bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/Cas9-mediated mutagenesis of CAROTENOID CLEAVAGE DIOXYGENASE 8 in tomato provides resistance against the parasitic weed Phelipanche aegyptiaca
Authors: Bari Vinay Kumar , Nassar Jackline Abu , Kheredin Sally Marzouk , Gal-On Amit , Ron Mily , Britt Anne , Steele Daniel , Yoder John , Aly Radi 
Published: August 2019

AbstractBroomrapes (Phelipanche aegyptiaca and Orobanche spp.) are obligate plant parasites that cause extreme damage to crop plants. The parasite seeds have strict requirements for germination, involving preconditioning and exposure to specific chemicals strigolactones [SLs] exuded by the host roots. SLs are plant hormones derived from plant carotenoids via a pathway involving the Carotenoid Cleavage Dioxygenase 8 (CCD8). Having no effective means to control parasitic weeds in most crops, and with CRISPR/Cas9 being an effective gene-editing tool, here we demonstrate that CRISPR/Cas9-mediated mutagenesis of the CCD8 gene can be used to develop host resistance to the parasitic weed P. aegyptiaca. Cas9/single guide (sg) RNA constructs were targeted to the second exon of CCD8 in tomato (Solanum lycopersicum L.) plants. Several CCD8Cas9 mutated tomato lines with variable insertions or deletions in CCD8 were obtained with no identified off-targets. Genotype analysis of T1 plants showed that the introduced CCD8 mutations are inherited. Compared to control tomato plants, the CCD8Cas9 mutant had morphological changes that included dwarfing, excessive shoot branching and adventitious root formation. In addition, SL-deficient CCD8Cas9 mutants showed a significant reduction in parasite infestation compared to non-mutated tomato plants. In the CCD8Cas9 mutated lines, orobanchol (SL) content was significantly reduced but total carotenoids level and expression of genes related to carotenoid biosynthesis were increased, as compared to control plants. Taking into account, the impact of plant parasitic weeds on agriculture and difficulty to constitute efficient control methods, the current study offers insights into the development of a new, efficient method that could be combined with various collections of resistant tomato rootstocks.
The relationship of comorbidities to mortality and cause of death in patients with differentiated thyroid carcinoma
Authors: Lee Young Ki , Hong Namki , Park Se Hee , Shin Dong Yeob , Lee Cho Rok , Kang Sang-Wook , Lee Jandee , Jeong Jong Ju , Nam Kee-Hyun , Chung Woong Youn , Lee Eun Jig 
Published: August 2019

AbstractUnderstanding how comorbidities contribute to death in cancer patients is becoming an important topic. The present study assessed the role of comorbidities in overall mortality and causes of death in patients with differentiated thyroid carcinoma (DTC). This retrospective cohort study included 2070 patients who underwent thyroidectomy for DTC at a single institution between 2002 and 2005. Probabilities of overall, DTC-specific and other-cause death were examined according to the number of comorbidities, with consideration for competing events. The estimated 15-year cumulative incidences of overall, DTC-specific, and other-cause death were 7.3%, 1.6%, and 5.7%, respectively. Taking the group without comorbidities as a reference, we found that the group with 1–2 comorbidities and the group with ≥3 comorbidities had higher probabilities of other-cause death (subhazard ratios = 2.48 and 9.41, respectively; p < 0.01) and consequently shorter overall survival (hazard ratio = 1.95 and 5.33, respectively; p < 0.01), with adjustment for age, sex, and tumor-node-metastasis classification. In contrast, the probability of DTC-specific death was reduced in patients with ≥3 comorbidities (subhazard ratio = 6.81e-10, p < 0.01). For overall death, the relative proportion of death from DTC reduced when the number of comorbidities increased, and DTC-specific death was not observed in patients with ≥3 comorbidities. Our results show that death from DTC itself accounted for only a fraction of the overall deaths among patients who underwent surgery for DTC. Comorbidities increased overall mortality by increasing the probability of other-cause death. Patients with multiple comorbidities had a low probability of dying from DTC because they died earlier from comorbidities.
Therapeutic PD-L1 antibodies are more effective than PD-1 antibodies in blocking PD-1/PD-L1 signaling
Authors: De Sousa Linhares Annika , Battin Claire , Jutz Sabrina , Leitner Judith , Hafner Christine , Tobias Joshua , Wiedermann Ursula , Kundi Michael , Zlabinger Gerhard J. , Grabmeier-Pfistershammer Katharina , Steinberger Peter 
Published: August 2019

AbstractInhibitors of PD-1 signaling have revolutionized cancer therapy. PD-1 and PD-L1 antibodies have been approved for the treatment of cancer. To date, therapeutic PD-1 inhibitors have not been compared in a functional assay. We used an efficient T cell reporter platform to evaluate the efficacy of five clinically used PD-1 inhibitors to block PD-1 signaling. The half maximal effective concentrations (EC50) for nivolumab and pembrolizumab were 76.17 ng/ml (95% CI 64.95–89.34 ng/ml) and 39.90 ng/ml (34.01–46.80 ng/ml), respectively. The EC50 values of the PD-L1 inhibitors were 6.46 ng/ml (5.48–7.61 ng/ml), 6.15 ng/ml (5.24–7.21 ng/ml) and 7.64 ng/ml (6.52–8.96 ng/ml) for atezolizumab, avelumab, and durvalumab, respectively. In conclusion, a functional assay evaluating antibodies targeting PD-1 inhibition in vitro revealed that pembrolizumab is a slightly more effective PD-1 blocker than nivolumab, and that PD-L1 antibodies are superior to PD-1 antibodies in reverting PD-1 signaling.
Role of p53 isoforms in the DNA damage response during Drosophila oogenesis
Authors: Park Ji-Hong , Nguyen Tram Thi Ngoc , Lee Eun-Mi , Castro-Aceituno Veronica , Wagle Ram , Lee Kwang-Soon , Choi Juyoung , Song Young-Han 
Published: August 2019

AbstractThe tumor suppressor p53 is involved in the DNA damage response and induces cell cycle arrest or apoptosis upon DNA damage. Drosophila p53 encodes two isoforms, p53A and p53B, that induce apoptosis in somatic cells. To investigate the roles of Drosophila p53 isoforms in female germline cells, the DNA damage response was analyzed in the adult ovary. Early oogenesis was sensitive to irradiation and lok-, p53-, and hid-dependent cell death occurred rapidly after both low- and high-dose irradiation. Both p53 isoforms were responsible for this cell death. On the other hand, delayed cell death in mid-oogenesis was induced at a low level only after high-dose irradiation in a p53-independent manner. The daily egg production, which did not change after low-dose irradiation, was severely reduced after high-dose irradiation in p53 mutant females due to the loss of germline stem cells. When the p53A or p53B isoform was expressed in the germline cells in the p53 mutant females at levels that do not affect normal oogenesis, p53A, but not p53B, restored the fertility of the irradiated female. In summary, moderate expression of p53A is critical to maintain the function of germline stem cells during normal oogenesis as well as after high-dose irradiation.
Bacteria isolated from the cuticle of plant-parasitic nematodes attached to and antagonized the root-knot nematode Meloidogyne hapla
Authors: Topalović Olivera , Elhady Ahmed , Hallmann Johannes , Richert-Pöggeler Katja R. , Heuer Holger 
Published: August 2019

AbstractPlant-parasitic nematodes are associated with specifically attached soil bacteria. To investigate these bacteria, we employed culture-dependent methods to isolate a representative set of strains from the cuticle of the infective stage (J2) of the root-knot nematode Meloidogyne hapla in different soils. The bacteria with the highest affinity to attach to J2 belonged to the genera Microbacterium, Sphingopyxis, Brevundimonas, Acinetobacter, and Micrococcus as revealed by 16S rRNA gene sequencing. Dynamics of the attachment of two strains showed fast adhesion in less than two hours, and interspecific competition for attachment sites. Isolates from the cuticle of M. hapla J2 attached to the lesion nematode Pratylenchus penetrans, and vice versa, suggesting similar attachment sites on both species. Removal of the surface coat by treatment of J2 with the cationic detergent CTAB reduced bacterial attachment, but did not prevent it. Some of the best attaching bacteria impaired M. hapla performance in vitro by significantly affecting J2 mortality, J2 motility and egg hatch. Most of the tested bacterial attachers significantly reduced the invasion of J2 into tomato roots, suggesting their beneficial role in soil suppressiveness against M. hapla.
Shape programming of polymeric based electrothermal actuator (ETA) via artificially induced stress relaxation
Authors: Sun Yu-Chen , Leaker Benjamin D. , Lee Ji Eun , Nam Ryan , Naguib Hani E. 
Published: August 2019

AbstractElectrothermal actuators (ETAs) are a new generation of active materials that can produce different motions from thermal expansion induced by Joule heating. It is well-known that the degree of deformation is determined by the amount of Joule heating and the coefficient of thermal expansion (CTE) of the material. Previous works on polymeric ETAs are strongly focused on increasing electrical conductivity by utilizing super-aligned carbon nanotube (CNT) sheets. This allows greater deformation for the same drive voltage. Despite these accomplishments with low-voltage actuation, many of the ETAs were constructed to have basic geometries such as a simple cantilever shape. In this paper, it was discovered that shape of polymeric ETA can be programmed into a desired configuration by applying an induced stress relaxation mechanism and post secondary curing. By utilizing such effects, an ETA can be programmed into a curled resting state which allows the actuator to achieve an active bending angle over 540°, a value far greater than any previous studies. This shape programming feature also allows for tailoring the actuator configuration to a specific application. This is demonstrated here by fabricating a small crawling soft robot similar to mimic an inchworm motion.
Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test
Authors: Tomas Cara , Lodge Tiffany A. , Potter Michelle , Elson Joanna L. , Newton Julia L. , Morten Karl J. 
Published: August 2019

AbstractThe mitochondrial energy score (MES) protocol, developed by the Myhill group, is marketed as a diagnostic test for chronic fatigue syndrome/Myalgic Encephalomyelitis (CFS/ME). This study assessed the reliability and reproducibility of the test, currently provided by private clinics, to assess its potential to be developed as an NHS accredited laboratory test. We replicated the MES protocol using neutrophils and peripheral blood mononuclear cells (PBMCs) from CFS/ME patients (10) and healthy controls (13). The protocol was then repeated in PBMCs and neutrophils from healthy controls to investigate the effect of delayed sample processing time used by the Myhill group. Experiments using the established protocol showed no differences between CFS/ME patients and healthy controls in any of the components of the MES (p ≥ 0.059). Delaying blood sample processing by 24 hours (well within the 72 hour time frame quoted by the Myhill group) significantly altered many of the parameters used to calculate the MES in both neutrophils and PBMCs. The MES test does not have the reliability and reproducibility required of a diagnostic test and therefore should not currently be offered as a diagnostic test for CFS/ME. The differences observed by the Myhill group may be down to differences in sample processing time between cohorts.
Beta-blocker choice and exchangeability in patients with heart failure and chronic obstructive pulmonary disease: an Italian register-based cohort study
Authors: Sessa Maurizio , Mascolo Annamaria , Rasmussen Daniel Bech , Kragholm Kristian , Jensen Magnus Thorsten , Sportiello Liberata , Rafaniello Concetta , Tari Giuseppe Michele , Pagliaro Claudia , Andersen Morten , Rossi Francesco , Capuano Annalisa 
Published: August 2019

AbstractClinical guidelines suggest that for patients with heart failure and concurrent chronic obstructive pulmonary disease (COPD), metoprolol/bisoprolol/nebivolol should be preferred over carvedilol. However, studies suggest a high proportion of carvedilol usage that remains unexplained. Therefore, we aimed to investigate the predictors of carvedilol choice in patients with heart failure and COPD that were naïve to carvedilol or metoprolol/bisoprolol/nebivolol. Caserta Local Health Unit databases (Italy) were used as data sources. Age, sex, chronic/acute comorbidities, and co-medications were included in a logistic regression model to assess predictors of carvedilol choice. Chronic comorbidities include those defined in the Elixhauser comorbidity index and all hospitalizations within two years prior to the first beta-blocker prescription. Comedications include all redeemed prescriptions within one year prior to the beta-blocker prescription. Kernel density estimations were used to assess the overlap in propensity and preference scores distributions for receiving carvedilol and thereby potential beta-blocker exchangeability. Totally, 10091 patients composed the study population; 2011 were exposed to carvedilol. The overlapping of propensity scores distributions was 57%. Accordingly, the exchangeability was not reached. Atrioventricular block (Odds Ratio, OR 8.20; 95% Confidence Interval, 95% CI 1.30–51.80), cerebrovascular thrombosis (OR 7.06; 95% CI 1.14–43.68), chronic kidney disease (OR 4.32; 95% CI 1.16–16.02), and acute heart failure (OR 1.97; 95% CI 1.28–3.03) hospitalizations were statistically significantly associated with carvedilol choice. Analogously, human insulin (OR 3.00; 95% CI 1.24–7.24), fondaparinux (OR 2.47; 95% CI 1.17–5.21) or strontium ranelate (OR 2.03; 95% CI 1.06–3.90) redeemed prescriptions. In conclusion, this study suggests the absence of beta-blockers exchangeability and a preferential choice of carvedilol in patients with heart failure, COPD and concurrent chronic kidney disease, atrioventricular block, cerebrovascular thrombosis, acute heart failure or redeeming human insulin, fondaparinux or strontium ranelate prescriptions. Therefore, it suggests that choice of prescribing carvedilol over metoprolol/bisoprolol/nebivolol is driven by differences in comorbidities and co-treatments.
Uniform two-dimensional crystals of polystyrene nanospheres fabricated by a surfactant-assisted spin-coating method with polyoxyethylene tridecyl ether
Authors: Park Byoungchoo , Na Seo Yeong , Bae In-Gon 
Published: August 2019

AbstractSpin-coated self-assemblies of colloidal particles have been developed recently as an attractive close-packed monolayer of the particles for a variety of applications, but they are limited by the small area of their monolayers, especially given their low uniformity and monolayer coverage on large-area substrates. We report several noteworthy characteristics of a close-packed monolayer of polystyrene nanospheres (PS NSs) fabricated using a simple and inexpensive spin-coating method with a PS NS suspension mixed using the nonionic surfactant polyoxyethylene (12) tridecyl ether (PEO-TDE). In our study, we show that the PEO-TDE surfactant offers excellent wettability, surface tension, and a slow solvent evaporation rate of the PS NS suspension, similar to the conventional surfactant Triton X-100. We demonstrate that the relatively high monolayer coverage with reduced defects is produced when introducing the PEO-TDE surfactant. Specifically, monolayer coverage of more than 95% on a Si substrate was achieved, which is much better than that with the typical Triton X-100, and is one of the highest coverage rates realized by a spin-coating method. This excellent uniformity of the PS NS monolayer with high monolayer coverage is mainly attributed to the relatively low viscosity of the PS NS suspension, even at high concentrations of PEO-TDE. Moreover, the PEO-TDE surfactant provides highly uniform monolayers on a large-scale glass substrate even for large-sized PS NSs. We also highlight the fact that the PEO-TDE surfactant has another advantage in that the spin-coating process of the PS NS suspension can be done under common ambient laboratory conditions, unlike those required for the highly toxic Triton X-100. We therefore conclude that PEO-TDE can be a useful surfactant during the fabrication of close-packed monolayers for various applications owing to its simple and straightforward control of PS NSs, its uniform and high surface coverage, and due to the safety of the fabrication process.
Encapsulation of Isoniazid-conjugated Phthalocyanine-In-Cyclodextrin-In-Liposomes Using Heating Method
Authors: Nkanga Christian Isalomboto , Krause Rui Werner Maçedo 
Published: August 2019

AbstractLiposomes are reputed colloidal vehicles that hold the promise for targeted delivery of anti-tubercular drugs (ATBDs) to alveolar macrophages that host Mycobacterium tuberculosis. However, the costly status of liposome technology, particularly due to the use of special manufacture equipment and expensive lipid materials, may preclude wider developments of therapeutic liposomes. In this study, we report efficient encapsulation of a complex system, consisting of isoniazid-hydrazone-phthalocyanine conjugate (Pc-INH) in gamma-cyclodextrin (γ-CD), in liposomes using crude soybean lecithin by means of a simple organic solvent-free method, heating method (HM). Inclusion complexation was performed in solution and solid-state, and evaluated using UV-Vis, magnetic circular dichroism, 1H NMR, diffusion ordered spectroscopy and FT-IR. The HM-liposomes afforded good encapsulation efficiency (71%) for such a large Pc-INH/γ-CD complex (PCD) system. The stability and properties of the PCD-HM-liposomes look encouraging; with particle size 240 nm and Zeta potential −57 mV that remained unchanged upon storage at 4 °C for 5 weeks. The release study performed in different pH media revealed controlled release profiles that went up to 100% at pH 4.4, from about 40% at pH 7.4. This makes PCD-liposomes a promising system for site-specific ATBD delivery, and a good example of simple liposomal encapsulation of large hydrophobic compounds.
A Novel Decision Making Procedure during Wakefulness for Screening Obstructive Sleep Apnea using Anthropometric Information and Tracheal Breathing Sounds
Authors: Elwali Ahmed , Moussavi Zahra 
Published: August 2019

AbstractObstructive sleep apnea (OSA) is an underdiagnosed common disorder. Undiagnosed OSA, in particular, increases the perioperative morbidity and mortality risks for OSA patients undergoing surgery requiring full anesthesia. OSA screening using the gold standard, Polysomnography (PSG), is expensive and time-consuming. This study offers an objective and accurate tool for screening OSA during wakefulness by a few minutes of breathing sounds recording. Our proposed algorithm (AWakeOSA) extracts an optimized set (3–4) of breathing sound features specific to each anthropometric feature (i.e. age, sex, etc.) for each subject. These personalized group (e.g. age) classification features are then used to determine OSA severity in the test subject for that anthropomorphic parameter. Each of the anthropomorphic parameter classifications is weighted and summed to produce a final OSA severity classification. The tracheal breathing sounds of 199 individuals (109 with apnea/hypopnea index (AHI) < 15 as non-OSA and 90 with AHI ≥ 15 as moderate/severe-OSA) were recorded during wakefulness in the supine position. The sound features sensitive to OSA were extracted from a training set (n = 100). The rest were used as a blind test dataset. Using Random-Forest classification, the training dataset was shuffled 1200–6000 times to avoid any training bias. This routine resulted in 81.4%, 80.9%, and 82.1% classification accuracy, sensitivity, and specificity, respectively, on the blind-test dataset which was similar to the results for the out-of-bag-validation applied to the training dataset. These results provide a proof of concept for AWakeOSA algorithm as an accurate, reliable and quick OSA screening tool that can be done in less than 10 minutes during wakefulness.
Up-regulation of heat shock protein 27 inhibits apoptosis in lumbosacral nerve root avulsion-induced neurons
Authors: Zhou Zhi-bin , Huang Gao-xiang , Lu Jia-jia , Ma Jun , Yuan Qi-jun , Cao Yan , Zhu Lei 
Published: August 2019

AbstractLumbosacral nerve root avulsion leads to widespread death of neurons in the anterior horn area of the injured spinal cord, which results in dysfunction in the lower extremities. Heat shock protein 27 (Hsp27) has been found to play cytoprotective roles under adverse conditions. However, the role of Hsp27 in neurons after lumbosacral nerve root avulsion is unknown. The aim of the present study was to investigate the effects and mechanism of action of Hsp27 on neurons after lumbosacral nerve root avulsion. It was found that Hsp27 expression was elevated in the anterior horn area of the injured spinal cord and the up-regulation of Hsp27 protected neurons against apoptosis after lumbosacral nerve root avulsion. In addition, Hsp27 plays an anti-apoptotic role by suppressing oxidative stress reactions. These findings indicated that Hsp27 may play a key role in resistance to lumbosacral nerve root avulsion-induced neuron apoptosis and may prove to be a potential strategy for improving prognosis after lumbosacral nerve root avulsion.
Glycerylphytate compounds with tunable ion affinity and osteogenic properties
Authors: Mora-Boza Ana , López-Donaire María Luisa , Saldaña Laura , Vilaboa Nuria , Vázquez-Lasa Blanca , San Román Julio 
Published: August 2019

AbstractPhytic acid (PA) is a natural-occurring antioxidant, which plays an important role in many biological processes. PA is recognized as a potent inhibitor of lipid peroxidation because of its high affinity to multivalent cations, and it can play a role in osteogenic processes. However, its powerful chelating capacity is controversial because it can lead to a severe reduction of mineral availability in the organism. For this reason, compounds with beneficial biological properties of PA, but a modular ion binding capacity, are of high interest. In this work, we report the synthesis and physicochemical characterization of two hydroxylic derivatives of PA, named glycerylphytates (GPhy), through a condensation reaction of PA with glycerol (G). Both derivatives present antioxidant properties, measured by ferrozine/FeCl2 method and chelating activity with calcium ions depending on the content of glyceryl groups incorporated. Besides, the hydroxylic modification not only modulates the ion binding affinity of derivatives but also improves their cytocompatibility in human bone marrow mesenchymal cells (MSCs). Furthermore, GPhy derivatives display osteogenic properties, confirmed by COL1A and ALPL expression depending on composition. These positive features convert GPhy compounds into potent alternatives for those skeletal diseases treatments where PA is tentatively applied.