bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal Stromal Cell Mutations and Wound Healing Contribute to the Etiology of Desmoid Tumors
Authors: Carothers Adelaide M. , Rizvi Hira , Hasson Rian M. , Heit Yvonne I. , Davids Jennifer S. , Bertagnolli Monica M. , Cho Nancy L. 
Published: November 2011

AbstractDesmoid tumors are nonmalignant neoplasms of mesenchymal origin that mainly contain fibroblast lineage cells. These tumors often occur in patients with familial adenomatous polyposis (FAP) coli who have germ line mutations in the APC gene. Given emerging data that has implicated multipotent mesencyhmal stromal cells (MSC) in the origin of mesenchymal tumors, we hypothesized that desmoid tumors may arise in patients with FAP after MSCs acquire somatic mutations during the proliferative phase of wound healing. To test this idea, we examined 16 desmoid tumors from FAP-associated and sporadic cases, finding that all 16 of 16 tumors expressed stem cell markers, whereas matching normal stromal tissues were uniformly negative. Desmoid tumors also contained a subclass of fibrocytes linked to wound healing, angiogenesis, and fibrosis. Using an MSC cell line derived from an FAP-associated desmoid tumor, we confirmed an expected loss in the expression of adenomatous polyposis coli (APC) and the transcriptional repressor BMI-1 while documenting the coexpression of markers for chondrocytes, adipocytes, and osteocytes. Together, our findings argue that desmoid tumors result from the growth of MSCs in a wound healing setting that is associated with deregulated Wnt signaling due to APC loss. The differentiation potential of these MSCs combined with expression of BMI-1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggests that desmoid tumors may respond to therapies targeting these pathways. Cancer Res; 72(1); 346–55. ©2011 AACR.
Lymphatic Invasion Is Independently Prognostic of Metastasis in Primary Cutaneous Melanoma
Authors: Xu Xiaowei , Chen Lianjun , Guerry DuPont , Dawson Peter R. , Hwang Wei-ting , VanBelle Patricia , Elder David E. , Zhang Paul J. , Ming Michael E. , Schuchter Lynn , Gimotty Phyllis A. 
Published: November 2011

Abstract
Purpose: Lymphatic invasion (LI) in primary cutaneous melanomas was recently found to be common. In this study, we evaluated LI as an independent prognostic factor.
Experimental Design: This study included 251 patients with vertical growth phase (VGP) primary cutaneous melanomas who had paraffin-fixed lesional tissue and were in a prospective cohort seen between 1972 and 1991, had no clinical evidence of regional nodal disease at diagnosis, and had at least ten years of follow-up. Dual immunohistochemical staining was used to detect lymphatic endothelium (podoplanin) and melanoma cells (S-100). Multivariate logistic regression for ten-year metastasis was used to define independent prognostic factors, and a prognostic tree was developed to characterize and discriminate risk groups. Kaplan–Meier disease-free survival curves for those with and without LI within current American Joint Committee on Cancer stages were compared using the log-rank statistic.
Results: LI was observed in 43% (108 of 251) of the study melanomas. The multivariate model for ten-year metastasis identified four independent prognostic factors: tumor thickness, mitotic rate, LI, and anatomic site. The prognostic tree identified a group of patients with thin (≤1 mm thick) melanomas and poor prognosis: stage IB melanomas with LI. Survival curves for time to first metastasis showed significantly poorer prognosis for patients with LI compared with those without it for both stages IB and IIA.
Conclusions: LI is common across the range of tumor thicknesses in primary VGP melanomas. It is an independent prognostic factor and significantly increases the risk of metastasis in patients in clinical stages IB and IIA. Clin Cancer Res; 18(1); 229–37. ©2011 AACR.
G Protein–Coupled Receptor Kinase-5 Attenuates Atherosclerosis by Regulating Receptor Tyrosine Kinases and 7-Transmembrane Receptors
Authors: Wu Jiao-Hui , Zhang Lisheng , Fanaroff Alexander C. , Cai Xinjiang , Sharma Krishn C. , Brian Leigh , Exum Sabrina T. , Shenoy Sudha K. , Peppel Karsten , Freedman Neil J. 
Published: November 2011

Objective—
G protein–coupled receptor kinase-5 (GRK5) is a widely expressed Ser/Thr kinase that regulates several atherogenic receptors and may activate or inhibit nuclear factor-κB (NF-κB). This study sought to determine whether and by what mechanisms GRK5 affects atherosclerosis.

Methods and Results—

Grk5
−/−
/
Apoe
−/−
mice developed 50% greater aortic atherosclerosis than
Apoe
−/−
mice and demonstrated greater proliferation of macrophages and smooth muscle cells (SMCs) in atherosclerotic lesions. In
Apoe
−/−
mice, carotid interposition grafts from
Grk5
−/−
mice demonstrated greater upregulation of cell adhesion molecules than grafts from wild-type mice and, subsequently, more atherosclerosis. By comparing
Grk5
−/−
with wild-type cells, we found that GRK5 desensitized 2 key atherogenic receptor tyrosine kinases: the platelet-derived growth factor receptor-β in SMCs, by augmenting ubiquitination/degradation; and the colony-stimulating factor-1 receptor (CSF-1R) in macrophages, by reducing CSF-1-induced tyrosyl phosphorylation. GRK5 activity in monocytes also reduced migration promoted by the 7-transmembrane receptor for monocyte chemoattractant protein-1 CC chemokine receptor-2. Whereas GRK5 diminished NF-κB-dependent gene expression in SMCs and endothelial cells, it had no effect on NF-κB activity in macrophages.

Conclusion—
GRK5 attenuates atherosclerosis through multiple cell type-specific mechanisms, including reduction of SMC and endothelial cell NF-κB activity and desensitization of receptor-specific signaling through the monocyte CC chemokine receptor-2, macrophage CSF-1R, and the SMC platelet-derived growth factor receptor-β.
Physician Procedure Volume and Complications of Cardioverter-Defibrillator Implantation
Authors: Freeman James V. , Wang Yongfei , Curtis Jeptha P. , Heidenreich Paul A. , Hlatky Mark A. 
Published: November 2011

Background—
The outcomes of procedures are often better when they are performed by more experienced physicians. We assessed whether the rate of complications after implantable cardioverter-defibrillator (ICD) placement varied with the volume of procedures a physician performed.

Methods and Results—

We studied 356 515 initial ICD implantations in the National Cardiovascular Data Registry–ICD Registry, performed by 4011 physicians in 1463 hospitals. We examined the relationship between physician annual ICD implantation volume and in-hospital complications, using hierarchical logistic regression to adjust for patient characteristics, implanting physician certification, hospital characteristics, hospital annual procedure volume, and the clustering of patients within hospitals and by physician. We repeated this analysis for ICD subtypes: single chamber, dual chamber, and biventricular. There were 10 994 patients (3.1%) with a complication after ICD implantation, and 1375 died (0.39%). The complication rate decreased with increasing physician procedure volume from 4.6% in the lowest quartile to 2.9% in the highest quartile (
P
<0.0001), and the mortality rate decreased from 0.72% to 0.36% (
P
<0.0001). The inverse relationship between physician procedure volume and complications remained significant after adjusting for patient, physician, and hospital characteristics (OR 1.55 for complications in lowest-volume quartile compared with highest; 95% confidence interval, 1.34–1.79;
P
<0.0001). This inverse relationship was independent of physician specialty and of hospital volume, was consistent across ICD subtypes, and was also evident for in-hospital mortality.

Conclusion—
Physicians who implant more ICDs have lower rates of procedural complications and in-hospital mortality, independent of hospital procedure volume, physician specialty, and ICD type.
Feeling without Seeing? Engagement of Ventral, but Not Dorsal, Amygdala during Unaware Exposure to Emotional Faces
Authors: Lerner Yulia , Singer Neomi , Gonen Tal , Weintraub Yonatan , Cohen Oded , Rubin Nava , Ungerleider Leslie G. , Hendler Talma 
Published: November 2011

Abstract
The ability to selectively perceive items in the environment may be modulated by the emotional content of those items. The neural mechanism that underlies the privileged processing of emotionally salient content is poorly understood. Here, using fMRI, we investigated this issue via a binocular rivalry procedure when face stimuli depicting fearful or neutral expressions competed for awareness with a house. Results revealed an interesting dissociation in the amygdala during rivalry condition: Whereas its dorsal component exhibited dominant activation to aware fearful faces, a ventral component was more active during the suppression of fearful faces. Moreover, during rivalry, the dorsal and ventral components of the amygdala were coupled with segregated cortical activations in the brainstem and medial PFC, respectively. In summary, this study points to a differential involvement of two clusters within the amygdala and their connected networks in naturally occurring perceptual biases of emotional content in faces.
Motor Simulation during Action Word Processing in Neurosurgical Patients
Authors: Tomasino Barbara , Ceschia Martina , Fabbro Franco , Skrap Miran 
Published: November 2011

AbstractThe role that human motor areas play in linguistic processing is the subject of a stimulating debate. Data from nine neurosurgical patients with selective lesions of the precentral and postcentral sulcus could provide a direct answer as to whether motor area activation is necessary for action word processing. Action-related verbs (face-, hand-, and feet-related verbs plus neutral verbs) silently read were processed for (i) motor imagery by vividness ratings and (ii) frequency ratings. Although no stimulus- or task-dependent modulation was found in the RTs of healthy controls, patients showed a task × stimulus interaction resulting in a stimulus-dependent somatotopic pattern of RTs for the imagery task. A lesion affecting a part of the cortex that represents a body part also led to slower RTs during the creation of mental images for verbs describing actions involving that same body part. By contrast, no category-related differences were seen in the frequency judgment task. This task-related dissociation suggests that the sensorimotor area is critically involved in processing action verbs only when subjects are simulating the corresponding movement. These findings have important implications for the ongoing discussion regarding the involvement of the sensorimotor cortex in linguistic processing.
Twenty-First-Century Arctic Climate Change in CCSM4
Authors: Vavrus Stephen J. , Holland Marika M. , Jahn Alexandra , Bailey David A. , Blazey Benjamin A. 
Published: November 2011

Abstract
The authors summarize the twenty-first-century Arctic climate simulated by NCAR’s Community Climate System Model, version 4 (CCSM4). Under a strong radiative forcing scenario, the model simulates a much warmer, wetter, cloudier, and stormier Arctic climate with considerably less sea ice and a fresher Arctic Ocean. The high correlation among the variables composing these changes—temperature, precipitation, cloudiness, sea level pressure (SLP), and ice concentration—suggests that their close coupling collectively represents a fingerprint of Arctic climate change. Although the projected changes in CCSM4 are generally consistent with those in other GCMs, several noteworthy features are identified. Despite more global warming in CCSM4, Arctic changes are generally less than under comparable greenhouse forcing in CCSM3, as represented by Arctic amplification (16% weaker) and the date of a seasonally ice-free Arctic Ocean (20 years later). Autumn is the season of the most pronounced Arctic climate change among all the primary variables. The changes are very similar across the five ensemble members, although SLP displays the largest internal variability. The SLP response exhibits a significant trend toward stronger extreme Arctic cyclones, implying greater wave activity that would promote coastal erosion. Based on a commonly used definition of the Arctic (the area encompassing the 10°C July air temperature isotherm), the region shrinks by about 40% during the twenty-first century, in conjunction with a nearly 10-K warming trend poleward of 70°N. Despite this pronounced long-term warming, CCSM4 simulates a hiatus in the secular Arctic climate trends during a decade-long stretch in the 2040s and to a lesser extent in the 2090s. These pauses occur despite averaging over five ensemble members and are remarkable because they happen under the most extreme greenhouse-forcing scenario and in the most climatically sensitive region of the world.
General condition of hikikomori (prolonged social withdrawal) in Japan: Psychiatric diagnosis and outcome in mental health welfare centres
Authors: Kondo Naoji , Sakai Motohiro , Kuroda Yasukazu , Kiyota Yoshikazu , Kitabata Yuji , Kurosawa Mie 
Published: November 2011

Background: The issue of hikikomori (prolonged social withdrawal) among Japanese youth has attracted attention from international experts. In previous research, the unique cultural and social factors of Japanese society have been the focus; however, in order to resolve the problem of hikikomori, individual mental health problems must be included. Aim: We examined the psychiatric background of individuals with hikikomori. Methods: We recruited 337 individuals with hikikomori; 183 subjects who utilized the centres were designated as the help-seeking group. We examined the multi-axial psychiatric diagnosis based on the DSM-IV-TR, treatment policies and treatment outcomes. We also examined 154 subjects who did not utilize the centers (non-help-seeking group). Results: Most of the subjects in the utilization group were classified into one of the diagnostic categories. Forty-nine (33.3%) subjects were diagnosed with schizophrenia, mood disorders or anxiety disorders, and this group needed pharmacotherapy. Other subjects were diagnosed with personality disorders or pervasive developmental disorders, and they mainly needed psycho-social support. The Global Assessment of Functioning (GAF) scores of the non-help-seeking group were significantly lower than the GAF scores of those who used treatments. Conclusion: Most hikikomori cases can be diagnosed using current diagnostic criteria. Individuals with hikikomori are much worse if they do not seek help.
Representations of Culture in Theater of the Oppressed and Participatory Budgeting in Brazil
Authors: Dalla Déa Ariane 
Published: November 2011

Critical examination of stories originating in everyday individual experiences of oppression as reenacted in Theater of the Oppressed and as articulated in the speech performances of participatory budgeting meetings shows how the rhetoric of oppression operates either to reproduce or to transform historically established cultural practices. The application of theories of mimesis, performance, representation, experience, and frame analysis helps explain how cultural patterns counter Theater of the Oppressed’s proposals, simply providing a cathartic release, and how public participation in budgetary meetings is effective in producing social change. Um olhar crítico das experiências individuais com opressão re-encenadas no Teatro do Oprimido e articuladas nas falas de residentes nos distritos do orçamento participativo mostra como as retóricas de opressão opera para reproduzir ou transformar as práticas culturais estabelecidas históricamente. O uso de teorias de mimesis, performance, representação, experiência e analisis de ponto de referência social ajuda em compreender como os padrões culturais agem contra a proposta de transformação social no Teatro do Oprimido, providenciando nada mais que uma liberação catártica, e exemplifica como a participação pública no orçamento do governo é mais eficaz em trazer mudanças sociais.
Risk Factors for Anterior Cruciate Ligament Injury
Authors: Smith Helen C. , Vacek Pamela , Johnson Robert J. , Slauterbeck James R. , Hashemi Javad , Shultz Sandra , Beynnon Bruce D. 
Published: November 2011

Context: Injuries to the anterior cruciate ligament (ACL) of the knee are immediately debilitating and can cause long-term consequences, including the early onset of osteoarthritis. It is important to have a comprehensive understanding of all possible risk factors for ACL injury to identify individuals who are at risk for future injuries and to provide an appropriate level of counseling and programs for prevention. Objective: This review, part 1 of a 2-part series, highlights what is known and still unknown regarding anatomic and neuromuscular risk factors for injury to the ACL from the current peer-reviewed literature. Data Sources: Studies were identified from MEDLINE (1951–March 2011) using the MeSH terms anterior cruciate ligament, knee injury, and risk factors. The bibliographies of relevant articles and reviews were cross-referenced to complete the search. Study Selection: Prognostic studies that utilized the case-control and prospective cohort study designs to evaluate risk factors for ACL injury were included in this review. Results: A total of 50 case-control and prospective cohort articles were included in the review, and 30 of these studies focused on neuromuscular and anatomic risk factors. Conclusions: Several anatomic and neuromuscular risk factors are associated with increased risk of suffering ACL injury—such as female sex and specific measures of bony geometry of the knee joint, including decreased intercondylar femoral notch size, decreased depth of concavity of the medial tibial plateau, increased slope of the tibial plateaus, and increased anterior-posterior knee laxity. These risk factors most likely act in combination to influence the risk of ACL injury; however, multivariate risk models that consider all the aforementioned risk factors in combination have not been established to explore this interaction.
Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure
Authors: DeBaun Michael R. , Sarnaik Sharada A. , Rodeghier Mark J. , Minniti Caterina P. , Howard Thomas H. , Iyer Rathi V. , Inusa Baba , Telfer Paul T. , Kirby-Allen Melanie , Quinn Charles T. , Bernaudin Françoise , Airewele Gladstone , Woods Gerald M. , Panepinto Julie Ann , Fuh Beng , Kwiatkowski Janet K. , King Allison A. , Rhodes Melissa M. , Thompson Alexis A. , Heiny Mark E. , Redding-Lallinger Rupa C. , Kirkham Fenella J. , Sabio Hernan , Gonzalez Corina E. , Saccente Suzanne L. , Kalinyak Karen A. , Strouse John J. , Fixler Jason M. , Gordon Mae O. , Miller J. Phillip , Noetzel Michael J. , Ichord Rebecca N. , Casella James F. 
Published: November 2011

AbstractThe most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.
Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus?
Authors: Della Chiesa Mariella , Falco Michela , Podestà Marina , Locatelli Franco , Moretta Lorenzo , Frassoni Francesco , Moretta Alessandro 
Published: November 2011

Abstract
Natural killer (NK) cells play a crucial role in early immunity after hematopoietic stem cell transplantation because they are the first lymphocyte subset recovering after the allograft. In this study, we analyzed the development of NK cells after intrabone umbilical cord blood (CB) transplantation in 18 adult patients with hematologic malignancies. Our data indicate that, also in this transplantation setting, NK cells are the first lymphoid population detectable in peripheral blood. However, different patterns of NK-cell development could be identified. Indeed, in a group of patients, a relevant fraction of NK cells expressed a mature phenotype characterized by the KIR+NKG2A− signature 3-6 months after transplantation. In other patients, most NK cells maintained an immature phenotype even after 12 months. A possible role for cytomegalovirus in the promotion of NK-cell development was suggested by the observation that a more rapid NK-cell maturation together with expansion of NKG2C+ NK cells was confined to patients experiencing cytomegalovirus reactivation. In a fraction of these patients, an aberrant and hyporesponsive CD56−CD16+p75/AIRM1− NK-cell subset (mostly KIR+NKG2A−) reminiscent of that described in patients with viremic HIV was detected. Our data support the concept that cytomegalovirus infection may drive NK-cell development after umbilical CB transplantation.
In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling
Authors: Nishimura Satoshi , Manabe Ichiro , Nagasaki Mika , Kakuta Shigeru , Iwakura Yoichiro , Takayama Naoya , Ooehara Jun , Otsu Makoto , Kamiya Akihide , Petrich Brian G. , Urano Tetsumei , Kadono Takafumi , Sato Shinichi , Aiba Atsu , Yamashita Hiroshi , Sugiura Seiryo , Kadowaki Takashi , Nakauchi Hiromitsu , Eto Koji , Nagai Ryozo 
Published: November 2011

AbstractThe mechanism by which thrombotic vessel occlusion occurs independently of plaque development or endothelial cell (EC) disruption remains unclear, largely because of an inability to visualize the formation of thrombus, especially at the single-platelet level in real time. Here we demonstrate that rapidly developing thrombi composed of discoid platelets can be induced in the mesenteric capillaries, arterioles, and large-sized arteries of living mice, enabling characterization of the kinetics of thrombosis initiation and the multicellular interrelationships during thrombus development. Platelet aggregation without EC disruption was triggered by reactive oxygen species (ROS) photochemically induced by moderate power laser irradiation. The inflammatory cytokines TNF-α and IL-1 could be key components of the EC response, acting through regulation of VWF mobilization to the cell surface. Thrombus formation was then initiated by the binding of platelet GPIbα to endothelial VWF in our model, and this effect was inhibited by the ROS scavenger N-acetylcysteine. Actin linker talin-dependent activation of alphaIIb-beta3 integrin or Rac1 in platelets was required for late-phase thrombus stability. Our novel imaging technology illustrates the molecular mechanism underlying inflammation-based thrombus formation by discoid platelets on undisrupted ECs and suggests control of ROS could be a useful therapeutic target for the prevention of thrombotic diseases.