bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review: Clinical, genetic and neuroimaging features of frontotemporal dementia
Authors: Convery R. , Mead S. , Rohrer J. D. 
Published: December 2018

Frontotemporal dementia (FTD) is a heterogeneous group of disorders causing neurodegeneration within a network of areas centred on the frontal and temporal lobes. Clinically, patients present with behavioural symptoms (behavioural variant FTD) or language disturbance (primary progressive aphasia), although there is an overlap with motor neurone disease and atypical parkinsonian disorders. Whilst neuroimaging commonly reveals abnormalities in the frontal and temporal lobes, a closer review identifies a more complex picture with variable asymmetry of neuronal loss, widespread subcortical involvement and in many cases more posterior cortical atrophy. An autosomal‐dominant genetic disorder is found in around a third of people with mutations in progranulin, C9orf72 and the microtubule‐associated protein tau being the commonest causes. In the other two‐thirds, the disorder is sporadic, although recent genome‐wide association studies have started to identify genetic risk factors within this group. Much of this knowledge has been understood only in the past 10 years and so this review will discuss the current knowledge about the clinical, genetic and neuroimaging features of FTD.
Review: Modelling the pathology and behaviour of frontotemporal dementia
Authors: Solomon D. A. , Mitchell J.C. , Salcher‐Konrad M.‐T. , Vance C.A. , Mizielinska S. 
Published: December 2018

Frontotemporal dementia (FTD) encompasses a collection of clinically and pathologically diverse neurological disorders. Clinical features of behavioural and language dysfunction are associated with neurodegeneration, predominantly of frontal and temporal cortices. Over the past decade, there have been significant advances in the understanding of the genetic aetiology and neuropathology of FTD which have led to the creation of various disease models to investigate the molecular pathways that contribute to disease pathogenesis. The generation of in vivo models of FTD involves either targeting genes with known disease‐causative mutations such as GRN and C9orf72 or genes encoding proteins that form the inclusions that characterize the disease pathologically, such as TDP‐43 and FUS. This review provides a comprehensive summary of the different in vivo model systems used to understand pathomechanisms in FTD, with a focus on disease models which reproduce aspects of the wide‐ranging behavioural phenotypes seen in people with FTD. We discuss the emerging disease pathways that have emerged from these in vivo models and how this has shaped our understanding of disease mechanisms underpinning FTD. We also discuss the challenges of modelling the complex clinical symptoms shown by people with FTD, the confounding overlap with features of motor neuron disease, and the drive to make models more disease‐relevant. In summary, in vivo models can replicate many pathological and behavioural aspects of clinical FTD, but robust and thorough investigations utilizing shared features and variability between disease models will improve the disease‐relevance of findings and thus better inform therapeutic development.
Development and evaluation of a genome‐wide Coffee 8.5K SNP array and its application for high‐density genetic mapping and for investigating the origin of Coffea arabica L.
Authors: Merot‐L'anthoene Virginie , Tournebize Rémi , Darracq Olivier , Rattina Vimel , Lepelley Maud , Bellanger Laurence , Tranchant‐Dubreuil Christine , Coulée Manon , Pégard Marie , Metairon Sylviane , Fournier Coralie , Stoffelen Piet , Janssens Steven B. , Kiwuka Catherine , Musoli Pascal , Sumirat Ucu , Legnaté Hyacinthe , Kambale Jean‐Léon , Ferreira da Costa Neto João , Revel Clara , de Kochko Alexandre , Descombes Patrick , Crouzillat Dominique , Poncet Valérie 
Published: December 2018

SummaryCoffee species such as Coffea canephora P. (Robusta) and C. arabica L. (Arabica) are important cash crops in tropical regions around the world. C. arabica is an allotetraploid (2n = 4x = 44) originating from a hybridization event of the two diploid species C. canephora and C. eugenioides (2n = 2x = 22). Interestingly, these progenitor species harbour a greater level of genetic variability and are an important source of genes to broaden the narrow Arabica genetic base. Here, we describe the development, evaluation and use of a single‐nucleotide polymorphism (SNP) array for coffee trees. A total of 8580 unique and informative SNPs were selected from C. canephora and C. arabica sequencing data, with 40% of the SNP located in annotated genes. In particular, this array contains 227 markers associated to 149 genes and traits of agronomic importance. Among these, 7065 SNPs (~82.3%) were scorable and evenly distributed over the genome with a mean distance of 54.4 Kb between markers. With this array, we improved the Robusta high‐density genetic map by adding 1307 SNP markers, whereas 945 SNPs were found segregating in the Arabica mapping progeny. A panel of C. canephora accessions was successfully discriminated and over 70% of the SNP markers were transferable across the three species. Furthermore, the canephora‐derived subgenome of C. arabica was shown to be more closely related to C. canephora accessions from northern Uganda than to other current populations. These validated SNP markers and high‐density genetic maps will be useful to molecular genetics and for innovative approaches in coffee breeding.
Structural and Functional Consequences of the Weak Binding of Chlorin e6 to Bovine Rhodopsin
Authors: Mitchell James , Yanamala Naveena , Tan Yi Lei , Gardner Eric E. , Tirupula Kalyan C. , Balem Fernanda , Sheves Mordechai , Nietlispach Daniel , Klein‐Seetharaman Judith 
Published: December 2018

AbstractThe chlorophyll‐derivative chlorin e6 (Ce6) identified in the retinas of deep‐sea ocean fish is proposed to play a functional role in red bioluminescence detection. Fluorescence and 1H NMR spectroscopy studies with the bovine dim‐light photoreceptor, rhodopsin, indicate that Ce6 weakly binds to it with μm affinity. Absorbance spectra prove that red light sensitivity enhancement is not brought about by a shift in the absorbance maximum of rhodopsin. 19F NMR experiments with samples where 19F labels are either placed at the cytoplasmic binding site or incorporated as fluorinated retinal indicate that the cytoplasmic domain is highly perturbed by binding, while little to no changes are detected near the retinal. Binding of Ce6 also inhibits G‐protein activation. Chemical shift changes in 1H‐15N NMR spectroscopy of 15N‐Trp labeled bovine rhodopsin reveal that Ce6 binding perturbs the entire structure. These results provide experimental evidence that Ce6 is an allosteric modulator of rhodopsin.
Comparative Study of the Effects of Ferrochelatase‐siRNA Transfection Mediated by Ultrasound Microbubbles and Polyethyleneimine in Combination with Low‐dose ALA to Enhance PpIX Accumulation in Human Endometrial Cancer Xenograft Nude Mice Models
Authors: Zhang Xian , Chen Longfei , Gao Lvfen , Gao Xuesong , Li Nan , Song Yuwei , Huang Xinke , Lin Shaoqiang , Wang Xiaoyu 
Published: December 2018

AbstractComparison of the fluorescence intensity caused by the accumulation of PpIX in endometrial cancer xenografts in nude mice after low‐dose 5‐Aminolevulinic acid (ALA) injection combined with siRNA transfection was mediated by ultrasound microbubbles and polyethyleneimine (PEI) to explore the feasibility of the ultrasound microbubble technique as transfection agents. Knockdown of ferrochelatase (FECH) in human endometrial cancer xenografts in nude mice was performed by transfection with FECH‐siRNA mediated by PEI and ultrasound microbubbles alone or in combination; then, low‐dose ALA was injected. Subsequently, an in vivo animal imaging system was employed to detect the fluorescence intensity in xenografts. Red fluorescence was observed in xenografts given more than 6.25 mg kg−1 of ALA. When the dose of ALA was greater than 50 mg kg−1, there was a significant difference in the fluorescence between tumor and other tissues. After the nude mice were transfected with siRNA and treated with low‐dose ALA (1.0 mg kg−1), apparent PpIX fluorescence of the xenografts was observed, and the fluorescence intensity was PEI+ ultrasound microbubbles > PEI > ultrasound microbubbles. Ultrasound microbubbles in combination with PEI could generate a higher fluorescence intensity of PpIX than that obtained with ultrasound microbubbles or PEI alone, and ultrasound microbubbles could wholly or partially replace PEI under certain conditions.
Risk and Planning in Agriculture: How Planning on Dairy Farms in Ireland Is Affected by Farmers’ Regulatory Focus
Authors: Garvey John , Sirr Gordon , O'Shea Deirdre , O'Brien Fergal 
Published: December 2018

AbstractThis article examines how planning on dairy farms is affected by farmers' motivation. It argues that farmers' choice of expansion strategies can be specified in terms of risk decision making and understood as either prevention‐focused or promotion‐focused motivation. This relationship was empirically examined using mediated regression analyses where promotion/prevention focus was the independent variable and its effect on total milk production via planned expansion strategies was examined. The results indicate that promotion focus among farmers has an indirect effect on farm expansion via planning strategies that incur greater risk to the farm enterprise. Regulatory focus on the part of farmers has an influence on farmers' planning and risk management activities and must be accounted for in the design and implementation of policy and risk management tools in agriculture.
Recalibration of the Grunow–Finke Assessment Tool to Improve Performance in Detecting Unnatural Epidemics
Authors: Chen Xin , Chughtai Abrar Ahmad , MacIntyre Chandini Raina 
Published: December 2018

AbstractSuccessful identification of unnatural epidemics relies on a sensitive risk assessment tool designed for the differentiation between unnatural and natural epidemics. The Grunow–Finke tool (GFT), which has been the most widely used, however, has low sensitivity in such differentiation. We aimed to recalibrate the GFT and improve the performance in detection of unnatural epidemics. The comparator was the original GFT and its application in 11 historical outbreaks, including eight confirmed unnatural outbreaks and three natural outbreaks. Three steps were involved: (i) removing criteria, (ii) changing weighting factors, and (iii) adding and refining criteria. We created a series of alternative models to examine the changes on the parameter likelihood of unnatural outbreaks until we found a model that correctly identified all the unnatural outbreaks and natural ones. Finally, the recalibrated GFT was tested and validated with data from an unnatural and natural outbreak, respectively. A total of 238 models were tested. Through the removal of criteria, increasing or decreasing weighting factors of other criteria, adding a new criterion titled “special insights,” and setting a new threshold for likelihood, we increased the sensitivity of the GFT from 38% to 100%, and retained the specificity at 100% in detecting unnatural epidemics. Using test data from an unnatural and a natural outbreak, the recalibrated GFT correctly classified their etiology. The recalibrated GFT could be integrated into routine outbreak investigation by public health institutions and agencies responsible for biosecurity.
Treatment, prevention and public health management of impetigo, scabies, crusted scabies and fungal skin infections in endemic populations: a systematic review
Authors: May Philippa J. , Tong Steven Y. C. , Steer Andrew C. , Currie Bart J. , Andrews Ross M. , Carapetis Jonathan R. , Bowen Asha C. 
Published: December 2018

SummaryWe conducted a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource‐limited settings where skin infections are endemic. The aim is to inform strategies, guidelines and research to improve skin health in populations that are inequitably affected by infections of the skin and the downstream consequences of these. The systematic review is reported according to the PRISMA statement. From 1759 titles identified, 81 full text studies were reviewed and key findings outlined for impetigo, scabies, crusted scabies and tinea. Improvements in primary care and public health management of skin infections will have broad and lasting impacts on overall quality of life including reductions in morbidity and mortality from sepsis, skeletal infections, kidney and heart disease.
The Use of the High School 12th-Grade Geography Textbook by Students in Turkey
Authors: Şahin Vedat , İnce Ziya 
Published: December 2018

Textbooks are one of the most used teaching materials for attaining educational goals in secondary education institutions. Textbooks still maintain their importance at the present time, when a lot of technological developments are taking place. It is important to evaluate textbooks, which also play an important part in geography education, from the perspective of students who have just completed their high school education. To this end, the purpose of this study is to determine to what extent the geography textbook is used by high school 12th graders in their classes. The study employs the mixed research model. A Likert-type survey composed of ten questions and five variables was prepared by obtaining expert opinion. The Cronbach’s alpha coefficient of the survey was found to be 0.761. At the end of the survey, an open-ended question was addressed to the students. The study was conducted on the newly enrolled first-grade students of four verbal departments of Namık Kemal University Faculty of Arts and Sciences in the 2018-2019 academic year. The data obtained from the student survey are presented in tables along with frequency and percentage values.The students’ responses to the five-variable, ten-question Likert-type survey prepared by the researchers imply that students do not frequently use the geography textbook when they are in the 12th grade, especially in the process of preparing for the university entrance exam.
Comparison of pulse contour, aortic Doppler ultrasound and bioelectrical impedance estimates of stroke volume during rapid changes in blood pressure
Authors: Gibbons Travis D. , Zuj Kathryn A. , Peterson Sean D. , Hughson Richard L. 
Published: December 2018

New Findings
What is the central question of this study?
Pulse contour analysis of the finger arterial pressure by Windkessel modelling is commonly used to estimate stroke volume continuously. But is it valid during dynamic changes in blood pressure?

What is the main finding and its importance?
Second‐by‐second analysis revealed that pulse contour analysis underestimated stroke volume by up to 25% after standing from a squat, and 16% after standing thigh‐cuff release, when compared with aortic Doppler ultrasound estimates. These results reveal that pulse contour analysis of stroke volume should be interpreted with caution during rapid changes in physiological state.

AbstractDynamic measurements of stroke volume (SV) and cardiac output provide an index of central haemodynamics during transitional states, such as postural changes and onset of exercise. The most widely used method to assess dynamic fluctuations in SV is the Modelflow method, which uses the arterial blood pressure waveform along with age‐ and sex‐specific aortic properties to compute beat‐to‐beat estimates of aortic flow. Modelflow has been validated against more direct methods in steady‐state conditions, but not during dynamic changes in physiological state, such as active orthostatic stress testing. In the present study, we compared the dynamic SV responses from Modelflow (SVMF), aortic Doppler ultrasound (SVU/S) and bioelectrical impedance analysis (SVBIA) during two different orthostatic stress tests, a squat‐to‐stand (S‐S) transition and a standing bilateral thigh‐cuff release (TCR), in 15 adults (six females). Second‐by‐second analysis revealed that when compared with estimates of SV by aortic Doppler ultrasound, Modelflow underestimated SV by up to 25% from 3 to 11 s after standing from the squat position and by up to 16% from 3 to 7 s after TCR (P < 0.05). The SVMF and SVBIA were similar during the first minute of the S‐S transition, but were different 3 s after TCR and at intermittent time points between 34 and 44 s (P < 0.05). These findings indicate that the physiological conditions elicited by orthostatic stress testing violate some of the inherent assumptions of Modelflow and challenge models used to interpret bioelectrical impedance responses, resulting in an underestimation in SV during rapid changes in physiological state.
Paravascular spaces: entry to or exit from the brain?
Authors: Bakker Erik N. T. P. , Naessens Daphne M. P. , VanBavel Ed 
Published: December 2018

New Findings
What is the topic of this review?
In this symposium report, we review the glymphatic clearance from the brain.

What advances does it highlight?
Evaluation of the evidence indicates that cerebrospinal fluid flows along paravascular spaces at the surface of the brain. However, bulk flow along penetrating arteries into the brain, followed by exit along veins, requires further confirmation. Clearance from the brain, based on mixing, might provide an alternative explanation for experimental findings.

AbstractThe interstitial fluid of the brain provides the environment for proper neuronal function. Maintenance of the volume and composition of interstitial fluid requires regulation of the influx and removal of water, ions, nutritive and waste products. The recently described glymphatic pathway might contribute to some of these functions. It is proposed that cerebrospinal fluid enters the brain via paravascular spaces along arteries, mixes with interstitial fluid, and leaves the brain via paravascular spaces along veins. In this symposium report, we review the glymphatic concept, its concerns, and alternative views on interstitial fluid–cerebrospinal fluid exchange.
Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial–Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis
Authors: Yang Fan , Takagaki Yuta , Yoshitomi Yasuo , Ikeda Takayuki , Li Jinpeng , Kitada Munehiro , Kumagai Asako , Kawakita Emi , Shi Sen , Kanasaki Keizo , Koya Daisuke 
Published: December 2018

Abstract

Dipeptidyl peptidase (DPP)-4 is a multifunctional glycoprotein involved in various biological and pathologic processes. DPP-4 has been widely recognized as a therapeutic target for type 2 diabetes mellitus but is also implicated in the development of human malignancies. Here, we show that inhibition of DPP-4 accelerates breast cancer metastasis via induction of CXCL12/CXCR4, which activates mTOR to promote epithelial–mesenchymal transition (EMT). In cultured cells, DPP-4 knockdown induced EMT and cell migration. Treatment with the DPP-4 inhibitor KR62436 (KR) promoted primary tumor growth and lung metastasis in a 4T1 tumor allograft mouse model; DPP-4 knockdown in 4T1 cells displayed similar phenotypes in vivo and in vitro. KR treatment enhanced the levels of CXCL12/CXCR4 and phosphorylated mTOR, which were associated with the induction of EMT in metastatic cancer cells. KR-induced EMT in cancer cells was inhibited by treatment with the CXCR4 inhibitor AMD3100 or the mTOR inhibitor rapamycin, and AMD3100 suppressed KR-induced metastasis in vivo. Our findings suggest that DPP-4 plays a significant role in cancer biology and that inhibition of DPP-4 promotes cancer metastasis via induction of the CXCL12/CXCR4/mTOR/EMT axis.

Significance:
These findings reveal that inhibition of DPP-4 increases the metastatic potential of breast cancer. This is especially important given the potential use of DPP-4 inhibition as a therapeutic strategy for type 2 diabetes.
Hemodynamic Markers in the Anterior Circulation as Predictors of Recurrent Stroke in Patients With Intracranial Stenosis
Authors: Wabnitz Ashley M. , Derdeyn Colin P. , Fiorella David J. , Lynn Michael J. , Cotsonis George A. , Liebeskind David S. , Waters Michael F. , Lutsep Helmi , López-Cancio Elena , Turan Tanya N. , Montgomery Jean , Janis L. Scott , Lane Bethany , Chimowitz Marc I. ,   for the SAMMPRIS Investigators
Published: December 2018

Background and Purpose—
Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS.

Methods—

This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ
2
tests were performed to assess associations of infarct patterns and collateral flow with rates of recurrent stroke.

Results—

Of 101 patients who qualified, 14 of 53 (26.4%) with borderzone infarcts, 2 of 24 (8.3%) with core middle cerebral artery infarcts, and 3 of 24 (12.5%) with perforator infarcts had a recurrent stroke in the territory (
P
=0.14 for comparing the 3 groups,
P
=0.052 for borderzone versus nonborderzone). Of 82 patients with collateral flow assessment, 30 of 43 (70%) with borderzone infarcts, 7 of 19 (37%) with core middle cerebral artery infarcts, and 11 of 20 (55%) with perforator infarcts had impaired collateral flow distal to the stenosis (
P
=0.049). Patients with borderzone infarcts and impaired collateral flow had the highest risk of recurrent stroke (37%).

Conclusions—
Borderzone infarcts and impaired collateral flow identify a subgroup of patients with intracranial stenosis who are at particularly high risk of recurrent stroke on medical treatment.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
.

Unique identifier: NCT00576693.