bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parent Experience With Volunteers and Support Groups in a Multidisciplinary Difference of Sex Development Clinic
Authors: Nokoff Natalie , Ariefdjohan Merlin , Travers Sharon , Buchanan Cindy 
Published: September 2019

Objective: Despite recommendations that clinics for children with a difference of sex development (DSD) should include peer support, information on how to provide this support is lacking. We utilized a mixed-methods program evaluation to evaluate family satisfaction with our clinic-based volunteers (who either have a DSD themselves or are a parent of a child with a DSD) and to understand the experience of these volunteers. Method: Parents ( n = 29) of a child with a DSD completed an electronic survey. Interviews were conducted with 3 clinic volunteers. Results: Most participants (72%) met with a clinic volunteer, and the majority (81%) rated their interaction as helpful. Most common topics discussed between parents and volunteers included connecting to support groups (81%), their child’s future (62%), and learning about their child’s diagnosis (48%). Half of the parents (48%) attended an postclinic support group lunch, and 43% of these attendees rated the lunch session as helpful. Parents who attended a lunch liked the experience because they met other families with a child with a similar medical condition (100%) and met volunteers with a similar medical condition (64%), and this helped them think more positively about their child’s future (64%). Those who did not attend a lunch cited logistical reasons for not attending. Conclusions: Incorporating clinic volunteers into a multidisciplinary DSD clinic is associated with high reported rates of satisfaction by families and volunteers. Implications for Impact Statement Adult volunteers with a difference of sex development are rarely incorporated into multidisciplinary pediatric programs. This single-site study showed that most parents who met with a volunteer in the clinic found their interaction to be helpful in coping with their child’s condition.
Active PLK1-driven metastasis is amplified by TGF-β signaling that forms a positive feedback loop in non-small cell lung cancer
Authors: Shin Sol-Bi , Jang Hay-Ran , Xu Rong , Won Jae-Yeon , Yim Hyungshin 
Published: September 2019

AbstractEarly findings that PLK1 is highly expressed in cancer have driven an exploration of its functions in metastasis. However, whether PLK1 induces metastasis in vivo and its underlying mechanisms in NSCLC have not yet been determined. Here, we show that the expression of active PLK1 phosphorylated at T210, abundant in TGF-β-treated lung cells, potently induced metastasis in a tail-vein injection model. Active PLK1 with intact polo-box and ATP-binding domains accelerated cell motility and invasiveness by triggering EMT reprogramming, whereas a phosphomimetic version of p-S137-PLK1 did not, indicating that the phosphorylation status of PLK1 may determine the cell traits. Active PLK1-driven invasiveness upregulated TGF-β signaling and TSG6 encoded by TNFAIP6. Loss of TNFAIP6 disturbed the metastatic activity induced by active PLK1 or TGF-β. Clinical relevance shows that PLK1 and TNFAIP6 are strong predictors of poor survival rates in metastatic NSCLC patients. Therefore, we suggest that active PLK1 promotes metastasis by upregulating TGF-β signaling, which amplifies its metastatic properties by forming a positive feedback loop and that the PLK1/TGF-β-driven metastasis is effectively blocked by targeting PLK1 and TSG6, providing PLK1 and TSG6 as negative markers for prognostics and therapeutic targets in metastatic NSCLC.
A checklist for maximizing reproducibility of ecological niche models
Authors: Feng Xiao , Park Daniel S. , Walker Cassondra , Peterson A. Townsend , Merow Cory , Papeş Monica 
Published: September 2019

AbstractReporting specific modelling methods and metadata is essential to the reproducibility of ecological studies, yet guidelines rarely exist regarding what information should be noted. Here, we address this issue for ecological niche modelling or species distribution modelling, a rapidly developing toolset in ecology used across many aspects of biodiversity science. Our quantitative review of the recent literature reveals a general lack of sufficient information to fully reproduce the work. Over two-thirds of the examined studies neglected to report the version or access date of the underlying data, and only half reported model parameters. To address this problem, we propose adopting a checklist to guide studies in reporting at least the minimum information necessary for ecological niche modelling reproducibility, offering a straightforward way to balance efficiency and accuracy. We encourage the ecological niche modelling community, as well as journal reviewers and editors, to utilize and further develop this framework to facilitate and improve the reproducibility of future work. The proposed checklist framework is generalizable to other areas of ecology, especially those utilizing biodiversity data, environmental data and statistical modelling, and could also be adopted by a broader array of disciplines.
Glucagon-like peptide-2 rescues memory impairments and neuropathological changes in a mouse model of dementia induced by the intracerebroventricular administration of streptozotocin
Authors: Sasaki-Hamada Sachie , Ikeda Masaatsu , Oka Jun-Ichiro 
Published: September 2019

AbstractGlucagon-like peptide 2 (GLP-2) is derived from the proglucagon gene expressed in the intestines, pancreas and brain. Our previous study showed that GLP-2 improved lipopolysaccharide-induced memory impairments. The current study was designed to further investigated the potential of GLP-2 in memory impairment induced by intracerebroventricular administration of streptozotocin (ICV-STZ) in mice, which have been used as an animal model of sporadic Alzheimer’s disease (AD). STZ was administered on alternate days (Day-1 and Day-3) in order to induce dementia in male ddY mice. ICV-STZ-treated mice were administered GLP-2 (0.6 μg/mouse, ICV) for 5 days from 14 days after the first ICV administration of STZ. In these mice, we examined spatial working memory, the biochemical parameters of oxidative stress, or neurogenesis. The GLP-2 treatment restored spatial working memory in ICV-STZ-treated mice. ICV-STZ-treated mice showed markedly increased thiobarbituric acid reactive species (TBARS) and decreased glutathione (GSH) levels, and GLP-2 significantly restored these ICV-STZ-induced changes. GLP-2 also significantly restored neurogenesis in the subgranular zone of the dentate gyrus in ICV-STZ-treated mice. We herein demonstrated that GLP-2 significantly restored ICV-STZ-induced memory impairments as well as biochemical and histopathological alterations, and accordingly, propose that the memory restorative ability of GLP-2 is due to its potential to reduce oxidative stress.
Integration of flux measurements and pharmacological controls to optimize stable isotope-resolved metabolomics workflows and interpretation
Authors: Lorkiewicz Pawel K. , Gibb Andrew A. , Rood Benjamin R. , He Liqing , Zheng Yuting , Clem Brian F. , Zhang Xiang , Hill Bradford G. 
Published: September 2019

AbstractStable isotope-resolved metabolomics (SIRM) provides information regarding the relative activity of numerous metabolic pathways and the contribution of nutrients to specific metabolite pools; however, SIRM experiments can be difficult to execute, and data interpretation is challenging. Furthermore, standardization of analytical procedures and workflows remain significant obstacles for widespread reproducibility. Here, we demonstrate the workflow of a typical SIRM experiment and suggest experimental controls and measures of cross-validation that improve data interpretation. Inhibitors of glycolysis and oxidative phosphorylation as well as mitochondrial uncouplers serve as pharmacological controls, which help define metabolic flux configurations that occur under well-controlled metabolic states. We demonstrate how such controls and time course labeling experiments improve confidence in metabolite assignments as well as delineate metabolic pathway relationships. Moreover, we demonstrate how radiolabeled tracers and extracellular flux analyses integrate with SIRM to improve data interpretation. Collectively, these results show how integration of flux methodologies and use of pharmacological controls increase confidence in SIRM data and provide new biological insights.
Structural modeling and role of HAX-1 as a positive allosteric modulator of human serine protease HtrA2
Authors: Chaganti Lalith K. , Dutta Shubhankar , Kuppili Raja Reddy , Mandal Mriganka , Bose Kakoli 
Published: September 2019

AbstractHAX-1, a multifunctional protein involved in cell proliferation, calcium homeostasis, and regulation of apoptosis, is a promising therapeutic target. It regulates apoptosis through multiple pathways, understanding of which is limited by the obscurity of its structural details and its intricate interaction with its cellular partners. Therefore, using computational modeling, biochemical, functional enzymology and spectroscopic tools, we predicted the structure of HAX-1 as well as delineated its interaction with one of it pro-apoptotic partner, HtrA2. In this study, three-dimensional structure of HAX-1 was predicted by threading and ab initio tools that were validated using limited proteolysis and fluorescence quenching studies. Our pull-down studies distinctly demonstrate that the interaction of HtrA2 with HAX-1 is directly through its protease domain and not via the conventional PDZ domain. Enzymology studies further depicted that HAX-1 acts as an allosteric activator of HtrA2. This ‘allosteric regulation’ offers promising opportunities for the specific control and functional modulation of a wide range of biological processes associated with HtrA2. Hence, this study for the first time dissects the structural architecture of HAX-1 and elucidates its role in PDZ-independent activation of HtrA2.
Silencing of SPARC represses heterotopic ossification via inhibition of the MAPK signaling pathway
Authors: Wang Qianjun , Yang Qianqian , Zhang Ali , Kang Zhiqiang , Wang Yingsheng , Zhang Zhentao 
Published: September 2019

Abstract
Heterotopic ossification (HO), the pathologic formation of extraskeletal bone, can be disabling and lethal. However, the underlying molecular mechanisms were largely unknown. The present study aimed to clarify the involvement of secreted protein acidic and rich in cysteine (SPARC) and the underlying mechanism in rat model of HO. The mechanistic investigation on roles of SPARC in HO was examined through gain- and loss-of-function approaches of SPARC, with alkaline-phosphatase (ALP) activity, mineralized nodules, and osteocalcin (OCN) content measured. To further confirm the regulatory role of SPARC, levels of mitogen-activated protein kinase (MAPK) signaling pathways-related proteins (extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38, nuclear factor κ-B (NF-κB), and IkB kinase β (IKKβ)) were determined. Bone marrow mesenchymal stem cells were treated with pathway inhibitor to investigate the relationship among SPARC, MAPK signaling pathway, and HO. The results suggested that SPARC expression was up-regulated in Achilles tendon tissues of HO rats. Silencing of SPARC could decrease phosphorylation of ERK, JNK, p38, NF-κB, and IKKβ. Additionally, silencing of SPARC or inhibition of MAPK signaling pathway could reduce the ALP activity, the number of mineralized nodules, and OCN content, thus impeding HO. To sum up, our study identifies the inhibitory role of SPARC gene silencing in HO via the MAPK signaling pathway, suggesting SPARC presents a potential target for HO therapy.
Fluency Strategies of Spanish–English Bilinguals Who Stutter: A Thematic Analysis
Authors: Medina Angela M. , Pereira Tiziana , Muñoz Diana , Palacios Grisel , Perez Vanessa 
Published: September 2019

Purpose
Stuttering is multifaceted in that the frequency and types of behaviors vary across speakers, contexts, and languages. Similarly, bilingualism varies in language history, levels of proficiency, and languages spoken. The variations in bilingualism make it difficult to investigate and result in knowledge gaps about the bilingual stuttering experience. The purpose of this exploratory, qualitative study is to identify and examine fluency-inducing strategies used by Spanish–English bilingual adults who stutter.

Method
Twenty Spanish–English bilingual adults who stutter, ages 18–61 years, answered open-ended questions about their stuttering and language history via an online survey. Thematic analysis procedures were used to explore participants' narrative responses to 2 survey items regarding fluency-inducing strategies.

Result
Three major themes emerged from participants' responses regarding self-reported strategies: (a) clinical techniques, (b) focused breathing, and (c) idiosyncratic practices. Participants reported using clinical techniques classified as fluency shaping, stuttering modification, or both approaches. Focused breathing was used as both an anticipatory and a recovery strategy. Idiosyncratic practices included physiological changes, listener-focused strategies, emotional regulation, and switching words. When asked specifically about use of code-switching for the 2nd question, half of the participants stated that they do switch languages to induce fluency.

Conclusion
Clinical implications include the need for individualized client education, a thorough assessment of avoidance and escape behaviors, and customized treatment programs for bilinguals who stutter.
Thermal evolution of rocky exoplanets with a graphite outer shell
Authors: Hakim Kaustubh , van den Berg Arie , Vazan Allona , Höning Dennis , van Westrenen Wim , Dominik Carsten 
Published: September 2019

Context.The presence of rocky exoplanets with a large refractory carbon inventory is predicted by chemical evolution models of protoplanetary disks of stars with photospheric C/O > 0.65, and by models studying the radial transport of refractory carbon. High-pressure high-temperature laboratory experiments show that most of the carbon in these exoplanets differentiates into a graphite outer shell.Aims.Our aim is to evaluate the effects of a graphite outer shell on the thermal evolution of rocky exoplanets containing a metallic core and a silicate mantle.Methods.We implemented a parameterized model of mantle convection to determine the thermal evolution of rocky exoplanets with graphite layer thicknesses up to 1000 km.Results.We find that because of the high thermal conductivity of graphite, conduction is the dominant heat transport mechanism in a graphite layer for long-term evolution (>200 Myr). The conductive graphite shell essentially behaves like a stagnant lid with a fixed thickness. Models of Kepler-37b (Mercury-size) and a Mars-sized exoplanet show that a planet with a graphite lid cools faster than a planet with a silicate lid, and a planet without a stagnant lid cools the fastest. A graphite lid needs to be approximately ten times thicker than a corresponding silicate lid to produce similar thermal evolution.
VLTI/PIONIER survey of disks around post-AGB binaries
Authors: Kluska J. , Van Winckel H. , Hillen M. , Berger J.-P. , Kamath D. , Le Bouquin J.-B. , Min M. 
Published: September 2019

Context.Post-asymptotic giant branch (AGB) binaries are surrounded by circumbinary disks of gas and dust that are similar to protoplanetary disks found around young stars.Aims.We aim to understand the structure of these disks and identify the physical phenomena at play in their very inner regions. We want to understand the disk-binary interaction and to further investigate the comparison with protoplanetary disks.Methods.We conducted an interferometric snapshot survey of 23 post-AGB binaries in the near-infrared (H-band) using VLTI/PIONIER. We fit the multi-wavelength visibilities and closure phases with purely geometrical models with an increasing complexity (including two point-sources, an azimuthally modulated ring, and an over-resolved flux) in order to retrieve the sizes, temperatures, and flux ratios of the different components.Results.All sources are resolved and the different components contributing to theH-band flux are dissected. The environment of these targets is very complex: 13/23 targets need models with thirteen or more parameters to fit the data. We find that the inner disk rims follow and extend the size-luminosity relation established for disks around young stars with an offset toward larger sizes. The measured temperature of the near-infrared circumstellar emission of post-AGB binaries is lower (Tsub~ 1200 K) than for young stars, which is probably due to a different dust mineralogy and/or gas density in the dust sublimation region.Conclusions.The dusty inner rims of the circumbinary disks around post-AGB binaries are ruled by dust sublimation physics. Additionally a significant amount of the circumstellarH-band flux is over-resolved (more than 10% of the non-stellar flux is over-resolved in 14 targets). This hints that a source of unknown origin, either a disk structure or outflow. The amount of over-resolved flux is larger than around young stars. Due to the complexity of these targets, interferometric imaging is a necessary tool to reveal the interacting inner regions in a model-independent way.
Probing planet formation and disk substructures in the inner disk of Herbig Ae stars with CO rovibrational emission
Authors: Bosman Arthur D. , Banzatti Andrea , Bruderer Simon , Tielens Alexander G. G. M. , Blake Geoffrey A. , van Dishoeck Ewine F. 
Published: September 2019

Context. CO rovibrational lines are efficient probes of warm molecular gas and can give unique insights into the inner 10 AU of proto-planetary disks, effectively complementing ALMA observations. Recent studies find a relation between the ratio of lines originating from the second and first vibrationally excited state, denoted as v2∕v1, and the Keplerian velocity or emitting radius of CO. Counterintuitively, in disks around Herbig Ae stars the vibrational excitation is low when CO lines come from close to the star, and high when lines only probe gas at large radii (more than 5 AU). The v2∕v1 ratio is also counterintuitively anti-correlated with the near-infrared (NIR) excess, which probes hot and warm dust in the inner disk.
Aims. We aim to find explanations for the observed trends between CO vibrational ratio, emitting radii and NIR excess, and to identify their implications in terms of the physical and chemical structure of inner disks around Herbig stars.
Methods. First, slab model explorations in local thermal equilibrium (LTE) and non-LTE are used to identify the essential parameter space regions that can produce the observed CO emission. Second, we explore a grid of thermo-chemical models using the DALI code, varying gas-to-dust ratio and inner disk radius. Line flux, line ratios, and emitting radii are extracted from the simulated lines in the same way as the observations and directly compared to the data.
Results. Broad CO lines with low vibrational ratios are best explained by a warm (400–1300 K) inner disk surface with gas-to-dust ratios below 1000 (NCO < 1018 cm−2); no CO is detected within or at the inner dust rim, due to dissociation at high temperatures. In contrast, explaining the narrow lines with high vibrational ratios requires an inner cavity of a least 5 AU in both dust and gas, followed by a cool (100–300 K) molecular gas reservoir with gas-to-dust ratios greater than 10 000 (NCO > 1018 cm−2) at the cavity wall. In all cases, the CO gas must be close to thermalization with the dust (Tgas ~ Tdust).
Conclusions. The high gas-to-dust ratios needed to explain high v2∕v1 in narrow CO lines for a subset of group I disks can be naturally interpreted as due to the dust traps that are proposed to explain millimeter dust cavities. The dust trap and the low gas surface density inside the cavity are consistent with the presence of one or more massive planets. The difference between group I disks with low and high NIR excess can be explained by gap opening mechanisms that do or do not create an efficient dust trap, respectively. The broad lines seen in most group II objects indicate a very flat disk in addition to inner disk substructures within 10 AU that can be related to the substructures recently observed with ALMA. We provide simulated ELT-METIS images to directly test these scenarios in the future.
Kinematics around the B335 protostar down to au scales
Authors: Bjerkeli Per , Ramsey Jon P. , Harsono Daniel , Calcutt Hannah , Kristensen Lars E. , van der Wiel Matthijs H. D. , Jørgensen Jes K. , Muller Sébastien , Persson Magnus V. 
Published: September 2019

Context. The relationship between outflow launching and the formation of accretion disks around young stellar objects is still not entirely understood, which is why spectrally and spatially resolved observations are needed. Recently, the Atacama Large Millimetre/sub-millimetre Array (ALMA) carried out long-baseline observations towards a handful of young sources, revealing connections between outflows and the inner regions of disks.
Aims. Here we aim to determine the small-scale kinematical and morphological properties of the outflow from the isolated protostar B335 for which no Keplerian disk has, so far, been observed on scales down to 10 au.
Methods. We used ALMA in its longest-baseline configuration to observe emission from CO isotopologues, SiO, SO2, and CH3OH. The proximity of B335 provides a resolution of ~3 au (0.03′′). We also combined our long-baseline data with archival observations to produce a high-fidelity image covering scales up to 700 au (7′′).
Results. 12CO has an X-shaped morphology with arms ~50 au in width that we associate with the walls of an outflow cavity, similar to what is observed on larger scales. Long-baseline continuum emission is confined to <7 au from the protostar, while short-baseline continuum emission follows the 12CO outflow and cavity walls. Methanol is detected within ~30 au of the protostar. SiO is also detected in the vicinity of the protostar, but extended along the outflow.
Conclusions. The 12CO outflow does not show any clear signs of rotation at distances ≳30 au from the protostar. SiO traces the protostellar jet on small scales, but without obvious rotation. CH3OH and SO2 trace a region <16 au in diameter, centred on the continuum peak, which is clearly rotating. Using episodic, high-velocity, 12CO features, we estimate the launching radius of the outflow to be <0.1 au and dynamical timescales of the order of a few years.