bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac structure and function in response to a multi-stage marathon over 4486 km
Authors: Klenk Christopher , Brunner Horst , Nickel Thomas , Sagmeister Florian , Yilmaz Atilgan , Infanger Denis , Billich Christian , Scharhag Jürgen , Vogeser Michael , Beer Meinrad , Schütz Uwe , Schmidt-Trucksäss Arno
Published: October 2019

Aims

To investigate whether participation in the Trans Europe Foot Race 2009 (TEFR), an ultramarathon race held over 64 consecutive days and 4486 km, led to changes in cardiac structure and function.

Methods

Cardiac magnetic resonance imaging was performed in 20 of 67 participating runners (two women; mean ± SD age 47.8 ± 10.4 years) at three time points (baseline scan at 294 ± 135 km (B), scan two at 1735 ± 86 km (T1) and scan three at 3370 ± 90 km (T2)) during the TEFR. Imaging included an assessment of left ventricular structure (mass) and function (strain). In parallel, cardiac troponin I, NT-pro-BNP, myostatin and GDF11 were determined in venous blood samples. A subsample of ten runners returned for a follow-up scan eight months after the race.

Results

Left ventricular mass increased significantly (B, 158.5 ± 23.8 g; T1, 165.1 ± 23.2 g; T2, 167 ± 24.6 g; p < 0.001) over the course of the race, although no significant change was seen in the remaining structural and functional parameters. Serum concentrations of cardiac troponin I and NT-proBNP significantly increased 1.5 - and 3.5-fold, respectively, during the first measurement interval, with no further increase thereafter (cardiac troponin I, 6.8 ± 3.1 (B), 16.9 ± 10.4 (T1) and 17.1 ± 9.7 (T2); NT-proBNP, 30.3 ± 22.8 (B), 135.9 ± 177.5 (T1) and 111.2 ± 87.3 (T2)), whereas the growth markers myostatin and GDF11 did not change. No association was observed with functional parameters, including the ejection fraction and the volume of both ventricles. The follow-up scans showed a reduction to baseline values (left ventricular mass 157 ± 19.3 g).

Conclusions

High exercise-induced cardiac volume load for >2 months in ultra-endurance runners results in a physiological structural adaptation with no sign of adverse cardiovascular remodelling.
Oxygen treatment of ventilated critically ill children: Nursing assessment and cognitive processes in clinical decision-making
Authors: Soini Ulla Marie , Andenæs Randi , Solberg Marianne Trygg
Published: October 2019

The aim of this study was to describe nurses’ opinions regarding assessments of oxygen requirements and which modes of cognition they used about oxygen treatment in ventilated children aged 0–3 years. The method was survey design with descriptive statistics. The sample included 90 nurses from intensive care units within all university hospitals in Norway. The questionnaire covered use of physiological, clinical, and technical observations in assessments, and the Nursing Decision-Making Instrument was used to map the mode of cognition. Respondents perceived they used many of the physiological criteria except for the haemoglobin–oxygen dissociation curve, pulse and blood pressure. Most respondents used clinical and technical criteria to assess oxygen needs, but more than half would exceed 10% oxygen at each regulation. They considered written guidelines to be necessary. A majority demonstrated a flexible use of analytical and intuitive modes of cognition in the decision-making processes. The results indicate that assessment of children’s need for oxygen may be based on insufficient information, and written guidelines should be developed.
Structural Allograft Versus PEEK Implants in Anterior Cervical Discectomy and Fusion: A Systematic Review
Authors: Jain Amit , Marrache Majd , Harris Andrew , Puvanesarajah Varun , Neuman Brian J. , Buser Zorica , Wang Jeffrey C. , Yoon S. Tim , Meisel Hans Jörg ,   AOSpine Knowledge Forum Degenerative
Published: October 2019

Study Design:

Systematic literature review.

Objective:

Our primary objective was to compare reported fusion rates after anterior cervical discectomy and fusion (ACDF) using structural allograft versus polyetheretherketone (PEEK) interbody devices in patients with cervical spine degeneration. Our secondary objectives were to compare differences in rates of subsidence and reoperation and in patient-reported outcomes between the 2 groups.

Methods:

Through a systematic review of the English-language literature using various databases, we identified 4702 articles. After we applied inclusion and exclusion criteria, 14 articles (7 randomized controlled trials, 4 prospective studies, and 3 retrospective studies) reporting fusion rates of structural allograft or PEEK interbody devices were eligible for our analysis. No randomized controlled trials compared outcomes of structural allograft versus PEEK interbody devices. Extracted data included authors, study years, study designs, sample sizes, patient ages, duration of follow-up, types of interbody devices used, fusion rates, definition of fusion, reoperation rates, subsidence rates, and patient-reported outcomes.

Results:

Fusion rates were 82% to 100% for allograft and 88% to 98% for PEEK interbody devices. The reported data were insufficient to perform meta-analysis. Structural allograft had the highest reported rate of reoperation (14%), and PEEK interbody devices had the highest reported subsidence rate (18%). Patient-reported outcomes improved in both groups. There was insufficient high-quality evidence to compare the associations of various PEEK modifications with fusion rates.

Conclusion:

Fusion rates were similar between structural allograft and PEEK interbody devices when used for ACDF for cervical spine degeneration. Currently, there is insufficient high-quality evidence to assess associations of PEEK modifications with fusion rates.

Level of Evidence:

II.
Leaving no one behind? The influence of civil society participation on the Sustainable Development Goals
Authors: Sénit Carole-Anne
Published: October 2019

Spaces for civil society participation within intergovernmental negotiations on sustainability have multiplied since the 1992 Earth Summit. Such participatory spaces are often uncritically accepted as a remedy for an assumed democratic deficit of intergovernmental policymaking. I argue, however, that civil society’s capacity to democratize global sustainability governance is constrained by the limited influence of these spaces on policymaking. The article explores the relationship between the format of participatory spaces and their influence on the negotiations of the Sustainable Development Goals. It finds that civil society is more likely to influence within informal and exclusive participatory spaces, and when these spaces are provided early in the negotiating process, at international and national level. This reveals a democracy–influence paradox, as the actors with the capacities to engage repeatedly and informally with negotiators are seldom those that are most representative of global civil society.
Synthesis of Gold Nanoparticles Using Mimosa tenuiflora Extract, Assessments of Cytotoxicity, Cellular Uptake, and Catalysis
Authors: Rodríguez-León Ericka , Rodríguez-Vázquez Blanca E. , Martínez-Higuera Aarón , Rodríguez-Beas César , Larios-Rodríguez Eduardo , Navarro Rosa E. , López-Esparza Ricardo , Iñiguez-Palomares Ramón A.
Published: October 2019

Synthesis of gold nanoparticles (AuNPs) with plant extracts has gained great interest in the field of biomedicine due to its wide variety of health applications. In the present work, AuNPs were synthesized with Mimosa tenuiflora (Mt) bark extract at different metallic precursor concentrations. Mt extract was obtained by mixing the tree bark in ethanol-water. The antioxidant capacity of extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl and total polyphenol assay. AuNPs were characterized by transmission electron microscopy, X-ray diffraction, UV-Vis and Fourier transform infrared spectroscopy, and X-ray photoelectron spectrometry for functional group determination onto their surface. AuMt (colloids formed by AuNPs and molecules of Mt) exhibit multiple shapes with sizes between 20 and 200 nm. AuMt were tested on methylene blue degradation in homogeneous catalysis adding sodium borohydride. The smallest NPs (AuMt1) have a degradation coefficient of 0.008/s and reach 50% degradation in 190s. Cell viability and cytotoxicity were evaluated in human umbilical vein endothelial cells (HUVEC), and a moderate cytotoxic effect at 24 and 48 h was found. However, toxicity does not behave in a dose-dependent manner. Cellular internalization of AuMt on HUVEC cells was analyzed by confocal laser scanning microscopy. For AuMt1, it can be observed that the material is dispersed into the cytoplasm, while in AuMt2, the material is concentrated in the nuclear periphery.
MIC_Locator: a novel image-based protein subcellular location multi-label prediction model based on multi-scale monogenic signal representation and intensity encoding strategy
Authors: Yang Fan , Liu Yang , Wang Yanbin , Yin Zhijian , Yang Zhen
Published: October 2019

Background

Protein subcellular localization plays a crucial role in understanding cell function. Proteins need to be in the right place at the right time, and combine with the corresponding molecules to fulfill their functions. Furthermore, prediction of protein subcellular location not only should be a guiding role in drug design and development due to potential molecular targets but also be an essential role in genome annotation. Taking the current status of image-based protein subcellular localization as an example, there are three common drawbacks, i.e., obsolete datasets without updating label information, stereotypical feature descriptor on spatial domain or grey level, and single-function prediction algorithm’s limited capacity of handling single-label database.

Results

In this paper, a novel human protein subcellular localization prediction model MIC_Locator is proposed. Firstly, the latest datasets are collected and collated as our benchmark dataset instead of obsolete data while training prediction model. Secondly, Fourier transformation, Riesz transformation, Log-Gabor filter and intensity coding strategy are employed to obtain frequency feature based on three components of monogenic signal with different frequency scales. Thirdly, a chained prediction model is proposed to handle multi-label instead of single-label datasets. The experiment results showed that the MIC_Locator can achieve 60.56% subset accuracy and outperform the existing majority of prediction models, and the frequency feature and intensity coding strategy can be conducive to improving the classification accuracy.

Conclusions

Our results demonstrate that the frequency feature is more beneficial for improving the performance of model compared to features extracted from spatial domain, and the MIC_Locator proposed in this paper can speed up validation of protein annotation, knowledge of protein function and proteomics research.
The anti-phytoalexin gene Bx-cathepsin W supports the survival of Bursaphelenchus xylophilus under Pinus massoniana phytoalexin stress
Authors: Wang Feng , Chen Qiaoli , Zhang Ruizhi , Li Danlei , Ling Yaming , Song Ruiqing
Published: October 2019

Background

Pine trees challenged byBursaphelenchus xylophilusinvasion produce phytoalexins to combat this nematode. Nevertheless, the phytoalexins of Asian pine trees are ineffective againstB. xylophilus. The anti-phytoalexin genes ofB. xylophilusdisable almost all Asian pine phytoalexins, which has allowedB. xylophilusto devastate pine forests in eastern Asia over the last four decades. However, to date, the factors that stimulate anti-phytoalexin gene expression and the mechanisms by which these genes act are not well understood.

Results

Here, we described anti-phytoalexin genes inB. xylophilususing transcriptomic and bioinformatics analyses. The genes that were induced by bothPinus massonianaand carvone and had similarly elevated expression trends were considered anti-phytoalexin genes. Altogether, 187 anti-phytoalexin genes were identified, including 4 cathepsin genes. KEGG pathway enrichment indicated that those cathepsins were related to the Lysosome pathway. Since cathepsins help to maintain metabolic homeostasis by participating in the degradation of heterophagic and autophagic material, the lysosomal cathepsin geneBx-cathepsin Wwas cloned and characterized. The results of the RNAi assessment indicated that the knockdown ofBx-cathepsin Wreduced the survival rates ofB. xylophilusunder carvone orP. massonianastress. The correlation betweenBx-cathepsin Wand the susceptibility of pines showed thatBx-cathepsin Wmight help improve the anti-phytotoxin ability ofB. xylophilus.

Conclusions

The results indicated that the anti-phytoalexin geneBx-cathepsin Wsupported the survival ofB. xylophilusunderP. massonianaphytoalexin stress. The cDNA library sequencing, differentially expressed gene identification, and WGCNA algorithm analysis provided insight at a systemic level into the gene regulation ofB. xylophilusin response to the immune reaction ofP. massoniana. These results will lead to a better understanding of the function of nematode defenses in host innate immunity.
Physiological and transcriptome analysis reveal molecular mechanism in Salvia miltiorrhiza leaves of near-isogenic male fertile lines and male sterile lines
Authors: Wang Ruihong , Jiang Han , Zhou Ziyun , Guo Hongbo , Dong Juane
Published: October 2019

Background

Our previous study finds that male sterility in Salvia miltiorrhiza could result in stunted growth and reduced biomass, but their molecular mechanisms have not yet been revealed. In this article, we investigate the underlying mechanism of male sterility and its impact on plant growth and metabolic yield by using physiological analysis and mRNA sequencing (RNA-Seq).

Results

In this study, transcriptomic and physiological analysis were performed to identify the mechanism of male sterility in mutants and its impact on plant growth and metabolic yield. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, it is found that the pathways are mainly enriched in processes including organ development, primary metabolic process and secondary metabolic process. Physiological analysis show that the chloroplast structure of male sterile mutants of S. miltiorrhiza is abnormally developed, which could result in decrease in leaf gas exchange (A, E and gs), chlorophyll fluorescence (Fv, Fm and Fv/Fm), and the chlorophyll content. Expression level of 7 differentially expressed genes involved in photosynthesis-related pathways is downregulated in male sterile lines of S. miltiorrhiza, which could explain the corresponding phenotypic changes in chlorophyll fluorescence, chlorophyll content and leaf gas exchange. Transcriptomic analysis establishes the role of disproportionating enzyme 1 (DPE1) as catalyzing the degradation of starch, and the role of sucrose synthase 3 (SUS3) and cytosolic invertase 2 (CINV2) as catalyzing the degradation of sucrose in the S. miltiorrhiza mutants. The results also confirm that phenylalanine ammonialyase (PAL) is involved in the biosynthesis of rosmarinic acid and salvianolic acid B, and flavone synthase (FLS) is an important enzyme catalyzing steps of flavonoid biosynthesis.

Conclusions

Our results from the physiological and transcriptome analysis reveal underlying mechanism of plant growth and metabolic yield in male sterile mutants, and provide insight into the crop yield of S. miltiorrhiza.
Dynamic metabolic modelling of overproduced protein secretion in Streptomyces lividans using adaptive DFBA
Authors: Valverde Jósé R. , Gullón Sonia , García-Herrero Clara A. , Campoy Iván , Mellado Rafael P.
Published: October 2019

Background

Streptomyces lividans is an appealing host for the production of proteins of biotechnological interest due to its relaxed exogenous DNA restriction system and its ability to secrete proteins directly to the medium through the major Sec or the minor Tat routes. Often, protein secretion displays non-uniform time-dependent patterns. Understanding the associated metabolic changes is a crucial step to engineer protein production. Dynamic Flux Balance Analysis (DFBA) allows the study of the interactions between a modelled organism and its environment over time. Existing methods allow the specification of initial model and environment conditions, but do not allow introducing arbitrary modifications in the course of the simulation. Living organisms, however, display unexpected adaptive metabolic behaviours in response to unpredictable changes in their environment. Engineering the secretion of products of biotechnological interest has systematically proven especially difficult to model using DFBA. Accurate time-dependent modelling of complex and/or arbitrary, adaptive metabolic processes demands an extended approach to DFBA.

Results

In this work, we introduce Adaptive DFBA, a novel, versatile simulation approach that permits inclusion of changes in the organism or the environment at any time in the simulation, either arbitrary or interactively responsive to environmental changes. This approach extends traditional DFBA to allow steering arbitrarily complex simulations of metabolic dynamics. When applied to Sec- or Tat-dependent secretion of overproduced proteins in S. lividans, Adaptive DFBA can overcome the limitations of traditional DFBA to reproduce experimental data on plasmid-free, plasmid bearing and secretory protein overproducing S. lividans TK24, and can yield useful insights on the behaviour of systems with limited experimental knowledge such as agarase or amylase overproduction in S. lividans TK21.

Conclusions

Adaptive DFBA has allowed us to overcome DFBA limitations and to generate more accurate models of the metabolism during the overproduction of secretory proteins in S. lividans, improving our understanding of the underlying processes. Adaptive DFBA is versatile enough to permit dynamical metabolic simulations of arbitrarily complex biotechnological processes.
Expression patterns of two pal genes of Pleurotus ostreatus across developmental stages and under heat stress
Authors: Hou Ludan , Wang Lining , Wu Xiangli , Gao Wei , Zhang Jinxia , Huang Chenyang
Published: October 2019

Background

Phenylalanine ammonia-lyase (PAL, EC 4.3.1.24) is the first key enzyme in the phenylpropanoid pathway. The pal gene has been widely studied in plants and participates in plant growth, development and defense systems. However, in Pleurotus ostreatus, the biological functions of pal during organismal development and exposure to abiotic stress have not been reported.

Results

In this study, we cloned and characterized the pal1 (2232 bp) and pal2 (2244 bp) genes from the basidiomycete P. ostreatus CCMSSC 00389. The pal1 and pal2 genes are interrupted by 6 and 10 introns, respectively, and encode proteins of 743 and 747 amino acids, respectively. Furthermore, prokaryotic expression experiments showed that PAL enzymes catalyzed the conversion of L-phenylalanine to trans-cinnamic acid. The function of pal1 and pal2 was determined by constructing overexpression (OE) and RNA interference (RNAi) strains. The results showed that the two pal genes had similar expression patterns during different developmental stages. The expression of pal genes was higher in the reproductive growth stage than in the vegetative growth stage. And the interference of pal1 and pal2 delayed the formation of primordia. The results of heat stress assays showed that the RNAi-pal1 strains had enhanced mycelial tolerance to high temperature, while the RNAi-pal2 strains had enhanced mycelial resistance to H2O2.

Conclusions

These results indicate that two pal genes may play a similar role in the development of P. ostreatus fruiting bodies, but may alleviate stress through different regulatory pathways under heat stress.
Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation
Authors: Naor Noga , Gadot Omer , Meir Michal , Barkan Daniel
Published: October 2019

Background

Co-translational processes in bacteria are attractive drug targets, but while some processes are essential, others are not. The essentiality of Peptide Deformylase (PDF,def) for vitality of mycobacteria was speculated, but never unequivocally proven.

Results

Here we show by targeted deletion experiments thatdefcan only be deleted fromM. smegmatiswhen an additional copy is present; that prior deletion of tRNAfMet-Formyl Transferase (FMT, encoded byfmt) rendersdefcompletely dispensable; and that re-introduction offmtinto aΔdefmutant is not possible – constituting a definitive proof for the essentiality ofdefin mycobacteria.

Conclusions

Peptide deformylase is essential inM. smegmatis, but the fact that inactivation offmtrenders the gene completely dispensable, and thus any inhibitor ofdefuseless, casts doubt on the usefulness of PDF as a drug-target in mycobacteria.
Incorporating repeated measurements into prediction models in the critical care setting: a framework, systematic review and meta-analysis
Authors: Plate Joost D. J. , van de Leur Rutger R. , Leenen Luke P. H. , Hietbrink Falco , Peelen Linda M. , Eijkemans M. J. C.
Published: October 2019

Background

The incorporation of repeated measurements into multivariable prediction research may greatly enhance predictive performance. However, the methodological possibilities vary widely and a structured overview of the possible and utilized approaches lacks. Therefore, we [1] propose a structured framework for these approaches, [2] determine what methods are currently used to incorporate repeated measurements in prediction research in the critical care setting and, where possible, [3] assess the added discriminative value of incorporating repeated measurements.

Methods

The proposed framework consists of three domains: the observation window (static or dynamic), the processing of the raw data (raw data modelling, feature extraction and reduction) and the type of modelling. A systematic review was performed to identify studies which incorporate repeated measurements to predict (e.g. mortality) in the critical care setting. The within-study difference in c-statistics between models with versus without repeated measurements were obtained and pooled in a meta-analysis.

Results

From the 2618 studies found, 29 studies incorporated multiple repeated measurements. The annual number of studies with repeated measurements increased from 2.8/year (2000–2005) to 16.0/year (2016–2018). The majority of studies that incorporated repeated measurements for prediction research used a dynamic observation window, and extracted features directly from the data. Differences in c statistics ranged from − 0.048 to 0.217 in favour of models that utilize repeated measurements.

Conclusions

Repeated measurements are increasingly common to predict events in the critical care domain, but their incorporation is lagging. A framework of possible approaches could aid researchers to optimize future prediction models.
Partial ALPPS versus complete ALPPS for staged hepatectomy
Authors: Wu Xukun , Rao Jiawei , Zhou Xiaozhuan , Deng Ronghai , Ma Yi
Published: October 2019

Background

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce a stronger regenerative ability than traditional 2-stage hepatectomy (TSH). ALPPS has become popular for achieving fast hypertrophy in patients with an insufficient future liver remnant (FLR). However, ALPPS is associated with high morbidity and mortality. Partial ALPPS is a variation that may decrease the morbidity and mortality. The purpose of this study was to perform a meta-analysis comparing outcomes of ALLPS and partial ALLPS.

Methods

PubMed, Embase, and Cochrane Library databases were searched for studies comparing partial ALPPS and complete ALPPS up to April 2019. Included studies were assessed by the Newcastle-Ottawa Scale (NOS). Weighted mean difference (WMD)/standard mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CIs) were calculated to compare FLR, time interval between stages, postoperative complications, and mortality between partial and complete ALPPS.

Results

Four studies including 124 patients were included. FLR hypertrophy of partial ALPPS was comparable to complete ALPPS (p = 0.09). The time interval between stages was not different between the 2 procedures (p = 0.57). The postoperative complications rate of partial ALPPS was significantly lower than that of complete ALPPS (OR = 0.38; p = 0.03). The mortality rate of partial ALLPS (4.9%) was lower than that of complete ALLPS (18.9%), but the difference was not significant (OR = 0.37; p = 0.12).

Conclusions

Partial ALLPS is associated with similar FLR hypertrophy and time interval between stages as complete ALLPS, and a lower complication rate. Further studies are needed to examine patient selection and outcomes of the 2 procedures.
Impact of a delirium prevention project among older hospitalized patients who underwent orthopedic surgery: a retrospective cohort study
Authors: Choi Jung-Yeon , Kim Kwang-il , Kang Min-gu , Lee Young-Kyun , Koo Kyung-Hoi , Oh Joo Han , Park Young Ho , Suh Jeewon , Kim Nak-Hyun , Yoo Hyun-Jung , Koo Jahyun , Moon Hyun Mi , Kim Eun Hui , Park Kayoung , Kim Cheol-Ho
Published: October 2019

Background

Postoperative delirium (POD) is a common clinical syndrome with significant negative outcomes. Thus, we aimed to evaluate the feasibility and effectiveness of a delirium screening tool and multidisciplinary delirium prevention project.

Methods

A retrospective cohort study was conducted at a single teaching center in Korea. A cohort of patients who underwent a delirium prevention program using a simple delirium screening tool from December 2018 to February 2019 (intervention group,N = 275) was compared with the cohort from the year before implementation of the delirium prevention program (December 2017 to February 2018) (control group,N = 274). Patients aged ≥65 years who were admitted to orthopedic wards and underwent surgery were included. The incidence rates of delirium before and after implementation of the delirium prevention program, effectiveness of the delirium screening tool, change in the knowledge score of nurses, and length of hospital stay were assessed.

Results

The sensitivity and specificity of the screening tool for the incidence of POD were 94.1 and 72.7%, respectively. The incidence rates of POD were 10.2% (control group) and 6.2% (intervention group). The odds ratio for the risk reduction effect of the project related to the incidence of POD was 0.316 (95% confidence interval: 0.125–0.800,p = 0.015) after adjustment for possible confounders. The delirium knowledge test score increased from 40.52 to 43.24 out of 49 total points (p < 0.001). The median length of hospital stay in the intervention and control groups was 6.0 (interquartile range, 4–9) and 7.0 (interquartile range, 4–10) days, respectively (p = 0.062).

Conclusion

The screening tool successfully identified patients at a high risk of POD at admission. The POD prevention project was feasible to implement, effective in preventing delirium, and improved knowledge regarding delirium among the medical staff.

Trial registration

None.
Case report: whole genome sequencing based investigation of maternal-neonatal listeriosis in Sichuan, China
Authors: Luo Lijuan , Chen Xi , Payne Michael , Cao Xiaolong , Wang Yan , Zhang Jie , Deng Jianping , Wang Hong , Zhang Zhengdong , Li Qun , Lan Ruiting , Ye Changyun
Published: October 2019

Background

Neonatal listeriosis is a rare but severe disease manifesting as septicemia and central nervous system (CNS) infections with a high fatality rate of around 20 to 30%. Whole genome sequencing (WGS) is a promising technique for pathogen identification and infection source tracing with its high resolution.

Case presentation

A case of neonatal sepsis with listeriosis was reported with positive blood culture for Listeria monocytogenes. The case was investigated to confirm the vertical transmission of the infection and identify the potential food source of the maternal L. monocytogenes infection using WGS. L. monocytogenes was isolated from the neonate’s blood sample the day after caesarean delivery and from the mother’s genital and pudenda swab samples 5 days and 13 days after caesarean delivery. WGS showed that the isolate from the neonate was identical to the genome type of the isolates from the mother, with only one of the 4 isolates from the mother differing by one single nucleotide polymorphism (SNP). By WGS, one L. monocytogenes isolate from a ready-to-eat (RTE) meat sample in the patients’ community market shared the same sequence type but was ruled out as the cause of infection, with 57 SNP differences to the strain causing the maternal-neonatal infection. The food isolate also carried a novel plasmid pLM1686 that harbored heavy metal resistance genes. After caesarean section, the mother was treated with a third generation cephalosporin which L. monocytogenes is naturally resistant to, which may explain why genital and pudenda swabs were still culture-positive for L. monocytogenes 13 days after delivery.

Conclusions

Genital swab culture for L. monocytogenes had been informative in the diagnosis of maternal listeriosis in this case. The high resolution of WGS confirmed the maternal-neonatal transmission of L. monocytogenes infection and ruled out the L. monocytogenes contaminated RTE meat from the local market as the direct source of the mother’s infection.
Decoding of novel missense TSC2 gene variants using in-silico methods
Authors: Sudarshan Shruthi , Kumar Manoj , Kaur Punit , Kumar Atin , G. Sethuraman , Sapra Savita , Gulati Sheffali , Gupta Neerja , Kabra Madhulika , Roy Chowdhury Madhumita
Published: October 2019

Background

Mutations in TSC1 or TSC2 gene cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by the formation of non-malignant hamartomas in multiple vital organs. TSC1 and TSC2 gene products form TSC heterodimer that senses specific cell growth conditions to control mTORC1 signalling.

Methods

In the present study 98 TSC patients were tested for variants in TSC1 and TSC2 genes and 14 novel missense variations were identified. The pathogenecity of these novel variations was determined by applying different bioinformatics tools involving computer aided protein modeling.

Results

Protein modelling could be done only for ten variants which were within the functional part of the protein. Homology modeling is the most reliable method for structure prediction of a protein. Since no sequence homology structure was available for the tuberin protein, three dimensional structure was modeled by a combination of homology modeling and the predictive fold recognition and threading method using Phyre2 threading server. The best template structures for model building of the TSC1 interacting domain, tuberin domain and GAP domain are the crystal structures of clathrin adaptor core protein, Rap1GAP catalytic domain and Ser/Thr kinase Tor protein respectively.

Conclusions

In this study, an attempt has been made to assess the impact of each novel missense variant based on their TSC1-TSC2 hydrophobic interactions and its effect on protein function.
Liddle syndrome due to a novel mutation in the γ subunit of the epithelial sodium channel (ENaC) in family from Russia: a case report
Authors: Kozina Anastasiya A. , Trofimova Tatiana A. , Okuneva Elena G. , Baryshnikova Natalia V. , Obuhova Varvara A. , Krasnenko Anna Yu. , Tsukanov Kirill Yu. , Klimchuk Olesya I. , Surkova Ekaterina I. , Shatalov Peter A. , Ilinsky Valery V.
Published: October 2019

Background

Liddle syndrome is a monogenic disease with autosomal dominant inheritance. Basic characteristics of this disease are hypertension, reduced concentration of aldosterone and renin activity, as well as increased excretion of potassium leading to low level of potassium in serum and metabolic alkalosis. The cause of Liddle syndrome is missense or frameshift mutations in SCNN1A, SCNN1B, or SCNN1G genes that encode epithelial sodium channel subunits.

Case presentation

We describe a family with Liddle syndrome from Russia. 15-year-old proband has arterial hypertension, hypokalemia, hyporeninemia, metabolic alkalosis, but aldosterone level is within the normal range. At 12 years of age, arterial hypertension was noticed for the first time. We identified novel frameshift mutation c.1769delG (p.Gly590Alafs) in SCNN1G, which encodes the γ subunit of ENaC in vertebrates. The father and younger sister also harbor this heterozygous deletion. Treatment with amiloride of proband and his sister did not normalize the blood pressure, but normalized level of plasma renin activity.

Conclusions

Our results expand the mutational spectrum of Liddle syndrome and provide further proof that the conserved PY motif is crucial to control of ENaC activity. Genetic analysis has implications for the management of hypertension, specific treatment with amiloride and counselling in families with Liddle syndrome.
Risk factors and consequences of undiagnosed cesarean scar pregnancy: a cohort study in China
Authors: Xie Ri-hua , Guo Xiaoyan , Li Meng , Liao Yan , Gaudet Laura , Walker Mark , Lei Huizhong , Wen Shi Wu
Published: October 2019

Background

The historically high cesarean section rate and the recent change in second-child policy could increase the risk of cesarean scar pregnancy (CSP) in China. This study aims to assess risk factors and consequences of undiagnosed CSP in China.

Methods

We conducted a retrospective cohort study between January 2013 and December 2017 in Qingyuan, Guangdong, China. Independent risk factors for undiagnosed CSP at the first contact with healthcare providers were assessed by log binomial regression analysis. Occurrence of serious complications was compared between undiagnosed and diagnosed CSP cases.

Results

A total of 195 women with CSP were included in the analysis. Of them, 81 (41.5%) women were undiagnosed at the first contact with healthcare providers. Women initially cared in primary or secondary hospitals were at increased risk for undiagnosed CSP: adjusted relative risks (95% confidence intervals) were 3.28 (2.06, 5.22) and 1.91 (1.16, 3.13), respectively, compared with women initially cared in the tertiary hospital. Undiagnosed CSP cases had higher incidences in serious complications (11 versus 0) and post-surgery anemia (23 (28.4%) versus 8 (7.0%)), stayed longer in hospital, and cost higher than diagnosed CSP cases.

Conclusions

Initial care provided at primary or secondary maternity care facilities is an important risk factor for undiagnosed CSP, with serious consequences to the affected women.
Clinical factors associated with treatment outcomes in EGFR mutant non-small cell lung cancer patients with brain metastases: a case-control observational study
Authors: Chen Yung-Hsuan , Chen Yen-Fu , Chen Chung-Yu , Shih Jin-Yuan , Yu Chong-Jen
Published: October 2019

Background

Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations often develop brain metastases. Treatment with EGFR-tyrosine kinase inhibitors (TKIs) has shown the effectiveness; however, knowledge of the clinical factors associated with outcomes in NSCLC patients with EGFR mutations remains limited.

Methods

Treatment-naive patients diagnosed with advanced non-squamous NSCLC with brain metastases harboring EGFR mutations and treated with an EGFR-TKI as first-line therapy were enrolled with analysis of their medical records.

Results

A total of 134 advanced NSCLC patients with brain metastases harboring EGFR mutations received an EGFR-TKI (gefitinib: 62, erlotinib: 49, and afatinib: 23) as the first-line therapy. Sixty-nine had exon 19 deletions (51.5%), and 56 (41.8%) had L858R mutations. There was no statistically significant difference in progression-free survival (PFS) and overall survival (OS) among the EGFR-TKIs. Significantly shorter OS was noted in patients with multiple brain metastases (hazard ratio [HR]: 2.43, p = 0.007), uncommon EGFR mutations (HR: 3.75, p = 0.009), and liver metastases. Thirty-eight patients (29.1%) received brain radiotherapy for brain metastases before disease progression, and had a significantly longer time until intracranial progression. However, the brain radiotherapy had no statistically significant impact on PFS or OS.

Conclusions

Patients with uncommon mutations, multiple brain metastases, and concomitant liver metastases tended to have shorter OS. Brain radiotherapy could delay the time to intracranial disease progression but had no impact on survival. The different first-line EGFR-TKIs achieved similar treatment responses in terms of PFS and OS in the EGFR-mutated NSCLC patients with brain metastases.
The use of PanDrugs to prioritize anticancer drug treatments in a case of T-ALL based on individual genomic data
Authors: Fernández-Navarro Pablo , López-Nieva Pilar , Piñeiro-Yañez Elena , Carreño-Tarragona Gonzalo , Martinez-López Joaquín , Sánchez Pérez Raúl , Aroca Ángel , Al-Shahrour Fátima , Cobos-Fernández María Ángeles , Fernández-Piqueras José
Published: October 2019

Background

Acute T-cell lymphoblastic leukaemia (T-ALL) is an aggressive disorder derived from immature thymocytes. The variability observed in clinical responses on this type of tumours to treatments, the high toxicity of current protocols and the poor prognosis of patients with relapse or refractory make it urgent to find less toxic and more effective therapies in the context of a personalized medicine of precision.

Methods

Whole exome sequencing and RNAseq were performed on DNA and RNA respectively, extracted of a bone marrow sample from a patient diagnosed with tumour primary T-ALL and double negative thymocytes from thymus control samples. We used PanDrugs, a computational resource to propose pharmacological therapies based on our experimental results, including lists of variants and genes. We extend the possible therapeutic options for the patient by taking into account multiple genomic events potentially sensitive to a treatment, the context of the pathway and the pharmacological evidence already known by large-scale experiments.

Results

As a proof-of-principle we used next-generation-sequencing technologies (Whole Exome Sequencing and RNA-Sequencing) in a case of diagnosed Pro-T acute lymphoblastic leukaemia. We identified 689 disease-causing mutations involving 308 genes, as well as multiple fusion transcript variants, alternative splicing, and 6652 genes with at least one principal isoform significantly deregulated. Only 12 genes, with 27 pathogenic gene variants, were among the most frequently mutated ones in this type of lymphoproliferative disorder. Among them, 5 variants detected inCTCF, FBXW7, JAK1, NOTCH1andWT1genes have not yet been reported in T-ALL pathogenesis.

Conclusions

Personalized genomic medicine is a therapeutic approach involving the use of an individual’s information data to tailor drug therapy. Implementing bioinformatics platform PanDrugs enables us to propose a prioritized list of anticancer drugs as the best theoretical therapeutic candidates to treat this patient has been the goal of this article. Of note, most of the proposed drugs are not being yet considered in the clinical practice of this type of cancer opening up the approach of new treatment possibilities.
Early maladaptive schemas impact on long-term outcome in patients treated with group behavioral therapy for obsessive-compulsive disorder
Authors: Sunde Tor , Hummelen Benjamin , Himle Joseph A. , Walseth Liv Tveit , Vogel Patrick A. , Launes Gunvor , Haaland Vegard Øksendal , Haaland Åshild Tellefsen
Published: October 2019

Background

Some studies have previously found that certain elevated early maladaptive schemas (EMSs) are negative predictors for outcome for patients with obsessive-compulsive disorder (OCD) treated with Cognitive-Behavioral Therapy (CBT) or Exposure and Response Prevention (ERP). The current study explores whether EMS were related to reductions in OCD symptom severity at long-term follow-up (Mean = 8 years) after group ERP for patients with OCD. The central hypothesis was that patients with no response to treatment or patients who relapsed during the follow-up period were more likely to have elevated pre-treatment EMSs compared to those who responded to initial treatment and maintained gains over time. We also investigated whether there were any differences in change over time of overall EMS between patients who were recovered versus patients who were not recovered at extended follow-up.

Methods

Young Schema Questionnaire –Short Form (YSQ-SF), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI) were measured in 40 OCD patients in a general outpatient clinic before and after group ERP, after 12-months and at extended follow-up. To analyze the predictors, a multiple regression analyses was conducted. Changes in overall EMS was analyzed by mixed models procedures.

Results

The major finding is that patients with high pre-treatment YSQ-SF total scores were less likely to respond to initial treatment or were more likely to relapse between post-treatment and the extended follow-up. The YSQ-SF total score at pre-treatment explained 10.5% of the variance of extended long-term follow-up outcome. The entire sample experienced a significant reduction in overall EMS over time with largest reduction from pre- to post-test. There were no statistically significant differences in total EMS change trajectories between the patients who were recovered at the extended follow-up compared to those who were not.

Conclusion

The results from the present study suggest that patients with higher pre-treatment EMSs score are less likely to recover in the long-term after receiving group ERP for OCD. A combined treatment that also targets early maladaptive schemas may be a more effective approach for OCD patients with elevated EMS who don’t respond to standard ERP.
“He can send her to her parents”: The interaction between marriageability, gender and serious mental illness in rural Ethiopia
Authors: Hailemariam Maji , Ghebrehiwet Senait , Baul Tithi , Restivo Juliana L. , Shibre Teshome , Henderson David C. , Girma Eshetu , Fekadu Abebaw , Teferra Solomon , Hanlon Charlotte , Johnson Jennifer E. , Borba Christina P. C.
Published: October 2019

Background

For women in most low- and middle-income countries, the diagnosis with serious mental illness (SMI) leads to stigma and challenges related to starting or maintaining marriages. The purpose of this qualitative study was to explore perspectives on marriage, divorce and family roles of women with SMI in rural Ethiopia.

Methods

A qualitative study was conducted in a rural setting of Butajira, South Central Ethiopia. A total of 39 in-depth interviews were carried out with service users (n = 11), caregivers (n = 12), religious leaders (n = 6), health extension workers (n = 4), police officers (n = 2), teachers (n = 2) and government officials (n = 2). Data were analyzed using a thematic approach.

Results

Three themes emerged. (1) Marriage and SMI: Chances of getting married for individuals with SMI in general was perceived to be lower: Individuals with SMI experienced various challenges including difficulty finding romantic partner, starting family and getting into a long-term relationship due to perceived dangerousness and the widespread stigma of mental illness. (2) Gendered experiences of marriageability: Compared to men, women with SMI experienced disproportionate levels of stigma which often continued after recovery. SMI affects marriageability for men with SMI, but mens' chances of finding a marital partner increases following treatment. For women in particular, impaired functioning negatively affects marriageability as ability to cook, care and clean was taken as the measure of suitability. (3) Acceptability of divorce and separation from a partner with SMI: Divorce or separation from a partner with SMI was considered mostly acceptable for men while women were mostly expected to stay married and care for a partner with SMI. For men, the transition from provider to dependent was often acceptable. However, women who fail to execute their domestic roles successfully were considered inept and would be sent back to their family of origin.

Conclusion

Women with SMI or those married to partners with SMI are at greater disadvantage. Reducing vulnerabilities through stigma reduction efforts such as community outreach and mental health awareness raising programs might contribute for better social outcomes for women with SMI.
Population-based surveys and interventions for mental health literacy in China during 1997–2018: a scoping review
Authors: Lu Shurong , Oldenburg Brian , Li Wenjing , He Yanling , Reavley Nicola
Published: October 2019

Background

This scoping review maps population-based surveys and mental health literacy (MHL) interventions undertaken in China during 1997–2018 in order to identify research gaps.

Method

Following Arksey and O’Malley’s framework for a scoping review, five English databases (Medline, PsycINFO, Cochrane library, Web of Science and CINAHL) and two Chinese ones (CNKI and WanFang) were systematically searched, identifying both reports of surveys and evaluation of interventions from Jan 1997 to Oct 2018.

Results

MHL research has developed rapidly in China in terms of numbers of studies and geographic coverage over the past two decades. There were 350 peer-reviewed publications included in this review, covering diverse settings and participants. Of these publications, 313 (89.4%) were published in Chinese-language journals and 37 in English-language journals; 303 (86.6%) reported on survey findings and 47 reported on the evaluation of MHL interventions. MHL research in China has mainly focused on the assessment of mental health-related knowledge and beliefs. Much less attention has been given to developing and evaluating relevant interventions. MHL related to general mental health and suicide were most commonly studied, with less focus on specific disorders, although some studies covered depression, psychosis and anxiety disorders. The majority of MHL tools utilized in the studies reported in this review were developed in China (n = 97, 80.2% ) and almost half of these studies (57.8%) did not provide enough details concerning psychometrics.

Conclusions

More interventions targeting the general public and aiming to improve MHL and promote behaviour change, are needed in China. These should be evaluated with high-quality study designs, such as randomised controlled trials. Proper validation of tools used for measuring MHL should also be addressed in future studies.