bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local anesthetics counteract cell proliferation and migration of human triple‐negative breast cancer and melanoma cells
Authors: Castelli Vanessa , Piroli Alba , Marinangeli Franco , d'Angelo Michele , Benedetti Elisabetta , Ippoliti Rodolfo , Zis Panagiotis , Varrassi Giustino , Giordano Antonio , Paladini Antonella , Cimini Annamaria 
Published: September 2019

AbstractIn different retrospective studies, a protective role of regional anesthetics in reducing cancer recurrence after surgery was indicated. Accordingly, it has been previously demonstrated a protective effect of anesthetics in breast cancer cells and in other types of cancer. On the other hand, how anesthetics influence cancer needs in‐depth investigations. For this purpose, two different human cancer cell lines, MDA‐MB‐231, triple‐negative breast cancer, and A375, melanoma, were used in this study. By means of Western blotting and immunofluorescence and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses, the signal transduction pathways activated by the anesthetics, such as ropivacaine and levobupivacaine, were analyzed. The data obtained demonstrated that both anesthetics are able to counteract cell proliferation by positively modulating cell death signaling and by decreasing cell proliferation and survival pathways.
The effect of learning on heart rate and behavior of European starlings (Sturnus vulgaris)
Authors: Glassman Laura W. , Hagmann  Carl E. , Qadri Muhammad A. , Cook Robert G. , Romero L. Michael 
Published: September 2019

AbstractWild‐caught European starlings (Sturnus vulgaris) were exposed to a learning task to determine whether heart rate (HR) and behavior responses to the learning activated the sympathetic nervous system. Birds learned to discriminate between images of opposite convexity (concave and convex) based on shading cues in a closed economy (food only available through task completion). Once learned, the task was changed in three ways: (a) manipulating the angle and shape of the image; (b) altering the availability of the task; and (c) reversing the positive stimulus. HR, used as an index of catecholamine release, was measured during each change to determine whether having to alter previously established behaviors to learn new behaviors elicited a sympathetic response. Starlings decreased their HR during the initial discrimination training and did not alter their HR when presented with modified images or when the positive stimulus was reversed. However, HR increased when the task became unavailable and decreased upon its return, suggesting that preventing task performance was perceived as stressful. Birds also modified their behavior when tasks were changed. The number of trials per minute decreased during the reversal treatment, as did the success rate, suggesting that starlings may try to conserve energy when access to food diminishes. This is also supported by the decrease in perch hops per minute when the task was unavailable and the subsequent increase upon its return. Overall, these results suggest that learning per se does not activate the sympathetic nervous system and, therefore, is not a stressor for wild birds.
Advances in Conservation and Management of the Alligator Gar: A Synthesis of Current Knowledge and Introduction to a Special Section
Authors: Smith N. G. , Daugherty D. J. , Brinkman E. L. , Wegener M. G. , Kreiser B. R. , Ferrara A. M. , Kimmel K. D. , David S. R. 
Published: September 2019

Abstract
Growing appreciation of biodiversity and the role of apex predators, along with the increasing popularity of multispecies and trophy-oriented angling, has elevated the status of gars—in particular, the Alligator Gar Atractosteus spatula—among anglers and biologists alike. As a result, considerable effort has been spent in recent years to gain a working knowledge of the biology and ecology of the species in order to advance science-based management. In January 2019, the Alligator Gar Technical Committee of the Southern Division of the American Fisheries Society hosted a symposium entitled “Advances in the Conservation and Management of North American Gars” to showcase the results of research and management efforts conducted throughout the species’ range. Fishery researchers and managers presented a diversity of works, furthering our understanding of population dynamics, stock assessment, genetics, hatchery practices and stocking, habitat use, and angler desires associated with Alligator Gar fisheries. In our introduction to this special section, we introduce these works and provide a synthesis of the current state of scientific knowledge regarding the Alligator Gar. We hope that this will provide context to the works presented in the symposium and will serve to guide the development of future research that addresses the remaining knowledge gaps concerning the species and its growing fishery.
Ba‐Wei‐Die‐Huang‐Wan (Hachimi‐jio‐gan) can ameliorate ketamine‐induced cystitis by modulating neuroreceptors, inflammatory mediators, and fibrogenesis in a rat model
Authors: Lee Wei‐Chia , Tain You‐Lin , Chuang Yao‐Chi , Tsai Cheng‐Nan , Yu Chun‐Chieh , Su Chia‐Hao 
Published: September 2019

AbstractAimWe investigated the effects of Ba‐Wei‐Die‐Huang‐Wan (BWDHW) on ketamine‐induced cystitis (KIC) in a rat model.MethodsFemale Sprague‐Dawley rats were distributed into three groups: control (saline), ketamine (25 mg/kg/day for 28 days), or ketamine (25 mg/kg/day for 28 days) plus BWDHW (90 mg/kg/day, started from day 14). Functional magnetic resonance imaging (fMRI), metabolic cage study, and cystometry were evaluated. Bladder histology was evaluated. Western blots of the bladder proteins were carried out.ResultsCompared with controls, ketamine‐treated rats showed stronger fMRI intensity in the periaqueductal gray area and bladder overactivity in the bladder functional study, but the ketamine/BWDHW‐treated rats did not. Furthermore, ketamine breached the uroplakin III membrane at the apical surface of the urothelium, enhanced substance P spread over the urothelium, induced suburothelial hemorrhage and monocyte/macrophage infiltration, and caused interstitial fibrosis deposition. By contrast, the BWDHW‐treated rats exhibited less substance P spread, lower suburothelial monocyte/macrophage infiltration, and lower interstitial fibrosis deposition. The ketamine group showed significant overexpression of neuroreceptors in the bladder mucosa (the transient receptor potential vanilloid 1 and M2‐ and M3‐muscarinic receptors) and detrusor (M2‐ and M3‐muscarinic receptors); inflammatory mediators in the detrusor (interleukin‐1β [IL‐1β], IL‐6, tumor necrosis factor‐α, nuclear factor‐κB, cyclooxygenase‐2, and intercellular adhesion molecule‐1); and fibrogenesis molecules in the detrusor (transforming growth factor‐β1, collagen I, collagen III, and fibronectin). However, no significant changes were noted between the ketamine/BWDHW and control groups.ConclusionBWDHW could exert therapeutic effects by inhibiting the upregulation of neuroreceptors, modulating inflammatory mediators, suppressing fibrogenesis, and ameliorating bladder overactivity in rats with KIC.
Tubulointerstitial nephritis antigen‐like 1 deficiency alleviates age‐dependent depressed ovulation associated with ovarian collagen deposition in mice
Authors: Akaiwa Masato , Fukui Emiko , Matsumoto Hiromichi 
Published: September 2019

AbstractPurposeThis study aimed to examine whether the Tinagl1 might be associated with ovulation in aged females and reproductive age‐associated fibrosis in the stroma of the ovary.MethodsTo address the ovulatory ability and quality of ovulated oocytes, we induced ovulation by treatment with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) followed by in vitro fertilization. We also performed Picrosirius Red (PSR) staining to evaluate ovarian collagen deposition.ResultsAs compared to ovulation in 8‐ to 9‐month‐old Tinagl1flox/flox mice, the number of ovulated oocytes from Tinagl1flox/flox mice decreased in an age‐dependent manner in mice more than 10‐11 months old, whereas the ovulated oocyte numbers in Tinagl1−/− mice decreased significantly at 14‐15 months. In vitro fertilization followed by embryo culture demonstrated the normal developmental potential of Tinagl1‐null embryos during the preimplantation period. PSR staining indicated that collagen was found throughout the ovarian stroma in an age‐dependent manner in Tinagl1flox/flox females, whereas those distributions were delayed to 14‐15 months in Tinagl1−/− females. This timing was consistent with the delayed timing of age‐related decline of ovulation in Tinagl1−/− females.ConclusionsThe alleviation of age‐associated depression of ovulation was caused by delayed ovarian collagen deposition in Tinagl1‐null female mice.
Immigrants’ mental health service use compared to that of native Finns: a register study
Authors: Kieseppä Valentina , Torniainen-Holm Minna , Jokela Markus , Suvisaari Jaana , Gissler Mika , Markkula Niina , Lehti Venla 
Published: September 2019

Abstract

Purpose
Many aspects related to migration might predispose immigrants to mental health problems. Yet immigrants have been shown to underuse mental health services. The aim of this study was to compare the intensity of psychiatric care, as an indicator of treatment adequacy, between natives and immigrants living in Finland.

Methods
We used nationwide register data that included all the immigrants living in Finland at the end of 2010 (n = 185,605) and their matched controls. Only those who had used mental health services were included in the analyses (n = 14,285). We used multinomial logistic regression to predict the categorized treatment intensity by immigrant status, region and country of origin, length of residence, and other background variables.

Results
Immigrants used mental health services less than Finnish controls and with lower intensity. The length of residence in Finland increased the probability of higher treatment intensity. Immigrants from Eastern Europe, sub-Saharan Africa, the Middle East, and Northern Africa were at the highest risk of receiving low-intensity treatment.

Conclusions
Some immigrant groups seem to persistently receive less psychiatric treatment than Finnish-born controls. Identification of these groups is important and future research is needed to determine the mechanisms behind these patterns.
Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development
Authors: McCluskey Stuart P. , Plisson Christophe , Rabiner Eugenii A. , Howes Oliver 
Published: September 2019

Abstract
Purpose
A limit on developing new treatments for a number of central nervous system (CNS) disorders has been the inadequate understanding of the in vivo pathophysiology underlying neurological and psychiatric disorders and the lack of in vivo tools to determine brain penetrance, target engagement, and relevant molecular activity of novel drugs. Molecular neuroimaging provides the tools to address this. This article aims to provide a state-of-the-art review of new PET tracers for CNS targets, focusing on developments in the last 5 years for targets recently available for in-human imaging.

Methods
We provide an overview of the criteria used to evaluate PET tracers. We then used the National Institute of Mental Health Research Priorities list to identify the key CNS targets. We conducted a PubMed search (search period 1st of January 2013 to 31st of December 2018), which yielded 40 new PET tracers across 16 CNS targets which met our selectivity criteria. For each tracer, we summarised the evidence of its properties and potential for use in studies of CNS pathophysiology and drug evaluation, including its target selectivity and affinity, inter and intra-subject variability, and pharmacokinetic parameters. We also consider its potential limitations and missing characterisation data, but not specific applications in drug development. Where multiple tracers were present for a target, we provide a comparison of their properties.

Results and conclusions
Our review shows that multiple new tracers have been developed for proteinopathy targets, particularly tau, as well as the purinoceptor P2X7, phosphodiesterase enzyme PDE10A, and synaptic vesicle glycoprotein 2A (SV2A), amongst others. Some of the most promising of these include 18F-MK-6240 for tau imaging, 11C-UCB-J for imaging SV2A, 11C-CURB and 11C-MK-3168 for characterisation of fatty acid amide hydrolase, 18F-FIMX for metabotropic glutamate receptor 1, and 18F-MNI-444 for imaging adenosine 2A. Our review also identifies recurrent issues within the field. Many of the tracers discussed lack in vivo blocking data, reducing confidence in selectivity. Additionally, late-stage identification of substantial off-target sites for multiple tracers highlights incomplete pre-clinical characterisation prior to translation, as well as human disease state studies carried out without confirmation of test-retest reproducibility.
Alternative dosing regimens for atezolizumab: an example of model-informed drug development in the postmarketing setting
Authors: Morrissey Kari M. , Marchand Mathilde , Patel Hina , Zhang Rong , Wu Benjamin , Phyllis Chan H. , Mecke Almut , Girish Sandhya , Jin Jin Y. , Winter Helen R. , Bruno René 
Published: September 2019

Abstract

Purpose
To determine the exposure–response (ER) relationships between atezolizumab exposure and efficacy or safety in patients with advanced non-small cell lung cancer (NSCLC) or urothelial carcinoma (UC) and to identify alternative dosing regimens.

Methods
ER analyses were conducted using pooled NSCLC and UC data from phase 1 and 3 studies (PCD4989g, OAK, IMvigor211; ClinicalTrials.gov IDs, NCT01375842, NCT02008227, and NCT02302807, respectively). Objective response rate, overall survival, and adverse events were evaluated vs pharmacokinetic (PK) metrics. Population PK-simulated exposures for regimens of 840 mg every 2 weeks (q2w) and 1680 mg every 4 weeks (q4w) were compared with the approved regimen of 1200 mg every 3 weeks (q3w) and the maximum assessed dose (MAD; 20 mg/kg q3w). Phase 3 IMpassion130 (NCT02425891) data were used to validate the PK simulations for 840 mg q2w. Observed safety data were evaluated by exposure and body weight subgroups.

Results
No significant ER relationships were observed for safety or efficacy. Predicted exposures for 840 mg q2w and 1680 mg q4w were comparable to 1200 mg q3w and the MAD and consistent with observed PK data from IMpassion130. Observed safety was similar between patients with a Cmax above and below the predicted Cmax for 1680 mg q4w and between patients in the lowest and upper 3 body weight quartiles.

Conclusion
Atezolizumab regimens of 840 mg q2w and 1680 mg q4w are expected to have comparable efficacy and safety as the approved regimen of 1200 mg q3w, supporting their interchangeable use and offering patients greater flexibility.
Coarse-graining molecular dynamics: stochastic models with non-Gaussian force distributions
Authors: Erban Radek 
Published: September 2019

Abstract
Incorporating atomistic and molecular information into models of cellular behaviour is challenging because of a vast separation of spatial and temporal scales between processes happening at the atomic and cellular levels. Multiscale or multi-resolution methodologies address this difficulty by using molecular dynamics (MD) and coarse-grained models in different parts of the cell. Their applicability depends on the accuracy and properties of the coarse-grained model which approximates the detailed MD description. A family of stochastic coarse-grained (SCG) models, written as relatively low-dimensional systems of nonlinear stochastic differential equations, is presented. The nonlinear SCG model incorporates the non-Gaussian force distribution which is observed in MD simulations and which cannot be described by linear models. It is shown that the nonlinearities can be chosen in such a way that they do not complicate parametrization of the SCG description by detailed MD simulations. The solution of the SCG model is found in terms of gamma functions.
Do anticoagulants affect outcomes of hip fracture surgery? A cross-sectional analysis
Authors: Hoerlyck Caroline , Ong Terence , Gregersen Merete , Damsgaard Else Marie , Borris Lars , Chia Jac Kie , Yap Ying Yi Wendy , Weerasuriya Namal , Sahota Opinder 
Published: September 2019

Abstract

Introduction
The management of patients with a hip fracture is affected by the use of oral anticoagulants. A cross-sectional analysis was undertaken to investigate health outcome differences in those anticoagulated compared to those not anticoagulated.

Methods
Patients aged 50 years and over presenting to a large university hospital with hip fractures were identified from the service registry. Patient characteristics and health outcomes between those not anticoagulated were compared with those anticoagulated (warfarin and direct oral anticoagulants, DOAC).

Results
200/2307 (9%) patients were anticoagulated. 84% were on warfarin, and the rest a DOAC. Compared to those anticoagulated, there was a higher prevalence of dementia (25% vs. 18%, p = 0.02) and a lower prevalence of cardiovascular disease (54% vs. 78%, p < 0.01), atrial fibrillation (10% vs. 82%, p < 0.01), and polypharmacy (55% vs. 76%, p < 0.01). Renal function was lower in the anticoagulated group. Time to operation for those not anticoagulated and anticoagulated was a median (IQR) of 25 (15) and 27 (18) hours. There was no difference in blood transfusion and hospital mortality. Postoperative complications were similar except a higher rate of renal failure (14% vs. 19%, p = 0.04) and heart failure (1% vs. 5%, p < 0.01), and a longer length of stay [median (IQR): 14 (10) vs. 16 (12) days] in the anticoagulated group. This was no longer significant after adjustment of confounders.

Conclusion
There was no statistically significant difference in health outcomes between those anticoagulated and those not after adjusting for patient characteristics. It was feasible to avoid significant delay in hip fracture surgery in those anticoagulated.
The effect of solid solution on the stability of talc and 10-Å phase
Authors: Howe Harriet , Pawley Alison R. 
Published: September 2019

Abstract
Talc and 10-Å phase are hydrous phases that are implicated in fluid processes and rheological behaviour in subduction zones. Natural samples of talc show limited compositional variation away from the MgO–SiO2–H2O (MSH) endmember, with only substitution of Fe2+ for Mg occurring in significant amounts. In experiments at 2 GPa, talc containing 0.48 apfu Fe2+ begins to break down in the divariant field talc + anthophyllite + quartz at ~ 550 °C, a temperature ~ 270 °C lower than in the MSH system. At 4 GPa, Fe-bearing talc breaks down over a wide temperature interval in the divariant field talc + enstatite + coesite. The large decrease in temperature of the beginning of talc breakdown shows that Fe2+ is partitioned strongly into enstatite and anthophyllite with respect to talc. In phase reversal experiments at 6.5 GPa, the beginning of the dehydration of 10-Å phase containing 0.48 apfu Fe2+ was bracketed between 575 °C and 600 °C, a temperature ~ 100 °C lower than the MSH endmember reaction. The relative positions of the talc and 10-Å phase dehydration reactions indicate that the latter is able to accommodate greater Fe substitution, and is, therefore, more stable in Fe-bearing systems. In experiments at 6.2 GPa, 650 °C in the systems MgO–Al2O3–SiO2–H2O (MASH) and Na2O–MgO–Al2O3–SiO2–H2O (NMASH), 10-Å phase was synthesised that contains up to 0.5 apfu Al in the system MASH (compared to 0.8 in the starting material) and up to 0.4 apfu Al + 0.4 apfu Na in the system NMASH (compared to 0.7 of each of Al and Na in the starting material). Further experiments are required to determine if higher Al and Na contents in 10-Å phase are possible. The much higher Al and Na contents than found in talc indicate that, as with Fe, substitution of these elements enlarges the 10-Å phase stability field with respect to talc. In contrast to the effect of Fe, Al and Na also increase the stability of 10-Å phase relative to its thermal breakdown products enstatite + coesite.
GORTS: genetic algorithm based on one-by-one revision of two sides for dynamic travelling salesman problems
Authors: Xu Xiaolong , Yuan Hao , Matthew Peter , Ray Jeffrey , Bagdasar Ovidiu , Trovati Marcello 
Published: September 2019

Abstract
The dynamic travelling salesman problem (DTSP) is a natural extension of the standard travelling salesman problem, and it has attracted significant interest in recent years due to is practical applications. In this article, we propose an efficient solution for DTSP, based on a genetic algorithm (GA), and on the one-by-one revision of two sides (GORTS). More specifically, GORTS combines the global search ability of GA with the fast convergence feature of the method of one-by-one revision of two sides, in order to find the optimal solution in a short time. An experimental platform was designed to evaluate the performance of GORTS with TSPLIB. The experimental results show that the efficiency of GORTS compares favourably against other popular heuristic algorithms for DTSP. In particular, a prototype logistics system based on GORTS for a supermarket with an online map was designed and implemented. It was shown that this can provide optimised goods distribution routes for delivery staff, while considering real-time traffic information.
Dynamic sampling rate algorithm (DSRA) implemented in self-adaptive software architecture: a way to reduce the energy consumption of wireless sensors through event-based sampling
Authors: Algabroun Hatem 
Published: September 2019

Abstract
With the recent digitalization trends in the industry, wireless sensors are, in particular, gaining a growing interest. This is due to the possibility of being installed in inaccessible locations for wired sensors. Although great success has already been achieved in this area, energy limitation remains a major obstacle for further advances. As such, it is important to optimize the sampling with a sufficient rate to catch important information without excessive energy consumption, and one way to achieve sufficient sampling is using adaptive sampling for sensors. As software plays an important role in the techniques of adaptive sampling, a reference framework for software architecture is important in order to facilitate their design, modeling, and implementation. This study proposes a software architecture, named Rainbow, as the reference architecture, also, it develops an algorithm for adaptive sampling. The algorithm was implemented in the Rainbow architecture and tested using two datasets; the results show the proper operation of the architecture as well as the algorithm. In conclusion, the Rainbow software architecture has the potential to be used as a framework for adaptive sampling algorithms, and the developed algorithm allows adaptive sampling based on the changes in the signal.