bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel strategy to enhance terpenoids production using cambial meristematic cells of Tripterygium wilfordii Hook. f.
Authors: Song Yadi , Chen Shang , Wang Xiujuan , Zhang Rui , Tu Lichan , Hu Tianyuan , Liu Xihong , Zhang Yifeng , Huang Luqi , Gao Wei 
Published: November 2019

AbstractBackgroundTripterygium wilfordiiHook. f. (T. wilfordii) is an important medicinal plant with anti-inflammatory, immunosuppressive and anti-tumor activities. The main bioactive ingredients are diterpenoids and triterpenoids, such as triptolide, triptophenolide and celastrol. However, the production of terpenoids from original plants, hairy roots and dedifferentiated cells (DDCs) are not satisfactory for clinical applications. To find a new way to further improve the production of terpenoids, we established a new culture system of cambial meristematic cells (CMCs) with stem cell-like properties, which had strong vigor and high efficiency to produce large amounts of terpenoids ofT. wilfordii.ResultsCMCs ofT. wilfordiiwere isolated and cultured for the first time. CMCs were characterized consistent with stem cell identities based on their physiological and molecular analysis, including morphology of CMCs, hypersensitivity to zeocin, thin cell wall and orthogonal partial least square-discriminant analysis, combination of transcriptional data analysis. After induction with methyl jasmonate (MJ), the maximal production of triptolide, celastrol and triptophenolide in CMCs was 312%, 400% and 327% higher than that of control group, respectively. As for medium, MJ-induced CMCs secreted 231% triptolide and 130% triptophenolide at the maximum level into medium higher than that of control group. Maximal celastrol production of induced CMCs medium was 48% lower than that of control group. Long-term induction significantly enhanced the production of terpenoids both in cells and medium. The reason for increasing the yield of terpenoids was that expression levels of1-deoxy-d-xylulose-5-phosphate synthase(DXS),1-deoxy-d-xylulose-5-phosphate reductoisomerase(DXR) andhydroxymethylglutaryl-CoA synthase(HMGS) were upregulated in CMCs after induction.ConclusionsFor the first time, CMCs ofT. wilfordiiwere isolated, cultured, characterized and applied. Considering the significant enrichment of terpenoids in CMCs ofT. wilfordii, CMCs could provide an efficient and controllable platform for sustainable production of terpenoids, which can be a better choice than DDCs.
Two-step derivatization for determination of sugar phosphates in plants by combined reversed phase chromatography/tandem mass spectrometry
Authors: Rende Umut , Niittylä Totte , Moritz Thomas 
Published: November 2019

Abstract

Background
Sugar phosphates are important intermediates of central carbon metabolism in biological systems, with roles in glycolysis, the pentose–phosphate pathway, tricarboxylic acid (TCA) cycle, and many other biosynthesis pathways. Understanding central carbon metabolism requires a simple, robust and comprehensive analytical method. However, sugar phosphates are notoriously difficult to analyze by traditional reversed phase liquid chromatography.

Results
Here, we show a two-step derivatization of sugar phosphates by methoxylamine and propionic acid anhydride after chloroform/methanol (3:7) extraction from Populus leaf and developing wood that improves separation, identification and quantification of sugar phosphates by ultra high performance liquid chromatography–electrospray ionization–mass spectrometry (UHPLC–ESI–MS). Standard curves of authentic sugar phosphates were generated for concentrations from pg to ng/μl with a correlation coefficient R2 > 0.99. The method showed high sensitivity and repeatability with relative standard deviation (RSD) < 20% based on repeated extraction, derivatization and detection. The analytical accuracy for Populus leaf extracts, determined by a two-level spiking approach of selected metabolites, was 79–107%.

Conclusion
The results show the reliability of combined reversed phase liquid chromatography–tandem mass spectrometry for sugar phosphate analysis and demonstrate the presence of two unknown sugar phosphates in Populus extracts.
Functional outcome of surgical treatment of adults with extremity osteosarcoma after megaprosthetic reconstruction—single-center experience
Authors: Goryń Tomasz , Pieńkowski Andrzej , Szostakowski Bartłomiej , Zdzienicki Marcin , Ługowska Iwona , Rutkowski Piotr 
Published: November 2019

Abstract

Background
Osteosarcoma is the most common primary malignant bone tumor in adults and is usually located in the long bones. Standard treatment consists of perioperative chemotherapy and radical surgical resection. Limb-sparing surgery using a variety of reconstructive techniques remains the gold standard.

Methods
In our study, we retrospectively analyzed 90 adult patients operated at our institution between 2000 and 2017 for extremity osteosarcoma that underwent limb-sparing reconstruction with the megaprosthesis. Sixty-one patients underwent resection and reconstruction of the distal femur, 9 patients—proximal femur, 7 patients—proximal tibia, 5 patients—total femoral resection and reconstruction, 5 patients—proximal humeral resection, and 3 patients—other types of resection with endoprosthetic reconstruction. The median follow-up time was 41 months, median overall survival was 86 months (3–225 months), and progression-free survival was 81 months (1–86 months). Functional assessment was made on 48 out of 56 living patients, after endoprosthetic reconstruction. The assessment was made according to MSTS functional scale.

Results
In 14 cases (15%), the endoprosthesis had to be explanted, or amputation was performed for local recurrence or septic complication. Due to a mechanical failure of the implant, we had to perform a revision in 5 patients (5%). Eighteen out of 74 patients with endoprosthesis died of the disease. The median MSTS score was 84% (53–100%), and the best result of 85% was achieved in patients after distal femoral resection with endoprosthetic reconstruction.

Conclusion
Careful planning of the treatment of patients with extremity osteosarcoma that is performed at the referral centers gives the possibility of long-term survival with a good and excellent functional result.
Comparison of postoperative complications between segmentectomy and lobectomy by video-assisted thoracic surgery: a multicenter study
Authors: Bédat Benoît , Abdelnour-Berchtold Etienne , Perneger Thomas , Licker Marc-Joseph , Stefani Alexandra , Krull Matthieu , Perentes Jean Yannis , Krueger Thorsten , Triponez Frédéric , Karenovics Wolfram , Gonzalez Michel 
Published: November 2019

Abstract

Background
Compared to lobectomy by video-assisted thoracic surgery (VATS), segmentectomy by VATS has a potential higher risk of postoperative atelectasis and air leakage. We compared postoperative complications between these two procedures, and analyzed their risk factors.

Methods
We reviewed the records of all patients who underwent anatomical pulmonary resections by VATS from January 2014 to March 2018 in two Swiss university hospitals. All complications were reported. A logistic regression model was used to compare the risks of complications for the two interventions. Adjustment for patient characteristics was performed using a propensity score, and by including risk factors separately.

Results
Among 690 patients reviewed, the major indication for lung resection was primary lung cancer (86.4%) followed by metastasis resection (5.8%), benign lesion (3.9%), infection (3.2%) and emphysema (0.7%). Postoperatively, there were 80 instances (33.3%) of complications in 240 segmentectomies, and 171 instances (38.0%) of complications in 450 lobectomies (P = 0.73). After adjustment for the patient’s propensity to be treated by segmentectomy rather than lobectomy, the risks of a complication remained comparable for the two techniques (odds ratio for segmentectomy 0.91 (0.61–1.30), p = 0.59). Length of hospital stay and drainage duration were shorter after segmentectomy. On multivariate analysis, an American Society of Anesthesiologists score above 2 and a forced expiratory volume in one second below 80% of predicted value were significantly associated with the occurrence of complications.

Conclusions
The rate of complications and their grade were similar between segmentectomy and lobectomy by VATS.
Predictors of mortality among HIV exposed infants at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia
Authors: Wubneh Chalachew Adugna , Endalamaw Aklilu , Tebeje Nigusie Birhan 
Published: November 2019

Abstract

Background
In the era of highly active antiretroviral therapy, vertical HIV transmission has been decreased. This may increase fertility desire of HIV infected women and an increasing number of HIV exposed infants as a result. A high probability of mortality among HIV exposed infants was reported across different countries. However, few studies are found on mortality of HIV exposed infants, in particular, no study was conducted before in the current study area.

Methods
Institution based retrospective cohort study from July 2013 to December 2017 was conducted. A total of 408 HIV exposed children were selected through simple random sampling technique. Data were extracted from registration book by using data extraction tool, which is adapted from the Ethiopian Federal Ministry of Health HIV exposed infant follow-up form. Kaplan–Meier survival curve was used to show the probability of mortality rate. Bivariable and multivariable cox regression models were used to identify predictors of mortality.

Results
Overall mortality rate was found to be 8.88 (95% CI: 6.36–12.36) per 100 child-year. Infant with death of at least one parent (AHR = 3.32; 95% CI: 1.503–7.32), non-exclusive breastfeeding (AHR = 0.10; 95% CI: 0.037–0.302), growth failure (AHR = 2.9; 95% CI: 1.09–8.09), presence of sign and symptom of HIV infection (AHR = 2.99; 95% CI: 1.33–6.74), and low birth weight (AHR = 2.6; 95% CI: 1.007–6.78) were found to be predictors of infant mortality.

Conclusions
Mortality of HIV exposed infants was high in Ethiopia. Prevention of the occurrence of HIV infection symptom, growth failure, and low birth weight is essential and further treat early whenever they occurred. Still, behavioral change interventions on mother who practice non-exclusive breastfeeding are indicated. Especial care for orphan infants is required due to their nature of vulnerability to varieties of health problem.
Pre- to postdiagnosis leisure-time physical activity and prognosis in postmenopausal breast cancer survivors
Authors: Jung Audrey Y. , Behrens Sabine , Schmidt Martina , Thoene Kathrin , Obi Nadia , Hüsing Anika , Benner Axel , Steindorf Karen , Chang-Claude Jenny 
Published: November 2019

Abstract

Background
Physical activity (PA) before and after breast cancer diagnosis has been reported to be associated with lower mortality. However, whether changes in the activity after diagnosis impact prognosis is unclear and has not received much attention. This study aimed to examine pre- to postdiagnosis leisure-time PA and breast cancer prognosis.

Methods
We used data from the MARIE study, a prospective population-based patient cohort study of 3813 postmenopausal breast cancer patients, aged 50–74 at diagnosis, recruited from 2002 to 2005, re-interviewed in 2009, and followed up until June 2015. Prediagnosis PA was assessed at recruitment; postdiagnosis PA was assessed at re-interview in 2009. To examine pre- to postdiagnosis change in PA, women were categorized by pre- and postdiagnosis PA using a cut-off of 7.5 MET-h/week for meeting PA recommendations and combined into four groups: insufficiently active, increasingly active, decreasingly active, and sufficiently active. Cox regression models with delayed entry were used to assess associations between pre- to postdiagnosis patterns of PA and overall mortality (OM), breast cancer mortality (BCM), and recurrence-free survival (RFS). Additional analyses of pre- and postdiagnosis PA (no activity (reference), low activity, sufficient activity) with cancer outcomes, such as using a time-dependent model, were performed. In total, 2042 patients were included in the analyses.

Results
There were 206 deaths (114 from breast cancer) after a median follow-up time of 6.0 years after the 2009 interview. Compared to insufficiently active women, increasingly active women were at lower risk of OM, BCM, and RFS (HR (95%CI) of 0.50 (0.31–0.82), 0.54 (0.30–1.00), 0.58 (0.40–0.84), respectively). In sufficiently active women, associations for OM (0.75 (0.48–1.15)), BCM (0.61 (0.33–1.13)), and RFS 0.80 (0.57–1.14)) were similar to increasingly active women but attenuated, and decreasingly active women were not at lower risk for OM (0.91 (0.61–1.36)), BCM (0.80 (0.45–1.42)), and RFS (1.04 (0.76–1.43)). In time-dependent analyses, sufficient activity vs. no activity was associated with better OM (0.73 (0.57–0.93)), BCM (0.64 (0.46–0.89)), and RFS (0.82 (0.68–0.99)). Low activity was not significantly associated with prognosis.

Conclusion
Our data support benefits for breast cancer prognosis in being physically active pre- and postdiagnosis particularly for women who were insufficiently active prediagnosis.
Pleiotropic regulation of a glucose-specific PTS in Clostridium acetobutylicum for high-efficient butanol production from corn stover without detoxification
Authors: Wu Youduo , Bai Yidi , Zhang Daojing , Cheng Chi , Chen Lijie , Bai Fengwu , Xue Chuang 
Published: November 2019

Abstract

Background
Corn stover (CS) is evaluated as the most favorable candidate feedstock for butanol production via microbial acetone–butanol–ethanol (ABE) fermentation by Clostridium acetobutylicum. By independent acid pretreatment and enzymatic hydrolysis, fermentable sugars (mainly glucose and xylose) were released, of which glucose was naturally utilized as the most preferred carbon source by C. acetobutylicum. However, the ABE fermentation using corn stover hydrolysate (CSH) without detoxification is typically limited to poor sugars utilization, butanol production and productivity. In the presence of pretreatment-derived inhibitors, the intracellular ATP and NADH, as important factors involved in cell growth, solventogenesis initiation and stress response, are exceedingly challenged owing to disrupted glucose phosphotransferase system (PTS). Therefore, there is a necessity to develop effective engineering approaches to overcome these limitations for high-efficient butanol production from CSH without detoxification.

Results
PTS-engineered C. acetobutylicum strains were constructed via overexpression and knockout of gene glcG encoding glucose-specific PTS IICBA, which pleiotropically regulated glucose utilization, cell growth, solventogenesis and inhibitors tolerance. The PTSGlcG-overexpressing strain exhibited high fermentation efficiency, wherein butanol production and productivity was 11.1 g/L and 0.31 g/L/h, compared to those of 11.0 g/L and 0.15 g/L/h with the PTSGlcG-deficient strain. During CSH culture without detoxification, the PTSGlcG-overexpressing strain exhibited desirable inhibitors tolerance and solventogenesis with butanol production of 10.0 g/L, increased by 300% and 400% compared to those of 2.5 and 2.0 g/L with the control and PTSGlcG-deficient strains, respectively. As a result of extra glucose and 10 g/L CaCO3 addition into CSH, butanol production and productivity were further maximized to 12.5 g/L and 0.39 g/L/h. These validated improvements on the PTSGlcG-overexpressing strain were ascribed to not only efficient glucose transport but also its cascading effects on intracellular ATP and NADH generation, solventogenesis initiation and inhibitors tolerance at the exponential growth phase.

Conclusion
The PTSGluG regulation could be an effective engineering approach for high-efficient ABE fermentation from lignocellulosic hydrolysates without detoxification or wastewater generation, providing fundamental information for economically sustainable butanol production with high productivity.
From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
Authors: Lindstrand Anna , Eisfeldt Jesper , Pettersson Maria , Carvalho Claudia M. B. , Kvarnung Malin , Grigelioniene Giedre , Anderlid Britt-Marie , Bjerin Olof , Gustavsson Peter , Hammarsjö Anna , Georgii-Hemming Patrik , Iwarsson Erik , Johansson-Soller Maria , Lagerstedt-Robinson Kristina , Lieden Agne , Magnusson Måns , Martin Marcel , Malmgren Helena , Nordenskjöld Magnus , Norling Ameli , Sahlin Ellika , Stranneheim Henrik , Tham Emma , Wincent Josephine , Ygberg Sofia , Wedell Anna , Wirta Valtteri , Nordgren Ann , Lundin Johanna , Nilsson Daniel 
Published: November 2019

Abstract

Background
Since different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.

Methods
We analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n = 68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n = 156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.

Results
First, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850 kb (min 500 bp, max 155 Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (> 10 kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.
Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.

Conclusion
The overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
Does the nitrogen single-breath washout test contribute to detecting pulmonary involvement in rheumatoid arthritis? A pilot study
Authors: Bessa Elizabeth Jauhar Cardoso , Ribeiro Felipe de Miranda Carbonieri , Pinheiro Geraldo da Rocha Castelar , Lopes Agnaldo José 
Published: November 2019

Abstract

Objective
There has been growing interest in studying small airway disease through measures of ventilation distribution, thanks to the resurgence of the nitrogen single-breath washout (N2SBW) test. Therefore, this study evaluated the contribution of the N2SBW test to the detection of pulmonary involvement in patients with rheumatoid arthritis (RA).

Results
Twenty-one patients with RA underwent clinical evaluation, pulmonary function tests (PFTs), including the N2SBW test, and computed tomography (CT). The main tomographic findings were air trapping and bronchiectasis (57.1% and 23.8% of cases, respectively). According to the phase III slope of the N2SBW (phase III slope), 11 and 10 patients had values < 120% predicted and > 120% predicted, respectively. Five patients with limited involvement on CT had a phase III slope > 120%. The residual volume/total lung capacity ratio was significantly different between patients with phase III slopes < 120% and > 120% (P = 0.024). Additionally, rheumatoid factor positivity was higher in patients with a phase III slope > 120% (P = 0.021). In patients with RA and airway disease on CT, the N2SBW test detects inhomogeneity in the ventilation distribution in approximately half of the cases, even in those with normal conventional PFT results.
Screening and quantification of anti-quorum sensing and antibiofilm activities of phyllosphere bacteria against biofilm forming bacteria
Authors: Theodora Nadine Amabel , Dominika Vania , Waturangi Diana Elizabeth 
Published: November 2019

Abstract

Objective
The objectives of this research were to screen anti-quorum sensing activity of phyllosphere bacteria and quantify their antibiofilm activity against biofilm forming bacteria (Bacillus cereus, Staphylococcus aureus, Enterococcus faecalis, Salmonella typhimurium, Vibrio cholerae, Pseudomonas aeruginosa).

Results
We found 11 phyllosphere bacteria isolates with potential anti-quorum sensing activity. Most of the crude extracts from phyllosphere bacteria isolates had anti-quorum sensing activity against Chromobacterium violaceum at certain concentration (20 and 10 mg/mL), but not crude extract from isolate JB 7F. Crude extract showed the largest turbid zone (1,27 cm) using isolate JB 14B with concentration of 10 mg/mL and the narrowest turbid zone isolate (1 cm) using JB 18B with concentration of 10 mg/mL. Crude extracts showed various antibiofilm activities against all tested pathogenic bacteria, it showed the highest biofilm inhibition (90%) and destruction activities (76%) against S. aureus.
Preclinical studies on the toxicology, pharmacokinetics and safety of K1-70TM a human monoclonal autoantibody to the TSH receptor with TSH antagonist activity
Authors: Furmaniak Jadwiga , Sanders Jane , Clark Jill , Wilmot Jane , Sanders Paul , Li Yang , Rees Smith Bernard 
Published: November 2019

Abstract

Background
The human monoclonal autoantibody K1-70™ binds to the TSH receptor (TSHR) with high affinity and blocks TSHR cyclic AMP stimulation by TSH and thyroid stimulating autoantibodies.

Methods
The preclinical toxicology assessment following weekly intravenous (IV) or intramuscular (IM) administration of K1-70™ in rats and cynomolgus monkeys for 29 days was carried out. An assessment of delayed onset toxicity and/or reversibility of toxicity was made during a further 4 week treatment free period. The pharmacokinetic parameters of K1-70™ and the effects of different doses of K1-70™ on serum thyroid hormone levels in the study animals were determined in rats and primates after IV and IM administration.

Results
Low serum levels of T3 and T4 associated with markedly elevated levels of TSH were observed in the study animals following IV and IM administration of K1-70™. The toxicological findings were attributed to the pharmacology of K1-70™ and were consistent with the hypothyroid state. The no observable adverse effect level (NOAEL) could not be established in the rat study while in the primate study it was 100 mg/kg/dose for both males and females.

Conclusions
The toxicology, pharmacodynamic and pharmacokinetic data in this preclinical study were helpful in designing the first in human study with K1-70™ administered to subjects with Graves’ disease.