bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK/Erk signaling inhibition
Authors: Yang Li , Shen MingJing , Xu Li Jun , Yang Xiaodong , Tsai Ying , Keng Peter C. , Chen Yuhchyau , Lee Soo Ok 
Published: August 2017

AbstractMajor progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell’s function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells.
miR-12 and miR-124 contribute to defined early phases of long-lasting and transient memory
Authors: Michely Julia , Kraft Susanne , Müller Uli 
Published: August 2017

AbstractMicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in long-lasting synaptic plasticity and long-term memory (LTM). Since recent findings demonstrated a role of epigenetic regulation of gene expression in early memory phases we investigated whether epigenetic regulation by miRNAs also contributes to early memory phases. We used the olfactory associative learning paradigm in honeybees and addressed the contribution of miRNAs depending on the conditioning strength. We selected miR-12, miR-124, and miR-125 that have been implicated in processes of neuronal plasticity and analysed their contribution to non-associative and associative learning using miRNA inhibitors. Blocking miR-12, miR-124, or miR125 neither affects gustatory sensitivity nor habituation nor sensitization. Blocking the function of miR-12 and miR-124 during and shortly after 3-trial conditioning impairs different early memory phases. Although different, the function of miR-12 and miR-124 is also required for early phases of transient memory that is induced by 1-trial conditioning. Blocking miR-125 has no effect on early memory independent of the conditioning strength. These findings demonstrate that distinct miRNAs contribute to early phases of both, transient memories as well as long-lasting memories.
Inputs of humic fluorescent dissolved organic matter via submarine groundwater discharge to coastal waters off a volcanic island (Jeju, Korea)
Authors: Kim Jeonghyun , Kim Guebuem 
Published: August 2017

AbstractThe abundance of fluorescent dissolved organic matter (FDOM) in the surface ocean plays a critical role in the growth of marine microorganisms and corals by affecting the optical properties (i.e., the penetration of UV radiation) of seawater. In general, it is known that rivers are the main source of FDOM to surface ocean waters. Here, however, we show that the concentrations of FDOM in coastal seawater off a volcanic island, Jeju, Korea, are dependent primarily on submarine groundwater discharge (SGD). Based on a significant correlation between 222Rn and salinity in seawater, fresh groundwater was found to be the main source of groundwater as well as fresh water in the bay. The addition of dissolved organic carbon (DOC) and protein-like FDOM to the bay via SGD was generally negligible or negative. However, SGD enhanced the inventory of humic-like FDOM (FDOMH) in seawater by 2–3 times over all seasons, with conservative behavior of FDOMH in bay seawater. These results suggest that SGD-driven fluxes of FDOM regulate its inventory in seawater and consequently play a significant role in determining the optical properties of coastal waters off islands and associated coastal ecosystems (i.e., corals).
Atomic Force Microscopy Reveals the Dynamic Morphology of Fenestrations in Live Liver Sinusoidal Endothelial Cells
Authors: Zapotoczny B. , Szafranska K. , Owczarczyk K. , Kus E. , Chlopicki S. , Szymonski M. 
Published: August 2017

AbstractHere, we report an atomic force microscopy (AFM)-based imaging method for resolving the fine nanostructures (e.g., fenestrations) in the membranes of live primary murine liver sinusoidal endothelial cells (LSECs). From data on topographical and nanomechanical properties of the selected cell areas collected within 1 min, we traced the dynamic rearrangement of the cell actin cytoskeleton connected with the formation or closing of cell fenestrations, both in non-stimulated LSECs as well as in response to cytochalasin B and antimycin A. In conclusion, AFM-based imaging permitted the near real-time measurements of dynamic changes in fenestrations in live LSECs.
Effects of disulfide bridges and backbone connectivity on water sorption by protein matrices
Authors: Kim Sang Beom , Singh Rakesh S. , Paul Prem K. C. , Debenedetti Pablo G. 
Published: August 2017

AbstractUnderstanding the water sorption behavior of protein powders is important in applications such as the preservation of protein-based pharmaceuticals. Most globular proteins exhibit a characteristic sigmoidal water adsorption isotherm at ambient conditions. However, it is not well understood how water sorption behavior is influenced by intrinsic factors that are related to structural properties of proteins. We investigate computationally how structural constraints on proteins influence the water sorption isotherms of amorphous protein powders. Specifically, we study the effects of non-local disulfide linkages and backbone connectivity using pheromone ER-23 and lysozyme as model proteins. We find that non-local disulfide linkages can significantly restrict structural changes during hydration and dehydration, and this in turn greatly reduces the extent of hysteresis between the adsorption and desorption branches. Upon removing the backbone connectivity by breaking all peptide bonds in lysozyme, we find that the hysteresis shifts towards the lower humidity regime, and the water uptake capacity is significantly enhanced. We attribute these changes to the higher aggregation propensity of the constraint-free amino acids in dehydrated condition, and the formation of a spanning water network at high hydration levels.
Ultra-fast Hygrometer based on U-shaped Optical Microfiber with Nanoporous Polyelectrolyte Coating
Authors: Chen George Y. , Wu Xuan , Kang Yvonne Qiongyue , Yu Li , Monro Tanya M. , Lancaster David G. , Liu Xiaokong , Xu Haolan 
Published: August 2017

AbstractReal-time measurement of the relative humidity of air has applications ranging from process control to safety. By using a microfiber form-factor, we demonstrate a miniature and fast-response hygrometer with the shortest-ever response time (3 ms). The sensor head consists of an optical microfiber of 10 µm diameter and 2 mm length configured to form a compact U-shaped probe, and functionalized with a polyelectrolyte multilayer coating of 1.0 bilayer. The sensing mechanism is primarily water-absorption-based optical loss. We have measured a response time of 3 ms and a recovery time of 36 ms. The sensitivity is as high as 0.4%/%RH, and the detection limit is as low as 1.6%RH. The maximum relative humidity is 99%RH, before reaching a recoverable dew-point.
Spray-cast multilayer perovskite solar cells with an active-area of 1.5 cm2
Authors: Bishop James E. , Mohamad David K. , Wong-Stringer Michael , Smith Alex , Lidzey David G. 
Published: August 2017

AbstractWe utilise spray-coating under ambient conditions to sequentially deposit compact-TiO2, mesoporous-TiO2, CH3NH3PbI(3−x)Clx perovskite and doped spiro-OMeTAD layers, creating a mesoporous standard architecture perovskite solar cell (PSC). The devices created had an average power conversion efficiency (PCE) of 9.2% and a peak PCE of 10.2%; values that compare favourably with control-devices fabricated by spin-casting that had an average efficiency of 11.4%. We show that our process can be used to create devices having an active-area of 1.5 cm2 having an independently verified efficiency of 6.6%. This work demonstrates the versatility of spray-coating as well as its potential as a method of manufacturing low-cost, large-area, efficient perovskite devices.
Hyaluronic acid coatings as a simple and efficient approach to improve MSC homing toward the site of inflammation
Authors: Corradetti Bruna , Taraballi Francesca , Martinez Jonathan O. , Minardi Silvia , Basu Nupur , Bauza Guillermo , Evangelopoulos Michael , Powell Sebastian , Corbo Claudia , Tasciotti Ennio 
Published: August 2017

AbstractA major challenge in regenerative medicine is to improve therapeutic cells’ delivery and targeting using an efficient and simple protocol. Mesenchymal stem cells (MSC) are currently employed for the treatment of inflammatory-based diseases, due to their powerful immunosoppressive potential. Here we report a simple and versatile method to transiently overexpress the hyaluronic acid (HA) receptor, CD44, on MSC membranes, to improve their homing potential towards an inflammatory site without affecting their behavior. The effect of HA-coatings on murine MSC was functionally determined both, in vitro and in vivo as a consequence of the transient CD44 overexpression induced by HA. Data obtained from the in vitro migration assay demonstrated a two-fold increase in the migratory potential of HA-treated MSC compared to untreated cells. In an LPS-induced inflamed ear murine model, HA-treated MSC demonstrated a significantly higher inflammatory targeting as observed at 72 hrs as compared to untreated cells. This increased accumulation for HA-treated MSC yielded a substantial reduction in inflammation as demonstrated by the decrease in the expression of pro-inflammatory markers and by the induction of a pro-regenerative environment.
CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport
Authors: Tomoishi Shotaro , Fukushima Shinichi , Shinohara Kentaro , Katada Toshiaki , Saito Kota 
Published: August 2017

AbstractHepatic fibrosis is caused by exaggerated wound healing response to chronic injury, which eventually leads to hepatic cirrhosis. Differentiation of hepatic stellate cells (HSCs) to myofibroblast-like cells by inflammatory cytokines is the critical step in fibrosis. This step is accompanied by enlargement of the endoplasmic reticulum (ER) and Golgi apparatus, suggesting that protein synthesis and secretion are augmented in the activated HSCs. However, the process of rearrangement of secretory organelles and their functions remain to be fully elucidated. Here, we revealed that differentiation alters early secretory gene expression. We observed significant isoform-specific upregulation of the inner coat protein complex II (COPII) components, Sec23A and Sec24D, via the transmembrane bZIP transcription factor, CREB3L2/BBF2H7, during HSC activation. Moreover, knockdown of these components abrogated the activation, suggesting that Sec23A/Sec24D-mediated ER to Golgi trafficking is required for HSC activation.
Assessment of Three New Loci from Genome-wide Association Study in Essential Tremor in Chinese population
Authors: Zhang Yuan , Zhao Yuwen , Zhou Xiaoting , Li Kai , Yi Minhan , Guo Jifeng , Yan Xinxiang , Tang Beisha , Sun Qiying 
Published: August 2017

AbstractEssential tremor (ET) is the most common tremor disorder. Evidences indicated that genetics plays an essential role in the researches of etiology. A new genome-wide association study (GWAS) from European population identified three novel loci in ET, which were rs10937625 in STK32B, rs17590046 in PPARGC1A, and rs12764057, rs10822974 and rs7903491 in CTNNA3. Due to the different genetic background in different population, we performed a case-control study to investigate these variants in a cohort of 533 subjects in Chinese population. We found a significant difference in the distributions of genotypes and alleles frequencies between ET and control groups of rs10937625 (genotype p = 0.037, OR = 0.69[0.48–0.98]; allele p = 0.033, OR = 0.82[0.69–0.99]) and rs7903491 (genotype p = 0.030, OR = 1.34[1.03–1.74]; allele p = 0.029, OR = 1.16[1.02–1.32]) after adjusted for age and gender. And no associations were detected between rs17590046 (genotype p = 0.794; allele p = 0.791), rs12764057 (genotype p = 0.337; allele p = 0.337), rs10822974 (genotype p = 0.102; allele p = 0.100) and ET in Chinese population individually. Our research supports that C allele of rs10937625 in STK32B is a protective factor and G allele of rs7903491 in CTNNA3 is a risk factor for ET in Chinese population.
Clinical Characteristics in a Sample of Transsexual People
Authors: Lerri Maria Rita , Romão Adriana Peterson Mariano Salata , Santos Manoel Antônio dos , Giami Alain , Ferriani Rui Alberto , Lara Lúcia Alves da Silva 
Published: August 2017

Purpose To assess the clinical characteristics of subjects with gender dysphoria (GD).
Method A cross-sectional study of adults with GD. Symptoms of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Sociodemographic data, clinical data and life habits were recorded.
Results Total of 44 subjects participated in the study: 36 (82%) trans women and 8 (18%) trans men. Forty-three (98%) of the GD patients had anxiety (36 [100%] trans women and 7 [87.5%] trans men), and 36 (82%) had depression (29 [80.5%] trans women and 7 [87.5%] trans men). Suicide had been attempted by 32 (73%) subjects. The rates of depression were lower among the subjects living with partners, parents, or other people than among those living alone (p = 0.03), and it was also lower among the subjects who were married compared to those who were dating or single (p = 0.03).
Conclusion Improving the relationship status may reduce the prevalence of depressive symptoms in GD patients. There was a high rate of attempted suicide in this sample.
Ocular Changes During Pregnancy
Authors: Marcos-Figueiredo Pedro , Marcos-Figueiredo Ana , Menéres Pedro , Braga Jorge 
Published: August 2017

AbstractPregnancy is needed for the perpetuation of the human species, and it leads to physiological adaptations of the various maternal organs and systems. The eye, although a closed space, also undergoes some modifications, most of which are relatively innocuous, but they may occasionally become pathological. For women, pregnancy is a susceptibility period; however, for many obstetricians, their knowledge of the ocular changes that occur during pregnancy tends to be limited. For this reason, this is a important area of study as is necessary the development of guidelines to approach those changes. Of equal importance are the knowledge of the possible therapies for ophthalmological problems in this period and the evaluation of the mode of delivery in particular conditions. For this article, an extensive review of the literature was performed, and a summary of the findings is presented.
Hearing Disorders in Congenital Toxoplasmosis: A Literature Review
Authors: Corrêa Camila , Maximino Luciana , Weber Silke 
Published: August 2017

Introduction Several studies show correlations between congenital toxoplasmosis and hearing loss, with a broad diversity of levels of hearing loss and specifications of hearing disorders.
Objective To describe the studies found in the literature regarding hearing disorders in congenital toxoplasmosis.
Data Synthesis A literature review was conducted on the Lilacs, SciELO, PubMed and Scopus databases by combining the following keywords: congenital toxoplasmosis and hearing. Based on this search strategy, 152 papers were found, the majority published on the Scopus and PubMed databases from 1958 to 2015. After the application of the inclusion criteria, 8 articles published between 1980 and 2015 were included in the present study.
Conclusion This review showed a moderate evidence of the association between hearing disorders and congenital toxoplasmosis, which is characterized by sensorineural hearing loss. However, there are gaps in the description of the specific characteristics of the type and level of hearing loss, or of other possible disorders involved in the auditory processing.
Immuntherapie von Hirntumoren
Authors: Roth Patrick , Weller Michael 
Published: August 2017

ZusammenfassungImmuntherapeutische Behandlungsansätze bei Hirntumoren werden schon seit Jahrzehnten als potenziell hilfreich und attraktiv angesehen. Im Gegensatz zum erheblich gestiegenen Verständnis der immunologischen Grundlagen von Tumoren im Gehirn waren die klinischen Fortschritte jedoch lange Zeit vergleichsweise bescheiden. Diese Situation hat sich in den letzten Jahren grundlegend geändert, u. a. durch die Entwicklung neuartiger Vakzinierungskonzepte. Impfstoffe, die aus einem oder mehreren Peptiden bestehen, befinden sich in einem fortgeschrittenen Stadium der klinischen Entwicklung zur Behandlung von Gliomen. Im Rahmen individualisierter Konzepte wird zudem versucht, Vakzinen herzustellen, deren Zusammensetzung auf einer umfangreichen Analyse des Tumorgewebes basiert und somit tumor- bzw. patientenspezifisch ist. Parallel wird derzeit in der Neuroonkologie die Wirksamkeit von Immun-Checkpoint-Inhibitoren untersucht. Diese Medikamente interagieren mit Immunzellrezeptoren, z. B. CTLA-4 oder PD-1, bzw. den dazugehörigen Liganden und sorgen für stärkere und anhaltende Immunantworten, u. a. auch gegen Tumorzellen. Mittlerweile sind immer mehr Daten verfügbar, die nahelegen, dass diese Immuntherapeutika bei Hirnmetastasen wirksam sein können. Unklar ist aber noch, ob auch Patienten mit primären Hirntumoren, z. B. Glioblastomen, von diesem Therapieansatz profitieren. Mehrere Studien untersuchen derzeit den Einsatz von Immun-Checkpoint-Inhibitoren allein oder in Kombination mit Strahlen- bzw. Chemotherapie bei Patienten mit neu diagnostiziertem oder rezidiviertem Glioblastom. Die Ergebnisse der laufenden Studien werden zeigen, ob sich immuntherapeutische Behandlungsansätze in Zukunft als Ergänzung zu den bisher zur Verfügung stehenden Therapieoptionen in der Neuro-Onkologie etablieren können.
Kalziumhomöostase in der Multiplen Sklerose
Authors: Hundehege Petra , Epping Lisa , Meuth Sven 
Published: August 2017

ZusammenfassungKalzium ist als Signalmolkül entscheidend für nahezu alle zellulären Prozesse. Eine Störung der Kalziumhomöostase ist ursächlich für eine Vielzahl von pathologischen Zuständen. Dieser Übersichtsartikel fasst rezente Erkenntnisse über den Einfluss von Kalzium in der Multiplen Sklerose zusammen.
Variability in, and factors associated with, sizing of polyps by endoscopists at a large community practice
Authors: Elwir Saleh , Shaukat Aasma , Shaw Michael , Hughes John , Colton Joshua 
Published: August 2017

Abstract
Background and aims Accurate sizing of polyps at time of colonoscopy is critical for determining surveillance intervals. Endoscopists routinely over- or underestimate the size of polyps at colonoscopy. We evaluated the variability in sizing of polyps among multiple endoscopists, and the effect of patient and physician related factors on polyp size estimation in a large community-based practice.
Methods Adult patients who underwent a colonoscopy with polypectomy at five endoscopy centers in Minneapolis/St. Paul by one of 52 endoscopists in 2013 were included in this study. Association of patient, physician, and procedure related factors on polyp sizing was assessed.
Results In the study time frame, 38 624 colonoscopies were performed at five ambulatory endoscopy centers. Of these, 16 336 had one or more polyp removed with size information available, and were included in this analysis. There was significant inter-physician variation for estimating polyp sizes larger than 5 mm (intraclass correlation coefficient [ICC] 0.13). Older patient age (OR 1.08, 95 %CI 1.06 – 1.11), and male physician gender (OR 1.92, 95 %CI 1.26 – 2.94) were associated with increased odds of physicians sizing polyps as larger in size. Surveillance procedures had a higher odds of larger polyp sizing compared to screening (OR 0.91, 95 %CI 0.86 – 0.97) and diagnostic procedures (OR 0.86, 95 %CI 0.78 – 0.94).
Conclusion In a large community setting, variation of polyp sizing estimates exists between physicians. Male physicians were more likely to size polyps as larger in size. Older patients and patients undergoing surveillance procedures were more likely to have polyps that were sized as larger in size.
Use of endocytoscopy for identification of sessile serrated adenoma/polyps and hyperplastic polyps by quantitative image analysis of the luminal areas
Authors: Ogawa Yushi , Kudo Shin-ei , Mori Yuichi , Ikehara Nobunao , Maeda Yasuharu , Wakamura Kunihiko , Misawa Masashi , Kudo Toyoki , Hayashi Takemasa , Miyachi Hideyuki , Katagiri Atsushi , Ishida Fumio , Inoue Haruhiro 
Published: August 2017

Abstract
Background and study aims Recent studies that used magnifying chromoendoscopy and endocytoscopy (EC) to investigate endoscopic features of sessile serrated adenoma/polyps (SSA/Ps) suggested that a dilated crypt opening was an important indicator of SSA/Ps. However, no studies to date have measured the actual extent of dilatation. Hence, we investigated retrospectively the luminal areas using EC to determine a cutoff value for differentiating SSA/Ps from hyperplastic polyps (HPs).
Patients and methods A total of 101 lesions, including 25 SSA/Ps, 66 HPs, and 10 normal mucosal samples, assessed by an integrated-type EC were collected. For each lesion, 1 image that showed the widest lumen was selected and the average area of the contiguous 3 lumens were calculated. The cutoff value differentiating SSAPs from HPs was determined by receiver operating curve (ROC) analysis.
Results The mean luminal areas of SSA/Ps and HPs were 4152 μm2 and 2117 μm2, respectively. ROC analysis found that a luminal area cutoff of 3068 μm2 had a sensitivity of 80.0 %, a specificity of 77.3 %, an accuracy of 78.0 %, and an area under the ROC curve of 0.865. Furthermore, a cutoff of ≥ 556 μm2 was found to accurately distinguish between HPs and normal mucosa (sensitivity 98.5 %, specificity 100 %, accuracy 98.7 %, and AUC 0.998).
Conclusions EC analysis of the luminal area is useful for differentiating between SSAPs and HPs. This approach could be adapted for computer-aided diagnosis of SSA/P.