bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting RNF8 Effectively Reverse Cisplatin and Doxorubicin Resistance in Endometrial Cancer
Authors: Yang Ben , Ke Wang , Wan Yingchun , Li Tao
Published: September 2020

Background
Endometrial cancer (EC) is one of the most frequent gynecological malignancy worldwide. However, resistance to chemotherapy remains one of the major difficulties in the treatment of EC. Thus, there is an urgent requirement to understand mechanisms of chemoresistance and identify novel regimens for patients with EC.
Methods
Cisplatin and doxorubicin resistant cell lines were acquired by continuous exposing parental EC cells to cisplatin or doxorubicin for 3 months. Cell viability was determined by using MTT assay. Protein Expression levels of protein were examined by western blotting assay. mRNA levels were measured by quantitative polymerase chain reaction (qPCR) assay. Ring finger protein 8 (RNF8) knockout cell lines were generated by clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing assay. Nonhomologous end joining (NHEJ) efficiency were quantified by plasmid based NHEJ assay. DNA double strand breaks (DSB) were generated using laser micro-irradiation. Protein recruitment to DSB was analyzed by immunofluorescent assay. Tumor growth was examined by AN3CA xenograft mice model.
Results
We found that protein and mRNA expression levels of RNF8 were significantly increased in both cisplatin and doxorubicin resistant EC cells. Cell survival assay showed that RNF deficiency significantly enhanced the sensitivity of resistant EC cells to cisplatin and doxorubicin (P < 0.01). In addition, chemoresistant EC cells exhibited increased NHEJ efficiency. Knockout of RNF8 in chemoresistant EC cells significantly reduced NHEJ efficiency and prolonged Ku80 retention on DSB. Moreover, cisplatin resistant AN3CA xenograft showed that RNF8 deficiency overcame cisplatin resistance.
Conclusions
Our in vitro and in vivo assays provide evidence for RNF8, which is a NHEJ factor, serving as a promising, novel target in EC chemotherapy.
Atopic dermatitis and psoriasis as overlapping syndromes.
Authors: Bozek Andrzej , Zając Magdalena , Krupka Magdalena
Published: September 2020

Background: Concomitant atopic dermatitis (AD) and psoriasis (PS) are not common. However, both diseases are still of interest because of their comprehensive and diverse mechanism. The aim of the study was to present the clinical and immunological profile of patients with concomitant AD and PS coexist in comparison to patients with one of these diseases.Methods: In this observational study, 38 children with concomitant AD and PS with a mean age of 6.5 ± 3.2 yrs. were compared with similar 41 patients with only AD (5.3± 5.1 yrs) and with 28 with PS (6.4± 4.3 yrs). All patients underwent the dermatological examination including SCORAD and PASI questionnaire. TNF-α, IFN-γ, Il-2, Il-4, Il-5, Il-6, Il-8, Il-12, I-17, Il-18, Il-22, Il-33, TARC/CCL17 were measured by the use ELISA method and according manufacturer (ThermoFischer Scientific, US).Results: Patients with concomitant AD and PS were frequently boys or with overweight and with a proportional area distribution of skin lesions. A positive family history of atopic disease was more frequently reported by children with concomitant AD and PS, and with AD vs. PS. Significant differences were observed in the concentration of Il-17 in patients with AD and PS compared with that in AD or PS patients as follows: 9.1±3.7 pg/ml vs. 4.8±2.9 pg/ml and 5.2±3.9 pg/ml (PD vs. AD, p = 0.01; PD vs. PS, p = 0.03).Conclusion: AD and PS might coexist as overlapping disease. The role of T-helper 17 may be more meaningful than it appeared.
Signal Molecules Crosstalk and the Critical Role of Jasmonic Acid in Triterpenoid Synthesis Inducement of Aspergillus Niger Elicitor in Suspension Cultured Cyclocarya Paliurus Cells
Authors: Wang Meng , Tang Daobang , Xiong QiongQiong , Chen Jiguang , Xu Xiaoxiang , Zhang Qingfeng , Zhou Xiangju , Yin Zhongping
Published: September 2020

Background: Cyclocarya paliurus (C. paliurus) leaves contain multiple health benefical metabolites, and therefore are often used in functional foods and Chinese herbal medicines. However, breeding difficulties confines its utilization. Consequently, cell suspension culture was developed to produce the bioactive secondary metabolites of C. paliurus leaves, but the content was comparatively low. In the present paper, Aspergillus Niger Elicitor (ANE) was used to stimulate the synthesis of triterpenoids in the suspension cultured C. paliurus cells, and the signal molecules crosstalk involved in this elicitation was further studied to interpret the underlying mechanism. Results: Total triterpenoids accumulation of the cultured C. paliurus cells elicited by 200 µg/mL ANE was 9.17 times higher than that of the untreated cells. Nitric oxide (NO), hydrogen peroxide (H2O2) and jasmonic acid (JA) played important roles in the elicitation as signal molecules. Under the ANE stimulation, the concentrations of NO, H2O2 and JA all increased significantly, but presented different change profiles and peaked at different times. Based on series experiments of NO quenching by C-PTIO, H2O2 blocking by DMTU, and JA synthesis inhibition by IBU and NDGA, together with exogenous NO, H2O2 and JA addition experiments, it was deduced that ANE improved triterpenoids synthesis in the suspension cultured C. paliurus cells via a complex signal transduction network, in which three deduced and three hypothetical signal transduction pathways might be involved. JA was not only the junction of NO and H2O2 signal pathways, but also the critical point in the whole signal network. RNA-seq analysis showed that a total of 3 candidate JA synthesis pathway genes including 1 LOX and 2 OPR were found to be significantly up-regulated under the ANE stimulation, along with 5 down-regulated JAZs and 1 up-regulated JAR1 regulating to JA signal transduction.Conclusions: ANE can significantly increase the triterpenoids synthesis in the suspension cultured C. paliurus cells. RNA-seq analysis validated the pivotal role of JA in this ANE elicitation. Our results provided references for the further studies on triterpenoids synthesis in C. paliurus under ANE treatment.
Transcriptome Analysis of Grafted Potato Rootstock for Improvement of Scion Late-Blight Resistance
Authors: Li Yuexin , Zhao Degang
Published: September 2020

Late blight seriously threatens potato cultivation worldwide. Damage caused by the fungus, which is severe and widespread, can lead to drastic reductions in potato yield and even total loss. Although grafting technology has been widely used to improve crop resistance, the effects and associated molecular mechanisms of grafting on resistance to potato late blight are unclear. In this study, we therefore performed RNA transcriptome sequencing of the scion when potato late blight-resistant variety Qingshu 9 and susceptible variety Favorita were used as the rootstock and scion, respectively, and vice versa. Using the sequencing results, we analyzed the influence of the rootstock on scion resistance and related molecular mechanisms. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that plant–pathogen interactions, the plant MAPK signaling pathway, and genes on the SA pathway were significantly up-regulated in the scion when Qingshu 9 was used as the rootstock. When Favorita was used as the rootstock, β-ketoacyl-CoA synthase-related genes in the scion, Qingshu 9, were significantly down-regulated. Resistance to late blight on scion leaves were also tested in vitro, which results consistent with those obtained by sequencing. All the generated evidence indicates that the use of resistant and susceptible varieties as rootstocks can respectively increase and reduce resistance to late blight. Our sequencing results further elucidate the molecular mechanism underlying the post-grafting effects of rootstocks on late blight resistance and provide a theoretical basis for the transfer of resistance genes between scions and rootstocks after grafting.
Level of Abusive Maternal Care and Associated Factors During Childbirth in Northeast Ethiopia: A Cross-sectional Study
Authors: Lebeza Tenaw , Endalifer Melese Linger
Published: September 2020

Background: The maternal mortality rate is 412 per 100,000 live births in Ethiopia which is the highest in the world. Skilled birth attendance during childbirth and immediate postpartum care can prevent 75% of maternal mortality but women are not willing to deliver in the health institutions due to ignorance of their sensitive issues by health professionals. Additionally, the care given in the health institution is not psychologically supportive of what they need. Therefore, this study aimed to assess the level of abusive maternal care and associated factors during childbirth in North Wollo Hospitals, Northeast Ethiopia.Methods: Institutional based cross-sectional study design was implemented in 2018 with a sample size of 394. Stratified systematic random sampling was applied to select the study participants. Data was collected by using a structured questionnaire adapted from the White Ribbon Alliance Declaration of women's right during childbirth. Data were entered by EPI- data version 3.1 and analysed by using SPSS version 23. Bivariate and multivariable logistic regression analyses were carried out. Model fitness was assured.Result: The level of abusive care among childbearing women was 47.1%. Women who attended their childbirth at general hospital (AOR =0.13, 95% CI: 0.06, 0.26), women who had no antenatal care (AOR =2.08, 95% CI: 1.27, 3.39) and women who had two birth attendants (AOR =0.56, 95% CI: 0.35, 0.92) were significant association with abusive maternal care.Conclusion: The level of abusive maternal care in health institutions is high as compared to national and international standards. Women who attend their childbirth at general hospitals, having antenatal care and the number of birth attendants were factors associated with abusive maternal care. The interventions better to focus on increasing pregnant women’s ANC follow up. The health institutions also better increase the number of professional skilled birth attendants to address women’s concerns during childbirth.
Targeted inhibition of Wnt signaling with a bacterial toxin fragment suppresses breast cancer tumor-initiating/chemo-resistant cells
Authors: He Aina , Xiang Dongxi , Kopper Oded , Horan Daniel , Chen Peng , Bronson Roderick , Sheng Ren , Wu Hao , Sui Lufei , Zhou Kun , Tao Liang , Tian Songhai , Wu Quan , Huang Yujing , Shen Zan , Chen Hong , He Xi , Robling Alexander , Jin Rongsheng , Clevers Hans , Li Zhe , Dong Min
Published: September 2020

BRCA1 germ-line mutations are a major cause of hereditary breast cancer and BRCA1-deficient breast cancer shares many characteristics as sporadic basal-like breast cancer (BLBC). Effective therapeutic targets for BRCA1-deficient BLBC remain lacking. By utilizing a BRCA1-deficient BLBC mouse model based on intraductal injection of Krt8-Cre adenovirus to inactivate Brca1 and Trp53 in luminal mammary epithelial cells, here we report that the Wnt receptor Frizzled 7 (FZD7) serves as a biomarker and therapeutic target in the resulting mammary tumor cells and is particularly enriched in cancer stem cells / tumor-initiating cells (CSCs/TICs). Inhibiting FZD7-mediated Wnt signaling using a nontoxic FZD-binding fragment of C. difficile toxin B (TcdBFBD) attenuates growth of BRCA1-deficient tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Finally, FZD1/2/7-positive cells are enriched in chemotherapy-resistant cells in both BLBC and luminal breast tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These findings demonstrate the therapeutic value for targeting FZD1/2/7 in treating breast cancers and establish TcdBFBD as a potential therapeutic agent targeting TICs and chemotherapy-resistant cancer cells.
The Trans-omics Landscape of COVID-19
Authors: Wu Peng , Chen Dongsheng , Ding Wencheng , Wu Ping , Hou Hongyan , Bai Yong , Zhou Yuwen , Li Kezhen , Xiang Shunian , Liu Panhong , Ju Jia , Guo Ensong , Liu Jia , Yang Bin , Fan Junpeng , He Liang , Sun Ziyong , Feng Ling , Wang Jian , Wu Tangchun , Wang Hao , Cheng Jin , Xing Hui , Meng Yifan , Li Yongsheng , Zhang Yuanliang , Luo Hongbo , Xie Gang , Lan Xianmei , Tao Ye , Li Jiafeng , Yuan Hao , Huang Kang , Sun Wan , Qian Xiaobo , Li Zhichao , Huang Mingxi , Ding Peiwen , Wang Haoyu , Qiu Jiaying , Wang Feiyue , Wang Shiyou , Zhu Jiacheng , Ding Xiangning , Chai Chaochao , Liang Langchao , Wang Xiaoling , Luo Lihua , Sun Yuzhe , Yang Ying , Zhuang Zhenkun , Li Tao , Tian Lei , Zhang Shaoqiao , Zhu Linnan , Chang Ashley , Chen Lei , Wu Yiquan , Ma Xiaoyan , Chen Fang , Ren Yan , Xu Xun , Liu Siqi , Wang Jian , Yang Huanming , Wang Lin , Sun Chaoyang , Ma Ding , Jin Xin , Chen Gang
Published: September 2020

The outbreak of coronavirus disease 2019 (COVID-19) has been causing a global health emergency. Although previous studies investigated COVID-19 at different omics levels, the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here, we presented a trans-omics landscape for COVID-19 based on integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles from blood samples of 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Notably, we found neutrophils heterogeneity existed between asymptomatic and critically ill patients. Expression discordance of inflammatory cytokines at mRNA and protein levels in asymptomatic patients could possibly be explained by post-transcriptional regulation by RNA binding proteins (RBPs) and microRNAs. Neutrophils over-activation, induced arginine depletion, and tryptophan metabolites accumulation contributed to T/NK cell dysfunction in critical patients. Anti-virus interferons were gradually suppressed along with disease severity. Overall, our study systematically revealed multi-omics characteristics of COVID-19, and the data we generated could hopefully help illuminate COVID-19 pathogenesis and provide valuable clues about potential therapeutic strategies for COVID-19.
Thyroid hormone (T3) plus dual-specificity phosphatase-5 siRNA therapy regenerates the myocardium lost as a result of doxorubicin cardiotoxicity
Authors: Tan Lin , Bogush Nikolay , Naqvi Emmen , Calvert J , Graham Robert , Taylor W. Robert , Naqvi Nawazish , Husain Ahsan
Published: September 2020

Doxorubicin is a widely used antineoplastic drug. However, its major side effect, cardiotoxicity, results from cardiomyocyte loss that causes left ventricle (LV) wall thinning, chronic LV dysfunction and heart failure. Here, we show that transient therapy with thyroid hormone (triiodothyronine, T3) and dual-specificity phosphatase-5 (DUSP5) siRNA results in cardiomyocyte proliferation. siRNA-directed depletion of DUSP5, a nuclear localized p-ERK1/2-specific phosphatase, sensitizes cardiomyocytes to the proliferative effects of T3 by potentiating p-ERK1/2 accumulation resulting from the activation of T3-mediated insulin-like growth factor-1 (IGF-1) signaling. In mice with chronic doxorubicin cardiotoxicity, this therapy regenerates the LV myocardium by cardiomyocyte proliferation, reverses LV dysfunction and prevents progressive chamber dilatation, providing a strategy for addressing a currently untreatable condition.
Garlic skin induced shifts in the rumen microbiome and metabolome of fattening sheep
Authors: Zhu Wen , Su Zhen , Xu Wei , Sun Hanxue , Gao Jinfeng , Tu Danfeng , Ren Chunhuan , Zhang Zijun , Cao Hongguo
Published: September 2020

Background

Garlic and its constituents exhibit activities on modifying rumen fermentation and improving growth performance. As a by-product of garlic processing, garlic skin contains similar bioactive components as garlic bulb. However, studies in ruminants using garlic skin are scarce. This study was conducted to investigate the effects of garlic skin supplementation on rumen fermentation characterizes, growth performance, ruminal microbes and metabolites in ruminants. Twelve Hu lambs were randomly assigned into one of two treatments: basal diet (CON) or basal diet supplemented with 80 g/kg DM of gallic skin (GAS). The experiment lasted for10 weeks, with the first 2 weeks for adaptation.
Results

The results revealed that the average daily gain and volatile fatty acid concentration were higher (P < 0.05) in lambs fed GAS than that in the control group. Garlic skin supplementation did not significantly (P > 0.10) affect the α-diversity indices. Increased (P < 0.05) abundances of Prevotella, Bulleidia, Howardella, Methanosphaera but a decreased (P < 0.05) abundance of Fretibacterium were observed in GAS-fed lambs. In addition, the garlic skin supplementation favorably regulated (P < 0.05) pyrimidine metabolism, purine metabolism, vitamin B6 and B1 metabolism. Moreover, high correlations were observed between fluctuant rumen microbiota and metabolites.
Conclusions

Supplementation of garlic skin improved the growth performance of sheep by modifying rumen fermentation through inducing shifts in the rumen microbiome and metabolome.
In Silico Identification of Nsp12 and Nsp13 as Potential Targets for Development of Broad-spectrum Antiviral Agents Against SARS-CoV, MERS-CoV, and 2019-nCoV (SARS-CoV-2)
Authors: Dong Shengjie , Sun Jiachen , Mao Zhuo , Lu Yilin , Li Jiesen
Published: September 2020

Background2019 novel coronavirus (2019-nCoV) is officially named severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), and is a positive-sense, single-stranded RNA coronavirus. The virus is the pathogen of coronavirus disease 2019 (COVID-19) and is infectious through human-to-human transmission. The fact that 2019-nCoV is very close to SARS-CoV has been proved by several evidences, but there are significant differences between MERS-CoV and them. Therefore, in this work, we used MERS-CoV as a probe to find the homology proteins with conserved sequences among these three known human highly pathogenic coronaviruses.MethodsThe primary protein sequences of three viruses translated from the complete genome were downloaded from National Center for Biotechnology Information (NCBI). The sequence alignments of ORF1ab proteins of three viruses were done by using Clustal Omega. The assessments of the feasibility of homology modeling were performed by using SWISS-MODEL.ResultsHere, by using computational biology, we propose that four nonstructural proteins nsp12, nsp13, nsp14, and nsp16 exhibit considerable homology among SARS-CoV, MERS-CoV, and 2019-nCoV. Among them, nsp12 and nsp13 amino acid sequences are more conserved. Considering the crucial role of these two proteins in the process of virus invasion and pathological response, we first proposed these two proteins as priority targets to design new or screen existing broad-spectrum antiviral drugs. The high consistency of primary sequence indicates the great similarity of three-dimensional structure and similar targets are likely to be inhibited by the same inhibitor. The inhibitors designed for these targets are likely to have broad-spectrum antiviral effect.ConclusionVery recently, some clinical trial reports preliminarily proved that Favipiravir and Remdesivir are effective for COVID-19. These clinical data provide some proof and basis for our conjecture in some degree. It is believed that the effective broad-spectrum antiviral drugs are not only helpful for the current epidemic situation, but also more beneficial for the future unpredictable epidemic situation.
Plasma Fibrinogen Can be Used as a New Auxiliary Diagnostic Marker for Periprosthetic Joint Infection
Authors: Huang Jincheng , Chen Xiao , Qiang Shuo , Zheng Wendi , Zheng Jia , Jin Yi
Published: September 2020

Background: To test the meaning of serum CRP, ESR, Platelet Count and Mean Platelet Volume ratio (PC/MPV), plasma Fibrinogen and D-Dimer in periprosthetic joint infection diagnosis (PJI). Methods: Clinical data of 149 patients diagnosed with osteoarthritis (Group A), PJI (Group B) and aseptic loosening after joint arthroplasy (Group C) were retrospectively studied. General data and preoperative serum CRP, ESR, Platelet Count and Mean Platelet Volume ratio (PC/MPV), plasma Fibrinogen and D-Dimer levels were analyzed. The sensitivity and specificity of serum CRP, ESR, Platelet Count and Mean Platelet Volume ratio (PC/MPV), plasma Fibrinogen and D-Dimer in PJI diagnosis were compared.Results: Expression level of serum CRP, ESR, PC/MPV and plasma Fibrinogen in Group B are higher than Group A and C. Expression level of plasma D-Dimer in Group B are higher than Group A but similar with Group C. When PC/MPV>31.70, plasma Fibrinogen > 4.01 μg/mL and plasma D-Dimer > 1.17 mg/L were set as the threshold value for the diagnosis of PJI, the sensitivity of PC/MPV in PJI diagnosis is lower than ESR and Plasma Fibrinogen. Whereas, there are no statistically significant differences when compared specificity of serum CRP, ESR, PC/MPV, plasma Fibrinogen and D-Dimer in PJI diagnosis.Conclusion: PC/MPV and plasma D-Dimer should not be used as the first screen markers for PJI diagnosis, whereas, the plasma Fibrinogen can be used as a new auxiliary marker for PJI diagnosis.
Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma
Authors: Pu Ning , Chen Qiangda , Gan Wei , Kinny-Köster Benedict , Yin Hanlin , Habib Joseph R , Li Junhao , Cui Ming , Dong Yiran , Gao Shanshan , Nagai Minako , Liu Lingxiao , Wu Wenchuan , Yu Jun , Lou Wenhui
Published: September 2020

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Its larger mass size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. Thus, this study aims to quantitatively identify the objective relationship between tumor size and prevalence of LN metastases across primary tumor size spectrums.METHODS: 9,958 resected PDAC patients without distant metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The prevalence of LN metastases, LN ratio (LNR) and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were depicted by matched curves. RESULTS: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy and radiotherapy were identified as significant independent predictors for overall survival (OS) and cancer-specific survival (CSS). For tumors within 1-40 mm in size, the prevalence of node positive disease is closely modelled using a logarithmic formula [0.249×ln (size) + 0.452] × 100%, and then fluctuated between 70.0% and 80.0% when beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR=0.024) to 41-45 mm (LNR=0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1=0.286) to 41-45 mm (N2/N1=1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. CONCLUSION: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in resectable PDAC patients. The probability of metastasis in each regional LN for resectable PDAC patients with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70%-80%. Among which, 50% of patients had an N2 stage.
Response of Intestinal Mucosal Microbiota in Diarrheal Mice to Ge-gen-qin-lian Decoction
Authors: Li Xiaoya , Zhang Chenyang , Hui Huaying , Peng Xinxin , Xiao Nenqun , Tan Zhoujin
Published: September 2020

Background: Ge-gen-qin-lian Decoction (GD) has been extensively used for the treatment of diarrhea with intestinal dampness heat syndrome(IDHS) with a satisfying therapeutic effect. However, the active ingredients and mechanism of GD against diarrhea with IDHS have not been fully elucidated. The occurrence of diarrhea is closely related to the intestinal flora, and the compound of Traditional Chinese Medicine(TCM) can exert its curative effect by regulating the intestinal flora, and exploring the relationship between the two is conducive to the clarification of pharmacology. Results: Animal experiments indicted that the OTU number and Alpha diversity index in the intestinal mucosa flora of the treatment group(cttm) recovered and higher than that of the control group(ctcm). PCoA results showed that there were differences in the community structure between the Con and GD. At the species level, the abundance of Lactobacillus crispatus and Muribaculum intestinal in the model group(ctmm) decreased, and the Neisseria mucosa increased (p<0.05). After being treated with GD, Muribaculum intestinal increased, and Lactobacillus curlyus and Neisseria mucosa decreased (p<0.05). Combined with network pharmacology analysis, we screened out 146 active ingredients in GD corresponding to 252 component targets, and 328 disease targets in diarrhea to obtain 31 drug-disease common targets. The key targets involved TNF, IL-6, EFGR etc. KEGG pathway enrichment resulted in HIF-1 signaling pathway, VEGFA signaling pathway, Adipocytokine signaling pathway and so on (p<0.05). Conclusions: GD could restore the diversity and abundance of intestinal mucosa in diarrheal mice with IDHS, promote the abundance of Muribaculum intestinal, inhibit the abundance of Neisseria mucosa. Through the characteristic of multiple targets and multiple channels, the active ingredients of GD intervened from oxidative stress and inflammatory response to adjust the balance of intestinal mucosa flora, thereby playing the role of treating diarrhea.
Discussing Personalized Prognosis in Amyotrophic Lateral Sclerosis: Development of a Communication Guide
Authors: Eenennaam Remko M. van , Kruithof Willeke J. , Es Michael A. van , Reenen Esther T. Kruitwagen-van , Westeneng Henk-Jan , Visser-Meily Johanna M.A. , Berg Leonard H. van den , Beelen Anita
Published: September 2020

Background: Personalized ENCALS survival prediction model reliably estimates the personalized prognosis of patients with amyotrophic lateral sclerosis. Concerns were raised on discussing personalized prognosis without causing anxiety and destroying hope. Tailoring communication to patient readiness and patient needs mediates the impact of prognostic disclosure. We developed a communication guide to support physicians in discussing personalized prognosis tailored to individual needs and preferences of people with ALS and their families.Methods: A multidisciplinary working group of neurologists, rehabilitation physicians, and healthcare researchers A) identified relevant topics for guidance, B) conducted a systematic review on needs of patients regarding prognostic discussion in life-limiting disease, C) drafted recommendations based on evidence and expert opinion, and refined and finalized these recommendations in consensus rounds, based on feedback of an expert advisory panel (patients, family member, ethicist and spiritual counsellor).Results: A) Topics identified for guidance were 1) filling in the ENCALS survival model, and interpreting outcomes and uncertainty, and 2) tailoring discussion to individual needs and preferences of patients (information needs, role and needs of family, severe cognitive impairment or frontotemporal dementia, and non-western patients). B) 17 studies were included in the systematic review. C) Consensus procedures on drafted recommendations focused on selection of outcomes, uncertainty about estimated survival, culturally sensitive communication, and lack of decisional capacity.Communication guide: We recommend discussing prognosis based on the prognostic groups and their median survival, or, if more precise information is desired, on the interquartile range of the survival probability. Regardless of cultural background, investigate needs and preferences of the patients and their families regarding prognostic disclosure. If the patient does not want to know their prognosis, with patient permission this can be discussed with their family. If the patient is judged to lack decisional capacity, ask the family if they want to discuss the prognosis. Tailor prognostic disclosure step by step, discuss it in terms of time range, and emphasize uncertainty of individual survival time.Conclusion: This communication guide supports physicians in tailoring discussion of personalized prognosis to the individual needs and preferences of people with ALS and their families.
Impacts on Surgery Resident Education at a first wave COVID-19 Epicenter
Authors: Ostapenko Alexander , McPeck Samantha , Liechty Shawn , Kleiner Daniel
Published: September 2020

Background: This study aims to identify the effects of the COVID-19 pandemic on surgical resident training and education at Danbury Hospital.Methods: We conducted an observational study at a Western Connecticut hospital heavily affected by the first wave of the COVID-19 pandemic to assess its effects on surgical residents, focusing on surgical education, clinical experience, and operative skills development. Objective data was available through recorded work hours, case logs, and formal didactics. In addition, we created an anonymous survey to assess resident perception of their residency experience during the pandemic. Results: There are 22 surgical residents at our institution; all were included in the study. Resident weekly duty hours decreased by 23.9 hours with the majority of clinical time redirected to caring for COVID-19 patients. Independent studying increased by 1.6 hours (26.2%) while weekly didactics decreased by 2.1 hours (35.6%). The operative volume per resident decreased by 65.7% from 35.0 to 12.0 cases for the period of interest, with a disproportionately high effect on junior residents, who experienced a 76.2% decrease. Unsurprisingly, 70% of residents reported a negative effect of the pandemic on their surgical skills.Conclusions: During the first wave of the COVID-19 pandemic, surgical residents’ usual workflows changed dramatically, as much of their time was dedicated to the critical care of patients with COVID-19. However, the consequent opportunity cost was to surgery-specific training; there was a significant decrease in operative cases and time spent in surgical didactics, along with elevated concern about overall preparedness for their intended career.
Culinary nutrition course equips future physicians to educate patients on healthy diet
Authors: Wood Nathan I , Gleit Rebecca D , Levine Diane L
Published: September 2020

BACKGROUND

Poor-quality diet is associated with one in five deaths globally. In the United States, it is the leading cause of death, representing a bigger risk factor than even smoking. For many, education on a healthy diet comes from their physician. However, as few as 25% of medical schools currently offer a dedicated nutrition course. We hypothesized that an active learning, culinary nutrition experience for medical students would improve the quality of their diets and better equip them to counsel future patients on food and nutrition.
METHODS

This was a prospective, interventional, uncontrolled, non-randomized study. Ten first-year medical students at the Wayne State University School of Medicine completed a 4-part, 8-hour course in culinary-nutritional instruction and hands-on cooking. Online assessment surveys were completed immediately prior to, immediately following, and 2 months after intervention. There was a 100% retention rate and 98.8% item-completion rate on the questionnaires. The primary outcome was changes in attitudes regarding counseling patients on a healthy diet. Secondary outcomes included changes in dietary habits and acquisition of culinary knowledge. Average within-person change between timepoints was determined using ordinary least squares fixed-effect models. Statistical significance was defined as P ≤ .05.
RESULTS

Participants felt better prepared to counsel patients on a healthy diet immediately post-intervention (coefficient = 2.8; 95% confidence interval: 1.6 to 4.0 points; P < .001) and 2 months later (2.2 [1.0, 3.4]; P = .002). Scores on the objective test of culinary knowledge increased immediately after (3.6 [2.4, 4.9]; P < .001) and 2 months after (1.6 [0.4, 2.9]; P = .01) the intervention. Two months post-intervention, participants reported that a higher percentage of their meals were homemade compared to pre-intervention (13.7 [2.1, 25.3]; P = .02).
CONCLUSIONS

An experiential culinary nutrition course may improve medical students’ readiness to provide dietary counseling. Further research will be necessary to determine what effects such interventions may have on the quality of participants’ own diets.
Construction and Comprehensive Analysis of the Competing Endogenous Rna Network in Endometrial Adenocarcinoma
Authors: Feng Chong , Cui Lei , Jin Zhen , Sun Lei , Wang Xiaoyan , Chi Xinshu , Sun Qian , Lian Siyu
Published: September 2020

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors. In this study, we constructed gene co-expression networks to identify key modules and hub genes involved in the pathogenesis of EC. Methods: The RNA profiles of adenocarcinoma and non-adenocarcinoma tissues of patients with EC from The Cancer Genome Atlas were analyzed. MicroRNA, mRNA, and long non-coding RNA networks were constructed based on the differentially expressed RNAs between the two tissues. RNAs from the competing endogenous RNA (ceRNA) networks were then used to construct co-expression networks by weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by the Database for Annotation, Visualization and Integrated Discovery tool. Results: The MEturquoise module was found to be significantly related to hypertension and the MEbrown module was significantly related to the history of other malignancies. Functional enrichment analysis showed that the MEturquoise module was associated with the GO biological process terms of transcription from RNA polymerase II promoter, positive regulation of male gonad development, endocardial cushion development, and endothelial cell differentiation. The MEbrown module was associated with GO terms DNA binding, epithelial-to-mesenchymal transition, and transcription from RNA polymerase II promoter. A total of 10 hub genes were identified and validated at transcriptional and translational levels. Conclusions: The identified ceRNAs may play a critical role in the progression and metastasis of EC and are thus candidate therapeutic targets and potential prognostic biomarkers. The two modules constructed further provide a useful reference that will advance understanding of the mechanisms of tumorigenesis in EC.
Endostar Rebuilding Vascular Homeostasis and Enhancing Chemotherapy Efficacy in Cervical Cancer Treatment
Authors: guan liming
Published: September 2020

Background:The incidence rate of cervical cancer is the highest in the reproductive tract, and is not sensitive to chemotherapy. An appropriate amount of antiangiogenic agents can reconstruct tumor blood vessels in a short period of time and form vascular homeostasis, increase the function of blood vessel perfusion and reverse the multidrug resistance of chemotherapy, which is also called "vascular normalization".Endostar(a recombinant human endostatin) was developed by China and as a multi-target anti-angiogenesis agent.Endostar was mainly used in the treatment of non-small cell lung cancer, fewer reported in the treatment of cervical cancer.Purpose:To determine whether endostar can rebuild tumor vascular homeostasis and enhance chemotherapy effects for patients with cervical cancer.Methods:In this study,the patients with cervical cancer within stage IIB2 were selected,endostar combined with cisplatin+paclitaxel neoadjuvant chemotherapy(NACT) before radical surgical operation was adopted, patients outcome and adverse reaction were followed up.The changes of tumor vascular structure and perfusion function before and after endostar given were evaluated by histopathology and dynamic contrast-enhanced magnetic resonance imaging(DEC-MRI). VEGF-Notch signal pathway was detected for the regulating mechanism of vascular proliferation in different groups. GraphPad Prism 6 software were used for statistical analysis of the study results.Results:Endostar enhanced short-term (2 year) overall survival(OS) ,progression free survival(PFS) rates for cervical cancer patients.All the same,endostar increased long term (5 year) OS and PFS for cervical cancer patients.Endostar therapy exhibited with mild adverse reaction.MRI showed endostar+NACT further reduce tumor volume than NACT alone.The parameters of Ktrans,Ve for DEC-MRI in endostar group exhibited obviously increase than NACT group.Tumor vascular maturation index α-SMA/CD31 in endostar group increased obviously than NACT group, correspondingly Ki67 staining for tumor proliferative rates,lymphvascular space invasion in endostar group further declined than NACT group. The genes and proteins expression of VEGFR2,Notch1,Notch1,4,Dll4,Jagged-1 were obviously down regulated in endostar group comparing to NACT group.Conclusions: Endorstar restored vascular homeostasis in cervical cancer temporarily, enhanced chemotherapeutic agents resistance in cervical cancer, increased patient overall survival ratio.The VEGF-Notch connection blocked by endostar may play a role in this effects.
Screening of cognitive impairment in childhood acute lymphoblastic leukemia survivors with P300 event-related potentials: comparison of different treatment protocols.
Authors: Kroczka Slawomir , Stepien Konrad , Skoczen Szymon
Published: September 2020

BackgroundModern treatment protocols in childhood acute lymphoblastic leukemia (ALL) resulted in high cure rate and improved long-term survival. However, due to their high intensity, they are also associated with many side effects, including central nervous system toxicity. The aim of our study was to evaluate the use of P300 event-related potentials in screening of cognitive impairment in childhood ALL survivors.MethodsA group of 136 patients, 66 males (48.5%), aged 4.9 to 27.9 years who have completed ALL therapy, were screened for cognitive impairment with endogenous P300 potentials. ALL therapy was conducted according to modified New York (NY) (30 patients) and subsequent revisions of modified Berlin-Frankfurt-Münster (BFM): previous BFM protocols (pBFM) (32 patients) and BFM95 (74 patients). The control group consisted of 58 patients, 34 males (58.6%), aged 6 to 17 years after a syncope episode (n = 29) as well as healthy subjects (n = 29).ResultsThe total group of ALL survivors had significantly prolonged the mean latency of P300 (331.31 vs 298.14 ms, P < 0.001) and reaction time (439.51 vs 380.11 ms, P = 0.002) compared to the control group. Abnormalities in endogenous evoked potentials were observed in 10 (33.33%) NY, 5 (15.63%) pBFM and 21 (28.38%) BFM95 patients. The mean latency time was significantly longer compared to the control group (298.14 ms) in all analyzed protocols and the highest values were observed in pBFM patients (NY: 329.13 ms, P = 0.001; pBFM: 332.97 ms, P < 0.001; BFM95: 331.47 ms, P < 0.001). The reaction time was similarly prolonged compared to the control group. The largest and also significant prolongation was recorded in the NY group (461.8 vs 380.1 ms, P = 0.039).Analyzing the effect of radiotherapy on P300 potentials, a significantly higher frequency of prolonged reaction time in non-irradiated BFM95 patients was found (21.62 vs 15.85%, P=0.007). Radiotherapy methods used in NY and pBFM protocols have also significantly reduced the P300 wave amplitude (mean values: 10.395 vs 12.739 ms, P=0.027).ConclusionsEndogenous P300 event-related potentials may be useful in screening assessment of late cognitive impairment in ALL survivors. The type of treatment protocol significantly modulates the individual parameters of the registered P300 potentials.
Maternal pregestational glucose level and adverse neonatal outcomes: a population-based retrospective cohort study
Authors: Zeng Mengyao , He Yang , Li Min , Yang Liu , Zhu Qianxi , Liu Jun , Mao Yanyan , Chen Qing , Du Jing , Zhou Weijin
Published: September 2020

Background: Women with diabetes or hyperglycemia during the pregnancy have been proved to be at increased risk for adverse outcomes such as primary cesarean section rate and macrosomia. However, a lack of studies have focused on the maternal glucose level prior to the pregnancy and the effect of maternal pregestational hyperglycemia or hypoglycemia on pregnancy outcomes is unclear. Hence, we conducted this study to investigate the association between maternal pregestational fasting blood glucose level and adverse neonatal outcomes.Methods: A retrospective cohort study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. A total of 54365 women with their live birth singletons from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project were included. They all took a once fasting glucose testing within one year prior to pregnancy and without a definite diagnosis of diabetes at that point. Our primary outcomes were preterm birth, very preterm birth, macrosomia, large for gestational age (LGA), low birth weight (LBW) and small for gestational age (SGA). Results: Of the 54365 women, 2813 (5.17%) were hypoglycemia, 48400 (89.03%) were normoglycemia, 2582 (4.75%) had impaired fasting glucose (IFG) and 570 (1.05%) were diabetic hyperglycemia. Compared to the normoglycemia group, women with pregestational glucose at the diabetic level had a higher rate of macrosomia (4.16% vs. 6.18%), while impaired fasting glucose group seemed to be associated with decreased risks for preterm birth (7.38% vs. 5.78%), very preterm birth (1.25% vs. 0.74%), LBW (1.18% vs. 0.59%) and SGA (5.92% vs. 4.29%), p<.05 for all. No significant difference was found between hypoglycemia and normoglycemia in the neonatal outcomes. After adjusting for potential confounders, pregestational diabetic hyperglycemia was remained significantly associated with an increased risk for macrosomia (aRR, 1.49; 95%CI, 1.07-2.09). Conclusion: Though without an overt diabetes mellitus, women with once diabetic fasting glucose level during their preconception examinations were still associated with an increased risk for macrosomia. Once fasting glucose within one year before pregnancy might also be considered as an early sign to help the obstetricians to prejudge and control the risk of macrosomia in advance.
Knee ankle joint line angle: a critical value at 10。 for decompensated knee joint line obliquity in medial opening wedge osteotomy.
Authors: Tseng Tzu-Hao , Hsu Kuan-Hung , Wang Jyh-Horng
Published: September 2020

Background: Medial opening wedge high tibial osteotomy (MOWHTO) changes the knee joint inclination in the coronal plane, which can be compensated by the ankle joint. Once there is a decompensated knee joint obliquity, it can induce excessive shear force on the articular cartilage. This study aimed to investigate the capacity of the compensation by analyzing the correlation of the knee-ankle joint line angle (KAJA) and the knee joint line obliquity (KJLO).Methods: The correlations between postoperative KJLO and body mass index (BMI), correction amount, KAJA, mechanical lateral distal femoral angle (mLDFA), preoperative medial proximal tibia angle (MPTA), ankle joint line obliquity (AJLO), KJLO and mechanical hip-knee-ankle angle (mHKA) were analyzed using Pearson correlation coefficient. The contribution of significant factors was further analyzed using multiple linear regression. The KJLO between ≦ 5。, 5。-10。And ≧ 10。KAJA groups were compared using Kruskal-Wallis test.Results: Postoperative KAJA and preoperative KJLO moderately correlated to postoperative KJLO. Preoperative MPTA, mHKA, AJLO weakly correlated to postoperative KJLO. After multiple linear regression, only postoperative KAJA, preoperative MPTA and mHKA still showed significant contribution, while preoperative KAJA made the greatest contribution. The KJLO was substantial higher in the ≧ 10。KAJA group with a high rate (68%) of high-degree KJLO.Conclusions: 10。postoperative KAJA is a critical value for decompensated KJLO. The results suggest us carefully assess the KAJA intraoperatively. Double osteotomy should be considered if ideal alignment cannot be achieved when the KAJA reach 10。.
Selection of metastasis competent subclones in the tumour interior: TRACERx renal
Authors: Zhao Yue , Fu Xiao , Lopez Jose , Rowan Andrew , Au Lewis , Fendler Annika , Hazell Steve , Xu Hang , Horswell Stuart , Shephard Scott , Spain Lavinia , Byrne Fiona , Stamp Gordon , O'Brien Tim , Nicol David , Augustine Marcellus , Chandra Ashish , Rudman Sarah , Toncheva Antonia , Pickering Lisa , Larkin James , Sahai Erik , Bates Paul , Swanton Charles , Turajlic Samra , Litchfield Kevin
Published: September 2020

While the genetic evolutionary features of solid tumour growth are becoming increasingly described, the spatial and physical nature of subclonal growth remains unclear. Here we utilise 102 macroscopic whole tumour images from clear cell renal cell carcinoma (ccRCC) patients, with matched genetic and phenotypic data from 756 biopsies. Utilising a digital image processing pipeline the boundaries between tumour and normal tissue were marked by a renal pathologist, and positions of boundary line and biopsy regions were extracted to X- and Y-coordinates. The coordinates were then integrated with genomic data to map exact spatial subclone locations, revealing how genetically distinct subclones grow and evolve spatially. A phenotype of advanced and more aggressive subclonal growth was present in the tumour centre, characterised by an elevated burden of somatic copy number alterations, higher necrosis, proliferation rate and Fuhrman grade. Moreover, metastasising subclones were found to preferentially originate from the tumour centre. Collectively these observations suggest a model of accelerated evolution in the tumour interior, with harsh hypoxic environmental conditions leading to heightened cellular turnover and greater opportunity for driver SCNAs to arise and expand due to selective advantage. Tumour subclone growth was found to be predominantly spatially contiguous in nature, with subclone dispersal a rare event found in two cases, which notably was associated with metastasis. In terms of genetic events, the largest subclones spatially were dominated by driver somatic copy number alterations, suggesting a large selective advantage can be conferred to subclones upon acquisition of these alterations. In conclusion, spatial dynamics is strongly associated with genomic alterations and plays an important role in tumour evolution.