bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a Diagnostic Polymerase Chain Reaction Assay forNeisseria meningitidisin North America and Field Experience During an Outbreak
Authors: Pollard Andrew J. , Probe Gary , Trombley Colleen , Castell Annette , Whitehead Sue , Bigham J. Mark , Champagne Sylvie , Isaac-Renton Judy , Tan Rusung , Guiver Malcolm , Borrow Ray , Speert David P. , Thomas Eva 
Published: January 2021

AbstractContext.—Meningococcal infection has a high public profile because of its dramatic presentation, high fatality rate, and propensity to occur in outbreaks and clusters of cases. Use of a diagnostic polymerase chain reaction (PCR) assay could enhance laboratory confirmation of cases and guide the public health response in North America.Objective.—To assess the performance of a PCR assay for the diagnosis of meningococcal disease after its implementation in a North American setting and to evaluate sensitivity and specificity of the assay for the detection of prevalent bacterial isolates.Design.—Laboratory evaluation of the sensitivity and specificity of a PCR assay for Neisseria meningitidis and observational study of a series of cases comparing molecular diagnosis against the criterion standard of conventional laboratory diagnostic tests.Setting.—A Canadian province with a population of 4 million people.Patients.—Children and adults presenting with suspected meningococcal disease in British Columbia.Main Outcome Measures.—The sensitivity and specificity of the PCR assay when compared against standard laboratory methods.Results.—The PCR assay correctly identified all of 38 Canadian isolates of Neisseria meningitidis and correctly assigned the serogroup to each isolate. None of 57 other gram-positive or gram-negative bacteria or yeasts were detected by the PCR assay. In a clinical evaluation, for diagnosis of meningococcal disease, the PCR assay had a sensitivity and specificity of 91% and 76%, respectively, against conventional methods of diagnosis. Use of the PCR assay increased the laboratory confirmation of clinically suspected cases by 36%. During an outbreak, the PCR assay allowed serogroup determination in 3 of 7 cases, aiding in the public health decision to launch an immunization campaign.Conclusions.—The PCR assay is more sensitive than conventional methods for the diagnosis of meningococcal disease, and enhanced surveillance may help direct the public health response to the changing epidemiology of disease in North America.
Primary Large Cell Neuroendocrine Carcinoma of the Urinary Bladder
Authors: Evans Andrew J. , Al-Maghrabi Jaudah , Tsihlias John , Lajoie Ginette , Sweet Joan M. , Chapman William B. 
Published: January 2021

Abstract
Reports of primary large cell neuroendocrine carcinomas of the urinary bladder are few; we identified only 2 cases in the literature. Both of these cases involved male patients with rapid progression of disease culminating in death with widespread metastases. We report a case of primary large cell neuroendocrine carcinoma of the bladder, with an admixed minor element of adenocarcinoma, in an 82-year-old man. This solitary lesion arose in a bladder diverticulum lateral to the left ureteric orifice. Two attempts at transurethral resection were unsuccessful at achieving local control. The patient underwent a partial cystectomy with left-sided pelvic lymphadenectomy following preoperative staging investigations that found no metastatic disease. Pathologically, the tumor invaded into the deep aspect of the muscularis propria, without extension into perivesical fat. The lateral resection margin was microscopically positive for tumor, but no malignancy was found in the pelvic lymph nodes. The adenocarcinoma comprised less than 5% of total tumor volume, and areas of transition between the neuroendocrine and adenocarcinoma components were apparent. The patient developed a local recurrence 8 months postoperatively, which was managed by a combination of transurethral resection and radiation therapy. Currently, the patient has no evidence of local or metastatic disease 2 years after initial diagnosis.
Phyllodes Tumor Metastatic to Thyroid HürthleCell Adenoma
Authors: Giorgadze Tamar , Ward Richard M. , Baloch Zubair W. , LiVolsi Virginia A. 
Published: January 2021

Abstract
We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.
Clinical and Laboratory Management of the Prothrombin G20210A Mutation
Authors: McGlennen Ronald C. , Key Nigel S. 
Published: January 2021

AbstractObjective.—To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field.Data Sources.—Review of the medical literature, primarily since 1996.Data Extraction and Synthesis.—After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.Conclusions.—Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.
Hyperhomocyst(e)inemia and Thrombophilia
Authors: Key Nigel S. , McGlennen Ronald C. 
Published: January 2021

AbstractObjective.—To review the role of an elevated total plasma homocysteine level (hyperhomocyst[e]inemia) in patients with venous or arterial thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field.Data Sources.—Review of the medical literature, primarily from the last 10 years.Data Extraction and Synthesis.—The literature was reviewed to identify key points defining the condition, and the clinical study design of each article was examined. A draft manuscript was prepared and circulated prior to the conference to every participant in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. Each of the key points and associated recommendations was then presented for discussion at the conference. Recommendations were accepted if a consensus of the 70% of the experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.Conclusions.—Consensus was reached on 9 recommendations concerning the criteria for diagnosis, the method of testing, and the approach for clinical management. A major point of consensus was that no causal role of hyperhomocyst(e)inemia in venous or arterial thrombosis is yet established. Testing methods used to measure homocysteine directly are sensitive and reliable, and provide more information than does genotyping for markers linked to abnormal plasma homocysteine.
Antiphospholipid Antibodies
Authors: Triplett Douglas A. 
Published: January 2021

Abstract
Objective.—To review the role of lupus anticoagulants in the pathogenesis of both venous and arterial thromboembolic events, as well as in recurrent spontaneous abortions. The pathophysiology of lupus anticoagulants and associated antiphospholipid antibodies (eg, anticardiolipin antibodies) is also discussed.
Data Sources.—Review of the recent medical literature.
Data Extraction and Synthesis.—Key articles in the recent medical literature dealing with lupus anticoagulants and their role in pathogenesis of thromboembolic events were reviewed. Plasma proteins that have an affinity for binding to “perturbed cellular membranes” have been identified as the antigenic targets for antiphospholipid antibodies. Thus, the concept of antiphospholipid antibodies needs to be reevaluated. Perhaps a better term is antiprotein-phospholipid antibodies. The principal antigenic protein targets are β2-glycoprotein I, prothrombin, and a wide range of additional proteins that interact with activated cellular membranes, including protein C, protein S, annexin V, etc. Most research reported in the literature has focused on β2-glycoprotein I and human prothrombin.
Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndrome
Authors: Moake Joel L. 
Published: January 2021

AbstractObjective.—To evaluate the usefulness and feasibility of measuring plasma von Willebrand factor (vWF)-cleaving metalloprotease activity (ADAMTS 13) in the differential diagnosis of thrombotic thrombocytopenic purpura (TTP), the hemolytic uremic syndrome, and other thrombotic microangiopathies.Data Sources.—Articles published in the medical literature.Data Extraction and Synthesis.—In TTP, a multimeric form of vWF that is larger than that ordinarily found in the plasma may cause systemic platelet aggregation under the high-shear conditions of the microcirculation. ADAMTS 13 is a divalent cation-activated, vWF-cleaving metalloprotease that converts unusually large vWF multimers derived from endothelial cells into smaller vWF forms in normal plasma. ADAMTS 13 is severely reduced or absent in most patients with TTP. The vWF-cleaving metalloprotease is present in fresh-frozen plasma, cryoprecipitate-depleted plasma (cryosupernatant), and in plasma that has been treated with solvent and detergent. The enzyme is defective in children with chronic relapsing TTP. Infusion of any of the plasma products that contain the vWF-cleaving metalloprotease stops or prevents (for about 3 weeks) TTP episodes in these patients. An immunoglobulin (Ig) G autoantibody to the vWF-cleaving metalloprotease is found transiently in many adult patients with acquired acute idiopathic, recurrent, and ticlopidine/clopidogrel-associated TTP. Patients with acquired TTP require plasma exchange, that is, both infusion of a plasma product containing vWF-cleaving metalloprotease and removal of autoantibody and/or unusually large vWF multimers by plasmapheresis. The pathophysiology of platelet aggregation in bone marrow transplantation/chemotherapy-associated thrombotic microangiopathy, as well as in hemolytic uremic syndrome, is not established. In neither condition is there a severe decrease in plasma vWF-cleaving metalloprotease activity, as there is in TTP.Conclusions.—The presently available lengthy and complicated procedure for estimation of plasma vWF-cleaving metalloprotease activity is not yet practical for rapid diagnostic use. This test has supplanted the equally lengthy and difficult, less specific analysis of plasma vWF multimeric pattern. If the clinical distinction between TTP and hemolytic uremic syndrome is uncertain, it is appropriate to acquire (before therapy) a citrate-plasma sample for the ultimate determination of vWF-cleaving metalloprotease activity.
Proficiency Testing for Laboratories Performing Fluorescence In Situ Hybridization With Chromosome-Specific DNA Probes
Authors: Mascarello James T. , Brothman Arthur R. , Davison Keri , Dewald Gordon W. , Herrman Marille , McCandless Danette , Park Jonathan P. , Persons Diane L. , Rao Kathleen W. , Schneider Nancy R. , Vance Gail H. , Cooley Linda D. 
Published: January 2021

Abstract
Objective.—To assess laboratory performance, use, and limitations in the joint College of American Pathologists and American College of Medical Genetics proficiency testing program for laboratories performing cytogenetic tests based on fluorescence in situ hybridization (FISH).
Data Sources.—Eight proficiency surveys dealing with FISH detection of microdeletions or microduplications, aneuploidy in interphase cells, gene amplification, and neoplasm-specific translocations. Participating laboratories used their own DNA probes (commercial or home-brew), hybridization methods, and analytic criteria to answer clinical questions about cases represented by slides included in the survey materials. They also described their test results according to the International System for Human Cytogenetic Nomenclature (ISCN) and answered supplementary questions relating to their experience with the subject test systems.
Data Extraction.—In addition to evaluating diagnostic accuracy, we evaluated survey use, laboratory experience, variation in methodologic approach, and the practicality of using ISCN nomenclature for describing test results.
Synthesis and Conclusions.—With the exception of one challenge, at least 80% of the participants reached the correct diagnostic conclusion. In the sole exception, there was still a consensus of 91.7% of participants with the same (albeit erroneous) diagnostic conclusion. The overall outstanding performance of participating laboratories clearly shows the reliability of current FISH methods. Despite the fact that a large number of laboratories reported little or no experience with the specific test systems, the overwhelming majority performed very well. This result shows that the program's strategy of targeting classes of abnormalities (vs a single abnormality associated with a specific disease) did not put at a disadvantage participants who did not routinely perform all of the potential tests in the class. The extraordinary variation in ISCN descriptions submitted by participants showed that the existing system for human cytogenetic nomenclature is not suitable for facile communication of FISH test results.
Proteomic Approaches to Tumor Marker Discovery
Authors: Rai Alex J. , Zhang Zhen , Rosenzweig Jason , Shih Ie-ming , Pham Thang , Fung Eric T. , Sokoll Lori J. , Chan Daniel W. 
Published: January 2021

Abstract
Context.—Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids.
Objective.—To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer.
Design.—We analyzed plasma samples that had been collected between 1998 and 2001 from patients with sporadic ovarian serous neoplasms before tumor resection at various International Federation of Gynecology and Obstetrics stages (stage I [n = 11], stage II [n = 3], and stage III [n = 29]) and from women without known neoplastic disease (n = 38) using proteomic profiling and bioinformatics. We compared results between the patients with and without cancer and evaluated their discriminatory performance against that of the cancer antigen 125 (CA125) tumor marker.
Results.—We selected 7 biomarkers based on their collective contribution to the separation of the 2 patient groups. Among them, we further purified and subsequently identified 3 biomarkers. Individually, the biomarkers did not perform better than CA125. However, a combination of 4 of the biomarkers significantly improved performance (P ≤ .001). The new biomarkers were complementary to CA125. At a fixed specificity of 94%, an index combining 2 of the biomarkers and CA125 achieves a sensitivity of 94% (95% confidence interval, 85%–100.0%) in contrast to a sensitivity of 81% (95% confidence interval, 68%–95%) for CA125 alone.
Conclusions.—The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125. Additional studies are required to further validate these biomarkers.
Reactivity of Resident Immunocytes in Normal and Prepsoriatic Skin Using an Ex Vivo Skin-Explant Model System
Authors: Curry Jonathan L. , Qin Jian-Zhong , Robinson June , Nickoloff Brian J. 
Published: January 2021

AbstractContext.—While it is well known that both exogenous and endogenous stimuli can trigger appearance of psoriatic lesions, the initial cellular and molecular events mediated by immunocompetent cells normally resident in prepsoriatic (PN) skin are not well understood. Moreover, it is unclear whether there are any fundamentally important differences in the innate immune response of normal healthy skin (NN skin) versus PN skin. Since acute tissue responses to stimuli involve both resident cells and immunocytes recruited rapidly from circulation, it is difficult to discern the contribution of endogenous cells normally present in skin.Objective.—To solely characterize the reactivity of resident immunocytes using an experimental system.Design.—To probe the activation potential of resident immunocytes in NN (n = 18) and PN skin (n = 10), a short-term ex vivo organ culture system containing interleukin (IL)-2 was established and characterized. To mimic exogenous or environmental trigger factors, bacteria-derived superantigens and lipopolysaccharide were added to the skin-explant assays, whereas endogenous trigger factors were investigated using heat shock proteins.Results.—Using this skin-explant assay, both NN and PN skin gave rise to an expansion of various T-cell subsets, which could differentially produce various cytokines and a growth factor (keratinocyte growth factor), depending on the stimulus and source of skin. Bacterial superantigens were relatively potent inducers of interferon-γ, and natural killer–T cells were observed proliferating from PN skin.Conclusions.—Despite relatively few T cells normally residing in either NN or PN skin, initiation of skin explants from both sets of individuals in the presence of IL-2 triggered vigorous T-cell proliferation and cytokine/growth factor release. These results demonstrate the utility of this skin-explant assay system to further investigate quantitative and qualitative immune responses of NN and PN skin.
Pulmonary Expression of Vascular Endothelial Growth Factor in Sepsis
Authors: Tsokos Michael , Pufe Thomas , Paulsen Friedrich , Anders Sven , Mentlein Rolf 
Published: January 2021

Abstract
Context.—Vascular endothelial growth factor (VEGF), an angiogenic and chemotactic peptide, is abundantly expressed in normal lung tissue, especially in alveolar and bronchial epithelium, glandular cells of the bronchi, and activated alveolar macrophages.
Objective.—To investigate the role of VEGF in progressively impaired lung function as the major complication and cause of death in septic patients.
Materials and Methods.—We evaluated pulmonary VEGF expression in lung autopsy material from septic patients who had been cared for by intensive care medicine using enzyme-linked immunosorbent assay (ELISA), reverse transcriptase–polymerase chain reaction (RT-PCR), and immunohistochemical methods.
Results.—Compared with expression in nonseptic control individuals (n = 10), pulmonary VEGF expression as determined by ELISA was significantly (P &lt; .001) decreased in septic patients (n = 8). As monitored by RT-PCR, mRNA for the 2 splice variants, VEGF121 and VEGF165, and for VEGFR-2/KDR were expressed in both groups, the yields being lower in the sepsis group. Samples from septic patients lacked or showed only sparse immunoreaction on bronchial and alveolar epithelium, whereas this reaction was strong in all control samples. However, alveolar macrophages were similarly immunopositive in both groups.
Conclusions.—The precise underlying mechanisms for the distinctly different expression of pulmonary VEGF in septic patients and nonseptic control individuals are not clear at present. Particularly the role of VEGF in the development of sepsis-induced lung injury and acute respiratory distress syndrome in mechanically ventilated patients suffering from severe sepsis remains to be clarified.
Pleomorphic Adenoma of the Breast
Authors: Reid-Nicholson M. , Bleiweiss I. , Pace B. , Azueta V. , Jaffer S. 
Published: January 2021

Abstract
Pleomorphic adenoma of the breast is a rare, benign tumor accounting for 68 cases in the literature. It is most commonly seen in postmenopausal women and is characterized by an admixture of epithelial and myoepithelial cells embedded in abundant myxomatous stroma. Its clinical and histologic appearance can be challenging and may lead to a misdiagnosis of invasive carcinoma. We report a case of mammary pleomorphic adenoma in an asymptomatic 59-year-old woman and briefly discuss its distinction from mucinous carcinoma through the use of special stains.