bluuebunny/crossref_metadata_2025 huggingface dataset:
Hard-threshold neural network-based prediction of organic synthetic outcomes
Authors: Hu Haoyang , Yuan Zhihong
Published: February 2020

Retrosynthetic analysis is a canonical technique for planning the synthesis route of organic molecules in drug discovery and development. In this technique, the screening of synthetic tree branches requires accurate forward reaction prediction, but existing software is far from completing this step independently. Previous studies attempted to apply a neural network to forward reaction prediction, but the accuracy was not satisfying. Through using the Edit Vector-based description and extended-connectivity fingerprints to transform the reaction into a vector, this study focuses on the update of the neural network to improve the template-based forward reaction prediction. Hard-threshold activation and the target propagation algorithm are implemented by introducing mixed convex-combinatorial optimization. Comparative tests were conducted to explore the optimal hyperparameter set. Using 15,000 experimental reaction data extracted from granted United States patents, the proposed hard-threshold neural network was systematically trained and tested. The results demonstrated that a higher prediction accuracy was obtained than that for the traditional neural network with backpropagation algorithm. Some successfully predicted reaction examples are also briefly illustrated.
The Fair Decision-making of Children and Adolescents with High-functioning Autism Spectrum Disorder from the Perspective of Dual-process Theories
Authors: Jin Peiying , Wang Yao , LI Yun , Xiao Yunhua , Li Chunyan , Qiu Nana , Weng Jiao , Fang Hui , Ke Xiaoyan
Published: February 2020

Background: Fairness has received much attention in our society. At present, the findings regarding fair decision-making in high-functioning autism spectrum disorder (HF-ASD) are inconsistent. Previous studies have shown that the fair decision-making of typically developing children is influenced by theory of mind (ToM) and executive functioning (EF). As those with HF-ASD have defects in both domains, this study aims to explore the differences in fair decision-making between children and adolescents with HF-ASD and those with typical development (TD). Methods: We used a simply ultimatum game (UG) to explore 31 children and adolescents with HF-ASD and 38 children and adolescents with TD. T tests and chi-square tests were used to compare group differences, and Pearson correlation analysis and stepwise regression analysis were used to analyse the mechanisms influencing the two groups' unfair acceptance rates. Results: The results show that children with HF-ASD are more likely to accept unfair offers, but for adolescents, the difference is not significant. Regression analysis showed that the interaction between the behavior regulation index (BRI) and age could negatively predict the unfair acceptance rate of children and adolescents with HF-ASD. Working memory and ToM can negatively predict the unfair acceptance rate of those with TD. Conclusion: This study concluded that the development of fair decision-making by children and adolescents with HF-ASD falls far behind that of those with TD. Intuition processes play a dominant role in the fair decision-making processes of children and adolescents with HF-ASD, and we believe that comorbidity, age, experience and emotional management are important factors influencing the fair decision-making of individuals with HF-ASD.
Factors contributing to post-stroke health care utilization and costs. Secondary results from the Life After Stroke (LAST) study, a pragmatic randomized controlled trial
Authors: Døhl Øystein , Halsteinli Vidar , Askim Torun , Gunnes Mari , Hansen Hege Ihle , Indredavik Bent , Langhammer Birgitta , Phan Ailan , Magnussen Jon
Published: February 2020

Background The result from the Life After Stroke (LAST) study showed that an 18-month follow up program as part of the primary health care, did not improve maintenance of motor function for stroke survivors. In this study we evaluated whether the follow-up program could lead to a reduction in the use of health care compared to standard care. Furthermore, we analyse to what extent differences in health care costs for stroke patients could be explained by individual need factors (such as physical disability, cognitive impairment, age, gender and marital status), and we tested whether a generic health related quality of life (HRQoL) is able to predict the utilisation of health care services for patients post-stroke as well as more disease specific indexes. Methods The Last study was a multicentre, pragmatic, single-blinded, randomized controlled trial. Adults (age ≥18 years) with first-ever or recurrent stroke, community dwelling, with modified Rankin Scale <5. The study included 380 persons recruited 10 to 16 weeks post-stroke, randomly assigned to individualized coaching for 18 months (n=186) or standard care (n=194). Individual need was measured by the Motor assessment scale (MAS), Barthel Index, Hospital Anxiety and Depression Scale (HADS), modified Rankin Scale (mRS) and Gait speed. HRQoL was measured by EQ-5D-5L. Health care costs were estimated for each person based on individual information of health care use. Multivariate regression analysis was used to analyse cost differences between the groups and the relationship between individual costs and determinants of health care utilisation. Results There were higher total costs in the intervention group. MAS, Gait speed, HADS and mRS were significant identifiers of costs post-stroke, as was EQ-5D-5L. Conclusion Long term, regular individualized coaching did not reduce health care costs compared to standard care. We found that MAS, Gait speed, HADS and mRS were significant predictors for future health care use. The generic EQ-5D-5L performed equally well as the more detailed battery of outcome measures, suggesting that HRQoL measures may be a simple and efficient way of identifying patients in need of health care after stroke and targeting groups for interventions. Clinical Trial Registration : https://www.clinicaltrials.gov NCT01467206.
Epidemiology and etiology of lower limb injuries in Iranian recreational runners
Authors: Mousavi Seyed Hamed , Hijmans Juha , Minoonejad Hooman , Rajabi Reza , Alizadeh Behrooz , Zwerver Johannes
Published: February 2020

The authors have withdrawn this preprint from Research Square
Biological Potential Alterations of Migratory Chondrogenic Progenitor Cells during Knee Osteoarthritic Progression
Authors: Wang Yu-Xing , Zhao Zhi-Dong , Wang Qian , Li Zhong-Li , Huang Ya , Zhao Sen , Hu Wei , Liang Jia-Wu , Li Pei-Lin , Wang Hua , Mao Ning , Wu Chu-Tse , Zhu Heng
Published: February 2020

Background: Although increasing studies have demonstrated that chondrogenic progenitor cells (CPCs) remain present in human osteoarthritic cartilage, the biological alterations of the CPCs from the less diseased lateral tibial condyle and the more diseased medial condyle of same patient remain to be investigated. Methods: CPCs were isolated from paired grade 1-2 and grade 3-4 osteoarthritic cartilage by virtue of cell migratory capacities. The cell morphology, immunophenotype, self-renewal, multi-differentiation, and cell migration of these CPCs were evaluated. Additionally, the distributions of CD105+/CD271+ cells in OA osteochondral specimen were determined. Furthermore, a high-through mRNA sequencing was performed. Results: Migratory CPCs (mCPCs) robustly outgrew from mildly collagenases-digested osteoarthritic cartilages. The mCPCs from grade 3-4 cartilages (mCPCs, grade 3-4) harbored morphological characteristics, cell proliferation and colony formation capacity that were similar to those of the mCPCs from the grade 1-2 OA cartilages (mCPCs, grade 1-2). However, the mCPCs (grade 3-4) highly expressed CD271. In addition, the mCPCs (grade 3-4) showed enhanced osteo-adipogenic activities and decreased chondrogenic capacity. Furthermore, the mCPCs (grade 3-4) exhibited stronger cell migration in response to osteoarthritis synovial fluids. More CD105+/CD271+ cells resided in grade 3-4 articular cartilages. Moreover, the results of mRNA sequencing showed that mCPCs (grade 3-4) expressed higher migratory molecules. Conclusions: Our data suggest that more mCPCs (grade 3-4) migrate to injured articular cartilages but with enhanced osteo-adipogenic and decreased chondrogenic capacity, which might explain the pathological changes of mCPCs during the progression of OA from early to late stages. Thus, these dysfunctional mCPCs might be optional cell targets for OA therapies.
Determining a Critical Threshold for G6PD Activity below which RBC Response to Oxidative Stress is Poor
Authors: Swastika Maria , Harahap Alida R , Panggalo Lydia V , Jusman Sri Widia A , Satyagraha Ari W
Published: February 2020

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in RBC. G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine which has a long half-life, screening for G6PD deficiency becomes a necessity where those with <70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration. Methods: RBC models were developed to analyze the effect of oxidant on RBC oxidative markers namely total glutathione (GSH) and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from two G6PD heterozygous women with different G6PD activities were also analyzed for comparison. Results: There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, our CuCl RBC model showed that in low G6PD activities (10-30%) cells, the MDA level is lower compared to the rest of the models (p<0.05). Our ex vivo model however were in line with the hypothesis, although the result was not significant (p=0.5). There was a significant difference between RBC with <60% and those with >80% G6PD activities in CuCl RBC model but not in ex vivo RBC (p=0.5). Genotyping heterozygous subjects showed G6PD Viangchan variant with 2.97 U/gHb (33% activity) and 6.58 U/gHb (74% activity). Conclusions: The GSH analysis has pointed to the 60% G6PD activity cut-off and this data is supportive of the old WHO threshold for intermediate upper limit of 60% G6PD activity. However, there are significant limitations in using MDA assay with CuCl RBC model because the RBC was already stressed due to the copper treatment and thus present a different result when compared to the ex-vivo model.
Influential Factors on Sexual Function in Infertile Women with Endometriosis: A Path Analysis
Authors: Author) samaneh youseflu(Former Corresponding , Author) Shahideh Jahanian Sadatmahalleh(New Corresponding , Khomami Mahnaz Bahri , Nasiri Malihe
Published: February 2020

Background: Endometriosis have a negative influence on women’s sexual life. The aim of the current study was to test a conceptual model considering the interrelated role of anxiety, depression, sleep quality, physical activity, BMI, stage of endometriosis, the intensity of dyspareunia and pelvic pain on sexual function (SF) in infertile women with endometriosis. Also test the mediating role of sleep quality, anxiety, and depression.
Method: In the present cross-sectional study, 220 infertile women with a laparoscopically confirmed endometriosis were recruited. Data were collected using a socio-demographic checklist, Female Sexual Function Index (FSFI), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Visual Analog Scale (VAS).
Results: We found that anxiety, depression, sleep quality, BMI, level of education, stage of endometriosis, and dyspareunia have a direct effect on women’s SF. In our study, sleep quality, anxiety, pelvic pain, and depression were the four major mediators that the higher scores lead to a decrease in the SF of endometriosis patients. The intensity of pelvic pain with an effect on sleep quality and dyspareunia change women’s SF. The lower level of physical activity, and higher BMI with indirect effect thorough anxiety, and sleep quality can worsen SF. Also, a higher level of anxiety leads to poor sleep quality and depression. Anxiety with both direct and indirect effect impress women’s SF.
Conclusion: It seems that the main risk factors for sexual dysfunction in women with endometriosis are higher rates of anxiety, depression, poor sleep quality, pelvic pain, and dyspareunia. In the care of women with endometriosis, not only laparoscopy and medical treatment should be performed but also psychotherapeutic and psychosexual help should be offered.
Biomechanical and morphological changes of rabbit corneas under collagenase type II and negative pressure: three months follow-up observation
Authors: Chen Xinyan , Qin Xiao , Yu Mengyao , Zhang Haixia , Li Lin
Published: February 2020

Background

To investigate biomechanical and morphological changes of rabbit cornea ectasia induced by collagenase type II and negative pressure during 3 months after treatment.

Method

Eighteen New Zealand white rabbits were randomly and evenly arranged into three groups. In group NP, the corneas were continuously attracted by negative pressure with 500 mmHg for 30 min, treated by every other day, three times in total. In group CII, the corneal central zone was soaked in the collagenase type II solution (200 μL of 3 mg/ml) for 30 min. In group CP, the corneas were disposed as group CII firstly, then applied negative pressure as group NP for once after 5 days. All right eyes were treated as control eyes. Corneal morphology and biomechanical related parameters were observed in vivo once a week for three weeks after treatment and before execution. Histology and biomechanics were tested in vitro at the third month after treatment.

Results

Corneal diopter and corneal central thickness (CCT) changed to some extent after treatment immediately as a result of negative pressure in group NP. The corneas in Group NP had smaller elastic modulus and slower relaxation degree compared with the control one 3 months after treatment. In Group CII, corneal diopter increased, CCT and CH decreased at the second week after treatment, which showed the characters of ectatic corneas. At the third month after treatment, elastic modulus (EL) of the experimental eyes decreased slightly compared with the control eyes. Due to the large individual differences, there were no regular changes on experimental corneas in Group CP.

Conclusions

Cornea socked with collagenase type II showed the obvious characteristics of ectatic cornea at the second week after treatment, but the characteristics disappeared gradually. Negative pressure can result in the change of corneal thickness and diopter in a short period of time, and the degree of swelling and duration are far less than Group CII, but the changes of biomechanical parameters are more obviously than Group CII.
Parenting stress and competence in borderline personality disorder: The influence of mental health, trauma history, attachment and reflective capacity.
Authors: Steele Kayla R , Townsend Michelle L , Grenyer Brin F.S.
Published: February 2020

Background: Individuals with borderline personality disorder (BPD) may experience additional challenges in their parenting role, including increased stress and lower self-efficacy and satisfaction. These difficulties have been shown to impact their children, and may be implicated in the potential intergenerational transmission of personal vulnerabilities.Methods: Parental stress and competence variables was explored in 284 parents (94.72% female, M=37.37, SD=8.04 years), of which 69 (24.30%) met caseness for BPD criteria. We completed a multivariate analysis of variance to compare parents with ‘high BPD features’ (meeting caseness for BPD) to those with ‘low BPD features’ on a range of parenting and mental health variables. Multivariate linear regression modelling was then utilised to investigate how these parenting variables were influenced by personality and psychological wellbeing, recalled trauma history, orientation to attachment relationships and reflective capacity.Results: Individuals high in BPD features experienced more stress and lower competence in their parenting role than those low in BPD features. These parents also reported more personality vulnerabilities, poorer psychological wellbeing, recalled more traumatic experiences in their childhood, were more likely to endorse insecure attachment styles and had poorer reflective capacity. Parenting stress and competence was also influenced by personality traits, general psychological wellbeing, recalled trauma history, attachment style and reflective capacity variables. Parental reflective capacity had the strongest influence on parenting stress, satisfaction, efficacy and the perception of having a difficult child and a difficult parent-child relationship. Whilst a parent’s psychological wellbeing had the greatest influence on their parenting distress. Conclusions: Parents who were able to imaginatively enter the subjective world of the child and hold the child’s mind in mind with less certainty, reported reduced parenting stress and greater parenting satisfaction and efficacy. Helping to improve personality and mental health functioning, increasing parental reflective capacity and strengthening parent-child attachment relationships, may reduce parenting stress and increase parenting competence in individuals with BPD.
Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: analysis of 126 Chinese patients
Authors: Zhang Lei , Yun Shuang , Wu Tiange , He Yujie , Guo Jinyan , Han Lishuai , Lu Jiameng , Liu Xiaojun , Yang Rui , Zhang Shitao , Li Tianfang , Liu Shengyun
Published: February 2020

Objective To explore the clinical patterns of relapsing polychondritis(RPC) to improve clinicians’ comprehensive understanding of the disease. Methods The electronic records of RPC patients that were hospitalized and followed-up by rheumatologists at our hospital between January 1, 2008 and August 31,2019 were retrospectively analyzed. Results Sixty-six males and 60 femaleswere included with onset age of 47.1±13.8 years and followed up for a median of 18 months. Eighty-seven patients (69.1%) did not met with the traditional criteria.Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r=-0.75，P<0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%) and patients with Ear pattern and Airway pattern were subdivided as limited and systemic form of RPC (27.8%with limited form of Ear pattern and 24.6% with limited form of Airway pattern). During follow-up, a small part of patients with Ear pattern and Airway pattern progressed into Overlap pattern andsome Airway-Ear negative patternpatients progressed into Ear pattern. Most of the limited RPC patientsremained limited form during follow-up whilesome patients with limited form progressed into systemic form. Patients with Ear pattern had the highest survival rate and relative lower inflammatory status. Conclusion RPC patients can be categorized as 4 differentclinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement.Limited form of RPC is not uncommon in Chinese patients and traditional criteria of RPC are not suitable for early diagnosis.
A daf-7-related TGF-β ligand (Hc-tgh-2) shows important regulations on the development of Haemonchus contortus
Authors: He Li , Liu Hui , Zhang Biying , Li Fangfang , Di Wenda , Wang Chunqun , Zhou Caixian , Liu Lu , Li Tingting , Zhang Ting , Fang Rui , Hu Min
Published: February 2020

Background In most multicellular organisms, transforming growth factor-β (TGF-β) signalling pathway is involved in regulating the growth and stem cell differentiation. Previous studies have demonstrated the importance of three key molecules in this pathway in the parasitic nematode Haemonchus contortus , including one TGF-β type I receptor ( Hc-tgfbr1 ), one TGF-β type II receptor ( Hc-tgfbr2 ), and one co-Smad ( Hc-daf-3 ), which regulated the developmental transition from the free-living to the parasitic stages of this parasite. However, almost nothing is known about the function of the TGF-β ligand ( Hc-tgh-2 ) of H. contortus . Methods Here, the temporal transcription profiles of Hc-tgh-2 at eight different developmental stages and spacial expression patterns of Hc- TGH-2 in adult female and male worms of H. contortus have been examined by real-time PCR and immunohistochemistry, respectively. In addition, RNA interference (RNAi) by feeding was employed to assess the importance of Hc-tgh-2 in the development from exsheathed third-stage larvae (xL3s) to fourth-stage larvae (L4s) in H. contortus . Results Hc-tgh-2 was continuously transcribed in all eight developmental stages of H. contortus studied with the highest level in the infective third-stage larvae (iL3) and Hc -TGH-2 was located in the muscle of the body wall, intestine, ovary of adult females and testes of adult males. Silencing Hc-tgh-2 by the specific double-stranded RNA (dsRNA), decreased the transcript level of Hc-tgh-2 and resulted in fewer xL3s developing to L4s in vitro. Conclusions These results suggested that the TGF-β ligand, Hc -TGH-2, could play important roles in the developmental transition from the free-living (L3s) to the parasitic stage (L4s). Furthermore, it may also take part in the processes such as digestion, absorption, host immune response and reproductive development in H. contortus adults.
Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury
Authors: Wang Han , Zhou Xiaoming , Wu Lingyun , Liu Guangjie , Xu Weidong , Zhang Xiangsheng , Gao Yongyue , Tao Tao , Zhou Yan , Lu Yue , Wang Juan , Deng Chulei , Zhuang Zong , Hang Chunhua , Li Wei
Published: February 2020

Background: Aucubin (Au) has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.Methods: Neuronal apoptosis, brain water content, histological damages and neurological deficits and cognitive functions were measured. We performed western blot, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA). RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with intraperitoneal injection of Au.Results: We found that Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.
Relationship between the Inflammation/immune Indexes and Deep Venous Thrombosis (DVT) following Tibial Plateau Fractures
Authors: Liu Dawei , Chen Wei , Li Junyong , Zhao Kuo , Zhang Junzhe , Meng Hongyu , Zhu Yanbin , Zhang Yingze
Published: February 2020

Objective To determine the relationship between inflammation/immune-based indexes and preoperative DVT of lower extremities following tibial plateau fracturesMethods Retrospective analysis of a prospectively collected data on patients undergoing surgeries of tibial plateau fractures between October 2014 and December 2018 was performed. Duplex ultrasonography (DUS) was routinely used to screen for preoperative DVT of bilateral lower extremities. Data on biomarkers (neutrophil-, lymphocyte-, monocyte- and platelet counts) at admission were collected, based on which neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte/lymphocyte (MLR) and systemic immune-inflammation index (SII, neutrophil* platelet/ lymphocyte) were calculated. Receiver operating characteristic (ROC) was used to determine the optimal cut-off value for each variable. Multivariate logistic regression analysis was used to evaluate the independent relationship of each biomarker or index with DVT, after adjustment for demographics, co-morbidities and injury-related variables.Results Among 1179 patients included, 16.3% (192/1179) of them had (16.3%) had a preoperative DVT. Among the biomarkers and indexes, only platelet and neutrophil were identified to be independently associated with DVT, and their predictive ability was stable regardless of open fracture with or without included. The other independent variables were elevated D-dimer level (>0.55mg/L), male gender and hypertension in the sensitivity analysis with open fractures excluded.Conclusion These identified factors are conducive to the initial screening for patients at-risk of DVT, individualized risk assessment, risk stratification and accordingly development of targeted prevention programs.
Biomechanical evaluation and finite element analysis of axial-loading simulated experiment of wrist fracture
Authors: Zhang Yuan-Wei , Xiong Liang-Yu , Huang Zu-Tai , Xiao Xin , Zhang Su-Li , Ni Wen-Yan , Deng Liang
Published: February 2020

Objectives

This study combined mechanical experiments and finite element analysis (FEA), and verified each other, to assess the biomechanical analysis and effect of wrist fracture, providing theoretical basis for the simulation experiments of wrist fracture and optimal design of wrist protector.

Methods and Materials

Six cadaveric wrists were included to create experimental specimens. After grouping, the wrist models were axially loaded under physiological load of 600 N, the stress magnitude and distribution of experimental group and control group were obtained. Moreover, a three-dimensional (3D) wrist finite element model (FEM) of a healthy volunteer was developed to verify the rationality and effectiveness of wrist models.

Results

Within the range of physiological load, the stress of radioulnar palmar unit was high and in shape of pressure, while the stress of radioulnar dorsal unit was relatively lower and in shape of tension. The stresses of radial distal palmar, ulnar distal palmar, radial distal dorsal, ulnar distal dorsal, radial proximal palmar and ulnar proximal palmar units in experimental group were less than those in control group. However, the stresses of radial proximal dorsal and ulnar proximal dorsal units were higher than those in control group.

Conclusions

Under physiological load, wearing wrist protector can apparently reduce the stress on radioulnar distal palmar, radioulnar proximal palmar and radioulnar distal dorsal units, while has no obvious effect on radioulnar proximal dorsal units. During the process of designing and improving the wrist protector, it is reasonable to place the stress center on radioulnar distal palmar and dorsal units.
Comparison the effects of aqueous and ethanolic extracts of Rheum ribes on insulin resistance and apolipoprotein AI (ApoA1), apolipoprotein B (ApoB) and Apo B to ApoA1 ratio in patients with type 2 diabetes mellitus: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial
Authors: Ghafouri Atieh , Karegar Sahar Jafari , Hajiluian Ghazaleh , Hosseini Sharieh , Shidfar Shahrzad , Kamalinejad Mohamad , Hosseini AghaFatemeh , Heydari Iraj , Shidfar Farzad
Published: February 2020

Background: This study was conducted to determine the effect of Rheum ribes supplementation on glycemic indices and apolipoproteins in patients with type 2 diabetes mellitus (DMT2).Methods: In this randomized controlled trial, sixty type 2 diabetic patients, aged 30-60 years with body mass index (BMI) of 20-30 kg/m 2 , and hemoglobin A1c (HbA1c) of 6-8% were included. The patients were randomly assigned to receive 450 mg of Rheum ribes aqueous extract (AG), 450 mg of Rheum ribes ethanolic extract (EG) or placebo (PG), three times daily for 6 weeks. Then glucose, the homeostatic model assessment (HOMA-IR and HOMA-B) and apolipoprotein A-I (ApoA1) and apolipoprotein B (ApoB) were measured.Results: According to these findings, in the AG and EG intervention groups, we observed a significant reduction in serum levels of insulin (P=0.003 and P=0.001, respectively), HOMA-IR (P=0.01 and P=0.001, respectively) and HOMA-B (P=0.002 and P=0.001, respectively) indices, without no significant changes in glucose. There was also a significant reduction in serum levels of ApoB (P=0.006 and P=0.03, respectively) and ApoB/ApoA1 ratio (P=0.016 and P=0.04, respectively) in both AG and EG. Intervention in both AG and EG had increasing effects on ApoA1 (P=0.08 and P=0.05, respectively). None of these variables had a significant change in PG. At the end of study, there were significant differences in insulin (P=0.04), HOMA-IR (P=0.03), HOMA-B (P=0.01), ApoB (P=0.02), and ApoB/ApoA1 (P=0.03) ratio among groups.Conclusions: Rheum ribes intake may have favorable effects on insulin resistance and apolipoproteins in diabetic patients.Trial registration: The study was recorded in Iranian Registry of Clinical Trials under the registration number of IRCT201410142709N31 (Registration date: 2014-12-11, https://en.irct.ir/trial/2543 ).
Adipokines: The possible association between low carbohydrate diet score and depression
Authors: Setayesh Leila , Pooyan Sara , Ebrahimi Reyhane , Yarizadeh Habib , Rashidbeygi Elaheh , Badrooj Negin , Imani Hossein , Mirzaei Khadijeh
Published: February 2020

Background Due to lack of enough date to confirm the association of obesity and depression in middle east, We aimed to explore the possible mediatory role of adipokines such as galactin1, transforming growth factor beta (TGF-beta), and endothelial plasminogen activator inhibitor (PAI-1) in the association between obesity and depression.Methods A total of 256 women ranged between 18-48 years old were grouped based on their low carbohydrate diet (LCD) score. Body composition and dietary intake were assessed. Enzyme-linked immunosorbent assay was used to measure serum adipokines levels.Results There was a negative association between LCD score as a covariant and depression as an independent variable (P= 0.02) (beta ±SE= -0.143±0.031) (CI= -0.129 to -0.08). A regression model linear analysis using galactin1, TGF-β, and PAI 1 as a covariant indicated the mediatory effects of these adipokines (P > 0.05). The higher adherence to LCD was associated with a decrease of anthropometric components (p < 0.05).Conclusion We indicated that a higher adherence to LCD would probably ameliorate depression through the mediatory role of the study adipokines. The higher adherence of LCD in depressive obese individuals due to possible improvement effects on mental health.
Prenatal Exposure to Ambient Air Multi-Pollutant Mixture Significantly Impairs Intrauterine Fetal Development Trajectory
Authors: Shao Xiaowen , Cheng Haoxiang , Zhou Jonathan , zhang Jushan , Zhu Yujie , Yang Chun , Narzo Antonio Di , Yu Jing , Shen Yuan , Li Yuanyuan , Xu Shunqing , Zhang Zhongyang , Chen Jia , Cheng Jiajing , Hao Ke
Published: February 2020

Background Impaired in utero fetal growth trajectory may have long term health consequences of the newborns and increase risk of adulthood metabolic diseases. Prenatal exposure to air pollution has been linked to fetal development restriction; however, the impact of exposure to ambient air pollutants on the entire course of intrauterine fetal development has not been comprehensively investigated. Methods During 2015 – 2018, two cohorts of mother-infant dyads (N=678 and 227) were recruited in Shanghai China, from which three categories of data were systematically collected: (1) daily exposure to six air pollutants during pregnancy, (2) fetal biometry in the 2 nd (gestational week 24, [GW24]) and 3 rd trimester (GW36), and (3) neonatal outcomes at birth. We investigated the impact of prenatal exposure to a mixture of air pollutants on the trajectory of fetal development during the course of gestation, adjusting for a broad set of potential confounds. Results Prenatal exposure to PM 2.5 , PM 10 , SO 2 and O 3 significantly reduced fetal biometry at GW24, where SO 2 had the most potent effect. For every 10 ug/m 3 increment increase of daily SO 2 exposure during the 1 st trimester shortened femur length by 2.20 mm (p=6.7E-21) translating to 5.3% reduction from population average. Prenatal air pollution exposure also decreased fetal biometry at GW36 with attenuated effect size. Comparing to the lowest exposed quartile, fetus in the highest exposed quartile had 6.3% (p=3.5E-5) and 2.1% (p=2.4E-3) lower estimated intrauterine weight in GW24 and GW36, respectively; however, no difference in birth weight was observed, indicating a rapid catch-up growth in the 3 rd trimester. Conclusions To our knowledge, for the first time, we demonstrated the impact of prenatal exposure to ambient air pollutants on the course of intrauterine fetal development. The altered growth trajectory and rapid catch-up growth in associated with high prenatal exposure may lead to long-term predisposition for adulthood metabolic disorders.
Identification of a dynamic middle ear microbiome in healthy adults
Authors: Lee Joo-Young , Kashefi Kazem , Reguera Gemma
Published: February 2020

Background The entrenched dogma of a sterile middle ear in health is incongruent with its periodic exposure to exhaled air when the tympanic (Eustachian) tube opens while swallowing, yawning or inhaling deeply. Tubal patency is brief but frequent to provide adequate aeration, equalize pressure across the eardrum and drain mucus down the sides of the oropharynx. It also provides a mechanism for aerial dispersal of microorganisms from the aerodigestive tract. Method We designed a pilot study and received institutional approval to collect otic secretions that naturally drain on the sides of the oropharynx, behind the palatopharyngeal arch. This protocol bypassed the need to surgically access the middle ear through or around the eardrum, allowed us to collect samples from individuals with no underlying otic conditions, and prevented sample cross-contamination. As controls, we also collected samples from the center of the oropharynx and buccal mucosae seeded by saliva, which may serve as sources of microbial dispersal into the middle ear. Results We sequenced 16S rRNA-V4 amplicons from otic, oropharyngeal and buccal samples collected from a cohort of 19 healthy young adults. The survey identified in the otic samples a diverse bacterial community with many oropharyngeal and buccal keystone taxa and most of the functional traits of the neighboring oral microbiomes. Neutral community models predicted a large contribution of oral dispersal to the composition of the otic microbiome as well as several taxa responsive to positive selection. This was further supported by the enrichment in the otic communities of obligate anaerobes of Bacteroidetes and Fusobacteria over facultative anaerobic Proteobacteria and Firmicutes. Furthermore, the prevalence of the anaerobic members decreased with the more frequent otic aeration predicted from the equalization training of scuba divers recruited to the study. Conclusions These results challenge the long held view of a sterile middle ear and suggest instead that frequent seeding with oral microbes supports the establishment of a rich and robust otic community dynamically adapted to the episodic ventilation of the tympanic space.
Dynamic simulations of microbial communities under perturbations: opportunities for microbiome engineering
Authors: García-Jiménez Beatriz , Carrasco Jorge , Medina Joaquín , Wilkinson Mark D
Published: February 2020

Background : There are few large longitudinal microbiome studies, and fewer that include controlled, well-annotated perturbations between sampling-points. Thus, there are few opportunities to employ data-driven computational analyses of perturbed microbial communities over time. Results : Our novel computational system simulates the dynamics of microbial communities under perturbations using genome-scale metabolic models (GEMs). Perturbations include modifications to a) the nutrients available in the medium, allowing modelling of prebiotics; and/or b) the microorganisms present in the community to model, for example, probiotics or pathogen infection. These simulations generate the quantity and types of information required by MDPbiome, an AI system which builds predictive models suggesting the perturbation(s) required to engineer microbial communities to a desired state. We call this novel combination of technologies "MDPbiomeGEM"'. We demonstrate, in a Crohn’s disease microbiome, that MDPbiomeGEM correctly models the influence of both prebiotic fiber and a probiotic, resulting in a recommendation to consume inulin to recover from dysbiosis, consistent with prior biomedical knowledge. When used to model the soil microbiome's ability to degrade the herbicide Atrazine, differing recommendations arise depending on the highly variable state of the initial soil microbial composition, highlighting the relevance of both phosphate and microbes (i.e. Halobacillus sp. and H.stevensii ) in a directed microbiome engineering strategy, consistent with previously published observations. Conclusions : MDPbiomeGEM generates large volumes of longitudinal data of complex microbial communities experiencing perturbations. Machine learning on these data reveal patterns consistent with existing biological knowledge, supporting the validity of the approach. MDPbiomeGEM could save research resources by optimizing sample collection in metagenomics studies through identification of "informative" scenarios/time-points, or by predicting optimal in-vitro culture formulations for generating performant synthetic microbial communities. Finally, MDPbiomeGEM outputs include detailed information about the metabolic state of the community, which can be used to further interpret the impact of perturbations, and potentially could be used to predict novel metabolic biomarkers of a microbiome's state.
Copy number variation in the carboxylesterase 1 gene and the risk of non-alcoholic fatty liver in a Chinese Han population-a case control study
Authors: Chen Bing bing , Peng Xian-E , Yan Jianhui , Peng Hewei , Cai Xiaoling , Pan Xinting , Li Huiquan , Hong Qizhu
Published: February 2020

Background: A recent genome-wide copy number variations (CNVs) scan identified a 16q12.2 deletion that included the carboxylesterase 1 (CES1) gene, which is important in the metabolism of fatty acids and cholesterol. We aimed to investigate whether CES1 CNVs was associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in a Chinese Han population. Methods: A case-control study was conducted among 303 patients diagnosed with NAFLD and 303 age (± 5) and sex-matched controls from the Affiliated Nanping First Hospital of Fujian Medical University in China. The copy numbers of CES1 were measured using TaqMan quantitative real-time polymerase chain reaction (qPCR) and serum CES1 was measured using enzyme-linked immunosorbent assays. The Chi-squared test and a logistic regression model were used to evaluate the association between CES1 CNVs and NAFLD susceptibility. Results: The distribution of CES1 CNVs showed a higher frequency of CNVs loss (< 2) among patients; however, the difference was not significant (P = 0.05). After controlling for other known or suspected risk factors for NAFLD, CES1 CNVs loss was significantly associated with greater risk of NAFLD (adjusted OR = 2.75, 95% CI: 1.30–5.85, P = 0.01); while CES1 CNVs gain (>2) was not. There was a suggestion of an association between increased CES1 serum protein levels and CNVs losses among cases, although this was not statistically significant (P=0.07). Conclusions: Copy number losses (< 2) of CES1 contribute to susceptibility to NAFLD in the Chinese Han population.
Evaluating Blood-brain Barrier Permeability in a Rat Model of Type 2 Diabetes
Authors: Qiao Ju , Lawson Christopher M , Rentrup Kilian FG , Kulkarni Praveen , Ferris Craig
Published: February 2020

Background: This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. Methods: The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas.Results: In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected. Conclusion: Small vessel disease as assessed by permeability in the blood brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.
Dual HER-2 blockade therapy increases the risk of developing cardiac toxicities in HER-2 positive breast cancer: an up-to-date comprehensive meta-analysis
Authors: Qi Wei-Xiang , Cao Lu , Xu Cheng , Zhao Shengguang , Chen Jiayi
Published: February 2020

Background To investigate the incidence and risk of cardiac toxicities between dual HER-2 blockade and anti-HER-2 monotherapy.Materials and Methods We searched PubMed, EMBASE and Cochrane library databases to identify relevant trials between January 1 1990 and October 31 2019. Statistical analyses were conducted to calculate the summary incidence, Petro odds radio (Peto ORs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models.Results A total of 16,375 patients from 15 randomized controlled trials were included for analysis; the pooled incidence of LVEF decline and CHF in dual HER-2 blocked were 4.6% and 0.9%, which was higher than that in anti-HER-2 monotherapy (3.2% and 0.7%, respectively). Dual HER-2 blockade therapy in breast cancer patients significantly increased the risk of developing LVEF decline (OR:1.19, 95%CI: 1.02-1.40, p=0.031) and CHF (OR:1.45, 95%CI: 1.00-2.11, p=0.049) when compared to anti-HER2 monotherapy. Sub-group analysis showed that addition of dual HER-2 blockade to adjuvant treatment for breast cancer significantly increased the risk of developing LVEF decline (p=0.048) and CHF (p=0.005). In addition, dual HER-2 blockade in breast cancer patients significantly increased the risk of developing LVEF decline (p=0.004) when compared to lapatinib alone, but not for CHF (p=0.11, respectively).Conclusion Dual HER-2 targeted therapy in HER-2 positive breast cancer significantly increase the risk of developing LVEF and CHF when compared to anti-HER-2 alone, though the overall incidence of cardiac toxicities is very low. Physicians should be aware of this risk and provide close monitoring during the administration of dual HER-2 targeted therapy.
Identification and Functional Analysis of the Doublesex Gene in the Redclaw Crayfish, Cherax quadricarinatus
Authors: Zheng Jianbo , Cai Lina , Jia Yongyi , Chi Meili , Cheng Shun , Liu Shili , Gu Zhimin
Published: February 2020

Background: Crustaceans often exhibit significant sexual dimorphism during their growth process. However, their sex determination system is relatively complex, and still lacks of related studies that involved in sex determination and differentiation.Results: In the present study, the gene of Doublesex (Cqdsx) was identified and characterized for the first time in the redclaw crayfish, Cherax quadricarinatus. The full-length cDNA was 1271 bp, comprising a 155 bp 5’-untranslated region (5’-UTR), a 885 bp predicted open reading frame (ORF) encoding 294 amino acid polypeptides, and a 231 bp 3’-UTR. The deduced amino acid sequence of Cqdsx was predicted to contain a highly conserved DM domain and shared nearly 50% identity to DM-peptides from other species. The results of quantitative Real-time PCR in various tissues revealed that Cqdsx was strongly expressed in gonads, while was almost undetectable in gill, heart, hepatopancreas, muscle and intestine. Comparing expression level in different embryonic stages found that Cqdsx was gradually increased with the development of the embryos. In situ hybridization to gonad sections showed that intensive hybridization signals were mainly observed in oocytes and ovarian lamellae and weak signals were detected in spermatocyte. Additional, Cqdsx gene exhibited the higher transcript levels in the early stage of ovarian development. Furthermore, RNAi-targeting Cqdsx silencing induced a decrease of Cq-IAG trascripts, which regulated the male sexual differentiation in crustacean.Conclusion: DM-domain genes play an important role in the sex determination and differentiation among animal kingdom. The full-length cDNA of Cqdsx in C. quadricarinatus was isolated and characterized. Our findings strongly suggests an essential role for Cqdsx in the female ovarian development/differentiation of the redclaw crayfish. These data may provide us a better understanding of sex determination in C. quadricarinatus.