bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatally bitten ammonites from the lower Lias Group (Lower Jurassic) of Lyme Regis, Dorset
Authors: Andrew Chris , Howe Paddy , Paul Christopher R. C. , Donovan Stephen K. 
Published: May 2011

SUMMARY

Little is known about ammonites as prey. Two papers report single British examples of fatally bitten ammonites. Globally, two previous papers describe damage similar to that recorded herein. Nevertheless, in the Charmouth Mudstone Formation of the lower Lias Group at Lyme Regis, up to 20% of small ammonites (
Promicroceras
,
Xipheroceras
,
Cymbites
,
Arnioceras
,
Asteroceras
,
Caenisites
,
Eoderoceras
and
Paltechioceras
?) show ventral damage at the rear of the body chamber that is far too consistent in morphology and position to result from accidents. Single pieces of shell, which extend almost symmetrically on either side and reach the umbilical seam on one side, are missing. Midpoint of the damage lies at 80% of the body chamber length back from the aperture, with a coefficient of variation of 10%. Damage at this position would sever attachment muscles and facilitate removal of the body from the aperture. Lack of shell chips preserved adjacent to damaged ammonites precludes scavenging or post-burial crushing as causes of the damage. Ammonites were caught in the water column, manipulated into a horizontal position and bitten at a precise point. The most likely predator was an active swimmer, able to hold and manipulate a smooth, possibly slippery, ammonite shell. The slightly asymmetrical damage is consistent with bites made by robust, parrot-like, cephalopod jaws (rhyncholites), which are known from the same stratigraphic interval. Ammonites are less likely predators than teuthoids. Belemnites, lacking suckers, are discounted. Lobster-like crustaceans are unlikely to have been able to catch, hold and manipulate shells. Lack of tooth marks precludes most vertebrate predators. These bite marks are referred to
Bicrescomanducator rolli
Donovan, Paul, Andrew & Howe igen. et isp. nov.
Kingsdale: the evolution of a Yorkshire dale
Authors: Waltham T. , Murphy P. , Batty A. 
Published: May 2011

SUMMARY
The glaciated trough of Kingsdale is a classic feature of the Yorkshire Dales, and is drained by a complex of cave systems. Within some cave passages, sediments and stalagmites have been dated to establish an absolute chronology for at least part of the dale's evolution. Much of the excavation of Kingsdale dates back to fluvial erosion early in the Pleistocene; the dale was then modified by pre-Devensian glaciers and excavated to almost its present depth. Devensian ice increased the depth profile by only a few metres, before leaving moraines that impounded a short-lived lake at the lower end of the dale. A post-Devensian channel now cuts through the main recessional moraine at Raven Ray, beneath which lies a deep buried valley.
Delineation of a Cellular Hierarchy in Lung Cancer Reveals an Oncofetal Antigen Expressed on Tumor-Initiating Cells
Authors: Damelin Marc , Geles Kenneth G. , Follettie Maximillian T. , Yuan Ping , Baxter Michelle , Golas Jonathon , DiJoseph John F. , Karnoub Maha , Huang Shuguang , Diesl Veronica , Behrens Carmen , Choe Sung E. , Rios Carol , Gruzas Janet , Sridharan Latha , Dougher Maureen , Kunz Arthur , Hamann Philip R. , Evans Deborah , Armellino Douglas , Khandke Kiran , Marquette Kimberly , Tchistiakova Lioudmila , Boghaert Erwin R. , Abraham Robert T. , Wistuba Ignacio I. , Zhou Bin-Bing S. 
Published: May 2011

AbstractPoorly differentiated tumors in non–small cell lung cancer (NSCLC) have been associated with shorter patient survival and shorter time to recurrence following treatment. Here, we integrate multiple experimental models with clinicopathologic analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition were observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient–derived xenografts, treatment with an anti-5T4 antibody–drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy. Cancer Res; 71(12); 4236–46. ©2011 AACR.
Programmed Death Ligand 1 Is Expressed by Non–Hodgkin Lymphomas and Inhibits the Activity of Tumor-Associated T Cells
Authors: Andorsky David J. , Yamada Reiko E. , Said Jonathan , Pinkus Geraldine S. , Betting David J. , Timmerman John M. 
Published: May 2011

Abstract
Purpose: Programmed death ligand 1 (PD-L1) is expressed on antigen-presenting cells and inhibits activation of T cells through its receptor PD-1. PD-L1 is aberrantly expressed on some epithelial malignancies and Hodgkin lymphomas and may prevent effective host antitumor immunity. The role of PD-L1 in non–Hodgkin lymphomas (NHL) is not well characterized.
Experimental Design: PD-L1 expression was analyzed in cell lines and lymphoma specimens by using flow cytometry and immunohistochemistry. Functional activity of PD-L1 was studied by incubating irradiated lymphoma cells with allogeneic T cells with or without anti-PD-L1 blocking antibody; T-cell proliferation and IFN-γ secretion served as measures of T-cell activation. Similar experiments were conducted using cultures of primary lymphoma specimens containing host T cells.
Results: PD-L1 was expressed uniformly by anaplastic large cell lymphoma (ALCL) cell lines, but rarely in B-cell NHL, confined to a subset of diffuse large B-cell lymphomas (DLBCL) with activated B-cell features (3 of 28 cell lines and 24% of primary DLBCL). Anti-PD-L1 blocking antibody boosted proliferation and IFN-γ secretion by allogeneic T cells responding to ALCL and DLBCL cells. In autologous cultures of primary ALCL and DLBCL, PD-L1 blockade enhanced secretion of inflammatory cytokines IFN-γ, granulocyte macrophage colony-stimulating factor, interleukin (IL)-1, IL-6, IL-8, IL-13, TNF-α, and macrophage inflammatory protein-1α. In establishing cell lines from an aggressive PD-L1+ mature B-cell lymphoma, we also noted that PD-L1 expression could be lost under certain in vitro culture conditions.
Conclusions: PD-L1 may thwart effective antitumor immune responses and represents an attractive target for lymphoma immunotherapy. Clin Cancer Res; 17(13); 4232–44. ©2011 AACR.
Activated MET Is a Molecular Prognosticator and Potential Therapeutic Target for Malignant Peripheral Nerve Sheath Tumors
Authors: Torres Keila E. , Zhu Quan-Sheng , Bill Katelynn , Lopez Gonzalo , Ghadimi Markus P. , Xie Xianbiao , Young Eric D. , Liu Juehui , Nguyen Theresa , Bolshakov Svetlana , Belousov Roman , Wang Suizhau , Lahat Guy , Liu Jun , Hernandez Belinda , Lazar Alexander J. , Lev Dina 
Published: May 2011

Abstract
Purpose: MET signaling has been suggested a potential role in malignant peripheral nerve sheath tumors (MPNST). Here, MET function and blockade were preclinically assessed.
Experimental Design: Expression levels of MET, its ligand hepatocyte growth factor (HGF), and phosphorylated MET (pMET) were examined in a clinically annotated MPNST tissue microarray (TMA) incorporating univariable and multivariable statistical analyses. Human MPNST cells were studied in vitro and in vivo; Western blot (WB) and ELISA were used to evaluate MET and HGF expression, activation, and downstream signaling. Cell culture assays tested the impact of HGF-induced MET activation and anti-MET–specific siRNA inhibition on cell proliferation, migration, and invasion; in vivo gel-foam assays were used to evaluate angiogenesis. Cells stably transduced with anti-MET short hairpin RNA (shRNA) constructs were tested for growth and metastasis in severe combined immunodeficient (SCID) mice. The effect of the tyrosine kinase inhibitor XL184 (Exelixis) targeting MET/VEGFR2 (vascular endothelial growth factor receptor 2) on local and metastatic MPNST growth was examined in vivo.
Results: All three markers were expressed in MPNST human samples; pMET expression was an independent prognosticator of poor patient outcome. Human MPNST cell lines expressed MET, HGF, and pMET. MET activation increased MPNST cell motility, invasion, angiogenesis, and induced matrix metalloproteinase-2 (MMP2) and VEGF expression; MET knockdown had inverse effects in vitro and markedly decreased local and metastatic growth in vivo. XL184 abrogated human MPNST xenograft growth and metastasis in SCID mice.
Conclusions: Informative prognosticators and novel therapies are crucially needed to improve MPNST management and outcomes. We show an important role for MET in MPNST, supporting continued investigation of novel anti-MET therapies in this clinical context. Clin Cancer Res; 17(12); 3943–55. ©2011 AACR.
Epigenetic Alteration of DNA in Mucosal Wash Fluid Predicts Invasiveness of Colorectal Tumors
Authors: Kamimae Seiko , Yamamoto Eiichiro , Yamano Hiro-o , Nojima Masanori , Suzuki Hiromu , Ashida Masami , Hatahira Tomo , Sato Akiko , Kimura Tomoaki , Yoshikawa Kenjiro , Harada Taku , Hayashi Seiko , Takamaru Hiroyuki , Maruyama Reo , Kai Masahiro , Nishiwaki Morie , Sugai Tamotsu , Sasaki Yasushi , Tokino Takashi , Shinomura Yasuhisa , Imai Kohzoh , Toyota Minoru 
Published: May 2011

Abstract
Although conventional colonoscopy is considered the gold standard for detecting colorectal tumors, accurate staging is often difficult because advanced histology may be present in small colorectal lesions. We collected DNA present in mucosal wash fluid from patients undergoing colonoscopy and then assessed the methylation levels of four genes frequently methylated in colorectal cancers to detect invasive tumors. We found that methylation levels in wash fluid were significantly higher in patients with invasive than those with noninvasive tumors. Cytologic and K-ras mutation analyses suggested that mucosal wash fluid from invasive tumors contained greater numbers of tumor cells than wash fluid from noninvasive tumors. Among the four genes, levels of mir-34b/c methylation had the greatest correlation with the invasion and showed the largest area under the receiver operating characteristic curve (AUC = 0.796). Using cutoff points of mir-34b/c methylation determined by efficiency considerations, the sensitivity/specificity were 0.861/0.657 for the 13.0% (high sensitivity) and 0.765/0.833 for the 17.8% (well-balanced) cutoffs. In the validation test set, the AUC was also very high (0.915), the sensitivity/specificity were 0.870/0.875 for 13.0% and 0.565/0.958 for 17.8%. Using the diagnostic tree constructed by an objective algorithm, the diagnostic accuracy of the invasiveness of colorectal cancer was 91.3% for the training set and 85.1% for the test set. Our results suggest that analysis of the methylation of DNA in mucosal wash fluid may be a good molecular marker for predicting the invasiveness of colorectal tumors. Cancer Prev Res; 4(5); 674–83. ©2011 AACR.
Lung-Cancer Chemoprevention by Induction of Synthetic Lethality in Mutant KRAS Premalignant Cells In Vitro and In Vivo
Authors: Huang Shaoyi , Ren Xiaoyang , Wang Lai , Zhang Ling , Wu Xiangwei 
Published: May 2011

Abstract
Lung cancer is the leading cause of cancer death in both men and women in the United States, with a low 5-year survival rate despite improved treatment strategies. These data underscore the great need for effective chemoprevention of this cancer. Mutations and activation of KRAS occur frequently in, and are thought to be a primary driver of the development of, non–small cell lung cancers (NSCLC) of the adenocarcinoma subtype. In this study, we developed a new approach for the chemoprevention of NSCLC involving specific targeting of apoptosis in mutant KRAS cells. This approach is based on a synthetic lethal interaction among TNF-related apoptosis-inducing ligand (TRAIL), the second mitochondria-derived activator of caspase Smac/DIABLO (Smac), and KRAS. Mutational activation of KRAS modulated the expression of TRAIL receptors by upregulating death receptors and downregulating decoy receptors. Furthermore, oncogenic KRAS repressed cellular FADD-like interleukin 1β–converting enzyme (FLICE)-like inhibitory protein (c-FLIP) expression through activation of Erk/mitogen-activated protein kinase (MAPK)-mediated activation of c-Myc. Smac overcame KRAS-induced cell-survival signaling by antagonizing X-linked inhibitor of apoptosis protein (XIAP). Therefore, the combination of TRAIL and a small molecule mimic of Smac induced apoptosis specifically in mutant KRAS cells without harming normal cells. We further showed that short-term, intermittent in vivo treatment with TRAIL and Smac mimic induced apoptosis in tumor cells and reduced tumor burden in a murine model of KRAS-induced lung cancer. These results reflect the potential benefit of a selective therapeutic approach for the chemoprevention of NSCLC. Cancer Prev Res; 4(5); 666–73. ©2011 AACR.
Aspirin and Familial Adenomatous Polyposis: Coming Full Circle
Authors: Chan Andrew T. 
Published: May 2011

Abstract
This perspective discusses the clinical trial reported by Burn and colleagues in this issue of the journal (beginning on page 655), which assessed aspirin and resistant starch for the prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP). The findings are examined in the context of previous clinical trials of aspirin in patients with sporadic adenomas and of sulindac or celecoxib in patients with FAP. This newly reported work raises important considerations of a role for aspirin in the clinical management of FAP patients and adds to considerations of a role for aspirin in the chemoprevention of colorectal cancer among broader populations. Cancer Prev Res; 4(5); 623–7. ©2011 AACR.
Atrioventricular Conduction Disturbance Characterization in Transcatheter Aortic Valve Implantation With the CoreValve Prosthesis
Authors: Rubín José M. , Avanzas Pablo , del Valle Raquel , Renilla Alfredo , Ríos Enrique , Calvo David , Lozano Iñigo , Anguera Ignasi , Díaz-Molina Beatriz , Cequier Angel , Morís de la Tassa César 
Published: May 2011

Background—
Atrioventricular (AV) block is one of the most frequent complications of CoreValve transcatheter aortic valve implantation (TAVI). The aim of this study was to analyze the effects of CoreValve implantation on AV conduction.

Methods and Results—

Electrophysiological study was performed immediately before and after CoreValve implantation in 18 consecutive, permanent pacemaker-free patients. An electrode was placed on the His bundle during valve implantation, and data were continuously recorded during the procedure. With surface ECG, a median (first, third quartile) QRS width of 96 (84, 116) to 150 (121, 164) ms (
P
=0.001) and PR interval of 180 (159, 216) to 210 (190, 240) ms (
P
=0.008) were significantly prolonged, and QRS axis was left deviated 30° (−32°, 46°) to −20° (−60°, 2°) (
P
=0.005). With intracardiac electrograms, the AH (97 [70, 123] to 115 [96, 135] ms,
P
=0.021) and HV (52 [42, 55] to 60 [50, 70] ms,
P
=0.002) intervals were increased. At the end of the procedure, we observed significant ECG- or electrophysiological study-persistent conduction disturbances in 14 (78%) patients. Five patients experienced transient changes (2 AV blocks and 3 left bundle branch blocks).

Conclusions—
CoreValve implantation worsens AV conduction in most patients, either transiently or permanently. This worsening is the result of direct damage either on the His bundle or on the AV node.
Typhoon Track Changes Associated with Global Warming
Authors: Wang Ruifang , Wu Liguang , Wang Chao 
Published: May 2011

Abstract
Increasing tropical cyclone (TC) influence in the subtropical East Asia and decreasing TC activity in the South China Sea over the past few decades have been researched in previous studies. The singular value decomposition (SVD) of observational data and the Intergovernmental Panel on Climate Change (IPCC) climate change simulations in the Fourth Assessment Report (AR4) shows that the observed TC track changes are linked to the leading SVD mode of global sea surface temperature (SST) warming and the associated changes in large-scale steering flows. The selected five IPCC models can generally simulate the leading mode in their ensemble control run and prediction, suggesting the possible persistence of the reported track changes by 2040.
Sentinel Node Biopsy for Head and Neck Melanoma
Authors: de Rosa Nicole , Lyman Gary H. , Silbermins Damian , Valsecchi Matias E. , Pruitt Scott K. , Tyler Douglas M. , Lee Walter T. 
Published: May 2011

ObjectiveThis systematic review was conducted to examine the test performance of sentinel node biopsy in head and neck melanoma, including the identification rate and false‐negative rate.Data SourcesPubMed, EMBASE, ASCO, and SSO database searches were conducted to identify studies fulfilling the following inclusion criteria: sentinel node biopsy was performed, lesions were located on the head and neck, and recurrence data for both metastatic and nonmetastatic patients were reported.Review MethodsDual‐blind data extraction was conducted. Primary outcomes included identification rate and test performance based on completion neck dissection or nodal recurrence.ResultsA total of 3442 patients from 32 studies published between 1990 and 2009 were reviewed. Seventy‐eight percent of studies were retrospective and 22% were prospective. Trials varied from 9 to 755 patients (median 55). Mean Breslow depth was 2.53 mm. Median sentinel node biopsy identification rate was 95.2%. More than 1 basin was reported in 33.1% of patients. A median of 2.56 sentinel nodes per patient were excised. Sentinel node biopsy was positive in 15% of patients. Subsequent completion neck dissection was performed in almost all of these patients and revealed additional positive nodes in 13.67%. Median follow‐up was 31 months. Across all studies, predictive value positive for nodal recurrence was 13.1% and posttest probability negative was 5%. Median false‐negative rate for nodal recurrence was 20.4%.ConclusionSentinel node biopsy of head and neck melanoma is associated with an increased false‐negative rate compared with studies of non–head and neck lesions. Positive sentinel node status is highly predictive of recurrence.
Repair of Focal Cartilage Defects with Scaffold-Assisted Autologous Chondrocyte Grafts
Authors: Kreuz Peter C. , Müller Sebastian , Freymann Undine , Erggelet Christoph , Niemeyer Philipp , Kaps Christian , Hirschmüller Anja 
Published: May 2011

Background Scaffold-assisted autologous chondrocyte implantation is a clinically effective procedure for cartilage repair, but biomechanical evaluations are still missing. Purpose This study was conducted to assess the clinical efficacy, including biomechanical analyses, of BioSeed-C treatment for traumatic and degenerative cartilage defects of the knee. Study Design Case series; Level of evidence, 4. Methods The authors evaluated the midterm clinical and biomechanical outcome of BioSeed-C, a cell-based fibrin-polymer graft for the treatment of cartilage defects. Clinical outcome at 4-year follow-up was assessed in 52 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) stage III and IV. Clinical scoring was performed preoperatively and 48 months after implantation using the Lysholm score, the International Knee Documentation Committee (IKDC) score, the ICRS score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes score. Cartilage regeneration was assessed by magnetic resonance imaging (MRI) using the Henderson-Kreuz score. Biomechanical evaluation was performed by isokinetic strength measurements, comparing healthy and operated knee of each patient. Results Clinical evaluation showed significant improvement in the Lysholm (from 51.8 preoperatively to 80.7 at 48 months postoperatively), IKDC (from 47.5 to 71.5), ICRS (from 3.8 to 2.0), KOOS (subcategory pain from 62 to 78, symptoms from 68 to 76, activities of daily living from 68 to 85, sports from 19 to 55, and quality of life from 30 to 55), and Noyes (from 31 to 59) scores ( P ≤ .001) 48 months after implantation of BioSeed-C compared with the preoperative situation. The MRI evaluations showed moderate to complete defect filling in 43 of 44 treated patients. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years. Isokinetic evaluation showed significantly reduced maximum strength capacities for knee flexion and extension at the operated knee compared with the healthy knee ( P < .05). Conclusion The clinical outcomes 4 years after graft implantation are good despite a persisting strength deficit. Implanting Bio-Seed-C is a promising treatment option for cartilage defects of the knee. More emphasis should be put on the rehabilitation of muscular strength.
Sociocultural study of immigrant suicide-attempters: An ecological perspective
Authors: Chung Irene 
Published: May 2011

•  Summary: This article discusses the findings of a qualitative study with a sample of suicide attempters in the Chinese immigrant community of New York City from an ecological perspective. •  Findings: The narratives of the participants delineate the pathway of their suicide attempts as the culmination of an interactive process of stressors, mental illness, and diminished help-seeking behavior, compounded by immigrant-specific issues, cultural meanings of distress and social barriers to resources. •  Application: The transactional dynamics of these risk factors underscore the importance of adopting an integrative and contextualized stance of inquiry in suicide studies and initiating a broad-based community effort in suicide prevention.
Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients
Authors: Elmaagacli Ahmet H. , Steckel Nina K. , Koldehoff Michael , Hegerfeldt Yael , Trenschel Rudolf , Ditschkowski Markus , Christoph Sandra , Gromke Tanja , Kordelas Lambros , Ottinger Hellmut D. , Ross Rudolf S. , Horn Peter A. , Schnittger Susanne , Beelen Dietrich W. 
Published: May 2011

AbstractThe impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.