bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmablastic Myeloma Versus Plasmablastic Lymphoma; Is MYC Rearrangement Helpful Towards A Precise Diagnosis?
Authors: Khedr M , Yusuf Y , Aftab L 
Published: October 2020

Abstract

Introduction/Objective
Plasmablastic myeloma (PBM) is a rare and aggressive plasma cell neoplasm. Differentiating PBM from plasmablastic lymphoma (PBL) represents a diagnostic challenge, as both diseases have overlapping cytomorphologic and immunophenotypic features. Genetic mutations in MYC occur in a majority of PBL cases but rarely in PBM, thus can theoretically be used to differentiate between both neoplasms.

Methods
We report a case of a 53-year-old female who presented with a rapidly growing mass in her right mandible. Biopsy revealed circumscribed nodules of immunoblastic cells with moderate cytoplasm, large vesicular nuclei and large prominent nucleoli. Apoptotic debris and brisk mitoses were present. Molecular testing revealed a C-MYC rearrangement. The location of the neoplasm and the above described morphological features were suggestive of PBL, especially with a positive C-MYC rearrangement. The neoplastic cells were positive for CD138, MUM1,CD56 and kappa; and negative for CD45, CD20, PAX5, CD3, CD5, CD30, EBER-ISH, HHV8, ALK-1, Lambda, EMA, CD21, CD23, pancytokeratin, CK20, CK7, Cam5.2, chromogranin, synaptophysin, HMB45, S100, P16, P40. MIB-1 showed high positivity, approximately 95%.

Results
Patient underwent further diagnostic work up, her HIV antibodies result were negative however, she was found to be anemic (Hemoglobin 6.6 g/dl; reference range 12-16 g/dl) and hypercalcemic (Calcium 12.3 mg/dl; reference range 8.5-10.5 mg/dl). PET scan revealed multiple hypermetabolic lytic bone lesions. The bone marrow biopsy showed 80% cellularity with extensive involvement by atypical plasmacytic cells forming large clusters. The patient’s final diagnosis was PBM.

Conclusion
Differentiating PBM from PBL is essential as treatment is different. Although MYC rearrangement in PBM is not common, it has been demonstrated and therefore should not be used to exclude this diagnosis. Here, we highlight the importance of correlating detailed clinical, radiological, laboratory, histological and genetics data for reaching the final diagnosis.
Evaluation of BRCA1 and BRCA2 Protein Dysfunction in Breast Cancer Cells among Women in Osun State, Southwest Nigeria
Authors: Iyiola S , Komolafe A , Samuel A , Onifade J A , Enweani I , Ngokere A 
Published: October 2020

Abstract

Introduction/Objective
Breast cancer among Nigeria women had been found to occur at a much younger age compared with their Caucasian age groups. BRCA1 and BRCA2 were suspected to responsible for breast cancers at a young age, therefore this work examined the BRCA1 and BRCA2 dysfunction among women suffering from breast cancer in Osun State, Nigeria.

Methods
This cross-sectional study was carried out at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife and Ladoke Akintola University Teaching Hospital, Osogbo, Nigeria. The request cards and tissue blocks were sorted from the year 2014 to 2017. The breast tissue blocks were sectioned, stained with H&E. A representative tissue block was selected for each patient. Sections obtained from the blocks were stained with BRCA 1 and BRCA 2 antibody using a diaminobenzidine horseradish peroxidase technique. The cells were semi-quantitatively scored as percentage of tumour cells stained brown. Score 0-5% were taken as negative as proposed by Karuna et al., 2013.
The value obtained was tabulated against the age of the patient.

Results
Out of 240 breast cancer patients sampled 16(6.7%), 32(13.3%), 85(35.4%), 43(17.9%), 64(26.7%) patients were between ages 21-30, 31-40, 41-50, 51-60 and 60+ years respectively. 54(22.5%) showed loss of BRCA 1 staining with only 1(0.4%) patient between age 21-40 years while 18(7.5%), 16(6.67), 19(7.9) patients between age 41-50, 51-60 and 60+ years respectively. 82(34.2%) showed loss of BRCA 2 staining; 7(2.9%), 12(5%), 31(12.9%), 15(6.25%),17(5.8%) patients for age between 21-30, 31-40, 41-50, 51-60 and 60+ years respectively. Among women aged 50 years and below, BRCA 1 and BRCA 2 dysfunctions were responsible for 14.3% and 37.6% of breast cancers respectively.

Conclusion
Increase in age increases the rate of BRCA 1 dysfunction while BRCA 2 dysfunction is not more associated to with any age. BRCA1 and BRCA2 are responsible for more than thirty percent of breast cancers among women less than 50 years of age in Osun state.
TRUU-Lab: Methods for Optimizing Test Names for Understanding and Utilization
Authors: Wang J , Garnett E , Singh I , Bierl C , Jackson B 
Published: October 2020

Abstract

Introduction/Objective
Poor understandability of laboratory test names increases the risk for inappropriate test utilization and medical errors. Yet, human understandability has not been a major consideration in existing laboratory test names or naming guidelines. TRUU-Lab (Test Renaming for Understanding and Utilization for Laboratory Test Names) is a national initiative that now has more than 45 members representing more than 20 academic and industry organizations, the CDC, and the FDA. The goals of the initiative include: 1) Identify root causes and challenges in understanding and using laboratory test names; 2) Share resources related to potential solutions; 3) Develop consensus guidelines for laboratory test naming; 4) Establish consensus names for existing laboratory tests; and 5) Promote the adoption and implementation of consensus laboratory test names.

Methods
We previously addressed the first two goals of this initiative by identifying problematic test names and features of test names that contribute to misutilization. We also identified the advantages and limitations of current test naming guidelines and previous standardization efforts. This current study addresses goals 3 and 4. We developed an iterative process of guideline development. This process includes collecting feedback on consensus names to improve guidelines, which then informs the improvement of the consensus names.

Results
By analyzing test name characteristics, we found that the requirements for understandability vary with respect to the clinical scenario and provider background. We have used these results to design a 30-min long survey to test candidate names. The survey will be distributed through the Brand Institute, which offers expertise in pharmaceutical name and brand identity development. This pilot survey will be sent to primary care providers to assesses intuitive name preferences given a short and specific prompt. The second phase will take place in a simulated electronic medical record environment to present clinical scenarios where physicians will select an appropriate test.

Conclusion
We expect that results from survey studies will directly inform the development of TRUU-Lab naming guidelines, in turn permitting development of better-optimized laboratory test names. This process represents a new strategy for the intentional design of laboratory test names that are understandable and promote correct provider utilization.
Gastroblastoma: Cytologic Findings with Resection and Molecular Correlation
Authors: Reardon J D , Hatfield B S , Kraft A O , Smith S C 
Published: October 2020

Abstract

Casestudy
Gastroblastoma is a rare tumor with biphasic components showing epithelial and mesenchymal differentiation. To date, &lt;15 cases have been reported, with molecular confirmation of the recently identified MALAT1-GLI1 translocations only in a subset. Aspiration cytologic and small biopsy findings have not yet been reported. We present a case of gastroblastoma, arising in a 22-year-old female.

Results
A CT scan was performed, showing a 7 cm heterogeneous mass in the distal stomach and pancreas, clinically suspected to represent at gastrointestinal stromal tumor (GIST). She underwent two preoperative samples, including endoscopic ultrasound guided-fine needle aspiration and core biopsy, followed by a distal gastrectomy. Diff- Quik stained touch preparations performed on the core needle biopsy during rapid on-site evaluation showed a hypercellular neoplasm composed of large, three-dimensional aggregates of neoplastic cells in a background of numerous isolated single cells and bare nuclei. The neoplastic cells were bland with spindled to epithelioid nuclei, occasional nuclear grooves, and small nucleoli. Immunostains were only helpful in excluding GIST (CD117 and DOG1 negative). Distal gastrectomy showed a nodular/plexiform tumor with variably epithelioid to spindle cell cytology and solid to focally myxoid/microcystic architecture. Pancytokeratins CAM5.2 (patchy) and AE1/AE3 (very focal) were positive, with negative S100, SMA, Desmin, Melan-A, Inhibin, Calretinin, and Synaptophysin. Based on the age, location, histology and immunophenotype, gastroblastoma was suspected, and multiplex NGS-based fusion sequencing identified a MALAT1-GLI1 fusion. Staging studies were negative for metastasis at presentation.

Conclusion
Based on this experience, we recommend consideration of gastroblastoma for a gastric tumor in a young patient, especially if encountering a cytologic sample showing non-pleomorphic epithelioid and spindle cell cytology. Lack of expression of GIST, smooth muscle, neuroendocrine, and neural sheath-associated markers should particularly raise consideration of this rare neoplasm. While in this case molecular studies clinched the diagnosis upon resection, increasingly used GLI1 immunostain may be of use prospectively for diagnosis of limited samples.
Validation/Verification of Abbott RealTime SARS-CoV-2 Assay on the Abbott m2000 System: The Veteran Affairs Medical Center (VAMC) Experience
Authors: Petersen J M , Dalal S , Jhala D 
Published: October 2020

Abstract

Introduction/Objective
The extraordinary circumstances of the highly contagious SARS-CoV-2 pandemic have led the FDA to approve diagnostic assays with emergency use authorizations (EUA). One of these assays is the Abbott RealTime SARS-CoV-2 assay (Abbott Park, Ill.). However, the literature is sparse on the validation of EUA assays for SARS-CoV-2 assays for this crisis; therefore, we present the Veteran Affairs Medical Center (VAMC) experience in validating/verifying this test for clinical use.

Methods
Validation/verification was performed in three parts as part of quality assurance/quality improvement; 1) sample/patient correlation, 2) precision, and 3) validation/verification of accuracy at the lower limit of detection (LOD). The results from these studies was compiled, reviewed by the laboratory, and after performance was deemed satisfactory, the test would be put for clinical use.

Results
For the sample/patient correlation, a total of 68 known positive and 59 known negative samples were run; these included 56 positive contrived samples or controls, 12 known positive patient samples, 31 negative contrived or controls, and 28 known negative patient samples. All results from the assay were as expected with 100% positive and negative percent agreement except for one sample that was quantity not sufficient for testing. The precision study with 4 known positive and 4 known negative samples run once per day for 5 days yielded perfect 100% precision for both the positive and negative samples. Replicates to determine accuracy at the lower LOD (100 virus copies/ml per instructions for use of the assay) demonstrated accuracy even with dilutions down to 50 virus copies/ml. For this third step, 3 replicates each had been performed at 1000, 500, 250, 70, 60 and 50 virus copies/ml. As 100 virus copies/ml was the provided manufacturer LOD, 7 replicates were performed at 100 virus copies/ml.

Conclusion
The validation/verification indicated that the Abbott RealTime SARS-CoV-2 assay performed with expectations including with real patient samples and could be put into clinical use at the VAMC. After this validation/verification, the assay has been very successfully used for in-house testing for SARS-CoV-2. In fact, the validation demonstrated an LOD as low as 50 virus copies/ml, suggesting the assay may be even more sensitive to low levels of viremia than is stated in the EUA.
Navigating the Diagnostics of COVID-19
Authors: Sanyaolu A , Okorie C , Marinkovic A , Ayodele O , Abbasi A , Prakash S , Ahmed M , Kayode D , Jaferi U , Haider N 
Published: October 2020

Abstract

Introduction/Objective
The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Hubei province, China in December 2019 and has spread worldwide at an alarming rate. With millions of individuals infected and over two hundred thousand deaths, the necessity to develop fast and efficient diagnostic methods is of high importance. Diagnostic modalities rely on a combination of epidemiology, clinical presentation, laboratory examination, and appropriate imaging to diagnose and distinguish SARS-CoV-2 from other pulmonary infections. The purpose of this paper is to report on currently available diagnostic screening methods for patients infected with SARS-CoV-2 to guide frontline healthcare workers involved with COVID-19 patient care.

Methods
An electronic literature search was performed for peer-reviewed articles published from January 1, 2020, until April 26, 2020. Articles were then reviewed and included based on the applicability to the topic.

Results
The preferred diagnostic approach is reverse transcription of the virus’ RNA followed by PCR amplification (RT-PCR). This method recognizes the gene-specific primers to target various viral protein genes, such as the envelope protein gene or the nucleocapsid protein gene, which enables this test to be both sensitive and specific toward SARS-CoV-2. However, this method has been proven to be time-consuming taking hours-to-days for the results. In order to improve the speed and efficiency of diagnostics, newer rapid diagnostic serological tests are being developed for testing SARS-CoV-2, each with its own unique advantages and disadvantages. They could potentially be used as triage tests to rapidly identify patients who are very likely to have COVID-19 in combination with other accurate diagnostic methods.

Conclusion
Therefore, a combination of diagnostic testing used in a timely manner may be beneficial for the rapid and accurate detection of SARS-CoV-2. This was evident in cases where despite initial negative RT-PCR tests for various patients, who later demonstrate chest CT scans with various degrees of consolidation and ground-glass opacity. Thus establishing the need for radiology diagnosis to be complementary to RT-PCR for COVID-19 patients. Hopefully, the continuous development and use of rapid diagnostic tests and the implementation of public health measures will help control the spread of the disease.
Detecting Lung Cancer Stages Earlier By Appropriate Markers Rather Than Biopsy And Other Techniques
Authors: Addissouky T A , Khalil A A 
Published: October 2020

Abstract

Introduction/Objective
Early detection of lung cancer stages is deeply under consideration of scientists. By day, high rate of mortality might be caused by cancer of lung over the world. The biopsy is still the golden standard as a histological predictor to determine lung cancer worldwide. However, a biopsy has various complications and hardness especially in collecting tissue samples. Therefore, detecting appropriate tools to determine the early stages of lung cancer is urgently needed. Some biomarkers levels have been determined in patient’s serum. The correlation between studied biomarkers and lung cancer has been studied by current research to avoid biopsy and other techniques.

Methods
The various biomarkers such as (CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4) were measured and calculated in 379 infected cases with lung cancer. Also, the same parameters were determined in 113 healthy persons as controls. Alternative markers’ levels were determined by using ELISA technique. Noninvasive markers were approved by comparison with CT chest scan and Biopsy techniques.

Results
Our research has indicated that Some of the studied biomarkers such as cytoskeleton-associated protein 4 (CKAP4), pro-gastrin-releasing peptide (ProGRP) and Prolactin (PRL) have high sensitivity from 77.05% to 96.72% and accuracy from 89.71% to 97.79% as well as their cut off which approved the aim of this study. However, other indicators (CEA, SCCA and CYFRA21-1) have low sensitivity from 62.49 % to 87.31% and accuracy between 71.27 % and 88.43 %. Meanwhile, CT scan has high sensitivity around 83% with specificity about 71%.

Conclusion
Alternative biomarkers (CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4) are considered as prospective markers to differentiate healthy individuals from lung cancer disease by their significant results in early stages detection. Thence, if serum CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4 are measured together, it would be the precise criterion of early levels of lung cancer rather than the lung biopsy definitely. However, further researches are needed to prove more reliable noninvasive markers of lung cancer.
Genomic Analysis Identifies Rare ALK Positive Cases In The TCGA Database
Authors: Patil A R , Dabrowski D S , Cotelingam J , Veillon D , Ong M , Dela Cruz N , Wei E , Tirupathi R , Ganti N , Vanga P , Gundale A 
Published: October 2020

Abstract

Introduction/Objective
The anaplastic lymphoma kinase (ALK) gene is a receptor tyrosine kinase gene located in the 2p23.2 region. Normally, dimerization of ALK receptor by binding to its ligand activates the ALK receptor by autophosphorylation of c-termius and activates downstream PI3K, MAPK and JAK3 pathways. The ALK gene is abnormally hyperactivated by fusion of the 3’ half containing the kinase domain with 5’ portion of other genes, resulting in the ligand independent dimerization and activation of the ALK receptor. The tumors harboring these translocations are termed as ALK-positive tumors and can be treated with ALK inhibitors.

Methods
We analyzed the status of clinically relevant ALK fusion driver mutations in 230 different cancer studies, containing tumors from 79222 different individuals, in The Cancer Genome Atlas database (TCGA) using the cbioportal web browser.

Results
We observed that, as expected ALK-positive mutations are predominantly present in NSCLC, with EML4- ALK being the most common. In addition, we were able to identify ALK positive mutations in colorectal carcinomas, papillary thyroid carcinomas, papillary renal cell carcinomas, sarcomas and invasive ductal carcinomas of the breast. Most important, our analysis identified extremely rare ALK positive cases in salivary duct carcinomas, urothelial carcinomas, cutaneous melanomas and prostatic adenocarcinomas.

Conclusion
Our analysis identified ALK positive cases were predominant in adenocarcinoma of lung with EML4-ALK being the most common ALK positive mutation, which is also consistent with the literature. However, the ALK positive mutations were at a lower prevalence rate than that described in the literature. We attribute the lower prevalence rate to underrepresentation of the Asian population in the TCGA database. In addition, we identified extremely rare ALK positive cases in salivary duct carcinomas, melanomas and prostate cancers, thus highlighting the need for testing for these mutations in these cancers.
Prometastatic CXCR4 and Histone Methyltransferase EZH2 are Upregulated in SMARCB1/INI1-deficient and TP53-mutated Metastatic Poorly Differentiated Chordoma to the Liver
Authors: Murzabdillaeva A , Elzamly S , Brown R , Buryanek J , Jafri S , Rowe J 
Published: October 2020

Abstract

Introduction/Objective
Chordoma is a rare tumor most commonly arising in the sacrococcygeal region from notochord remnants. Usually, these tumors are locally invasive and recurrent, but do not have the capability to metastasize. A newly described aggressive variant called poorly differentiated chordoma is different than conventional chordoma in that it does not have the well-differentiated histologic appearance of conventional chordoma and also exhibits loss of SMARCB1/INI1.

Methods
Herein, we describe a case of poorly differentiated chordoma with SMARCB1/INI1 loss, concurrent TP53 mutation and Rb1 loss.

Results
The patient is a 55-year-old man with a history of a previously resected sacrococcygeal chordoma, who was found to have new hepatic, lung, and adrenal lesions. Biopsy of the liver showed sheets of malignant epithelioid cells with vacuolated cytoplasm, areas of necrosis, and up to 5 mitoses in one high power field. No physaliferous features or matrix material were seen. After an extensive panel of immunohistochemical markers, the origin of the metastatic tumor could not be determined and the tumor was only positive for Cam5.2, EMA, and CD56. Brachyury was performed due to the patient’s previous history and was positive. Genomic testing showed a SMARCB1 mutation, a TP53 mutation, and RB1 loss. Additional markers were performed and the tumor showed a Ki-67 proliferation index of approximately 80%, mutant p53 protein, loss of INI1, and strong expression of prometastatic CXCR4 and the histone methyltransferase EZH2. The most recent follow-up of the patient showed that the patient was receiving palliative care.

Conclusion
Poorly differentiated chordoma is a highly aggressive variant of chordoma with few cases reported. This case of SMARCB1/INI-deficient, poorly differentiated chordoma also showed concurrent TP53 mutation and loss of RB1, which resulted in malignant transformation with loss of differentiation, cell cycle progression, up-regulation of prometastatic CXCR4 and the histone methyltransferase EZH2 causing aggressive behavior and metastasis.
In-Silico Screening: Accurately Predicting Results of the Direct Antiglobulin Test using Commonly Available Lab Data
Authors: Cardillo A , Syposs C , Refaai M 
Published: October 2020

Abstract

Introduction/Objective
The Direct Antiglobulin Test (DAT) is a useful screening test to determine whether a patient’s red blood cells have been sensitized to immunoglobulin or complement. Like the majority of screening tests, the DAT compromises specificity for sensitivity in order to quickly assess for hemolysis and its dangerous sequelae. Because of the high sensitivity of the DAT, improper ordering of this test can confuse the clinical picture at best and result in misdiagnosis at worst. Pre-tests for ruling-out disease have proven effective in limiting test ordering, such as the Pulmonary Embolism Rule-out Criteria (“PERC rule”) for limiting the use of D-dimers. A similar pre-test could prove useful in DATs. We use “in silico testing” – testing via computer simulation – to predict the likelihood of any DAT being positive, given common patient attributes and laboratory values.

Methods
A three-layer deep-learning artificial neural network (ANN) was created using Python and the machine learning framework Keras. The ANN was compiled to maximize specificity while retaining 100% sensitivity. Input variables to the model were patient sex and age, along with most recent lab values for hemoglobin, hematocrit, white blood cell count, platelet count, total bilirubin, direct bilirubin, and haptoglobin, where available. The output of the ANN was a binary variable: “ruled-out” versus “further testing necessary”. The ANN was trained on all positive (n=30) and negative (n=63) DATs performed on November 2019 through March 2020, with a final total of ninety-three patients. A 10-fold cross-validation of the entire dataset was used to measure performance.

Results
The ANN was able to maximize specificity to 83% while retaining 100% sensitivity. A ROC curve of the model shows performance well above that of the no-discrimination line.

Conclusion
“In-silico testing” can accurately screen the likelihood of a positive result for a labor and time-intensive test, such as the DAT, before the actual test is performed. This has the potential to reduce unnecessary testing if validated in clinical practice. Analogous to their clinical counterpart “the PERC rule,” computer models that maximize specificity while retaining 100% sensitivity could achieve more effective test utilization and more informative results.