bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting T cell Metabolism to Combat Autoimmunity: Implications for the Future of Type 1 Diabetes Therapeutics
Authors: Martins Christina P. , Piganelli Jon D.
Published: February 2020

Advances in the field of immunometabolism have indicated that cellular metabolic programs control T cell differentiation and effector functions. As CD4+ T cells are significant contributors to destruction of the insulin-secreting β cell in Type 1 Diabetes (T1D), strategies to limit autoreactive T cell activation and promote durable tolerance have been explored in an effort to prevent or delay disease onset. Interestingly, substantial evidence indicates that autoreactive T cells are at a heightened activation status associated with dysregulation of metabolic pathways, with distinct nutrient preferences and needs of their own. While largely unexplored in T1D, specific metabolic pathways have been exploited to correct known defects in several autoimmune diseases including but not limited to Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), and Rheumatoid Arthritis (RA). These therapeutic strategies have been focused on targeting glycolysis, which is the major pathway used by activated T cells as it is required for acquisition of effector functions. Use of glycolysis inhibitors such as 2-Deoxy-d-glucose (2-DG), have shown impressive success in limiting T cell mediated damage that could prevent or reverse onset of autoimmunity. More importantly, while specificity has been a major hurdle for use of immunotherapies, regulating immunity by targeting metabolism resulted in selective targeting of autoreactive T cells while leaving global immune function intact, a phenomenon commonly referred to as “cellular selectivity based on demand”. This review will outline examples of metabolic regulation success in autoimmunity and provide evidence to support use of these inhibitors in T1D, where new therapeutic strategies are desperately needed.
The Correlation between Rotational Gravity and Magnetic Field of Celestial Body
Authors: Gu Ying-Qiu
Published: February 2020

The magnetic field of the earth plays an important role in the ecosystem, and the magnetic field of celestial bodies is also important in the formation of cosmic large-scale structures, but the origin and evolution of the celestial magnetic field is still an unresolved mystery. Many hypotheses to explain the origin have been proposed, but there are some insurmountable difficulties for each one. At present, the theory widely accepted in scientific society is the dynamo model, it says that, the movement of magnetofluid inside celestial bodies, which can overcome the Ohmic dissipative effect and generate persistent weak electric current and macroscopic magnetic field. However, this model needs an initial seed magnetic field, and the true values of many physical parameters inside the celestial body are difficult to obtain, and there is no stable solution to the large range of fluid motion. These are all difficulties for the dynamo model. Furthermore, it is difficult for the dynamo to explain the correlation between the dipole magnetic field and angular momentum of a celestial body. In this paper, by calculating the interaction between spin of particles and gravity of celestial body according to Clifford algebra, we find that a rotational celestial body provides a field $\Omega^\alpha$ for spins, which is similar to the magnetic field of a dipole, and the spins of charged particles within the celestial body are arranged along the flux line of $\Omega^\alpha$, then a macroscopic magnetic field is induced. The calculation shows that the strength of $\Omega^\alpha$ is proportional to the angular momentum of the celestial body, which explains the correlation between the magnetic intensity and angular momentum. The results of this paper suggest that further study of the effects of internal variables such as density, velocity, pressure and temperature of a celestial body on $\Omega^\alpha$ may provide some new insights into the origin and evolution of celestial magnetic field.
Comparison of the Level and Mechanisms of Toxicity of Carbon Nanotubes, Carbon Nanofibers, and Silicon Nanotubes in Bioassay with Four Marine Microalgae
Authors: Pikula Konstantin , Chaika Vladimir , Zakharenko Alexander , Markina Zhanna , Vedyagin Aleksey A. , Kuznetsov Vladimir L. , Gusev Alexander , Park Soojin , Golokhvast Kirill
Published: February 2020

Nanoparticles (NPs) have various applications in medicine, cosmetics, optics, catalysis, environmental purification, and other areas nowadays. With an increasing annual production of NPs, the risks of their harmful influence to the environment and human health is rising. Currently, our knowledge about the mechanisms of interaction between NPs and living organisms is limited. Additionally, poor understanding of how physical and chemical characteristic and different conditions influence the toxicity of NPs restrict our attempts to develop the standards and regulations which might allow us to maintain the safe living conditions. The marine species and their habitat environment are under continuous stress due to anthropogenic activities which result in the appearance of NPs in the aquatic environment. Our study aimed to evaluate and compare biochemical effects caused by the influence of different types of carbon nanotubes, carbon nanofibers, and silica nanotubes on four marine microalgae species. We have evaluated the changes in growth-rate, esterase activity, membrane polarization, and size changes of microalgae cells using flow cytometry method. Our results demonstrated that toxic effects caused by the carbon nanotubes strongly correlated with the content of heavy metal impurities in the NPs. More hydrophobic carbon NPs with less ordered structure had a higher impact on the red microalgae P. purpureum because of higher adherence between the particles and mucous covering of the algae; silica NPs caused significant inhibition of microalgae growth-rate predominantly produced by mechanical influence.
Which Attributes Matter the Most for Loan Origination? A Neural Attention Approach
Authors: Alexos Antonios , Chatzis Sotirios
Published: February 2020

In this paper we address the understanding of the problem, of why a deep learning model decides that an individual is eligible for a loan or not. Here we propose a novel approach for inferring, which attributes matter the most, for making a decision in each specific individual case. Specifically we leverage concepts from neural attention to devise a novel feature wise attention mechanism. As we show, using real world datasets, our approach offers unique insights into the importance of various features, by producing a decision explanation for each specific loan case. At the same time, we observe that our novel mechanism, generates decisions which are much closer to the decisions generated by human experts, compared to the existent competitors.
Careful Breakthrough Cancer Pain Treatment through Rapid-Onset Transmucosal Fentanyl Improves the Quality of Life in Cancer Patients: Results from the BEST Multicenter Study
Authors: Cuomo Arturo , Cascella Marco , Forte Cira Antonietta , Bimonte Sabrina , Esposito Gennaro , De Santis Stefano , Cavanna Luigi , Fusco Flavio , Dauri Mario , Natoli Silvia , Maltoni Marco , Morabito Alessandro , Mediati Rocco Domenico , Lorusso Vito , Barni Sandro , Porzio Giampiero , Mercadante Sebastiano , Crispo Anna
Published: February 2020

Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Well-controlled chronic background pain during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). Results: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (Linear p-value = 0.1) and dyspnoea (Linear p-value =0.05). The ESAS and PSQI questionnaires confirmed these positive results (p<0.0001 and p=0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance
Phytochemical and comparative transcriptome analyses reveal different regulatory mechanisms in the terpenoid biosynthesis pathways between Matricaria recutita L. and Chamaemelum nobile L.
Authors: Tai Yuling , Hou Xiaojuan , Liu Chun , Sun Jiameng , Guo Chunxiao , Su Ling , Jiang Wei , Ling Chengcheng , Wang Chengxiang , Wang Huanhuan , Pan Guifang , Si Xiongyuan , Yuan Yi
Published: February 2020

Background Matricaria recutita (German chamomile) and Chamaemelum nobile (Roman chamomile) belong to the botanical family Asteraceae. These two herbs are not only morphologically distinguishable, but their secondary metabolites – especially the essential oils present in flowers are also different, especially the terpenoids. The aim of this project was to preliminarily identify regulatory mechanisms in the terpenoid biosynthetic pathways that differ between German and Roman chamomile by performing comparative transcriptomic and metabolomic analyses. Results We determined the content of essential oils in disk florets and ray florets in these two chamomile species, and found that the terpenoid content in flowers of German chamomile is greater than that of Roman chamomile. In addition, a comparative RNA-seq analysis of German and Roman chamomile showed that 54% of genes shared >75% sequence identity between the two species. In particular, more highly expressed DEGs (differentially expressed genes) and TF (transcription factor) genes, different regulation of CYPs (cytochrome P450 enzymes), and rapid evolution of downstream genes in the terpenoid biosynthetic pathway of German chamomile could be the main reasons to explain the differences in the types and levels of terpenoid compounds in these two species. In addition, a phylogenetic tree constructed from single copy genes showed that German chamomile and Roman chamomile are closely related to Chrysanthemum nankingense. Conclusion This work provides the first insights into terpenoid biosynthesis in two species of chamomile. The candidate unigenes related to terpenoid biosynthesis will be important in molecular breeding approaches to modulate the essential oil composition of Matricaria recutita and Chamaemelum nobile.
Incidence and Predictors of Tuberculosis Occurrence among Adults on Antiretroviral Therapy at Debre Markos Referral Hospital, Northwest Ethiopia: Retrospective Follow-up Study
Authors: Aemro Agazhe , Jember Abebaw , Anlay Degefaye Zelalem
Published: February 2020

Background: In resource limited settings, Tuberculosis (TB) is a major cause of morbidity and mortality among patients on antiretroviral treatment. Ethiopia is one of the 30 high TB burden countries. TB causes burden in healthcare system and challenge the effectiveness of HIV care. This study was to assess incidence and predictors of Tuberculosis among adults on antiretroviral therapy at Debre Markos Referral Hospital, Northwest Ethiopia, 2019. Methods: Institution based retrospective follow up study was conducted among adults on ART newly enrolled from 2014 to 2018 at Debre Markos Referral Hospital. Simple random sampling technique was used to select patients chart. Data was entered to EPI- INFO version 7.2.2.6 and analyzed using Stata 14.0. Tuberculosis incidence rate was computed and described using frequency tables. Both bivariable and multivariable Cox proportional hazard models was fitted to identify predictors of TB. Results: Out of the 536 patients chart reviewed, 494 patient records were included in the analysis. A total of 62 patients developed new TB cases during the follow up period of 1000.22 Person Years (PY); which gives an overall incidence rate of 6.19 cases per 100 PY (95% CI: 4.83 - 7.95). The highest rate was seen within the first year of follow up. After adjustment base line Hemoglobin < 10 g/dl (AHR= 5.25; 95% CI: 2.52 - 10.95), ambulatory/bedridden patients at enrolment (AHR = 2.31; 95% CI: 1.13 - 4.73), having fair or poor ART adherence (AHR = 3.22; 95% CI: 1.64 – 6.31) were associated with increased risk of tuberculosis whereas taking Isoniazid Preventive Therapy (IPT) (AHR = 0.33; 95% CI: 0.12 - 0.85) were protective factors of TB occurrence. Conclusion: TB incidence was high among adults on ART especially in the first year of enrollment to ART. Low hemoglobin level, ambulatory or bedridden functional status, non-adherence to ART and IPT usage status were found to be independent predictors. Hence, continuous follow up for ART adherence and provision of IPT has a great importance to reduce the risk of TB.
Endogenous endophthalmitis caused by group B streptococcus; case reports and review of 35 reported cases
Authors: Yoshida Masaaki , Yokokura Shunji , Nishida Takashi , Mochizuki Kiyofumi , Suzuki Takashi , Maruyama Kazuichi , Otomo Takaaki , Nishiguchi Koji M , Kunikata Hiroshi , Nakazawa Toru
Published: February 2020

Background: Group B streptococcus (GBS), a gram-positive coccus that occasionally causes neonatal sepsis or invasive infection in the elderly, has been considered a rare cause of endogenous bacterial endophthalmitis (EBE). However, the number of invasive GBS infections is increasing, particularly in elderly patients with underlying conditions such as diabetes mellitus (DM), cardiovascular disease and cancer. We report 6 cases of EBE caused by GBS and review the literature. Methods: Retrospective case series and literature review Results: In the current case series, 6 eyes of 6 patients developed EBE caused by GBS. The average age was 73.5 years. The focus of infection included the urinary tract, cellulitis, arthritis, peritonitis, catheter-associated infection and endocarditis. Four patients had DM. While all 6 strains were sensitive to β-lactams (penicillins and cephems), 4 strains were resistant to levofloxacin (no data for 1 isolate). Each case was treated with the systemic antibiotic to which the individual strain was sensitive. All cases showed poor visual acuity at presentation (decimal visual acuity: less than 0.03). Vitrectomy with intravitreal antibiotics injection was performed in 4 cases. Visual acuity recovered in 4 cases and did not recover in 2 cases, even after vitrectomy. The literature review of 53 eyes of 41 patients revealed that 60% of eyes finally lost all vision, and death occurred in 2 cases. Initial visual acuity of less than counting fingers was associated with a final outcome of lost vision. Of 41 patients, 13 (32%) had DM as an underlying medical condition. The most common extra-ocular infection focus was endocarditis (37%). Conclusions: DM is common in patients with EBE caused by GBS. While the 4 cases in the current report had a relatively good visual acuity outcome, despite poor initial visual acuity, the literature review indicated that EBE caused by GBS is generally a severe condition with a poor prognosis. The current study also indicates the importance of considering the possibility of endocarditis on encountering EBE caused by GBS.
Healthcare Utilization and Out-of-Pocket Expenditures Associated with Depression in Adults: A Cross-Sectional Analysis in Nepal
Authors: Rajan Selina , Rathod Sujit D , Luitel Nagendra P , Murphy Adrianna , Roberts Tessa , Jord Mark JD
Published: February 2020

Background:
Despite attempts to improve universal healthcare coverage (UHC) in low income countries like Nepal, most healthcare utilization is still financed by out-of-pocket (OOP) payments, with detrimental effects on the poorest and most in need. Evidence from high income countries shows that depression is associated with increased healthcare utilization, which may lead to increased OOP expenditures, placing greater stress on families. To inform policies for integrating mental healthcare into UHC in LMIC, we must understand healthcare utilization and OOP expenditure patterns in people with depression.
Aims:
We examined associations between symptoms of depression and frequency and type of healthcare utilization and OOP expenditure among adults in Chitwan District, Nepal.
Methods:
We analysed data from a population-based survey of 2040 adults in 2013, who completed the PHQ-9 screening tool for depression and answered questions about healthcare utilization. We examined associations between increasing PHQ-9 score and healthcare utilization frequency and OOP expenditure using negative binomial regression. We also compared utilization of specific outpatient service providers and their related costs among adults with and without probable depression, determined by a PHQ-9 score of 10 or more.
Results:
We classified 80 (3.6%) participants with probable depression, 70.9% of whom used some form of healthcare in the past year compared to 43.9% of people without probable depression. Mean annual OOP healthcare expenditures were $118 USD in people with probable depression, compared to $110 USD in people without. With each unit increase in PHQ-9 score, there was a 14% increase in total healthcare visits (95% CI 7%-22%, p<0.0001) and $9 USD increase in OOP expenditures (95% CI $2-$17; p<0.0001). People with depression sought most healthcare from pharmacists (30.1%) but reported the greatest expenditure on specialist doctors ($36 USD).
Conclusions:
In this population-based sample from Central Nepal, we identified dose-dependent increases in healthcare utilization and OOP expenditure with increasing PHQ-9 scores. Future studies should evaluate whether provision of mental health services as an integrated component of UHC can improve overall health and reduce healthcare utilisation and expenditure, thereby alleviating financial pressures on families.
Community-level socioeconomic inequality in the incidence of ischemic heart disease: a nationwide cohort study
Authors: Gwon Jun Gyo , Choi Jimi , Han Young Jin
Published: February 2020

Background
The purpose of this study was to confirm that inequalities in community-level social economic status (SES) do actually impact the incidence of ischemic heart disease (IHD) using the Korean population-based cohort study of the National Health Insurance Service–National Sample Cohort (NHIS-NSC) database.
Methods
This study used the NHIS-NSC database, a population-based cohort database established by the NHIS in South Korea. Community-level SES was classified into three categories, i.e. low, moderate, and high, according to the rank. The outcome measure of interest was IHD, which was defined according to the International Classification of Disease, 10th Revision (ICD-10) codes.
Results
In the low community-level SES group, the incidence of IHD was 3.56 per 1,000 person years (cumulative incidence rate, 1.78%), and in the high community level SES group, it was 3.13 per 1,000 person years (cumulative incidence rate, 1.57%). Multivariate analysis showed that the incidence of IHD was higher in the low community-level SES group (p=0.029). The log-rank test showed that the cumulative incidence of IHD was higher in the low community level SES group than the high community-level SES group (adjusted hazard ratio, 1.16; 95% CI, 1.01-1.32)
Conclusions
People living in areas with low community-level SES show an increased incidence of IHD. Therefore, intervention in active, health-risk behavior corrections at the local level will be required to reduce the incidence of IHD.
Modular stem in total hip arthroplasty for patients with trochanter valgus deformity: surgical technique and case series
Authors: Kong Xiangpeng , Chai Wei , Yang Minzhi , Ong Alvin , Chen Jiying , Wang Yan , Zhou Yonggang
Published: February 2020

Background: Trochanter valgus deformity (TVD) is a rare condition of total hip arthroplasty (THA). Femoral osteotomy could be required in correcting the deformity to implant femoral stem in severe TVD. In this study, we described one unpublished technique of reverse sleeve of S-ROM to get through the complex situation. This study aimed to summarize and evaluate its technical challenges, safety and effectiveness.Methods: From January 2006 to December 2014, we enrolled patients whose sleeves were implanted towards the great trochanter in THA with TVD. Their demographics, perioperative and postoperative information were recorded. To explore its indication, we measured and analyzed the ratio of greater trochanter/lesser trochanter (G/L ratio) and trochanter valgus angle (TVA).Results: Twelve patients (1 male and 11 female, average age 42.30±10.23) had mean follow-up of 6 years. Among them, only two patients had intraoperative femoral fracture. The survivorship of femoral prosthesis was 100%. The Harris hip score (HHS) increased from preoperative 34.31±14.43 to postoperative 84.12±11.33. All patients’ G/L ratio were larger than 1.50.Conclusions: The reverse sleeve of S-ROM was a reliable method for the patients with severe TVD, which brought satisfying clinical outcomes in mid-term follow-up.Keywords: cementless modular stem; reverse sleeve; total hip arthroplasty; trochanter valgus deformity.
Different profiles of body mass index variation among patients with multidrug-resistant tuberculosis: a retrospective cohort study.
Authors: Diallo Alhassane , Diallo Boubacar Djelo , Camara Lansana Mady , Kounoudji Lucrèce Ahouéfa Nadège , Bah Boubacar , N’Zabintawali Fulgence , Carlos-Bolumbu Miguel , Diallo Mamadou Hassimiou , Sow Oumou Younoussa
Published: February 2020

Background: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. Methods: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. Results: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0087). Conclusion: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.
Milk exosome-derived miRNAs from water buffalo are implicated in immune response and metabolism process
Authors: Chen Zujing , Xie Yueqin , Luo Junyi , Chen Ting , Xi Qianyun , Zhang Yongliang , SUN JIAJIE
Published: February 2020

Background: Buffalo milk is rich in various nutritional components and bioactive substances that provide more essential health benefits to human body. Recently, exosome identified in the breast milk has been reported as a neotype nutrient and can mediate intercellular communication with exosomal miRNAs. In the present study, we therefore hypothesized that exosome-derived miRNAs from buffalo milk would play the potential physiological importance of consumption of buffalo milk.Results: We isolated exosomes from buffalo and cow milk samples that were obtained at mid-lactation period, and the exosomal miRNA profiles were then generated using miRNA-seq. In addition, miRNAomes of pig, human and panda milk exosomes were downloaded from GEO database. Finally, a total of 27 milk exosomal miRNA profiles that included 4 buffalo, 4 cow, 8 pig, 4 human and 7 panda were analyzed using the miRDeep2 program. A total of 558 unique miRNA candidates existed across all species, and the top 10 highly expressed miRNA were evolutionarily conserved across multiple species. Functional analysis revealed that these milk enriched miRNAs targeted 400 putative sites to modulate disease resistance, immune responsiveness and basic metabolism events. In addition, a total of 32 miRNAs in buffalo milk were significantly up-regulated compared with non-buffalo milks, while 16 were significantly down-regulated. Of interest, functional analysis showed that up-regulated miRNA were mainly related to host metabolism processes, while the predicted functions of down-regulated miRNAs were enriched in immune response.Conclusion: In this study, we explored the exosomal miRNAome differences between milks of different animals, expanding the theoretical basis for potential applications of the miRNA-containing vesicles.
Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema
Authors: Loo Evelyn , Zain Amanda , Yap Gaik Chin , Purbojati Rikky W , Drautz-Moses Daniela I , koh Yan Qing , Chong Yap Seng , Tan Kok Hian , Gluckman Peter D , Yap Fabian , Eriksson Johan Gunnar , Tham Elizabeth , shek lynette , kjelleberg Staffan , Schuster Stephan C , Banerjee Ritu , Lee Bee Wah
Published: February 2020

Background While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)- producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing .E coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. Methods We analysed ARGs in the first year of life among 75 infants who had stool samples collected at multiple timepoints using metagenomics. Results The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. Conclusion In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that the majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.
MiR-423-5p may regulate ovarian response to ovulation induction via CSF1
Authors: Xie Shi , Zhang Qiong , Zhao Jing , Hao Jie , Fu Jing , Li Yanping
Published: February 2020

Background
We have previously shown that hsa-miR-423-5p expression in ovarian granulosa cells is decreased in high ovarian response populations. The objective of the present study was to find the target gene and mechanism for miR-423-5p involved in ovarian response regulation.
Methods
(a) TargetScan was used to predict the target gene of hsa-miR-423-5p. (b) A model for hsa-miR-423-5p overexpression or inhibition was constructed by transfecting KGN cells with lentivirus. CSF1 mRNA and protein expression and luciferase activity were measured. (c) The cell cycles of control and lentivirus treated KGN cells were analyzed. Western blot was used to measure the expression of CDKN1A in KGN cells. (d) The concentration of estradiol in KGN cell culture medium were measured.
Results
(a) TargetScan revealed that the 3′ un-translated region of CSF1 matched 11 bases at the 5′ end of miR-423-5p, making it a likely target gene. (b) Overexpression or inhibition of miR-423-5p were associated with respective decreases or increases in CSF1 expression (both mRNA and protein) (p < 0.05) and luciferase activity (p < 0.05). (c) When miR-423-5p expression increased, the number of G0/G1 phase cells and the expression of CDKN1A protein increased while estradiol concentrations in the cell culture solution decreased (p<0.05). However, when miR-423-5p expression decreased, the number of S phase cells increased and estradiol concentrations increased while the expression of CDKN1A protein decreased (p < 0.05).
Conclusions
Colony stimulating factor 1 is a target gene of miR-423-5p and that it may regulate ovarian response to ovulation induction by affecting granulosa cells proliferation and estrogen secretion.
Oxidative stress and gut-derived lipopolysaccharides in children affected by Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.
Authors: Loffredo Lorenzo , Spalice Alberto , Salvatori Francesca , Giovanna De Castro , Guido Cristiana Alessia , Zicari Anna Maria , Ciacci Paolo , Battaglia Simona , Brindisi Giulia , Ettorre Evaristo , Nocella Cristina , Salvatori Guglielmo , Duse Marzia , Violi Francesco , Carnevale Roberto
Published: February 2020

Background: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to assess NOX2 levels, as well as serum 8-iso-prostaglandin F2α (iso-PGF2α) and lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut of patients with PANDAS. Methods: a cross sectional study was performed to compare serum levels of soluble NOX-2-dp (sNOX-2-dp), isoprostanes and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used to assess gut permeability. Results: compared with CT, PANDAS children had higher values of sNOX-2-dp, 8-iso-PGF2-alpha and LPS. Simple linear regression analysis showed that sNOX2-dp was signiﬁcantly correlated with serum LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and iso-PGF2α (Rs=0.704; p<0.001). LPS signiﬁcantly correlated with serum zonulin (Rs=0.610; p<0.001), and iso-PGF2α (Rs=0.591; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Isoprostanes and zonulin emerged as the only independent predictive variables associated with sNOX2-dp (R2=68%). Conclusion: this study provides evidences that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be potentially implicated in the process of neuroinflammation.
Continuous Renal Replacement Therapy in patients with HIV/AIDS
Authors: Guo Hebing , Liu Jingyuan , Pu Lin , Hao Jingjing , Yin Ningning , Liu Yufeng , Xiong Haofeng , Li Ang
Published: February 2020

Background :AKI is a common complication among human immunodeficiency virus (HIV)--infecting patients and resulting in increased morbidity and mortality. CRRT is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in ICU and explore the influence factors correlated with CRRT and prognosis.Methods: We performed a retrospective case-control study, in ICU of Beijing Ditan Hospital Capital Medical University, which is a top three hospital majoring in infectious diseases. From June 1,2005 to May 31,2017, 225 cases were enrolled in this research eventually.Results: 122(54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1/2/3 were respectively 38(31.1%)/23(18.9%)/61(50%). 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By multivariate logistics analysis, it showed that the use of vasoactive agents (OR=174.31,95% CI 1.743-65.271, p=0.018), diagnosis of PCP(OR=27.136,95% CI 1.855-397.066, p=0.016) and longer duration of CRRT (OR=1.034,95% CI 1.004-1.065, p=0.028) were independent risk factors for predicting patients’ death of CRRT in ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p =0.309).Conclusions: The incidence of AKI was 54.2% in HIV-infected patients admitted to the ICU, and about 26.2% AKI patients received CRRT during the stay of ICU.56.25%CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. The use of vasoactive agents, diagnosis of PCP were independent risk factors for predicting patients’ death of CRRT in ICU. The cumulative survival of AKI 3 patients between CRRT and non-CRRT groups shows no significant differences.
Association of ABO Polymorphisms and Pancreatic Cancer/ Cardiocerebrovascular Disease: a Meta-analysis.
Authors: Li Yanxia , Liu Luyang , Huang Yubei , Zheng Hong , Li Lian
Published: February 2020

Background: ABO gene polymorphisms have been reported to be associated with the risk of multiple cancers and cardiocerebrovascular disease s. However, the results remained controversial. In this study, we conducted a systematic review and meta-analysis to clarify the association between two SNPs (rs505922 and rs657152) in ABO gene and cancers/ cardiocerebrovascular disease s.
Method: All eligible case-control studies come from PubMed, Embase and Web of Science up to Jan. 1, 2019. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the corresponding associations. Sensitivity analysis, publication bias assessment, and heterogeneity test were performed using STATA 12.0.
Results : A total of nineteen articles involving twenty-two case-control populations were included according to inclusion and exclusion criteria. Twelve populations (20,820 cases and 27,837 controls) were used to evaluate the relationship between rs505922 and overall cancers and nine populations (22,275 cases and 71,549 controls) were included to assess the association between rs505922 and cardiocerebrovascular diseases. The results showed a significant association between the rs505922 polymorphism and cancers (CvsT: OR=1.13, 95%CI=1.05-1.22, P =0.001), and cardiocerebrovascular diseases (OR=1.36, 95%CI=1.19-1.57, P <0.001). Five populations (8,660 cases and 10,618 controls) were included to evaluate association between rs657152 and cancers and five populations (8,105 cases and 6,712 controls) were included to estimate the relationship between rs657152 and cardiocerebrovascular diseases. The result of meta-analysis reveals that rs657152 was significantly associated with cancers (OR=1.18, 95%CI=1.13-1.23, P <0.001) and cardiocerebrovascular diseases (OR=1.54, 95%CI=1.24-1.92, P <0.001).
Conclusion: Our study suggested that ABO polymorphisms might serve as a risk factor of pancreatic cancers and cardiocerebrovascular diseases.
Hypoxia promotes tenocyte differentiation of mesenchymal stem cells
Authors: Chen Guanyin , zhang wangqian , Gu Jintao , Gao Yuan , He Lei , wang shuning , Li Weina , Zhang Cun , Li Meng , Zhang Wei , Hao Qiang , Zhang Yingqi
Published: February 2020

Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.
A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice
Authors: Wang Liqiang , Xu Fei , Song Zhenfeng , Han Dan , Zhang jingyi , Chen Linjun , Na Lixin
Published: February 2020

Background: Differential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0) relative to the shorter-chain SFAs have drawn an interest for more accurate nutritional guidelines. But specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by high C18:0 diet and high palmitic acid (C16:0) diet.
Methods: Male C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0 / C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0 / C16:0 ratio (LSF) for 10 weeks. Oral glucose tolerance test, 72h-energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an auto-biochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α)，and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using Gas Chromatography-Mass Spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in liver. Pathway analysis and Gene Ontology analysis were applied to describe the roles of differentially expressed mRNAs.
Results: Compared with NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups, which were much higher in HSF group than those in LSF group. There were much more differentially expressed lncRNAs and mRNAs in HSF mice than those in LSF mice, with distinguishable lncRNA, microRNA, and mRNA expression profiles between these two groups. And some biological functions and pathways, except for energy metabolism regulation, were identified that differentially expressed mRNAs between HSF group and LSF group probably involved in.
Conclusion: The high fat diet with a high C18:0/C16:0 ratio induced much severe glucose and lipid metabolic disorders and inflammation, and affected more lncRNAs and mRNAs expression than an isocaloric low C18:0/C16:0 ratio diet in mice.
Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol
Authors: Fonseca Liliana , Paredes Sílvia , Ramos Helena , Oliveira José Carlos , Palma Isabel
Published: February 2020

Purpose: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c), although the CVD risk could be better reflected by other lipid parameters. This study aimed the evaluation of a comprehensive lipid profile in patients with type 2 diabetes mellitus (T2DM) and comparation of those achieving and not achieving LDL-c control in respect to other non-conventional lipid parameters. Methods: We characterized a comprehensive lipid profile in 96 T2DM patients. ESC/EAS 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. Atherogenic lipoprotein profile was compared in patients with LDL-c within and above the target. Results: Only 28.1% and 16.7% of patients had mean LDL-c levels within the 2016 and 2019 guidelines, respectively. In patients with LDL-c within target by the 2016 guidelines, 22%, 25% and 44% presented levels above the recommended range for non-HDL-c, ApoB and oxidized LDL-c, respectively, whereas accordingly to the 2019 guidelines, 50%, 39% and 44% had elevated levels of -HDL-c, ApoB and oxidized LDL-c, respectively. There was a significant strong association of LDL-c and non-HDL-c (r=0.850), ApoB (r=0.656) and oxidized LDL-c (r=0.508). Similarly, non-HDL-c was significantly strongly correlated with ApoB (r=0.808) and oxidized LDL-c (r=0.588). Conclusions: These findings emphasize the limitations of a sole LDL-c measurement for CV risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM individuals. Our data suggest that non-HDL-c, ApoB and oxidized LDL-c could be considered as part of these patients’ evaluation allowing a more accurate estimation of CV risk and treatment among these high-risk patients.
Influences of advanced glycosylation end products on the inner blood-retinal barrier in a co-cultural cell model in vitro
Authors: Yuan Chen , Mo Ya , Yang Jie , Zhang Mei , Xie Xuejun
Published: February 2020

Background: Advanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood-retinal barrier (iBRB). However, their effects on iBRB co-culture models in vitro have not been reported. This study is to understand the interactive effects of different concentrations of AGEs at different time points on rat retinal microvascular endothelial cells (RMEC) and rat retinal Müller glial cell (RMGC) co-culture models. Methods: RMEC of Sprague-Dawley rat was isolated and cultured, identified by anti-CD31 flow cytometry and immunocytometry with von Willebrand factor polyclonal antibody. Similarly, RMGC of Sprague-Dawley rat was identified by H&E staining, and immunohistochemical method with antibodies of Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). The transepithelial electrical resistance (TEER) value was measured with the Millicell electrical resistance system to observe the leakage of the barrier. The Transwell cell for co-cultured RMEC with RMGC were used to construct an iBRB model and tested with the addition of AGEs at final concentrations of 50 mg/L and 100 mg/L, respectively, for 24 hours, 48 hours, and 72 hours.Results: AGEs in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of VEGF and PEDF, and the permeability of the RMEC layer increased because TEER decreased in a dose- and time-dependent manner. In the AGEs intervention the vascular endothelial growth factor (VEGF) was increased, while pigment epithelial derivative factor (PEDF) decreased, respectively, in a dose- and time-dependent manner by enzyme-linked immunosorbent assay.Conclusions: The intervention with AGEs led to change of the RMEC layer transendothelial resistance and ratio of VEGF/PEDF. The iBRB in vitro model is a good tool to study the pathogenesis of retinal vascular diseases such as diabetic retinopathy and to evaluate the candidate drugs on the diseases.
Detection of carbapenemase-resistant Enterobacterales in blood culture in 15 minutes
Authors: Baer Daria , Azrad Maya , Saleh Nora , Peretz Avi
Published: February 2020

Background: Bacteremia leading to sepsis and organ dysfunction is a life-threatening situation. One major challenge in treatment of sepsis is the uprising prevalence of antibiotic resistant bacteria, such as Carbapenem-resistant Enterobacterales (CRE). In recent years several molecular assays have been developed for the detection of CRE mechanisms, enabling rapid results reporting. We evaluated the performance of NG-Test CARBA 5 (NG Biotech) kit for detection of CRE, directly from patients’ blood culture.Methods: Carbapenemase-producing (CP) CRE-positive isolates (n=38) and non-carbapenemase CRE (non-CP) isolates (n=10), previously identified using the routine methods practiced at the clinical microbiology laboratory of the Baruch Padeh Medical Center, Israel were used in this analysis. Variable concentrations of the bacterial isolates were added to a suspension composed of blood unit and saline simulating the composition of a blood culture. Samples were then transferred to an anaerobic blood culture bottle and later tested it with the NG-Test CARBA 5 (NG Biotech) kit, that identifies the CRE mechanism in 15 minutes.Results: The NG-Test CARBA 5 kit correctly identified 43 samples (89.5%). The sensitivity and specificity of the kit were 86.8% and 100%, respectively.Conclusions: The NG-Test CARBA 5 kit is a reliable and accessible tool for the rapid diagnosis of CRE bloodstream infections.