend of fatty acids in the three HSP groups was similar to the healthy controls, as well as the untreated group and regular treated group changed more obviously than the withdrawal group. Almitate (C16:0) and 18 carbon atoms (C18) of fatty acids were abundant in all three HSP groups, divided according to the treatment of glucocorticoid. Some fatty acids were found having considerable differences (p < 0.05) in three groups. Monounsaturated fatty acids (MUFAs), including elaidate (C18:1T), cis-11,14,17-eicosatrienoic acid ester (C20:1), and cis-15-tetracosenoate (C24:1), were distinctly higher in HSP children with renal damage.

Conclusion: Our study revealed that the abnormalities in MLCFA may be associated with the development of HSP. Another interesting finding was that fatty acids contents were changing during the glucocorticoid treatment. Meanwhile, long-chain MUFAs may have an impact on renal damage in HSP patients. Further studies need to be carried out in order to explore the specific mechanism of fatty acids in the course of HSP.
Aqueous Extract of Salvia miltiorrhiza Bunge-Radix Puerariae Herb Pair Attenuates Osteoporosis in Ovariectomized Rats Through Suppressing Osteoclast Differentiation
Authors: Qin Huan , Zhao Wenwen , Jiao Yang , Zheng Haoyi , Zhang Hao , Jin Jingyu , Li Qiu , Chen Xiuping , Gao Xia , Han Yantao
Published: January 2021

Traditional herb pair Salvia miltiorrhiza Bunge-Radix Puerariae (DG) owns various biological activities including anti-inflammatory and anti-oxidative stress. Oxidative stress is one high-risk factor for osteoporosis, then effect of DG on osteoporosis and underlying mechanisms was explored both in vivo and in vitro. Firstly, the predication from network pharmacology hinted that DG has the potential for ameliorating osteoporosis. Consistent with predication, DG significantly restored bone loss and deficiency of type II collagen, decreased TRAP and Cathepsin K positive areas in femur. Meanwhile it improved important characteristics of microarchitectural deterioration of tissue, reduced the numbers of NFATc1-positive osteoclast in the vertebra as well as decreased the serum osteoclast-specific cytokine RANKL and OPG release in OVX rats exhibiting its protective effect against osteoporosis. In vitro, DG noticeably decreased osteoclastic-special marker protein expressions of RANK, c-Fos and NFATc1. Furthermore, autophagy pathway p62/LC3B, ROS production and NF-κB were all activated by RANKL stimulation and blocked by DG pretreatment. Moreover, autophagy inhibitors, ROS scavenger, Ca2+ chelator and NF-κB inhibitor remarkably suppressed c-Fos and NFATc1 expressions. Taken together, DG may ameliorate osteoporosis by regulating osteoclast differentiation mediated by autophagy and oxidative stress. This study provided a mechanistic basis for DG treating osteoporosis and offered a safe dose for DG in preventing and improving bone diseases.