bluuebunny/crossref_metadata_2025_split huggingface dataset:
The IL-33/ST2 Axis Is Associated with Human Visceral Leishmaniasis and Suppresses Th1 Responses in the Livers of BALB/c Mice Infected with Leishmania donovani
Authors: Rostan Octavie , Gangneux Jean-Pierre , Piquet-Pellorce Claire , Manuel Christelle , McKenzie Andrew N. J. , Guiguen Claude , Samson Michel , Robert-Gangneux Florence 
Published: September 2013

ABSTRACTDuring visceral leishmaniasis, the control of hepatic parasite burden is mainly due to granuloma assembly in a microenvironment consisting of both Th1 and Th2 components. Using enzyme-linked immunosorbent assay (ELISA) dosages, quantitative PCR (qPCR), immunohistochemistry, and flow cytometry, we studied the role of interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, during visceral leishmaniasis. We showed that a higher level of IL-33 was detected in the serum of patients with visceral leishmaniasis than in that from healthy donors and demonstrated the presence of IL-33+cells in a liver biopsy specimen from a patient. Similarly, in BALB/c mice experimentally infected withL. donovani, a higher level of IL-33 was detected in the serum, as well as the presence of IL-33+cells and ST2+cells in the mouse liver. In ST2−/−BALB/c mice, better control of the hepatic parasite burden and reduced hepatomegaly were observed. This was associated with strong induction of Th1 cytokines (gamma interferon [IFN-γ] and IL-12) compared to the level in wild-type (WT) mice and better recruitment of myeloid cells associated with strongly induced chemokines (CCL2 and CXCL2) and receptors (CCR2 and CXCR2). Conversely, BALB/c mice treated twice weekly with recombinant IL-33 showed a dramatically reduced induction of Th1 cytokines and delayed inhibition of monocyte and neutrophil recruitment in the liver, which was associated with reduced KC/CXCL1 and CXCR2 expression. Taken together, our results suggest that IL-33 could be a new deleterious regulator of the hepatic immune response againstLeishmania donovani, via the repression of the Th1 response and myeloid cell recruitment.IMPORTANCEVisceral leishmaniasis is a life-threatening systemic disease due to theLeishmaniaprotozoaL. infantumandL. donovaniand is ranked by the World Health Organization as the second most important protozoan parasitic disease after malaria for its grave morbidity, high mortality, and global distribution.Leishmaniaparasites subvert the host’s immune response to propagate to target organs, including the spleen, the bone marrow, and the liver. Control of hepatic parasite burdens depends on a delicate and poorly understood Th1/Th2 immune balance. To better understand this complex immune response, new cytokines are interesting targets for research studies. IL-33 is a newly described cytokine usually associated with Th2 response and involved in different diseases, including infectious diseases and hepatitis. Our results suggest that IL-33 could be a new factor of susceptibility and a potential prognostic marker during visceral leishmaniasis.
How do emergency physicians make discharge decisions?
Authors: Calder Lisa A , Arnason Trevor , Vaillancourt Christian , Perry Jeffrey J , Stiell Ian G , Forster Alan J 
Published: September 2013

BackgroundOne of the most important decisions that emergency department (ED) physicians make is patient disposition (admission vs discharge).ObjectivesTo determine how ED physicians perceive their discharge decisions for high-acuity patients and the impact on adverse events (adverse outcomes associated with healthcare management).MethodsWe conducted a real-time survey of staff ED physicians discharging consecutive patients from high-acuity areas of a tertiary care ED. We asked open-ended questions about rationale for discharge decisions and use of clinical judgement versus evidence. We searched for 30-day flagged outcomes (deaths, unscheduled admissions, ED or clinic visits). Three trained blinded ED physicians independently reviewed these for adverse events and preventability. We resolved disagreements by consensus. We used descriptive statistics and 95% CIs.ResultsWe interviewed 88.9% (32/36) of possible ED physicians for 366 discharge decisions. Respondents were mostly male (71.9%) and experienced (53.1% >10 years). ED physicians stated they used clinical judgement in 87.6% of decisions and evidence in 12.4%. There were 69 flagged outcomes (18.8%) and 10 adverse events (2.7%, 95% CI 1.1 to 4.5%). All adverse events were preventable (1 death, 4 admissions, 5 return ED visits). No significant associations occurred between decision-making rationale and adverse events.ConclusionsExperienced ED physicians most often relied on clinical acumen rather than evidence-based guidelines when discharging patients from ED high-acuity areas. Neither approach was associated with adverse events. In order to improve the safety of discharge decisions, further research should focus on decision support solutions and feedback interventions.
Along-strike variations in the composition of sandstones derived from the uplifting western Greater Caucasus: causes and implications for reservoir quality prediction in the Eastern Black Sea
Authors: Vincent Stephen J. , Hyden Fiona , Braham William 
Published: September 2013

Abstract
Oligo-Miocene outcrops along the southern margin of the western Greater Caucasus preserve a record of sediments shed from the range into the northern and central parts of the Eastern Black Sea. Sandstones in the Russian western Caucasus are significantly more quartz-rich than those located farther SE in western Georgia. The latter contain appreciably more mudstone and volcanic rock fragments. Oligo-Miocene turbidite systems derived from the Russian western Caucasus in the Tuapse Trough and central Eastern Black Sea may therefore form better-quality reservoirs at shallow to moderate depths than sediments derived from west Georgian volcaniclastic sources in the easternmost part of the basin. Palynomorph analysis indicates sediment derivation predominantly from Jurassic and Cretaceous strata in the Russian western Caucasus and from Eocene strata, and an increasing proportion of Cretaceous strata upsection, in western Georgia. An Eocene volcaniclastic source is proposed for the increased rock fragment component in west Georgian sandstones. Eocene volcaniclastic rocks are no longer exposed in the Greater Caucasus, but similar rocks form the inverted fill of the Adjara–Trialet Basin farther south in the Lesser Caucasus. The former presence of a northern strand of this basin in the west Georgian Caucasus is supported by earlier thermochronological work.

Supplementary material:

A sample data table, petrographic data table, petrographic key, QFL sandstone compositional plot and palynomorph reworking Stratabugs™ charts are available at
www.geolsoc.org.uk/SUP18662
.
Molecular Imaging of Death Receptor 5 Occupancy and Saturation Kinetics In Vivo by Humanized Monoclonal Antibody CS-1008
Authors: Burvenich Ingrid J.G. , Lee Fook T. , Cartwright Glenn A. , O'Keefe Graeme J. , Makris Dahna , Cao Diana , Gong Sylvia , Chueh Anderly C. , Mariadason John M. , Brechbiel Martin W. , Beckman Robert A. , Fujiwara Kosaku , von Roemeling Reinhard , Scott Andrew M. 
Published: September 2013

Abstract
Purpose: CS-1008 (tigatuzumab; phase I/II), an antihuman death receptor 5 (DR5) agonist, induces apoptosis and has cytotoxic activity against human cancer cell lines. This study reports on the preclinical validation of 111In-labeled anti-DR5 humanized antibody CS-1008 as a diagnostic tool to study the DR5 occupancy in patients with cancer and establish dose ranges for receptor saturation kinetics in vivo.
Experimental Design: CS-1008 was radiolabeled and characterized for DR5 binding and labeling efficiency on TRAIL-sensitive DR5–positive colorectal cancer cells (COLO 205 and WiDr). Pharmacokinetic and biodistribution studies were conducted in BALB/c nu/nu mice bearing COLO 205, WiDr, or DR5-negative CT26 colon tumors. Planar gamma camera imaging and computerized tomography (CT) images were obtained to study receptor occupancy in vivo.
Results: Scatchard analysis showed high and specific binding affinity (Kd, 1.05 ± 0.12 nmol/L) of 111In-labeled CS-1008. 111In-labeled CS-1008 was specifically taken up in mice bearing COLO 205 and WiDr tumors with prolonged tumor retention (26.25 ± 2.85%ID/g vs. 12.20 ± 2.24 at 168 hours post injection; n = 5, SD), and uptake correlated both with DR5 expression on tumor cells and antitumor activity. DR5 saturation was shown in vivo via both biodistribution studies and planar gamma camera imaging/CT imaging of 111In-labeled CS-1008. Saturation of DR5 corresponded to maximal in vivo antitumor efficacy.
Conclusions: Imaging of DR5 receptor occupancy in vivo correlates with tumor concentration and in vivo efficacy, and is a novel molecular imaging technique that can be used to determine receptor occupancy and effective dose levels of DR5 agonist antibodies in the clinic. Clin Cancer Res; 19(21); 5984–93. ©2013 AACR.
A Phase I Study of the HSP90 Inhibitor Retaspimycin Hydrochloride (IPI-504) in Patients with Gastrointestinal Stromal Tumors or Soft-Tissue Sarcomas
Authors: Wagner Andrew J. , Chugh Rashmi , Rosen Lee S. , Morgan Jeffrey A. , George Suzanne , Gordon Michael , Dunbar Joi , Normant Emmanuel , Grayzel David , Demetri George D. 
Published: September 2013

Abstract
Purpose: Heat shock protein 90 (HSP90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFRα) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase I study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective HSP90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS).
Experimental Design: IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m2 twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging.
Results: Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m2 twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26 of 37) of patients with GIST and 59% (10 of 17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11 of 29 (38%) patients with GIST.
Conclusions: In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of antitumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy. Clin Cancer Res; 19(21); 6020–9. ©2013 AACR.
Harsh Voice Quality and Its Association with Blackness in Popular American Media
Authors: Moisik Scott Reid 
Published: September 2013

Abstract
Performers use various laryngeal settings to create voices for characters and personas they portray. Although some research demonstrates the sociophonetic associations of laryngeal voice quality, few studies have documented or examined the role of harsh voice quality, particularly with vibration of the epilaryngeal structures (growling). This article qualitatively examines phonetic properties of vocal performances in a corpus of popular American media and evaluates the association of voice qualities in these performances with representations of social identity and stereotype. In several cases, contrasting laryngeal states create sociophonetic contrast, and harsh voice quality is paired with the portrayal of racial stereotypes of black people. These cases indicate exaggerated emotional states and are associated with yelling/shouting modes of expression. Overall, however, the functioning of harsh voice quality as it occurs in the data is broader and may involve aggressive posturing, comedic inversion of aggressiveness, vocal pathology, and vocal homage.
On How Accent Distribution Can Signal Speaker Adaptation
Authors: Kaland Constantijn , Krahmer Emiel , Swerts Marc 
Published: September 2013

Abstract
Some dialogues are perceived as running more smoothly than others. To some extent that impression could be related to how well speakers adapt their prosody to each other. Adaptation in prosody can be signaled by the use of pitch accents that indicate how utterances are structurally related to those of the interlocutor (prosodic function) or by copying the interlocutor's prosodic features (prosodic form). The same acoustic features, such as pitch, are involved in both ways of adaptation. Further, function and form may require a different prosody for successful adaptation in certain discourse contexts. In this study we investigate to what extent interlocutors are perceived as good adapters, depending on whether the prosody of both speakers is functionally coherent or similar in form. This is done in two perception tests using prosodically manipulated dialogues. Results show that coherent functional prosody can be a cue for speaker adaptation and that this cue is more powerful than similarity in prosodic form.
Pygopus Maintains Heart Function in Aging
Drosophila
Independently of Canonical Wnt Signaling
Authors: Tang Min , Yuan Wuzhou , Fan Xiongwei , Liu Ming , Bodmer Rolf , Ocorr Karen , Wu Xiushan 
Published: September 2013

Background—

Heart function declines with age, but the genetic factors underlying such deterioration are largely unknown. Wnt signaling is known to play a role in heart development, but it has not been shown to be important in adult heart function. We have investigated the nuclear adapter protein encoded by
pygopus
(
pygo
), which mediates canonical Wnt signaling, for roles in aging-related cardiac dysfunction.

Methods and Results—

Using the
Drosophila
heart model, we show that cardiac-specific
pygo
knockdown in adult flies causes a significant (4- to 5-fold) increase in cardiac arrhythmias (
P
<0.001) that worsened with age and caused a significant decrease in contractility (−54%;
P
<0.001) with systolic dysfunction. Immunohistochemistry revealed structural abnormalities that worsened with age, and both functional and morphological alterations were ameliorated by
pygo
overexpression. Unexpectedly, knockdown of 2 other Wnt signaling components,
β-cat/armadillo
or
TCF/pangolin
, had relatively milder effects on cardiac function. Double-heterozygous combinations of mutants for
pygo
and canonical Wnt signaling components had no additional effect on heart function over
pygo
heterozygotes alone. However, double knockdown of pygo and Ca
2+
/calmodulin-dependent protein kinase II caused additional arrhythmia compared with pygo knockdown alone, suggesting that some of the effects of pygo are mediated by Ca
2+
signaling. In the isoproterenol-induced hypertrophic mouse model, we show that Pygo1 protein levels are increased.

Conclusions—
Our data indicate that Pygo plays a critical role in adult heart function that is Wnt signaling independent and is likely conserved in mammals.
Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-κB Signaling in Endothelial Cells
Authors: Jane-wit Dan , Manes Thomas D. , Yi Tai , Qin Lingfeng , Clark Pamela , Kirkiles-Smith Nancy C. , Abrahimi Parwiz , Devalliere Julie , Moeckel Gilbert , Kulkarni Sanjay , Tellides George , Pober Jordan S. 
Published: September 2013

Background—
Cardiac allograft vasculopathy is the major cause of late allograft loss after heart transplantation. Cardiac allograft vasculopathy lesions contain alloreactive T cells that secrete interferon-γ, a vasculopathic cytokine, and occur more frequently in patients with donor-specific antibody. Pathological interactions between these immune effectors, representing cellular and humoral immunity, respectively, remain largely unexplored.

Methods and Results—

We used human panel reactive antibody to form membrane attack complexes on allogeneic endothelial cells in vitro and in vivo. Rather than inducing cytolysis, membrane attack complexes upregulated inflammatory genes, enhancing the capacity of endothelial cells to recruit and activate allogeneic interferon-γ––producing CD4
+
T cells in a manner dependent on the activation of noncanonical nuclear factor-κB signaling. Noncanonical nuclear factor-κB signaling was detected in situ within endothelial cells both in renal biopsies from transplantation patients with chronic antibody-mediated rejection and in panel-reactive antibody––treated human coronary artery xenografts in immunodeficient mice. On retransplantation into immunodeficient hosts engrafted with human T cells, panel-reactive antibody––treated grafts recruited more interferon-γ––producing T cells and enhanced cardiac allograft vasculopathy lesion formation.

Conclusions—
Alloantibody and complement deposition on graft endothelial cells activates noncanonical nuclear factor-κB signaling, initiating a proinflammatory gene program that enhances alloreactive T cell activation and development of cardiac allograft vasculopathy. Noncanonical nuclear factor-κB signaling in endothelial cells, observed in human allograft specimens and implicated in lesion pathogenesis, may represent a target for new pharmacotherapies to halt the progression of cardiac allograft vasculopathy.
Veto and Vacillation: A Neural Precursor of the Decision to Withhold Action
Authors: Misirlisoy Erman , Haggard Patrick 
Published: September 2013

Abstract
The capacity to inhibit a planned action gives human behavior its characteristic flexibility. How this mechanism operates and what factors influence a decision to act or not act remain relatively unexplored. We used EEG readiness potentials (RPs) to examine preparatory activity before each action of an ongoing sequence, in which one action was occasionally omitted. We compared RPs between sequences in which omissions were instructed by a rule (e.g., “omit every fourth action”) and sequences in which the participant themselves freely decided which action to omit. RP amplitude was reduced for actions that immediately preceded a voluntary omission but not a rule-based omission. We also used the regular temporal pattern of the action sequences to explore brain processes linked to omitting an action by time-locking EEG averages to the inferred time when an action would have occurred had it not been omitted. When omissions were instructed by a rule, there was a negative-going trend in the EEG, recalling the rising ramp of an RP. No such component was found for voluntary omissions. The results are consistent with a model in which spontaneously fluctuating activity in motor areas of the brain could bias “free” decisions to act or not.
The Impact of Early Amygdala Damage on Juvenile Rhesus Macaque Social Behavior
Authors: Bliss-Moreau Eliza , Moadab Gilda , Bauman Melissa D. , Amaral David G. 
Published: September 2013

Abstract
The present experiments continue a longitudinal study of rhesus macaque social behavior following bilateral neonatal ibotenic acid lesions of the amygdala or hippocampus, or sham operations. Juvenile animals (approximately 1.5–2.5 years) were tested in four different social contexts—alone, while interacting with one familiar peer, while interacting with one unfamiliar peer, and in their permanent social groups. During infancy, the amygdala-lesioned animals displayed more interest in conspecifics (indexed by increased affiliative signaling) and paradoxically demonstrated more submission or fear (Bauman, Lavenex, Mason, Capitanio, & Amaral, 2004a, this journal). When these animals were assessed as juveniles, differences were less striking. Amygdala-lesioned animals generated fewer aggressive and affiliative signals (e.g., vocalizations, facial displays) and spent less time in social interactions with familiar peers. When animals were observed alone or with an unfamiliar peer, amygdala-lesioned animals, compared with other subjects, spent more time being inactive and physically explored the environment less. Despite the subtle, lesion-based differences in the frequency and duration of specific social behaviors, there were lesion-based differences in the organization of behavior such that lesion groups could be identified based on the patterning of social behaviors in a discriminant function analysis. The findings indicate that, although overall frequencies of many of the observed behaviors do not differ between groups, the general patterning of social behavior may distinguish the amygdala-lesioned animals.
Extensive Left Temporal Pole Damage Does Not Impact on Theory of Mind Abilities
Authors: Michel Caroline , Dricot Laurence , Lhommel Renaud , Grandin Cécile , Ivanoiu Adrian , Pillon Agnesa , Samson Dana 
Published: September 2013

Abstract
The temporal poles (TPs) are among the brain regions that are often considered as the brain network sustaining our ability to understand other people's mental states or “Theory of Mind” (ToM). However, so far the functional role of the left and right TPs in ToM is still debated, and it is even not clear yet whether these regions are necessary for ToM. In this study, we tested whether the left TP is necessary for ToM by assessing the mentalizing abilities of a patient (C.M.) diagnosed with semantic dementia. Converging evidence from detailed MRI and 18F-fluoro-2-deoxy-d-glucose PET examinations showed a massive atrophy of the left TP with the right TP being relatively unaffected. Furthermore, C.M.'s atrophy encompassed most regions of the left TP usually activated in neuroimaging studies investigating ToM. Given C.M.'s language impairments, we used a battery of entirely nonverbal ToM tasks. Across five tasks encompassing 100 trials, which probed the patient's ability to attribute various mental states (intentions, knowledge, and beliefs), C.M. showed a totally spared performance. This finding suggests that, despite its consistently observed activation in neuroimaging studies involving ToM tasks, the left TP is not necessary for ToM reasoning, at least in nonverbal conditions and as long as its right counterpart is preserved. Implications for understanding the social abilities of patients with semantic dementia are discussed.
The Maritime Influence on Diurnal Temperature Range in the Chesapeake Bay Area
Authors: Scheitlin Kelsey 
Published: September 2013

Abstract
This study analyzes the influence of the Atlantic Ocean and Chesapeake Bay on the diurnal temperature range (DTR) reported by nearby weather stations. Coastal locations reported the smallest DTRs and DTR fluctuations, and DTR increased with distance from the ocean. Month of the year and airmass type also proved to be significant predictors of DTR. All locations showed a bimodal annual DTR pattern with peaks during the transitional seasons and experienced the greatest DTR during dry and/or warm air masses. Proximity to the ocean had the largest (smallest) influence on DTR during dry (moist) air masses with extreme (moderate) temperatures. Seasonally, the proximity to the ocean had the strongest impact on DTR during early–middle spring. A multiple regression model using distance from water, month, and airmass type explains over 30% of DTR variability in the area (p &lt; 0.01). Airmass type has the largest influence on DTR, and changes in both air mass and month impacted the DTR of continental locations more than coastal locations. Land use, cloud cover, and wind speed/direction are additional variables that could account for differences not explained by the model.