bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular markers confirm the presence of the alien snowflake coral Carijoa riisei (Octocorallia: Alcyonacea) in Cabo Verde Islands (Central-East Atlantic).
Authors: Lopes Evandro Pires , Freitas Rui , Xavier Raquel , Soares João Deus , Santos António M
Published: May 2021

The snowflake coral Carijoa riisei is one of the most invasive and successfully adapting species in the coastal marine environment. This species can disperse through ballast waters or fouling on the hull of ships, which allows it to expand very quickly to areas where it is not native. Recently C. riisei was identified in the Porto Grande Bay in São Vicente island in Cabo Verde Islands. We analysed mitochondrial and nuclear DNA sequences from specimens collected at this locality to determine the potential origin of this invasion. Lack of genetic variation in both mitochondrial and nuclear genes suggest a very recent invasion (bottleneck effect) but did not permit to establish its origin with total confidence.
Population Genetic Structure of Wild Boar And Dispersal Performance Based On Kinship Analysis In The Northern Region of South Korea
Authors: Han Seung Woo , Park Han Chan , Kim Jee Hyun , Suh Jae Hwa , Lee Hang , Min Mi Sook
Published: May 2021

Wild boar (Sus scrofa) is one of the most challenging mammalian species to manage in the wild because of its high reproductive rate, population density, and lack of predators in much of its range. A recent outbreak of African swine fever (ASF) and the transmission into domestic pigs in commercial farms empower the necessity of establishing management strategies of the wild boar population in the northern region of South Korea. A population genetic study, including the dispersal distance estimation of wild boars, is required to prepare fine-scale population management strategies in the region. In this study, both population structure analysis and dispersal distance estimation based on kinship were conducted using 13 microsatellite markers. The results revealed a high level of genetic diversity compared to a previous study. The population was not structured obviously, but there was a slight level of genetic differentiation between groups mainly formed by isolation by distance rather than mountain ridges. The dispersal distance estimation of Korean wild boars based on kinship analysis showed a philopatric pattern in females. However, extensive dispersal ability in both sexes was observed with a considerable proportion. The population genetic status and dispersal traits of wild boars may provide valuable data for planning detailed ASF and wild boar population management strategies in South Korea.
Twin Vaginal Deliveries: Impact of Delivery Time Interval on Twin B
Authors: Levine Elliot M , Ginsberg Norman A , Delfinado Leah , Ghobrial Mora
Published: May 2021

Background:A vaginal twin delivery is a natural commonplace occurrence, but which can sometimes present a concern which may require action. Recently, the delivery time interval has been recognized as a variable that can be helpful for its safe conduct.Objectives:To view the delivery time interval in an obstetric population undergoing a twin vaginal trial of labor in consecutive deliveries during a specified time period.Study Design:A retrospective observational cohort of twin vaginal trials of labor was investigated to view the delivery time interval and its association with other factors, such as birth weights and the need for cesarean delivery of the second twin. The twin deliveries were divided into 2 groups, those with a delivery time interval of ≤ 30 minutes (Group A) and those with a delivery time interval of > 30 minutes (Group B), in a single institution.Results:No perinatal outcome difference was found between Group A (248 patients) or Group B (72 patients). However, 13 patients in Group B required a cesarean birth for a safe delivery, and 3 patients in Group A. The birth weight difference between each Baby A and Baby B varied according to the delivery time interval. Conclusion:The delivery time interval for vaginal twin deliveries may be useful to predict the need for a cesarean delivery of the second twin. The birth weight difference between Baby A and Baby B may be responsible for this finding.
Dilemmas Regarding Abdominal Re-Exploration for War Casualties Following On-Site Abdominal Trauma Surgery and Subsequently Delayed Arrival to Medical Care Abroad – An Unusual Scenario
Authors: Bickel Amitai , Akinichev Konstantin , Weiss Michael , Ganam Samer , Kakiashvili Eli
Published: May 2021

Background: During the Syrian civil war, casualties were treated on-site and only later transferred to foreign medical centers. Significant number needed abdominal re-operation. Our aim is to present our approach to abdominal trauma casualties who survived the on-site surgery and needed abdominal reoperation abroad.Methods: Medical data from all medical records were retrospectively analyzed. Each patient underwent total body computerized tomography on arrival, revealing diverse multi-organ trauma. We divided the casualty population involving abdominal trauma into 4 sub-groups according to the location of abdominal surgical intervention, focusing on missed injuries and post-operative complications in the re-laparotomy sub-group. Results: By July 2018, 236 casualties suffering abdominal trauma (among 1331 trauma casualties) had been admitted to our hospital. Life-saving abdominal interventions had been done in 138 subjects in Syria before arrival to our medical center. Seventy-nine underwent abdominal surgery in Israel, of whom, 46 (33.3%) needed abdominal re-laparotomy. Indications for re-exploration included severe peritoneal inflammation, neglected abdominal foreign bodies, hemodynamic instability and intestinal fistula. Mortality occurred in 37/236 patients, with abdominal trauma as the main cause of fatality in 10 of them (4.2%), usually following urgent re-laparotomy. Conclusions: Clinical presentation of the Syrian casualties following emergency medical care outside our borders, and the fact that re-operation was not done by the same team responsible for the initial abdominal intervention posed major diagnostic challenges and necessitated increased suspicion and changes in our medical approach.
A Tumor of Composite Cervical Adenocarcinoma with MUCIN Gene Mutation：A Case Report
Authors: Guo Meijun , Li Guoping , Jiang Xiuxiu , Lv Shiming
Published: May 2021

Background:There are reports about the coexistence of two kinds of tumors in the same patient,which is believed that this phenomenon is caused by the dedifferentiation between the two tumors.In this paper, we report an human papillomavirus (HPV) negative cervical adenocarcinoma in a patient composed of two adenocarcinoma components,which is first reported.Histologically, both minimal deviation adenocarcinoma (MDA) and poorly differentiated gastric type adenocarcinoma (GTA) components, as well as their transitional area, were observed.Methods:This case of cervical cancer was screened by gene sequencing. For detection of specific somatic mutations in MDA and GTA, we filtered out mutations in malignant cervical cancer blood sample and 7 common cervical carcinoma. Then the genes were screened and identified based on the enrichment analysis of GO and KEGG and related literature reports. Results:We found 13 specific somatic gene mutations in total. Among these genes, only Mucin gene was transformed from gene level to protein level, and was positive in both MDA and GTA components of the patient by immunohistochemistry.Both components had genes mutation of MUC4 and MUC17,the component in MDA had gene mutation of MUC3A,and we found that MUC3A and MUC17 were on the same chromosome. Moreover,MUC3A and MUC4 genes were found to be fused in FusionGDB database. Conclusion:According to the reports of MUC3A,MUC4 and MUC17 genes mutation in cervical adenocarcinoma and gene fusions in tumorigenesis, we speculate that the occurrence of the transformation of pathological type from MDA to GTA in this case of cervical cancer is related to the mechanism of MUC3A and MUC4 gene fusion.We would advice, for HPV negative or atypical cervical lesions, immunohistochemistry of MUCIN genes staining and gene sequencing should be considered, which may find unusual cancer types and change the prognosis of patients.
SPOP Could Play a Potential Inhibitory Role in Human Renal Cell Carcinoma
Authors: chen zhi , Li Zuan , Nong Deyong , Li Ximing , Huang Guihai , Lin Junhao , Li Wei
Published: May 2021

Background: SPOP, a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and determine the expression levels of SPOP in human tissue microarrays (TMAs) and kidney tissues.Methods: Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, Transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-α2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues.Results: Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-α2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan-Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients.Conclusions: In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.
Paleofluid flow: answers in the quartz.
Authors: Freville Kevin , Sizaret Stanislas
Published: May 2021

The search for carbon-free energy sources is at the heart of our concerns. It has become necessary to develop our capacities to harness the active energy flows of our environment while trying to have the lowest possible impact. Among these flows, one of the most stable is that linked to terrestrial thermal anomalies. Geothermal energy is an attractive option due to its regularity and the development of knowledge is encouraged, in France, by the national research funding agency. Geothermal systems are mainly associated with active hydrothermal circulations, fluids can be considered as a source of heat but also of metals. However, fluid circulation within active hydrothermal fields occurs at considerable depths and cannot be observed directly. In this study we propose a method for reconstructing the paleo-flow velocities recorded by quartz. The relative thickness of quartz growth bands is used to deduce the sense and velocity of the paleofluid flow. This contribution highlights the paleofluid flows velocities and the recharge/discharge area in the Limagne Basin geothermal province, which is currently under investigation. Finally, this study provides a tool to be used to study fossil hydrothermal systems containing quartz veins with comb textures.
CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling
Authors: Lin Xian , Wang Feng , Liu Jing , Lin Yibin , Li Li , Li Zirong , Pan Junping , Song Yanwen , Chen Chuanben , Xu Qin
Published: May 2021

Background

Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. It is meaningful to develop alternative targets for eliminating cancer stem cells (CSCs) properties, suppressing metastasis, and alleviating chemoresistance in cervical cancer. This study clarifies the role of CENPK in cervical cancer stemness and chemoresistance and its clinical significance in cancer progression.
Methods

Human cervical cancer cell lines, xenografts, and clinical samples were used for expression and functional analysis. CENPK expression in cervical cancer was analyzed by bioinformatics based on a microarray and TCGA database and immunohistochemistry based on 119 paraffin-embedded cervical cancer specimens and 35 paraffin-embedded adjacent normal tissues in a tissue chip.
Results

CENPK served as an oncogene by promoting CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication, thus inducing cisplatin/carboplatin resistance, cell metastasis and proliferation in cervical cancer. Intriguingly, targeting CENPK markedly prolonged the survival time of cervical cancer-bearing mice, and improved chemotherapy sensitivity of cervical cancer cells in vivo. CENPK also interacted with tumor suppressor gene SOX6 to activate Wnt signaling and inactivate p53 signaling. CENPK modulated expression of key regulators in CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication by disrupting SOX6-β-catenin interaction, promoting β-catenin expression and nuclear translocation, and facilitating SOX6-mediated p53 ubiquitination and nuclear export, thus stimulating cervical cancer stemness, chemoresistance, metastasis and proliferation by. Interestingly, the RAD21/SMC3 complex, downstream targets of β-catenin, enhanced CENPK transcription to form a positive regulatory circuit through Wnt signaling. Facilitation of Wnt signaling by iRhom2 further activated the CENPK/SOX6-β-catenin-RAD21/SMC3 loop and conferred cervical cancer progression, suggesting a Wnt-p53 pathway crosstalk. Importantly, CENPK was upregulated in cervical cancer, correlated with cancer recurrence, and independently predicted poor patient prognosis.
Conclusions

This work identifies CENPK as a prognostic indicator and highlights targeting of CENPK as a novel strategy in the treatment of cervical cancer.
Prevalence, Correlations, and Impact of Sleep Disturbance in Chinese Meningioma Patients
Authors: Zhang Dandan , Wang Jing , Gu Xixi , Gu Zhifeng , Li Liren , Dong Chen , Zhang Xiaomei , Zhao Rui
Published: May 2021

Purpose

Sleep disturbance is common in meningioma patients and may lead to disease aggravation and decreases health-related quality of life (HRQoL). However, the sleep quality of meningioma patients newly diagnosed and ready for surgery has not been well clarified in China. This study aims to evaluate the prevalence, correlates, and impact of sleep disturbance among Chinese meningioma patients.
Methods

In this cross-sectional study, meningioma patients were recruited from the Affiliated Hospital of Nantong University from January 2020 to November 2020. A series of questionnaires were applied: the 0–10 Numerical Rating Scale (NRS), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), the Epworth Sleepiness Scale (ESS), the Short-Form 36 (SF-36), the Pittsburgh Sleep Quality Index (PSQI). Independent samples t test, Mann-Whitney U test, chi-square analysis, Pearson/Spearman correlation, and binary logistic regression were used to analyze the data.
Results

100 meningioma patients completed the questionnaires. Sleep disturbance affected 43% of the meningioma patients and was linked to many concomitant symptoms, such as headache, fatigue, anxiety and depression. Binary logistic regression indicated that fatigue and headache were predictors of sleep disturbance in meningioma patients. Meanwhile, severe sleep disturbance led to lower quality of life.
Conclusions

These findings demonstrated that a considerable number of meningioma patients newly diagnosed and ready for surgery suffered from sleep disturbance, potentially contributing to impair HRQoL. Medical personnel should pay more attention to meningioma patients with sleep disturbance and take effective measures to improve sleep quality, with the ultimate goal to improve their HRQoL.
Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation
Authors: Lv Xuyang , Sun Jiangchuan , Hu Linfeng , Qian Ying , Fan Chunlei , Tian Nan
Published: May 2021

Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.
Daurisoline Suppresses Growth of Esophageal Squamous Cell Carcinoma by Inhibiting MEK1/2 In Vitro and In Vivo
Authors: Wang Donghao , Yang Ning , Zhang Xiaofan , Li Mingzhu , Li Xin , Zhao Lili , Yuan Qiang , Yu Yin , Lu Jing , Zhao Jimin , Jiang Yanan , Dong Zigang , Liu Kangdong
Published: May 2021

Background

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of esophageal cancer and has a high mortality rate worldwide. The clinical treatment of ESCC is mainly surgical resection. The five-year survival rate of ESCC patients in developing countries is less than 20%. Therefore, identifying new and effective drugs that can prevent the occurrence and recurrence of ESCC is clinically significant. Here, daurisoline, a bis-benzylisoquinoline alkaloid, was found to have an anticancer effect on ESCC.
Methods

We investigated the effects of daurisoline on ESCC cell growth and proliferation using ESCC cell lines (KYSE150 and KYSE450 cells) and tumor growth in an ESCC patient-derived xenograft model. Phosphoproteomics was used to identify changes in protein phosphorylation after daurisoline treatment. Molecular docking simulation, pull down assay and amino acid mutation experiments were conducted to determine the target proteins and specific amino acid binding sites of daurisoline. In vitro kinase assay was used to determine the effect of daurisoline on protein phosphorylation. The correlation between MEK1/2 and ERK1/2 expression levels in ESCC was analyzed using TCGA database.
Results

In vitro experiments showed that daurisoline inhibited the proliferation and anchorage-independent growth of ESCC cells. In vivo experiments indicated that daurisoline significantly inhibited tumor growth. Phosphoproteomics analysis revealed that daurisoline reduced ERK1/2 phosphorylation. A pull down assay showed that daurisoline could bind to MEK1/2. In vitro kinase assay confirmed that daurisoline inhibited the biological functions of MEK1/2. We observed a significant correlation between MEK1 and ERK2 in ESCC from the TCGA database.
Conclusion

Daurisoline is a MEK1/2 inhibitor that suppressed ESCC growth in vitro and in vivo.
Evaluation of hierarchical model of trait and disorder- specific intolerance of uncertainty in anxiety disorder symptoms
Authors: Moloodi Reza , Mohebban Fatemeh , Taremian Farhad , Poursharifi hamid
Published: May 2021

Background: Research suggests that Intolerance of Uncertainty is a transdiagnostic risk and maintaining factor in anxiety disorders. The aim of this study was to evaluate the hierarchical model of trait Intolerance of Uncertainty and disorder-specific Intolerance of Uncertainty in symptoms of anxiety disorders in Iranian university students.Methods: Participants (N = 561) completed a battery of questionnaires which assess intolerance of uncertainty, disorder-specific intolerance of uncertainty, metacognition beliefs, fear of negative evaluation, obsessive cognitions, agoraphobic cognitions, obsessive compulsive symptoms, generalized anxiety disorder symptoms, social phobia symptoms, and panic disorder symptoms. Results: Results showed hierarchical model of trait Intolerance of Uncertainty and disorder-specific Intolerance of Uncertainty fit with data. Trait intolerance of uncertainty and disorder-specific intolerance of uncertainty had significant direct and indirect association with various cognitive vulnerabilities and symptoms of anxiety disorders. Conclusion: The findings showed trait intolerance of uncertainty and disorder-specific intolerance of uncertainty have significant contribution to various anxiety disorders. These findings have important implications in conceptualization, prevention and treatment of anxiety disorders.
KCTD1 Downregulation Suppresses Hepatocellular Carcinoma by Regulating Angiogenesis and Influencing the HIF-1α/VEGF Pathway
Authors: Zhu Xinyu , Li Zhiwei , Li Limin , Chen Li , Ouyang Mi , Zhou Hao , Xiao Kai , Lin Ling , Chu Paul K. , Zhou Chang , Xun Chengfeng , Yang Liu , Huang Wenhuan , Ding Xiaofeng
Published: May 2021

Background: Potassium channel tetramerization domain-containing 1 (KCTD1) plays a critical role in transcriptional regulation and adipogenesis, but the significance of KCTD1 in hepatocellular cancer (HCC) has not been reported. Methods: KCTD1 expression was detected by immunohistochemistry, Western blotting, and quantitative RT-PCR. Malignant behaviors of cells were analyzed by MTT assays, liquid colony formation, scratch, transwell assays and FACS analysis. The in vivo functional assays were examined by mouse models using subcutaneous, tail vein, intrahepatic injection combined with sorafenib or exosome treatment. The angiogenesis was analyzed by tube formation and Matrigel plug model. The protein-protein interaction was demonstrated by Co-immunoprecipitation. The protein-DNA binding was confirmed by luciferase assays and chromatin immunoprecipitation.Results: KCTD1 expression is increased in human HCC tissues and closely associated with advanced tumor stages. KCTD1 overexpression enhances HCC growth, migration, and invasion both in vitro and in vivo, while KCTD1 knockdown reverses these effects. Moreover, KCTD1 overexpression promotes the in vitro growth, migration, and tube formation of human umbilical-vein endothelial cells (HUVECs) and induces in vivo angiogenesis. Mechanistically, KCTD1 interacts with HIF-1α to activate the VEGF pathway in HCC cells, which is concurrent with increased M2 macrophage infiltration. Sorafenib blocks the expression of KCTD1 protein and synergistically inhibits subcutaneous and intrahepatic tumor growth. miR-129-5p downregulates KCTD1 expression by binding with KCTD1 3′ UTR and abrogates the oncogenic role of KCTD1 in vitro. Finally, exosomes derived from miR-129-5p-overexpressing HCC cells combine with sorafenib to decrease HCC tumor size. Conclusions: These results suggest that KCTD1 expression activates the VEGF signaling cascade to enhance HCC progression, and angiogenesis. Therefore, KCTD1 may serve as a novel target of sorafenib and pave the way for an efficient therapy for advanced human HCC.
GPBAR1 Promotes Proliferation and Is Related to Poor Prognosis of High-Grade Glioma via Inducing MAFB Expression
Authors: Sun Suohui , Guo Hui , Liang Nan , Wu Tao , Zhang Chunpu , Li Huaqing
Published: May 2021

Background

Glioma is the most prevalent brain tumors with extremely poor prognosis, but the prognostic biomarkers of high-grade (grade III and IV) gliomas (HGG) are still insufficient.
Methods

In our study, we investigated the expression of GPBAR1 in HGG by qRT-PCR and immunohistochemistry (IHC), and evaluated the clinical significance of GPBAR1 with univariate and multivariate analyses. By retrieving the data from TCGA, we screened the genes significantly associated with GPBAR1, and identified the correlation between GPBAR1 and MAFB. By experiments in vitro, we showed the pivotal role of MAFB in GPBAR1-induced proliferation of HGG.
Results

GPBAR1 expression in HGGs was significantly higher than that in normal brain tissues. GPBAR1 was an independent prognostic biomarker of HGG. GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. MAFB was also a prognostic biomarker of HGG, and patients with co-expression of MAFB and GPBAR1 had worse prognosis.
Conclusions

GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. Both GPBAR1 and MAFB were prognostic biomarkers of HGG, and patients with co-expression of MAFB and GPBAR1 had worse prognosis than those with only GPBAR1 or MAFB expression.
A Formal Outpatient Parenteral Antimicrobial Therapy Program for Patients with Solid Tumors
Authors: Robins Alison , Dishner Emma , McDaneld Patrick , Rowan Meagan , Bartek Jalen , Jiang Ying , Adachi Javier , Garnes Natalie J.M. Dailey
Published: May 2021

Background and Objectives: Outpatient parenteral antimicrobial therapy (OPAT) for infections has been in use for nearly 40 years, and although it has been found safe and efficacious, its use has been studied primarily among otherwise healthy patients. We aimed to develop and evaluate an OPAT program for patients with cancer, particularly solid tumors. Methods: We implemented multiple quality improvement interventions between June 2018 and January 2020. We retrospectively and prospectively collected data on demographics, the quality of infectious diseases (ID) physician consultation notes, rates of laboratory test result monitoring, ID clinic follow-up, and 30-day outcomes, including unplanned OPAT-related readmissions, OPAT-related emergency center visits, and deaths. Results: Completeness of ID provider notes improved from a baseline of 77% to 100% (p<.0001) for antimicrobial recommendations, 75% to 97% (p<.0001) for follow-up recommendations, and 19% to 98% (p<.0001) for laboratory test result monitoring recommendations. Completion of laboratory tests increased from a baseline rate of 24% to 56% (p=.027). Thirty-day unplanned OPAT-related readmission, ID clinic follow-up, 30-day emergency center visit, and death rates improved without reaching statistical significance. Conclusions: Sustained efforts, multiple interventions, and multidisciplinary engagement can improve laboratory test result monitoring among solid tumor patients discharged with OPAT. Although demonstrating a decrease in unplanned readmissions through institution of a formal OPAT program among patients with solid malignancies may be more difficult compared with the general population, the program may still result in improved safety.
Suboptimal birth spacing practice and associated factors among women of reproductive age in West Badwacho district, Hadyia zone, South Ethiopia, 2020: Cross-sectional study design
Authors: Wassihun Alemu Workineh , Hunegnaw Yilkal Simachew , Abebo Teshome Abuka , Bekele Alex Yeshaneh
Published: May 2021

Introduction: Birth spacing is the time gaps between two consecutive life births. One of the key strategies to reduce fertility and promote the health status of mothers and their children is optimal birth spacing. Recent evidences showed that the health of mothers and children with the birth interval of 3 to 5 years is safer than 2 years or less. However, women still have shorter birth intervals and studies addressing their associated factors were scarce. Objectives: To assess prevalence of suboptimal birth spacing practice and its associated factors among women of reproductive age in West Badwacho district, Hadyia Zone, South Ethiopia, 2020.Method and materials: Community based cross sectional study was conducted from February to March, 2020. Multi stage sampling technique was used to select samples of 626 women. Structured and pretested interview based questionnaire was used to collect the data. Data was checked for completeness and entered using EPI data version 3.1 and analyzed using SPSS version 25. Bivariable logistic regression was done and variables with a p-value of < 0.25 in bi-variable logistic regression were recruited as candidate variable for the final multivariable logistic regression model and P value less than 0.05 at 95 % confidence level was taken as statistically significant. Result: The prevalence of suboptimal birth interval in this study was 60.4 %. Independent predictors of suboptimal birth spacing were: age at first marriage less than 18 years (AOR: 2.18, 95% CI=1.34,3.53), HEWs education about birth sapcing (AOR: 1.89, 95% CI=1.02,3.48), non -formal maternal education (A0R: 2.25, 95%CI=1.31,3.87), non -formal husband education (AOR: 2.64, 95%CI=1.74,4.01), sex of index child being female (AOR:1.58, 95%CI=1.06, 2.38),, having poor knowledge on optimal birth interval (AOR: 2.96, 95%CI=1.64,5.37), duration of breast feeding for less than 24 months (AOR: 4.64, 95%CI=2.32,9.29), and modern contraceptive non users (AOR: 6.31, 95%CI=3.99,9.96),Conclusion and recommendation: More than half of the study respondents were practicing suboptimal birth interval. Educational status, age at first marriage, HEWs education about birth sapacing, short duration of breastfeeding was some of the factors associated with the outcome variable. Thus, to optimize birth spacing, strategies of providing information using HEWs, education and communication targeting associated variables should be improved.
Uptake, Translocation and Subcellular Distribution of Three Triazole Pesticides in Rice
Authors: Li Haocong , Li Yong , Wang Wenfeng , Wan Qun , Yu Xiang-Yang , Sun Wenjing
Published: May 2021

Triazole pesticide is a widely-used pesticide for the control of pathogenic fungi in crops and its extensive use has caused food safety issues due to its uptake byedible crops. The residue of triazole pesticides has caused many toxicity risks and food safety problems. In this study, the uptake, translocation, and subcellular distribution of three triazole pesticides (triadimefon, tebuconazole, and epoxiconazole) in rice were investigated. The results showed that the three selected triazole pesticides could be taken up by rice roots, but their distribution in plant tissues was different. The accumulation of the three pesticides in rice root followed the order of epoxiconazole > tebuconazole > triadimefon, while a reversed order was observed in rice shoots. The movement of triazole pesticides within rice tissues involved both symplast and apoplast pathways, with triadimefon preferentially through the symplast pathway and epoxiconazole throughby the symplast pathway. The subcellular distribution reveals that all pesticides have a higher proportion in cell walls than in cell organelles and soluble components. Epoxiconazole has the highest accumulated capacity in the cell wall (45%-67%) and triadimefon was more concentrated in the soluble components (24%-29%). However, there exists no significant difference in the amount of three pesticides in cell organelles. The pesticide uptake, the movement of pesticides in symplast and apoplast, and the subcellular distribution of the three pesticides are related to the hydrophobicity of the three pesticides.
Neutrophil Extracellular Traps and Macrophage Polarization Formation In The Inner And Outer Area of Carotid Plaque Arteries
Authors: Saberianpour Shirin , Modaghegh Mohammad hadi saeed , Kamyar Mohammad Mahdi
Published: May 2021

Introduction: It is noteworthy that vast data exists which links NETs to arterial and venous thrombosis in both animal models and humans. In the current study, the level of extracellular neutrophil networks and macrophage polarization in the area outside and inside the carotid plaque of patients with carotid stenosis were assessed.Material and Methods: Ten patients were included in this pilot study. Confirmed cases of carotid stenosis were selected to participate in the study using the simple sampling method. Samples of carotid plaques of each patient were divided into two halves with a transverse incision; the terms inner part and outer part were used for the plaque’s inner part and the adjacent area, respectively. Carotid plaque was excised, and half of them were sorted in 10% formalin for CD163,CD11c ,MPO and histone H3 immunohistochemistry assessment while the other halves were stored at -80 ° C for western blotting assay with PDA4 marker. For statistical analysis, we used independent samples T-test or its non-parametric equivalents.Results: Results of this study showed that the extracellular neutrophil chicks in the inner part of the carotid plaque were significantly increased (P <0.0001), while the number of M1 and M2 macrophages was higher in the inner part compared with the outer part of the carotid plaque (P <0.0001).Conclusion: NETs and Macrophages have great potential for further investigation to find a better treatment for carotid plaque.
Brusatol Sensitizes Endometrial Hyperplasia and Cancer to Progestin by Suppressing Nrf2-Tet1-AKR1C1-Mediated Progestin Metabolism
Authors: Hu Meiyan , Sun Di , Yu Jing , Fu Yue , Qin Zuoshu , Huang Baozhu , Zhang Qiuju , Chen Xiong , Wei Youheng , Zhu Huiting , Wang Yue , Feng Youji , Zheng Wenxin , Liao Hong , Li Jingjie , Wu Sufang , Zhang Zhenbo
Published: May 2021

BackgroundProgestin resistance is the main obstacle for the conservative therapy to maintain fertility in women with endometrial hyperplasia and cancer. Up to 30% of endometrial cancers fail to respond to progestin, a rate that has not significantly changed due to the lack of a detailed understanding of progestin resistance.MethodsCell Counting Kit-8 (CCK-8) assays were used to detect the synergistic effects of brusatol in combination with progestin. Using commercial kits, the conversion of progestin to 20α-dihydroxyprogesterone following btusatol treatment or AKR1C1 silence was investigated. The correlation betwwen AKR1C1 expression profile and prgestin response was further analyzed in paired endometrial hyperplasia and cancer samples from the same individuals before and after progestin therapy. The effects of brusatol-mediated reversal of progestin resistance was explored in both mouse xenograft and human organoid models. DNA dot blot, HMeDIP, and dural-luciferase reporter assays were performed to uncover the mechanism through which brusatol inhibits AKR1C1 and sensitizes endometrial hyperplasia and cancer to progestin.ResultsBrusatol sensitizes endometrial cancer cell to progestin by downregulating the expression of Nrf2 and its target AKR1C1. Increased AKR1C1 facilitated production of 20-α-dihydroxyprogeserone and was associated with declined progesterone. Suppression of AKR1C1 by brusatol resulted in decreased progesterone catabolism and maintained potent progesterone to inhibit endometrial cancer growth. Aberrant overexpression of AKR1C1 was found in paired endometrial hyperplasia and cancer samples from the same individuals with progestin resistance, whereas attenuated or loss of AKR1C1 was observed in post-treatment samples with well progestin response as compared with paired pre-treatment tissues. Tet1 was identified as a novel Nrf2 target gene. It in turn upregulated AKR1C1 expression by increasing hydroxymethylation levels in its promoter regions. ConclusionsWe found that Nrf2-Tet1-AKR1C1 axis plays an essential role in progestin resistance, and brusatol sensitizes endometrial hyperplasia and cancer to progestin by suppressing Nrf2-Tet1-AKR1C1-mediated progestin metabolism. Our findings suggest that AKR1C1 expression pattern may serve as an important biomarker of progestin resistance in endometrial hyperplasia and cancer .
The Burden of Drug Resistant Tuberculosis in a predominantly nomadic population in Uganda. A Mixed Methods Study
Authors: Simbwa Brenda Nakafeero , Katana Elizabeth B. , Nabatanzi Sandra , Sendaula Emmanuel , Karamagi Charles A. , Kalyango Joan N. , Opio Denis , Laker Eva A.O. , Katamba Achilles , Worodria William , Ictho Jerry , Lochoro Peter
Published: May 2021

Background: Emergence of Drug Resistant Tuberculosis (DR-TB) has aggravated the Tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3,500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB. Methods: We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews. Results: The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI: 1.552 – 110.135) and drug stock-outs aOR 0.027 (95%CI: 0.002-0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB. Conclusion: Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.
Expression and Purification of the Extracellular Domain of Luteinizing Hormone Receptor From Ovis Aries Testicle
Authors: Villalpando-Aguilar Jose Luis , López-Rosas Itzel , Montero-Pardo Arnulfo , Azuara-Liceaga Elisa Irene , Valencia-Méndez Javier de Jesus , Trejo-Muñoz Cynthia R. , Cetzal-Ix William Rolando , Kubli-Garfias Carlos
Published: May 2021

The luteinizing hormone receptor (LHR) is a glycoprotein member of the G protein-coupled receptor superfamily. Physiologically, this receptor participates in corpus luteum formation and ovulation in females. In males, it acts in testosterone synthesis and spermatogenesis and is involved in some fertility disorders. RNA was extracted from Ovis aries testicles, and the corresponding cDNA was synthesized to amplify the lhr gene, termed lhr-bed here, consisting of 762 bp that encodes 273 amino acids of the extracellular domain of LHR. Thus, the lhr-bed was cloned into pJET1.2/blunt, subcloned into the pCOLD II expression vector and finally transformed into E. coli BL21 cells. Since the induced rLHR-Bed protein was found in the insoluble fraction, the purification protocol was modified as follows: induction at 25°C, denaturing conditions (8 M UREA and 0.1% CHAPS) and refolding in the column to increase solubility. The rLHR-Bed expression was corroborated by western blotting and mass spectrometry (MS) analysis. This successful method to obtain the recombinant LHR extracellular domain yields 0.2 mg/L of the protein with approximately 90% purity from a single chromatographic purification step. The present approach demonstrates the feasibility of obtaining large quantities of rLHR-Bed. This might be useful to accomplish future studies regarding the structure and functional analysis of the binding interplay with its ligand luteinizing hormone and its isoforms. Additionally, this biotechnological strategy might be used to improve and to develop new drugs for the treatment of reproductive disorders and might also be applied to species reproduction in the livestock industry.
Design and Analysis of a Novel MEMS Piezoresistive Pressure Sensor with Annular Groove Membrane and Centre Mass for Low Pressure Measurements
Authors: SAHAY ROHAN , HIRWANI JAGRITI , Jindal Sumit Kumar , K SREEKANTH P , KUMAR AJAY
Published: May 2021

Purpose: Micro Electronic Mechanical System (MEMS) based pressure sensors have found their use in multiple applications lately in the field of healthcare, automotive etc. These sensors however face a trade-off between sensitivity and linearity which limits sensor performance. The proposed design aims to achieve an enhanced sensor performance by alleviating the sensitivity and linearity trade-off.Methods: Novel structures such as annular grooves and center mass have been introduced for providing better sensor performance along with membrane dimension optimization. Annular grooves generate Stress Concentrated Regions (SCRs) on membrane surface on application of external pressure which enhances sensor sensitivity while center mass provides partial stiffening of the membrane and hence reduces non-linearity.Results: The proposed sensor achieves a low non-linearity error of 0.15% FSS with a well-balanced sensitivity of 28.0 mV/V/psi. Conclusion: The proposed novel sensor structure achieves a relatively better performance in comparison to conventional membrane variants. With a high sensitivity and appreciable linearity, the novel structure proves to be ideal for low pressure measurements in the range (0-5)KPa.
The effect of Curcumin on Multi-Level Immune Checkpoint Blockade and T Cell Dysfunction in Head and Neck Cancer
Authors: Liu Lihua , Lim Mi Ae , Jung Seung-Nam , Oh Chan , Won Ho-Ryun , Jin Yan Li , Piao Yudan , Kim Hae Jong , Chang Jae Won , Koo Bon Seok
Published: May 2021

BackgroundDespite recent advances in understanding the complex immunologic dysfunction in the tumor microenvironment (TME), fewer than 20% of patients with head and neck squamous cell carcinoma (HNSCC) respond to immune checkpoint blockade (ICB). Thus, it is important to understand how inhibitory IC receptors maintain the suppressed dysfunctional TME, and to develop more effective combination immunotherapy. This study evaluated the immune-modulating effects of Curcumin, which has well-established anti-cancer and chemopreventive properties, and its long-term safety as a phytochemical drug.MethodsWe carried out the western blot and small interfering RNA (siRNA) transfection assayto evaluate the effects of Curcumin on IC ligands and IC ligands function in HNSCC. Through T-cell cytotoxicity assay and measurements of cytokine secretion, we assessed the effects of combination of Curcumin with programmed death-ligand 1 (PD-L1) Ab on cancer cell killing. Flow cytometry were used to analyze the effects of Curcumin on the expression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain3 (TIM-3) on CD4, CD8 and Treg. Immunofluorescence, immunohistochemistry and western blot were used to detecte the cytokine (IFN-γ, Granzyme B), IC receptors (PD-1 and TIM-3) and its ligands (PD-L1, PD-L2, Galectin-9) in xenograft mouse model and 4-nitroquinoline-1-oxide (4-NQO) oral cancer model. ResultsWe found that Curcumin decreased the expression of IC ligands such as PD-L1, PD-L2, and Galectin-9 in HNSCC, leading to regulation of epithelial-to-mesenchymal transition-associated tumor invasion. Curcumin also effectively restored the ability of CD8+ cytotoxic T cells to lyse cancer cells. To evaluate the effect of Curcumin on the TME further, the 4-NQO oral cancer model was used. Curcumin increased T-cell proliferation, tumor-infiltrating lymphocytes (TILs), and effector cytokines, and decreased the expression of PD-1, TIM-3, suppressive IC receptors and their ligands (PD-L1, PD-L2, and Galectin-9) in the TME, implying reinvigoration of the exhausted CD8+ T cells. In addition, Curcumin inhibited expression of CD4+CD25+FoxP3+ Treg cells as well as PD-1 and TIM-3. ConclusionsThese results show that Curcumin reinvigorates defective T cells via multiple (PD-1 and TIM-3) and multi-level (IC receptors and its ligands) IC axis suppression, thus providing a rationale to combine Curcumin with conventional targeted therapy or ICB as a multi-faceted approach for treating patients with HNSCC.
Nucleus Accumbens Dopamine D3 Receptor Regulates Microglial M1 Polarization Through Akt Signaling Pathway in the Depressive-Like Behavior
Authors: Wang Jing , Lai Simin , Wang Rui , Zhou Ting , Dong Nan , Zhu Li , Chen Teng , Chen Yanjiong
Published: May 2021

Background: Nucleus accumbens (NAc) inflammation is implicated in the development and progression of depression but the underlying mechanism remains largely unclear. We previously reported that dopamine D3 receptor (D3R) expressed in the NAc strongly correlated with inflammation-related depression. The objective of the present study is to determine the exact mechanism of D3R in the NAc inflammation relevant depression.Methods: Bilateral NAc injection of Lipopolysaccharide (LPS)-induced NAc inflammation mouse model was used to explore the relationship between NAc inflammation and depressive-like behaviors. Either conditional knockout of D3R in the NAc in the adult mice or restoration of D3R expression in the NAc in D3R mutant mice was applied to investigate the effects of D3R in the NAc on depressive disorders. The exact molecular mechanism of D3R in the NAc inflammation-induced depressive-like phenotype was ascertained by in vivo and in vitro studies. Results: NAc inflammation induced by intra-NAc LPS triggered a series of depressive-like disorders, and the interaction of D3R and microglia activation involved in the NAc inflammation-induced depressive-like phenotype. We observed that selective knock-down of D3R in the NAc elicited the depressive-like behaviors, but re-expression of D3R in the NAc alleviated the depressive-like behaviors established by D3R mutation. Finally, D3R in the NAc mediated microglial polarization to M1 phenotype mainly through Akt signaling pathway. Conclusions: These findings provide direct evidence that not only NAc inflammation but also down-regulation of D3R in the NAc has a role in regulation the initiation and development of depression, and indicate that D3R negatively regulated microglial M1 polarization mainly via Akt signaling pathway that may be involved in the NAc inflammation and thereby depressive-like behaviors.