bluuebunny/crossref_metadata_2025 huggingface dataset:
Images and Performative Vision in the Middle Ages
Authors: Bino Carla Maria
Published: February 2021

During the Middle Ages, images had to be tied to the truth. Otherwise, they were considered idols. And the idols are always dangerous and, therefore, banned. So, to be justified, the imago had to be true or really refer to truth. It follows that the images were not considered just objects ‘to see’, but were perceived as almost ‘alive bodies’, real bodies: they could act as if were actually present. This essay studies the image concept in Christian thought, with particular attention to Eastern Europe, in connection to the patristic and conciliar sources. The result is the shift of its ontological meaning: contrary to the mimetic idea of greek-hellenistic culture, the christian image is an ‘impression of similarity’. This conceptual revolution implies change of visualization strategies, which are specifically performative: ‘seeing the icon’ is doing something which involves ‘physically’ the viewer, as if he came into a scene and became an actor.
Maestro Mateo en el Museo Catedral de Santiago de Compostela
Authors: Yzquierdo Peiró Ramón
Published: February 2021

En noviembre de 2016 se inauguraba en el Museo Nacional del Prado la exposición Maestro Mateo, primera monográfica dedicada a un artista gallego y al arte medieval celebrada en dicha institución museística en sus casi doscientos años de historia. Tras la clausura de la muestra, en abril de 2017, esta se trasladó al Museo Catedral de Santiago, donde completó sus contenidos con nuevas piezas de los fondos de ambos museos, permaneciendo abierta al público hasta el 23 de febrero de 2018, fecha en que se conmemoró el 850 aniversario de la concesión a Mateo, por el rey Fernando II, de una pensión vitalicia por la dirección de las obras en la catedral compostelana, momento que suele considerarse como el punto de partida del proyecto mateano. Entre los años 1168 y 1211, el Maestro Mateo llevó a cabo, con su taller, un ambicioso proyecto que supuso la conclusión de las obras de construcción de la catedral románica, así como la adecuación de sus espacios para un ceremonial acorde a su singularidad; nacía, con ello, un arte gallego con personalidad propia que habría de tener gran influencia posterior. Sin duda, el Maestro Mateo es el gran artista de la catedral de Santiago y como tal se considera, desde la referida exposición, en su Museo, donde hay una importante presencia de fondos, a través de los cuales es posible recuperar la memoria de un proyecto clave para la catedral y para la historia del arte medieval. Desde abril de 2018, el Museo Catedral cuenta con un nuevo espacio monográfico dedicado al Maestro Mateo, con una selección de piezas originales que se centran, fundamentalmente, en el inicio del proyecto, en la arquitectura y escultura de la fachada exterior del Pórtico de la Gloria, en el coro pétreo y, por fin, en aquellos talleres de influencia mateana que tomaron su testigo a lo largo de todo el siglo XIII.
O enigma do protagonismo imperial no Tapiz de la Creación
Authors: Queiroz de Souza Guilherme
Published: February 2021

O Tapiz de la Creación (séculos XI-XII) pode ser considerado a obra mais famosa e enigmática do românico catalão. Nossa pesquisa focaliza o friso inferior parcialmente perdido, que exibe os topos de uma cruz e de uma coroa imperial. O enigma central é: quem portava tais objetos? Se considerarmos a proporção/tamanho deles, o personagem teria um significativo destaque no bordado. Alguns estudiosos cunharam hipóteses sobre essa problemática, apontando três possibilidades: a imperatriz Helena (c. 250- 330), o imperador Constantino I (272-337) e o basileus Heráclio I (c. 575-641), com destaque para os dois últimos. Não temos a presunção de desvendar a identidade do protagonista imperial no Tapiz; nossa principal intenção é apresentar o estado da questão, além de comentar algumas teorias à luz de novos indícios. Uma aproximação à identidade do personagem conduziria não somente a uma reinterpretação dessa famosa obra (simbologia, funcionalidade), mas também ao mapeamento da introdução do mito imperial (constantiniano ou heracliano) na Catalunha dos séculos XI-XII, o que contribui para entender sua influência sobre a religiosidade, comportamento sociopolítico, etc.
La Capilla del Cristo de la Columna de la Catedral de Toledo
Authors: Franco Mata Ángela
Published: February 2021

Resumen. En la catedral de Toledo existe una capilla ubicada en la girola, que da nombre al contenido, de especial interés desde el punto de vista iconográfico y teatral. Ostenta un retablo con la representación de Cristo a la columna entre san Pedro y san Juan. Es la interpretación plástica del Auto de la pasión, de Alonso del Campo, escrito entre 1486 y 1499. Se completa con la figura de la Verónica. Tuvo una cierta difusión en el campo de la miniatura, como en el Libro de Horas de Alonso de Zúñiga, conservado en la Real Biblioteca de El Escorial, y en la escultura, en el grupo de Cristo a la columna y san Pedro (se ha perdido san Juan) en Alcaraz (Albacete).
Biofeedback Enriches the Counseling Experience
Authors: Fragedakis Tami Maes , Leierer Stephen , Toriello Paul , Russoniello Carmen , Sherlin Leslie
Published: February 2021

Counseling has been identified as an effective form of treatment, assisting individuals in dealing with stress, fulfilling their personal goals, and establishing healthy lifestyles. While talk therapy is effective, high noncompliance rates lead to further dysfunction and additional health conditions. Incorporating biofeedback with counseling may enrich the overall counseling experience, particularly when considering process variables, including the working alliance and treatment satisfaction, as a means to further reduce noncompliance rates.
A Happy Heart Comes First: Heart-Based Compassion Training
Authors: Ehrenreich Yossi
Published: February 2021

Practicing mindfulness, acceptance, and compassion have in recent years become widely accepted as part of biofeedback therapy. Compassion, in particular, has a measurable physiological basis through the conventional HRV biofeedback instrumentation. The present article reviews the research basis for the integration of compassion in the treatment of biofeedback beyond the essential eclectic use of compassionate practices in biofeedback therapy. Also, it offers two ways of integrating compassion within biofeedback-based interventions.
Armonización de las Carreras de Educación en Nicaragua: experiencia y proyecciones
Authors: Escobar Soriano Álvaro , Videa Xiomara Lisbeth , De Armas Roberto
Published: February 2021

Armonizar currículos de educación en Nicaragua es integrarlos mediante dispositivos políticos, académicos y culturales, pero respetando las particularidades institucionales y las características de las sociedades regionales a las cuales responden los planes de estudios. Este proceso se desarrolla mediante la organización e instalación de los diferentes equipos de trabajo, diseño o rediseño de planes y programas educativos, implementación del diseño o rediseño curricular y seguimiento y evaluación.   Por tanto, el trabajo de los colectivos de académicos y las comisiones de armonización con el apoyo de los dirigentes institucionales y el oportuno acompañamiento y asesoría, ha tenido un avance significativo, a diferentes ritmos, en el diseño de los mismos.
Inventario de mariposas diurnas en agroecosistemas tropicales como bioindicadores de la calidad ambiental
Authors: Flores Pacheco Juan Asdrúbal , Saldivar Solano Denis Jonathan , Rigby Omier Keldeem Kadovic , Murillo Gaitán Yenmi Yoset
Published: February 2021

El presente estudio se desarrolló en el Centro de Transferencia Agroforestal (CeTAF), Comunidad Indígena de Tiktik Kaanu. Con el objetivo de describir la distribución taxonómica de los lepidópteros diurnos capturados con relación a sus distintos agroecosistemas. Así como dar a conocer la riqueza, abundancia y funciones ecológicas de cada grupo taxonómico. A través de un estudio exploratorio y descriptivo, se realizó un inventario con el objetivo de identificar la diversidad de especies presentes en el sitio. El muestreo reflejó un total de 409 individuos con 41 especies de mariposas pertenecientes a ocho subfamilias. La familia y subfamilia más representativas en número de especies y abundancia fueron Nymphalidae y Heliconinae respectivamente siendo la especie más abundante Heliconius erato. Petiverana. Se presentaron diferencias significativas en la riqueza y diversidad de las localidades de estudio, existiendo una disminución a medida que la estructura del paisaje cambia conforme a características que influencian la comunidad de mariposas. Es posible que la transformación de hábitats naturales en áreas de uso agrícola se constituya en un factor que modifica la estructura de las comunidades de mariposas en la región. El inventario de mariposas diurnas en el área del CeTAF es el primer inventario de lepidópteros que se realiza en la zona del caribe, la cual está dentro de la Reserva Natural de Cerro Silva en el Territorio Rama – Kriol que sin lugar a duda genera una base de datos importante para la región.
Remoción de Cromo, Hierro y Manganeso de aguas contaminadas utilizando criogeles como adsorbente
Authors: Jarquín Pascua Martha , López Hernández Maybis , Guillén Castillo Wilton , Lacayo Romero Martha
Published: February 2021

El objetivo de este estudio fue remover el cromo (Cr3+), hierro (Fe3+) y manganeso (Mn2+) de aguas contaminadas utilizando macroporos gel de poliacriamina (MPAAG) llamado criogel o hidrogel como material adsorbente. El criogel MPAAG fue preparado a una concentración de 7,5 % (w/v), cuya polimerización se realizó a -12 oC por 1 horas. Se adicionó grupos ligandos de aminas y carboxilos como el tris (2aminoethyl) amine (TREN) seguido del ácido bromo acético (BA). Las soluciones de los iones de los metales de Cr3+, Fe3+ y Mn2+ a concentración de 74 mg/L, 24 mg/L y 27 mg/L respectivamente, estuvieron en contacto con el adsorbente (MPAAG-TBA) ajustados a pH 2, 3 y 5 para Cr3+, pH 3 y 5 para Fe3+ y pH 3, 5 y 7 para Mn2+; la solución fue  agitada a 200 rpm durante 3 horas; se tomaron alícuotas de 10 ml a los 5, 10, 30, 60, 120 y 180 minutos. La concentración de los metales fue determinada utilizando la técnica de Espectrometría de Emisión Óptica por Plasma Acoplado Inductivamente (ICP-OES). Mediante la aplicación del modelo de isoterma de Langmuir se determinó la capacidad máxima de adsorción para el Cr3+, (7,52 mg/g) a pH 3, Fe3+ (1,13 mg/g) a pH 5 y Mn2+ (1,51 mg/g) a pH 7. Los resultados obtenidos de la isoterma de adsorción del MPAAG-TBA fue mejor representada por el modelo Freundlich, demostrando una adsorción en multicapas de una superficie heterogénea. Asimismo, el factor de separación fue igual a uno, indicando una adsorción lineal basada en el modelo de isotherma Langmuir.  Los resultados indican que el criogel MPAAG-TBA posee propiedades quelantes para la remoción de Cr3+, Fe3+ y Mn2+ en aguas contaminadas.
The roles of central and local government in pre-disaster planning
Authors: O'Dea Patrick
Published: February 2021

Proceedings of the seminar on the social and economic effects of earthquake prediction, 12 October, 1977.
Scientific Research Conducted at the Department of Mycology, University of Warmia and Mazury in Olsztyn
Authors: Biedunkiewicz Anna , Ejdys Elżbieta , Kubiak Dariusz , Sucharzewska Ewa
Published: February 2021

This paper presents a review of the research conducted by the staff of the Department of Mycology at UWM, Olsztyn since its establishment to the present. This unit was established and has been headed for over 20 years by Prof. Maria Dynowska. Since 2004, the Department has been conducting extensive mycological research, which is reflected in the dynamic growth of specialist staff involved in teaching activities and popularizing scientific research. Owing to the particular care of Prof. Dynowska, and maintenance of the principal interdisciplinary character of the research, the Department has been occupying a significant position in mycology in Poland recently. This paper attempts to provide a summary of the major scientific accomplishments of the team headed by Prof. Dynowska.
S-Wave Site Amplification Factors from Observed Ground Motions in Japan: Validation of Delineated Velocity Structures and Proposal for Empirical Correction
Authors: Ito Eri , Nakano Kenichi , Senna Shigeki , Kawase Hiroshi
Published: February 2021

We first derived site amplification factors (SAFs) from the observed strong motions by the Japanese nationwide networks, namely, K-NET and KiK-net of National Institute of Earthquake Research and Disaster Resilience and Shindokei (Instrumental Seismic Intensity) Network of Japan Meteorological Agency by using the so-called generalized spectral inversion technique. We can use these SAFs for strong motion prediction at these observation sites, however, we need at least observed weak motion or microtremor data to quantify SAF at an arbitrary site. So we tested the capability of the current velocity models in Japan whether they can reproduce or not the observed SAFs at the nearest grid of every 250 m as the one-dimensional theoretical transfer functions (TTF). We found that at about one-half of the sites the calculated 1D TTFs show more or less acceptable fit to the observed SAFs, however, the TTFs tend to underestimate the observed SAFs in general. Therefore, we propose a simple, empirical method to fill the gap between the observed SAFs and the calculated TTFs. Validation examples show that our proposed method effectively predict better SAFs than the direct substitute of TTFs at sites without observed data.
TiO2 Thin Films Produced by Ultrasonic-Agitation Assisted Sol-Gel for Propane Gas Sensor
Authors: Acosta-Najarro Dwight , A. Garduño-Wilches Ismael , de la Luz Olvera Maria , Maldonado Arturo
Published: February 2021

TiO2 films were deposited by the sol–gel dip coating method assisted by ultra sonic agitation, for their use as propane gas sensors. XRD anlaysis revealed the TiO2 anatase phase for all samples. The film thickness was controlled with the number of the dip-coating immersion cycles, obtaining thicknesses from 10 to 130 nm and a growing rate of 18 nm per immersion. Surface morphology shows that films grow more compact and densely packed as the number of immersion cycles increase. Gas sensing studies indicate that work temperatures above 300°C are needed for sensing activation of the films. Gas sensors sensitivity as a function of propane concentration and film thickness revealed a two-regime behavior: for partial pressures of propane above 400 ppm the sensitivity is not dependent of the film thickness, whereas it is dependent on this parameter at lower partial pressures. Such behavior is attributed to a space charge region and a change in surface structure. For the low concentration regime, the maximum sensitivity was obtained for a film thickness of 110 nm or 5 inmersions.
The Moderating Effect of Firm Visibility on the Corporate Social Responsibility-Firm Financial Performance Relationship: Evidence from France
Authors: Achour Zyed , Boukattaya Sonia
Published: February 2021

This research aims to analyze the role played by firm visibility in moderating the relationship between Corporate Social Responsibility (CSR) and Firm Financial Performance (FFP). Based on the legitimacy theory, a firm’s responses to stakeholder’s expectations would be affected by its public visibility; we hypothesize a positive link between CSR and firm visibility. Moreover, visibility is expected to moderate the CSR-FFP relationship. We applied a Moderated Regression Analysis using the aggregate ESG scores as a CSR proxy on a panel data of listed French Companies (SBF120) over the period 2008–2017. Our findings are in line with legitimacy theory, suggesting that social initiatives would be mean to strengthen the legitimacy and to secure “license to operate”. Furthermore, firm visibility would be a contingency variable that moderates positively CSR-FFP relationship.
Acute Appendicitis: After Correct Diagnosis Conservative Treatment or Surgery?
Authors: Charalampopoulos Anestis , Koliakos Nikolaos , Bagias George , Bompetsi Georgia , Zavras Nikolaos , Davris Dimitrios , Farrugia Frederich , Kopanakis Konstantinos
Published: February 2021

Acute appendicitis is the most common surgical disease presented in ED. Ongoing evidence in the literature, in the last 20 years, shows a lot of benefits in favor of conservative treatment. Despite that conservative treatment does not gain the correct position at the daily practice up to day. A large number of parameters related to acute appendicitis, present diversity in their appearance, so the final estimation of the disease may by unclear and the decision for treatment may be incorrect. We analyze these parameters, aiming to clarify their role in correct diagnosis and decision making on appropriate treatment. In the present study a review of the literature is performed, regarding the etiology, pathology, clinical presentation, laboratory, and imaging data of acute appendicitis. The collection and correct estimation of these parameters, is the key for the correct diagnosis of acute appendicitis. Complicated or uncomplicated cases should be diagnosed preoperatively. The next step is the appropriate treatment, conservative or by surgery. At the present time, excluding generalized peritonitis and sepsis, the majority of patients with uncomplicated acute appendicitis and selected complicated cases can by treated successfully by conservative treatment. The majority of patients do not benefit from appendectomy.
A Current Overview of Two Viroids Prevailing in Citrus Orchards: Citrus Exocortis Viroid and Hop Stunt Viroid
Authors: Belabess Zineb , Radouane Nabil , Sagouti Tourya , Tahiri Abdessalem , Lahlali Rachid
Published: February 2021

Citrus exocortis viroid (CEVd) and hop stunt viroid (HSVd) are the main viroids circulating in all citrus-growing areas worldwide, and causing two well-known diseases on citrus trees; exocortis and cachexia, respectively. These viroids are small, covalently closed single-stranded RNA, allocated to the Pospiviroidae family. CEVd is the first viroid being described on citrus trees in 1948 in California. It is considered the largest citrus viroid at 371 nucleotides. It causes bark scaling disorder on the rootstock of citrus trees grafted on trifoliate orange and its hybrids and can cause dwarfing of trees grown on these rootstocks. HSVd was first observed in 1945 in Florida. It consists of 299 nucleotides. Stunting, chlorosis, bark gumming, stem pitting, decline, and depressions in the wood are the main symptoms of HSVd in mandarin and its hybrids. The introduction and propagation of infected budwoods are the main causes of viroids spread in citrus orchards. These agents are mechanically sap-transmissible and spread by contaminated tools. Neither seed transmission nor vectors have been reported for both viroids. Root transmission, though possible, would be overshadowed by mechanical transmission. Rapid and sensitive molecular-based detection methods specific to both viroids are available. Both diseases are controlled by using viroids-free budwoods for new plantations, launching budwood certification programs, and establishing a quarantine system for new citrus varieties introduction. The most important achievements in CEVd and HSVd researches are outlined in this chapter. This would help to provide a clearer understanding of the diseases they cause and contribute to the development of better control strategies.
Molecular Cloning of a New Bi-Functional Fusion Protein of Clostridium perfringens Type A Alpha and Clostridium septicum Alpha Toxin Genes in E. coli
Authors: Haghroosta Ali , Goudarzi Hossein , Ghalavand Zohreh , Faghihloo Ebrahim , Pilehchian Langroudi Reza
Published: February 2021

Background: A synthetic construct bi-functional protein fusion includes two protein domains, or proteins bind by a fragment. The synthetic construct is designed to achieve better characterize and new functionality. Therefore, having proper cells is essential for cloning fusion genes. Clostridium perfringens type A produces the alpha-toxin and can cause gas gangrene and gastrointestinal diseases. C. septicum produces the alpha-toxin and can cause non-traumatic and traumatic gas gangrene. Objectives: The current study aimed to investigate molecular cloning of a new bi-functional fusion protein of C. perfringens alpha (cpa) and C. septicum alpha (csa) toxin genes in E. coli TOP10. In silico analysis was used for the chimeric fusion protein structural prediction. Methods: To produce chimeric fusion protein, the alpha-alpha (α-α) fusion gene was designed according to nucleotide sequences of cpa (KY584046.1) and csa (JN793989.2) genes. Tertiary structural prediction and validation of the fusion protein were determined by online software. In the new synthetic construction, α-α fusion protein genes are bind via the linker AEAAAKEAAAKA. The linker was introduced between the two domains by fusion PCR. The synthetic fusion gene was cloned into the pUC57cloning vector and then transferred into the host cell. Results: Analysis of the chimeric protein fusion is showed using the I-TASSER server as C-score equal to -2.68 as well as Rampage software in order to confirm the geometrical model as a natural like protein. Also, 1.0% agarose gel electrophoresis of fusion PCR product and sequencing analysis revealed a DNA fragment length of 2346 bp. Screening gel electrophoresis showed 996 bp length, which the designed linker was contained in it. Gel electrophoresis of extracted and purified recombinant plasmid (pUC57/αα) showed that a pUC57/αα of 5056 bp. The digested recombinant pUC57/αα showed one 2.3 kb (our fusion gene) band and one 2.7 kb (pUC57) band. Conclusions: This study presented a new approach for the fusion of cpa and csa genes based on the fusion PCR strategy. According to the latest information, this is the first time that α-α fusion gene is designed and cloned into a suitable cloning vector.
Characteristics of Hepatitis B and D Co-infection: A Descriptive Study
Authors: Hajiabdolbaghi Mahbobeh , Abdiliae Zahra , Bayani Jaleh , Qaempanah Mehdi , Ghiasvand Fereshteh
Published: February 2021

: About 5% of cases with chronic hepatitis B virus (HBV) are co-infected with hepatitis D virus (HDV), and this co-infection possesses a high risk for hepatocellular carcinoma (HCC) and cirrhosis. We aimed to evaluate the epidemiological and histopathological characteristics ‎and response to treatment in patients with HBV and HDV co-infection in a hepatitis clinic in Tehran, Iran. In this study, 80 patients were enrolled and evaluated for age, sex, degree of liver fibrosis, virologic status, and response rate. The incidence of co-infection of hepatitis B and D was 4.9% (80/1,631 HBV-infected cases) in our clinic. Thirty-seven (46.25%) patients had liver cirrhosis, and four (5%) patients had HCC. Besides, HDV Ribonucleic Acid (RNA) polymerase chain reaction (PCR) was positive for 31 (38.75 %) patients. Among 30 patients, 14 (46.6%) completed interferon therapy (for equal to or more than 48 weeks) and had a response with undetectable HDV RNA PCR after treatment. According to our results, for cirrhotic patients in HBV/HDV co-infection that was about 46%, it seems that the early detection of HDV antibody (Ab) plays a significant role in the prevention of progressive liver failure, and treatment with interferon can help these patients by improving the prognosis.
Ocular Chemical Burn with an Unusual Presentation: A Case Report
Authors: Nikandish Malihe
Published: February 2021

Introduction: Ocular chemical injury is an ophthalmic emergency that may be challenging to manage. Here, we presented a case of persistent corneal astigmatism secondary to chemical burn with superficial limbal injury and no corneal involvement. Case Presentation: The case was a 36-year-old man who presented with a chemical acid injury in the right eye. He had sectorial superficial involvement of inferior limbus from 4 to 5 o'clock hours, and the cornea was clear. Corneal topography showed high irregular astigmatism that was not corrected with glass. In long-term follow-up, changes in topographic parameters happened very slowly. Conclusions: In conclusion, optical corneal changes should be considered in the ocular surface chemical burn, especially in sectorial involvement despite clear cornea.
Contribution to the taxonomic knowledge of Ampharetidae (Annelida) from Antarctica with the description of Amage giacomobovei sp. nov.
Authors: Schiaparelli Stefano , Jirkov Igor A.
Published: February 2021

Thanks to newly collected material from the Terra Nova Bay area (Ross Sea, Antarctica), we discuss the taxonomy of the ampharetid genera Amage Malmgren, 1866 and Amythas Benham, 1921. A new species of Amage, A. giacomobovei sp. nov., is described based on morpho-anatomical data. This is the second new species described from an area which appears to be rich in ampharetids, a coastal embayment at ~500 m depth near the Italian “Mario Zucchelli” research station. The new species is characterized by having 16 abdominal uncinigers and four pairs of branchiae that readily distinguish it from its congeners. Tubes of A. giacomobovei sp. nov. are also characteristic in showing a large amount of embedded sponge spicules, suggesting a possible close association to spicule mats. Based on the amended diagnoses of the two genera, Amage septemdecima Schüller & Jirkov, 2013 is transferred to the genus Amythas. Finally, to simplify the task of ampharetid genera recognition for untrained people, we provide a dichotomic key for ampharetid genera found in Antarctica and a checklist of species occurring in Terra Nova Bay.
CD10 Is Helpful in Detecting Occult or Inconspicuous Endometrial Stromal Cells in Cases of Presumptive Endometriosis
Authors: Groisman Gabriel M. , Meir Alona
Published: February 2021

Background.—Previous studies have shown that CD10 is a marker for normal, ectopic, and neoplastic endometrial stromal cells. However, its value in confirming a diagnosis of presumptive endometriosis has not been extensively studied.

Objective.—To assess the reactivity of CD10 in a series of cases of presumptive endometriosis and to establish the potential usefulness of this antibody in confirming the diagnosis.

Design.—We studied hematoxylin-eosin sections and immunoreactivity of CD10 in 20 cases diagnosed as “suspicious for,” “suggestive of,” or “compatible with” endometriosis as well as in 12 cases of lesions that may be confused with endometriosis (3 endosalpingioses, 3 mesothelial hyperplasias, 3 ovarian follicular cysts, and 3 hemorrhagic corpora lutea).

Results.—Routine sections from cases of presumptive endometriosis showed glands lacking a distinct cuff of endometrial stromal cells because of atrophy or because of changes secondary to hemorrhage, inflammation, fibrosis, and/or cystic dilatation. In a few cases, the distinction between endometrial and ovarian stroma could not be assessed with certainty. CD10 immunostaining confirmed the diagnosis in 17 (85%) of the cases, as it strongly stained endometrial stromal cells that were not apparent on hematoxylin-eosin sections. All sections from lesions that may simulate endometriosis were CD10−.

Conclusion.—CD10 is helpful in detecting occult or inconspicuous ectopic endometrial stromal cells and in distinguishing endometriosis from its potential mimickers. We recommend its use to confirm or exclude the presence of endometrial stromal cells in cases of presumptive endometriosis and in lesions that may be mistaken for this entity.
Genomics, Transcriptomics, Proteomics, and Numbers
Authors: Kiechle Frederick L. , Holland-Staley Carol A.
Published: February 2021

Objective.—To review the advances in clinically useful molecular biologic techniques and to identify their applications in clinical practice, as presented at the 11th Annual William Beaumont Hospital DNA Symposium.

Data Sources.—The 8 manuscripts submitted were reviewed, and their major findings were compared with literature on the same or related topics.

Study Selection.—Manuscripts address the use of molecular techniques in microbiology to evaluate infectious disease and epidemiology; molecular microbiology methods, including rapid-cycle real-time polymerase chain reaction; peroxisome proliferator–activated receptor γ as a potential therapeutic target in inflammatory bowel disease or colon cancer; the effect of nonapoptotic doses of the bisbenizamide dye Hoechst 33342 on luciferase expression in plasmid-transfected BC3H-1 myocytes; the routine use of cystic fibrosis screening and its challenges; and the use of flow cytometry and/or chromosomal translocation in the diagnostic evaluation of hematopoietic malignancies.

Data Synthesis.—Three current issues related to the use of molecular tests in clinical laboratories are (1) the restriction on introducing new tests secondary to existing patents or licenses; (2) the preanalytic variables for the different specimen types currently in use, including whole blood, plasma, serum, fresh or frozen tissues, and free-circulating DNA; and (3) the interpretation of studies evaluating the association of complex diseases with a single mutation or single-nucleotide polymorphism. Molecular methods have had a major impact on infectious disease through the rapid identification of organisms, the evaluation of outbreaks, and the characterization of drug resistance when compared with standard culture techniques. The activation of peroxisome proliferator–activated receptor γ stimulated by thiazolidinedione is useful in the treatment of type II diabetes mellitus and may have value in preventing inflammatory bowel disease or colon cancer. Hoechst 33342 binding to adenine-thymine–rich regions in the minor groove of DNA is a fluorescent stain for DNA and initiates apoptosis at >10 μg/mL. Lower doses of Hoechst 33342 promote luciferase expression by a mechanism that may involve binding to cryptic promoters facilitated by dye-associated misalignment of the tertiary structure of DNA. The routine use of cystic fibrosis screening is complicated by the more than 1000 mutations associated with the disease. The use of 4-color flow cytometry and the detection of chromosomal translocation are both invaluable aids in establishing the diagnosis of lymphoid or myeloid hematopoietic malignancies.

Conclusions.—The current postgenomic era will continue to emphasize the use of microarrays and database software for genomic, transcriptomic, and proteomic screening in the search for useful clinical assays. The number of molecular pathologic techniques will expand as additional disease-associated mutations are defined.
Prevalence and Role of Methylenetetrahydrofolate Reductase 677 C→T and 1298 A→C Polymorphisms in Coronary Artery Disease in Arabs
Authors: Abu-Amero Khaled K. , Wyngaard Carol A. , Dzimiri Nduna
Published: February 2021

Context.—Previous studies reported an association of 677 C→T and 1298 A→C methylenetetrahydrofolate reductase (MTHFR) variants with coronary artery disease (CAD). No previous studies concerning the prevalence of these 2 MTHFR variants or their possible association with CAD in Arabs are currently available in the literature.

Objective.—To determine the prevalence of MTHFR variants and their potential relevance to CAD among Arabs.

Design.—We used polymerase chain reaction and restriction enzyme digestion to determine the prevalence of these 2 MTHFR polymorphisms in 625 healthy blood donors (BDs) and 545 angiographically confirmed CAD patients of Arab origin.

Results.—For the 677 C→T variant within the CAD group, 64.2% were homozygous wild-type C/C, 32.1% were heterozygous C/T, and 3.7% were homozygous T/T genotype. Within the BD group tested for the 677 C→T variant, 72.2% were homozygous wild-type C/C, 25.8% were heterozygous C/T, and 2% were homozygous T/T genotype. Within the CAD group tested for the 1298 A→C variant (n = 540), 45.7% were homozygous wild-type A/A, 46.9% were heterozygous A/C, and 7.4% were homozygous C/C genotype. Within the BD group tested for the 1298 A→C variant (n = 625), 39.4% were homozygous wild-type A/A, 51.5% were heterozygous A/C, and 9.1% were homozygous C/C genotype. The distribution and allele frequency of these 2 MTHFR variants followed the Hardy-Weinberg equilibrium and were similar in the CAD and BD study groups. The prevalence of the 677 C→T and 1298 A→C compound heterozygosity was 9.6% for the BD group and 12.3% for the CAD group.

Conclusion.—The 2 MTHFR variants tested in this study, individually or compound, are not associated with CAD. Therefore, neither of these 2 variants can be considered an independent risk factor or a predictor for CAD in this population.
Quality Assurance in Human Molecular Genetics Testing: Status and Recommendations
Authors: Williams Laurina O. , Cole Eugene C. , Lubin Ira M. , Iglesias Norma I. , Jordan Ruth L. , Elliott Lauren E.
Published: February 2021

Objective.—The role of genetic testing has expanded with rapidly developing technology and completion of the International Human Genome Project. Development of universally acceptable quality control methods and quality assurance standards trails technology. The principle that high-quality genetic testing is important for public health motivated the Centers for Disease Control and Prevention to formulate ways for improving quality assurance of human molecular genetics testing.

Participants.—Twenty-eight panelists were chosen based on expertise in molecular genetics testing and knowledge of quality assurance practices. Representatives of professional organizations, industries, and federal agencies participated in one or more of 3 panel meetings. Consensus recommendations were developed by the 15 panelists in the third meeting.

Evidence.—Evidence was derived from experts' opinion during 3 panel meetings. Data compiled through laboratory visits and literature review were used as reference information. Need for this project was derived from the Final Report of the Task Force on Genetic Testing, produced by the National Institutes of Health and the Department of Energy in 1997, and the Summary Report of the Subcommittee Meeting on Genetics of the Clinical Laboratory Improvement Act Advisory Committee in 1997.

Consensus Process.—Research and development needs were identified using a participatory visioning approach. A modified nominal group process was used to reach consensus.

Conclusions.—Five core consensus recommendations were made: research for developing positive samples for quality assurance purposes, performance evaluation programs supplementing those in existence, establishment and support of laboratory-oriented consortia, establishment of a laboratory-focused database, and support of molecular genetics training programs.
Differential Amplification and Overexpression of HER-2/neu, p53, MIB1, and Estrogen Receptor/Progesterone Receptor Among Medullary Carcinoma, Atypical Medullary Carcinoma, and High-Grade Invasive Ductal Carcinoma of Breast
Authors: Xu Ruliang , Feiner Helen , Li Peng , Yee Herman , Inghirami Giorgio , Delgado Yara , Perle Mary Ann
Published: February 2021

Context.—Medullary carcinoma (MC) is a special type of breast cancer that has a better prognosis than atypical medullary carcinoma (AMC) and high-grade invasive ductal carcinoma (HGIDC) with prominent lymphocytic infiltrates. What accounts for the different clinical courses of these carcinomas, despite their similar histology, is unknown. To address this issue, we performed a comparative study of amplification and overexpression of HER-2/neu and expression of several other important biochemical markers (p53, MIB1, and estrogen receptor [ER]/progesterone receptor [PR]) in these 3 cancer groups.

Objective.—To evaluate HER-2/neu, p53, MIB1, and ER/PR as markers in the differential diagnosis of MC, AMC, and HGIDC.

Design.—Nine cases of MC, 13 cases of AMC, and 16 cases of HGIDC with prominent lymphocytic infiltrates were identified according to strict histologic criteria. All tests were performed on formalin-fixed, paraffin-embedded archival tissues. HER-2/neu gene amplification was examined by fluorescence in situ hybridization using PathVysion HER-2 DNA probes. Expression of HER-2/neu, p53, MIB1, and ER/PR was detected by immunohistochemistry. χ2 and Student t tests were applied for statistical analyses.

Results.—None of 9 cases of MC examined had either amplification or overexpression of HER-2/neu (0%). In contrast, HER-2/neu amplification was observed in AMC (46%, P < .025) and HGIDC (56%, P < .005). All 3 categories of tumors had similar percentages of expression of p53 (78% of MC, 77% of AMC, and 69% of HGIDC) and MIB1 (89% of MC, 92% of AMC, and 94% of HGIDC). Immunostaining for ER/PR was rarely positive in either MC or AMC, and there were no significant differences of expression of ER/PR between these 2 lesions (P > .05). However, the expression rate of ER/PR (31%/44%) in HGIDC is higher than in both MC (P = .05) and AMC (P = .01).

Conclusions.—Medullary carcinoma of breast is distinct from AMC and HGIDC with prominent lymphocytic infiltrates in amplification and overexpression of HER-2/neu. This difference may account for its different clinical and biological behavior, and may potentially aid in diagnosis and management of these groups of patients.
Growth Factors and Receptors in Juvenile Nasopharyngeal Angiofibroma and Nasal Polyps: An Immunohistochemical Study
Authors: Zhang Paul J. , Weber Randal , Liang Ho-Hi , Pasha Teresa L. , LiVolsi Virginia A.
Published: February 2021

Background.—Juvenile nasopharyngeal angiofibroma is a rare nasopharyngeal tumor that occurs exclusively in adolescent boys. It is a histologically benign but locally persistent growth of stromal and vascular tissue. Although male hormones and some growth factors, such as transforming growth factor β1 (TGF-β1), insulin-like growth factor II (IGF-II), and, lately, the proto-oncogene β-catenin, have been implicated in the histogenesis of the tumor, the biologic signaling pathways that drive this peculiar fibrovascular proliferation are still nuclear.

Objective.—To evaluate immunoexpressions of β-catenin, c-Kit, p130Cas, TGF-β3, bone morphogenic protein 4, nerve growth factor (NGF), and the IGF receptor (IGF-1R) in a series of juvenile nasopharyngeal angiofibromas and to compare to that of a group of nasal polyps.

Design.—A standard immunohistochemical technique was used on paraffin sections of 12 sporadic juvenile nasopharyngeal angiofibromas and 15 nasal polyps with microwave or steam antigen retrieval. Immunoreactivity was analyzed semiquantitatively in stromal cells and endothelial cells of each case.

Results.—The expressions of β-catenin (nuclear), c-Kit (cytoplasmic), and NGF (cytoplasmic) were higher and more frequent in stromal cells of juvenile nasopharyngeal angiofibromas than those of nasal polyps. Both juvenile nasopharyngeal angiofibromas and nasal polyps showed similarly frequent and strong immunoreactivity for p130Cas and TGF-β3 and weak immunoreactivity for bone morphogenic protein 4 in both stromal cells and endothelial cells. No IGF-1R immunoreactivity was detected in any case of either group.

Conclusions.—Our results support the role of β-catenin in juvenile nasopharyngeal angiofibromas and suggest a potential involvement of c-Kit and NGF signaling pathways in the juvenile nasopharyngeal angiofibromas. Although the biologic significance of c-Kit in juvenile nasopharyngeal angiofibromas has yet to be defined, the finding of frequent and high c-Kit expression might have therapeutic importance for patients with juvenile nasopharyngeal angiofibromas.
Bioelectronic Sensor Technology for Detection of Cystic Fibrosis and Hereditary Hemochromatosis Mutations
Authors: Bernacki Susan H. , Farkas Daniel H. , Shi Wenmei , Chan Vivian , Liu Yenbou , Beck Jeanne C. , Bailey Karen Snow , Pratt Victoria M. , Monaghan Kristin G. , Matteson Karla J. , Schaefer Frederick V. , Friez Michael , Shrimpton Antony E. , Stenzel Timothy T.
Published: February 2021

Context.—Bioelectronic sensors, which combine microchip and biological components, are an emerging technology in clinical diagnostic testing. An electronic detection platform using DNA biochip technology (eSensor) is under development for molecular diagnostic applications. Owing to the novelty of these devices, demonstrations of their successful use in practical diagnostic applications are limited.

Objective.—To assess the performance of the eSensor bioelectronic method in the validation of 6 Epstein-Barr virus–transformed blood lymphocyte cell lines with clinically important mutations for use as sources of genetic material for positive controls in clinical molecular genetic testing. Two cell lines carry mutations in the CFTR gene (cystic fibrosis), and 4 carry mutations in the HFE gene (hereditary hemochromatosis).

Design.—Samples from each cell line were sent for genotype determination to 6 different molecular genetic testing facilities, including the laboratory developing the DNA biochips. In addition to the bioelectronic method, at least 3 different molecular diagnostic methods were used in the analysis of each cell line. Detailed data were collected from the DNA biochip output, and the genetic results were compared with those obtained using the more established methods.

Results.—We report the successful use of 2 applications of the bioelectronic platform, one for detection of CFTR mutations and the other for detection of HFE mutations. In all cases, the results obtained with the DNA biochip were in concordance with those reported for the other methods. Electronic signal output from the DNA biochips clearly differentiated between mutated and wild-type alleles. This is the first report of the use of the cystic fibrosis detection platform.

Conclusions.—Bioelectronic sensors for the detection of disease-causing mutations performed well when used in a “real-life” situation, in this case, a validation study of positive control blood lymphocyte cell lines with mutations of public health importance. This study illustrates the practical potential of emerging bioelectronic DNA detection technologies for use in current molecular diagnostic applications.
CD117, but Not Lysozyme, Is Positive in Cutaneous Plasmacytoma
Authors: Bayer-Garner Ilene B. , Schwartz Mary R. , Lin Pei , Smoller Bruce R.
Published: February 2021

Context.—CD117 (c-Kit) and lysozyme are frequently expressed by myeloblasts and are sensitive markers for the diagnosis of extramedullary myeloid tumor. The diagnosis of cutaneous plasmacytoma presents a degree of difficulty, particularly with the plasmablastic variant, which can mimic hematologic as well as epithelioid malignancies. Approximately 25% of multiple myelomas express CD117 in the bone marrow by flow cytometry. Lysozyme immunoreactivity has been previously shown in 30% of poorly differentiated myelomas, while it is nonreactive in nonmalignant plasma cells.

Objective.—To ascertain whether CD117 and lysozyme can aid in the diagnosis of cutaneous plasmacytomas, particularly the plasmablastic type.

Design.—Pathology reports of 2357 patients with a diagnosis of multiple myeloma were reviewed to find 13 cutaneous plasmacytomas (8 Bartl grade II, 5 Bartl grade III). Formalin-fixed, paraffin-embedded tissue sections were stained with CD117 and lysozyme on the Dako Autostainer system.

Setting.—Patients with the diagnosis of multiple myeloma who developed cutaneous plasmacytoma(s).

Results.—The cutaneous plasmacytomas uniformly expressed CD117 in a cytoplasmic or membranous and cytoplasmic distribution with varying degrees of staining intensity unrelated to the Bartl grade of the lesion, while they were uniformly negative for lysozyme.

Conclusions.—CD117 is a sensitive marker for malignant plasma cells in paraffin-embedded tissue, while lysozyme does not help identify poorly differentiated malignant plasma cells. While CD117 alone does not distinguish extramedullary myeloid tumor from poorly differentiated myeloma, the combination of CD117 and lysozyme may allow their differentiation. The possibility of c-kit inhibitors being used in the treatment of other hematopoietic malignancies allows speculation regarding implications for the treatment of multiple myeloma.
Primary Malignant Gastrointestinal Stromal Tumor of the Liver
Authors: Hu Xuejiao , Forster Jameson , Damjanov Ivan
Published: February 2021

We report the case of a malignant, primary, hepatic gastrointestinal stromal tumor (GIST) that was resected from the liver of a 79-year-old woman. To our knowledge, this is the first primary, hepatic GIST on record. The tumor expressed CD117 (c-Kit protein) and vimentin and had the ultrastructural features of GISTs. Sixteen months after partial hepatectomy and resection of the tumor, a hilar lymph node metastasis was found. The metastatic tumor had the same morphologic features as the primary tumor, but in addition it contained numerous multinucleated giant cells. This case shows that GIST can occur as a primary liver tumor, and accordingly, we point out that not all hepatic tumors with a GIST phenotype should be automatically considered to be metastases from a primary gastrointestinal site.
Human Papillomavirus Biology and Cervical Neoplasia: Implications for Diagnostic Criteria and Testing
Authors: Stoler Mark H.
Published: February 2021

Human papillomaviruses are necessary for the development of cervical neoplasia. Progress in our understanding of the epithelial biology of this common pathogen has greatly influenced current concepts of cervical carcinogenesis. This understanding has provided a framework for understanding the biologic basis of many diagnostic criteria. Furthermore, classification schemes, diagnostic testing, and clinical management have been modified and clarified in light of this knowledge.
Successfully Integrating Human Papillomavirus Testing Into Your Practice
Authors: Lozano Richard
Published: February 2021

Integrating human papillomavirus (HPV) testing into the practice of cervical cancer screening is a continuous process that begins and ends with education. An understanding of the basic science and clinical relevance are critical to proper implementation. One must have knowledge of one's own laboratory statistics, clinician awareness, and market forces before the final steps are taken. Additional logistical issues are often laboratory specific or state specific, but are addressed here.
The Nested Variant of Urothelial Carcinoma: Clinicopathology of 2 Cases
Authors: Xiao Guang-Qian , Savage Stephen J. , Gribetz Michael E. , Burstein David E. , Miller Lorraine K. , Unger Pamela D.
Published: February 2021

The nested variant of urothelial carcinoma is a recently described bladder tumor entity with a rare incidence. Two cases of this disease are presented in this report; the patients in both cases were elderly men, with a predominant involvement of the trigone region. Histologically, the tumor cells were arranged in ill-defined nests and had low-grade nuclear features. Both cases had a diffusely infiltrating growth pattern with widespread local disease at cystectomy. Strong immunohistochemical staining for p63 in the neoplastic cells supports the urothelial cell nature of this neoplasm. High p53 and Ki-67 indices of this tumor correlate with the aggressiveness of this subtype.
Neurobrucellosis Presenting as Leukoencephalopathy: The Role of Cytotoxic T Lymphocytes
Authors: Seidel Gregory , Pardo Carlos A. , Newman-Toker David , Olivi Alessandro , Eberhart Charles G.
Published: February 2021

A 65-year-old man developed a leukoencephalopathy associated with neurobrucellosis. The disease followed a 15-month progressive course with neurologic symptoms, and magnetic resonance imaging revealed bilateral symmetrical T2 signal hyperintensities in the white matter. Biopsy of the cerebral cortex and white matter was significant for nongranulomatous meningoencephalitis with reactive microgliosis and astrogliosis. The inflammatory infiltrate was predominantly composed of T lymphocytes, including numerous cytotoxic T cells. There was no evidence of significant myelin destruction. No organisms were detected microscopically, but elevated immunoglobulin G titers to Brucella were found in the cerebrospinal fluid. An abscess formed at the biopsy site, and Brucella melitensis was cultured from abscess contents. Neurobrucellosis is difficult to diagnose outside endemic regions and is associated with leukoencephalopathy-like pathology. Cytotoxic T lymphocytes and microglia activation play an immunopathogenic role in this rare disease.