bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398
Authors: Wang Yanan , Hu Mo , Liu Qian , Qin Juanxiu , Dai Yingxin , He Lei , Li Tianming , Zheng Bing , Zhou Fan , Yu Kaiwen , Fang Jingyuan , Liu Xiaoyun , Otto Michael , Li Min 
Published: April 2016

AbstractNovel Staphylococcus aureus clones continue to emerge that cause infections in otherwise healthy people. One example is the sequence type (ST) 398 lineage, which we show here is increasing in importance as a significant cause of community-associated (CA) human infections in China. We have a profound lack of understanding about what determines the considerable virulence potential of such newly emerging clones. Information about the contribution to virulence of the more recently discovered ESAT-6 secretion system (ESS) has remained particularly scarce. The Chinese ST398 isolates exhibited significantly increased expression of ESS genes as compared to predominant hospital-associated clones, which we found is likely due to increased expression of the accessory gene regulator (Agr) system and control of ESS by Agr. Importantly, deletion of essB in ST398 resulted in significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models. Our results demonstrate a key function of ESS in promoting virulence and mechanisms of resistance to innate host defense in an important emerging CA-S. aureus lineage. They suggest that ESS has a so far underestimated role in promoting aggressive virulence and epidemiological success of S. aureus.
Tick receptor for outer surface protein A from Ixodes ricinus — the first intrinsically disordered protein involved in vector-microbe recognition
Authors: Urbanowicz Anna , Lewandowski Dominik , Szpotkowski Kamil , Figlerowicz Marek 
Published: April 2016

AbstractThe tick receptor for outer surface protein A (TROSPA) is the only identified factor involved in tick gut colonization by various Borrelia species. TROSPA is localized in the gut epithelium and can recognize and bind the outer surface bacterial protein OspA via an unknown mechanism. Based on earlier reports and our latest observations, we considered that TROSPA would be the first identified intrinsically disordered protein (IDP) involved in the interaction between a vector and a pathogenic microbe. To verify this hypothesis, we performed structural studies of a TROSPA mutant from Ixodes ricinus using both computational and experimental approaches. Irrespective of the method used, we observed that the secondary structure content of the TROSPA polypeptide chain is low. In addition, the collected SAXS data indicated that this protein is highly extended and exists in solution as a set of numerous conformers. These features are all commonly considered hallmarks of IDPs. Taking advantage of our SAXS data, we created structural models of TROSPA and proposed a putative mechanism for the TROSPA-OspA interaction. The disordered nature of TROSPA may explain the ability of a wide spectrum of Borrelia species to colonize the tick gut.
Subgenual cingulate cortical activity predicts the efficacy of electroconvulsive therapy
Authors: Argyelan M , Lencz T , Kaliora S , Sarpal D K , Weissman N , Kingsley P B , Malhotra A K , Petrides G 
Published: April 2016

AbstractElectroconvulsive therapy (ECT) is the most effective treatment for depression, yet its mechanism of action is unknown. Our goal was to investigate the neurobiological underpinnings of ECT response using longitudinally collected resting-state functional magnetic resonance imaging (rs-fMRI) in 16 patients with treatment-resistant depression and 10 healthy controls. Patients received bifrontal ECT 3 times a week under general anesthesia. We acquired rs-fMRI at three time points: at baseline, after the 1st ECT administration and after the course of the ECT treatment; depression was assessed with the Hamilton Depression Rating Scale (HAM-D). The primary measure derived from rs-fMRI was fractional amplitude of low frequency fluctuation (fALFF), which provides an unbiased voxel-wise estimation of brain activity. We also conducted seed-based functional connectivity analysis based on our primary findings. We compared treatment-related changes in HAM-D scores with pre- and post-treatment fALFF and connectivity measures. Subcallosal cingulate cortex (SCC) demonstrated higher BOLD signal fluctuations (fALFF) at baseline in depressed patients, and SCC fALFF decreased over the course of treatment. The baseline level of fALFF of SCC predicted response to ECT. In addition, connectivity of SCC with bilateral hippocampus, bilateral temporal pole, and ventromedial prefrontal cortex was significantly reduced over the course of treatment. These results suggest that the antidepressant effect of ECT may be mediated by downregulation of SCC activity and connectivity. SCC function may serve as an important biomarker of target engagement in the development of novel therapies for depression that is resistant to treatment with standard medications.
GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons
Authors: Lu Jun-Mei , Wang Chang-Ying , Hu Changlong , Fang Yan-Jia , Mei Yan-Ai 
Published: April 2016

GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K+ currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca2+ concentration ([Ca2+]i) in response to membrane depolarization, as determined by Ca2+ imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca2+ current (ICa) without altering steady-state activation of Ca2+ channels. Treatment with nifedipine, an inhibitor of L-type Ca2+ channels, abrogated GDF-15-induced increases in [Ca2+]i and ICa. The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TβRII phosphorylation. Given that Cav1.3 is not only a channel for Ca2+ influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TβRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons.
Pretreatment Acoustic Predictors of Gender, Femininity, and Naturalness Ratings in Individuals With Male-to-Female Gender Identity
Authors: Hardy Teresa L. D. , Boliek Carol A. , Wells Kristopher , Dearden Carol , Zalmanowitz Connie , Rieger Jana M. 
Published: April 2016

Purpose
The purpose of this study was to describe the pretreatment acoustic characteristics of individuals with male-to-female gender identity (IMtFGI) and investigate the ability of the acoustic measures to predict ratings of gender, femininity, and vocal naturalness.

Method

This retrospective descriptive study included 2 groups of participants. Speakers were IMtFGI who had not previously received communication feminization treatment (
N
= 25). Listeners were members of the lay community (
N
= 30). Acoustic data were retrospectively obtained from pretreatment recordings, and pretreatment recordings also served as stimuli for 3 perceptual rating tasks (completed by listeners).

Results

Acoustic data generally were within normal limits for male speakers. All but 2 speakers were perceived to be male, limiting information about the relationship between acoustic measures and gender perception. Fundamental frequency (reading) significantly predicted femininity ratings (
p
= .000). A total of 3 stepwise regression models indicated that minimum frequency (range task), second vowel formant (sustained vowel), and shimmer percentage (sustained vowel) together significantly predicted naturalness ratings (
p
= .005,
p
= .003, and
p
= .002, respectively).

Conclusions
Study aims were achieved with the exception of acoustic predictors of gender perception, which could be described for only 2 speakers. Future research should investigate measures of prosody, voice quality, and other aspects of communication as predictors of gender, femininity, and naturalness.
Reevaluation of the Amsterdam Inventory for Auditory Disability and Handicap Using Item Response Theory
Authors: Boeschen Hospers J. Mirjam , Smits Niels , Smits Cas , Stam Mariska , Terwee Caroline B. , Kramer Sophia E. 
Published: April 2016

Purpose
We reevaluated the psychometric properties of the Amsterdam Inventory for Auditory Disability and Handicap (AIADH; Kramer, Kapteyn, Festen, & Tobi, 1995) using item response theory. Item response theory describes item functioning along an ability continuum.

Method
Cross-sectional data from 2,352 adults with and without hearing impairment, ages 18–70 years, were analyzed. They completed the AIADH in the web-based prospective cohort study “Netherlands Longitudinal Study on Hearing.” A graded response model was fitted to the AIADH data. Category response curves, item information curves, and the standard error as a function of self-reported hearing ability were plotted.

Results
The graded response model showed a good fit. Item information curves were most reliable for adults who reported having hearing disability and less reliable for adults with normal hearing. The standard error plot showed that self-reported hearing ability is most reliably measured for adults reporting mild up to moderate hearing disability.

Conclusions
This is one of the few item response theory studies on audiological self-reports. All AIADH items could be hierarchically placed on the self-reported hearing ability continuum, meaning they measure the same construct. This provides a promising basis for developing a clinically useful computerized adaptive test, where item selection adapts to the hearing ability of individuals, resulting in efficient assessment of hearing disability.
Academic, Clinical, and Educational Experiences of Self-Identified Fluency Specialists
Authors: Coalson Geoffrey A. , Byrd Courtney T. , Rives Elizabeth 
Published: April 2016

Purpose
The purpose of the present study is to examine whether the academic, clinical, and fluency-related student experiences of professionals who self-identify as having specialized knowledge of fluency disorders differ from those who do not.

Method
An online survey was developed to identify the academic, clinical, and specific fluency-related experiences professionals had when they were undergraduate and graduate students. The survey was completed by 219 professionals within the field of speech-language pathology (122 self-identified specialists, 97 self-identified non-specialists).

Results
Considerable overlap was observed in training experiences of self-identified specialists and non-specialists. However, Chi-square analyses revealed a significantly greater proportion of self-identified specialists reported (a) completion of a dedicated course in fluency disorders during undergraduate and graduate curriculum, (b) interaction with five or more fluency clients during clinical practicum, and (c) exposure to specific fluency-related activities such as voluntary stuttering and attendance at a fluency-related support group.

Conclusions
Findings suggest that despite the degree of overlap between self-identified specialists' and non-specialists' pre-professional training, the quantity and quality of certain experiences may influence future decisions to focus more exclusively on working with persons who stutter.
W‐type highly erbium‐doped active soft‐glass fibre with high nonlinearity
Authors: Vazquez‐Zuniga L.A. , Feng X. , Kwon Y. , Kim H. , Shi J. , Loh W. , Jeong Y. 
Published: April 2016

A highly nonlinear W‐type erbium‐doped fibre with high dopant concentration made of three lead silicate glass materials (Schott SF57, LLF1 and SF6) is presented. The fibre is designed to have a flat anomalous dispersion at ∼1.55 μm, which is critical for enhancing parametric wavelength conversion. With this fibre, signals at ∼ 1.55 μm are successfully amplified in continuous‐wave and pico‐second‐pulsed formats with a 1.48 μm pump source. In particular, spectral broadening of over 350 nm together with strong degenerate four‐wave‐mixing effects is demonstrated. The authors highlight that this novel fibre combines, for first time to their knowledge, the benefits of highly doped active fibres with those of dispersion/nonlinearity‐engineered fibres.
The First Two Years of Instituto Estadual do Cérebro Paulo Niemeyer: Initial Results of a Brazilian Public Hospital Dedicated to Neurosurgery
Authors: Cavalcanti Daniel , Mata Paulo , Niemeyer Filho Paulo 
Published: April 2016

AbstractThe dissemination of specialty hospitals throughout the urban centers has revolutionized the full spectrum of care for cardiology, oncology and orthopedics during the last decades. To centralize care, from translational and basic research to clinicians and surgeons, in the same dedicated institution leads to a decrease in complications rates, mortality and possible reductions in the length of hospital stays. Moreover, there has been a significant impact on hospital costs and on the quality of care. The Insituto Estadual do Cérebro Paulo Niemeyer (IECPN, in the Portuguese acronym) was opened in June 2013 in Rio de Janeiro, Brazil. It is the very first high-volume neurosurgical institution in the country. The core foundation of this institution is that the anesthesiologists, intensive care practitioners, nurses, pathologists, radiologists and rehabilitation staffs are trained and live the full management of neurosurgical lesions at the same facility on a daily basis. The present paper seeks to analyze the circumstances in which the institution was planned and opened as well as its complexity, infrastructure and initial results following its first 24 months of operation.
Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18
Authors: Wynn James Lawrence , Wilson Chris S. , Hawiger Jacek , Scumpia Philip O. , Marshall Andrew F. , Liu Jin-Hua , Zharkikh Irina , Wong Hector R. , Lahni Patrick , Benjamin John T. , Plosa Erin J. , Weitkamp Jörn-Hendrik , Sherwood Edward R. , Moldawer Lyle L. , Ungaro Ricardo , Baker Henry V. , Lopez M. Cecilia , McElroy Steven J. , Colliou Natacha , Mohamadzadeh Mansour , Moore Daniel Jensen 
Published: April 2016

Significance
Infants born prematurely suffer the greatest incidence of and impact from sepsis among all age groups. Therapeutic interventions aimed at reducing morbidity and mortality in this vulnerable population have been unsuccessful. Interleukin (IL)-18 is a proinflammatory member of the IL-1 superfamily. Serum IL-18 concentrations in uninfected premature infants are increased as compared with healthy adults. We show that IL-18 in the setting of sepsis results in gut injury, a potentiation of the host’s inflammatory response, increased bacteremia, and mortality mediated by IL-1 receptor 1 (IL-1R1)–dependent IL-17A produced by γδT and myeloid cells. The discovery of this novel IL-18/IL-1R1/IL-17A axis brings new hope for therapeutic interventions that target downstream IL-17A and ultimately reduce the increased mortality from sepsis in this understudied population.
Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids
Authors: Geddes Sean D. , Assadzada Saleha , Lemelin David , Sokolovski Alexandra , Bergeron Richard , Haj-Dahmane Samir , Béïque Jean-Claude 
Published: April 2016

Significance
There is a vast literature linking individual neurotransmitters with specific brain function and disorders, often with significant overlap. For instance, serotonin (5-HT), glutamate, and endocannabinoids have been linked to several biological functions, such as mood regulation, reward, and decision making, as well as to pathologies, such as depressive and anxiety disorders. It is becoming axiomatic that such neurochemical-based models need to be incorporated within comprehensive and dynamic circuit-based frameworks to apprehend fully the neural basis of these functions. Here, we defined the mesoscale-level functional organization of the medial prefrontal cortex input to the dorsal raphe nucleus and how this circuit is modulated by cannabinoid (CB) signalling. This network-based functional framework may help to explain several of the mood-regulating features of both 5-HT and CBs.
MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G
Authors: Arfi Yonathan , Minder Laetitia , Di Primo Carmelo , Le Roy Aline , Ebel Christine , Coquet Laurent , Claverol Stephane , Vashee Sanjay , Jores Joerg , Blanchard Alain , Sirand-Pugnet Pascal 
Published: April 2016

SignificanceMycoplasmas are minimal pathogenic bacteria able to infect humans and a wide range of economically important animals; as such, they are major causes of concern in the medical and veterinary fields. These pathogens often lead to chronic infections, and their mechanisms of immunity evasion are poorly known. Here we describe a two-protein system from the ruminant pathogenMycoplasma mycoidessubspeciescaprithat is involved in the capture and cleavage of antibodies. MIB is able to capture the antibodies and to subsequently recruit MIP, a protease that is able to cleave the antibody heavy chain. The MIB–MIP system appears to be widespread among pathogenic mycoplasmas and is potentially a key player for the virulence and immunity evasion mechanisms of these bacteria.
Development of the turtle plastron, the order-defining skeletal structure
Authors: Rice Ritva , Kallonen Aki , Cebra-Thomas Judith , Gilbert Scott F. 
Published: April 2016

Significance
The plastron, the order-defining skeletal structure for turtles, provides a bony exoskeleton for the ventral side of the turtle. We provide here the first molecular analysis of plastron bone formation. We show that plastron bone morphogenesis in the ventral mesenchyme employs a program of bone formation that usually characterizes the vertebrate face and skull. The plastron bones, however, have a preliminary step that is not included in head formation: They must suppress the usual chondrogenic programs that would create the sternum cartilage. We suggest that the early osteogenic fate adopted by the ventral mesenchyme prevents the chondrogenic sternal development in turtles and that this was a critical step in forming the ossification centers for this new type of vertebrate structure.
Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies
Authors: Torchia James , Weiskopf Kipp , Levy Ronald 
Published: April 2016

Significance
Idiotype is a true tumor-specific surface marker on lymphoma cells, and cross-linking idiotype can directly trigger lymphoma cell death. It has not been practical, however, to target idiotype with antibodies because its sequence is unique to each patient. By chemically linking short synthetic patient-specific idiotype-binding peptides to a patient-invariant IgG Fc domain, we created a modular, antibody-like molecule that is more practical to customize. These semisynthetic peptibodies kill lymphoma cells directly, trigger tumor cell phagocytosis by macrophages, and clear human lymphoma in a mouse model of disseminated disease. This technology could add a new mechanism of action to the armament of lymphoma therapies and would not possess the toxicities and immunosuppression inherent to the current standard of care.
On Williamson and simplicity in modal logic
Authors: Sider Theodore 
Published: April 2016

AbstractAccording to Timothy Williamson, we should accept the simplest and most powerful second-order modal logic, and as a result accept an ontology of "bare possibilia". This general method for extracting ontology from logic is salutary, but its application in this case depends on a questionable assumption: that modality is a fundamental feature of the world.
Executive Summary: Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America
Authors: Barlam Tamar F. , Cosgrove Sara E. , Abbo Lilian M. , MacDougall Conan , Schuetz Audrey N. , Septimus Edward J. , Srinivasan Arjun , Dellit Timothy H. , Falck-Ytter Yngve T. , Fishman Neil O. , Hamilton Cindy W. , Jenkins Timothy C. , Lipsett Pamela A. , Malani Preeti N. , May Larissa S. , Moran Gregory J. , Neuhauser Melinda M. , Newland Jason G. , Ohl Christopher A. , Samore Matthew H. , Seo Susan K. , Trivedi Kavita K. 
Published: April 2016

Abstract
Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Dynamical impact of the Planet Nine scenario: N-body experiments
Authors: de la Fuente Marcos Carlos , de la Fuente Marcos Raúl , Aarseth Sverre J. 
Published: April 2016

Abstract
The Planet Nine hypothesis has now enough constraints to deserve further attention in the form of detailed numerical experiments. The results of such studies can help us improve our understanding of the dynamical effects of such a hypothetical object on the extreme trans-Neptunian objects or ETNOs and perhaps provide additional constraints on the orbit of Planet Nine itself. Here, we present the results of direct N-body calculations including the latest data available on the Planet Nine conjecture. The present-day orbits of the six ETNOs originally linked to the hypothesis are evolved backwards in time and into the future under some plausible incarnations of the hypothesis to investigate if the values of several orbital elements, including the argument of perihelion, remain confined to relatively narrow ranges. We find that a nominal Planet Nine can keep the orbits of (90377) Sedna and 2012 VP113 relatively well confined in orbital parameter space for hundreds of Myr, but it may make the orbits of 2004 VN112, 2007 TG422 and 2013 RF98 very unstable on time-scales of dozens of Myr, turning them retrograde and eventually triggering their ejection from the Solar system. Far more stable orbital evolution is found with slightly modified orbits for Planet Nine.