bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncologic outcome of hypopharyngeal carcinoma treated with different modalities at 2 different university hospitals
Authors: Bussu Francesco , Mura Federica , Miccichè Francesco , Bertino Giulia , Occhini Antonio , Almadori Giovanni , Galli Jacopo , Pandolfini Manlio , Gallus Roberto , Autorino Rosa , Guidi Maria Lavinia , Dinapoli Nicola , Valentini Vincenzo , Paludetti Gaetano , Benazzo Marco 
Published: December 2014

AbstractBackgroundThe hypopharynx is the site with the worst prognosis among head and neck squamous cell carcinomas (SCCs). The purpose of this study was to evaluate the oncologic outcomes of hypopharyngeal SCCs to identify the major clinical predictive factors and to compare the different primary therapeutic modalities.MethodsThe medical records of 123 consecutive patients diagnosed with primary resectable hypopharyngeal SCC were reviewed. The correlations of oncologic endpoints with tumor parameters and primary treatment were evaluated.ResultsThe overall survival (OS) rate was 76% and the disease‐specific survival (DSS) rate was 80% at 3 years in the entire group. Sex and T and N classifications significantly influenced survival in both univariate and multivariate analyses. Seventy‐four percent of our patients underwent both surgery and radiotherapy (RT), and the temporal sequence of the 2 modalities did not affect prognosis.ConclusionThe primary treatment modality in patients with resectable hypopharyngeal SCC did not affect prognosis in univariate and multivariate analyses for any stage considered. © 2015 Wiley Periodicals, Inc. Head Neck 38: 606–612, 2016
Surviving mossy cells enlarge and receive more excitatory synaptic input in a mouse model of temporal lobe epilepsy
Authors: Zhang Wei , Thamattoor Ajoy K. , LeRoy Christopher , Buckmaster Paul S. 
Published: December 2014

ABSTRACTNumerous hypotheses of temporal lobe epileptogenesis have been proposed, and several involve hippocampal mossy cells. Building on previous hypotheses we sought to test the possibility that after epileptogenic injuries surviving mossy cells develop into super‐connected seizure‐generating hub cells. If so, they might require more cellular machinery and consequently have larger somata, elongate their dendrites to receive more synaptic input, and display higher frequencies of miniature excitatory synaptic currents (mEPSCs). To test these possibilities pilocarpine‐treated mice were evaluated using GluR2‐immunocytochemistry, whole‐cell recording, and biocytin‐labeling. Epileptic pilocarpine‐treated mice displayed substantial loss of GluR2‐positive hilar neurons. Somata of surviving neurons were 1.4‐times larger than in controls. Biocytin‐labeled mossy cells also were larger in epileptic mice, but dendritic length per cell was not significantly different. The average frequency of mEPSCs of mossy cells recorded in the presence of tetrodotoxin and bicuculline was 3.2‐times higher in epileptic pilocarpine‐treated mice as compared to controls. Other parameters of mEPSCs were similar in both groups. Average input resistance of mossy cells in epileptic mice was reduced to 63% of controls, which is consistent with larger somata and would tend to make surviving mossy cells less excitable. Other intrinsic physiological characteristics examined were similar in both groups. Increased excitatory synaptic input is consistent with the hypothesis that surviving mossy cells develop into aberrantly super‐connected seizure‐generating hub cells, and soma hypertrophy is indirectly consistent with the possibility of axon sprouting. However, no obvious evidence of hyperexcitable intrinsic physiology was found. Furthermore, similar hypertrophy and hyper‐connectivity has been reported for other neuron types in the dentate gyrus, suggesting mossy cells are not unique in this regard. Thus, findings of the present study reveal epilepsy‐related changes in mossy cell anatomy and synaptic input but do not strongly support the hypothesis that mossy cells develop into seizure‐generating hub cells. © 2014 Wiley Periodicals, Inc.
Low‐intensity daily walking activity is associated with hippocampal volume in older adults
Authors: Varma Vijay R. , Chuang Yi‐Fang , Harris Gregory C. , Tan Erwin J. , Carlson Michelle C. 
Published: December 2014

ABSTRACTHippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low‐intensity walking activity, which may be related to leisure‐time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher‐intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low‐intensity walking activity, independent of moderate‐ to vigorous‐intensity activity and self‐reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings suggest the importance of examining whether increasing nonexercise, lifestyle physical activities may produce measurable cognitive benefits and affect hippocampal volume through molecular pathways unique to those related to moderate‐intensity exercise. © 2014 Wiley Periodicals, Inc.
Hippocampus, delay discounting, and vicarious trial‐and‐error
Authors: Bett David , Murdoch Lauren H. , Wood Emma R. , Dudchenko Paul A. 
Published: December 2014

ABSTRACTIn decision‐making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial‐and‐error at the decision point. Rats were trained on a recently developed, adjustable delay‐discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513–526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham‐lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham‐ and hippocampus‐lesioned rats showed a greater amount of vicarious trial‐and‐error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham‐lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham‐lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude. © 2014 Wiley Periodicals, Inc.
Modelling and assessment of hydrological changes in a developing urban catchment
Authors: Guan Mingfu , Sillanpää Nora , Koivusalo Harri 
Published: December 2014

AbstractUrbanization strongly changes natural catchment by increasing impervious coverage and by creating a need for efficient drainage systems. Such land cover changes lead to more rapid hydrological response to storms and change distribution of peak and low flows. This study aims to explore and assess how gradual hydrological changes occur during urban development from rural area to a medium‐density residential catchment. The Stormwater Management Model (SWMM) is utilized to simulate a series of scenarios in a same developing urban catchment. Sub‐hourly hydro‐meteorological data in warm season is used to calibrate and validate the model in the fully developed catchment in 2006. The validated model is then applied to other cases in development stage and runoff management scenarios. Based on the simulations and observations, three key problems are solved: (1) how catchment hydrology changes with land cover change, (2) how urban development changes pre‐development flows, and (3) how stormwater management techniques affect catchment hydrology. The results show that the low‐frequency flow rates had remarkably increased from 2004 to 2006 along with the increase of impervious areas. Urbanization in the residential catchment expands the runoff contributing area, accelerates hydrological response, raises peak flows in an order of magnitude of over 10, and more than doubles the total runoff volume. The effects of several LID controls on runoff hydrograph were simulated, and the techniques were able to reduce flows towards the pre‐development levels. However, the partly restored flow regime was still clearly changed in comparison to the pre‐development flow conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Conceptual modelling to assess how the interplay of hydrological connectivity, catchment storage and tracer dynamics controls nonstationary water age estimates
Authors: Birkel Christian , Soulsby Chris , Tetzlaff Doerthe 
Published: December 2014

AbstractAlthough catchment storage is an intrinsic control on the rainfall–runoff response of streams, direct measurement remains a major challenge. Coupled models that integrate long‐term hydrometric and isotope tracer data are useful tools that can provide insights into the dynamics of catchment storage and the volumes of water involved. In this study, we use a tracer‐aided hydrological model to characterize catchment storage as a dynamic control on system function related to streamflow generation, which also allows direct estimation of the nonstationarity of water ages. We show that in a wet Scottish upland catchment dominated by runoff generation from riparian peats (histosols) with high water storage, nonstationarity in water age distributions is only clearly detectable during more extreme wet and dry periods. This is explained by the frequency and longevity of hydrological connectivity and the associated relative importance of flow paths contributing younger or older waters to the stream. Generally, these saturated riparian soils represent large mixing zones that buffer the time variance of water age and integrate catchment‐scale partial mixing processes. Although storage simulations depend on model performance, which is influenced by input variability and the degree of isotopic damping in the stream, a longer‐term storage analysis of this model indicates a system that is only sensitive to more extreme hydroclimatic variability. Copyright © 2014 John Wiley & Sons, Ltd.
CD24 activates the NLRP3 inflammasome through c‐Src kinase activity in a model of the lining epithelium of inflamed periodontal tissues
Authors: Guo Wei , Ye Ping , Yu Hong , Liu Zhonghao , Yang Pishan , Hunter Neil 
Published: December 2014

AbstractChronic periodontitis is characterized by perturbation of the epithelial attachment to the tooth with subsequent migration of the lining epithelium and formation of a cleft or pocket. This non‐keratinized lining epithelium provides initial responses to bacterial products by signalling through receptors of innate immunity to activate inflammasome pathways. These comprise an intracellular network of regulatory and effector molecules leading to synthesis and activation of pro‐inflammatory cytokines. Conversely, CD24 is characteristically strongly expressed by the pocket epithelium and is reported to function as an important negative regulator for danger signals, protecting tissues from excessive leukocyte activity. The objective of the study was to determine the impact of ligation of CD24 on expression of inflammasome components. An epithelial mimic of pocket epithelium was used to evaluate activation of the NLRP3 inflammasome pathway. Surprisingly, antibody ligation of CD24 enhanced expression of NLRP3 together with co‐activators ASC and caspase‐1 resulting in burst release of activated interleukin (IL)‐18. Potent product inhibition was detected with IL‐18 suppressing expression of NLRP3, ASC, and caspase‐1. Scant distribution of these products within pocket epithelium compared with healthy gingival attachment provided indication of potential cycling of NLRP3 inflammasome expression. As subjects with mild chronic periodontitis have increased titres of serum antibodies auto‐reactive with CD24 compared with those of subjects with severe periodontitis, a molecular mechanism for regulated expression of the NLRP3 inflammasome mediated by c‐Src kinase activity, is proposed. This pathway could be regionally disrupted by products of pathogenic bacteria with profound downregulation in the dysbiosis associated with severe disease.
Netrin-1 Is a Critical Autocrine/Paracrine Factor for Osteoclast Differentiation
Authors: Mediero Aránzazu , Ramkhelawon Bhama , Perez-Aso Miguel , Moore Kathryn J. , Cronstein Bruce N. 
Published: December 2014

Abstract

Bone metabolism is a vital process that involves resorption by osteoclasts and formation by osteoblasts, which is closely regulated by immune cells. The neuronal guidance protein Netrin-1 regulates immune cell migration and inflammatory reactions, but its role in bone metabolism is unknown. During osteoclast differentiation, osteoclast precursors increase expression of Netrin-1 and its receptor Unc5b. Netrin-1 binds, in an autocrine and paracrine manner, to Unc5b to promote osteoclast differentiation in vitro, and absence of Netrin-1 or antibody-mediated blockade of Netrin-1 or Unc5b prevents osteoclast differentiation of both murine and human precursors. We confirmed the functional relationship of Netrin-1 in osteoclast differentiation in vivo using Netrin-1-deficient (Ntn1-/-) or wild-type (WT) bone marrow transplanted mice. Notably, Ntn1-/- chimeras have markedly diminished osteoclasts, as well as increased cortical and trabecular bone density and volume compared with WT mice. Mechanistic studies revealed that Netrin-1 regulates osteoclast differentiation by altering cytoskeletal assembly. Netrin-1 increases regulator of Rho-GEF subfamily (LARG) and repulsive guidance molecule (RGMa) association with Unc5b, which increases expression and activation of cytoskeletal regulators RhoA and focal adhesion kinase (FAK). Netrin-1 and its receptor Unc5b likely play a role in fusion of osteoclast precursors because Netrin-1 and DC-STAMP are tightly linked. These results identify Netrin-1 as a key regulator of osteoclast differentiation that may be a new target for bone therapies. © 2015 American Society for Bone and Mineral Research.
Thymol and Carvacrol Prevent Cisplatin‐Induced Nephrotoxicity by Abrogation of Oxidative Stress, Inflammation, and Apoptosis in Rats
Authors: EM El‐Sayed , AR Abd‐Allah , AM Mansour , AA EL‐Arabey 
Published: December 2014

ABSTRACTThe aim of the present study is to assess the possible protective effects of thymol and carvacrol against cisplatin (CP)‐induced nephrotoxicity. A single dose of CP {6 mg/kg, intraperitoneally (i.p.)} injected to male rats revealed significant increases in serum urea, creatinine, and tumor necrosis factor alpha levels. It also increased kidney contents of malondialdehyde and caspase‐3 activity with significant reduction in serum albumin, kidney content of reduced glutathione as well as catalase, and superoxide dismutase activity as compared to that of the control group. In contrast, administration of thymol {20 mg/kg, orally (p.o.)} and/or carvacrol (15 mg/kg, p.o.) for 14 days before CP injection and for 7 days after CP administration restored the kidney function and examined oxidative stress parameters. In conclusion, thymol was more effective nephroprotective than carvacrol. Moreover, a combination of thymol and carvacrol had a synergistic nephroprotective effect that might be attributed to antioxidant, anti‐inflammatory, and antiapoptotic activities.
Semaglutide, a once‐weekly human GLP‐1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel
Authors: Kapitza Christoph , Nosek Leszek , Jensen Lene , Hartvig Helle , Jensen Christine B. , Flint Anne 
Published: December 2014

AbstractThe effect of semaglutide, a once‐weekly human glucagon‐like peptide‐1 (GLP‐1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide‐free) and during (steady‐state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI for the ratio of pharmacokinetic parameters during semaglutide steady‐state and semaglutide‐free periods was within prespecified limits (0.80–1.25). The bioequivalence criterion was met for ethinylestradiol area under the curve (AUC0–24 h) for semaglutide steady‐state/semaglutide‐free; 1.11 (1.06–1.15). AUC0–24 h was 20% higher for levonorgestrel at semaglutide steady‐state vs. semaglutide‐free (1.20 [1.15–1.26]). Cmax was within bioequivalence criterion for both contraceptives. Reductions (mean ± SD) in HbA1c (–1.1 ± 0.6%) and weight (–4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were compatible with once‐weekly dosing; the semaglutide dose and dose‐escalation regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild to moderate in severity. Asymptomatic increases in mean amylase and lipase were observed. Three subjects had elevated alanine aminotransferase levels ≥3x the upper limit of normal during semaglutide/oral contraceptive coadministration, which were reported as adverse events, but resolved during follow‐up. Semaglutide did not reduce the bioavailability of ethinylestradiol and levonorgestrel.
Dynamics of testis‐ova in a wild population of Japanese pond frogs, Rana nigromaculata
Authors: Kobayashi Tohru , Kumakura Masahiko , Yoshie Sumio , Sugishima Tomomi , Horie Yoshifumi 
Published: December 2014

ABSTRACTAlthough many studies have reported the occurrence of testis‐ova in wild frog populations, the origin and trigger of testis‐ova differentiation/development remain unclear. A high frequency of testis‐ova has been previously reported for wild populations of the Japanese pond frog, Rana nigromaculata (cf. Iwasawa and Asai, '59). In the present study, we aimed to clarify the dynamics of testis‐ova in this frog species, including the origin and artificial induction of testis‐ova. Testis‐ova were observed in both mature frogs and puberty‐stage frogs (i.e., 0‐ and 1‐year‐old frogs). However, the early stages of testis‐ova (∼pachytene stage) were mostly observed in puberty‐stage male frogs at the onset of spermatogenesis. The early stages of testis‐ova were observed in the cysts of early secondary spermatogonia and the single cysts of the primary spermatogonium. This finding indicates that testis‐ova differentiation occurs during spermatogonial proliferation and that it is correlated with the initiation of spermatogenesis. We also examined whether estrogen exposure induced testis‐ova differentiation and how it is correlated with the progression of spermatogenesis. When 1‐year‐old frogs were exposed to estradiol‐17β during spring (i.e., when spermatogenesis was initiated), testis‐ova differentiation was induced in a dose‐dependent manner. However, this phenomenon did not occur in 1‐year‐old frogs during summer, (i.e., when the transition from spermatogonia to spermatocytes mainly occurs). These results present the first evidence that testis‐ova of the Japanese pond frog are derived from primary and early secondary spermatogonia, and that estrogen exposure induces testis‐ova differentiation accompanied by the initiation of spermatogenesis. J. Exp. Zool. 323A: 74–79, 2015. © 2014 Wiley Periodicals, Inc.
Vertex Cuts
Authors: Dunwoody M. J. , Krön B. 
Published: December 2014

AbstractGiven a connected graph, in many cases it is possible to construct a structure tree that provides information about the ends of the graph or its connectivity. For example Stallings' theorem on the structure of groups with more than one end can be proved by analyzing the action of the group on a structure tree and Tutte used a structure tree to investigate finite 2‐connected graphs, that are not 3‐connected. Most of these structure tree theories have been based on edge cuts, which are components of the graph obtained by removing finitely many edges. A new axiomatic theory is described here using vertex cuts, components of the graph obtained by removing finitely many vertices. This generalizes Tutte's decomposition of 2‐connected graphs to k‐connected graphs for any k, in finite and infinite graphs. The theory can be applied to nonlocally finite graphs with more than one vertex end, i.e. ends that can be separated by removing a finite number of vertices. This gives a decomposition for a group acting on such a graph, generalizing Stallings' theorem. Further applications include the classification of distance transitive graphs and k‐CS‐transitive graphs.