bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of ENMD-2076 in advanced soft tissue sarcoma (STS)
Authors: Veitch Zachary , Zer Alona , Loong Herbert , Salah Samer , Masood Maryam , Gupta Abha , Bradbury Penelope A. , Hogg David , Wong Andrew , Kandel Rita , Charames George S. , Abdul Razak Albiruni R. 
Published: May 2019

AbstractENMD-2076, an aurora-A kinase inhibitor with anti-angiogenic properties, has shown activity in solid and hematologic malignancies. We investigated oral ENMD-2076 in an open-label, single-arm phase II study using 275 mg daily on a 28-day cycle in patients with advanced soft-tissue sarcomas (STS) receiving ≤1 line of prior therapy. Primary endpoint was 6-month progression-free survival (PFS) with ≤15% indicating no interest, and ≥40% indicating further interest in ENMD-2076. Secondary/exploratory endpoints included clinical benefit (CBR ≥6-months) and objective response (ORR) rates, PFS, OS, safety, and whole-exome sequencing (WES) for potentially associated biomarkers. Overall, 23/25 (92%) patients receiving ENMD-2076 were efficacy evaluable with median follow-up of 14 months (range 2.2–39.5). Common subtypes were leiomyosarcoma (n = 10), undifferentiated pleomorphic sarcoma (n = 3), angiosarcoma (n = 3), and alveolar soft-part sarcoma (n = 3). The 6-month PFS was 20.8% (95% CI:3.2–38.4) with a CBR of 17% (95% CI:1.55–33.23) and ORR of 9% (95% CI:3.08–20.46). Median PFS was 2.5 months (95% CI:2.20–4.47) and OS was 14.1 months (95% CI:6.07–20.07). The most common high-grade treatment-related adverse event was hypertension (60%). WES identified PTPRB mutations in 3/4 patients (p = 0.018) benefiting from ENMD-2076. Although this study failed to meet its primary endpoint, occasional responses and prolonged stable disease was noted. ENMD-2076 evaluation in PTPRB mutated tumors and/or angiosarcoma is warranted.
Parasympathetic activity correlates with subjective and brain responses to rectal distension in healthy subjects but not in non-constipated patients with irritable bowel syndrome
Authors: Kano Michiko , Yoshizawa Makoto , Kono Keiji , Muratsubaki Tomohiko , Morishita Joe , Van Oudenhove Lukas , Yagihashi Mao , Mugikura Shunji , Dupont Patrick , Takase Kei , Kanazawa Motoyori , Fukudo Shin 
Published: May 2019

AbstractThe nociceptive and autonomic nervous systems (ANS) are significantly intertwined. Decoupling of these systems may occur in pathological pain conditions, including irritable bowel syndrome (IBS). We investigated ANS activity and its association with visceral perception and brain activity during rectal distention in 27 patients with non-constipated IBS and 33 controls by assessing heart rate variability (HRV) using electrocardiography at rest, before, and during colorectal distention. Brain responses to colorectal distention were measured using functional magnetic resonance imaging and correlated with individual ANS function parameters. The IBS group displayed blunted sympathovagal balance [low/high-frequency ratio (LF:HF) of HRV] in response to colorectal distention compared with controls (P = 0.003). In controls, basal parasympathetic tone (HF component of HRV) was significantly negatively correlated with toleration threshold to the rectal distention, but not in patients with IBS (group comparison P = 0.04). Further, a positive correlation between baseline HF values and neural responses to rectal distension was found in the right caudate, bilateral dorsolateral anterior cingulate cortex, and pregenual anterior cingulate cortex in the control group but not in the IBS group. The results indicate abnormal interactions between ANS activity and the brain mechanisms underlying visceral perception in patients with IBS.
Early maturing Bt cotton requires more potassium fertilizer under water deficiency to augment seed-cotton yield but not lint quality
Authors: Shahzad Ahmad Naeem , Rizwan Muhammad , Asghar Malik Ghulam , Qureshi Muhammad Kamran , Bukhari Syed Asad Hussain , Kiran Aysha , Wakeel Abdul 
Published: May 2019

AbstractExhaustive crops such as cotton require potassium (K) in copious amounts as compared to other crops. High yielding cultivars in cotton-wheat cropping system, have further increased its demand in cotton growing areas of Pakistan. As cotton is grown in arid and semiarid areas, therefore often prone to water deficiency. The reproductive growth particularly flowering and boll setting are highly sensitive to low soil water potentials, where enough K supply can play a vital role. In this two-year field studies, three cultivars (early, mid and late maturing) were cultivated at two K fertilizer levels 100, 200 kg K ha−1 along with control with no K fertilizer application at two irrigation levels. In first irrigation level, water was applied as per full irrigation schedule, while in water deficit irrigation water was applied at deficit irrigation schedule started after flowering till harvesting. It has been revealed that K application has impact on boll setting as well as seed cotton yield, however early and mid-maturing cultivars are more responsive to K fertilization. Furthermore, irrigation level had significant impact against K fertilization and relatively better response was observed in deficit irrigation as compared to full irrigation. Nevertheless, fiber quality parameters were unaffected by K fertilization. Considering the best benefit cost ratio under water deficiency, it is concluded that 100 kg K2O ha−1 should be applied at the time of seed bed preparation for economical seed-cotton yield of early maturing Bt cotton.
Calcium phosphate mineralization in bone tissues directly observed in aqueous liquid by atmospheric SEM (ASEM) without staining: microfluidics crystallization chamber and immuno-EM
Authors: Sato Chikara , Yamazaki Daiju , Sato Mari , Takeshima Hiroshi , Memtily Nassirhadjy , Hatano Yuri , Tsukuba Takayuki , Sakai Eiko 
Published: May 2019

AbstractThe malformation and disordered remodeling of bones induce various diseases, including osteoporosis. We have developed atmospheric SEM (ASEM) to directly observe aldehyde-fixed bone tissue immersed in radical scavenger buffer without thin sectioning. The short procedure realized the observation of bone mineralization surrounded by many cells and matrices in natural aqueous buffer, decreasing the risk of changes. In osteoblast primary cultures, mineralization was visible without staining. Correlative energy dispersive X-ray spectrometry indicated the formation of calcium phosphate mineral. Fixed bone was sectioned, and the section surface was inspected by ASEM. Mineralized trabeculae of talus spongy bone were directly visible. Associated large and small cells were revealed by phosphotungstic acid staining, suggesting remodeling by bone-absorbing osteoclasts and bone-rebuilding osteoblasts. In tibia, cortical bone layer including dense grains, was bordered by many cells with protrusions. Tissue immuno-EM performed in solution for the first time and anti-cathepsin-K antibody, successfully identified osteoclasts in femur spongy bone. A microfluidics chamber fabricated on the silicon nitride film window of an ASEM dish allowed mineralization to be monitored in vitro; calcium phosphate crystals as small as 50 nm were imaged. ASEM is expected to be widely applied to study bio-mineralization and bone-remodeling, and to help diagnose bone-related diseases.
Tumour-treating fields (TTFields): Investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis
Authors: Berkelmann Lukas , Bader Almke , Meshksar Saba , Dierks Anne , Hatipoglu Majernik Gökce , Krauss Joachim K. , Schwabe Kerstin , Manteuffel Dirk , Ngezahayo Anaclet 
Published: May 2019

AbstractTumour-treating fields (TTFields) use alternating electric fields which interfere with dividing cells, thereby reducing tumour growth. Previous reports suggest that electrical forces on cell structure proteins interfered with the chromosome separation during mitosis and induced apoptosis. In the present report we evaluate electromagnetic exposure of cells in telophase/cytokinesis in order to further analyse the mechanism of action on cells. We performed numerical electromagnetic simulations to analyse the field distribution in a cell during different mitotic phases. Based thereon, we developed an electric lumped element model of the mitotic cell. Both the electromagnetic simulation and the lumped element model predict a local increase of the specific absorption rate (SAR) as a measure of the electromagnetically induced power absorption density at the mitotic furrow which may help to explain the anti-proliferative effect. In accordance with other reports, cell culture experiments confirmed that TTFields reduce the proliferation of different glioma cell lines in a field strength- and frequency-dependent manner. Furthermore, we found an additional dependence on the commutation time of the electrical fields. The report gives new insights into TTFields’ anti-proliferative effect on tumours, which could help to improve future TTFields application systems.
High-Performance Copper Oxide Visible-Light Photodetector via Grain-Structure Model
Authors: Song Hyeon-Joo , Seo Min-Ho , Choi Kwang-Wook , Jo Min-Seung , Yoo Jae-Young , Yoon Jun-Bo 
Published: May 2019

AbstractRecently, copper oxide (CuO)-based visible-light photodetectors have attracted great interest due to their narrow bandgap (1.2 eV), low cost, and ease of fabrication. However, there has been insufficient theoretical analysis and study of CuO-based photodetectors, resulting in inferior performance in terms of responsivity, detectivity, and response speed. This work develops a method to enhance the performance of CuO photodetectors by engineering a grain structure based on a newly-developed theoretical model. In the developed theoretical grain-structure model, the grain size and the connections between grains are considered because they can strongly affect the optoelectronic characteristics of CuO photodetectors. Based upon the proposed model, the engineered CuO device achieves enhanced optoelectronic performance. The engineered device shows high responsivity of 15.3 A/W and detectivity of 1.08 × 1011 Jones, which are 18 and 50 times better than those of the unoptimized device, and also shows fast rising and decaying response speeds of 0.682 s and 1.77 s, respectively. In addition, the proposed method is suitable for the mass-production of performance-enhanced, reliable photodetectors. By using a conventional semiconductor fabrication process, a photodetector-array is demonstrated on a 4-inch wafer. The fabricated devices show uniform, high, and stable optoelectronic performance for a month.
Quantified forces between HepG2 hepatocarcinoma and WA07 pluripotent stem cells with natural biomaterials correlate with in vitro cell behavior
Authors: Harjumäki Riina , Nugroho Robertus Wahyu N. , Zhang Xue , Lou Yan-Ru , Yliperttula Marjo , Valle-Delgado Juan José , Österberg Monika 
Published: May 2019

AbstractIn vitro cell culture or tissue models that mimic in vivo cellular response have potential in tissue engineering and regenerative medicine, and are a more economical and accurate option for drug toxicity tests than animal experimentation. The design of in vivo-like cell culture models should take into account how the cells interact with the surrounding materials and how these interactions affect the cell behavior. Cell-material interactions are furthermore important in cancer metastasis and tumor progression, so deeper understanding of them can support the development of new cancer treatments. Herein, the colloidal probe microscopy technique was used to quantify the interactions of two cell lines (human pluripotent stem cell line WA07 and human hepatocellular carcinoma cell line HepG2) with natural, xeno-free biomaterials of different chemistry, morphology, and origin. Key components of extracellular matrices –human collagens I and IV, and human recombinant laminin-521−, as well as wood-derived, cellulose nanofibrils –with evidenced potential for 3D cell culture and tissue engineering– were analysed. Both strength of adhesion and force curve profiles depended on biomaterial nature and cell characteristics. The successful growth of the cells on a particular biomaterial required cell-biomaterial adhesion energies above 0.23 nJ/m. The information obtained in this work supports the development of new materials or hybrid scaffolds with tuned cell adhesion properties for tissue engineering, and provides a better understanding of the interactions of normal and cancerous cells with biomaterials in the human body.
Proof of principle study of a detailed whole-body image analysis technique, “Imiomics”, regarding adipose and lean tissue distribution
Authors: Lind Lars , Kullberg Joel , Ahlström Håkan , Michaëlsson Karl , Strand Robin 
Published: May 2019

AbstractThis “proof-of-principle” study evaluates if the recently presented “Imiomics” technique could visualize how fat and lean tissue mass are associated with local tissue volume and fat content at high/unprecedented resolution. A whole-body quantitative water-fat MRI scan was performed in 159 men and 167 women aged 50 in the population-based POEM study. Total fat and lean mass were measured by DXA. Fat content was measured by the water-fat MRI. Fat mass and distribution measures were associated to the detailed differences in tissue volume and fat concentration throughout the body using Imiomics. Fat mass was positively correlated (r > 0.50, p < 0.05) with tissue volume in all subcutaneous areas of the body, as well as volumes of the liver, intraperitoneal fat, retroperitoneal fat and perirenal fat, but negatively to lung volume. Fat mass correlated positively with volumes of paravertebral muscles, and muscles in the ventral part of the thigh and lower limb. Fat mass was distinctly correlated with the fat content in subcutaneous adipose tissue at the trunk. Lean mass was positively related to the large skeletal muscles and the skeleton. The present study indicates the Imiomics technique to be suitable for studies of fat and lean tissue distribution, and feasible for large scale studies.
A comparison of coffee floral traits under two different agricultural practices
Authors: Prado Sara Guiti , Collazo Jaime A. , Stevenson Philip C. , Irwin Rebecca E. 
Published: May 2019

AbstractFloral traits and rewards are important in mediating interactions between plants and pollinators. Agricultural management practices can affect abiotic factors known to influence floral traits; however, our understanding of the links between agricultural practices and floral trait expression is still poorly understood. Variation in floral morphological, nectar, and pollen traits of two important agricultural species, Coffea arabica and C. canephora, was assessed under different agricultural practices (sun and shade). Corolla diameter and corolla tube length were larger and pollen total nitrogen content greater in shade plantations of C. canephora than sun plantations. Corolla tube length and anther filament length were larger in shade plantations of C. arabica. No effect of agricultural practice was found on nectar volume, sugar or caffeine concentrations, or pollen production. Pollen total nitrogen content was lower in sun than shade plantations of C. canephora, but no difference was found between sun and shade for C. arabica. This study provides baseline data on the influence of agronomic practices on C. arabica and C. canephora floral traits and also helps fill a gap in knowledge about the effects of shade trees on floral traits, which can be pertinent to other agroforestry systems.
TET1 contributes to allergic airway inflammation and regulates interferon and aryl hydrocarbon receptor signaling pathways in bronchial epithelial cells
Authors: Burleson J. D. , Siniard Dylan , Yadagiri Veda K. , Chen Xiaoting , Weirauch Matthew T. , Ruff Brandy P. , Brandt Eric B. , Hershey Gurjit K. Khurana , Ji Hong 
Published: May 2019

AbstractPrevious studies have suggested a role for Tet1 in the pathogenesis of childhood asthma. However, how Tet1 contributes to asthma remains unknown. Here we used mice deficient for Tet1 in a well-established model of allergic airway inflammation and demonstrated that loss of Tet1 increased disease severity including airway hyperresponsiveness and lung eosinophilia. Increased expression of Muc5ac, Il13, Il33, Il17a, Egfr, and Tff2 were observed in HDM-challenged Tet1-deficient mice compared to Tet1+/+ littermates. Further, transcriptomic analysis of lung RNA followed by pathway and protein network analysis showed that the IFN signaling pathway was significantly upregulated and the aryl hydrocarbon receptor (AhR) pathway was significantly downregulated in HDM-challenged Tet1−/− mice. This transcriptional regulation of the IFN and AhR pathways by Tet1 was also present in human bronchial epithelial cells at base line and following HDM challenges. Genes in these pathways were further associated with changes in DNA methylation, predicted binding of transcriptional factors with relevant functions in their promoters, and the presence of histone marks generated by histone enzymes that are known to interact with Tet1. Collectively, our data suggest that Tet1 inhibits HDM-induced allergic airway inflammation by direct regulation of the IFN and AhR pathways.
Rapid environmental change in games: complications and counter-intuitive outcomes
Authors: Trimmer Pete C. , Barrett Brendan J. , McElreath Richard , Sih Andrew 
Published: May 2019

AbstractHuman-induced rapid environmental change (HIREC) has recently led to alterations in the fitness and behavior of many organisms. Game theory is an important tool of behavioral ecology for analyzing evolutionary situations involving multiple individuals. However, game theory bypasses the details by which behavioral phenotypes are determined, taking the functional perspective straight from expected payoffs to predicted frequencies of behaviors. In contrast with optimization approaches, we identify that to use existing game theoretic models to predict HIREC effects, additional mechanistic details (or assumptions) will often be required. We illustrate this in relation to the hawk-dove game by showing that three different mechanisms, each of which support the same ESS prior to HIREC (fixed polymorphism, probabilistic choice, or cue dependency), can have a substantial effect on behavior (and success) following HIREC. Surprisingly, an increase in the value of resources can lead to a reduction in payoffs (and vice versa), both in the immediate- and long-term following HIREC. An increase in expected costs also increases expected payoffs. Along with these counter-intuitive findings, this work shows that simply understanding the behavioral payoffs of existing games is insufficient to make predictions about the effects of HIREC.
Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast
Authors: Yukawa Masashi , Okazaki Masaki , Teratani Yasuhiro , Furuta Ken’ya , Toda Takashi 
Published: May 2019

AbstractBipolar mitotic spindles play a critical part in accurate chromosome segregation. During late mitosis, spindle microtubules undergo drastic elongation in a process called anaphase B. Two kinesin motors, Kinesin-5 and Kinesin-6, are thought to generate outward forces to drive spindle elongation, and the microtubule crosslinker Ase1/PRC1 maintains structural integrity of antiparallel microtubules. However, how these three proteins orchestrate this process remains unknown. Here we explore the functional interplay among fission yeast Kinesin-5/Cut7, Kinesin-6/Klp9 and Ase1. Using total internal reflection fluorescence microscopy, we show that Klp9 forms homotetramers and that Klp9 is a processive plus end-directed motor. klp9Δase1Δ is synthetically lethal. Surprisingly, this lethality is not ascribable to the defective motor activity of Klp9; instead, it is dependent upon a nuclear localisation signal and coiled coil domains within the non-motor region. We isolated a cut7 mutant (cut7-122) that displays temperature sensitivity only in the absence of Klp9. Interestingly, cut7-122 alone is impaired in spindle elongation during anaphase B, and furthermore, cut7-122klp9Δ double mutants exhibit additive defects. We propose that Klp9 plays dual roles during anaphase B; one is motor-dependent that collaborates with Cut7 in force generation, while the other is motor-independent that ensures structural integrity of spindle microtubules together with Ase1.
A self-assembled plasmonic optical fiber nanoprobe for label-free biosensing
Authors: Liang Yuzhang , Yu Zhiyong , Li Lixia , Xu Ting 
Published: May 2019

AbstractThe plasmonic optical fiber sensors have attracted wide attention for label-free biosensing application because of their high integration, small footprint and point-of-care measurement. However, the integration of plasmonic nanostructures on optical fiber probes always relies on the top-down nanofabrication approaches, which have several inherent shortcomings, including high cost, time-consuming, and low yields. Here, we develop a plasmonic nanohole-patterned multimode optical fiber probe by self-assembly nanosphere lithography technique with low fabrication cost and high yields. The multimode optical fiber possesses large facet area and high numerical aperture, which not only simplifies fabrication process, but also increases coupling efficiency of incident light. Originating from the resonant coupling of plasmonic modes, the plasmonic fiber nanoprobe has a distinct reflection dip in the spectrum and exhibits strong near-field electromagnetic enhancement. We experimentally investigate the sensing performances of plasmonic fiber nanoprobe, and further demonstrate it in real-time monitoring specific binding of protein molecules. The experimental results imply that the nanohole-patterned multimode optical fiber probe is a good candidate for developing miniaturized and portable biosensing systems.
Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study
Authors: Enomoto Noriyuki , Egashira Ryoko , Tabata Kazuhiro , Hashisako Mikiko , Kitani Masashi , Waseda Yuko , Ishizuka Tamotsu , Watanabe Satoshi , Kasahara Kazuo , Izumi Shinyu , Shiraki Akira , Miyamoto Atsushi , Kishi Kazuma , Kishaba Tomoo , Sugimoto Chikatosi , Inoue Yoshikazu , Kataoka Kensuke , Kondoh Yasuhiro , Tsuchiya Yutaka , Baba Tomohisa , Sugiura Hiroaki , Tanaka Tomonori , Sumikawa Hiromitsu , Suda Takafumi 
Published: May 2019

AbstractThoracic diseases in patients with systemic lupus erythematosus (SLE), especially interstitial pneumonia (SLE-IP), are rare and have been poorly studied. The aims of this multicentre study were to evaluate SLE-IP and elucidate its clinical characteristics and prognosis. Fifty-five patients with SLE-IP who had attended the respiratory departments of participating hospitals were retrospectively evaluated in this multicentre study. Clinical information, high-resolution computed tomography (HRCT), and surgical lung biopsy/autopsy specimens were analysed by respiratory physicians, pulmonary radiologists, and pulmonary pathologists. IP patterns on HRCT and lung specimens were classified based on the international classification statement/guideline for idiopathic interstitial pneumonias. The most frequent form of SLE-IP at diagnosis was chronic IP (63.6%), followed by subacute (20.0%), and acute IP (12.7%). Radiologically, the most common HRCT pattern was “Unclassifiable” (54%). Histologically, “Unclassifiable” was the most frequently found (41.7%) among 12 patients with histologically proven IP. Interestingly, accompanying airway diseases were present in nine of these patients (75%). In multivariate analysis, current smoking (hazard ratio [HR] 6.105, p = 0.027), thrombocytopenia (HR 7.676, p = 0.010), anti-double-strand DNA titre (HR 0.956, p = 0.027), and nonspecific interstitial pneumonia (NSIP) + organizing pneumonia (OP) pattern on HRCT (vs. NSIP, HR 0.089, p = 0.023) were significant prognostic factors. In conclusion, chronic IP was the most frequent form of IP in patients with SLE-IP, and “Unclassifiable” was the commonest pattern radiologically and histologically.