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Variation in health system performance for managing diabetes among states in India: a cross-sectional study of individuals aged 15 to 49 years
BMC Medicine. 2019 May 13;17(1):92Abstract Background Understanding where adults with diabetes in India are lost in the diabetes care cascade is essential for the design of targeted health interventions and to monitor progress in health system performance for managing diabetes over time. This study aimed to determine (i) the proportion of adults with diabetes in India who have reached each step of the care cascade and (ii) the variation of these cascade indicators among states and socio-demographic groups. Methods We used data from a population-based household survey carried out in 2015 and 2016 among women and men aged 15–49 years in all states of India. Diabetes was defined as a random blood glucose (RBG) ≥ 200 mg/dL or reporting to have diabetes. The care cascade—constructed among those with diabetes—consisted of the proportion who (i) reported having diabetes (“aware”), (ii) had sought treatment (“treated”), and (iii) had sought treatment and had a RBG < 200 mg/dL (“controlled”). The care cascade was disaggregated by state, rural-urban location, age, sex, household wealth quintile, education, and marital status. Results This analysis included 729,829 participants. Among those with diabetes (19,453 participants), 52.5% (95% CI, 50.6–54.4%) were “aware”, 40.5% (95% CI, 38.6–42.3%) “treated”, and 24.8% (95% CI, 23.1–26.4%) “controlled”. Living in a rural area, male sex, less household wealth, and lower education were associated with worse care cascade indicators. Adults with untreated diabetes constituted the highest percentage of the adult population (irrespective of diabetes status) aged 15 to 49 years in Goa (4.2%; 95% CI, 3.2–5.2%) and Tamil Nadu (3.8%; 95% CI, 3.4–4.1%). The highest absolute number of adults with untreated diabetes lived in Tamil Nadu (1,670,035; 95% CI, 1,519,130–1,812,278) and Uttar Pradesh (1,506,638; 95% CI, 1,419,466–1,589,832). Conclusions There are large losses to diabetes care at each step of the care cascade in India, with the greatest loss occurring at the awareness stage. While health system performance for managing diabetes varies greatly among India’s states, improvements are particularly needed for rural areas, those with less household wealth and education, and men. Although such improvements will likely have the greatest benefits for population health in Goa and Tamil Nadu, large states with a low diabetes prevalence but a high absolute number of adults with untreated diabetes, such as Uttar Pradesh, should not be neglected. -
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Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL)
Journal of Intensive Care. 2019 Apr 17;7(1):23Background Sphingosine 1-phosphate (S1P) is a signaling lipid essential in regulating processes involved in sepsis pathophysiology, including endothelial permeability and vascular tone. Serum S1P is progressively reduced in sepsis patients with increasing severity. S1P function depends on binding to its carriers: serum albumin (SA) and high-density lipoproteins (HDL). The aim of this single-center prospective observational study was to determine the contribution of SA- and HDL-associated S1P (SA-S1P and HDL-S1P) to sepsis-induced S1P depletion in plasma with regard to identify future strategies to supplement vasoprotective S1P. Methods Sequential precipitation of lipoproteins was performed with plasma samples obtained from 100 ICU patients: surgical trauma (n = 20), sepsis (n = 63), and septic shock (n = 17) together with healthy controls (n = 7). Resultant fractions with HDL and SA were analyzed by liquid chromatography coupled to triple-quadrupole mass spectrometry (LC-MS/MS) for their S1P content. Results Plasma S1P levels significantly decreased with sepsis severity and showed a strong negative correlation with increased organ failure, quantified by the Sequential Organ Failure Assessment (SOFA) score (rho − 0.59, P < 0.001). In controls, total plasma S1P levels were 208 μg/L (187–216 μg/L). In trauma patients, we observed an early loss of SA-S1P (− 70%) with a concurrent increase of HDL-S1P (+ 20%), resulting in unaltered total plasma S1P with 210 μg/L (143–257 μg/L). The decrease of plasma S1P levels with increasing SOFA score in sepsis patients with 180.2 μg/L (123.3–253.0 μg/L) and in septic shock patients with 99.5 μg/L (80.2–127.2 μg/L) was mainly dependent on equivalent reductions of HDL and not SA as carrier protein. Thus, HDL-S1P contributed most to total plasma S1P in patients and progressively dropped with increasing SOFA score. Conclusions Reduced plasma S1P was associated with sepsis-induced organ failure. A constant plasma S1P level during the acute phase after surgery was maintained with increased HDL-S1P and decreased SA-S1P, suggesting the redistribution of plasma S1P from SA to HDL. The decrease of plasma S1P levels in patients with increasing sepsis severity was mainly caused by decreasing HDL and HDL-S1P. Therefore, strategies to reconstitute HDL-S1P rather than SA-S1P should be considered for sepsis patients. -
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Correction to: Agricultural trade policies and child nutrition in low- and middle-income countries: a cross-national analysis
Globalization and Health. 2019 Apr 10;15(1):28. -
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On and off the rocks: persistence and ecological diversification in a tropical Australian lizard radiation
BMC Evolutionary Biology. 2019 Mar 20;19(1):81Abstract Background Congruent patterns in the distribution of biodiversity between regions or habitats suggest that key factors such as climatic and topographic variation may predictably shape evolutionary processes. In a number of tropical and arid biomes, genetic analyses are revealing deeper and more localised lineage diversity in rocky ranges than surrounding habitats. Two potential drivers of localised endemism in rocky areas are refugial persistence through climatic change, or ecological diversification and specialisation. Here we examine how patterns of lineage and phenotypic diversity differ across two broad habitat types (rocky ranges and open woodlands) in a small radiation of gecko lizards in the genus Gehyra (the australis group) from the Australian Monsoonal Tropics biome. Results Using a suite of approaches for delineating evolutionarily independent lineages, we find between 26 and 41 putative evolutionary units in the australis group (versus eight species currently recognised). Rocky ranges are home to a greater number of lineages that are also relatively more restricted in distribution, while lineages in open woodland habitats are fewer, more widely distributed, and, in one case, show evidence of range expansion. We infer at least two shifts out of rocky ranges and into surrounding woodlands. Phenotypic divergence between rocky ranges specialist and more generalist taxa is detected, but no convergent evolutionary regimes linked to ecology are inferred. Conclusions In climatically unstable biomes such as savannahs, rocky ranges have functioned as zones of persistence, generators of diversity and a source of colonists for surrounding areas. Phenotypic divergence can also be linked to the use of differing habitat types, however, the extent to which ecological specialisation is a primary driver or secondary outcome of localised diversification remains uncertain. -
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Signal peptide replacement resulted in recombinant homologous expression of laccase Lcc8 in Coprinopsis cinerea
AMB Express. 2019 Mar 15;9(1):36Abstract Although the model agaricomycete Coprinopsis cinerea possess 17 different laccase genes, up to now only four C. cinerea laccases have been purified and characterized to some degree. By exchanging the nucleotide sequence of the deduced signal peptide of Lcc8 it was possible to homologously express lcc8 in C. cinerea under control of the Agaricus bisporus gdpII promoter and the C. cinerea lcc1 terminator. The purified Lcc8 showed two bands in the SDS-PAGE with a molecular weight of 64 kDa and 77 kDa, respectively. The IEF determined pI values of 3.3 and 3.4 for both bands. The optimal pH for oxidation of the substrates ABTS, 2,6-dimethoxyphenol, guaiacol and syringaldazine was pH 4.0, pH 5.0, pH 4.5 and pH 5.0, respectively. Best pH for enzyme storage was pH 8.0. The optimal temperature for oxidation of ABTS was 63 °C, while Lcc8 showed activity of at least 50% over 300 min at 50 °C. The comparable high stability of Lcc8 at alkaline pH and higher temperatures can be of interest for biotechnical applications. -
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The central nervous system of Oweniidae (Annelida) and its implications for the structure of the ancestral annelid brain
Frontiers in Zoology. 2019 Mar 12;16(1):6Abstract Background Recent phylogenomic analyses congruently reveal a basal clade which consists of Oweniidae and Mageloniidae as sister group to the remaining Annelida. These results indicate that the last common ancestor of Annelida was a tube-dwelling organism. They also challenge traditional evolutionary hypotheses of different organ systems, among them the nervous system. In textbooks the central nervous system is described as consisting of a ganglionic ventral nervous system and a dorsally located brain with different tracts that connect certain parts of the brain to each other. Only limited information on the fine structure, however, is available for Oweniidae, which constitute the sister group (possibly together with Magelonidae) to all remaining annelids. Results The brain of Oweniidae is ring- shaped and basiepidermal. Ganglia, higher brain centers or complex sensory organs do not exist; instead the central nervous system is medullary. Posterior to the brain the ventral medullary cord arises directly from the ventral region of the brain in Myriowenia sp. while in Owenia fusiformis two medullary cords arise perpendicular to the brain ring, extend caudally and fuse posterior. The central nervous system is composed of a central neuropil and surrounding somata of the neurons. According to ultrastructural and histological data only one type of neuron is present in the central nervous system. Conclusion The central nervous system of Oweniidae is the simplest in terms of enlargement of the dorsal part of the brain and neuron distribution found among Annelida. Our investigation suggests that neither ganglia nor commissures inside the brain neuropil or clusters of polymorphic neurons were present in the annelid stem species. These structures evolved later within Annelida, most likely in the stem lineage of Amphinomidae, Sipuncula and Pleistoannelida. Palps were supposedly present in the last common ancestor of annelids and innervated by two nerves originating in the dorsal part of the brain. A broader comparison with species of each major spiralian clade shows the medullary nervous system to be a common feature and thus possibly representing the ancestral state of the spiralian nervous system. Moreover, ganglia and clusters of polymorphic neurons seemingly evolved independently in the compared taxa of Spiralia and Annelida. -
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Agricultural trade policies and child nutrition in low- and middle-income countries: a cross-national analysis
Globalization and Health. 2019 Mar 15;15(1):21Abstract Background There has been growing interest in understanding the role of agricultural trade policies in diet and nutrition. This cross-country study examines associations between government policies on agricultural trade prices and child nutrition outcomes, particularly undernutrition. Methods This study links panel data on government distortions to agricultural incentives to data from 212,258 children aged 6 to 35 months participating in Demographic and Health Surveys from 22 countries between 1991 and 2010. Country fixed-effects regression models were used to examine the association between within-country changes in nominal rates of assistance to tradable agriculture (government price distortions as a percentage of original prices) and child nutritional outcomes (height-for-age, weight-for-age, and weight-for-height Z-scores) while controlling for a range of time-varying country covariates. Results Five-year average nominal rates of assistance to tradable agriculture ranged from − 72.0 to 45.5% with a mean of − 5.0% and standard deviation of 18.9 percentage points. A 10-percentage point increase in five-year average rates of assistance to tradable agriculture was associated with improved height-for-age (0.02, 95% CI,0.00–0.05) and weight-for-age (0.05, 95% CI: 0.02–0.09) Z-scores. Improvements in nutritional status were greatest among children who had at least one parent earning wages in agriculture, and effects decreased as a country’s proportion of tradable agriculture increased, particularly for weight-for-age Z-scores. Conclusions Government assistance to tradable agriculture, such as through reduced taxation, was associated with small but significant improvements in child nutritional status, especially for children with a parent earning wages in agriculture when the share of tradable agriculture was not high. -
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MetaCHIP: community-level horizontal gene transfer identification through the combination of best-match and phylogenetic approaches
Microbiome. 2019 Mar 04;7(1):36Abstract Background Metagenomic datasets provide an opportunity to study horizontal gene transfer (HGT) on the level of a microbial community. However, current HGT detection methods cannot be applied to community-level datasets or require reference genomes. Here, we present MetaCHIP, a pipeline for reference-independent HGT identification at the community level. Results Assessment of MetaCHIP’s performance on simulated datasets revealed that it can predict HGTs with various degrees of genetic divergence from metagenomic datasets. The results also indicated that the detection of very recent gene transfers (i.e. those with low levels of genetic divergence) from metagenomics datasets is largely affected by the read assembly step. Comparison of MetaCHIP with a previous analysis on soil bacteria showed a high level of consistency for the prediction of recent HGTs and revealed a large number of additional non-recent gene transfers, which can provide new biological and ecological insight. Assessment of MetaCHIP’s performance on real metagenomic datasets confirmed the role of HGT in the spread of genes related to antibiotic resistance in the human gut microbiome. Further testing also showed that functions related to energy production and conversion as well as carbohydrate transport and metabolism are frequently transferred among free-living microorganisms. Conclusion MetaCHIP provides an opportunity to study HGTs among members of a microbial community and therefore has several applications in the field of microbial ecology and evolution. MetaCHIP is implemented in Python and freely available at https://github.com/songweizhi/MetaCHIP . -
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Strain-encoded cardiac magnetic resonance imaging: a new approach for fast estimation of left ventricular function
BMC Cardiovascular Disorders. 2019 Mar 05;19(1):52Abstract Background Recently introduced fast strain-encoded (SENC) cardiac magnetic resonance (CMR) imaging (fast-SENC) provides real-time acquisition of myocardial performance in a single heartbeat. We aimed to test the ability and accuracy of real-time strain-encoded CMR imaging to estimate left ventricular volumes, ejection fraction and mass. Methods Thirty-five subjects (12 healthy volunteers and 23 patients with known or suspected coronary artery disease) were investigated. All study participants were imaged at 1.5 Tesla MRI scanner (Achieva, Philips) using an advanced CMR study protocol which included conventional cine and fast-SENC imaging. A newly developed real-time free-breathing SENC imaging technique based on the acquisition of two images with different frequency modulation was employed. Results All parameters were successfully derived from fast-SENC images with total study time of 105 s (a 15 s scan time and a 90 s post-processing time). There was no significant difference between fast-SENC and cine imaging in the estimation of LV volumes and EF, whereas fast-SENC underestimated LV end-diastolic mass by 7%. Conclusion The single heartbeat fast-SENC technique can be used as a good alternative to cine imaging for the precise calculation of LV volumes and ejection fraction while the technique significantly underestimates LV end-diastolic mass. -
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A constructive review of the State Forest Inventory in the Russian Federation
Forest Ecosystems. 2019 Mar 08;6(1):9Abstract The State Forest Inventory (SFI) in the Russian Federation is a relatively new project that is little known in the English-language scientific literature. Following the stipulations of the Forest Act of 2006, the first SFI sample plots in this vast territory were established in 2007. The 34 Russian forest regions were the basic geographical units for all statistical estimates and served as a first-level stratification, while a second level was based on old inventory data and remotely sensed data. The sampling design was to consist of a simple random sample of 84,700 circular 500 m2 sample plots over forest land. Each sample plot consists of three nested concentric circular subplots with radii of 12.62, 5.64 and 2.82 m and additional subplots for assessing and describing undergrowth, regeneration and ground vegetation. In total, 117 variables were to be measured or assessed on each plot. Although field work has begun, the methodology has elicited some criticism. The simple random sampling design is less efficient than a systematic design featuring sample plot clusters and a mix of temporary and permanent plots. The second-level stratification is mostly ineffective for increasing precision. Qualitative variables, which are not always essential, are dominant, while important quantitative variables are under-represented. Because of very slow progress, in 2018 the original plan was adjusted by reducing the number of permanent sample plots from 84,700 to 68,287 so that the first SFI cycle could be completed by 2020. - View Document
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Guidelines for open peer review implementation
Research Integrity and Peer Review. 2019 Feb 27;4(1):4Abstract Open peer review (OPR) is moving into the mainstream, but it is often poorly understood and surveys of researcher attitudes show important barriers to implementation. As more journals move to implement and experiment with the myriad of innovations covered by this term, there is a clear need for best practice guidelines to guide implementation. This brief article aims to address this knowledge gap, reporting work based on an interactive stakeholder workshop to create best-practice guidelines for editors and journals who wish to transition to OPR. Although the advice is aimed mainly at editors and publishers of scientific journals, since this is the area in which OPR is at its most mature, many of the principles may also be applicable for the implementation of OPR in other areas (e.g., books, conference submissions). -
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Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes a CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity
Journal of Neuroinflammation. 2019 Feb 26;16(1):49Abstract Background Quinoline-3-carboxamides, such as laquinimod, ameliorate CNS autoimmunity in patients and reduce tumor cell metastasis experimentally. Previous studies have focused on the immunomodulatory effect of laquinimod on myeloid cells. The data contained herein suggest that quinoline-3-carboxamides improve the immunomodulatory and anti-tumor effects of NK cells by upregulating the adhesion molecule DNAX accessory molecule-1 (DNAM-1). Methods We explored how NK cell activation by laquinimod inhibits CNS autoimmunity in experimental autoimmune encephalomyelitis (EAE), the most utilized model of MS, and improves immunosurveillance of experimental lung melanoma metastasis. Functional manipulations included in vivo NK and DC depletion experiments and in vitro assays of NK cell function. Clinical, histological, and flow cytometric read-outs were assessed. Results We demonstrate that laquinimod activates natural killer (NK) cells via the aryl hydrocarbon receptor and increases their DNAM-1 cell surface expression. This activation improves the cytotoxicity of NK cells against B16F10 melanoma cells and augments their immunoregulatory functions in EAE by interacting with CD155+ dendritic cells (DC). Noteworthy, the immunosuppressive effect of laquinimod-activated NK cells was due to decreasing MHC class II antigen presentation by DC and not by increasing DC killing. Conclusions This study clarifies how DNAM-1 modifies the bidirectional crosstalk of NK cells with CD155+ DC, which can be exploited to suppress CNS autoimmunity and strengthen tumor surveillance. -
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Protura are unique: first evidence of specialized feeding on ectomycorrhizal fungi in soil invertebrates
BMC Ecology. 2019 Feb 22;19(1):10Abstract Background Ectomycorrhizal fungi (ECM) play a central role in nutrient cycling in boreal and temperate forests, but their role in the soil food web remains little understood. One of the groups assumed to live as specialised mycorrhizal feeders are Protura, but experimental and field evidence is lacking. We used a combination of three methods to test if Protura are specialized mycorrhizal feeders and compared their trophic niche with other soil invertebrates. Using pulse labelling of young beech and ash seedlings we analysed the incorporation of 13C and 15N into Acerentomon gallicum. In addition, individuals of Protura from temperate forests were collected for the analysis of neutral lipid fatty acids and natural variations in stable isotope ratios. Results Pulse labelling showed rapid incorporation of root-derived 13C, but no incorporation of root-derived 15N into A. gallicum. The transfer of 13C from lateral roots to ectomycorrhizal root tips was high, while it was low for 15N. Neutral lipid fatty acid (NLFA) analysis showed high amounts of bacterial marker (16:1ω7) and plant marker (16:0 and 18:1ω9) fatty acids but not of the fungal membrane lipid 18:2ω6,9 in A. gallicum. Natural variations in stable isotope ratios in Protura from a number of temperate forests were distinct from those of the great majority of other soil invertebrates, but remarkably similar to those of sporocarps of ECM fungi. Conclusions Using three in situ methods, stable isotope labelling, neutral lipid fatty acid analysis and natural variations of stable isotope ratios, we showed that Protura predominantly feed on mycorrhizal hyphae via sucking up hyphal cytoplasm. Predominant feeding on ectomycorrhizal mycelia by Protura is an exception; the limited consumption of ECM by other soil invertebrates may contribute to carbon sequestration in temperate and boreal forests. -
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Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema
Clinical and Translational Allergy. 2019 Feb 14;9(1):9Abstract Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. We report a family from Northern Germany with six individuals suffering from recurrent swellings, indicating HAE. Laboratory tests and genetic diagnostics of the genes SERPING1, encoding C1 esterase inhibitor (C1-INH), and F12, encoding coagulation factor XII, were unremarkable. In three affected and one yet unaffected member of the family, we were then able to identify the c.988A > G (also termed c.1100A > G) mutation in the plasminogen (PLG) gene, which has recently been described in several families with HAE. This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the kringle 3 domain of plasminogen. There was no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in adulthood, with swellings of the face, tongue and larynx, including a fatal case of a 19 year-old female individual. The frequency of the attacks was variable, ranging between once per year to once a month. In one individual, we also found decreased serum levels of plasminogen as well as coagulation factor XII. As previously reported in patients with PLG defects, icatibant proved to be very effective in controlling acute attacks, indicating an involvement of bradykinin in the pathogenesis. -
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Rechtliche Rahmenbedingungen der Digitalisierung kulturellen Erbes
Bibliotheksdienst 2018; 52(9) p.687-697Die Digitalisierung bietet ein enormes Potenzial für Wissenschaft, Lehre und Forschung. Doch sind die derzeit geltenden rechtlichen Rahmenbedingungen geeignet, dieses Potenzial auszuschöpfen und gewinnbringend für alle nutzbar zu machen? Nicht nur die aufwändige Recherche nach Rechteinhabern, sondern auch die fehlenden Möglichkeiten, Digitalisate von urheberrechtlich geschützten Werken unter freien Lizenzen nachnutzbar zu machen, erschweren die praktische Umsetzung der gesellschaftlich gewünschten und vielfach auch gesetzlich geforderten digitalen Zugänglichmachung von Sammlungsgegenständen durch Kulturerbeeinrichtungen. -
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Implementing a digital communication assistance tool to collect the medical history of refugee patients: DICTUM Friedland - an action-oriented mixed methods study protocol
BMC Health Services Research. 2019 Feb 06;19(1):103Abstract Background Language barriers play a decisive role in determining the outcomes of medical consultations between healthcare providers and their foreign patients. This issue is a significant challenge to the German healthcare system, especially with the rising number of refugees in recent years. The communication gap between healthcare professionals and their non-German speaking patients sometimes leads to unnecessary medical re-admission, insufficient medical history, incorrect diagnosis, and treatment plans. In this study, we aim to assess the usability and accuracy of a novel digital translation tool in collecting medical history from patients in their native language and to check its effects on healthcare outcomes. Methods The study aims to monitor the implementation of a new digital communication assistance tool (DCAT) and to investigate its impact on the mutual understanding between refugee patients and their German general practitioners (GPs). In the first study phase, an action-oriented approach is used to implement DCAT. In the second study phase, DCAT use will be evaluated with a mixed methods design. The main outcome assesses the re-consultation rates of patients before and after using DCAT. Secondary outcomes include the usability of the tool, its acceptance and perceived quality by patients, the accuracy of the information collected as determined from analysing the reasons for the consultation (ICPC-2 codes), and diagnosis (ICD-10 codes). The acceptance by patients, socio-demographic factors and native language are also taken into account. The research designs for both study phases include questionnaires, semi-structured interviews, non-participant observation and analysis of collected patients’ data. All the collected data is pseudonymised. Discussion The DCAT study is one of the new research projects in primary healthcare investigating the usability, accuracy, and acceptance of digital translation tools during medical encounters. We aim to eliminate significant communication errors and misunderstandings in medical consultations, thereby improving the quality of healthcare outcomes. By applying an action research design, we will attain a more comprehensive evaluation of DCAT scopes and limits. The results of this study are expected to give an in-depth understanding of possible applications and benefits of digital translation tools for patient care. Trial registration German Clinical Trials Register DRKS00013076 , 29/09/2017. -
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Somatic and sociodemographic predictors of depression outcome among depressed patients with coronary artery disease - a secondary analysis of the SPIRR-CAD study
BMC Psychiatry. 2019 Feb 04;19(1):57Abstract Background Depressive symptoms are common in patients with coronary artery disease (CAD) and are associated with an unfavourable outcome. Establishing prognostic patient profiles prior to the beginning of mental health care may facilitate higher efficacy of targeted interventions. The aim of the current study was to identify sociodemographic and somatic predictors of depression outcome among depressed patients with CAD. Methods Based on the dataset of the multicentre SPIRR-CAD randomised controlled trial (n = 570 patients with CAD and ≥ 8 points on the Hospital Anxiety and Depression Scale (HADS)), 141 potential sociodemographic and somatic predictors of the change in the HADS-D depression score from baseline to 18-month-follow-up were derived in two different ways. We screened for univariable association with response, using either analysis of (co)variance or logistic regression, respectively, both adjusted for baseline HADS-D value and treatment group. To guard against overfitting, multivariable association was evaluated by a linear or binomial (generalised) linear model with lasso regularisation, a machine learning approach. Outcome measures were the change in continuous HADS-D depression scores, as well as three established binary criteria. The Charlson Comorbidity Index (CCI) was calculated to assess possible influences of comorbidities on our results and was also entered in our machine learning approach. Results Higher age (p = 0.002), unknown previous myocardial infarction (p = 0.013), and a higher heart rate variability during numeracy tests (p = .020) were univariably associated with a favourable depression outcome, whereas hyperuricemia (p ≤ 0.003), higher triglycerides (p = 0.014), NYHA class III (p ≤ 0.028), state after resuscitation (p ≤ 0.042), intake of thyroid hormones (p = 0.007), antidiabetic drugs (p = 0.015), analgesic drugs (p = 0.027), beta blockers (p = 0.035), uric acid drugs (p ≤ 0.039), and anticholinergic drugs (p = 0.045) were associated with an adverse effect on the HADS-D depression score. In all analyses, no significant differences between study arms could be found and physical comorbidities also had no significant influence on our results. Conclusion Our findings may contribute to identification of somatic and sociodemographic predictors of depression outcome in patients with CAD. The unexpected effects of specific medication require further clarification and further research is needed to establish a causal association between depression outcome and our predictors. Trial registration www.clinicaltrials.gov NCT00705965 (registered 27th of June, 2008). www.isrctn.com ISRCTN76240576 (registered 27th of March, 2008). -
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Siberian larch (Larix sibirica Ledeb.) chloroplast genome and development of polymorphic chloroplast markers
BMC Bioinformatics. 2019 Feb 05;20(Suppl 1):38Abstract Background The main objectives of this study were sequencing, assembling, and annotation of chloroplast genome of one of the main Siberian boreal forest tree conifer species Siberian larch (Larix sibirica Ledeb.) and detection of polymorphic genetic markers – microsatellite loci or simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs). Results We used the data of the whole genome sequencing of three Siberian larch trees from different regions - the Urals, Krasnoyarsk, and Khakassia, respectively. Sequence reads were obtained using the Illumina HiSeq2000 in the Laboratory of Forest Genomics at the Genome Research and Education Center of the Siberian Federal University. The assembling was done using the Bowtie2 mapping program and the SPAdes genomic assembler. The genome annotation was performed using the RAST service. We used the GMATo program for the SSRs search, and the Bowtie2 and UGENE programs for the SNPs detection. Length of the assembled chloroplast genome was 122,561 bp, which is similar to 122,474 bp in the closely related European larch (Larix decidua Mill.). As a result of annotation and comparison of the data with the existing data available only for three larch species - L. decidua, L. potaninii var. chinensis (complete genome 122,492 bp), and L. occidentalis (partial genome of 119,680 bp), we identified 110 genes, 34 of which represented tRNA, 4 rRNA, and 72 protein-coding genes. In total, 13 SNPs were detected; two of them were in the tRNA-Arg and Cell division protein FtsH genes, respectively. In addition, 23 SSR loci were identified. Conclusions The complete chloroplast genome sequence was obtained for Siberian larch for the first time. The reference complete chloroplast genomes, such as one described here, would greatly help in the chloroplast resequencing and search for additional genetic markers using population samples. The results of this research will be useful for further phylogenetic and gene flow studies in conifers. -
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Stepwise large genome assembly approach: a case of Siberian larch (Larix sibirica Ledeb)
BMC Bioinformatics. 2019 Feb 05;20(Suppl 1):37Background De novo assembling of large genomes, such as in conifers (~ 12–30 Gbp), which also consist of ~ 80% of repetitive DNA, is a very complex and computationally intense endeavor. One of the main problems in assembling such genomes lays in computing limitations of nucleotide sequence assembly programs (DNA assemblers). As a rule, modern assemblers are usually designed to assemble genomes with a length not exceeding the length of the human genome (3.24 Gbp). Most assemblers cannot handle the amount of input sequence data required to provide sufficient coverage needed for a high-quality assembly. Results An original stepwise method of de novo assembly by parts (sets), which allows to bypass the limitations of modern assemblers associated with a huge amount of data being processed, is presented in this paper. The results of numerical assembling experiments conducted using the model plant Arabidopsis thaliana, Prunus persica (peach) and four most popular assemblers, ABySS, SOAPdenovo, SPAdes, and CLC Assembly Cell, showed the validity and effectiveness of the proposed stepwise assembling method. Conclusion Using the new stepwise de novo assembling method presented in the paper, the genome of Siberian larch, Larix sibirica Ledeb. (12.34 Gbp) was completely assembled de novo by the CLC Assembly Cell assembler. It is the first genome assembly for larch species in addition to only five other conifer genomes sequenced and assembled for Picea abies, Picea glauca, Pinus taeda, Pinus lambertiana, and Pseudotsuga menziesii var. menziesii.