bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated total bile acid levels during late pregnancy are associated with the risk of small-for-gestational-age infants
Authors: Li Li , Chen Wei , Qin Xin-Xin , Ma Li , Liu Zhi-Bing , Lu Xue , Gao Xing-Xing , Wang Hua , Zhao Mei , Yang Yuan-Yuan , Li Xiao-Lan , Chen Yuan-hua , Xu De-Xiang
Published: September 2019

Background Intrahepatic cholestasis of pregnancy (ICP) is common in pregnant women and is diagnosed by detecting serum total bile acid (TBA) levels. We aimed to investigate the association between serum total bile acid (TBA) levels during late pregnancy and the incidence of small-for-gestational-age (SGA) infants in a Chinese population.Methods The present study was a retrospective cohort study that included 11811 eligible mother-and-singleton-offspring pairs. The correlations between TBA levels and birth sizes, including birth weight, birth length, head circumference and chest circumference, were explored. The relative risk (RR) with 95%CI for SGA infants were estimated among subjects with ICP by multiple logistic regression analysis.Results Serum TBA levels were inversely linked with birth sizes. According to TBA levels, 11120 pregnant women were controls, 563 mild ICP, and 128 severe ICP. Birth sizes in ICP groups were lower than control group, and were the lowest in severe ICP group. Further analysis showed that 24.51% neonates were SGA infants among subjects with mild ICP (adjusted RR: 3.44; 95%CI: 2.72, 4.34) and 39.06% among subjects with severe ICP (adjusted RR: 6.54; 95%CI: 4.27, 10.02), higher than 7.39% among controls. For adjusted models, linear regression analysis showed that each 1μmol/L increase in TBA levels was associated with 11.1g (95%CI: -12.7, -9.5) decrease in birth weight, 0.045cm (95%CI: -0.053, -0.036) decrease in birth length, 0.034cm (95%CI: -0.040, -0.028) decrease in head circumference, and 0.041cm (95%CI: -0.047, -0.034) decrease in chest circumference, respectively.Conclusion Elevated TBA levels during late pregnancy are associated with an increased risk of SGA infants.
Reducing Maternal Mortality: an Assessment of the Availability and Quality of Emergency Obstetric and Newborn Care in Esan Central Local Government Area of Edo State
Authors: JOMBO Sunday Emmanuel , ENABUDOSO Ehigha , NJOKU Anthonia , AFEKHOBE Jedidiah
Published: September 2019

BackgroundThere is global public health burden of maternal mortality and is worse in Sub-Saharan Africa. Esan Central LGA in Nigeria has an estimated maternal mortality of 1747 per 100,000 live births which is unacceptably high. Emergency obstetric care has been advocated as a measure to avert maternal mortality as about 15% of pregnancies developed complications which may be unpredictable. There is therefore need to access the availability and quality of EmOC in the area. This study aimed to assess the availability and quality of emergency obstetric and newborn care (EmONC) services in the areaMethodsWe conducted a descriptive cross-sectional study and an in-depth interview. Data was collected using UN/AMDD assessment tools (Handbook). Forty key informants’ interviews with major facility managers, pregnant women and health care providers were also done and triangulated. Analysis was done using IBM SPSS statistics- 20, while the in-depth interviews were audio taped, transcribed and analyzed by thematic coding. In addition EmONC services indicators were calculated.ResultThe availability of EmONC services in Esan central LGA was 3.7/500,000 population. The availability of EmONC services was limited at the primary and secondary level of health care. The comprehensive EmOC was adequate (3.7/500000 population) and it is available at the tertiary health facility. The met need for EmONC was 62.6%, obstetric case fatality was 1.2%, and caesarean section rate was 24 %, while the still birth rate was 2.6%. The respondents had adequate knowledge and concern about the burden of maternal death. Major causes of maternal death reported were haemorrhage, hypertension / convulsion in pregnancy and prolong labour. Major contributing factors to maternal death are lack of money, poor antenatal care, and poor attitudes of health care providers, inappropriate referral network, lack of equipment and EmONC drugs, inadequate skill birth attendants and delay in getting treatment. Overall remark on the quality of EmONC services was poor.Conclusion There are limited EmONC services at the primary and secondary health centers that require urgent attention in effort to reducing maternal mortality. There is need for supply of equipment, emergency obstetric care drugs, training and re-training of staff. The community and the health care providers need re-orientation as to the reproductive health care requirements of the people in such a manner that is client centered and with appropriate referral network.
Quality Of Life Questionnaire for women with Gestational Diabetes Mellitus (GDMQ-36): Development and Psychometric Properties
Authors: Mokhlesi Samira , Simbar Masoumeh , Tehrani Fahimeh Ramezani , Kariman Nourossadat , Majd Hamid Alavi
Published: September 2019

Background Gestational diabetes mellitus carries serious risks to mother and fetus and causes social, mental, and psychological consequences which can affect mothers’ quality of life. Accordingly, this study aims to develop and assess the psychometric properties of quality of life questionnaire for women with gestational diabetes mellitus. Methods A methodological study of sequential exploratory mixed method was developed and implemented. It included qualitative (development of a quality of life questionnaire for mothers with GDM) and quantitative (assessment of psychometric prosperities of quality of life questionnaire for mothers with GDM) phases. Results Based on the findings of the qualitative phase and literature review, the primary questionnaire was prepared with 142 items. The outcome of face validity and content validity assessment was a 67-item questionnaire. S-CVI and S-CVR turned out to be 0.92 and 0.68, respectively. The results of exploratory factor analysis yielded an instrument with 36 items in five domains including concerns about high-risk pregnancy, perceived constraints, disease complications, medication and treatment, and support. Five factors explained 46.68% of the total variance of the questionnaire. The results indicated a moderate and significant correlation between the questionnaire of “Diabetes Clients Quality Of Life” and the researcher-made questionnaire (r=0.63). Cronbach’s alpha coefficient for the entire scale was 0.93 and the intra-class correlation coefficient was 0.95. Conclusion Quality of life questionnaire for mothers with GDM is a valid and reliable tool capable of measuring the quality of life of women with GDM.
Long-term, Sustained Feeding by Asian citrus psyllid Disrupts Salicylic Acid Homeostasis in Sweet Orange
Authors: Ibanez Freddy , Suh Joon Hyuk , Wang Yu , Stelinski Lukasz L.
Published: September 2019

Background Phloem-feeding insects are known to modulate the salicylic acid (SA) signaling pathway in various plant-insect interaction models. Diaphorina citri is a phloem feeding vector of a deadly phytopathogen and interactions with its host that may modulate plant defense are not well understood. The objectives of this study were to investigate the molecular mechanisms involved in transcriptional regulation of SA modification and activation of defense-associated responses in sweet orange ( Citrus sinensis ) exposed to various durations (7-, 14- and 150- days) of continuous feeding by D. citri .. Results We quantified expression of genes involved in SA pathway activation and subsequent modification, as well as, associated SA metabolites (SA methyl ester, 2,3-Dihydroxybenzoic acid and SA 2-O-β-D-glucoside). NPR1 and PR-1 expression was upregulated in plants exposed to continuous feeding by D. citri for 14 days. Expression of BSMT-like , MES1-like and DMR6-like oxygenase , as well as, accumulation of their respective SA metabolites (SA methyl ester, 2,3-Dihydroxybenzoic acid) was significantly higher in plants exposed to continuous feeding by D. citri for 150 days than in those without D. citri infestation. Concomitantly, expression of UGT74F2-like was significantly downregulated and its metabolite, salicylic acid 2-β-D-glucoside, was highly accumulated in trees exposed to 150 d of feeding compared to control trees without D. citri . Conclusions D. citri herbivory differentially regulated transcription and SA-metabolite accumulation in citrus leaves, depending on duration of insect feeding. Our results suggest that prolonged and uninterrupted exposure (150 d) of citrus to D. citri feeding suppressed plant immunity and inhibited growth, which may highlight the importance of vector suppression as part of HLB management in citrus.
Regeneration of double haploid plants from unpollinated ovary cultures of watermelon
Authors: Zhu Yingchun , Sun Dexi , Deng Yun , Li Weihua , An Guolin , Si Wenjing , Gao Pu , Liu Junpu
Published: September 2019

Background: Watermelon (Citrullus lanatus), a major fresh fruit, is planted worldwide. Because double haploid plants may be used as parents to shorten watermelon breeding cycle, the present study optimized conditions for regenerating haploid plants from ovaries without pollination.Results: The results revealed that, the 10% sodium hypochlorite sterilized for 10 min is best for ovary enlargement. In addition, a dark culture period of 14 days promoted the ovary enlargement. The MS medium containing 0.5 mg/L NAA, 1.0 mg/L 6-BA and 0.5mg/L KT promoted the embryoid differentiation. The M2 medium containing 0.02 mg/L TDZ, 0.5 mg/L NAA, 0.5 mg/L 6-BA could be used for producing complete plants. The different genotypes affected the embryoid induction. The present study obtained regenerated plants that were established in field. Flow cytometry analyses revealed that the regenerated plants were haploid, diploid or tetraploid plant. The seedlings which were treated with culture medium can increase the chance of chromosome doubling. The SSR marker analyses showed that the diploid and tetraploid plants were homozygous at all six loci tested, indicating that these regenerated plants were double- or tetra-haploid plants.Conclusions: Haploid and homozygous diploid can be obtained through the culture of unpollinated ovary of watermelon, which is an effective way to innovate watermelon germplasm. The present study provides homozygous plants for future watermelon breeding.
In Vitro comparison of cyclic fatigue resistance of TruNatomy in single and double curvature canals compared with different nickel-titanium rotary instruments
Authors: Elnaghy Amr M. , Elsaka Shaymaa E , Mandorah Ayman
Published: September 2019

Background The purpose of this study was to compare the cyclic fatigue resistance of newly developed TruNatomy instruments (TRN) in single and double (S-shaped) curvature canals with HyFlex CM (HCM), Vortex Blue (VB) and RaCe (RC) instruments.Methods Size 20/0.04 taper and size 25/0.04 of HCM, VB and RC were used. For TRN instruments, size 20/0.04 taper (small) and size 26/0.04 taper (prime) were used. The instruments were tested in artificial canals with double curvature (coronal curve; 60° curvature, 5 mm radius and apical curve; 70° curvature and 2 mm radius) and single curvature (60° curvature, 5 mm radius). The number of cycles to failure (NCF) was recorded. Data were statistically analyzed and Weibull analysis was performed on NCF data. Statistical significance was set at p < 0.05.Results TRN and HCM revealed significantly higher NCF compared with the other instruments for both tested sizes in single and double curvature canals ( p < 0.05). TRN and HCM showed no significant difference in the NCF ( p > 0.05). The probability of survival was higher for HCM and TRN instruments than VB and RC instruments.Conclusion HCM and TRN instruments were more resistance to cyclic fatigue than VR and RC instruments in single and double curvature canals. HCM and TRN instruments were anticipated to survive with higher number of cycles than the other tested instruments. RC instrument had the lowest fatigue resistance than the other instruments.
Prioritization of risk factors of gingival hyperplasia during orthodontic treatment: the role of biofilm
Authors: VINCENT-BUGNAS Séverine , BORSA Leslie , GRUSS Apolline , LUPI Laurence
Published: September 2019

Background: The mechanism of gingival growth that may occur during fixed orthodontic treatment is not yet fully understood and the amount of dental plaque is often incriminated. The objective of this study was to evaluate the prevalence of gingival growth during multi-attachment orthodontic treatment and to prioritize its risk factors Methods: This comprehensive cross-sectional descriptive study was conducted on 193 orthodontic patients in good general health, treated by a fixed appliance. Periodontal clinical parameters such as plaque index, gingival index, probing pocket depth, periodontal phenotype and gingival enhancement index were recorded. Likewise, the brushing habits and the date of the last scaling were noted. The orthodontic parameters studied were the duration of the treatment, the type of attachment, they alloys used for the arches and the type of ligatures. Descriptive statistics were carried out, then univariate analyses were achieved thanks to cross sectional tables and lastly, a multivariate analysis allowed a hierarchization of the risk factors. Results: Gingival growth occurred for 49.7% of patients included. The risk factors for this pathology during fixed orthodontic treatment were conventional metal brackets (OR = 3.5), oral ventilation (OR = 3), male gender (OR = 2.2), thick periodontium (OR = 2) and elastomeric ligations (OR = 2). After achievement of the logistic regression, the amount of plaque would not be directly related to the development of this gingival increase. Conclusions: Among the risk factors that underlie gingival growth during multi-attachment therapy, the amount of plaque is not found. The qualitative assessment of the plaque and its evolution during treatment could clarify the role of the biofilm in the occurrence of gingival overgrowth.
Utilization of dental services and associated factors among preschool children in China
Authors: Gao Xiaoli , Ding Min , Xu Mengru , Wu Huijing , Zhang Chunzi , Wang Xing , Feng Xiping , Tai Baojun , Hu Deyu , Lin Huancai , Wang Bo , Zheng Shuguo , Liu Xuenan , Rong Wensheng , Wang Weijian , Wang Chunxiao , Si Yan
Published: September 2019

Background: This study sought to evaluate dental utilization among 3-,4-, and 5-year-old children in China and to use Andersen’s behavioural model to explore influencing factors, thereby providing a reference for future policy making.Methods: A cross-sectional study utilizing data from the Fourth National Oral Health Survey was performed from August 2015 to December 2016. Survey data for children in the 3- to 5-year-old age groups were extracted. Patient data were collected using a questionnaire answered by the child’s parents, and clinical data were collected during a clinical examination. Stratification and survey weighting were incorporated into the complex survey design. Descriptive statistics, bivariate correlations and logistic regression results were then analysed to assess associations.Results : The oral health service utilization rates during the prior 12 months were 9.5% among 3-year-old children, 12.1% among 4-year-old children, and 17.5% among 5-year-old children. “No dental diseases” and “dental disease was not severe” were the principal reasons that children had not attended a dental visit in the past 12 months. Greater child age, increased parental educational level, and good oral health brief by parents was associated with an increased likelihood that the child received dental services within the past 12 months. Children who lived in urban areas and who belonged to families with high annual per capita incomes tended to have relatively higher oral health service utilization rates in the past 12 months. In addition, dental pain, evaluated dental health, and decayed, missing, and filled surface (DMFS) scores were significantly linked to dental visits. The results also demonstrated that children were more likely to see a dentist if they brushed their teeth more frequently or brushed their teeth with their parents’ help.Conclusion: The rate of dental service utilization was relatively low among preschool children. It is necessary to strengthen oral health education for parents and children, thereby improving oral health knowledge as well as attitude, and promoting dental utilization.
A pilot trial on lithium disilicate partial crowns using a novel prosthodontic Functional Index for Teeth (FIT)
Authors: Cagidiaco Edoardo Ferrari , Grandini Simone , Goracci Cecilia , Joda Tim
Published: September 2019

Background Lithium disilicate is now a well accepted material for indirect restorations. The aim of this trial was to evaluate two lithium disilicate systems using a novel prosthodontic Functional Index for Teeth (FIT).Methods Partial adhesive crowns on natural abutment posterior teeth were made on sixty patients (clinicaltrial.gov # NCT 01835821). Patients were divided into two groups: Group 1 e.max press (Ivoclar), Group 2 LiSi press (GC Co.). The restorations were followed-up for 3 years. The FIT is composed of seven variables (Interproximal, Occlusion, Design, Mucosa, Bone, Biology and Margins), each of them to be evaluated using a 0-1-2 scoring scheme. The Mann-Whitney ‘U’ test was applied. The level of significance was set at p<0,05.Results Survival rate was 100%, without any biological or technical complication. No statistically significant difference emerged between the two groups in any of the assessed variables (p>0.05).Conclusions The results showed that it is possible to evaluate the clinical performance of partial crowns using FIT. The FIT proved to be an effective tool to foresee the possible risk of failures and to monitor the performance of the restorations at each recall. The two lithium dislocate materials showed same results after 3 years of clinical service.
Assessment of motor outcomes in multiple sclerosis patients with walking impairment treated with Fampridine using motor evoked potentials
Authors: TROFIN DANIELA MARILENA , TROFIN DAN , IGNAT BOGDAN , CIOBICA ANDREI , STAMATE TEODOR , BILD WALTHER
Published: September 2019

Backgound : the purpose of the study is to consider the utility of Transcranial Magnetic Stimulation (TMS) in patients with Multiple Sclerosis (MS) and walking impairment, treated with Fampridine, as correlated with the 25-Foot-Walk test (T25-FW). It is known that clinical benefits should be identified within two to four weeks after starting the treatment; otherwise, if there is no benefit reported by patients, it should be discontinued. Methods: 15 MS patients with walking impairment, ranked between 3.5 and 7 on the Expanded Disability Status Scale (EDSS), were investigated by T25-FW and TMS. Evaluations were performed prior to Fampridine 10 mg twice daily administration, 5 and 12 days afterwards, and also 1 and 3 months later. The medium age was 42.8 years and an average duration of the disease was 12.06 years. Results: we assessed an improvement of walking by 2.1 seconds measured on the T25-FW after the first 12 days in 9 patients, which correlated with a 2 miliseconds improvement of the Central Motor Conduction Time (CMCT). For the other 6 patients there was no visible clinical improvement. Nevertheless, CMCT dropped by 0.5 ms and the motor conduction speed by 1 millisecond in 4 of these 6 patients. Fampridine administration was continued in the 4 cases. At the end of the 3 months period, their walking speed measured as on the T25-FW also improved by 2 sec. Conclusions: the amelioration of TMS parameters anticipated the improvement of speed on the T25-FW. In spite of the early false negative clinical response, electrophysiological findings could predict a future clinical improvement if treatment is continued.
Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia
Authors: Radeke Leah J , Herman Michael
Published: September 2019

Background: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans , being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans . Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.
Genome-wide association study reveals novel genetic markers associated with endurance athlete status
Authors: Al-Khelaifi Fatima , Yousri Noha , Albagha Omar , Semenova Ekaterina A. , Kostryukova Elena , Kulemin Nickolay A , Borisov Oleg V , Andryushchenko Liliya B , Larin Andrey K , Generozov Edward V , Donati Francesco , Botrè Francesco , Abraham David , Hingorani Aron , Georgakopoulos Costas , Suhre Karsten , Ahmetov Ildus , Elrayess Mohamed
Published: September 2019

Background: The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite athletes using GWAS approach, followed by a functional validation of significant SNPs by metabolomics analysis.
Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 753 European international-level athletes (594 males, 159 females) by comparing allelic frequencies between athletes specialized in sports with high (n=630) and low/moderate (n=123) aerobic component. Validation of results was performed by comparing the frequencies of the most significant SNPs between 176 elite Russian endurance athletes and 173 Russian controls or 43 sprinters. Two novel SNPs showed significant associations with endurance athlete status at Bonferroni level of significance (rs56330321 in ATP2B2, p=1.46E-7) and FDR level of significance (rs2635438 in SYNE1, p=2.54E-7), respectively. Replication study using Russian cohorts and a subsequent meta-analysis have confirmed the association of rs56330321 and rs2635438 SNPs with endurance athlete status at genome-wide significance (P= 5.13E-09 and 1.91E-08, respectively). Metabolomics analysis revealed several amino acids and lipids associated with the identified SNPs with potential roles in performance enhancement.
Conclusions: This is the first report of GWAS significant SNPs and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.
Genetic markers-based genome assembly and the reference genome of the selfing fish Kryptolebias hermaphroditus: Identification of 63 cytochrome P450 genes and the interspecific syntenic comparison
Authors: Choi Beom-Soon , Han Jeonghoon , Kim Min-Sub , Sakakura Yoshitaka , Lee Bo-Young , Lee Jae-Seong
Published: September 2019

Background: The selfing fish Kryptolebias hermaphroditus has unique reproductive system for self-fertilization, making genetically homozygous offsprings. Here, we report on high density genetic map-based genome assembly for the K. hermaphroditus Panama line (PanRS).

Results: The numbers of scaffolds were 5,212 and the genome was 683,992,224 bp (N50=27.45 Mb). The length of anchored scaffold onto 24 linkage groups was 652,231,070 bp (95.3% of genome) with the gap 0.01% and GC content 39.33% and complete Benchmarking Universal Single-Copy Orthologs value was 96.6%. The numbers of annotated genes were 36,756 (average gene length 1,368 bp) with the GC content of 54.1%. To examine the difference of two sister species in the genus Kryptolebias, we compared the genomes of K. hermaphroditus PanRS and Kryptolebias marmoratus PAN line on the composition of transposable elements. Also we identified 63 cytochrome P450 (CYP) genes from K. hermaphroditus PanRS with their basal expression levels and compared the syntenies containing loci of CYP genes on five linkage groups.

Conclusions: In this paper, we discussed the potential use of the genome of K. hermaphroditus PanRS with the potential role of duplicated CYP genes, studying in defense mechanism in the view of molecular evolutionary ecotoxicology. This K. hermaphroditus genome information will be helpful for a better understanding on genome-wide mechanistic view of CYP genes over evolution in the view of fish environmental ecotoxicology.
Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis
Authors: Kato Tatsuya , Azegami Junya , Yokomori Ami , Dohra Hideo , Enshasy Hesham A. El , Park Enoch Y.
Published: September 2019

Background: Ashbya gossypii naturally overproduces riboflavin and has been utilized for industrial riboflavin production. To improve riboflavin production, various approaches have been developed. In this study, to investigate the change in metabolism of a riboflavin-overproducing mutant, namely, the W122032 strain (MT strain) that was isolated by disparity mutagenesis, genomic analysis was carried out.
Results: In the genomic analysis, 33 homozygous and 1377 heterozygous mutations were detected. Among these heterozygous mutations, the proportion of mutated reads in each gene was different, ranging from 21 to 75%. These results suggest that the MT strain exhibits a mixture of diploidy, triploidy and tetraploidy, or contains multiple nuclei containing different mutations. We tried to isolate haploid spores from the MT strain to prove it ploidy, but these spores were never isolated. This result indicate MT strain does not produce its spores. Homozygous and heterozygous mutations were found in genes encoding enzymes involved in amino acid metabolism, the TCA cycle, purine and pyrimidine nucleotide metabolism and the DNA mismatch repair system. Especially, genes encoding enzymes in mitochondria had many homozygous and heterozygous mutations intensively. These results suggest that the overproduction of riboflavin in the MT strain may be associated with mitochondrial dysfunction.
Conclusion: This study provides new insights into riboflavin production in A. gossypii and the usefulness of disparity mutagenesis for the creation of new types of mutants for metabolic engineering.
Transcriptomic analysis of dead end knockout testis reveals germ cell and gonadal somatic factors in Atlantic salmon
Authors: Kleppe Lene , Edvardsen Rolf Brudvik , Furmanek Tomasz , Andersson Eva , Skaftnesmo Kai Ove , Segafredo Frida Thyri , Wargelius Anna
Published: September 2019

Background
Sustainability challenges are currently hampering an increase in salmon production. Using sterile salmon can solve problems with precocious puberty and genetic introgression from farmed escapees to wild populations. Recently sterile salmon was produced by knocking out the germ cell-specific dead end (dnd). Several approaches may be applied to inhibit Dnd function, including gene knockout, knockdown or immunization. Since it is challenging to develop a successful treatment against a gene product already existing in the body, alternative targets are being explored. Germ cells are surrounded by, and dependent on, gonadal somatic cells. Targeting genes essential for the survival of gonadal somatic cells may be good alternative targets for sterility treatments. Our aim was to identify and characterize novel germ cell and gonadal somatic factors in Atlantic salmon.

Results
We have for the first time analysed RNA-sequencing data from germ cell-free (GCF)/dnd knockout and wild type (WT) salmon testis and searched for genes preferentially expressed in either germ cells or gonadal somatic cells. To exclude genes with extra-gonadal expression, our dataset was merged with available multi-tissue transcriptome data. We identified 389 gonad specific genes, of which 194 were preferentially expressed within germ cells, and 11 were confined to gonadal somatic cells. Interestingly, 5 of the 11 gonadal somatic transcripts represented genes encoding secreted TGF-β factors; gsdf, inha, nodal and two bmp6-like genes, all representative vaccine targets. Of these, gsdf and inha had the highest transcript levels. Expression of gsdf and inha was further confirmed to be gonad specific, and their spatial expression was restricted to granulosa and Sertoli cells of the ovary and testis, respectively. Finally, we show that inha expression increases with puberty in both ovary and testis tissue, while gsdf expression does not change or decreases during puberty in ovary and testis tissue, respectively.

Conclusions
This study contributes with transcriptome data on salmon testis tissue with and without germ cells. We provide a list of novel and known germ cell- and gonad somatic specific transcripts, and show that the expression of two highly active gonadal somatic secreted TGF-β factors, gsdf and inha, are located within granulosa and Sertoli cells.
IPEV: a web server for inferring pathogenic enhancers with variants
Authors: Zhang Guanxiong , Xie Aimin , Bai Jing , Luo Tao , Yuan Huating , Liao Gaoming , Luo Shangyi , Liao Jianlong , Xu Jinyuan , Shi Jian , Zhang Yong , Zhang Xinxin , Zhao Tingting , Xiao Yun , Li Xia
Published: September 2019

Background
Enhancer has been recognized as an important driver whose genetic alterations contribute to disease progression. However, there is still no easy-to-use tools to identify pathogenic enhancers, allowing for deciphering functional influence of genetic variants on enhancer.
Results
We developed a user-friendly one-stop shop platform, named inferring pathogenic enhancer with variant (IPEV), only requiring variants as input, to quickly infer the pathogenic enhancers that harbor variants affecting their activities. Results of IPEV are explored in an interactive, user-friendly web environment, which is designed to highlight the most probable pathogenic enhancers and their target genes. Furthermore, IPEV provides intuitive visualizations of how a variant affects the corresponding enhancer activity by mediating TF binding changes.
Conclusions
IPEV is specially designed to prioritize the potentially pathogenic enhancers with genetic variants, and provides intuitive visualizations how a variant affects the corresponding enhancer activity by mediating which transcription factor binding changes. The use of IPEV does not require any specialized computer skills. We believe that IPEV will be useful in interpreting non-coding variants by the inferring pathogenic enhancers. It is freely available at http://biocc.hrbmu.edu.cn/IPEV/ or http://210.46.80.168/IPEV and supports recent versions of all major browsers.
Unraveling the evolutionary origins of Histone fold motif (HFM) in plants
Authors: Kumar Amish , Yadav Gitanjali
Published: September 2019

Background The three helical Histone Fold Motif (HFM) of core histone proteins provides an evolutionarily favoured site for the protein-DNA interface. Despite significant variation in sequence, the HFM retains a distinctive structural fold that has diversified into several non-histone protein families in. In this work we explore the ancestry of non-histone HFM containing families in the plant kingdom.Results A sequence search algorithm was developed using iterative profile Hidden Markov Models to identify remote homologs of core-histone proteins. The resulting hits were functionally annotated, classified into families, and subjected to comprehensive phylogenetic analyses via Maximum likelihood and Bayesian methods. We have identified over 4000 HFM containing proteins in the plant kingdom that are not histones, mostly existing as diverse transcription factor families, distributed widely within and across taxonomic groups.Conclusion Patterns of homology suggest that core histone subunit H2A has evolved into newer families like NF-YC and DrAp1, whereas the H2B subunit of core histones shares a common ancestry with NF-YB and Dr1 class of TFs. Core histone subunits H3 and H4 were found to have evolved into DPE and TAF proteins, respectively. Taken together these results provide insights into diversification events during the evolution of the histone fold motif, including sub-functionalization and neo-functionalization of the HFM.
Multilocus phylogeny and cryptic diversity of white-toothed shrews (Mammalia, Eulipotyphla, Crocidura) in China
Authors: Chen Shunde , Qing Jiao , Liu Zhu , Liu Yang , Tang Mingkun , Murphy Robert W. , Pu Yingting , Wang Xuming , Guo Keji , Jiang Xuelong , Liu Shaoying
Published: September 2019

Background: Crocidura, the most speciose mammalian genus, occurs across much of Asia, Europe and Africa. In China, the taxonomy has been primarily based on cursory morphological comparisons and molecular phylogenetic relationships of the genus remain unexplored. In order to understand the phylogeny of this group in China, we estimated the first multi-loci phylogeny and conducted species delimitation, including taxon sampling throughout their distribution range.Results: We obtained one mitochondrial gene (~ 1, 134 bp) and three nuclear genes (~ 2, 170 bp) for 132 samples from 57 localities. Molecular analyses identified at least 14 putative species that occur within two major well-supported groups in China. Polyphyletic C. wuchihensis appears to be composed of two putative species. Two subspecies, C. rapax rapax and C. rapax kurodai should be elevated to full species status. A phylogenetic tree based on mitochondrial gene from Asian Crocidura species showed that C. rapax rapax was found embedded within C. attenuate, making the latter a paraphyletic group. Three strongly supported cryptic species are revealed from Motuo of Xizang, Zada of Xizang, Hunan and Zhejiang. The divergence time estimation suggested that China’s Crocidura species began to diversify during the late Pliocene (3.70 Ma) and the Early Pleistocene (2.33 Ma) periods, followed by a series of diversifications through the Pleistocene period.Conclusions: The cryptic diversity found in this study indicated that the number of species is strongly underestimated under the current taxonomy. We propose that the three cryptic species should be evaluated using extensive taxon sampling and comprehensive morphological and morphometric approaches. Climate change since the late Pliocene periods and the uplift of the Himalayas may have resulted in the diversification and speciation of China’s Crocidura species. In short, the underestimated diversity underlines the need for a taxonomic revision of China’s Crocidura species.
Side Effect Concerns and their Impact on Women’s Uptake of Modern Family Planning Methods in Rural Ghana: A Mixed Methods Study
Authors: Schrumpf Leah A. , Stephens Maya J. , Nsarko Nathaniel E. , Akosah Eric , Baumgartner Joy Noel , Ohemeng-Dapaah Seth , Watt Melissa H.
Published: September 2019

Background: Despite availability of modern family planning methods and a desire for smaller families, many women decide to forgo modern methods due to anticipated side effects. The goal of this study was to examine the use of modern family planning in one district in rural Ghana, and to understand the role that side effects play in women’s decisions to start or continue use. Methods: This exploratory mixed-methods study included 281 surveys and 33 in-depth interviews of women 18-49 years old from the Amansie West District of Ghana. The survey assessed contraceptive use and potential predictors of use. In-depth interviews examined the context around uptake and continuation of contraceptive use, with a particular focus on the role of perceived and experienced side effects. Results: The prevalence of unmet need for modern family planning among sexually active women who wanted to avoid pregnancy (n=135) was 68.9%. No factors were found to be significantly different in comparing those with a met need and unmet for modern family planning. Qualitative interviews revealed significant concerns about side effects stemming from previous method experiences and/or rumors regarding short-term impacts and perceived long-term consequences of family planning use. Conclusion: As programs have improved women’s ability to access modern family planning, it is paramount to address patient-level barriers to uptake, in particular information about side effects and misconceptions about long-term use. Unintended pregnancies can be reduced through comprehensive counseling about contraceptive options including accurate information about side effects, and the development of new contraceptive technologies that meet women’s needs in low-income countries.
Spectrometral and histopathological evaluation of metal ion levels in soft tissue around uncemented implants collected during revision hip replacement.
Authors: Kmieć Krzysztof , Kozłowski Piotr , Synder Marek , Borowski Andrzej
Published: September 2019

Background
The aim of the study was to measure metal ion concentration (Ti, Co, Cr, Mo, Ni, Al) around loosened uncemented hip implants and to compare their levels around the cups and steams.
Methods
Soft tissue samples were collected for analysis in 25 patients (25 hips) during revision hip arthroplasty for aseptic loosening in the years 2007-2009. All tissues collected during the revision arthroplasty were submitted for analysis under a light microscope and ICP –MS analysis. All tissues displayed “foreign body” type chronic inflammatory infiltration with PE and/or metal deposits and metallic inclusions.
Results
The Inductively Coupled Plasma Mass Spectrometry study of cementless hip implants revealed that the metal ions pass from loose elements of the implants to the surrounding tissues in significant concentrations ranging from a few hundred to several thousand μg / kg. Moreover, the tissues surrounding the loosened cups contained significantly higher concentrations of Ti and Ni metal ions than the tissue surrounding the steams.
Conclusions
Of all the metal ions used for construction of hip implants, the highest tissue concentration was noted in the case of Ti ions. In any case, regardless of the type of endoprosthesis, the concentrations of Ti and Ni metal ions were higher in tissues surrounding the cup rather than around the stem.
Relationship Between Postural Stability and Falls Risk in Elderly People with Lumbar Spondylosis During Local Vibratory Stimulation for Proprioception: A Cross-sectional Study
Authors: Ito Tadashi , Sakai Yoshihito , Nishio Reiya , Ito Yohei , Yamazaki Kazunori , Morita Yoshifumi
Published: September 2019

Background: The proprioceptive postural strategy for elderly people with lumbar spondylosis who are at risk for falls has not been extensively investigated.
Aims : We aimed to investigate the relationship between proprioceptive postural stability and falls risk in elderly people with lumbar spondylosis.
Methods : In this cross-sectional study, centre-of-pressure displacement was determined in elderly people with lumbar spondylosis during upright stance while standing on a Wii Balance Board with their eyes closed (falls risk group, n = 27; non-fall risk group, n = 88). Vibratory stimulations at 30 Hz were applied to the lumbar multifidus and gastrocnemius to evaluate the relative contribution of different proprioceptive signals used in postural control (relative proprioceptive weighting ratio [RPW]).
Results: Compared with the non-fall risk group, the falls risk group showed a high RPW at 30 Hz (P = 0.002) and high falls score (P < 0.001). Logistic regression analysis revealed that RPW at 30 Hz (odds ratio, 1.2; 95% confidence interval: 1.044–1.194) was independently associated with falls risk after controlling for confounding factors. Among variables of falls risk, RPW at 30 Hz was found to be a significant factor (P < 0.001).
Discussion: The falls risk group of elderly people with lumbar spondylosis was at a higher risk for falls, which was exacerbated by RPW at 30 Hz depending on the ankle strategy. A decrease in the input of the muscle spindles in the lumbar multifidus could be a possible mechanism underlying the decreased reliance on lumbar muscle proprioception in these individuals.
Managing clustering effects and learning effects in the design and analysis of multicentre randomised trials: A survey to establish current practice
Authors: Conroy Elizabeth J. , Blazeby Jane M. , Burnside Girvan , Cook Jonathan A , Gamble Carrol
Published: September 2019

Background

Patient outcomes can depend on the treating centre, or health professional, delivering the intervention. Skills of health professionals improve with experience in delivery, meaning that outcomes may also be associated with changes in skill, or learning. Considering any potential difference in intervention delivery at trial design will ensure that any adjustments can be made, as appropriate, at the analysis. The objective of this work was to establish current practice for the allowance of clustering and learning effects in the design and analysis of randomised multicentre trials.

Methods

A ten-question survey was developed comprising open and closed questions that drew upon quotes from existing guidelines, references to relevant publications, and example trial scenarios. It was piloted and checked for face validity within the research team. All registered UK Clinical Research Collaborative registered Clinical Trials Units were invited to participate.

Results

Completed surveys were obtained from 44 of 50 Units. Clustering was managed through design by stratification, commonly by centre and less commonly by treatment provider. Most Units had allowed for learning by design through defining a minimum level of expertise for treatment provider (89%). One third of Units reported experience of expertise-based designs. The majority of Units indicated experience in adjusting for clustering during analysis, by centre or treatment provider, although approaches to doing so varied. Analysis of learning was rarely performed for the main analysis (n=1), although many Units reported approaches to consider such effects, such as sensitivity analyses. Responders provided insight behind the approaches used within their Unit and reasons for, or against, alternative approaches.

Conclusion

This survey identifies widespread awareness of the potential methodological challenges associated with the design and analysis of multicentre trials, although approaches used and opinions on these vary. These results suggest that variation in approaches used exists both across Units and within, suggesting that this decision can depend on the type of trial being conducted. Reasons for approaches were provided and approaches justified by responders. These results highlight the need for more agreement between triallists about how to best design and analyse trials of different types and/or further research to establish optimal methods.
Implications of sex offender classification on reporting demographic characteristics, health, and criminal careers: Results from an Australia jurisdiction
Authors: Gullotta Mathew , Greenberg David M , Adily Armita , Cale Jesse , Butler Tony G
Published: September 2019

Background: Using cross-sectional and retrospective data to classify sex offenders has implications for epidemiological and survey research. However, there is little empirical evidence regarding the practical implications of these for applied research. This study describes the data linkage process and subsequent classification of sex offenders in a cohort of prisoners recruited as part of an Australian inmate health survey.
Methods: Data linkage was used to link the New South Wales (NSW) Inmate Health Surveys to the state’s offending database to identify men with histories of sexual offending. Sex offenders were classified into men who sexually offended against children only (ChildSOs), against adults only (AdultSOs), and men who sexually offended against both children and adults (PolySOs).
Results: By using historical offending data rather than the current offence information only, an additional 35.4% of men were identified who had histories of sexual offences. Differences were found between the sex offender subgroups in terms of demographic characteristics, health, and criminal careers. PolySOs were the least likely to report less than high school education, self-employment, being single, and children. Half the ChildSOs reported a mental health issue and, similarly to PolySOs, half reported four or more chronic health conditions. In terms of their criminal careers, PolySOs were the eldest when committing their first: non-sexual, non-violent crime (M=43.2 years, SD=13.8); violent crime (M=39.5 years, SD=11.1); and sexual crime (M=47.8 years, SD=11.2) compared to the other groups. These men also committed more sexual offences (M=5.91, SD=11.2) compared to those who only offended against one victim age group.
Conclusion: These findings suggested that whenever possible historical offending records should be used to more accurately identify sex offenders, and that differences in demographic, health, and criminal careers exist for the different sex offender subgroups.

Keywords: adult sex offender, child sex offender, classification, data linkage, health, polymorphous, specialisation.