bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurring genomic structural variation leads to clonal instability and loss of productivity
Authors: Bandyopadhyay Arpan A. , O’Brien Sofie A. , Zhao Liang , Fu Hsu‐Yuan , Vishwanathan Nandita , Hu Wei‐Shou 
Published: August 2018

AbstractChinese hamster ovary cells, commonly used in the production of therapeutic proteins, are aneuploid. Their chromosomes bear structural abnormality and undergo changes in structure and number during cell proliferation. Some production cell lines are unstable and lose their productivity over time in the manufacturing process and during the product’s life cycle. To better understand the link between genomic structural changes and productivity stability, an immunoglobulin G producing cell line was successively single‐cell cloned to obtain subclones that retained or lost productivity, and their genomic features were compared. Although each subclone started with a single karyotype, the progeny quickly diversified to a population with a distribution of chromosome numbers that is not distinctive from the parent and among subclones. The comparative genomic hybridization (CGH) analysis showed that the extent of copy variation of gene coding regions among different subclones stayed at levels of a few percent. Genome regions that were prone to loss of copies, including one with a product transgene integration site, were identified in CGH. The loss of the transgene copy was accompanied by loss of transgene transcript level. Sequence analysis of the host cell and parental producing cell showed prominent structural variations within the regions prone to loss of copies. Taken together, we demonstrated the transient nature of clonal homogeneity in cell line development and the retention of a population distribution of chromosome numbers; we further demonstrated that structural variation in the transgene integration region caused cell line instability. Future cell line development may target the transgene into structurally stable regions.
Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry
Authors: MacKenzie‐Graham Allan , Brook Jenny , Kurth Florian , Itoh Yuichiro , Meyer Cassandra , Montag Michael J. , Wang He‐Jing , Elashoff Robert , Voskuhl Rhonda R. 
Published: August 2018

AbstractIntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty‐two estriol‐ and forty‐nine placebo‐treated RRMS patients underwent clinical evaluations and brain MRI. Voxel‐based morphometry (VBM) was used to evaluate voxelwise GM sparing from high‐resolution T1‐weighted scans.ResultsA region of treatment‐induced sparing (TIS) was defined as the areas where GM was spared in estriol‐ as compared to placebo‐treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability‐specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol‐treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability‐specific biomarker for clinical trials of candidate neuroprotective treatments in MS.
Evaluation of anticoagulation use and subsequent stroke in patients with atrial fibrillation after empiric surgical left atrial appendage closure: A retrospective case‐control study
Authors: Johnsrud Daniel O. , Melduni Rowlens M. , Lahr Brian , Yao Xiaoxi , Greason Kevin L. , Noseworthy Peter A. 
Published: August 2018

BackgroundSurgical exclusion of the left atrial appendage (LAA) can be performed at the time of cardiac operation as a potential modality to decrease cardioembolic risk attributable to atrial fibrillation (AF), but it remains unclear if this decreases stroke incidence. Furthermore, it is not known whether LAA exclusion impacts the decision to discontinue anticoagulation impacting subsequent stroke risk.HypothesisLAA exclusion does not significantly alter subsequent anticoagulation use or stroke incidence.MethodsWe studied 124 patients from Olmsted County with prior history of AF who underwent cardiac surgery at our institution between 1993 and 2015. Patients were divided into two groups on the basis of LAA exclusion and matched (1:1) according to 16 pretreatment variables using propensity scores obtained from a logistic regression model. Outcome data collected through chart review for survival, stroke, and the presence and duration of anticoagulation were compared between groups.ResultsThe proportion of patients receiving anticoagulation at discharge and at 5 years was not significantly different between patients who underwent LAA exclusion and those who did not; 90% vs 81%, P = 0.156, 48% vs 49%, P = 0.722, respectively. On Kaplan‐Meier analysis there were no significant differences in time free from stroke between cases and controls. Patients discharged on oral anticoagulation (OAC) had significantly lower risk of stroke (HR = 0.19, 95% confidence interval [CI] = 0.06‐0.59, P = 0.004), independent of whether LAA closure was used.ConclusionLAA exclusion did not appear to reduce early or late stroke. Only OAC was associated with a reduction in stroke risk, underscoring the need for continued anticoagulation in high‐risk patients.
Predicting pain recovery in patients with acute low back pain: Updating and validation of a clinical prediction model
Authors: da Silva Tatiane , Macaskill Petra , Kongsted Alice , Mills Kathryn , Maher Chris G. , Hancock Mark J. 
Published: August 2018

AbstractBackgroundThe prognosis of acute low back pain (LBP) is typically good; however, there is substantial variation in individual patient's outcomes. We recently developed a prediction model that was able to predict the likelihood of pain recovery in patients with acute LBP who continue to have pain approximately 1 week after initially seeking care. The aims of the current study were to (a) re‐categorize the variables in the developmental dataset to be able to validate the model in the validation dataset; (b) refit the existing model in the developmental dataset; and (c) validate the model in the validation dataset.MethodsThe validation study sample comprised 737 patients with acute LBP, with a pain score of ≥2/10, 1 week after initially seeking care and with duration of current episode of ≤4 weeks. The primary outcome measure was days to pain recovery. Some of the variables from the development dataset were re‐categorized prior to refitting the existing model in the developmental dataset using Cox regression. The performance (calibration and discrimination) of the prediction model was then tested in the validation dataset.ResultsThree variables of the development dataset were re‐categorized. The performance of the prediction model with re‐categorized variables in the development dataset was good (C‐statistic = 0.76, 95% CI 0.70–0.82). The discrimination of the model using the validation dataset resulted in a C‐statistic of 0.71 (95% CI 0.63–0.78). The calibration for the validation sample was acceptable at 1 month. However, at 1 week the predicted proportions within quintiles tended to overestimate the observed recovery proportions, and at 3 months, the predicted proportions tended to underestimate the observed recovery proportions.ConclusionsThe updated prediction model demonstrated reasonably good external validity and may be useful in practice, but further validation and impact studies in relevant populations should be conducted.SignificanceA clinical prediction model based on five easily collected variables demonstrated reasonable external validity. The prediction model has the potential to inform patients and clinicians of the likely prognosis of individuals with acute LBP but requires impact studies to assess its clinical usefulness.
Effect of Crystallinity Modulation between Electron Transport Layer and Photo‐Generation Materials on ZnO‐Based Polymer Solar Cells
Authors: Zhang Xiaohua , Fan Pu , Han Yu , Yu Junsheng 
Published: August 2018

AbstractAs one of the most widely used electron transport layers (ETLs) for inverted polymer solar cells (PSCs), ZnO has great effect on the growth of photo‐generated layer. In this work, the ZnO‐based PSCs with the compositional blend of PffBT4T‐2OD: PCBM and PTB7‐Th: PCBM are fabricated to investigate the crystallinity modulation effect (CME) between electron transport layer and photo‐generation materials. The results showed that both the high crystallinity PffBT4T‐2OD: PCBM processed on the large nanoparticles ZnO and the low crystallinity PTB7‐Th: PCBM processed on small nanoparticles ZnO exhibit excellent photovoltaic performances. By verifying the combination of ZnO nanoparticles with photo‐generation materials, it proves that the CME can result in a smooth photo‐generated layer surface to ensure efficient electron transport as well as collection with suppressed bimolecular recombination, leading to the increase of photocurrent and the improvement of inverted PSCs performance accordingly.
What agricultural practices are most likely to deliver “sustainable intensification” in the UK?
Authors: Dicks Lynn V. , Rose David C. , Ang Frederic , Aston Stephen , Birch A. Nicholas E. , Boatman Nigel , Bowles Elizabeth L. , Chadwick David , Dinsdale Alex , Durham Sam , Elliott John , Firbank Les , Humphreys Stephen , Jarvis Phil , Jones Dewi , Kindred Daniel , Knight Stuart M. , Lee Michael R. F. , Leifert Carlo , Lobley Matt , Matthews Kim , Midmer Alice , Moore Mark , Morris Carol , Mortimer Simon , Murray T. Charles , Norman Keith , Ramsden Stephen , Roberts Dave , Smith Laurence G. , Soffe Richard , Stoate Chris , Taylor Bryony , Tinker David , Topliff Mark , Wallace John , Williams Prysor , Wilson Paul , Winter Michael , Sutherland William J. 
Published: August 2018

AbstractSustainable intensification is a process by which agricultural productivity is enhanced whilst also creating environmental and social benefits. We aimed to identify practices likely to deliver sustainable intensification, currently available for UK farms but not yet widely adopted. We compiled a list of 18 farm management practices with the greatest potential to deliver sustainable intensification in the UK, following a well‐developed stepwise methodology for identifying priority solutions, using a group decision‐making technique with key agricultural experts. The list of priority management practices can provide the focal point of efforts to achieve sustainable intensification of agriculture, as the UK develops post‐Brexit agricultural policy, and pursues the second Sustainable Development Goal, which aims to end hunger and promote sustainable agriculture. The practices largely reflect a technological, production‐focused view of sustainable intensification, including for example, precision farming and animal health diagnostics, with less emphasis on the social and environmental aspects of sustainability. However, they do reflect an integrated approach to farming, covering many different aspects, from business organization and planning, to soil and crop management, to landscape and nature conservation. For a subset of 10 of the priority practices, we gathered data on the level of existing uptake in English and Welsh farms through a stratified survey in seven focal regions. We find substantial existing uptake of most of the priority practices, indicating that UK farming is an innovative sector. The data identify two specific practices for which uptake is relatively low, but which some UK farmers find appealing and would consider adopting. These practices are: prediction of pest and disease outbreaks, especially for livestock farms; staff training on environmental issues, especially on arable farms.
Genomic analysis reveals recurrent deletion of JAK‐STAT signaling inhibitors HNRNPK and SOCS1 in mycosis fungoides
Authors: Bastidas Torres Armando N. , Cats Davy , Mei Hailiang , Szuhai Karoly , Willemze Rein , Vermeer Maarten H. , Tensen Cornelis P. 
Published: August 2018

AbstractMycosis fungoides (MF) is the most common cutaneous T‐cell lymphoma (CTCL). Causative genetic alterations in MF are unknown. The low recurrence of pathogenic small‐scale mutations (ie, nucleotide substitutions, indels) in the disease, calls for the study of additional aspects of MF genetics. Here, we investigated structural genomic alterations in tumor‐stage MF by integrating whole‐genome sequencing and RNA‐sequencing. Multiple genes with roles in cell physiology (n = 113) and metabolism (n = 92) were found to be impacted by genomic rearrangements, including 47 genes currently implicated in cancer. Fusion transcripts involving genes of interest such as DOT1L, KDM6A, LIFR, TP53, and TP63 were also observed. Additionally, we identified recurrent deletions of genes involved in cell cycle control, chromatin regulation, the JAK‐STAT pathway, and the PI‐3‐K pathway. Remarkably, many of these deletions result from genomic rearrangements. Deletion of tumor suppressors HNRNPK and SOCS1 were the most frequent genetic alterations in MF after deletion of CDKN2A. Notably, SOCS1 deletion could be detected in early‐stage MF. In agreement with the observed genomic alterations, transcriptome analysis revealed up‐regulation of the cell cycle, JAK‐STAT, PI‐3‐K and developmental pathways. Our results position inactivation of HNRNPK and SOCS1 as potential driver events in MF development.
Putative new childhood leukemia cancer predisposition syndrome caused by germline bi‐allelic missense mutations in DDX41
Authors: Diness Birgitte R. , Risom Lotte , Frandsen Thomas L. , Hansen Bente , Andersen Mette K. , Schmiegelow Kjeld , Wadt Karin A. W. 
Published: August 2018

Abstract
DDX41 has recently been identified as a new autosomal dominantly inherited cancer predisposition syndrome causing increased risk of adult onset acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We report for the first time compound heterozygote germline missense DDX41 mutations located in the DEAD‐box domain, identified in two siblings by exome sequencing. Both siblings have slight dysmorphic findings, psychomotor delays and intellectual disability, and one developed blastic plasmacytoid dendritic cell neoplasm (BPDCN) at age five. RNA‐sequencing of bone marrow showed DDX41 expression including both mutations. However, the allele fraction of p.Pro321Leu accounted for 96% in the RNA‐sequencing indicating this mutation to be the more significant variant. Exome sequencing of the leukemic blasts identified no additional known driver mutations. There is no pattern indicating autosomal dominantly inherited cancer predisposition in the family, but the father has sarcoidosis, which has been associated with heterozygous DDX41 mutation. We propose that bi‐allelic mutations in DDX41 could potentially be a new cancer predisposition syndrome associated with delayed psychomotor development.
Silibinin‐induced endoplasmic reticulum stress and mitochondrial dysfunction suppress growth of endometriotic lesions
Authors: Ham Jiyeon , Kim Jonggun , Bazer Fuller W. , Lim Whasun , Song Gwonhwa 
Published: August 2018

Silibinin is a flavonolignan extracted from milk thistle, which has been used for treating liver disorders, various cancers, and gynecological diseases. However, attempts for treating endometriosis with silibinin are lacking. In this study, we observed that silibinin exerts antiproliferative and apoptotic effects on human endometriotic cell lines VK2/E6E7 and End1/E6E7. We also identified that silibinin‐induced oxidative stress and lipid peroxidation in human endometriotic cells. Moreover, we observed upregulation of calcium concentration in the cytosol and mitochondrial matrix, which resulted in mitochondrial dysfunction. Furthermore, induction of endoplasmic reticulum stress signals with rapid mitogen‐activated protein kinase (MAPK) pathway signaling resulted in apoptosis of both cells. Using an animal model mimicking the retrograde menstruation hypothesis, we verified the effects of silibinin on reducing endometriotic lesions by inhibiting the expression of inflammatory cytokines in mice. Silibinin might be used as a novel therapeutic agent or supplement for inhibiting progression of endometriosis in vitro and in vivo.
Dual role of chemically functionalized activated carbon fibres: investigation of parameters influencing the degradation of organophosphorus compounds and antibacterial behaviour
Authors: Gopinath Ashitha , Krishna Kadirvelu 
Published: August 2018

AbstractBACKGROUNDAn efficient material possessing both photocatalytic and antimicrobial properties is necessary to remediate contaminated water resources. In the present study, zinc oxide nanorods (ZnO) have been impregnated on activated carbon fibres (ACF) to develop a heterogeneous photocatalytic system for the degradation of an organophosphorus compound, taking Malathion as a model pollutant, and to investigate the antibacterial efficiency of the former.RESULTSThe efficiency of Malathion removal varies with catalyst dosage, initial concentration of Malathion, and also depends on the interference from inorganic ions such as chloride, nitrate, sulfate, phosphate and bicarbonate in the contaminated solution. The role played by the highly active radicals in the degradation process is inevitable, confirmed by the addition of radical scavengers during the reaction. Hydroxyl radicals were found to be the most active species accountable for the degradation of Malathion. Moreover, OH trapping experiments conducted by measuring photoluminescence (PL) intensity concluded that greater amounts of OH radicals are generated with increase in time. Reusability and long‐term stability of the composite was validated for up to five degradation cycles. The developed composite also possesses microbial decontamination capabilities, verified by studying antibacterial assay against Gram positive Staphylococcus aureus and Gram negative strains of Pseudomonas aeruginosa and Klebsiella Pneumoniae.CONCLUSIONDual functional and reusable ZnO rods/ACF composites were developed using a simple, low cost hydrothermal method, and could be used as a potential candidate for water treatment applications. © 2018 Society of Chemical Industry
Effects of cobalt and chromium ions on oxidative stress and energy metabolism in macrophages in vitro
Authors: Salloum Zeina , Lehoux Eric A. , Harper Mary‐Ellen , Catelas Isabelle 
Published: August 2018

ABSTRACTCobalt and chromium ions released from cobalt‐chromium‐molybdenum (CoCrMo)‐based implants are a potential health concern, especially since both ions have been shown to induce oxidative stress in macrophages, the predominant immune cells in periprosthetic tissues. Ions of other transition metals (Cd, Ni) have been reported to inhibit the activity of mitochondrial enzymes in the electron transport chain. However, the effects of Co and Cr ions on the energy metabolism of macrophages remain largely unknown. The objective of the present study was to analyze the effects of Co2+ and Cr3+ on oxidative stress and energy metabolism in macrophages in vitro. RAW 264.7 murine macrophages were exposed to 6–18 ppm Co2+ or 50–150 ppm Cr3+. Results showed a significant increase in two markers of oxidative stress, reactive oxygen species level and protein carbonyl content, with increasing concentrations of Co2+, but not with Cr3+. In addition, oxygen consumption rates (OCR; measured using an extracellular flux analyzer) showed significant decreases in both mitochondrial respiration and non‐mitochondrial oxygen consumption with increasing concentrations of Co2+, but not with Cr3+. OCR results further showed that Co2+, but not Cr3+, induced mitochondrial dysfunction, including a decrease in oxidative phosphorylation capacity. Overall, this study suggests that mitochondrial dysfunction may contribute to Co2+‐induced oxidative stress in macrophages, and thereby to the inflammatory response observed in periprosthetic tissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3178–3187, 2018.
Effect of age on nutritional properties of Iberian wild red deer meat
Authors: Lorenzo José M , Maggiolino Aristide , Gallego Laureano , Pateiro Mirian , Serrano Martina Pérez , Domínguez Rubén , García Andrés , Landete‐Castillejos Tomás , De Palo Pasquale 
Published: August 2018

ABSTRACTBACKGROUNDThis study assessed the effect of age (L, less than 27 months old; M, from 27 to 42 months old; H, 43 months and older) on the fatty acid profile, cholesterol content, amino acid composition and mineral content of 150 Iberian wild red deer meat samples.RESULTSIntramuscular fat content increased (P < 0.05) with age (0.05 vs 0.12 vs 0.34% for L, M and H groups respectively), while cholesterol content decreased (P < 0.05) as the slaughter age increased (52.78 vs 48.72 vs 45.34 mg per 100 g meat for L, M and H groups respectively). The slaughter age showed differences among groups for saturated fatty acids, with the highest content in older animals (30.41 vs 34.55 vs 38.21% for L, M and H groups respectively), whereas younger deer displayed the highest polyunsaturated fatty acid levels (50.05 vs 45.24 vs 37.55% for L, M and H groups respectively). The n‐6/n‐3 ratio was more favorable (P < 0.05) for young and medium ages compared with that for older animals. In contrast, amino acid profile and mineral content were only slightly affected by age.CONCLUSIONAs a general conclusion, wild red deer meat could be considered a good alternative to red meats for human consumption. © 2018 Society of Chemical Industry
Comparison of the functional properties of RuBisCO protein isolate extracted from sugar beet leaves with commercial whey protein and soy protein isolates
Authors: Martin Anneke H , Castellani Oscar , de Jong Govardus AH , Bovetto Lionel , Schmitt Christophe 
Published: August 2018

AbstractBackgroundRuBisCO was extracted from sugar beet leaves using soft and food‐compatible technologies. Proximate composition, solubility, emulsifying, foaming and gelling properties of the protein isolate were determined. All these properties were systematically benchmarked against commercial whey and soy protein isolates used in food applications.ResultsRuBisCO protein isolate (RPI) contained 930 g kg−1 of crude protein. Protein solubility was higher than 80% at pH values lower than 4.0 or higher than 5.5. Foaming capacity of RPI was better at pH 4.0 than at pH 7.0. Interestingly, 10 g kg−1 protein foams were more stable (pH 7.0 and 4.0) than foams obtained with whey or soy protein. Moreover, 10 g kg−1 RPI emulsions at pH 4.0 or 7.0 exhibited good stability, being similar to whey protein isolate. Remarkable gelling properties were observed at pH 7.0, where 50 g kg−1 protein solutions of RPI formed self‐supporting gels while more concentrated solutions were needed for whey or soy protein.ConclusionRuBisCO showed comparable or superior functional properties to those of currently used whey and soy protein isolates. These results highlight the high potential of sugar beet leaf protein isolate as a nutritious and functional food ingredient to face global food security and protein supply. © 2018 Society of Chemical Industry