bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Y1 receptor signaling improves islet transplant outcome
Authors: Loh Kim , Shi Yan-Chuan , Walters Stacey , Bensellam Mohammed , Lee Kailun , Dezaki Katsuya , Nakata Masanori , Ip Chi Kin , Chan Jeng Yie , Gurzov Esteban N. , Thomas Helen E. , Waibel Michaela , Cantley James , Kay Thomas W. , Yada Toshihiko , Laybutt D. Ross , Grey Shane T. , Herzog Herbert 
Published: September 2017

AbstractFailure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.
Metabolic stress-induced cardiomyopathy is caused by mitochondrial dysfunction due to attenuated Erk5 signaling
Authors: Liu Wei , Ruiz-Velasco Andrea , Wang Shoubao , Khan Saba , Zi Min , Jungmann Andreas , Dolores Camacho-Muñoz Maria , Guo Jing , Du Guanhua , Xie Liping , Oceandy Delvac , Nicolaou Anna , Galli Gina , Müller Oliver J. , Cartwright Elizabeth J. , Ji Yong , Wang Xin 
Published: September 2017

AbstractThe prevalence of cardiomyopathy from metabolic stress has increased dramatically; however, its molecular mechanisms remain elusive. Here, we show that extracellular signal-regulated protein kinase 5 (Erk5) is lost in the hearts of obese/diabetic animal models and that cardiac-specific deletion of Erk5 in mice (Erk5-CKO) leads to dampened cardiac contractility and mitochondrial abnormalities with repressed fuel oxidation and oxidative damage upon high fat diet (HFD). Erk5 regulation of peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) is critical for cardiac mitochondrial functions. More specifically, we show that Gp91phox activation of calpain-1 degrades Erk5 in free fatty acid (FFA)-stressed cardiomyocytes, whereas the prevention of Erk5 loss by blocking Gp91phox or calpain-1 rescues mitochondrial functions. Similarly, adeno-associated virus 9 (AAV9)-mediated restoration of Erk5 expression in Erk5-CKO hearts prevents cardiomyopathy. These findings suggest that maintaining Erk5 integrity has therapeutic potential for treating metabolic stress-induced cardiomyopathy.
Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry
Authors: Stemmer Salomon M. , Steiner Mariana , Rizel Shulamith , Geffen David B. , Nisenbaum Bella , Peretz Tamar , Soussan-Gutman Lior , Bareket-Samish Avital , Isaacs Kevin , Rosengarten Ora , Fried Georgeta , McCullough Debbie , Svedman Christer , Shak Steven , Liebermann Nicky , Ben-Baruch Noa 
Published: September 2017

AbstractThe Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18–30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18–30, and ≥ 31 group, respectively. The 5-year Kaplan–Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2–3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18–30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1–3 positive nodes and Recurrence Score < 18.
Gated tuned superconductivity and phonon softening in monolayer and bilayer MoS2
Authors: Fu Yajun , Liu Erfu , Yuan Hongtao , Tang Peizhe , Lian Biao , Xu Gang , Zeng Junwen , Chen Zhuoyu , Wang Yaojia , Zhou Wei , Xu Kang , Gao Anyuan , Pan Chen , Wang Miao , Wang Baigeng , Zhang Shou-Cheng , Cui Yi , Hwang Harold Y. , Miao Feng 
Published: September 2017

AbstractSuperconductors at the atomic two-dimensional limit are the focus of an enduring fascination in the condensed matter community. This is because, with reduced dimensions, the effects of disorders, fluctuations, and correlations in superconductors become particularly prominent at the atomic two-dimensional limit; thus such superconductors provide opportunities to tackle tough theoretical and experimental challenges. Here, based on the observation of ultrathin two-dimensional superconductivity in monolayer and bilayer molybdenum disulfide (MoS2) with electric-double-layer gating, we found that the critical sheet carrier density required to achieve superconductivity in a monolayer MoS2 flake can be as low as 0.55 × 1014 cm−2, which is much lower than those values in the bilayer and thicker cases in previous report and also our own observations. Further comparison of the phonon dispersion obtained by ab initio calculations indicated that the phonon softening of the acoustic modes around the M point plays a key role in the gate-induced superconductivity within the Bardeen–Cooper–Schrieffer theory framework. This result might help enrich the understanding of two-dimensional superconductivity with electric-double-layer gating.
Freeform fabrication of tissue-simulating phantom for potential use of surgical planning in conjoined twins separation surgery
Authors: Shen Shuwei , Wang Haili , Xue Yue , Yuan Li , Zhou Ximing , Zhao Zuhua , Dong Erbao , Liu Bin , Liu Wendong , Cromeens Barrett , Adler Brent , Besner Gail , Xu Ronald X. 
Published: September 2017

AbstractPreoperative assessment of tissue anatomy and accurate surgical planning is crucial in conjoined twin separation surgery. We developed a new method that combines three-dimensional (3D) printing, assembling, and casting to produce anatomic models of high fidelity for surgical planning. The related anatomic features of the conjoined twins were captured by computed tomography (CT), classified as five organ groups, and reconstructed as five computer models. Among these organ groups, the skeleton was produced by fused deposition modeling (FDM) using acrylonitrile-butadiene-styrene. For the other four organ groups, shell molds were prepared by FDM and cast with silica gel to simulate soft tissues, with contrast enhancement pigments added to simulate different CT and visual contrasts. The produced models were assembled, positioned firmly within a 3D printed shell mold simulating the skin boundary, and cast with transparent silica gel. The produced phantom was subject to further CT scan in comparison with that of the patient data for fidelity evaluation. Further data analysis showed that the produced model reassembled the geometric features of the original CT data with an overall mean deviation of less than 2 mm, indicating the clinical potential to use this method for surgical planning in conjoined twin separation surgery.
Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug
Authors: Krishnan Poorani , Rajan Mariappan , Kumari Sharmilah , Sakinah S. , Priya Sivan Padma , Amira Fatin , Danjuma Lawal , Pooi Ling Mok , Fakurazi Sharida , Arulselvan Palanisamy , Higuchi Akon , Arumugam Ramitha , Alarfaj Abdullah A. , Munusamy Murugan A. , Hamat Rukman Awang , Benelli Giovanni , Murugan Kadarkarai , Kumar S. Suresh 
Published: September 2017

AbstractCamptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT’s solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.
Remarkable preservation of terpenoids and record of volatile signalling in plant-animal interactions from Miocene amber
Authors: Dutta Suryendu , Mehrotra Rakesh C. , Paul Swagata , Tiwari R. P. , Bhattacharya Sharmila , Srivastava Gaurav , Ralte V. Z. , Zoramthara C. 
Published: September 2017

AbstractPlants produce and release a large array of volatile organic compounds that play many ecological functions. These volatile plant metabolites serve as pollinator attractants, herbivore and pathogen repellents and protect plants from abiotic stresses. To date, the geological evolution of these organic compounds remains unknown. The preservation potential of these metabolites in the fossil record is very poor due to their low boiling points. Here we report a series of volatile sesquiterpenoids, including δ-elemene, α-copaene, β-elemene, β-caryophyllene, α-humulene, germacrene D, δ-cadiene and spathunenol, from early Miocene (~17 million year) amber from eastern India. The survival of these unaltered bioterpenoids can be attributed to the existence of extraordinary taphonomic conditions conducive to the preservation of volatile biomolecules through deep time. Furthermore, the occurrence of these volatiles in the early Miocene amber suggests that the plants from this period had evolved metabolic pathways to synthesize these organic molecules to play an active role in forest ecology, especially in plant-animal interactions.
Effects of Host-rock Fracturing on Elastic-deformation Source Models of Volcano Deflation
Authors: Holohan Eoghan P. , Sudhaus Henriette , Walter Thomas R. , Schöpfer Martin P. J. , Walsh John J. 
Published: September 2017

AbstractVolcanoes commonly inflate or deflate during episodes of unrest or eruption. Continuum mechanics models that assume linear elastic deformation of the Earth’s crust are routinely used to invert the observed ground motions. The source(s) of deformation in such models are generally interpreted in terms of magma bodies or pathways, and thus form a basis for hazard assessment and mitigation. Using discontinuum mechanics models, we show how host-rock fracturing (i.e. non-elastic deformation) during drainage of a magma body can progressively change the shape and depth of an elastic-deformation source. We argue that this effect explains the marked spatio-temporal changes in source model attributes inferred for the March-April 2007 eruption of Piton de la Fournaise volcano, La Reunion. We find that pronounced deflation-related host-rock fracturing can: (1) yield inclined source model geometries for a horizontal magma body; (2) cause significant upward migration of an elastic-deformation source, leading to underestimation of the true magma body depth and potentially to a misinterpretation of ascending magma; and (3) at least partly explain underestimation by elastic–deformation sources of changes in sub-surface magma volume.
Organic-Silica Interactions in Saline: Elucidating the Structural Influence of Calcium in Low-Salinity Enhanced Oil Recovery
Authors: Desmond J. L. , Juhl K. , Hassenkam T. , Stipp S. L. S. , Walsh T. R. , Rodger P. M. 
Published: September 2017

AbstractEnhanced oil recovery using low-salinity solutions to sweep sandstone reservoirs is a widely-practiced strategy. The mechanisms governing this remain unresolved. Here, we elucidate the role of Ca2+by combining chemical force microscopy (CFM) and molecular dynamics (MD) simulations. We probe the influence of electrolyte composition and concentration on the adsorption of a representative molecule, positively-charged alkylammonium, at the aqueous electrolyte/silica interface, for four electrolytes: NaCl, KCl, MgCl2, and CaCl2. CFM reveals stronger adhesion on silica in CaCl2compared with the other electrolytes, and shows a concentration-dependent adhesion not observed for the other electrolytes. Using MD simulations, we model the electrolytes at a negatively-charged amorphous silica substrate and predict the adsorption of methylammonium. Our simulations reveal four classes of surface adsorption site, where the prevalence of these sites depends only on CaCl2concentration. The sites relevant to strong adhesion feature the O−silica site and Ca2+in the presence of associated Cl−, which gain prevalence at higher CaCl2concentration. Our simulations also predict the adhesion force profile to be distinct for CaCl2compared with the other electrolytes. Together, these analyses explain our experimental data. Our findings indicate in general how silica wettability may be manipulated by electrolyte concentration.
Targeting Deficiencies in the TLR5 Mediated Vaginal Response to Treat Female Recurrent Urinary Tract Infection
Authors: Ali Ased S. M. , Mowbray Catherine , Lanz Marcelo , Stanton Anna , Bowen Samantha , Varley Claire L. , Hilton Paul , Brown Karen , Robson Wendy , Southgate Jennifer , Aldridge Phillip D. , Tyson-Capper Alison , Abraham Soman , Pickard Robert S. , Hall Judith 
Published: September 2017

AbstractThe identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NFκB pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle.
Role of interfacial mode coupling of optical phonons on thermal boundary conductance
Authors: Giri Ashutosh , Hopkins Patrick E. 
Published: September 2017

AbstractWe investigate the influence of optical phonon coupling across interfaces comprised of different materials with varying crystallographic orientations on the overall thermal boundary conductance. We show that for interfaces formed between a fcc solid and a L10 solid (where L10 solids exhibit alternating atomic layers in certain orientations), coupling between acoustic phonons in the fcc crystal and optical phonons on the L10-side of the interface leads to a highly anisotropic thermal boundary conductance, where optical phonons can considerably enhance the conductance in a preferred crystallographic orientation of the layered solid. We attribute this in part to directionally dependent group velocities of optical phonons in the different crystallographic directions. For interfaces comprised of materials exhibiting diamond cubic crystal structures, higher conductances are observed for interfaces where there is a better overlap of acoustic phonons on either side of the interface, whereas, acoustic phonons directly coupling with high frequency optical phonons is shown to lower the overall conductance, especially at high temperatures where anharmonic interactions become important. Unique to the interfaces formed between the materials with diamond cubic crystal structures studied in this work, the presence of localized interfacial optical modes mediate thermal conductance across these interfaces.
The Aging of the Social Mind - Differential Effects on Components of Social Understanding
Authors: Reiter Andrea M. F. , Kanske Philipp , Eppinger Ben , Li Shu-Chen 
Published: September 2017

AbstractResearch in younger adults dissociates cognitive from affective facets of social information processing, rather than promoting a monolithic view of social intelligence. An influential theory on adult development suggests differential effects of aging on cognitive and affective functions. However, this dissociation has not been directly tested in the social domain. Employing a newly developed naturalistic paradigm that disentangles facets of the social mind within an individual, we show multi-directionality of age-related differences. Specifically, components of the socio-cognitive route – Theory of Mind and metacognition – are impaired in older relative to younger adults. Nevertheless, these social capacities are still less affected by aging than factual reasoning and metacognition regarding non-social content. Importantly, the socio-affective route is well-functioning, with no decline in empathy and elevated compassion in the elderly. These findings contribute to an integrated theory of age-related change in social functioning and inform interventions tailored to specifically reinstate socio-cognitive skills in old age.
Complete sequence-based pathway analysis by differential on-chip DNA and RNA extraction from a single cell
Authors: van Strijp D. , Vulders R. C. M. , Larsen N. A. , Schira J. , Baerlocher L. , van Driel M. A. , Pødenphant M. , Hansen T. S. , Kristensen A. , Mir K. U. , Olesen T. , Verhaegh W. F. J. , Marie R. , van der Zaag P. J. 
Published: September 2017

AbstractWe demonstrate on-chip, differential DNA and RNA extraction from a single cell using a microfluidic chip and a two-stage lysis protocol. This method enables direct use of the whole extract, without additional washing steps, reducing sample loss. Using this method, the tumor driving pathway in individual cells from a colorectal cancer cell line was determined by applying a Bayesian computational pathway model to sequences obtained from the RNA fraction of a single cell and, the mutations driving the pathway were determined by analyzing sequences obtained from the DNA fraction of the same single cell. This combined functional and mutational pathway assessment of a single cell could be of significant value for dissecting cellular heterogeneity in tumors and analyzing single circulating tumor cells.
The association of young age with local recurrence in women with early-stage breast cancer after breast-conserving therapy: a meta-analysis
Authors: He Xiang-Ming , Zou De-Hong 
Published: September 2017

AbstractThe aim of this meta-analysis is to determine the relationship between young age and local recurrence in patients with early-stage breast cancer after breast-conserving therapy. Eligible studies were retrieved from various electronic databases. Among the 19 studies included, 14 studies were analyzed for 5-year local recurrence rate and 8 studies for 10-year local recurrence rate using random effects models. Both results showed that young patients were at higher risk of local recurrence compared to old patients (5-year: RR = 2.64, 95% CI (1.94–3.60); 10-year: RR = 2.37, 95% CI (1.57–3.58)). Harbord’s modified test showed the presence of publication bias in both 5- and 10-year local recurrence rates (P = 0.019 and P = 0.01, respectively). While the Trim and Fill analysis showed that the presence of publication bias did not affect the overall outcome of the 5-year local recurrence rate (RR = 2.21, 95% CI (1.62, 3.02)), it significantly affected the effect size of the 10-year local recurrence rate (RR = 1.47, 95% CI (0.96, 2.27)). Young age is a significant risk factor for local recurrence developed within 5 years of breast-conserving therapy in patients with early-stage breast cancer. Further high-quality studies are needed to elucidate the relationship between young age and the risk of local recurrence developed within 10 years.