bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification of candidate genes associated with β-glucan trait in a hulled and hulless barley (Hordeum vulgare L.) population
Authors: Zhou Longhua , He Ting , Guo Guimei , Li Jing , Lu Ruiju , Huang Jianhua , Li Yingbo , Liu Chenghong
Published: March 2020

Background: To date, excavating the genomic sites based on the whole barley assembled genome sequences associated with β-glucan trait remains blank, resulting in omission of several genetic loci or existence of false positive. Results: Here, of 87 barley resources (39 hulled and 48 hulless) collected from China, the β-glucan content ranged from 2.07% to 6.56%. GWAS (genome-wide association study) was carried out using 191,098 SNP markers by RRGS (Reduced-Representation Genome Sequencing) platform in FarmCPU model excuted in rMVP R package. Four subpopulations (POP1～POP4) were identified. GWAS showed one SNP, in chromosome 7 (chr7), negatively mapped and for two genes HORVU7Hr1G000320, HORVU7Hr1G000040, which are from nucleotide triphosphates hydrolases superfamily; previous study had proved the superfamily could inhibit β-glucan synthase activities. GWAS also showed that five SNPs for β-glucan trait were separately mapped in chr2, chr3, chr4, chr5 and chr6 non-coding regions and one SNP mapped for HORVU1Hr1G000010 in chr1, which is for plant sugar response. Conclusions: Through the highest density of SNP markers to date, this study identifys several SNP genetic loci with high degree of confidence for β-glucan trait, and has a certain value for β-glucan regulatory mechanism research in furture.
Dissection of the genetic basis of oil content in Chinese peanut cultivars by association mapping
Authors: Liu Nian , Huang Li , Chen Weigang , Wu Bei , Pandey Manish K. , Luo Huaiyong , Zhou Xiaojing , Guo Jianbin , Chen Haiwen , Huai Dongxin , Chen Yuning , Lei Yong , Liao Boshou , Ren Xiaoping , Varshney Rajeev K. , Jiang Huifang
Published: March 2020

Background Peanut is one of the primary sources for vegetable oil worldwide, and enhancing oil content is the main objective in these peanut breeding programs. Linked markers for oil content is required for use in genomics-assisted breeding (GAB), and association mapping is one of the promising approaches for discovery of associated markers. Results An association mapping panel consisting of 292 peanut varieties extensively distributed in China were phenotyped for oil content and genotyped with 583 polymorphic SSR markers. These markers amplified 3663 alleles with an average of 6.28 alleles per locus. The results of structure, phylogenetic relationship, and PCA analyses indicated two subgroups majorly differentiating based on geographic regions. Genome-wide association analysis using genetic and phenotypic data identified 12 associated markers including one (AGGS1014_2) highly stable association controlling up to 9.94% phenotypic variance explained (PVE) across multiple environments. Interestingly, the frequency of the favorable alleles for 12 associated markers showed a geographic difference. Two associated markers AGGS1014_2 and AHGS0798 with 6.90-9.94% PVE were verified to enhance oil content in an independent RIL population. The combined genotypes of AGGS1014_2 and AHGS0798 appeared to experience selection during the breeding program. Conclusion This study provided insights into the genetic basis of oil content in peanut and verified that two SSR markers were highly associated with oil content. Our results could facilitate marker-assisted selection for high-oil content breeding.
Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.
Authors: Matsuoka Hiroshi , Hayashi Takahiro , Takigami Karen , Imaizumi Kazuyoshi , Shiroki Ryoichi , Ohmiya Naoki , Sugiura Kazumitsu , Kawada Kenji , Sawaki Akira , Maeda Koutaro , Ando Yousuke , Uyama Ichiro
Published: March 2020

Background Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted. Methods This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival. Results The subjects were 280 patients including. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonia. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P=0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P<0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs. Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy. Conclusion Although the onset of irAEs was difficult to predict based on pre-treatment tests. Because ICIs were more effective in improving outcomes in patients with irAEs, the continuation of ICI therapy might be beneficial with the control of symptoms after the onset of irAEs.
Exercise training improves the adipocyte accumulation and muscle fibrosis of the muscle by TGF-β1 and α-SMA reduction after botulinum toxin type A administration in mice
Authors: Lee Esther , Im Song I , Kim Yu-jin , Kim Su Young , Na Jungtae , Kim Beom Joon
Published: March 2020

Background: We aimed to investigate the effect of treadmill exercise on functional recovery of the mouse gastrocnemius muscle and nerve after botulinum toxin type A (BoNT-A) administration. Methods: After injecting 0.5 units of BoNT-A into the gastrocnemius muscle of ICR mice, treadmill exercise was carried out for a six-week period, after which the muscle volume, weight, and sciatic functional index (SFI) were obtained and nerve conduction study (NCS) and histological evaluation were performed. Results: There was no change in the gastrocnemius weight and volume, but NCS and SFI increased after exercise. Exercise prevented induced adipocyte accumulation and muscle fibrosis. Moreover, TGF-β1 and α-SMA expression decreased and CD34, BDNF, and SNAP-25 expression increased when treadmill exercise was performed after BoNT-A injection. Conclusions: The exercise was effective in the recovery of nerve function and would help in the recovery of muscle function by preventing accumulation of fat cells and muscle fibrosis after BoNT-A administration.
Genome-wide Identification of ATP Binding Cassette (ABC) Transporter and Heavy Metal Associated (HMA) Gene Families in Flax (Linum usitatissimum L.)
Authors: Khan Nadeem , You Frank , Datla Raju , Ravichandhran Sridhar , Jia Bosen , Cloutier Sylvie
Published: March 2020

Background Flax (Linum usitatissimum L.) is a self-pollinated crop and diversified into two morphotypes for its stem fibre and seed oil. The availability of the flax reference genome sequence, previously assembled into 15 pseudomolecules, enables the characterization of important gene families. The ABC transporter and HMA gene families are considered important gene families in the control of cadmium (Cd) accumulation in crops. To date, the genome-wide analysis of these two gene families has been successfully conducted in several plant species but no systematic study is available for the flax genome. Results Here we described both gene families in flax to provide a comprehensive overview of its evolution and some support towards the functional annotation of its members. The 198 ABC transporter and 12 HMA genes identified in the flax genome were classified into eight ABC transporter and four HMA subfamilies based on their phylogenetic analysis and domain compositions. Nine of these genes, i.e., LuABCC9, LuABCC10, LuABCG58, LuABCG59, LuABCG71, LuABCG72, LuABCG73, LuHMA3, and LuHMA4, were orthologous with the Cd associated genes in Arabidopsis, rice and maize. Ten motifs were identified from all ABC transporter and HMA genes and several motifs were conserved for all genes with similar gene length, but different subfamilies had their different motif structures. Both the ABC transporter and HMA families were highly conserved among subfamilies of flax and with Arabidopsis. While four types of gene duplication were observed at different frequencies, whole-genome or segmental duplications were the most frequent with 162 genes, followed by 29 dispersed, 14 tandem and 4 proximal, suggesting that segmental duplications contributed substantially to the expansion of both gene families in flax. The rates of non-synonymous to synonymous (Ka/Ks) mutations of paired duplicated genes were mostly less than one, indicative of a predominant purifying selection. Only five pairs of genes clearly exhibited positive selection with a Ka/Ks ratio greater than one. Gene ontology analyses suggested that most flax ABC transporter and HMA genes functioned in ATP binding, transporter, catalytic, ATPase activity, and metal ion binding. The RNA-Seq analysis of eight different organs demonstrated diverse expression profiling patterns of the genes and revealed their functional or subfunctional conservation and neo-functionalization. Conclusion Characterization of the ABC transporter and HMA genes will help in the functional analysis of candidate genes in flax and other crop species.
Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4
Authors: zhao huihui , Gu Wenqing , Ouyang Huogui , Pan Wenbin , Zhang Hanbin , Shuai Ling , Diao Ruiying , Wang Liping
Published: March 2020

Background Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents a major cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear. Methods The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA). Results We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p , which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p . Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P <0.01; E 2 : P <0.01; FSH: P <0.01). Conclusions Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes aggravated POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.
Reduced insulin resistance partly mediated the association of high dietary magnesium intake with less metabolic syndrome in a large Chinese population
Authors: Yang Na , He Liyun , Li Yuxiu , Xu Lingling , Ping Fan , Li Wei , Zhang Huabing
Published: March 2020

Background High dietary magnesium intake may reduce insulin resistance (IR) and metabolic syndrome (MetS). However, previous studies were inconsistent in Asian population and there have been no study about the mediation of IR in the relationship between dietary magnesium intake and MetS. Thus, this cross-sectional analysis aimed to evaluate the association between dietary magnesium intake, IR and MetS using data from China Health and Nutrition Survey. Methods Dietary magnesium intake was defined as daily dietary magnesium intake divided by body weight. Logistic regression analysis was used to calculate the odds ratio (OR) for IRand the prevalence of MetS across the quartile categories of dietary magnesium intake. Results 8,254 participants were included in final analysis. We found a significant negative association between dietary magnesium intake and IR, the multivariable-adjusted OR for HOMA-IR comparing the highest to the lowest quartile of dietary magnesium intake was 0.435 (95% confidence intervals (CI) 0.376 to 0.502). The prevalence of the MetS was 33.5%, 24.9%, 18.4% and 13.4% for increasing quartiles of dietary magnesium intake (p <0.001). The direct effect and indirect effect of dietary magnesium on MetS was found significant, and the calculated percentage of mediation was 23.0%. Conclusion Our study demonstrated a significant and independent negative relationship among weight adjusted dietary magnesium intake, HOMA-IR and MetS in a large Chinese population. IR partly mediated the relationship between dietary magnesium intake and MetS.Keywords: diet magnesium intake; metabolic syndrome; insulin resistance; Chinese population; mediation effect
The clinical value of passive leg raising plus ultrasound to predict fluid responsiveness in children after cardiac surgery
Authors: Luo Deqiang , Dai Wei , Lei Lei , cai xueying
Published: March 2020

Background: There are few non-invasive monitoring methods that can reliably predict FR in children, this article aims to investigate the value of the doppler ultrasound evaluation of passive leg raising (PLR) induced changes in stroke volume (SV) and cardiac output(CO) in predicting the fluid responsiveness (FR) in children with mechanical ventilation after congenital cardiac surgery. Methods: A total of 40 children with mechanical ventilation after congenital cardiac surgery who requiring volume expansion (VE) were eventually included in this observational study. Hemodynamic parameters such as heart rate (HR), blood pressure, SV, and central venous pressure (CVP) were monitored before and after PLR and VE respectively, and changes of SV and CO were assessed by bedside ultrasound as well. The patients showing an increase in SV >10% in response to VE were considered responders (26 patients), and the rest were defined as nonresponders (14 patients). Results: The results showed that ΔSV-PLR and ΔCO- PLR were positively correlated with ΔSV-VE (r = 0.683, P<0.001 and r= 0.374, P = 0.017, respectively), and the area under the ROC curve (AUC) of ΔSV-PLR was 0.879 (95% CI [0.745 1.000], P < 0.001). The best cut-off value of ΔSV-PLR for predicting FR was 13%, with its sensitivity and specificity was 81.8% and 86.3%, respectively. ΔCVP, ΔHR, and ΔMAP were weak predictive FR in children patients. Conclusion: Our study demonstrated that SV changes assessed by noninvasive ultrasound combined with PLR could be a feasible method for evaluating fluid responsiveness in children with congenital cardiac surgery and mechanical ventilation. Keywords: congenital heart surgery; fluid responsiveness; passive leg raising; ultrasound.
Clear cell tumor of the lung Could Be Aggressive: a case report and review of the literature
Authors: shen leilei , LIN Jixing , REN Zhipeng , WANG Bailin , Liu You , Yuan Jing , ZHAN Lianbin
Published: March 2020

Background: Clear cell tumor of the lung (CCTL) is a rare and mostly benign pulmonary neoplasm arising from perivascular epithelioid cells. Only about 100 cases have been reported and half of them were in China. Limited details about CCTL often cause diagnostic or therapeutic problems. Case presentation: We describe a case of 28-year-old woman with gradually increased and enlarged multiple nodules in the left lower lobe. The patient underwent a fine-needle aspiration biopsy and was considered as CCTL. A left lower lobectomy and mediastinal lymph node dissection was performed. The gradual changes in size (1.4 cm to 2.8 cm) and quantity (10 to 49) of CCTL in this case was the biggest difference from previously reported cases. Conclusions: CCTL is a very uncommon and mostly benign PEComatous tumor with no specific morphologic features. We present a case of CCTL with multiplicity and rapid growth, which may indicate its aggressive nature. The accumulation of similar cases will help clarify its exact disease nature and to improve our understanding of such tumor.
Applying 3D-Eco Routing Model to Reduce Environmental Footprint of Road Transports in Addis Ababa City
Authors: Busho Seifu Woldemichael , Alemayehu Daniel
Published: March 2020

Climate change has emerged as a very important threat to economic development, atmosphere, and public health. One of the driving factors for global climate change was road transportation. therefore, this sector needs a responsibility of reducing its effect on the environment. this study finds ways to mitigate climate change impacts on environment especially greenhouse gas emissions and other selected air pollutants by anew navigation concept called eco route by applying a 3D Eco -Routing Model to reduce the environmental footprints of road transports in Addis Ababa city for distribution vehicles. The applied model in this study considered the road gradient, varying velocity or speed of vehicles, and weight of vehicles to evaluate gradient effects on consumption of fuel, CO 2 and also other air pollutants emission, the model is applied in three scenarios within different vehicle weight range and three different cases in the city of Addis Ababa, political capital of Africa, The attained results imply eco-routes emission Reduction potentials up to 39.81% from fuel and CO 2 and 25.65% from other air pollutant in the tested scenarios. The results showed that Eco Routes have the ability of reducing Fuel consumption, CO 2 and other air pollutant emission rate. Such potentials of eco routes make them an ecological solution for a future sustainable transportation in Addis Ababa City. This study recommends the use of Eco Routes, rather than Fastest and Shortest Routes, where significant road gradients exist.
Acquisition of Oral Microbiota is Driven by Environment, Not Host Genetics
Authors: Mukherjee Chiranjit , Moyer Christina O. , Steinkamp Heidi M. , Hashmi Shahr B. , Guo Xiaohan , Ni Ai , Leys Eugene J. , Griffen Ann L.
Published: March 2020

Background: The oral microbiota is acquired very early, but the factors shaping its acquisition are not well understood. Previous studies comparing monozygotic (MZ) and dizygotic (DZ) twins have suggested that host genetics plays a role. However, all twins share an equal portion of their parent’s genome, so this model is not informative for studying parent-to-child transmission. We used a novel study design that allowed us to directly examine the genetics of transmission by comparing the oral microbiota of biological versus adoptive mother-child dyads. Results: No difference was observed in how closely oral bacterial community profiles matched for adoptive versus biological mother-child pairs, indicating little if any effect of host genetics on the fidelity of transmission. Both adopted and biologic children more closely resembled their own mother as compared to unrelated women, supporting the role of contact and environment. Mother-child strain similarity increased with the age of the child, ruling out early effects that are lost over time. No effect on the fidelity of mother-child strain sharing from vaginal birth or breast feeding was seen. Analysis of extended families showed that fathers and mothers were equally similar to their children, and that cohabitating couples showed even greater strain similarity than mother-child pairs. These findings support the role of contact and shared environment, and age, but not genetics, as determinants of microbial transmission, and were consistent at both species and strain level resolutions, and across multiple oral habitats. In addition, analysis of individual species all showed similar results. Conclusions: The host is clearly active in shaping the composition of the oral microbiome, since only a few of the many bacterial species in the larger environment are capable of colonizing the human oral cavity. Our findings suggest that these host mechanisms are universally shared among humans, since no effect of genetic relatedness on fidelity of microbial transmission could be detected. Instead our findings point towards contact and shared environment being the driving factors of microbial transmission, with a unique combination of these factors ultimately shaping the highly personalized human oral microbiome.
Nutrient gradients simulate different adjustments of coral-algal symbiosis
Authors: Tong Haoya , Zhou Guowei , Zhang Fang , Sun Jin , Zhang Weipeng , Huang Hui , Qian Pei-Yuan
Published: March 2020

Background: Eutrophication is one of the major causes of coral reef degradation but the effect of eutrophication on coral and its symbiont algae remains unclear, particularly for the larval stage of coral. In the present study, the physiological and transcriptomic responses of the larvae of an ecologically important scleractinian coral Pocillopora damicornis were analyzed after a 5-day exposure to elevated nitrate in order to assess the survival and adaptation of coral-algal symbiosis under elevated nutrients. Results: The results showed that multiple larval transcripts were significantly correlated with Symbiodiniaceae transcripts. The major differentially expressed transcripts in coral/Symbiodiniaceae included those responsible for energy synthesis/comsumption, nitrogen metabolism and stressor response. Slightly elevated nitrate concentration could in fact promote the health of coral meta-organism. With increase in nitrate concentrations, coral larvae showed significant stress response to maintain the coral-algal symbiosis and coral-algal symbiosis was impaired, while Symbiodiniaceae switched photosynthetic states for ATP synthesis, material transport and nitrogen metabolism for symbiosis maintenance under the control of the coral hosts.Conclusions: Our results suggest that adjustment of coral-algal symbiosis via coral control and a shift in Symbiodiniaceae photosynthetic states serves as the basis of coral meta-organism adaptation under eutrophication stresses. The larvae of P. damicornis and Symbiodiniaceae displayed different transcriptomic responses to nitrate enrichment. Coral larva meta-organism can adapt to moderately elevated nutrient concentration while extreme eutrophication can impair coral-algal symbiosis and affect coral larvae survival ultimately.
Fungal succession in decomposing woody debris across a tropical forest disturbance gradient: A field experiment
Authors: Dossa Gbadamassi G.O. , Yang Yun-Qiang , Hu Weiming , Paudel Ekananda , Schaefer Douglas , Yang Yong-Ping , Cao Kun-Fang , Xu Jian-Chu , Bushley Kathryn E. , Harrison Rhett D.
Published: March 2020

Background: Fungi are essential agents in decomposing woody debris (WD), an important carbon pool in forests. However, the ecology and dynamics of these fungal communities are poorly understood, especially in tropical forests. A better understanding of anthropogenic impacts, such as forest disturbances, on WD decomposition is also needed to appreciate their consequences on ecosystem functioning. Here, we examined the impacts of forest degradation and roles of fungal diversity and composition on WD decomposition rates across a disturbance gradient in a tropical montane rain forest in Xishuangbanna, SW China over three years. We measured wood specific gravity (WSG) loss from 280 logs from Litsea cubeba (low-WSG) and Castanopsis mekongensis (high-WSG). We concomitantly monitored fungal communities from 418 samples using next-generation sequencing after 0, 18 and 36 months field exposure. Results: Incubation time, habitat and termite presence were key drivers of fungal community composition. Fungal community succession showed a priority effect of precedent communities. C. mekongensis WD consistently harbored ~1.4 times less fungal species than L. cubeba , but had ~1.4 times more unique operational taxonomic unit (OTU) at 18 mo. Shared OTUs between wood species increased with time up to ~63 % at 36 mo. Regardless of wood species, fungal diversity and both saprotrophs and white-rot abundances peaked at 18 months. However, fungal diversity was not a significant predictor of WSG loss. WSG loss did not vary among habitats. This may result from compensatory changes in dominant functional traits, such as decay mechanisms (e.g., proportion of white rot-fungi, soft-rot fungi). For example white- rot fungal proportions were double in open land compared to mature forest. Likewise, more saprothrophs colonized high-WSG wood. Finally, ascomycetes (mainly Sordariomycetes and Dothiodeomycetes) and basidiomycetes (mostly Agaricomycetes) were dominant fungal groups. Open land was dominated by Trichoderma, regenerating forest by Herpothrichiellaceae and mature forest by Penicillium . Conclusions: White- and soft-rot fungi co-dominated decomposition, with the later increasing through time. A succession of different fungal functional groups yielded similar decomposition rates across the disturbance gradient. Incorporating dominant fungal functional trait dynamics into biogeochemical models may improve predictions of carbon dynamics.
Host Genetic Determinants of the Vaginal Microbiome in Kenyan Women
Authors: Mehta Supriya D , Nannini Drew R , Otieno Fredrick , Green Stefan J. , Agingu Walter , Landay Alan , Zheng Yinan , Hou Lifang
Published: March 2020

Background Women with vaginal microbial community state types (CST) with high diversity and a paucity of Lactobacillus crispatus have increased risk of HIV acquisition. Identifying host genetic factors associated with the vaginal microbial composition may aid in elucidating the biological mechanisms regulating these microbial traits and inter-individual variations in associated diseases. Methods We conducted genome-wide associations studies (GWASs) on vaginal microbiome traits on 171 Kenyan women. Study participants were genotyped using the Infinium Global Screening Array and 16S rRNA gene amplicon sequencing was performed to characterize the vaginal microbiome. Linear and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between L. crispatus, L. iners, G. vaginalis, Shannon diversity index, and CST with host genetic single nucleotide polymorphisms (SNPs). Pathway enrichment analyses were performed to identify biological processes putatively associated with the vaginal microbiome traits. Results At baseline, the median age of study participants was 22 years (IQR: 22 – 25) with 22% having Bacterial vaginosis (Nugent score 7-10). L. crispatus and L. iners were present in 24% and 83% of samples with a mean relative abundance of 31% and 45%, respectively. The most significant SNPs associated were: rs73330467 located between LOC101927488-GRAMD2B ( P =4.79x10 -6 ) for L. crispatus ; rs527430 in the FOXD2-TRABD2B ( P =6.98x10 -7 ) region for L. iners ; rs1229660 in the SNX10-LOC441204 ( P =4.65x10 -6 ) region for G. vaginalis; rs972741 in the ZKSCAN2-HS3ST4 ( P =8.52x10 -7 ) region for Shannon diversity index; and rs2302902 in ELK3 ( P =3.09x10 -6 ) for CST. During pathway enrichment analysis, Toll-like receptors, cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP ( L. iners , Shannon), TLR2 (Shannon, CST), MBL2 ( L. iners , G. vaginalis , CST), and MYD88 ( L. iners, Shannon). Conclusions We identified numerous genetic loci on several pathways related to host immunity and infection that were associated with vaginal microbiome traits, providing insight into potential host genetic influences on vaginal microbiome composition. This new information should guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals, and across populations.
Clinical significance of circulating tumor cells and metabolic signatures in lung cancer after surgical removal
Authors: Yang Dawei , Yang Xiaofang , Li Yang , Zhao Peige , Fu Rao , Ren Tianying , Hu Ping , Wu Yaping , Yang Hongjun , Guo Na
Published: March 2020

Background Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain. Methods Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes. Results LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 164 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA and LB groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI = 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC. Conclusions These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.
Serum biomarkers discovery of steroid-induced femoral head osteonecrosis in Chinese female by comparative proteome
Authors: Zeng Ping , Zhang Chongxing , Zhou Yanqiong , Li Jinyi , Li Tao , Peng Dingding , Lai Chongrong , Liu Xiong , Chen Jinlong , Fan Siqi
Published: March 2020

Background Steroid-induced osteonecrosis of the femoral head (SONFH) is a disabling, aseptic and ischemic disease due to excessive glucocorticoids (GCs) usage. Patients with SONFH are commonly asymptomatic, which makes its early diagnosis is challenge, the pathological mechanisms of SONFH are not well-known, the purpose of the present study was to screen diagnostic biomarkers for SONFH. Methods The differential expression of serum proteins from SONFH, traumatic osteonecrosis of the femoral head (TONFH) patients and healthy volunteers (CK) in Chinese females was compared using iTRAQ, and potential diagnostic biomarkers were verified by western blotting. Results Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), Domain and Clusters of Orthologous Groups (COG) analyses revealed key groups of proteins, pathways and domains differentially regulated among SONFH, TONFH and healthy volunteers in Chinese female, the results showed that peptidase S1, fibrinogen, transferrin, lipid transport domains and hematopoietic cell lineage, fat digestion, absorption, peroxisome proliferator-activated receptor (PPAR) pathways were associated with the development of SONFH. Finally, C-reactive protein (CRP), serum amyloid A protein (SAA1), alpha-1-acid glycoprotein 1 (ORM1) and dopamine beta-hydroxylase were selected for verification of differential expression using western blotting. Conclusions Our data suggest that dysfunction of hematopoietic cell lineage, adhesion, fat digestion and absorption, PPAR pathways may be involved in the pathogenesis of SONFH, serum proteins SAA1, ORM1 could be used as new potential diagnostic biomarkers for SONFH.
Lactobacillus sakei suppresses collagen-induced arthritis and modulates the differentiation of T helper 17 cells and regulatory B cells
Authors: Jhun Jooyeon , Min Hong Ki , Ryu Jaeyoon , Lee Seon-Yeong , Ryu Jun-Geol , Choi Jeong Won , Na Hyun Sik , Jung Yunju , Park Sang-Jun , Park Myeong Soo , Kwon Bin , Ji Geun Eog , Cho Mi-La , Park Sung-Hwan
Published: March 2020

Background: To evaluate the immunomodulatory effect of Lactobacillus sakei in a mouse model of rheumatoid arthritis (RA) and in human immune cells. Methods: We evaluated whether L. sakei reduced the severity of collagen-induced arthritis (CIA) and modulated interleukin (IL)-17 and IL-10 levels, as well as whether it affected the differentiation of CD4 + T cells and regulatory B cells. We evaluated osteoclastogenesis after culturing bone marrow-derived mononuclear cells with L. sakei. Results: The differentiation of T helper 17 cells and the serum level of IL-17 were suppressed by L. sakei in both human peripheral blood mononuclear cells and mouse splenocytes. The serum level of IL-10 was significantly increased in the L. sakei -treated group, whereas the regulatory T cell population was unchanged. The population of regulatory B cells significantly increased the in L. sakei -treated group. Oral administration of L. sakei reduced the arthritis incidence and score in mice with CIA. Finally, osteoclastogenesis and the mRNA levels of osteoclast-related genes were suppressed in the L. sakei -treated group. Conclusion: L. sakei exerted an anti-inflammatory effect in an animal model of RA, regulated Th17 and regulatory B cell differentiation, and suppressed osteoclastogenesis. Our findings suggest that L. sakei has therapeutic potential for RA.
Using multimodal MRI to investigate alterations in brain structure and function in rats with type 2 diabetes.
Authors: Lawson Christopher M , Rentrup Kilian FG , Cai Xuezhu , Kulkarni Praveen P , Ferris Craig
Published: March 2020

Objectives This is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was assumed there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with non-invasive MRI. Methods The transgenic BBZDR/Wor rat, an animal model of T2MD, and age-matched controls were studied for changes in brain structure using voxel-based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site-specific data on over 168 different brain areas. Results There was an overall reduction in brain volume focused primarily on somatosensory cortex, cerebellum and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus. Conclusion Are the neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods common to the clinic, similar to those reported in T2DM patents? In comparison to the clinical findings, the data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.
Acacetin exert antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- mice
Authors: Wu Yao , Song Fei , Li Yunda , Li Jingzhou , Cui Yukai , Hong Yixiang , Han Weimin , Wu Weiyin , Lakhani Ishan , Li Gang , Wang Yan
Published: March 2020

Background : Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti-inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE -/- ) mice. Methods : Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non-induced by human oxidized low density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE -/- mice were fed either a western diet or a chow diet. Acacetin prodrug (15mg/kg) was injected subcutaneously two times a day for 12weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Results : Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3μM. Moreover, 3μM Acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo , acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet-fed apoE -/- mice. Conclusions : Our findings demonstrate the anti-oxidative and anti-atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic-related cardiovascular diseases (CVD).
Flexor hallucis longus tendon transfer through a single incision in the treatment of chronic Achilles tendon rupture with large defect
Authors: Xu Yangbo , Li Cui , Xiang Feifan , Deng Yong , Lu Xiaobo , Wei Daiqing
Published: March 2020

Background To evaluate the medium-to-long term clinical outcome of flexor hallucis longus tendon transfer through a single incision in the treatment of chronic Achilles tendon rupture with a defect greater than 5 cm. Methods Clinical data of patients treated with flexor hallucis longus tendon transfer due to chronic Achilles tendon rupture between January 2009 and December 2016 were reviewed retrospectively. All cases were presented with Achilles tendon rupture for more than 4 weeks after injury. The defect of the Achilles tendon was greater than 5 cm after debridement in all patients. Clinical outcomes were assessed with AOFAS Ankle-Hindfoot Scale (AOFAS-AH), Achilles tendon Total Rupture Score (ATRS) and AOFAS Hallux Metatarsophalangeal-lnterphalangeal Scale (AOFAS-HM). Results 18 patients were followed successfully for 24-83 months (mean follow-up time of 43.2 months) and 5 were lost. According to the complete datasets obtained from 18 patients, none of the tendons re-ruptured during the follow-up. The AOFAS-AH and ATRS at last follow-up visit was 94.4 ± 3.2 (87-100) and 89.6 ± 5.9 (72-98) respectively, which revealed statistically significant improvement from the preoperative score of 58.2 ± 6.3 (49-70) and 53.3 ± 7.3(42-68). The AOFAS-HM at last follow-up visit was 90.1 ± 5.2 (77-97). Conclusion The flexor hallucis longus tendon transfer through a single incision is a safe and simple method for chronic Achilles tendon rupture with minimal morbidity and complications.
Water quality analysis of municipality public water supply in the case of Asella town at the source of Ashebeka River, a cross-sectional study design.
Authors: Eshete Amde Eshete
Published: March 2020

Background Drinking water quality is the main concern because in developing countries like Ethiopia, where contaminated water was one of the main vehicles for the transmission of water borne diseases. Therefore, the objective of this research was to assess the physicochemical & bacteriological water quality in Asella town, Ethiopia. Methods A cross-sectional study was carried out from November, 2015 to April, 2016 G.C. 8 liter composite water samples in plastic bottles packed cold chain had been taken by the investigator from eight different sites with two round totally 192 parameters were analyzed. A standard instrument like AAS for heavy metal analysis was using APAH procedures. Statistical analysis was done by the use of software for data entry Epi info 7 & Minitab 19.2. Results The first round of laboratory had showed that mean± SD TH 59.5± 7.4 mg/L, COD 30± 25.8mg/L, calcium 15± 4.3 mg/L, magnesium 5.3± 0.9 mg/L, BOD5 3± 2.6 mg/L and Nitrate 1.5± 0.1mg/L. The result of microbial analysis was 180CFU/100ml for TF & FC, 40CFU/100ml was E.coli detected in the first study site. The second round physical analysis had showed that municipality water was colourles, odourles & tasteless. But the Mean ± SD turbidity was 32.6± 63.4 mg/L. The mean± SD pH 4.5±0.8,EC 101.8±23.1,TH 24± 2.5 mg/L, calcium 6.9± 0.8 mg/L, magnesium 1. ± 0.6 mg/L, Fluoride 0.4± 0.2mg/L, aluminum 0.3± 0.2 mg/L, DO 4.6± 1.2 mg/L, nitrate 3.3± 2.5 mg/L, nitrite 0.9± 2/5 mg/L, zinc 0.3± 0.4 mg/L, CO32- 7. ± 6 mg/l, chloride 6± 1.3 mg/L, alkalinity 6± 4.9 mg/L, total solid 96± 50.3 mg/L, TDS 62± 14.8 mg/L, sodium 3.9± 2.4 mg/L, potassium 1.7± 0.1 mg/L, iron 0. ± 1mg/L and ammonia 0.9± 0.3 mg/L. There was strong pair wise statistical correlation among water quality parameters with p value < 0.05 Conclusions The water quality analysis was below the limit of WHO standard, but some chemical, turbidity & microbes need a critical attention. So, efficient water treatment must be monitored by the municipality & homemade water treatment by urban community
Effect of intravitreal antibiotic injections on culture-negative keratitis-induced endophthalmitis
Authors: Sim Ha Eun , Kang Min Ji , Park Jae Yong , Kim Jae Suk , Hwang Je Hyung
Published: March 2020

Background: This study aimed to evaluate treatment outcomes of culture-negative keratitis-induced endophthalmitis (CNKE) . Methods: We reviewed the medical records of 13 patients with CNKE, who underwent treated from January 2011 to December 2017. All patients were referred from the emergency room or outpatient department of local clinics. Outcome evaluation included the assessment of visual acuity and any requirements of evisceration/enucleation. Results: Thirteen eyes of 13 patients were included in this study. The mean age of the patients was 75.0 ± 13.3 years. All patients used antibiotic eye drops before the initial visit. Visual acuity values at the initial visit ranged from no light perception to 2/100, while final visual acuity values ranged from no light perception to 2/100. All patients underwent a vitreous tap and intravitreal ceftazidime/vancomycin injection. Two eyes underwent evisceration after intravitreal injection. Conclusions: Intravitreal antibiotic injections demonstrated favorable results for the treatment of patients with CNKE .
Improving geographical accessibility modeling for operational use by local health actors
Authors: Ihantamalala Felana Angella , Herbreteau Vincent , Révillion Christophe , Randriamihaja Mauricianot , Commins Jérémy , Andréambeloson Tanjona , Rafenoarivamalala Feno H , Randrianambinina Andriamihaja , Cordier Laura F , Bonds Matthew H , Garchitorena Andres
Published: March 2020

Background Geographical accessibility to health facilities remains one of the main barriers to access care in rural areas of the developing world. Although methods and tools exist to model geographic accessibility, the lack of basic geographic information prevents their widespread use at the local level for targeted program implementation. The aim of this study was to develop very precise, context-specific estimates of geographic accessibility to care in a rural district of Madagascar to help with the design and implementation of interventions that improve access for remote populations. Methods We used a participatory approach to map all the paths, residential areas, buildings and rice fields on OpenStreetMap (OSM). We estimated shortest route from every household in the District to the nearest primary health care center (PHC) and community health site (CHS) with the Open Source Routing Machine (OSMR) tool. Then, we used remote sensing methods to obtain a high resolution land cover map, a digital elevation model and rainfall data to model travel speed. Travel speed models were calibrated with field data obtained by GPS tracking in a sample of 168 walking routes. Model results were used to predict travel time to seek care at PHCs and CHSs for all the shortest route estimated earlier. Finally, we integrated geographical accessibility results into an e-health platform developed with R Shiny. Results We mapped over 100,000 buildings, 23,000 km of footpaths, and 4,925 residential areas throughout Ifanadiana district; this data is freely available on OSM. We found that over three quarters of the population lived more than one hour away from a PHC, and 10-15% lived more than one hour away from a CHS. Moreover, we identified areas in the North and East of the district where the nearest PHC was further than 5 hours away, and vulnerable populations across the district with poor geographical access (>1 hour) to both PHCs and CHSs. Conclusion Our study demonstrates how to improve geographical accessibility modeling so that results can be context-specific and operationally actionable by local health actors. The importance of such approaches is paramount for achieving universal health coverage in rural areas throughout world.