bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II Trial of Humanized Anti-Lewis Y Monoclonal Antibody for Advanced Hormone Receptor-positive Breast Cancer That Progressed on Previous Endocrine Therapy
Authors: Testa Laura , Mano Max , Arai Roberto Jun , Bonadio Renata Colombo , Serrano Sergio V. , Zorzetto Marina M. Costa , Crocamo Susanne , Smaletz Oren , Freitas-Junior Ruffo , Hoff Paulo M.
Published: November 2020

Purpose: Lewis Y antigen is expressed in 44 to 90% of breast cancer. The expression of the antigen in carcinoma tissue is different from what occurs in normal tissue. The objective of the present study was to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive breast cancer, after progression on endocrine therapy.Methods: A single-arm phase II study was conducted in 7 centers. Patients with advanced hormone receptor-positive breast cancer who had failed previous first-line endocrine therapy were included. All patients were required to present tumoral expression of Lewis Y antigen by immunohistochemistry. Treatment consisted of hu3S193 antibody at intravenous doses of 20 mg/m2 weekly given at 8-week cycles. The primary endpoint was clinical benefit rate. Results: The study stopped accrual after an unplanned interim analysis since the hu3S193 antibody lacked sufficient activity to justify the study continuation. Twenty-two patients were enrolled; 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting stable disease confirmed after 24 weeks. One patient received the medication for more than 2 years, with prolonged stable disease. No partial or complete responses were observed. Median time to progression and overall survival were 5.4 and 37.5 months, respectively. Conclusions: The humanized anti-Lewis Y monoclonal antibody, hu3S193, showed insufficient activity in this cohort. However, we cannot rule out the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression.Trial registration: Clinicaltrials.gov, NCT01370239. Registered 9 June 2011, https://clinicaltrials.gov/ct2/show/NCT01370239
FPR2 Participates in Epithelial Ovarian Cancer (EOC) Progression Through RhoA Mediated M2 Macrophage Polarization: An Invitro Experimental Study
Authors: Xie Xiaohui , He Juan , Liu Yaqiong , Chen Weiwei , Shi Kun
Published: November 2020

Background: In our previous study, we found Formyl peptide receptor 2 (FPR2) promoted the invasion and metastasis of EOC and it could be a prognostic marker for EOC. In this study, we aimed to study the possible mechanism of FPR2 in promoting EOC progression.Methods: The FPR2 ectopic expression and knockdown EOC cell lines as well as their control cell lines were established and the expression change of RhoA in each cell lines was evaluated by RT-qPCR and Western-blot. Wound healing and Transwell assays were performed to detect the migrational ability of EOCs that affected by FPR2 and RhoA. The supernatant of each EOC cell lines were used to co-culture with the macrophages, and tested the M1 and M2 macrophges biomarkers by flow cytometry. THP-1 cell line was also indcued to differentiated to M1 and M2 macrophages, FPR2 and RhoA expression in each macrophage cell lines were detected by RT-qPCR and Western-blot. Results: RhoA expression was significantly increased in EOCs along with the overexpression of FPR2, which showed a positive correlation by Pearson correlation analysis. FPR2 ectopic expression would contribute to the migrational ability of EOCs, and RhoA inhibitor (C3 transferase) would impare EOCs migration. Furthermore, FPR2 stimulated the secretion of Th2 cytokines by EOCs, which induced macrophages differentiate to M2 phenotype, while RhoA inhibitor stimulate the secretion of Th1 cytokines and induce macrophages differentiate to M1 phenotype. Moreover, compared with M1 macrophages and THP-1 cells, FPR2 and RhoA expression were significantly up-regulated in M2 macrophages.Conclusion: FPR2 stimulated M2 macrophage polarization and promote invasion and metastasis of ovarian cancer cells through RhoA.
Geraniin Suppresses the Expression of Cathepsin K in Osteoclasts
Authors: Zhang Xiaochao , Guang Liu , He Bo , Liu Tao , Yang Yuan , Shen Zhiqiang , Chen Peng
Published: November 2020

Background: Cathepsin K (CatK) plays a critical role in osteoclast-induced bone degradation, and it may be a potential therapeutic target for osteoporosis treatment. In our previous experiments, geraniin was reported to have anti-osteoporotic effects against OVX-induced rat osteoporosis and inhibitory effects on bone resorption in vitro. However, it is not known whether geraniin exhibits an inhibitory effect on CatK expression in vitro. Method: In the present study, we investigated the effect of geraniin on the mRNA and protein expression of CatK in the primary osteoclasts isolated from rats. These cells were treated with different concentrations of geraniin, and the mRNA and proteins of CatK were quantified by in situ hybridization assay and immunocytochemical analysis. Results: The results showed that different concentrations of geraniin (10-9 to 10-7 mol/L) significantly decreased the values of integral optical density and mean optical density of CatK mRNA and protein expression in positive cells in a concentration-dependent manner, as determined by in situ hybridization and immunocytochemistry. Moreover, similar results were observed between 10-7 mol/L geraniin and 10-6 mol/L E-64. Conclusion: These results demonstrated that geraniin can decrease the expression of CatK in osteoclasts. It may be a novel and potential CatK inhibitor came from natural plant. As a traditional Chinese herbal medicine, it may be used to treat osteoporosis in addition to its anti-inflammatory effect.
Transdermal Delivery of Rhizoma Coptidis and Evodia Rutaecarpa: The Effects of Enhancers on Permeation Across SD Mouse Skin
Authors: Guan Yu yao , Liu Xue mei , Zheng Lei , Yang Jing , Ren Ji bo , Song Chao , Zhang Xiao li , Zhang Jin qing
Published: November 2020

Background: Oral ulceration is a common, painful condition of uncertain aetiology. Traditional Chinese medicine has good effect. One kind of treatment method is to use rhizoma coptidis, evodia rutaecarpa powder 10g each mixed with vinegar to paste in the foot springs point. The purpose of this study is to convert this prescription into a corresponding preparation for everyone's convenience. Methods: The enhancement effect of a series of different concentrations of fat-soluble azone, water-soluble azone, dimethyl sulfoxides, acetic acid, on the skin permeability of rhizoma coptidis, evodia rutaecarpa powder was studied in vitro by using Franz diffusion cells and SD mouse skin. The concentrations of the main components palmatine hydrochloride, berberine hydrochloride, evodiamine, rutacarpine in the preparation were determined by an HPLC method. Results: The addition of dimethyl sulfoxide, 2-8% w/w water-soluble azone, 8% w/w fat-soluble azone never increased palmatine hydrochloride and berberine hydrochloride flux with respect to the control preparation. The enhancing effects of 45% acetic acid, 1% water-soluble azone and 5% fat-soluble azone were evident on the palmatine hydrochloride and berberine hydrochloride permeability. The target substances evodiamine and rutacarpine were not detected in the receiving solution, and there were residues in the skin, respectively. The amount of evodiamine and rutacarpine residued in the skin obtained from formulations including 45% w/w acetic acid or 5% w/w fat-soluble azone were significantly higher (p<0.05) than that obtained from the blank control formulation. Conclusions: The experimental results revealed that 5% fat-soluble azone transdermal agent has the optimal performance in the rhizoma coptidis, evodia rutaecarpa preparation.
Mapping the FACT-G to EQ-5D Utility Index in Cancer: Data From a Cross-sectional Study in China
Authors: He ZhiKui , Yang Li , Liang WenJie , Xu WenJia , Huang WenXiu , Wang XiaoMin , Huang KaiYong
Published: November 2020

ObjectiveThis study aimed to develop a function for mapping the cancer-specific instrument (FACT–G) to a preference-based measure (EQ-5D-3L) utility index for HRQoL, in which the utility scores were generated using the Chinese value set.MethodThe data are based on a cross-sectional survey of 243 patients in China with different cancer types. Cancer patients who completed the EQ-5D-3 L and the FACT-G questionnaire, and patient demographics and clinical characteristics were included in this study. Regression models were used to predict the EQ-5D-3L utility index values based on four subscale scores of the FACT-G using the ordinary least squares (OLS) model, generalized linear models (GLM), censored least absolute deviations (CLAD), Tobit model, and two-part model (TPM) regression approaches. The performance and predictive power of each model were also evaluated using r2 and adj- r2, mean absolute error (MAE) and root mean squared error (RMSE).ResultsThe introduction of the square term and the interaction term improves the accuracy of the model. The social well-being subscale of the FACT-G was not associated with the EQ-5D-3L utility index, whereas, the physical, emotional, functional well-being, and FACT-G total scores were derived when mapping the FACT-G to the EQ-5D-3L utility index. For the FACT-G, the OLS model was the best at predicting mean EQ-5D-3L values among all the regression models and has 70% explanatory power for the observed EQ-5D-3L variation. Nevertheless, the OLS model overpredicted utilities for poorer health states and underestimated utilities for those with better health. The result of the OLS model, GLM, and CLAD models were similar to the MAE, MSE, and RMSE.ConclusionThe algorithm based on Chinese population development for mapping the FACT-G into the EQ-5D-3L utility index can be realized. We also recommend that OLS models be used to assess the economic evaluation of patients' health-related quality of life when the population is in moderate to good health for further cost-utility analysis in China.
Some aspects of the process development forecast
the spread of COVID 19 infection.
Authors: Kotelnikov Valeri , Krasilnikov Michail , Ryazanova Elena , Chysyma Rosa
Published: November 2020

The world community is experiencing a pandemic of the COVID-19 virus and is looking for ways to solve the problems that have arisen due the spread of a new infection. The Tuvinian Institute for the Exploration of Natural Resources of the SB RAS does not stand aside from important work to combat the spread of the virus. We tried to analyze the available data for the Republic of Tuva, Russia and the world. In this work, we used data from the sites of stopcoronavirus.rf, worldometers.info, Yandex.com and others. For successful control of SARS-CoV-2, it is important to take preventive measures as early as possible and prepare medical institutions to combat the spread of the virus, which can be ensured by analyzing the previous development of the process and building a model for planning. The analysis is carried out using the mathematical apparatus of the normal distribution (Gauss), which, in our opinion, most closely describes the laws of the process.
Genome wide identification, characterization and expression profiles of heavy metal ATPase3 (HMA3) in plants
Authors: Kabir Ahmad , Das Urmi , Haque AFM , Dutta Amit , Gohari Gholamreza , Reza Md
Published: November 2020

HMA (heavy metal associated) is a member of the ATPases protein family involved in metal transport in plants. This study characterizes several HMA3 homologs and infers their molecular functions in different plant species. Arabidopsis AtHMA3 (AT4G30120) was used as a reference to retrieve 11 HMA3 homologs having 97-100% query cover, 535-542 residues, 56983 to 58642 (Da) molecular weight, and 5.74 to 8.16 pI value, 29.10 to 33.89 instability index, and 0.222 to 0.380 grand average of hydropathicity. Topological analyses showed 4 transmembrane domains in these HMA3 homologs positioned similarly in terms of cytoplasmic and non-cytoplasmic regions along with ~22-28% 𝛼-helices, ~22-28% extended strands, and ~50% random coils. HMA3 protein of Arabidopsis lyrata subsp. lyrata and Eutrema salsugineum are located at chromosome 2, while others are positioned at chromosome 4. All these HMA3 homologs are localized in the plasma membrane sharing a few common biological and molecular functions. Besides, these HMA3 genes contain 8-9 exons in which promoter positions are varied among the homologs. The cis-acting elements of HMA3 genes were projected to be involved with stress response, anaerobic induction, and light responsive regulation in plants. Three out of five motifs encode E1-E2_ATPase involved in proton-pumping in the plasma membrane. The Arabidopsis thaliana HMA3 protein clustered with Camelina sativa and Capsella rubella show a close phylogenetic relationship. Also, AtHMA3 exhibits a close association with AtHMA3 with MTPA2, ZAT, NRAMP3, IRT2, and NRAMP2 under the local network of AtHMA3 linked to metal transport. Further, AtHMA3 is most potentially expressed during senescence, germinating seed, seedlings, young rosette, bolting, and young flower. In addition, AtHMA3 showed a significant upregulation (>6.0 fold) under Fe-deficiency. These findings may provide essential background to perform wet-lab experiments to understand the role of HMA3 in metal homeostasis.
A Decomposition of Differences in Concentration Indices: With an Application to Socio-economic Inequality in Over-nutrition in India
Authors: Aizawa Toshiaki
Published: November 2020

Background: This paper proposes a new semi-parametric method to decompose the differences between two concentration indices. Statistical property of copulas is used to model dependence between health and socioeconomic status. The proposed methods are applied to differences in socio-economic inequality in over-nutrition between rural and urban areas in India, along with existing decomposition Methods: Taking advantage of the statistical property of copulas, we first decompose the observed differences into the part which is due to the differences in the dependence structures (the dependence effect) and the other part due to the differences in the marginal distributions of health (the health effect). Next, we decompose both effects further into parts explained by differences in the covariates in the model and the part that cannot be explained by them.﻿Results: The results show that the difference in the proportion of Hindus and the proportion of households that use safe cooking fuel contribute the most to the observed differences. Conclusions: Comparison among different approaches suggests that the identifying assumptions play substantial roles in the decomposition analysis.
Interaction of Sex, Age, Body Mass Index and Race on Hypertension Prevalence in the American Population: A Cross-sectional Study
Authors: Zhang Zhenhong , Wang Qiuzhen , Zhang Tao , Zhao Enhui , Ding Shihan , Kang Xiao , Zhang Wenwen , Liu Bingkun , Liu Haoran , Cheng Anlan , Li Guoju
Published: November 2020

Background: Hypertension is a major risk factor for many chronic diseases and mortality. We carried out this study aimed to investigate the possible effects of the interaction of sex, age, BMI and race on the prevalence of hypertension. Methods: By using the data of a sample-adjusted 2656 women and 2515 men in the American National Health and Nutrition Examination Survey 2015-2016, we analyzed the interaction of sex, age, BMI and race by logistic regression. Hypertension was defined as an SBP ≥130 mmHg or DBP ≥80 mmHg or taking anti-hypertensive medication. Results: Totally, there were 2776 (53.68%) hypertensive patients. Interactions were found between sex and age, BMI and age, race and age. The adjusted odds ratio (aOR) for age 60-80 (aOR 19.26 [95% CI 14.14–26.23]) and 40 to 59 (4.56 [3.54–5.88]) were signiﬁcantly higher than the reference group (age 20 to 39) in women, and also in men (6.44 [4.80–8.63]) and (2.84[2.23–3.61]), respectively. And this risk trend was consistent in the BMI group and the race group. Conclusion: Association between obesity and the risk of hypertension varies according to the age and race of the population and age had a stronger effect on hypertension in women than in men. Differences in age and race should be considered when providing corresponding antihypertensive measures. Although the exact mechanism of hypertension remains to be further studied, these findings suggested that early prevention and intervention measures can effectively reduce the risk of hypertension, especially in women.
WITHDRAWN: Reuse of Waste Materials as Precursors of Activated Carbon Synthesis for the Abatement of Antibiotic Cefpodoxime Proxetil from Industrial Effluents.
Authors: Manzoor Suryyia , Abbas Naseem , Fernandez Javier , Mirza Amir , Yasmin Ghazala , Khan Muhammad Imran , Rao Zunaira , Rizwan Muhammad , Waqar Muhammad , Majeed Abdul
Published: November 2020

The release of antibiotics to aquatic environment creates aquatic ecotoxicity and their bioaccumulation results in antibiotic resistance. Hence to lessen the risk of ecotoxicity and depletion of natural resources, it is imperative to disclose alternate precursor raw materials that can be successfully employed for the synthesis of new sorbents capable to remove antibiotics from the environment. This research reports the synthesis of activated carbon based sorbents derived from waste biomaterials like coconut shell (CNAC), walnut shell & peach stone (WNAC) and Bombax ceiba fruit capsule (BCAC) and their ability to remove antibiotic Cefpodoxime from the industrial effluents. Activation of carbon was done by HNO3 and H3PO4. FTIR, BET and SEM techniques were used for characterization of sorbents. Langmuir and Freundlich isotherm models were applied to study the adsorption behavior. Moreover, the experimental adsorption capacity (qe) of the three activated carbons was found to be 32 mg/g for CNAC, 40 mg/g for WNAC and 10 mg/g for BCAC. The maximum removal efficiency of the drug was found to be 96% using the WNAC. HPLC analysis was performed to confirm the removal of Cefpodoxime from industrial effluent.
miR-141 and miR-200a are involved in Th17 cell differentiation by negatively regulating RARB expression
Authors: Bahmani Leila , Baghi Masoud , Peymani Maryam , Javeri Arash , Ghaedi Kamran
Published: November 2020

Background: Among T helper (Th) lineages differentiated from naïve CD4+ T cells, interleukin (IL)-17-producing Th17 cells are highly correlated with the pathogenesis of autoimmune disorders. Although a series of microRNAs (miRs) that modulate autoimmunity progress have been reported, further studies on microRNAs particularly involved in Th17 lineage commitment are still warranted. Results: In this study, to clarify the involvement of miR-141-3p and miR-200a-3p in Th17 cell differentiation, as well as to explore their potential target gene involved, purified human naïve CD4+ T cells were cultured under Th17 cell polarizing condition. Differentiation process was confirmed applying ELISA method to measure IL-17 secretion and RT-qPCR to assess Th17 cell-defining genes expression during differentiation period. miR-141 and miR-200a expression pattern as well as expression alteration of their predicted downstream genes, which were identified via consensus and integration in-silico approach, was then evaluated by RT-qPCR. Finally direct interaction between both microRNAs and their common predicted target sequence was approved by dual-luciferase reporter assay. Highly increased IL-17 secretion and Th17 lineage-specific genes expression confirmed Th17 cell differentiation. Conclusions: Results demonstrated that miR-141 and miR-200a were Th17 cell-associated microRNAs and their expression levels upregulated significantly during Th17 cell induction. We also found that retinoic acid receptor beta (RARB) gene, whose product has been reported as a negative regulator of Th17 cell generation, was a direct target of both microRNAs and its downregulation could affect the transcriptional level of JAK/STAT pathway genes. Overall, our results introduced two novel Th17 lineage-associated microRNAs and provided a rationale to further clarify the RARB-dependent mechanism of miR-141 and miR-200a to promote Th17 cell differentiation and hence Th17-mediated autoimmunity.
The Lipid-related Effects of Resveratrol on Human Ectopic Endometrial Stromal Cells and a Rat Model of Endometriosis
Authors: Chen Zhengyun , Wang Chunyan , Lin Cuicui , Zhang Lifeng , Zheng Huimei , Zhou Yong , Li Xiaoyong , Li Chen , Zhang Xinmei , Yang Xiaohang , Guan Minxin , Xi Yongmei
Published: November 2020

Background: Endometriosis is a complex disease in the field of gynecology that has certain limitations for its interim treatment. Resveratrol has been recently used for the treatment of endometriosis in experimental and clinical studies, but its molecular mechanism remaines elusive. Results: In this study, based on a case-control study, we identified that a decreased BMI and altered lipid profiles were associated with endometriosis patients. We applied resveratrol treatment on human ectopic endometrial stromal cells (HEcESCs) and a rat model of endometriosis. Lipidomics analysis showed that resveratrol altered lipid profiles in HEcESCs, with the sphingolipids Cer and SM increased significantly, while FA and most phospholipids were significantly reduced. Pathway enrichment analysis showed that several lipid-associated signaling pathways could be targeted by resveratrol. Our experiments in a rat model showed that resveratrol reduced the lesion and rectified lipid profiles in rats with endometriosis. In addition, resveratrol treatment significantly increased the expression of PPARα in lesion tissues of model rats and HEcESCs of EMs patients.Conclusion: Our data reveal that the development of EMs is closely related to lipid metabolism, and resveratrol may play a therapeutic role by targeting the lipid metabolism of ectopic endometrial stromal cells in endometrosis. Our study provides valuable insights for understanding the pathogenesis and clinical treatment of endometriosis.
The Prevalence and Characteristic of Sleep Problems among Children with Fetal Alcohol Spectrum Disorders (FASD).
Authors: Dyląg Katarzyna Anna , Bańdo Bożena , Baran Zbigniew , Dumnicka Paulina , Kowalska Katarzyna , Kułaga Paulina , Przybyszewska Katarzyna , Radliński Jakub , Roozen Sylvia , Curfs Leopold
Published: November 2020

BackgroundFetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate the prevalence and characterize sleep problems among individuals with FASD.Methods40 patients from FASD diagnostic center (median age 8 years (6; 11)) diagnosed with one of the FASD diagnosis and 40 patients from the control group (median age 10 years (8; 13)) participated in the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those who scored above 41 points were qualified to the 2nd phase of the study in which in-lab attended polysomnography (PSG) was performed. The measurements consisted of electroencephalographic channels, left and right electrooculograms, chin electromyogram, left and right tibialis electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position.ResultsThe number of participants with sleep disturbances was markedly higher in the study group as compared to controls (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54-12.11; p=0.005) for FASD patients as compared to the control group. Significant differences between the study and control groups were observed in the following subscales: sleep onset delay, night wakings , parasomnias , sleep disordered breathing, and daytime sleepiness. In PSG children from the FASD group and children from the control group experienced more arousals during the sleep than the children from the laboratory control group. ). There were no significant differences in comparison of respiratory indexes between FASD and control groups although indices in both groups were higher than previously published data for a normal population.ConclusionSleep disorders are more common among individuals with FASD than among healthy children. As distorted sleep can affect daily performance and worsen neurodevelopmental issues, it is vital for the pediatricians and other FASD specialists to include the question about sleep in the anamnesis.
Unusual presentation of a medulloblastoma mimicking an AARS (Atlanto axial rotatory subluxation). A case report.
Authors: Greggi Tiziana , Boriani Luca , Scarale Antonio , Martikos Konstantinos , Vommaro Francesco , Leggi Lucrezia , Ciani Giovanni , Battaglia Milva , Ghizzi Chiara , Zucchelli Mino
Published: November 2020

Background: Atlanto-Axial Rotatory Subluxation is an acquired condition, usually occurring in pediatric patients, because of either trauma or pharyngitis or ear-nose-throat ( ENT) surgery or upper respiratory tract infection. Post-traumatic C1-C2 rotational subluxation in pediatric age is a very frequent event. It mimics benign torticollis but may result in permanent disability. The atlanto-axial rotatory displacement, as defined initially by Fielding and Hawkins in 1977, is classified into four types: Type 1 is the most common form in children. It is a simple rotatory displacement without an anterior shift. Type 2 is potentially more dangerous. It is a rotatory displacement with an anterior shift of 5 mm or less. Type 3 is rotatory displacement with an anterior shift greater than 5 mm. Finally, type 4 is rotatory displacement with a posterior shift. Type 3 and 4 deformities are rare, but neurological involvement or even instant death may follow [Fig. 4] (18). The condition requires prompt diagnosis by thorough examination to avoid any treatment delays. The difficulties for a timely and correct diagnosis and then the correct treatment are described. Case presentation: A 5 year old girl comes to the emergency room with cervical pain and stiffness.This painful state, as mum reports, has been lasted for about ten days, after a mild trauma. The radiographic picture demonstrates a rotary subluxation C1-C2, type 1 according to Fielding and Hawkins classificationThe treatment is head-halter traction with 2kg, and nonsteroidal anti-inflammatory drugs (NSAIDs) . After 2 days the x-ray picture improves, but the painful symptoms persist. An in-depth diagnostic MRI of the cervical spine and brain revealed a medulloblastoma which made an immediate and effective neurosurgical intervention necessary. Conclusions: the C1-C2 rotatory dislocation must always be evaluated with extreme care, without neglecting any clinical and anamnestic information for a correct and timely differential diagnosis. Remember that children show very clearly what they feel, always .
Developing A New One-Dimensional Scale To Measure Pain in Children: Pencil Pain Scale
Authors: BEYAZ Emine , TÜFEKCİ Fatma GÜDÜCÜ
Published: November 2020

Background: The aim of this study was to develop the Pencil Pain Scale as a new one-dimensional scale for evaluating pain in school-age children (6-12 years old).Methods: The population of this study is composed of 6-12 year-old children who gave blood for examination rather than for an acute or severe cause. The research sample included randomly selected children (N= 464) who applied to the blood collection units of a state hospital between November 2017 - February 2018, on three days of the week (Monday, Wednesday, Friday).A questionnaire that specifies the characteristics of children, the newly developed Pencil Pain Scale, and the two widely used scales (Visual Analogue Scale and the Facial Expressions Rating Scale) were used to collect data. The data obtained were analyzed with percentage distributions, mean, chi-square, t-test, ANOVA, Kruskal Wallis, Mann Whitney U test and correlation. Ethical principles were followed in the study.Results: According to expert opinions, it was determined that the Pencil Pain Scale had content validity (Content Validity Index= +1.00). It was found that the scale made measurements similar to a previously conducted study and had convergent validity. Also, the scale was found to be sensitive enough to distinguish the differences and to be reliable (p<.001). It was also found that the Pencil Pain Scale performs measurements that are in agreement with the Visual Analog Scale and the Facial Expression Rating Scale and has parallel form reliability (p>.05). The Pencil Pain Scale was developed in a valid and reliable way. Conclusion: The Pencil Pain Scale is a valid and reliable scale. In order to make the Pencil Pain Scale a standard scale for measuring children's pain, it needs to be used in different studies and age groups with different scales for different pain types.
Therapeutic monitoring of the host-bacterium-phage interaction in a child
Authors: Khatami Ameneh , Lin Ruby , Petrovic-Fabijan Aleksandra , Alkalay-Oren Sivan , Almuzam Sulaiman , Britton Philip , Brownstein Michael , Dao Quang , Fackler Joseph , Hazan Ronen , Horne Bri’Anna , Nir-Paz Ran , Iredell Jonathan
Published: November 2020

Successful phage therapy for extensive chronic osteoarticular infection in a child resulted in an initial flush of bacterial contents into the bloodstream with an inflammatory response marked by fever, local pain and upregulation of genes associated with autophagy and innate immunity. Monitoring of phage and bacterial kinetics and the human host response allowed early dose adjustment and indicated a strong therapeutic effect within two weeks.
Metabolic profiling of neocortical tissue discriminates Alzheimer’s disease from mild cognitive impairment, high pathology controls, and normal controls
Authors: Jasbi Paniz , Shi Xiaojian , Chu Ping , Elliott Natalie , Hudson Haley , Jones Douglas , Serrano Geidy , Beach Thomas , Liu Li , Jentarra Garilyn , Gu Haiwei
Published: November 2020

Background

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for an estimated 60 to 80% of cases, and is the sixth-leading cause of death in the United States. While considerable advancements have been made in the clinical care of AD, it remains a complicated disorder that can be difficult to identify definitively in its earliest stages. Recently, mass spectrometry (MS)-based metabolomics has shown significant potential for elucidation of disease mechanisms and identification of therapeutic targets as well diagnostic and prognostic markers that may be useful in resolving some of the difficulties affecting clinical AD studies, such as effective stratification.
Methods

In this study, complementary gas chromatography- and liquid chromatography-MS platforms were used to detect and monitor 2,080 metabolites and features in 48 post-mortem tissue samples harvested from the superior frontal gyrus of male and female subjects. Samples were taken from four groups: 12 normal control (NC) patients, 12 cognitively normal subjects characterized as high pathology controls (HPC), 12 subjects with non-specific mild cognitive impairment (MCI), and 12 subjects with AD.
Results

Multivariate statistics informed the construction and cross-validation (p < 0.01) of partial least squares-discriminant analysis (PLS-DA) models defined by a 9-metabolite panel of disease markers (lauric acid, stearic acid, myristic acid, palmitic acid, palmitoleic acid, and four unidentified mass spectral features). Receiver operating characteristic analysis showed high predictive accuracy of the resulting PLS-DA models for discrimination of NC (97%), HPC (92%), MCI (~ 96%), and AD (~ 96%) groups. Pathway analysis revealed significant disturbances in lysine degradation, fatty acid metabolism, and the degradation of branched-chain amino acids. Network analysis showed significant enrichment of 11 enzymes, predominantly within the mitochondria.
Conclusions

The results expand basic knowledge of the metabolome related to AD and reveal pathways that can be targeted therapeutically. This study also provides a promising basis for the development of larger multi-site projects to validate these candidate markers in readily available biospecimens such as blood to enable the effective screening, rapid diagnosis, accurate surveillance, and therapeutic monitoring of AD.
Plasma Metabolomic Profiles and Clinical Features in Recovered COVID-19 Patients Without Previous Underlying Diseases 3 Months After Discharge
Authors: Wang Sufei , Xu Juanjuan , Luo Ping , Yang Lian , Song Siwei , Tan Xueyun , Chen Qing , Xia Hui , Zhang Shujing , Ma Pei , Ma Yanling , Yang Fan , Liu Yu , Li Yumei , Ma Guanzhou , Wang Zhihui , Duan Yanran , Jin Yang
Published: November 2020

Knowing the residual and future effect of SARS-CoV-2 on recovered COVID-19 patients is critical for optimized long-term patient management. Recent studies focus on the symptoms and clinical indices of recovered patients, but the pathophysiological change is still unclear. To address this question, we examined the metabolomic profiles of recovered asymptomatic (RA), moderate (RM) and severe and critical (RC) patients without previous underlying diseases discharged from the hospital for 3 months, along with laboratory and CT findings. We found that the serum metabolic profiles in recovered COVID-19 patients still conspicuously differed from that in healthy control (HC), especially in the RM, and RC patients. Additionally, these changes bore close relationship with the function of pulmonary, renal, hepatic, microbial and energetic metabolism and inflammation. These findings suggested that RM and RC patients sustained multi-organ and multi-system damage and these patients should be followed up on regular basis for possible organ and system damage.
Hyperbaric Oxygen Enhanced Mitochondria-Targeted Chemotherapy in Bladder Cancer
Authors: Shen Chongxing , Yue Xiaofeng , Dai Linyong , Wang Jianwu , Li Jinjin , Fang Qiang , Zhi Yi , Shi Chunmeng , Li weibing
Published: November 2020

Background: Bladder cancer has a high rate of recurrence and drug resistance due to a lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types. In the study, we aimed to investigate the anti-tumor effect of IR-780 combined with hyperbaric oxygen (HBO) on bladder cancer.Methods: Using in vitro cell line data, in vivo model data and clinical data, we tested the ability of IR-780 to selectively accumulate in bladder cancer. We also evaluated the anti-tumor effect of IR-780 combined or not with HBO both in vitro and in vivo, and explored the potential mechanism of its anti-tumor effect. Results: We revealed for the first time that IR-780 selectively accumulated in bladder cancer (bladder cancer cells, xenografts and bladder cancer samples from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. Further study displayed that the combination with HBO could significantly enhance the antitumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial reactive oxygen species (ROS) production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusions: These data identify for the first time a combination of IR-780 and HBO (IR-780+HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.
OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling
Authors: Ma Shize , Duan Lei , Dong Huateng , Ma Xiaodong , Guo Xinyu , Liu Jianli , Li Guoqiang , Yu Yue , Xu Yanlong , Yuan Guoqiang , Zhao Xingkun , Tian Guopeng , Zhai Shijia , Pan Yawen , Zhang Yinian
Published: November 2020

Background: Glioma is a highly heterogeneous and lethal tumor with extremely poor prognosis. Through analysis of TCGA data, we found that OLFML2A was significantly upregulated in glioma tissues and positively correlated with glioma grade and worse prognosis. However, the molecular function of OLFML2A and its underlying mechanism in glioma remain unclear.Methods: The expression of OLFML2A in glioma was determined by immunohistochemistry (IHC). Celigo assay, MTT assay and flow cytometry were utilized to evaluate the effects of OLFML2A on glioma proliferation and apoptosis. Gene chip microarray analysis and ingenuity pathway analysis were used to investigate the potential regulatory mechanisms of OLFML2A, which were further assessed by q-PCR, western blotting and IHC. An animal transplanting glioma model and spectral computed tomography scan were used to verify OLFML2A expression in vivo.Results: In this study, we found that the expression of OLFML2A was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan-Meier survival analysis of TCGA data revealed that glioma patients with higher expression of OLFML2A had shorter overall survival. Importantly, when we knocked down the expression of OLFML2A in glioma cells, cell proliferation was inhibited, and apoptosis was promoted. Mechanistically, downregulation of OLFML2A inhibited Wnt/β-catenin signaling by directly reducing the level of stabilized β-catenin and upregulating the expression of amyloid precursor protein (APP) to indirectly suppress β-catenin, leading to repression of MYC, CD44 and CSKN2A2 expression. Furthermore, we found that OLFML2A downregulation clearly suppressed the growth of subcutaneous glioma and intracranial transplantation of glioma by inhibiting Wnt/β-catenin pathway-dependent cell proliferation.Conclusion: Our data indicate the oncogenic effect of OLFML2A in glioma through regulation of Wnt/β-catenin signaling, which may provide a novel therapeutic target for glioma.
Occurrence of Mutidrug Resistant Escherichia Coli in Raw Meat and Cloaca Swabs in Poultry Processed in Slaughter Slabs in Dar Es Salaam, Tanzania
Authors: Mgaya Fauster X , Matee Mecky I , Muhairwa Amandus P , Hoza Abubakar S
Published: November 2020

Background Increased prevalence of multiple drug resistant Escherichia coli in chicken meat indicates excessive use of antimicrobials in poultry production systems. We determined the occurrence of multiple drug resistant E. coli in raw meat and cloaca swabs in poultry processed in slaughter slabs in Dar es Salaam, Tanzania.Methods This cross-sectional study was conducted between January and June 2020, in five large slaughter poultry slabs in Dar Es Salaam, Tanzania. Purposive sampling was used to select broilers and spent layers, from which meat and cloaca swabs were collected. MacConkey agar was used to isolate E. coli and identification was done using API 20E. Kirby Bauer disc diffusion technique was used in antimicrobial susceptibility testing and results were interpreted as per CLSI (2018) guidelines. EBSL (CTX- M) and plasmid mediated quinolone genes (qnr A, qnr B, qnr S and aac(6')-Ib-cr) were detected using PCR. Results Out of the 384 samples, 212 (55.2%) were positive for E. coli, of which 147(69.3%) were resistant to multiple drugs (MDR). Isolates were very highly resistant to tetracycline (91.9%), followed by sulfamethoxazole-trimethoprim (80.5%), ampicillin (70.9%), and moderately resistant to ciprofloxacin (40.2%) and 25% cefotaxime (CTX), but had low resistance to 10.8% gentamycin (CN) and 8.6% imipenem (IMP) (95% CI, P< 0.01). Ten (10/212) (4.7%) isolates were confirmed as extended spectrum beta lactamase (ESBL) producing E. coli, and were all MDR. The MDR E coli strains were highly resistant to cefotaxime (100%), ampicillin (90%) and moderately resistant to tetracycline (40%) and sulfamethoxazole-trimethoprim (40%) and ciprofloxacin, lowly resistant to imipenem (10%) but fully susceptible to gentamycin. Quinolones resistant genes were seen in 8 out of the 10 ESBL producers.Conclusion The high levels of resistance to the commonly used antibiotics in poultry production means these agents are ineffective, add unnecessary cost to farmers and facilitate emergence and spread of resistance. The uncontrolled disposal of waste, seen in all the poultry slabs, has the potential to contaminate the environment with MDR bacteria, with eventual spread to humans and animals and demands intensified surveillance. Advocacy for prudent use of antimicrobials cannot be underscored in poultry production systems, in Tanzania.
An Comprehensive Index (CIB) with Combination of Consistency in both Case Control and Cohort Study to Determine the Efficacy of a Biomarker
Authors: Hui Liu
Published: November 2020

Background: This study aimed to describe biomarkers using the comprehensive index of biomarker (CIB) based on consistency rate in both case control (Youden index, Yen) and cohort study (Crc) to determine the efficacy of a biomarker. Methods: The CIB is the geometric mean of Yen and Crc. The simulated data were generated to observe CIB features of sensitivity, specificity, and receiver operating characteristic (ROC) analysis for biomarkersResults: CIB was found to be related to the CRC values ROC analysis. The higher Spe could indicate better diagnostic power and the higher Sen could indicate better joint action for biomarkers with the same Yen. Although Yen is the common index used to evaluate the effectiveness of a biomarker, unfortunately, the Yen value was significantly larger than CIB value under the moderate Spe, showing overestimation.Conclusion: The CIB with combination of consistency in both case control and cohort study could be more reasonable. The CIB could provide a better understanding of the power of a biomarker and would be better at evaluating biomarkers from new systems or concepts.
Spatiotemporal Regulation of Circular RNA Expression During Ningxiang Pig Skeletal Muscle, Subcutaneous Fat, and Liver Development
Authors: Li Biao , Gong Yan , Zhang Yuebo , Kim Kyung Seok , Xiao Yu , Zeng Qinghua , Xu Kang , Duan Yehui , He Jianhua , Ma Haiming , He Jun
Published: November 2020

Background: In recent years, thousands of different circular RNA (circRNAs) have been discovered by comparative analysis of different pig breeds. However, very few studies have been conducted on the spatiotemporal expression pattern of circRNA during organ development which is crucial for functional and evolutionary analysis.Results: Here, we systematically analyzed circRNAs associated with fatty acid metabolism in the three main organs (muscle, fat and liver) for four growth time points (30d, 90d, 150d and 210d after birth) of Ningxiang pigs, a famous native pig breeds in China, known for its excellent meat quality. We identified 61,683 circRNAs and analyzed their molecular characteristics, potential functions, and interaction with miRNA. The circRNAs showed striking spatiotemporal specificity in the form of dynamic expression. At 90d, the number and complexity of differentially expressed circRNAs in the liver is the most obvious. We used STEM (Short Time Series Expression Miner) to perform time series analysis on differentially expressed circRNAs, and found that there are multiple model spectra that are significantly enriched with time changes in all the three organs. All the significantly changed circRNAs, miRNAs and mRNAs obtained from STEM analysis of each tissue were used to confirm that the circRNA and mRNA have a targeting relationship with miRNA. It is worth noting that we screened out 2384 (fat), 2672 (muscle) and 9187 (liver) circRNAs-miRNA-mRNA network pairs related to developmental time changes. Finally, we used fluorescence in situ hybridization（FISH）to show the dynamic subcellular localization of circRNA during development.Conclusion: To a certain extent, these data indicate that circRNA is highly abundant in muscle, fat and liver, and is dynamically expressed in a spatiotemporal manner. These results suggest that circRNAs play an important role in fat metabolism of Ningxiang pigs. Our findings also provide new ideas and perspectives for the study of Ningxiang pigs' lipid metabolism regulation pathway and meat quality traits.
Accuracy of Imputation of Microsatellite Markers from an SNP50K Chip in Spanish Assaf Sheep
Authors: Marina Hector , Suarez-Vega Aroa , Pelayo Rocio , Gutierrez-Gil Beatriz , Reverter Antonio , Esteban-Blanco Cristina , Arranz Juan-Jose
Published: November 2020

Background: Traditional and new genotyping technologies must be combined by applying bridge methodologies that avoid double genotyping costs. This study aims to identify and evaluate a reliable approach to precisely impute microsatellite markers from SNP-chip panels to perform parental verifications in sheep. Moreover, we will assess the optimum number of SNPs necessary to accurately impute microsatellite markers to develop a low-density SNP chip for parentage verification in the Assaf sheep breed.Results: A total of 4,423 animals belonging to the Spanish Assaf sheep breed were genotyped for 19 microsatellites and an ovine custom 49,897 SNP array. The accuracy of microsatellite marker imputation, performed with BEAGLE v5.1 software, was assessed with three metrics, namely, genotype concordance (C), genotype dosage (length r2), and allelic dosage (allelic r2), for all imputation scenarios tested (0.5-10 Mb microsatellite flanking SNP windows). The accuracy of our imputation results for the three metrics analyzed for all haplotype lengths tested was higher than 0.90 (C), 0.80 (length r2), and 0.75 (allelic r2). Considering that the objective of the study was to assess a SNP window length that provides the best accuracy for the microsatellite imputation procedure to design an affordable low-density SNP chip for parentage testing, we considered 2 Mb to be the best SNP haplotype length for further analyses (SNPs/window =74.05, C= 0.970; length r2= 0.952, allelic r2=0.899). We additionally evaluated imputation performance under two null models, naive and random, which showed weak genotype concordance averages in comparison with imputed microsatellites (0.41 and 0.15, respectively).Conclusions: We presented for the first time a precise methodology in dairy sheep to impute multiallelic microsatellite genotypes from biallelic SNP markers. The use of a 2 Mb SNP flanking window for each microsatellite has been shown to achieve high accuracy in the imputation procedure while providing a low-density SNP chip that could be cost-effective. The results from this study will undoubtedly have a significant impact on sheep breeders overcoming the problem of parentage verification when different genotyping platforms have been used across generations.