bluuebunny/crossref_metadata_2025_split huggingface dataset:
HepPar-1 and Arginase-1 Immunohistochemistry in Adenocarcinoma of the Small Intestine and Ampullary Region
Authors: Lagana Stephen , Hsiao Susan , Bao Fei , Sepulveda Antonia , Moreira Roger , Lefkowitch Jay , Remotti Helen 
Published: June 2015

Context
HepPar-1 and Arginase-1 are urea cycle enzymes used to distinguish hepatocellular carcinoma from other carcinomas. HepPar-1, but not Arginase-1, is known to be immunoreactive with normal human small intestine.

Objectives
To better define and compare the immunohistochemical staining patterns of HepPar-1 and Arginase-1 in adenocarcinomas arising in the small intestine, including the ampullary region.

Design
Staining for HepPar-1 and Arginase-1 was performed on 20 nonampullary small intestinal adenocarcinomas and 32 adenocarcinomas from the ampullary region. Ampullary adenocarcinomas were divided into intestinal morphology (15), pancreatobiliary morphology (14), and unclassifiable (3). Nonneoplastic small intestinal mucosa and colorectal adenocarcinomas were used as control groups.

Results
HepPar-1 stained 12 of 20 nonampullary small intestinal adenocarcinomas, with a median of 63% of cells staining in positive cases. It also stained 11 of 15 ampullary carcinomas with intestinal morphology, with a median of 75% of cells staining in positive cases. Two of 14 ampullary carcinomas with pancreatobiliary morphology were positive for HepPar-1. Arginase-1 showed positivity in 2 ampullary region carcinomas and diffuse positivity in 1 duodenal adenocarcinoma. Two of 22 colorectal carcinomas stained for HepPar-1 with none positive for Arginase-1.

Conclusions
HepPar-1, but not Arginase-1, usually shows positivity in small intestinal adenocarcinomas and ampullary adenocarcinomas with intestinal morphology, but only rarely shows positivity in ampullary adenocarcinomas with pancreatobiliary morphology. HepPar-1 positivity in metastatic adenocarcinoma with intestinal morphology is suggestive of an upper gastrointestinal primary site.
Determination of Genotypes Using a Fully Automated Molecular Detection System
Authors: Spizz Gwendolyn , Chen Zongyuan , Li Peng , McGuire I. Cristina , Klimkiewicz Paulina , Zysling Devin , Yasmin Rubina , Hungerford Whitney , Thomas Benjamin , Wilding Gregory , Mouchka Gregory , Young Lincoln , Zhou Peng , Montagna Richard A. 
Published: June 2015

ContextAlthough the value of pharmacogenomics to improve patient outcomes has become increasingly clear, adoption in medical practice has been slow, which can be attributed to several factors, including complicated and expensive testing procedures and required equipment, lack of training by private practice physicians, and reluctance of both private and commercial payers to reimburse for such testing.ObjectivesTo evaluate a fully automated molecular detection system for human genotyping assays, starting with anticoagulated whole blood samples, and to perform all sample preparation, assay, and analysis steps automatically with actionable results reported by the system's software.DesignThe genotypes of 254 random individuals were determined by performing bidirectional DNA sequencing, and that information was used to statistically train the imaging software of the automated molecular detection system to distinguish the 3 possible genotypes (ie, homozygous wild type, heterozygous, and homozygous mutant) at each of 3 different loci (CYP2C9*2, CYP2C9*3, and VKORC1).Results—The resulting software algorithm was able to correctly identify the genotypes of all 254 individuals (100%) evaluated without any further user analysis.ConclusionsThe EncompassMDx workstation (Rheonix, Inc, Ithaca, New York) is a molecular detection system that can automatically determine the genotypes of individuals in an unattended manner. Considerably less technical expertise was required to achieve results identical to those obtained using more complex, time-consuming, and expensive bidirectional DNA sequencing. This optimized system may dramatically simplify and reduce the costs of pharmacogenomics testing, thus leading to more-widespread use.
Multiphoton Microscopy: A Potential Intraoperative Tool for the Detection of Carcinoma In Situ in Human Bladder
Authors: Jain Manu , Robinson Brian D. , Shevchuk Maria M. , Aggarwal Amit , Salamoon Bekheit , Dubin Justin M. , Scherr Douglas S. , Mukherjee Sushmita 
Published: June 2015

Context
Urothelial carcinoma in situ (CIS) is a precursor of invasive bladder cancer, which if left untreated, will likely progress to more aggressive disease. Approximately 50% of CIS lesions are missed on routine cystoscopy owing to their flat architecture. Furthermore, many benign but abnormal-appearing areas may be biopsied owing to lack of cellular resolution of cystoscopes. Multiphoton microscopy (MPM) is an optical imaging technique that generates subcellular-resolution three-dimensional images from unfixed tissue without using exogenous dyes.

Objective
To assess the diagnostic potential of MPM in identifying and differentiating benign from malignant flat bladder lesions, especially CIS.

Design
Seventy-eight specimens (benign = 46, CIS = 23, invasive = 9, as diagnosed on histopathology) were obtained from flat bladder mucosa via transurethral resection of bladder, cold cup biopsy, or cystectomy, imaged fresh with a commercial benchtop MPM, and submitted for routine histopathology. Multiphoton microscopy and hematoxylin-eosin diagnoses were compared.

Results
In 77 of 78 specimens (99%), accurate MPM diagnoses (benign/malignant) were given on the basis of their architectural and cytologic features (nuclear to cytoplasmic ratio, pleomorphism, polarity/organization of urothelial layers, etc). The sensitivity and specificity were 97% and 100%, respectively, with positive (malignant) and negative (benign) predictive values of 100% and 98%, respectively. The interobserver agreement, κ, was 0.93.

Conclusions
Our study demonstrates the capability of MPM to identify and differentiate benign from malignant flat bladder lesions, especially CIS. With the advent of MPM endoscopes, we foresee their potential as a biopsy guidance tool for early detection and treatment of CIS, thus reducing the rate of biopsies with benign diagnoses and their associated complications.
Squamous Cell Carcinoma of the Cervix: A Cytology-Histology-Human Papillomavirus Correlation in Clinical Practice
Authors: Miller Ross A. , Waters Lindsay L. , Mody Dina R. , Tams Kimberlee C. 
Published: June 2015

ContextCervical cancer mortality has declined by 74% in the United States since the implementation of the Papanicolaou (Pap) test. Nevertheless, more than 12 000 US women annually develop cervical cancer, and squamous cell carcinoma (SqCa) remains the predominant cervical malignancy.ObjectiveTo evaluate screening techniques used in the detection of SqCa of the cervix and provide insights regarding which technique(s) is (are) most efficacious in our study population.DesignWe retrospectively reviewed all available cytologic, human papillomavirus (HPV), and histologic malignancy burden data from patients diagnosed with SqCa. The clinical data were collected from 2 geographically and socioeconomically diverse hospital systems. Cases in which identified patients had a Pap test with a negative result/unsatisfactory specimen within 5 years of SqCa tissue diagnosis were considered Pap test screening failures. Cases in which patients were diagnosed with HPV-negative SqCa were considered HPV screening failures.ResultsEighty-eight cases (patients' ages ranging from 19 to 73 years) were identified. Of those, cytologic history was available for 64 cases present in our electronic medical history record. Three cases were cytology screening failures (one being an unsatisfactory specimen) and 3 cases were HPV screening failures (one being the cytologic unsatisfactory case). Although measuring sensitivity in practice has limitations, we calculated the SqCa detection sensitivity at 95.3% by Pap test alone and 97% when HPV DNA testing was incorporated.ConclusionsOur results highlight the necessity of combining Pap and HPV testing. Although the number of cases identified is relatively small, our data suggest detection failures will decrease as the practice of combining HPV and Pap testing increases.
Molecular and Histologic Considerations in the Assessment of Serrated Polyps
Authors: Yang Hui-Min , Mitchell James M. , Sepulveda Jorge L. , Sepulveda Antonia R. 
Published: June 2015

Context
Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp–carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors.

Objective
To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance.

Data Sources
Published literature focused on serrated polyps and their association with colorectal cancer.

Conclusions
Three types of serrated polyps are currently recognized: hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. The BRAF V600E mutation is one of the most frequent molecular abnormalities identified in hyperplastic polyps and sessile serrated adenomas. In contrast, in traditional serrated adenomas, either BRAF V600E or KRAS mutations can be frequently identified. CpG methylation has emerged as a critical molecular mechanism in the sessile serrated pathway. CpG methylation of MLH1 often leads to reduced or lost expression in dysplastic foci and carcinomas arising in sessile serrated adenomas/polyps.
Le leadership et le discours dans la mobilisation d'acteurs du développement
Authors: Stecq Hervé , Simard Martin 
Published: June 2015

Le phénomène de la migration des jeunes affecte les espaces ruraux et les villes petites et moyennes depuis plusieurs décennies au Québec. Avec la baisse de la natalité, cette forme de migration est devenue plus visible à partir des années 1990 et elle a suscité une mobilisation des acteurs du milieu dans la région du Saguenay−Lac-Saint-Jean. Le regroupement Action-jeunesse (RAJ02) y a orchestré l’élaboration et la mise en oeuvre de la stratégie MigrAction, une politique originale conçue régionalement qui a nécessité la coordination fine d’un grand nombre d’acteurs sur plusieurs années. Notre recherche visait à comprendre les mécanismes d’activation d’une dynamique d’acteurs territorialisés. Le but précis de l’étude était de démontrer que la mobilisation des acteurs se manifeste à travers les interactions. Nous nous sommes particulièrement intéressés à deux éléments : le leadership et le discours. Sur le plan méthodologique, nous avons effectué des entrevues semi-dirigées d’acteurs régionaux et une revue de presse. La recherche a illustré les rôles du leadership et du discours lors de la mobilisation au sein d’un réseau d’acteurs. Ainsi, la construction d’un discours commun fait appel à l’exercice d’un leadership qui permet la coopération des acteurs. De plus, les jeunes acteurs du développement engagés dans la stratégie MigrAction y ont trouvé une forme d’auto-légitimation de leur choix résidentiel ainsi que des éléments d’affirmation identitaire.
Murine Models of Helicobacter (pylori or felis)‐associated Gastric Cancer
Authors: Duckworth Carrie A. , Burkitt Michael D. , Williams Jonathan M. , Parsons Bryony N. , Tang Joseph M.F. , Pritchard D. Mark 
Published: June 2015

AbstractGastric adenocarcinoma is the fifth most common cancer and third most common cause of cancer‐related death in the world. The majority of these cancers develop in genetically susceptible individuals who are chronically infected with the Gram‐negative bacterium Helicobacter pylori. Often these individuals have also been exposed to certain environmental factors that increase susceptibility, such as dietary components. Murine models of Helicobacter‐induced gastric cancer are valuable tools for investigating the mechanisms responsible for the stepwise pathological changes of chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric adenocarcinoma. Helicobacter felis colonization greatly accelerates the development of gastric neoplasia in mice, and causes pathologies similar to those observed with Helicobacter pylori‐associated gastric carcinogenesis in humans. These mouse models are therefore useful for investigating genetic and environmental factors that may be involved in the pathogenesis and treatment of gastric cancer. Detailed in these protocols are procedures for inducing Helicobacter‐associated carcinogenesis in mice as well as the histological analysis and interpretation of gastric pathology in these animals. © 2015 by John Wiley & Sons, Inc.
Time‐dependent compaction band formation in sandstone
Authors: Heap Michael J. , Brantut Nicolas , Baud Patrick , Meredith Philip G. 
Published: June 2015

AbstractCompaction bands in sandstone are laterally extensive planar deformation features that are characterized by lower porosity and permeability than the surrounding host rock. As a result, this form of localization has important implications for both strain partitioning and fluid flow in the Earth's upper crust. To better understand the time dependency of compaction band growth, we performed triaxial deformation experiments on water‐saturated Bleurswiller sandstone (initial porosity = 0.24) under constant stress (creep) conditions in the compactant regime. Our experiments show that inelastic strain accumulates at a constant stress in the compactant regime, manifest as compaction bands. While creep in the dilatant regime is characterized by an increase in porosity and, ultimately, an acceleration in axial strain rate to shear failure, compaction creep is characterized by a reduction in porosity and a gradual deceleration in axial strain rate. The global decrease in the rates of axial strain, acoustic emission energy, and porosity change during creep compaction is punctuated at intervals by higher rate excursions, interpreted as the formation of compaction bands. The growth rate of compaction bands formed during creep is lower as the applied differential stress, and hence, background creep strain rate, is decreased. However, the inelastic strain associated with the growth of a compaction band remains constant over strain rates spanning several orders of magnitude (from 10−8 to 10−5 s−1). We find that despite the large differences in strain rate and growth rate (from both creep and constant strain rate experiments), the characteristics (geometry and thickness) of the compaction bands remain essentially the same. Several lines of evidence, notably the similarity between the differential stress dependence of creep strain rate in the dilatant and compactant regimes, suggest that as for dilatant creep, subcritical stress corrosion cracking is the mechanism responsible for compactant creep in our experiments. Our study highlights that stress corrosion is an important mechanism in the time‐dependent porosity loss, subsidence, and permeability reduction of sandstone reservoirs.
In Vivo Delivery of Nitric Oxide‐Sensing, Single‐Walled Carbon Nanotubes
Authors: Iverson Nicole M. , Strano Michael S. , Wogan Gerald N. 
Published: June 2015

AbstractDetection of nitric oxide (NO) in vivo by single‐walled carbon nanotubes (SWNT) is based on the fluorescent properties of SWNT and the ability of NO to quench the fluorescence signal. Alterations of the signal can be utilized to detect a small molecule in vivo that has not previously been possible by other assay techniques. The protocols described here explain the techniques used to prepare NO‐detecting SWNTs and to administer them to mice by both intravenous and subcutaneous routes. These techniques can also be utilized with other SWNT sensors as well as non‐SWNT sensors. © 2015 by John Wiley & Sons, Inc.
Biosensing with Virus Electrode Hybrids
Authors: Mohan Kritika , Penner Reginald M. , Weiss Gregory A. 
Published: June 2015

AbstractVirus electrodes address two major challenges associated with biosensing. First, the surface of the viruses can be readily tailored for specific, high affinity binding to targeted biomarkers. Second, the viruses are entrapped in a conducting polymer for electrical resistance‐based, quantitative measurement of biomarker concentration. To further enhance device sensitivity, two different ligands can be attached to the virus surface, and increase the apparent affinity for the biomarker. In the example presented here, the two ligands bind to the analyte in a bidentate binding mode with a chelate‐based avidity effect, and result in a 100 pM experimentally observed limit of detection for the cancer biomarker prostate‐specific membrane antigen. The approach does not require enzymatic amplification, and allows reagent‐free, real‐time measurements. This article presents general protocols for the development of such biosensors with modified viruses for the enhanced detection of arbitrary target proteins. © 2015 by John Wiley & Sons, Inc.
SELMA: Selection with Modified Aptamers
Authors: Temme J. Sebastian , Krauss Isaac J. 
Published: June 2015

AbstractIn vitro selection of nucleic acid aptamers, coined SELEX, has led to the discovery of novel therapeutics and aided in the structural and mechanistic understanding of many ligand‐biomolecule interactions. A related method, selection with modified aptamers (SELMA), enables selection of DNA aptamers containing bases with a large modification that cannot undergo PCR. A key application of this method is the evolution of aptamers containing carbohydrate modifications. Carbohydrate‐binding proteins normally require several copies of the carbohydrate moiety for strong recognition. Whereas it may be difficult to rationally design synthetic scaffolds that cluster glycans in the optimal spacing and orientation for target recognition, SELMA furnishes glycoaptamers with highly optimized glycan clustering, achieving low‐nanomolar recognition. Although numerous applications can be envisioned, the protocols and discussions in this article describe procedures involved in applying SELMA to the discovery glycoDNAs that bind to the HIV broadly neutralizing antibody 2G12. © 2015 by John Wiley & Sons, Inc.
Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial
Authors: Dougados Maxime , Huizinga Tom W. J. , Choy Ernest H. , Bingham Clifton O. , Aassi Maher , Bernasconi Corrado 
Published: June 2015

ObjectiveTo assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28‐2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT‐RAY study.MethodsPatients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28‐2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28‐2 definition.ResultsAfter tocilizumab discontinuation, DAS28‐2 was sensitive (88–100%), but not specific (57–65%), for detecting investigator flare. Under constant treatment, DAS28‐2 criteria were met in 136 cases per 100 patient‐years despite stable disease activity. Sustained flares were infrequent. Other DAS28‐based criteria led to similar conclusions.ConclusionDAS28‐based flare occurred more often than investigator‐defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.
Catalytic Ketone Hydrodeoxygenation Mediated by Highly Electrophilic Phosphonium Cations
Authors: Mehta Meera , Holthausen Michael H. , Mallov Ian , Pérez Manuel , Qu Zheng‐Wang , Grimme Stefan , Stephan Douglas W. 
Published: June 2015

AbstractKetones are efficiently deoxygenated in the presence of silane using highly electrophilic phosphonium cation (EPC) salts as catalysts, thus affording the corresponding alkane and siloxane. The influence of distinct substitution patterns on the catalytic effectiveness of several EPCs was evaluated. The deoxygenation mechanism was probed by DFT methods.
Regioselective Nucleophilic Functionalization of Antiaromatic Nickel(II) Norcorroles
Authors: Nozawa Ryo , Yamamoto Keitaro , Shin Ji‐Young , Hiroto Satoru , Shinokubo Hiroshi 
Published: June 2015

AbstractTreatment of antiaromatic nickel(II) norcorrole with potassium cyanide provided nickel(II) 3‐cyanonorcorrole with perfect regioselectivity without the help of a catalyst. The reaction of the nickel(II) norcorrole with phenol or thiophenol in the presence of a base also yielded substitution products. The antiaromatic 16π conjugation system in the norcorrole core was preserved in the functionalized products. Introduction of phenylthio groups significantly decreased the HOMO–LUMO gap and enhanced the near IR absorption property.
Isolation and Total Synthesis of Kirkamide, an Aminocyclitol from an Obligate Leaf Nodule Symbiont
Authors: Sieber Simon , Carlier Aurélien , Neuburger Markus , Grabenweger Giselher , Eberl Leo , Gademann Karl 
Published: June 2015

AbstractThe new C7N aminocyclitol kirkamide (1) was isolated from leaf nodules of the plant Psychotria kirkii by using a genome‐driven 1H NMR‐guided fractionation approach. The structure and absolute configuration were elucidated by HRMS, NMR, and single‐crystal X‐ray crystallography. An enantioselective total synthesis was developed, which delivered kirkamide (1) on a gram scale in 11 steps and features a Ferrier carbocyclization and a Pd‐mediated hydroxymethylation. We propose that kirkamide is synthesized by Candidatus Burkholderia kirkii, the obligate leaf symbiont of Psychotria kirkii. Kirkamide (1) was shown to be toxic to aquatic arthropods and insects, thus suggesting that bacterial secondary metabolites play a protective role in the Psychotria/Burkholderia leaf nodule symbiosis.
An Alternative Anionic Polyelectrolyte for Aqueous PEDOT Dispersions: Toward Printable Transparent Electrodes
Authors: Hofmann Anna I. , Smaal Wiljan T. T. , Mumtaz Muhammad , Katsigiannopoulos Dimitrios , Brochon Cyril , Schütze Falk , Hild Olaf R. , Cloutet Eric , Hadziioannou Georges 
Published: June 2015

AbstractOrganic conducting polymers are promising electrode materials for printable organic electronics. One of the most studied conducting polymers is PEDOT:PSS, which is sufficiently conductive and transparent, but which shows some drawbacks, such as hygroscopicity and acidity. A new approach to stabilize PEDOT in aqueous dispersions involves the replacement of PSS with a basic polyanion based on a polystyrene backbone with (trifluoromethylsulfonyl)imide (TSFI) side groups. The PEDOT:PSTFSIK dispersions were obtained by oxidative polymerization of EDOT in an aqueous PSTFSIK solution and were characterized with regard to their composition, morphology, doping, rheological behavior, and optoelectronic performance. The PEDOT:PSTFSIK dispersions showed excellent printability and good optoelectronic performance (238 Ohm sq−1 at 91 % transmittance, σ>260 S cm−1) and were successfully integrated as flexible electrodes in OLED and OPV devices.