bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of oxidative stress in the pathogenesis of Graves’ orbitopathy
Authors: Londzin-Olesik Magdalena , Kos-Kudła Beata , Nowak Aleksandra , Nowak Mariusz
Published: January 2021

Graves' disease (GD) is a chronic autoimmune condition, in which the anti-thyroid stimulating hormone receptor antibodies (TRAb) activate the thyrotropin receptor (TSHR) located on thyrocytes, leading to excessive thyroid hormone production. TSHR is also expressed in extrathyroidal tissues, in particular, within the orbit. The serum levels of TRAb corelate with severity and activity of thyroid orbitopathy (TO). TO is the most common extrathyroidal manifestation of GD. It is an autoimmune inflammation of orbital tissues, that is, extraocular muscles, orbital adipose tissue or a lacrimal gland. Increased orbital fibroblast and adipocyte proliferation, overproduction of glycosaminoglycans, as well as extraocular muscle oedema result in an increased orbital tissue volume and trigger the onset of TO symptoms. The pathophysiology of TO is complex and has not been fully unexplained to date. Orbital fibroblasts show expression of the TSHR, which is the main target of autoimmunity. It has been hypothesised that T-cell activation induced by orbital receptor stimulation by the target antibody results in orbital tissue infiltration, triggering a cascade of events which leads to the production of cytokines, growth factors and reactive oxygen species (ROS). ROS cause damage to many components of the cell: the cell membrane through the peroxidation of lipids and proteins leading to a loss of their function and enzymatic activity. Oxidative stress leads to activation of the antioxidant system which operates through two mechanisms: enzymatic and non-enzymatic. Assessment of the concentration of oxidative stress markers and the concentration or activity of antioxidative system parameters enables evaluation of oxidative stress severity, which in the future may be utilized for assessment of treatment efficacy and prognosis in patients with active OT.
Nekilnojamojo turto rinkos pokyčiai ekonomikos šoko kontekste: Lietuvos atvejis
Authors: Pilinkienė Vaida , Stundžienė Alina , Stankevičius Evaldas , Grybauskas Andrius
Published: January 2021

2020 m. įvykęs ekonomikos šokas, sukeltas COVID-19 pandemijos, paveikė šalies ekonomiką ir nekilnojamojo turto rinką. Mokslo studijoje siekiama įvertinti Lietuvos nekilnojamojo turto rinkos pokyčius ekonomikos šoko kontekste. Aptariama ekonomikos šoko samprata, tipai, sąsajos su ekonomikos ciklais, pateikiami ekonomikos šokų stabilizavimo būdai, stabilumo ir ekonomikos šoko ryšio prielaidos, akcentuojant valstybės vaidmenį. Leidinys aktualus įvairiems ekonomikos dalyviams: namų ūkiams, dalyvaujantiems nekilnojamojo turto rinkoje ir ekonomikoje; įmonėms, tiesiogiai ir netiesiogiai susijusioms su šia rinka ir veikimu joje; vyriausybės ir valdžios organams; analitikams ir ekspertams.
Die Freiheitlich Demokratische Grundordnung im System der Grundrechte – Grundlage und Grenze verfassungsrechtlich gewährleisteter Freiheit
Authors: Heger Alexander , Schaupp Julian
Published: January 2021

The free democratic constitutional order is a legal institution of the German Constitution which captures a central position in the rulings of the Federal Constitutional Court. Pointing towards this decisive significance for the German Constitution, it is necessary to determine the position of the free democratic constitutional order within the constitution itself and its relationship to fundamental rights. In doing so, it must be shown that the free democratic constitutional order is the value system of the German Constitution which, in turn, has a decisive impact on the interpretation of fundamental rights. The resulting consequences necessitate critical reflection on the theory of value systems and culminate in a more restrictive understanding of the free democratic constitutional order.
Moral und Grenzverhalten im Steuerrecht – Zur Rechtsverwirklichung im Steuerrecht und zur neuen Anzeigepflicht für Steuergestaltungen
Authors: Lamprecht Philipp
Published: January 2021

The enforcement of tax law in practice depends to a large extent on the tax morale of taxpayers. Behaviour which goes to (or even exceeds) the legal limits in order to achieve tax benefits, such as aggressive tax planning, endangers tax morale. However, anti-abuse provisions in substantive law have not proved to be very effective against such behaviour. It is therefore of interest to the legal system as a whole that German tax law, with its obligation to report potentially aggressive cross-border tax planning arrangements, has introduced a means that promises to counteract such behaviour much more effectively than previous approaches.
Latenz
Authors: Haverkamp Anselm
Published: January 2021

Anselm Haverkamp fasst seine Arbeiten zum Begriff der Latenz systematisch zusammen und exemplifiziert die These der Latenz des Ästhetischen als historische Kategorie an einer Reihe von Beispielen aus Literatur und Kunst, die von Livius über Bruegel bis Beckett reicht.

Latenz ist ein methodisch unterbelichteter Aspekt der Theoriebildung, der eine Verlegenheit der historischen Einschätzung zum Ausdruck bringt. Sie scheint der kaum begriffene Inbegriff dessen, was man gemeinhin Historizität nennt. Weil das latent Wahrgenommene in der Anmutung historischer Quellen nur punktuell zu fassen ist, entzieht sich und widerspricht die Latenz den systematischen Unterstellungen von Tendenz oder Teleologie qua Entwicklung oder Fortschritt. Sie scheint pure Kontingenz, aber kontingent ist nur ihre Oberfläche. In Literatur und Kunst, Texten und Bildern, wird die Latenz als Vorstruktur im kontingent Erfahrenen auf eine paradoxe Weise greifbar, die seit Baumgarten ästhetisch heißt. In der Ästhetik der Latenz taucht aus der Unübersichtlichkeit des Geschehenen »Geschichte« auf.
Parental Self-Efficacy and Parenting through Adversity
Authors: Scannell Christian
Published: January 2021

This review examines the relationship between life adversities, parental well-being, parental self-efficacy, and social support as potential factors mediating parent-child relationships and children’s outcomes. Generally, research on adversity has focused on children’s experiences and the long-term impact of adversity on development and health trajectories. More recently, a focus on resilience and growth after adversity has received increasing attention. Existing literature has identified how parents can best support their children through adverse events and suggested parenting programs that emphasize skill-building to parent children who have experienced adversity. Yet often overlooked is the critical impact of adverse events on the parent and how this may interfere with the cultivation of an environment of support and increase stigmatization due to unmet parenting expectations. While parenting occurs in context, it is often judged based upon societal expectations of childrearing practices and optimal outcomes with little understanding of the factors that contribute to parenting behaviors. The experience of adversity has the potential to impact parental sense of competence and parenting practices. However, parental self-efficacy and social supports can play mediating role in the experience of adversity and parenting stress. The integration of these contextual factors allows for the development of expectations that are best suited to meet the needs of vulnerable family systems.
The Root Causes of Absenteeism in Medical Students: Challenges and Strategies Ahead
Authors: Bahadori Mohammd Hadi , Salari Arsalan , Alizadeh Iman , Moaddab Fatemeh , Rouhi Balasi Leila , Soodmand Mostafa
Published: January 2021

Background: Learning by students is the cornerstone of the educational system, as well as the issues associated with this basic axis. One of the foundations of learning is the attendance of students in classes and attention to the instructions. Objectives: The present study aimed to discover the root causes of absenteeism among medical students at Guilan University of Medical Sciences (GUMS). Methods: This descriptive-analytical study was conducted on 127 basic science students at GUMS. Data were collected using a valid questionnaire consisting of 24 items to investigate the four components of the influential factors in absenteeism (S-CVI/Ave = 0.93; CVR ≥ 0.62; α = 91%). Data analysis was performed in SPSS version 21 using descriptive and analytical statistics at the significance level of P ≤ 0.05. Results: Among the four influential factors, professors’ performance (mean score: 18.26 ± 7.12) had the most significant effect and students' personal and family issues (mean score: 14.89 ± 6.76) had the least significant effect on absenteeism. In addition, significant correlations were observed between the status of medical sciences in the community with the variables of age, marital status, and housing occupancy status, as well as students' personal and family issues with marital status, professors' performance with the students' grade point average, and housing occupancy status and personal and family issues with professors' performance. Conclusions: Based on the results, it is recommended that educational planners and policymakers pay more attention to the factors mentioned by students as the most important causes of absenteeism, so that students would become more willing to attend educational environments and the teaching-learning process could be promoted.
Exploring the Components of the Research Empowerment Program of the Faculty Members of Kermanshah University of Medical Sciences, Iran Based on the CIPP Model: A Qualitative Study
Authors: Jafari Mostafa , Laei Susan , Kavyani Elham , Jalali Rostam
Published: January 2021

Background: The promotion and organizational growth of the research empowerment program of faculty members require the accurate recognition of the influential components. Objectives: The present study aimed to explore the components of the research empowerment program of university faculty members using the context, input, process, and product model (CIPP). Methods: This qualitative study was conducted using content analysis on 15 faculty members of Kermanshah University of Medical Sciences, Iran in 2020. The participants were selected via purposive sampling. Data were collected via in-depth, semi-structured interviews, and the component analysis was performed using MAXQDA 20. Results: After data analysis, eight main categories were extracted based on the CIPP model, including context component (preparation and planning), input component (content and resources), process component (implementation and control), and product component (performance and correction). Conclusions: According to the results, the research empowerment program of the faculty members could be improved by considering the influential factors in the quality of these programs.
Phylogenetic Analysis of NS5B Region of Hepatitis C Genotype 3a Virus among Different Risk Groups in Iran
Authors: Ranjbar Kermani Fahimeh , Mousavi Hosseini Kamran , Amini-Kafiabad Sedigheh , Maghsudlu Mahtab , Sharifi Zohreh , Mansournia Mohammad Ali
Published: January 2021

Background: Hepatitis C virus (HCV) is a major cause of liver diseases. Transmission of HCV, as a blood-borne virus, is a major concern for the safety of blood products. In Iran, intravenous drug abuse is a major risk factor for HCV transmission. Recently a change in the distribution of HCV genotype among Iranian blood donors has been reported, and genotype 3a is reported as the most frequent genotype. Also, genotype 3a is the dominant genotype among IDUs. Objective: To investigate the association between HCV genotype 3a circulating in the community, sequences of HCV genotype 3a were analyzed among different risk groups in Iran. Methods: In this cross-sectional study, a partial sequence of the NS5B region of the HCV genome was isolated from 58 blood donors, 48 intravenous drug users (IDUs), and 31 patients with inherited bleeding disorders (IBDs) infected with HCV genotype 3a were included. The published sequence data were obtained from the Gen Bank database and were compared to construct the phylogenetic trees. Results: Of 58 blood donors infected with subtype 3a, 31 (53.5%) reported the risk of intravenous drug abuse. In the phylogenetic tree, no separate cluster was formed to differentiate between HCV sequences in blood donors and IDUs. A cluster at the middle level was found in the phylogenetic tree formed by sequences from blood donors, IDUs, and patients with inherited bleeding disorders. Conclusions: The phylogenetic tree showed the phylogenetic mixing of genotype 3a sequences in BDs, IBD patients, and IDUs. The results confirmed the extensive transmission of IDU-related genotype 3a towards the general population.
Cell wall functional activity and metal accumulation of halophytic plant species Plantago maritima and Triglochin maritima on the White Sea littoral zone (NW Russia)
Authors: Terebova Elena N. , Markovskaya Evgenya F. , Androsova Vera I. , Pavlova Maria A. , Oreshnikova Natalia V.
Published: January 2021

The presented study supplements the knowledge on ion-exchange capacity, swelling capacity (elasticity) of the plant cell wall, and the accumulation of heavy metals in halophytic species Plantago maritima and Triglochin maritima in the tidal zone of the White Sea western coast. The littoral soils of the coastal territories are sandy or rocky-sandy, medium and slightly saline with poor content of organic substances, Mn, Zn, Ni, and Pb. Studied soils are considered as uncontaminated by heavy metals because they contain background amounts of Fe and Cu. Sea water is significantly polluted by Fe (3.8 MPC) and Ni (55 MPC), has poor content of Zn and Cu and background level of Pb and Mn. The coastal dominant plant species P. maritima and T. maritima were characterized by intensive metals accumulation which was reflected in the coefficient of biological absorption (CBA) of metal by a whole plant. For P. maritima the following metal accumulation series was obtained: Cu (3.29)> Zn (2.81)> Ni (1.57)> Pb (1.30)> Mn (1.21)> Fe (0.97), and for T. maritima: Ni (3.80)> Fe (2.08)> Cu (1.91)> Zn (1.84)> Pb (1.51)> Mn (1.31). Roots accumulated 50–70% of Ni, Cu, Zn, Pb and Mn of the total metal content in the plant while leaves and stems contained 30–50%. Fe was allocated mainly in the roots (80%). The ion-exchange capacity of the plant cell wall for P. maritima and T. maritima was established as follows correspondingly: 3570–3700 and 2710–3070 μmol g-1 dry cell weight per leaf; 2310–2350 and 1160–1250 μmol g-1 dry cell weight per root.
Light regimen-induced variability of photosynthetic pigments and UV-B absorbing compounds in Luzula sylvatica from Arcto-Alpine tundra
Authors: Barták Miloš , Orekhova Alla , Nezval Jakub , Oravec Michal , Hájek Josef , Špunda Vladimír , Tříska Jan , Bednaříková Michaela , Maria Giudici Gabriella Nora , Pech Radek
Published: January 2021

The aim of this study was to evaluate the effects of different in situ light regimen on ecophysiological parameters of Luzula sylvatica leaves. Plants of L. sylvatica grown under natural sunny and shade conditions in arcto-alpine tundra were analyzed with respect to their leaf anatomy, content of photosynthetic pigments, UV absorbing compounds and phenanthrenoid compounds. Relationship between chlorophyll concentrations (Chla+b) and SPAD values was determined for sun and shade leaves measured repeatedly within summer and autumn seasons 2019 and 2020. Pooled data showed curvilinear Chla+b to SPAD relationship with the highest Chla+b and SPAD values found for shade leaves. Sun leaves had higher UV-B absorbing compounds contents than shade ones. The HPLC-DAD analysis revealed significant amount of soluble flavonoids in Luzula sylvatica leaves, amongst others the flavone-luteolin and its derivatives (e.g. tentatively identified luteolin-methyl-glucoside and luteolin-glucoside). The accumulation of luteolin based compounds in sun acclimated leaves is also plausible explanation for the higher antioxidant activity determined in sun leaf extraxts. Such response of flavonoid metabolism may help L.S. to cope with excessive-light stress through UV-attenuation mechanism and ROS scavanging. Additionally, phenanthrenoid compounds contents in L. sylvatica leaves were determined. Altogether, 9 phenanthrenoid compounds were identified by HPLC-HRMS. Their content was markedly different (up to the factor of 5) between sun and shade leaves of L.sylvatica.
A Method for Proficiency Testing of Small Peer Groups in the College of American Pathologists Coagulation Surveys
Authors: Cunningham Mark T. , Praestgaard Jens , Styer Patricia E. , Brandt John T. , Fairweather Robert B. , Laposata Michael , Olson John D. , Sosolik Randy C. , Triplett Douglas A.
Published: January 2021

Objective.—To develop a grading scheme for the proficiency testing of small peer groups of fewer than 10 members for the prothrombin time (PT) and activated partial thromboplastin time (APTT).

Methods.—A modified target value for small peer groups was derived based on the assumption that measurement variability in the PT and APTT is more greatly influenced by variations in reagents than in instruments. Criteria for grading were established by statistical simulation to achieve misclassification errors of less than 5% for both incorrectly passing and failing participants. College of American Pathologists Coagulation Survey data were analyzed to determine the number of additional laboratories graded using the proposed scheme, as well as the failure rates among participants in the small peer groups.

Results.—The modified target value for small peer groups is a weighted average between the mean of the peer group and the mean of all participants using the same reagent (reagent group). Peer groups with as few as 4 members can be graded provided that specific criteria are satisfied: there must be at least 5 peer groups for the same reagent, at least 3 of these 5 peer groups must have more than 3 members, and the coefficient of variation for the reagent group must be less than 10%. This proposed grading scheme decreased the number of ungraded laboratories by 44% to 46% for the PT and 42% to 55% for the APTT. The percentage of failing grades among participants in the small peer groups ranged from 1.3% to 4.1% for the PT and 1.4% to 7.2% for the APTT. These failure rates were 2.8- to 13.0-fold higher than the failure rates in large peer groups (P ≤ .05).

Conclusions.—The proposed small peer group grading scheme can improve the effectiveness of College of American Pathologists proficiency testing for the PT and APTT and may also be generally applicable to other test methods and analytes.
p53, c-erbB2, and PCNA Status in Benign, Proliferative, and Malignant Ovarian Surface Epithelial Neoplasms
Authors: Anreder Michael B. , Freeman Scott M. , Merogi Athir , Halabi Susan , Marrogi Aizen J.
Published: January 2021

Low malignant potential tumors of the ovary are believed to behave in a manner intermediate to their benign and malignant counterparts. However, recent evidence suggests these lesions are in fact benign and better classified as proliferative. Based on our previous work and evaluating p53, c-erbB2, and PCNA status in a full spectrum of ovarian surface epithelial tumors, with emphasis on low malignant potential tumors, we tested this hypothesis. Immunohistochemical stains with monoclonal antibodies were used on 75 archival ovarian neoplasms. The results demonstrated anti-p53 reactivity in 30 carcinomas (40%), 2 of which were proliferative, and no reactivity in the benign tumors. Overexpression of c-erbB2 was seen in 31 malignant neoplasms (64.5%), 4 of which were proliferative (22.1%), and none in benign tumors. The PCNA proliferative index showed means of 42.8%, 22.8%, and 14.9% with benign, low malignant potential, and malignant tumors, respectively. Predicting immunoreactivity in carcinomas for anti-PCNA (Student t test), anti-p53, and anti–c-erbB2 (Pearson χ2 test) versus a lack of immunoreactivity in proliferative tumors indicate P values of .001, <.001, and <.001, respectively. These data show significant differences in the expression of these markers in ovarian tumors and suggest a possible role for these oncogenes as supplemental tools in diagnostic pathology. Further, our findings also support the designation of proliferative as opposed to the current nomenclature of low malignant potential tumors.
Extensive Analysis of Mosaicism in a Case of Turner Syndrome
Authors: Park Jonathan P. , Brothman Arthur R. , Butler Merlin G. , Cooley Linda D. , Dewald Gordon W. , Lundquist Kurt F. , Palmer Catherine G. , Patil Shivanand R. , Rao Kathleen W. , Saikevych Irene A. , Schneider Nancy R. , Vance Gail H.
Published: January 2021

Objective.—To assemble and interpret karyotype data provided as part of the College of American Pathologists/American College of Medical Genetics Cytogenetics Proficiency Testing Program.

Data Sources, Extraction, and Synthesis.—The Cytogenetics Resource Committee requested data on all cells analyzed in a 1994 whole-blood specimen challenge. In that study, 287 participating laboratories analyzed a total of 14297 cells derived from a sample drawn from an adult donor with Turner syndrome. This individual had previously been found to have mosaicism, including cell lines with X structural anomalies along with monosomy X, making this an excellent challenge for a multicenter cytogenetic survey.

Results and Conclusions.—Analysis of the data from this extensive study revealed mosaicism of up to 10 different sex chromosome complements involving the X chromosome with and without a small ring X or a derivative X chromosome. In the routine cytogenetic analysis performed by the participating laboratories, cell lines observed, in decreasing order of prevalence, included 45,X (n = 8357 cells), 46,X,r(X) (n = 3597), 46,X,der(X)t(X;X) (n = 2237), 46,XX (n = 93), 47,X,r(X),r(X) (n = 5), 47,X,der(X)t(X;X),der(X)t(X;X) (n = 3), 47,XX,r(X) (n = 2), and one observation each of 47,XX,der(X)t(X;X), 47,X,der(X)t(X;X),r(X), and 47,XXX. Our molecular cytogenetic data, as well as detailed analysis of G-banded chromosomes, suggest the nomenclature for these 2 abnormal X chromosomes as r(X)(p11.3q21.3) and der(X)t(X;X)(p11.3;q21.3), and we discuss models for the concomitant formation of these 2 entities. Both the degree of analysis and the extensive mosaicism that was discovered in this study are exceptional, and similar reported cases as well as possible mechanisms for the observed X chromosome instability are reviewed.
Colorectal Polyps With Extensive Absorptive Enterocyte Differentiation
Authors: Yokoo Hidejiro , Usman M. Irtaza , Wheaton Susan , Kampmeier Patricia A.
Published: January 2021

Background.—The histologic classification of colorectal polyps is well established. However, practicing pathologists may still occasionally encounter colorectal polyps that are difficult to classify. We studied 6 colorectal polyps that showed uncommon histologic features that have not been described in the English language literature.

Materials and Methods.—The polyps were studied using standard hematoxylin-eosin stain, mucin histochemistry, and electron microscopy.

Results.—The 6 polyps we studied showed extensive papillary and villous structures with alternating villi and crypts. The villi were lined by well-differentiated absorptive cells, whereas the crypts were lined by immature glandular cells, thus mimicking the histology of the small intestinal mucosa.

Conclusions.—These polyps appear to represent a variant of the hyperplastic polyp, in as much as cellular maturation (immature glandular cells differentiate into the mature surface absorptive cells) is the essential feature distinguishing hyperplastic polyps from adenomas.
Performance Improvement in Transfusion Medicine: What Do Nurses Need and Want?
Authors: Mancini Mary Elizabeth
Published: January 2021

Transfusion medicine is a complex process dependent on a variety of professionals interacting effectively and efficiently across time and distance. To perform safely, professionals depend on their own knowledge and skills, the knowledge and skills of others, and the overall effectiveness of operating systems. Nursing is an essential link in the process. To be effective, nurses need to practice in environments that recognize the importance of reducing error and improving safety through use of nonpunitive system approaches to analyzing near misses and errors. The “off-with-their-heads” approach must be eliminated. To increase efficiency, pathologists and nurses should collaborate on form development, evaluation, and implementation. Documentation regarding transfusions needs to be simplified and coordinated. Knowledgeable staff is an essential element of safe systems. Basic knowledge should never be assumed. Mechanisms to monitor knowledge of key processes along with ongoing feedback and remediation are necessary to maximize performance. Working together, nursing and transfusion specialists will improve transfusion services.
Performance Improvement in a Hospital Transfusion Service: The American Association of Blood Banks' Quality Systems Approach
Authors: Smith Dennis M. , Otter Jean
Published: January 2021

Blood bankers have always embraced the concepts of quality exemplified by the American Association of Blood Banks' Standards for Blood Banks and Transfusion Services and its accreditation program. The emergence of a quality management system based on a set of quality system essentials represents a natural evolution of these quality initiatives. When fully implemented, a quality system provides a powerful tool with which to improve the quality of both intralaboratory and, importantly, extralaboratory processes related to transfusion medicine. In addition, a functional quality system enhances a transfusion service's ability to meet current and proposed requirements of the American Association of Blood Banks, the Food and Drug Administration, the Joint Commission on Accreditation of Healthcare Organizations, and the National Committee for Clinical Laboratory Standards.
Guiding the Decision to Transfuse: Interventions That Do and Do Not Work
Authors: Toy Pearl
Published: January 2021

Guiding the decision to transfuse can improve transfusion practices. Effective processes must first identify problem(s) in transfusion practice and then include the attending physician as an educational target. Process improvements that have been shown to be effective include the following: (1) briefly meeting one-on-one with physicians, (2) teaching at scheduled conferences, (3) making daily clinical rounds of patients who receive transfusion, (4) concurrently reviewing orders for transfusion before issue of the blood product, and (5) installing algorithms and guidelines in the operating room. Transfusion practices improved with these process improvements.
Managed Care Organizations' Assessment of Reimbursement for New Technology, Procedures, and Drugs
Authors: Zarkowsky Harold
Published: January 2021

Managed care organizations must establish formal processes for the evaluation of new technology, procedures, and drugs to enhance the quality of health care delivered and to support coverage and utilization decision making. Evidence-based research and the results of controlled clinical trials are the preferred sources of outcomes data to support the safety and effectiveness of the technology, procedure, or drug under review. In addition to extensive literature review, the opinion of experts in the field and acceptance by the medical community are considered. Assessments of new technology and drugs are available for purchase from several vendors, and managed care organizations can adopt or modify such evaluations to develop medical coverage policies. The research community can assist third-party payers by conducting studies on practices that might lead to substantial, rather than marginal, improvement in health, pay particular attention to study design when randomized controlled studies are not possible, and include functional and behavioral measures in analysis of outcomes.
The Use of Monoclonal Antibody R92F6 and Polymerase Chain Reaction to Confirm the Presence of Parvovirus B19 in Bone Marrow Specimens of Patients With Acquired Immunodeficiency Syndrome
Authors: Vadlamudi G. , Rezuke W. N. , Ross J. W. , Cartun R. W. , Ackroyd R. , Knibbs D. R. , Tsongalis G. J.
Published: January 2021

Background.—Parvovirus B19 infection is a cause of chronic anemia and red cell aplasia in patients with acquired immunodeficiency syndrome (AIDS) and in other immunocompromised hosts. Anemia in AIDS patients has a multifactorial etiology, with parvovirus B19 infection being an infrequent but nevertheless treatable cause. Therapy with intravenous immune globulin can result in rapid improvement of parvovirus-induced anemia. This treatment is expensive, therefore accurate and rapid confirmation of parvovirus infection is important in providing appropriate and cost-effective therapy.

Methods.—Bone marrow samples from 2 AIDS patients with severe anemia and reticulocytopenia were studied. Bone marrow morphology and serologic studies were evaluated for parvovirus B19 infection. An immunohistochemical method using a monoclonal antibody, R92F6, to B19 capsid proteins was utilized on decalcified, B5-fixed, paraffin-embedded bone marrow biopsies. Bone marrow aspirate cells were examined by electron microscopy for evidence of viral particles. In addition, polymerase chain reaction (PCR) studies using a nested PCR assay to the parvovirus B19 viral genome were performed in a case for which fresh cells were available.

Results.—Bone marrow findings included marked erythroid hypoplasia with characteristic giant pronormoblasts and intranuclear inclusions. Serologic studies were negative in one case, while the second case showed positive parvovirus B19 immunoglobulin M antibody. Immunohistochemical studies for parvovirus B19 were positive in both cases. The presence of intranuclear virions was demonstrated by electron microscopy and was confirmed by PCR analysis. Both patients were treated with intravenous immune globulin, and subsequent improvement was noted.

Conclusions.—Both immunohistochemistry and PCR studies on bone marrow specimens from AIDS patients with anemia are rapid and sensitive methods for the confirmation of parvovirus B19 infection. They are valuable tools, particularly when serologic studies are negative. When PCR is not available, immunohistochemical methods can be useful. The rapid confirmation of parvovirus B19 infection will allow for early and cost-effective therapy.
Papillary Thyroid Carcinoma With Nodular Fasciitis-like Stroma
Authors: Yang Yi J. , LiVolsi Virginia A. , Khurana Kamal K.
Published: January 2021

Papillary thyroid carcinoma with nodular fasciitis-like stroma is one of the rare variants of papillary thyroid carcinoma. The problems posed by the exuberant nodular fasciitis-like stroma, which obscures the neoplastic nature of the tumor, are recognized in surgical pathology but have received little attention in the cytopathology literature. We report a rare case of papillary thyroid carcinoma in which nodular fasciitis-like stroma posed difficulty on fine-needle aspiration cytology. The differential diagnosis of fibroproliferative processes in thyroid fine-needle aspirations is also discussed.
Impact of Viral Load Testing on Patient Care
Authors: Nolte Frederick S.
Published: January 2021

Quantitative human immunodeficiency virus (HIV) type 1 RNA tests have been essential tools in increasing our understanding of HIV pathogenesis and antiretroviral therapy. The plasma HIV RNA level is among the most powerful predictive tests in modern medicine for disease progression and has rapidly become the standard of practice for guiding clinicians in initiating, monitoring, and changing antiretroviral therapy. In this article the scientific rationale and clinical indications for viral load testing in HIV infection are reviewed.
Laboratory Determination of Hereditary Susceptibility to Breast and Ovarian Cancer
Authors: Frank Tom S.
Published: January 2021

Inherited mutations in the genes BRCA1 and BRCA2 are associated with a significantly increased risk of breast cancer, particularly before the age of 50 years, as well as an increased risk of ovarian cancer. Patients with early-onset breast cancer or ovarian cancer at any age with a family history of either disease are at higher risk of carrying a mutation in BRCA1 or BRCA2. Laboratory analysis of these genes can determine whether a patient has inherited an increased risk of breast and ovarian cancer. In the absence of a mutation that has been previously identified in a family member, most tests for hereditary breast-ovarian cancer risk analyze the entire coding sequences of BRCA1 and BRCA2. The gene sequencing process itself can be automated, but the data must be interpreted by an individual with training in molecular diagnostics. Management options generally available to individuals with hereditary susceptibility to breast and ovarian cancer include heightened surveillance, prophylactic surgery, and chemoprevention. The use of genetic techniques to identify women with increased risk of cancer demonstrates the application of recent advances in the understanding of the genetic basis of malignancy to laboratory medicine and clinical care.
Hereditary Hemochromatosis
Authors: Press Richard D.
Published: January 2021

Objective.—To review the current state-of-the-art regarding the role of iron- and DNA-based testing on the detection, treatment, and prevention of hereditary hemochromatosis (HH), the most common single-gene disorder in white people.

Sources.—Review of the medical literature, with particular emphasis on recent reports of the impact of DNA-based testing on the detection of symptomatic and presymptomatic patients with HH.

Conclusions.—Hereditary hemochromatosis, a common autosomal recessive iron overload disorder (with a population prevalence of 0.3%–0.8%), is a common cause of preventable liver, heart, joint, and endocrine disease. Since the associated clinical signs and symptoms are nonspecific, an accurate HH diagnosis demands both a high index of suspicion and the direct laboratory demonstration of elevated iron parameters. The substantial public health burden of HH as a common, deadly, detectable, and treatable chronic disease has led the College of American Pathologists to recommend that “systematic screening for hemochromatosis is warranted for all persons over the age of 20 years.” The recent discovery that most HH cases are the result of a single well-conserved homozygous missense mutation (C282Y) within a novel transferrin-receptor binding protein (HFE) has given rise to diagnostic clinical tests for the DNA-based detection of this pathologic mutation. This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in those with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestations may be prevented (with phlebotomy therapy).
Protocol for the Examination of Specimens From Patients With Carcinomas of the Anus and Anal Canal
Authors: Rickert Robert R. , Compton Carolyn C.
Published: January 2021

No Abstract Available
Protocol for the Examination of Specimens From Patients With Carcinomas of the Small Intestine, Including Those With Focal Endocrine Differentiation, Exclusive of Carcinoid Tumors, Lymphomas, and Stromal Tumors (Sarcomas)
Authors: Ruby Stephen G.
Published: January 2021

No Abstract Available
Dysembryoplastic Neuroepithelial Tumor
Authors: Gyure Kymberly A. , Sandberg Glenn D. , Prayson Richard A. , Morrison Alan L. , Armstrong Regina C. , Wong Kondi
Published: January 2021

Context.—The dysembryoplastic neuroepithelial tumor (DNT) is an uncommon lesion characterized by a heterogeneous population of neurons, astrocytes, and oligodendroglia-like cells (OLCs). The basic nature of the DNT and its constituent cells, particularly the OLCs, remains unresolved; some authors favor a neuronal origin, and others propose a glial or mixed origin for these cells.

Design.—We examined 11 DNTs with antibodies to myelin oligodendrocyte glycoprotein, a marker of mature oligodendrocytes.

Results.—All DNTs studied (7 from males, 4 from females; age range of patients, 2–37 years) were composed of varying proportions of neurons, astrocytes, and OLCs. Membrane or cytoplasmic immunoreactivity for myelin oligodendrocyte glycoprotein was found in many OLCs in 9 of 11 cases. The number of myelin oligodendrocyte glycoprotein–positive OLCs was variable: >75% of the OLCs were positive in 5 cases, 25% to 75% of the OLCs were positive in 2 cases, and <25% of the OLCs were positive in 2 cases.

Conclusion.—These findings suggest that many of the OLCs represent mature oligodendrocytes and support the notion that DNTs are heterogenous lesions composed of multiple, mature cell types.
CD44
Authors: Ylagan Lourdes R. , Scholes John , Demopoulos Rita
Published: January 2021

Objective.—To test the hypothesis that CD44 standard (CD44[s]) and its other variants, CD44v6 and CD44v7-8, might be useful markers of squamous differentiation in epithelial tumors.

Design.—We studied expression of CD44(s), CD44v6, and CD44v7-8 using immunohistochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, pancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplastic tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 33 adenosquamous tumors were used. All were stained with monoclonal antibodies against a conserved portion of CD44(s) and its variants, CD44v6 and CD44v7-8, using the avidin-biotin peroxidase method.

Results.—CD44(s) and its variants consistently and strongly stained areas of tumors with well-developed squamous differentiation. These markers also consistently and strongly stained normal squamous mucosa. Reactivity for CD44 and its variants was lacking in normal glandular type epithelium and in adenocarcinomas composed entirely of well-differentiated mucin-producing glands. Areas of well-differentiated carcinoma, both squamous and adenocarcinoma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with well-differentiated squamous foci being consistently positive, well-differentiated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less intense with the variants, it followed the same staining pattern as found for CD44(s). No differences in the extent or intensity of staining were identified in the metastatic versus primary tumor foci, nor was any difference identified between superficial and deeply invasive areas of primary tumors.

Conclusions.—Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epithelium and tumors, and that these markers can identify areas of well- to moderately differentiated elements in adenosquamous neoplasms. However, poorly differentiated tumors show an inconsistent staining pattern with CD44, such that it cannot be used as a reliable and practical marker of squamous differentiation in poorly differentiated neoplasms.
Overexpression of Cyclin A and Cyclin B1Proteins in Astrocytomas
Authors: Allan Katherine , Jordan Richard C. K. , Ang Lee-Cyn , Taylor Michael , Young Beverley
Published: January 2021

Background.—Cyclins are proteins that are expressed during the progression of a normal cell through the cell cycle. In a number of cancers, overexpression of cyclin A and cyclin B1 proteins has been reported, and in some instances the levels of expression correlated well with the grades of malignancy. The expression of cyclin A and cyclin B1 proteins in astrocytoma may be linked to the histologic grade or proliferative activities.

Objective.—To study the expression of cyclin A and cyclin B1 proteins in astrocytomas and correlate the labeling indices (LIs) of cyclin A and cyclin B1 with histologic grade and Ki-67 LI.

Design.—The surgical biopsy specimens from 65 adults with astrocytomas were reviewed and divided into grades based on the World Health Organization system. The paraffin sections were immunostained using primary antibodies against Ki-67, cyclin A, and cyclin B1. The LIs of these astrocytomas for the 3 different antibodies were determined by computerized image analysis.

Results.—The cyclin A LI showed good correlation with astrocytoma grade and Ki-67 LI. Both the nuclear and cytoplasmic cyclin B LIs correlated well with the tumor grade but showed poor correlation with Ki-67 LI.

Conclusions.—This study suggests that although both cyclin A and B protein expression are related to the grade of malignancy in astrocytomas, cyclin A levels more generally reflect the proliferative state of these tumors. We also provide indirect evidence that cyclin B1 is associated with the aberrant progression through the G2-M phase checkpoint in astrocytomas.
Testicular Regression Syndrome
Authors: Spires Susan E. , Woolums C. Stephen , Pulito Andrew R. , Spires Stephen M.
Published: January 2021

Context.—The vanishing or regressed testis is an entity well known to urologists and pediatric surgeons, affecting approximately 5% of patients with cryptorchidism. However, there is little review and discussion of this entity among pathologists with only 2 of 40 published reviews of testicular regression syndrome (TRS) found in the pathologic literature.

Objectives.—To assess recognition of TRS among a subset of pathologists and to determine the applicability of histologic criteria for TRS as published.

Design.—An 8-year retrospective review of cases submitted as atrophic or regressed testis was performed. Original diagnosis and diagnosis after review were compared to assess pathologic recognition of TRS. Pathologic assessment included identification of vas deferens, epididymis, dystrophic calcification, hemosiderin, dominant vein, pampiniform plexus–like vessels, and vascularized fibrous nodule formation. At minimum, the presence of a vascularized fibrous nodule (VFN) with calcification or hemosiderin or VFN with cord element(s) was required for diagnosis.

Setting and Participants.—Medical records and pathologic specimens of patients undergoing surgery for cryptorchidism or with specimens reviewed at a medium-sized university hospital were analyzed.

Results.—The original diagnosis in 3 (23%) of 13 cases was that of TRS. On secondary review, 11 (85%) of 13 cases showed features consistent with TRS. The diagnoses both before and after review showed a concurrence of 23% (3/13 cases). Two (15%) of 13 cases were correctly recognized and diagnosed as TRS at primary review; 1 case originally thought to represent TRS was not confirmed. Pathologic features correlated well with those reported in the literature. Among all 13 cases, the 11 confirmed TRS cases showed VFN in 11 (85%), intranodular calcification in 8 (62%), intranodular hemosiderin in 9 (69%), vas deferens in 9 (69%), epididymal structures in 5 (38%), and a dominant venous structure in 11 (85%). The average size of the VFN was 1.1 cm.

Conclusion.—A urologic and pediatric surgical problem, TRS may be unrecognized by many practicing pathologists. In the typical situation in which a blind ending spermatic cord is submitted for tissue analysis, characterization of such cases as consistent with regressed testis is desirable and achievable in a high percentage of cases. Pathologists may play a pivotal role in management of these patients since histologic confirmation of the testis as regressed reassures the surgeon and the family of the correctness of diagnosis and can eliminate the necessity for further intervention.
Hyalinizing Spindle Cell Tumor With Giant Rosettes—A Soft Tissue Tumor With Mesenchymal and Neuroendocrine Features
Authors: Bejarano Pablo A. , Padhya Tapan A. , Smith Roger , Blough Ruthann , Devitt James J. , Gluckman Jack L.
Published: January 2021

Context.—Hyalinizing spindle cell tumor with giant rosettes is a recently described biphasic neoplasm of soft tissues that shares mesenchymal and neuroendocrine features. Its morphologic structure is distinctive, with the presence of hyalinized paucicellular foci that are termed rosettes. The cells around the latter display positive immunoreactivity for neuroendocrine markers. The small number of cases described to date indicates that they tend to be localized in the extremities.

Objective.—To describe the clinicopathologic features of 2 unusual cases of hyalinizing spindle cell tumor with giant rosettes.

Methods and Results.—One tumor was located in the prestyloid parapharyngeal space and the second in the left thigh. Both tumors were well circumscribed and surrounded by a thin capsulelike fibrous band without infiltrating projections. The rosettes were embedded in a spindle cell proliferation. Immunohistochemical stains showed positive results for S100 protein, synaptophysin, CD57, protein gene product 9.5, and neuron-specific enolase exclusively in the cells palisading the rosettes. These markers were negative in the spindle cell portions of the tumor. The latter were immunoreactive for factor XIIIa, vimentin, HAM56, collagen IV, and CD68. Vimentin was the only marker shared by the rosette-forming cells and the spindle cells. Ultrastructurally, the rosette-forming cells contained neurosecretory granules. This study describes the first cytogenetic analysis in this type of tumor revealing 2 cell lines, both containing a balanced translocation between chromosomes 7 and 16. Follow-up of the patients at 16 and 8 months did not disclose evidence of recurrence.

Conclusions.—These 2 new cases increase the awareness of hyalinizing spindle cell tumor with giant rosettes and demonstrate that it is a spindle cell neoplasm of unique cytogenetic rearrangements composed of dendritic, histiocytic, and fibroblastic cells admixed with cells that have neuroendocrine differentiation.
Changes of Biochemical and Biomechanical Properties in Dupuytren Disease
Authors: Melling Mahmoud , Karimian-Teherani Daniela , Mostler Sascha , Behnam Mark , Sobal Grazyna , Menzel Ernst J.
Published: January 2021

Background.—The major biochemical characteristic of Dupuytren disease is the progressive and irreversible deposition of excess fibrous collagen characterized by an enhanced type III collagen proportion.

Objective.—To investigate the influence of changes of the collagen spectrum on the biophysical properties of the palmar aponeurosis.

Design.—Variably affected palmar regions from 30 individuals with Dupuytren disease were classified according to histologic test results and clinical stage. Biochemical, biomechanical, and thermal contracture studies were performed.

Results.—The relative type III collagen content increased with increasing tissue involvement and was found to correlate with calorimetric and biomechanical properties with the exception of the Young modulus. In experiments on the thermal isometric contracture, the collagen denaturation temperature decreased with increasing type III collagen content, ie, increasing involvement. To study the dependence of biophysical properties from the collagen type distribution independent of structural changes, as seen in Dupuytren disease, we investigated rat skins from animals of an age range characterized by dramatic changes in type III collagen content (0–18 months). Biomechanical data also correlated significantly with type III collagen content in rat skin with the exception of the time constant of stress relaxation.

Conclusion.—In light of these results, we suggest that structural changes, such as reduced collagen fibril diameters, associated with alterations in the type III collagen proportion may influence biophysical properties of connective tissues in the involved palmar aponeurosis in addition to alterations of the cross-linking pattern.