bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pragmatics in Action: Indirect Requests Engage Theory of Mind Areas and the Cortical Motor Network
Authors: van Ackeren Markus J. , Casasanto Daniel , Bekkering Harold , Hagoort Peter , Rueschemeyer Shirley-Ann 
Published: July 2012

Abstract
Research from the past decade has shown that understanding the meaning of words and utterances (i.e., abstracted symbols) engages the same systems we used to perceive and interact with the physical world in a content-specific manner. For example, understanding the word “grasp” elicits activation in the cortical motor network, that is, part of the neural substrate involved in planned and executing a grasping action. In the embodied literature, cortical motor activation during language comprehension is thought to reflect motor simulation underlying conceptual knowledge [note that outside the embodied framework, other explanations for the link between action and language are offered, e.g., Mahon, B. Z., & Caramazza, A. A critical look at the embodied cognition hypothesis and a new proposal for grouding conceptual content. Journal of Physiology, 102, 59–70, 2008; Hagoort, P. On Broca, brain, and binding: A new framework. Trends in Cognitive Sciences, 9, 416–423, 2005]. Previous research has supported the view that the coupling between language and action is flexible, and reading an action-related word form is not sufficient for cortical motor activation [Van Dam, W. O., van Dijk, M., Bekkering, H., & Rueschemeyer, S.-A. Flexibility in embodied lexical–semantic representations. Human Brain Mapping, doi: 10.1002/hbm.21365, 2011]. The current study goes one step further by addressing the necessity of action-related word forms for motor activation during language comprehension. Subjects listened to indirect requests (IRs) for action during an fMRI session. IRs for action are speech acts in which access to an action concept is required, although it is not explicitly encoded in the language. For example, the utterance “It is hot here!” in a room with a window is likely to be interpreted as a request to open the window. However, the same utterance in a desert will be interpreted as a statement. The results indicate (1) that comprehension of IR sentences activates cortical motor areas reliably more than comprehension of sentences devoid of any implicit motor information. This is true despite the fact that IR sentences contain no lexical reference to action. (2) Comprehension of IR sentences also reliably activates substantial portions of the theory of mind network, known to be involved in making inferences about mental states of others. The implications of these findings for embodied theories of language are discussed.
Inhibition of Return Impairs Phosphene Detection
Authors: Smith Daniel T. , Ball Keira , Ellison Amanda 
Published: July 2012

Abstract
Efficient visual exploration requires the ability to select possible target locations via spatial attention and to deselect previously inspected locations via inhibition of return (IOR). Although a great deal is known about the effects of spatial attention on processing in visual cortex, much less is known about the effects of IOR on early visual areas. One possibility is that IOR acts in an opposite way to spatial attention, such that, whereas spatial attention enhances target related neural signals in visual cortex, IOR suppress target-related signals. Using a novel dual-coil TMS protocol, we found that IOR reduced the probability of detecting a TMS-induced phosphene in extrastriate cortex (V5). Specifically, a nonpredictive spatial precue presented 500 or 800 msec before stimulation significantly reduced the probability of detecting a phosphene when the precue appeared contralaterally to the site of stimulation (i.e., ipsilaterally to the potential location of the phosphene), compared with ipsilaterally or centrally presented cues. This result demonstrates that IOR facilitates visual exploration by directly affecting the strength of target-related signals in extrastriate visual cortex. This result is consistent with neurophysiological models of attention, which postulate that IOR modulates perception by biasing competition between sensory representations.
The Effect of Aging on the Neural Correlates of Phonological Word Retrieval
Authors: Geva Sharon , Jones P. Simon , Crinion Jenny T. , Price Cathy J. , Baron Jean-Claude , Warburton Elizabeth A. 
Published: July 2012

Abstract
Age has a differential effect on cognition, with word retrieval being one of the cognitive domains most affected by aging. This study examined the functional and structural neural correlates of phonological word retrieval in younger and older adults using word and picture rhyme judgment tasks. Although the behavioral performance in the fMRI task was similar for the two age groups, the older adults had increased activation in the right pars triangularis across tasks and in the right pars orbitalis for the word task only. Increased activation together with preserved performance in the older participants would suggest that increased activation was related to compensatory processing. We validated this hypothesis by showing that right pars triangularis activation during correct rhyme judgments was highest in participants who made overall more errors, therefore being most error-prone. Our findings demonstrate that the effect of aging differ in adjacent but distinct right inferior frontal regions. The differential effect of age on word and picture tasks also provides new clues to the level of processing that is most affected by age in speech production tasks. Specifically, we suggest that right inferior frontal activation in older participants is needed to inhibit errors.
Novel incentive-based approaches to adherence
Authors: Kimmel Stephen E , Troxel Andrea B 
Published: July 2012

Background Adherence to medications for chronic conditions is often very low, limiting the benefit to patients, even when the medications are effective and have favorable side effect profiles. Purpose This article reviews some of the prior work on treatment adherence, introduces novel concepts from behavioral economics that can be used to design interventions to improve adherence, and proposes new approaches for clinical trials. Methods Relevant experience of the authors and insights from the literature were combined to identify key issues and propose methodological improvements. Specific examples regarding adherence to warfarin are provided. Results Several new approaches to trial design can be effectively applied in the context of medication adherence. These include tailored intervention strategies and sequential multiple assignment randomized trial (SMART) designs. Limitations While we have proposed to use these new approaches for ongoing studies of adherence in behavioral health, practical experience with their application is still somewhat limited. Conclusions Behavioral economics offer a variety of concepts that, when used in the design of interventions to improve adherence, may be more successful than traditional approaches. New clinical trial designs can also be adopted to improve the efficiency of studies that assess these approaches.
Synthetic genistein derivatives as modulators of glycosaminoglycan storage
Authors: Kloska Anna , Narajczyk Magdalena , Jakóbkiewicz-Banecka Joanna , Grynkiewicz Grzegorz , Szeja Wiesław , Gabig-Cimińska Magdalena , Węgrzyn Grzegorz 
Published: July 2012

AbstractBackgroundMucopolysaccharidoses (MPS) are severe metabolic disorders caused by accumulation of undegraded glycosaminoglycans (GAGs) in lysosomes due to defects in certain lysosomal hydrolases. Substrate reduction therapy (SRT) has been proposed as one of potential treatment procedures of MPS. Importantly, small molecules used in such a therapy might potentially cross the blood–brain barrier (BBB) and improve neurological status of patients, as reported for a natural isoflavone, 5, 7-dihydroxy-3- (4-hydroxyphenyl)-4 H-1-benzopyran-4-one, also known as genistein. Although genistein is able to cross BBB to some extent, its delivery to the central nervous system is still relatively poor (below 10% efficiency). Thus, we aimed to develop a set of synthetically modified genistein molecules and characterize physicochemical as well as biological properties of these compounds.MethodsFollowing parameters were determined for the tested synthetic derivatives of genistein: cytotoxicity, effects on cell proliferation, kinetics of GAG synthesis, effects on epidermal growth factor (EGF) receptor’s tyrosine kinase activity, effects on lysosomal storage, potential ability to cross BBB.ResultsWe observed that some synthetic derivatives inhibited GAG synthesis similarly to, or more efficiently than, genistein and were able to reduce lysosomal storage in MPS III fibroblasts. The tested compounds were generally of low cytotoxicity and had minor effects on cell proliferation. Moreover, synthetic derivatives of genistein revealed higher lipophilicity (assessedin silico) than the natural isoflavone.ConclusionSome compounds tested in this study might be promising candidates for further studies on therapeutic agents in MPS types with neurological symptoms.
A noninvasive mucinous cystic neoplasm with intermediate-grade dysplasia of the pancreas and extensive squamous metaplasia: a case report with clinicopathological correlation
Authors: Li Peifeng , Wang Yingmei , Zhang Qingqing , Liu Yixiong , Lv Yang , Wang Zhe 
Published: July 2012

Abstract

Abstract
Squamous metaplasia presenting in noninvasive mucinous cystic neoplasm (MCN) of the pancreas is extremely rare. We described a case of 39-year-old Chinese female with a 5-year history of a slow growing mass in the left upper abdomen and an 18-month history of surgical incision exudation. The patient underwent cystojejunostomy, laparotomy and distal pancreatectomy consecutively because of the initial diagnosis of “pancreatic cyst”. The histological section showed columnar mucin-producing epithelium formed small papillary projections and extensively visible squamous metaplasia. Therefore the diagnosis of “noninvasive MCN with intermediate-grade dysplasia of the pancreas and extensive squamous metaplasia” was made finally. The squamous component of the pancreas may be derived from pluripotent stem cells, and may be in association with cystojejunostomy.

Virtual slides
The virtual slide(s) for this article can be found here http://www.diagnosticpathology.diagnomx.eu/vs/1322364365718540
Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway
Authors: Wei Fangyuan , Moore Douglas C , Li Yanlin , Zhang Ge , Wei Xiaochun , Lee Joseph K , Wei Lei 
Published: July 2012

Abstract

Introduction

This study was performed to evaluate the attenuation of osteoarthritic (OA) pathogenesis via disruption of the stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling with AMD3100 in a guinea pig OA model.

Methods

OA chondrocytes and cartilage explants were incubated with SDF-1, siRNA CXCR4, or anti-CXCR4 antibody before treatment with SDF-1. Matrix metalloproteases (MMPs) mRNA and protein levels were measured with real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The 35 9-month-old male Hartley guinea pigs (0.88 kg ± 0.21 kg) were divided into three groups: AMD-treated group (n = 13); OA group (n = 11); and sham group (n = 11). At 3 months after treatment, knee joints, synovial fluid, and serum were collected for histologic and biochemical analysis. The severity of cartilage damage was assessed by using the modified Mankin score. The levels of SDF-1, glycosaminoglycans (GAGs), MMP-1, MMP-13, and interleukin-1 (IL-1β) were quantified with ELISA.

Results

SDF-1 infiltrated cartilage and decreased proteoglycan staining. Increased glycosaminoglycans and MMP-13 activity were found in the culture media in response to SDF-1 treatment. Disrupting the interaction between SDF-1 and CXCR4 with siRNA CXCR4 or CXCR4 antibody attenuated the effect of SDF-1. Safranin-O staining revealed less cartilage damage in the AMD3100-treated animals with the lowest Mankin score compared with the control animals. The levels of SDF-1, GAG, MMP1, MMP-13, and IL-1β were much lower in the synovial fluid of the AMD3100 group than in that of control group.

Conclusions

The binding of SDF-1 to CXCR4 induces OA cartilage degeneration. The catabolic processes can be disrupted by pharmacologic blockade of SDF-1/CXCR4 signaling. Together, these findings raise the possibility that disruption of the SDF-1/CXCR4 signaling can be used as a therapeutic approach to attenuate cartilage degeneration.
Risk factors for onset of hypothermia in trauma victims: The HypoTraum study
Authors: Lapostolle Frédéric , Sebbah Jean Luc , Couvreur James , Koch François Xavier , Savary Dominique , Tazarourte Karim , Egman Gerald , Mzabi Lynda , Galinski Michel , Adnet Frédéric 
Published: July 2012

Abstract
Introduction
Hypothermia is common in trauma victims and is associated with an increase in mortality. Its causes are not well understood. Our objective was to identify the factors influencing the onset of hypothermia during pre-hospital care of trauma victims.

Methods
This was a multicenter, prospective, open, observational study in a pre-hospital setting.
The subjects were trauma victims, over 18 years old, receiving care from emergency medical services (EMS) and transported to hospital in a medically staffed mobile unit.
Study variables included: demographics and morphological traits, nature and circumstances of the accident, victim's presentation (trapped, seated or lying down, on the ground, unclothed, wet or covered by a blanket), environmental conditions (wind, rain, ground temperature and air temperature on site and in the mobile unit), clinical factors, Revised Trauma Score (RTS), tympanic temperature, care provided (including warming, drugs administered, infusion fluid temperature and volume), and EMS and hospital arrival times.

Results
A total of 448 patients were included. Hypothermia (<35°C) on hospital arrival was present in 64/448 patients (14%). Significant factors associated with the absence of hypothermia in a multivariate analysis were no intubation: Odds Ratio: 4.23 (95% confidence interval 1.62 to 1.02); RTS: 1.68 (1.29 to 2.20); mobile unit temperature: 1.20 (1.04 to 1.38); infusion fluid temperature: 1.17 (1.05 to 1.30); patient not unclothed: 0.40 (0.18 to 0.90); and no head injury: 0.36 (0.16 to 0.83).

Conclusions
The key risk factor for the onset of hypothermia was the severity of injury but environmental conditions and the medical care provided by EMS were also significant factors. Changes in practice could help reduce the impact of factors such as infusion fluid temperature and mobile unit temperature.
Neuroventilatory efficiency and extubation readiness in critically ill patients
Authors: Liu Ling , Liu Huogen , Yang Yi , Huang Yingzi , Liu Songqiao , Beck Jennifer , Slutsky Arthur S , Sinderby Christer , Qiu Haibo 
Published: July 2012

Abstract
Introduction
Based on the hypothesis that failure of weaning from mechanical ventilation is caused by respiratory demand exceeding the capacity of the respiratory muscles, we evaluated whether extubation failure could be characterized by increased respiratory drive and impaired efficiency to generate inspiratory pressure and ventilation.

Methods
Airway pressure, flow, volume, breathing frequency, and diaphragm electrical activity were measured in a heterogeneous group of patients deemed ready for a spontaneous breathing trial. Efficiency to convert neuromuscular activity into inspiratory pressure was calculated as the ratio of negative airway pressure and diaphragm electrical activity during an inspiratory occlusion. Efficiency to convert neuromuscular activity into volume was calculated as the ratio of the tidal volume to diaphragm electrical activity. All variables were obtained during a 30-minute spontaneous breathing trial on continuous positive airway pressure (CPAP) of 5 cm H2O and compared between patients for whom extubation succeeded with those for whom either the spontaneous breathing trial failed or for those who passed, but then the extubation failed.

Results
Of 52 patients enrolled in the study, 35 (67.3%) were successfully extubated, and 17 (32.7%) were not. Patients for whom it failed had higher diaphragm electrical activity (48%; P < 0.001) and a lower efficiency to convert neuromuscular activity into inspiratory pressure and tidal volume (40% (P < 0.001) and 53% (P < 0.001)), respectively. Neuroventilatory efficiency demonstrated the greatest predictability for weaning success.

Conclusions
This study shows that a mixed group of critically ill patients for whom weaning fails have increased neural respiratory drive and impaired ability to convert neuromuscular activity into tidal ventilation, in part because of diaphragm weakness.

Trial Registration
Clinicaltrials.gov identifier NCT01065428. ©2012 Liu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comparing Empirical and Analytical Estimates of Earthquake Loss Assessment Studies for the City of Dehradun, India
Authors: Lang Dominik H. , Singh Yogendra , Prasad J. S. R. 
Published: July 2012

Very few earthquake risk studies exist for cities on the Indian subcontinent. The few studies that do exist typically focus on intensity as the parameter to describe the expected ground motion during an earthquake and on damage observations to represent building vulnerability. In contrast to these empirical studies, analytical loss computations, which are based on capacity spectrum methods (CSM), have recently become popular and are gaining wide acceptance. Analytical damage and loss computations have been conducted for the test bed Dehradun, a city of 500,000 inhabitants in the foothills of the Himalayas (northern India), and then compared with loss estimates from empirical studies recently performed for the city. The study illustrates the problems associated with trying to generate intensity-compatible ground motion estimates and comparing the damage and loss estimates of both approaches.
Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Gemcitabine/Cisplatin Alone or With Sorafenib for the First-Line Treatment of Advanced, Nonsquamous Non–Small-Cell Lung Cancer
Authors: Paz-Ares Luis G. , Biesma Bonne , Heigener David , von Pawel Joachim , Eisen Timothy , Bennouna Jaafar , Zhang Li , Liao Meilin , Sun Yan , Gans Steven , Syrigos Kostas , Le Marie Etienne , Gottfried Maya , Vansteenkiste Johan , Alberola Vincente , Strauss Uwe Phillip , Montegriffo Elaine , Ong Teng Jin , Santoro Armando 
Published: July 2012

Purpose This trial evaluated the efficacy and safety of sorafenib plus gemcitabine/cisplatin in chemotherapy-naive patients with unresectable stage IIIB to IV nonsquamous non–small-cell lung cancer (NSCLC). Patients and Methods Between February 2007 and March 2009, 904 patients were randomly assigned to daily sorafenib (400 mg twice a day) or matching placebo plus gemcitabine (1,250 mg/m2 per day on days 1 and 8) and cisplatin (75 mg/m2 on day 1) for up to six 21-day cycles. Because of safety findings from the Evaluation of Sorafenib, Carboplatin and Paclitaxel Efficacy in NSCLC (ESCAPE) trial, patients with squamous cell histology were withdrawn from the trial in February 2008 and excluded from analysis. The primary end point was overall survival (OS), and secondary end points included progression-free survival (PFS) and time-to-progression (TTP). Results The primary analysis population consisted of 772 patients (sorafenib, 385; placebo, 387); the two groups had similar demographic and baseline characteristics. Median OS was similar in the sorafenib and placebo groups (12.4 v 12.5 months; hazard ratio [HR], 0.98; P = .401). By investigator assessment, sorafenib improved median PFS (6.0 v 5.5 months; HR, 0.83; P = .008) and TTP (6.1 v 5.5 months; HR, 0.73; P < .001). Grade 3 to 4 drug-related adverse events more than two-fold higher in the sorafenib group included hand-foot skin reaction (8.6% v 0.3%), fatigue (7.3% v 3.6%), rash (5.7% v 0.5%), and hypertension (4.2% v 1.8%). No unexpected toxicities were observed. Conclusion This study did not meet its primary end point of improved OS when sorafenib was added to first-line gemcitabine/cisplatin in patients with advanced nonsquamous NSCLC. Identification of predictive biomarkers is warranted in future trials of sorafenib.
Neuropathy Is Not Associated With Clinical Outcomes in Patients Receiving Adjuvant Taxane-Containing Therapy for Operable Breast Cancer
Authors: Schneider Bryan P. , Zhao Fengmin , Wang Molin , Stearns Vered , Martino Silvana , Jones Vicky , Perez Edith A. , Saphner Tom , Wolff Antonio C. , Sledge George W. , Wood William C. , Davidson Nancy E. , Sparano Joseph A. 
Published: July 2012

Purpose Neuropathy is a common and potentially disabling complication of adjuvant taxane therapy. Recent studies have identified candidate single nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we sought to determine whether neuropathy was associated with breast cancer recurrence in a clinical trial population who received adjuvant taxane therapy. Patients and Methods Trial E1199 included 4,554 eligible women with operable breast cancer who received up to four cycles of doxorubicin and cyclophosphamide every 3 weeks followed by paclitaxel 175 mg/m2 every 3 weeks for four cycles (P3), paclitaxel 80 mg/m2 weekly for 12 cycles (P1), docetaxel 100 mg/m2 every 3 weeks for four cycles (D3), or docetaxel 35 mg/m2 weekly for 12 cycles (D1). A Cox proportional hazards model was used to determine the relationship between neuropathy and disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) by treating neuropathy status as a time dependent covariate and using a landmark analysis. Results Of 4,554 patients who received at least one taxane dose, grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and 13% of patients in the P3, P1, D3, and D1 arms, respectively. In a model that included age, race, obesity, menopausal status, tumor size, nodal status, treatment arm, neuropathy, and hyperglycemia, no significant relationship was found between neuropathy and DFS, OS, or RFS. Conclusion There was no association between taxane-induced neuropathy and outcome.