bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity
Authors: Weiskopf Daniela , Bangs Derek J. , Sidney John , Kolla Ravi V. , De Silva Aruna D. , de Silva Aravinda M. , Crotty Shane , Peters Bjoern , Sette Alessandro 
Published: July 2015

SignificanceInfections with any of the four dengue virus serotypes (DENV 1–4) are the most prevalent and rapidly spreading mosquito-borne viral infections in humans. There is no treatment or vaccine currently available. We found that the virus-specific cells display a highly polarized cytotoxic phenotype that correlated with expression of a protective HLA DR allele. Although the occurrence of cytotoxic CD4+T cells in humans has been described in the context of some chronic viral infections, to our knowledge, this is the first report of ex vivo cytotoxic CD4+activity after exposure with an acute virus. These results will help shed light on the specific role of CD4+T cells in DENV infection and may help in finding a correlate of protection.
How amide hydrogens exchange in native proteins
Authors: Persson Filip , Halle Bertil 
Published: July 2015

Significance
Proteins tend to be compactly folded but occasionally undergo conformational fluctuations that expose even the most deeply buried parts of the polypeptide chain to external solvent. As a consequence, the backbone amide hydrogens can exchange with water hydrogens. Monitoring such hydrogen exchange is a well-established method for characterizing protein flexibility, even though the nature of the ‟open” exchange-competent state is unknown. We have used an ultralong computer simulation to identify the elusive open state as transient (100 ps), locally distorted conformations where the N–H group coordinates two water molecules.
Knockout silkworms reveal a dispensable role for juvenile hormones in holometabolous life cycle
Authors: Daimon Takaaki , Uchibori Miwa , Nakao Hajime , Sezutsu Hideki , Shinoda Tetsuro 
Published: July 2015

Significance
The juvenile–adult transition is a key developmental process in organisms. A long-held paradigm in insect endocrinology is that juvenile hormones (JHs) prevent metamorphosis until larvae attain an appropriate size for the juvenile–adult transition. However, little is known about the roles for JHs during embryonic and very early larval stages. We established knockouts of the silkworm, a classic model insect, and show that embryogenesis and maintenance of juvenile status during the early larval stages are largely independent of JHs or the JH-signaling pathway. Our results also suggest that an unidentified factor or signal is required to acquire the competence for metamorphosis. The presence of this factor has long been overlooked because JHs may conceal its action.
The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions
Authors: Tapmeier Thomas T. , Moshnikova Anna , Beech John , Allen Danny , Kinchesh Paul , Smart Sean , Harris Adrian , McIntyre Alan , Engelman Donald M. , Andreev Oleg A. , Reshetnyak Yana K. , Muschel Ruth J. 
Published: July 2015

Significance
Acidic pH may distinguish aggressive from more indolent cancers. The limitation on testing this hypothesis to date has been the difficulty of measuring acidic pH in cancers. Here we show that retention of the pH low insertion peptide (pHLIP) Variant 3 (Var3) reflects acidic pH. Using pHLIP Var3, we show its ability to detect cancer with a low false-positive rate in a genetically engineered model of murine breast cancer, paving the way for testing this probe in clinical situations.
Norbin ablation results in defective adult hippocampal neurogenesis and depressive-like behavior in mice
Authors: Wang Hong , Warner-Schmidt Jennifer , Varela Santiago , Enikolopov Grigori , Greengard Paul , Flajolet Marc 
Published: July 2015

Significance
G protein-coupled receptors constitute an important class of receptors and represent a family of choice for therapeutic interventions for multiple diseases and disorders. One of these metabotropic glutamate receptors, mGluR5, is highly relevant because of its biological importance for various medical conditions, including major depressive disorder (MDD). In a search of mGluR5 modulators we identified Norbin as a key regulator. Here we demonstrate in vivo that Norbin significantly influences hippocampal neurogenesis and that both the proliferation and survival of newborn neurons are impaired in the absence of Norbin. Furthermore, the use of three well-established behavioral paradigms indicated that Norbin-KO mice display depressive-like characteristics. Thus interventions that could boost Norbin function might be beneficial to treat MDD symptoms.
Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord
Authors: Wang Yuxuan , Springer Simeon , Zhang Ming , McMahon K. Wyatt , Kinde Isaac , Dobbyn Lisa , Ptak Janine , Brem Henry , Chaichana Kaisorn , Gallia Gary L. , Gokaslan Ziya L. , Groves Mari L. , Jallo George I. , Lim Michael , Olivi Alessandro , Quinones-Hinojosa Alfredo , Rigamonti Daniele , Riggins Greg J. , Sciubba Daniel M. , Weingart Jon D. , Wolinsky Jean-Paul , Ye Xiaobu , Oba-Shinjo Sueli Mieko , Marie Suely K. N. , Holdhoff Matthias , Agrawal Nishant , Diaz Luis A. , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Bettegowda Chetan 
Published: July 2015

Significance
Outcomes for individuals with central nervous system (CNS) malignancies remain abysmal. A major challenge in managing these patients is the lack of reliable biomarkers to monitor tumor dynamics. Consequently, many patients undergo invasive surgical procedures to determine disease status or experience treatment delays when radiographic testing fails to show disease progression. We show here that primary CNS malignancies shed detectable levels of tumor DNA into the surrounding cerebrospinal fluid (CSF), which could serve as a sensitive and exquisitely specific marker for quantifying tumor burden without invasive biopsies. Therefore, assessment of such tumor-derived DNA in the CSF has the potential to improve the management of patients with primary CNS tumors.
Replacing SNAP-25b with SNAP-25a expression results in metabolic disease
Authors: Valladolid-Acebes Ismael , Daraio Teresa , Brismar Kerstin , Harkany Tibor , Ögren Sven Ove , Hökfelt Tomas G. M. , Bark Christina 
Published: July 2015

Significance
Our changed lifestyle, including decreased physical activity and increased food consumption, is leading to a pandemic of obesity and type 2 diabetes, the metabolic syndrome. Impaired release of hormones, such as insulin, from excitable cells usually is considered a symptom, not a cause, of this syndrome. Here, however, we show that a small genetic modification, replacing synaptosomal-associated protein of 25 kDa (SNAP-25), SNAP-25b with SNAP-25a in the machinery mediating stimulus-dependent release of hormones and neurotransmitters is sufficient to provoke hypothalamic dysfunction, obesity, and type 2 diabetes. When combined with a Western diet, this genetic condition triggers severe diabesity. Our work expands previous knowledge supporting the notion that many individuals have an increased susceptibility to developing metabolic disease because of a genetic predisposition.
Prospective isolation of human erythroid lineage-committed progenitors
Authors: Mori Yasuo , Chen James Y. , Pluvinage John V. , Seita Jun , Weissman Irving L. 
Published: July 2015

SignificanceWe have identified the first step of erythrocyte lineage commitment in human bone marrow as a CD71intermediate/+CD105+cell fraction of a previously defined megakaryocyte/erythrocyte progenitor population. This purification could be a useful tool for studying physiological and pathological red blood cell development, and should be analyzed in patients suffering from anemia or erythrocytosis such as in myelodysplastic syndrome or polycythemia vera.
Quantum dimer model for the pseudogap metal
Authors: Punk Matthias , Allais Andrea , Sachdev Subir 
Published: July 2015

Significance
The most interesting states of the copper oxide compounds are not the superconductors with high critical temperatures. Instead, the novelty lies primarily in the higher temperature metallic “normal” states from which the superconductors descend. Here, we develop a simple, intuitive model for the physics of the metal at low carrier density, in the “pseudogap” regime. This model describes an exotic metal that is similar in many respects to simple metals like silver. However, the simple metallic character coexists with “topological order” and long-range quantum entanglement previously observed only in exotic insulators or fractional quantum Hall states in very high magnetic fields. Our model is compatible with many recent observations, and we discuss more definitive experimental tests.
Conformational propensities of intrinsically disordered proteins influence the mechanism of binding and folding
Authors: Arai Munehito , Sugase Kenji , Dyson H. Jane , Wright Peter E. 
Published: July 2015

Significance
Intrinsically disordered proteins play a central role in cellular signaling and regulatory networks. Many regulatory proteins contain disordered recognition motifs that fold upon binding to their cellular targets, by mechanisms that are poorly understood. Here we show that the disordered transactivation domain of the transcription factor c-Myb binds to the KIX domain of the transcriptional coactivator cAMP-response element binding (CREB-binding) protein (CBP) by a mechanism that involves elements of conformational selection and induced fit. In contrast, the phosphorylated kinase-inducible activation domain of CREB binds to the same site on KIX by an induced-fit mechanism. The intrinsic secondary structure propensities of these two disordered proteins determine their binding mechanisms, consistent with their functions as inducible and constitutive transcriptional activators.
Characteristics of MHD instabilities limiting the beta value in LHD
Authors: Sakakibara S. , Watanabe K.Y. , Takemura Y. , Okamoto M. , Ohdachi S. , Suzuki Y. , Narushima Y. , Ida K. , Yoshinuma M. , Tanaka K. , Tokuzawa T. , Yamada I. , Yamada H. , Takeiri Y. 
Published: July 2015

Abstract
Effects of low-n magnetohydrodynamic instabilities on plasma performance have been assessed in the regime where an achieved beta value is limited by instabilities. The unstable regime of an ideal interchange mode is characterized by enhanced magnetic hill and reduced magnetic shear. Experiments have clarified that (i) low-n modes are significantly destabilized in the ideal-unstable configurations and lead to degradation of central beta by at most 60%, and (ii) the degree of their damages strongly depends on the mode rotation velocity. The occurrence of the minor collapse is independent of an existence of an error field.
Identification of the energetic-particle driven GAM in the LHD
Authors: Ido T. , Osakabe M. , Shimizu A. , Watari T. , Nishiura M. , Toi K. , Ogawa K. , Itoh K. , Yamada I. , Yasuhara R. , Yoshimura Y. , Kato S. 
Published: July 2015

Abstract

n = 0 modes with frequency chirping have been observed by a heavy ion beam probe and Mirnov coils in the large helical device plasmas, where n is the toroidal mode number. The spatial structures of the electrostatic potential fluctuation and the density fluctuation correspond to those of the geodesic acoustic mode (GAM). The modes are observed only during the tangential neutral beam injection with the energy of 175 keV. The energy spectra of fast ions measured by a neutral particle analyzer implies that the modes are excited by the fast ions through the inverse Landau damping. The absolute values and the temperature dependence of the frequency of the mode can be interpreted by the dispersion relation taking into account the measured energy spectra of the fast ions. Therefore, the observed n = 0 modes are identified as the energetic-particle driven GAM.
Experimental turbulence studies for gyro-kinetic code validation using advanced microwave diagnostics
Authors: Stroth U. , Bañón Navarro A. , Conway G.D. , Görler T. , Happel T. , Hennequin P. , Lechte C. , Manz P. , Simon P. , Biancalani A. , Blanco E. , Bottereau C. , Clairet F. , Coda S. , Eibert T. , Estrada T. , Fasoli A. , Guimarais L. , Gürcan Ö. , Huang Z. , Jenko F. , Kasparek W. , Koenen C. , Krämer-Flecken A. , Manso M.E. , Medvedeva A. , Molina D. , Nikolaeva V. , Plaum B. , Porte L. , Prisiazhniuk D. , Ribeiro T. , Scott B.D. , Siart U. , Storelli A. , Vermare L. , Wolf S. 
Published: July 2015

Abstract
For a comprehensive comparison with theoretical models and advanced numerical turbulence simulations, a large spectrum of fluctuation parameters was measured on the devices ASDEX Upgrade, TCV, and Tore-Supra. Radial profiles of scale-resolved turbulence levels in H-mode discharges are measured and compared with GENE simulations in the transition range from ion-temperature-gradient to trapped-electron-mode turbulence. Correlation reflectometry is used to study the microscopic structure of turbulence and GAMs in discharges where poloidal flow damping was varied by means of variations of the shape of the poloidal plasma cross-section and collisionality. Full-wave codes and synthetic diagnostics are applied for the interpretation of the data.
No Significant Association between Anesthesia Group Concentration and Private Insurer Payments in the United States
Authors: Sun Eric C. , Dexter Franklin , Macario Alex , Miller Thomas R. , Baker Laurence C. 
Published: July 2015

AbstractAbstract
In a review of payments from private insurers for five commonly billed anesthesia codes in 229 counties in the United States from 2002 through 2010, payments to anesthesiologists in more concentrated markets were not significantly different from payments in less concentrated markets.
Supplemental Digital Content is available in the text.

Background:
Markets for physician services are becoming increasingly concentrated, with many areas being dominated by a few groups. Antitrust authorities are concerned that increasing concentration will lead to inappropriately high payments for physician services from private insurers. The authors examined the association between market concentration and private insurer payments for anesthesia services.

Methods:
The authors obtained data on average payments from private insurers for five commonly used anesthesia Current Procedure Terminology codes for physicians located in 229 counties in the United States between 2002 and 2010. The authors calculated a measure of market concentration (the Herfindahl–Hirschman Index [HHI]) for anesthesiologists in each county using Medicare claims data. The authors then estimated the association between market concentration and private insurer payments using a difference-in-differences approach to minimize confounding.

Results:
Private insurer payments to anesthesiologists in more concentrated markets were not significantly different from payments in less concentrated markets. Compared with the 25% of counties with the least concentration (counties with an HHI in the 0th to 25th percentile), payments in counties in the 25th to 50th percentile of HHI were approximately 0.51% less (95% CI, −2.3 to 1.3%, P = 0.95), whereas payments in counties in the 50th to 75th percentile of HHI were approximately 2.8% less (95% CI, −6.7 to 1.4%, P = 0.41) and payments in counties in the 75th to 100th percentile were approximately 3.1% less (95% CI, −8.1 to 1.2%, P = 0.32).

Conclusion:
Increasing market concentration of anesthesia groups is not associated with significantly greater payments from private insurers.
Clinical Characteristics of 2 Groups of Children With Feeding Difficulties
Authors: Marshall Jeanne , Hill Rebecca J. , Ware Robert S. , Ziviani Jenny , Dodrill Pamela 
Published: July 2015

ABSTRACTObjectives:The primary aim of this study was to describe and compare the clinical characteristics of 2 groups of children presenting to a feeding clinic: children with autism spectrum disorder (ASD) and children with a nonmedically complex history (NMC). A secondary aim was to compare participants according to the degree of oral motor impairment, presence of oral hypersensitivity, and clinically significant parent stress.Methods:Children with feeding difficulties ages between 2 and 6 years were recruited. Prospective data were collected on dietary intake, general development, mealtime behaviors, oral motor skills, oral sensory processing, and parental stress via parent questionnaire and clinical assessment.Results:In total, 68 children (ASD = 33 and NMC = 35) participated in the study. Both groups presented with a large number of difficult mealtime behaviors. Although stress was elevated in both groups, parents of children in the ASD group reported significantly higher stress levels than those with children in the NMC group (mean difference 27.3 on a percentile scale, 95% confidence interval [CI] 15.5–39.2, P < 0.01). Across both groups, the majority of children presented with mild‐to‐moderate oral motor impairments (ASD = 28, 85%; NMC = 28, 80%). Children with heightened oral sensory sensitivity consumed significantly fewer unprocessed fruits and vegetables (mean difference 3.3 foods, 95% CI 1.3–5.3, P < 0.01), and their parents reported a significantly greater frequency of difficult mealtime behaviors (mean difference 5.8 behaviors, 95% CI 3.4–8.1, P < 0.01).Conclusions:Features of feeding difficulty presented similarly across the ASD and NMC groups in this study. Oral motor impairment, oral sensory sensitivity, and parental stress should not be overlooked in the management of children with feeding difficulties, regardless of etiology.
Pilot Study Evaluating Efficacy of 2 Regimens for Hypovitaminosis D Repletion in Pediatric Inflammatory Bowel Disease
Authors: Simek Robert Z. , Prince Jarod , Syed Sana , Sauer Cary G. , Martineau Bernadette , Hofmekler Tanya , Freeman Alvin J. , Kumar Archana , McElhanon Barbara O. , Schoen Bess T. , Tenjarla Gayathri , McCracken Courtney , Ziegler Thomas R. , Tangpricha Vin , Kugathasan Subra 
Published: July 2015

ABSTRACTObjectives:Vitamin D is critical for skeletal health; hypovitaminosis D is common in pediatric inflammatory bowel disease (IBD), yet optimal repletion therapy is not well studied. We aimed to conduct a pilot trial comparing the efficacy of 2 vitamin D regimens of weekly dosing for the repletion of hypovitaminosis D in pediatric IBD.Methods:Subjects identified from our IBD clinic with 25‐hydroxyvitamin D (25[OH]D) concentrations <30 ng/mL were randomized to 10,000 (n = 18) or 5000 (n = 14) IU of oral vitamin D3/10 kg body weight per week for 6 weeks. Serum 25(OH)D, Ca, and parathyroid hormone concentrations were measured at baseline, week 8, and week 12.Results:In the higher dosing group, serum 25(OH)D increased from 23.7 ± 8.5 ng/mL at baseline to 49.2 ± 13.6 ng/mL at 8 weeks; P < 0.001. In the lower dosing group, serum 25(OH)D increased from 24.0 ± 7.0 ng/mL at baseline to 41.5 ± 9.6 ng/mL at 8 weeks; P < 0.001. At 12 weeks, serum 25(OH)D concentrations were 35.1 ± 8.4 and 30.8 ± 4.2 ng/mL for the higher and lower dose regimens, respectively. Mean serum Ca and parathyroid hormone concentrations did not significantly change during the study. No patient exhibited hypercalcemia, and no serious adverse events occurred.Conclusions:Both treatment arms were safe and effective at normalizing vitamin D nutriture in pediatric IBD. Although significant repletion of 25(OH)D concentration was achieved in both dosing groups at 8 weeks, this effect was lost by the 12‐week follow‐up. Maintenance vitamin D therapy following initial repletion is likely required to maintain long‐term normalized vitamin D status.
A Rare Cause of Metabolic Acidosis
Authors: Sahbudak Bal Zumrut , Can Fulya Kamit , Anil Ayse Berna , Bal Alkan , Anil Murat , Gokalp Gamze , Yavascan Onder , Aksu Nejat 
Published: July 2015

Abstract
Oral methanol intoxication is common, but dermal intoxication is rare. We report a previously healthy 19-month-old female infant admitted to the emergency department (ED) with vomiting and tonic-clonic seizure. On physical examination, she was comatose and presented signs of decompensated shock with Kussmaul breathing. Her left thigh was edematous, with purple coloration. Methanol intoxication was suspected due to high anion gap metabolic acidosis (pH, 6.89; HCO3, <3 meq/L) and exposure to spirit-soaked bandages (%96 methanol) for 24 hours and 3 days. The patient's serum methanol level was 20.4 mg/dL. She was treated with fomepizole and continuous venovenous hemodialysis (CVVHD) in the pediatric intensive care unit, and methanol levels decreased to 0 mg/dL after 12 hours. During follow-up, massive edema and subarachnoid hemorrhage in the occipital lobe were detected by computed tomography of the brain. The patient died after 7 days.
Although methanol intoxication occurs predominantly in adults, it must be considered in children with high-anion gap metabolic acidosis. This case report demonstrates that fatal transdermal methanol intoxication can occur in children, and it is the second report in the English literature of transdermal methanol intoxication in an infant.
Tools and techniques for computational reproducibility
Authors: Piccolo Stephen R. , Frampton Michael B. 
Published: July 2015

AbstractWhen reporting research findings, scientists document the steps they followed so that others can verify and build upon the research. When those steps have been described in sufficient detail that others can retrace the steps and obtain similar results, the research is said to be reproducible. Computers play a vital role in many research disciplines and present both opportunities and challenges for reproducibility. Computers can be programmed to execute analysis tasks, and those programs can be repeated and shared with others. Due to the deterministic nature of most computer programs, the same analysis tasks, applied to the same data, will often produce the same outputs. However, in practice, computational findings often cannot be reproduced due to complexities in how software is packaged, installed, and executed—and due to limitations in how scientists document analysis steps. Many tools and techniques are available to help overcome these challenges. Here we describe seven such strategies. With a broad scientific audience in mind, we describe strengths and limitations of each approach, as well as circumstances under which each might be applied. No single strategy is sufficient for every scenario; thus we emphasize that it is often useful to combine approaches.
Scalable multi whole-genome alignment using recursive exact matching
Authors: Linthorst Jasper , Hulsman Marc , Holstege Henne , Reinders Marcel 
Published: July 2015

AbstractThe emergence of third generation sequencing technologies has brought near perfectde-novogenome assembly within reach. This clears the way towards reference-free detection of genomic variations.In this paper, we introduce a novel concept for aligning whole-genomes which allows the alignment of multiple genomes. Alignments are constructed in a recursive manner, in which alignment decisions are statistically supported. Computational performance is achieved by splitting an initial indexing data structure into a multitude of smaller indices.We show that our method can be used to detect high resolution structural variations between two human genomes, and that it can be used to obtain a high quality multiple genome alignment of at least nineteen Mycobacterium tuberculosis genomes.An implementation of the outlined algorithm called REVEAL is available on:https://github.com/jasperlinthorst/REVEAL