Correct Typing Research Articles

First branchial cleft anomalies in children: long-term outcome in 16 patients.

First branchial cleft anomalies (FBCA) are rare congenital head and neck malformations, often subject to incorrect diagnosis and treatment. We present our experience with FBCA, focusing on clinical presentation, diagnosis, perioperative relation to the facial nerve, surgical approach, complications and patient satisfaction. A consecutive cohort of 16 patients undergoing surgical treatment for FBCA between 1999 and 2021 was analyzed. Demographic and clinical information was extracted from their medical records. Additionally 14 patients were interviewed by telephone to assess postoperative outcomes and patient satisfaction using a Likert scale. Sixteen patients (11 females, 5 males) were surgically treated at an age ranging from 7months to 13years. Type I and type II FBCA were evenly distributed. Lesions presented as cysts (n = 4), sinuses (n = 7) or fistulas (n = 5). The main symptoms were swelling, inflammation and discharge. Otologic symptoms were present in 31%. In 80% of patients, magnetic resonance imaging was needed to reach the correct diagnosis. Ten patients (63%) had a history of a surgical attempt in another center before definitive surgical treatment in our center. Complete excision was accomplished in all patients. Postoperative complications included limited Frey syndrome (n = 4), temporary hypertrophic scarring (n = 4), minimal paresis of the marginal mandibular branch of the facial nerve (n = 1) and limited external auditory canal stenosis (n = 1). One patient experienced a recurrence at the level of the external auditory canal, that required minor revision surgery. The average patient satisfaction score was 13.64 out of 15. Thorough clinical examination, awareness of the different entities and awareness of expert head and neck radiological advice are crucial for correct FBCA diagnosis and typing, determining the correct surgical approach. It is crucial that patients diagnosed with FBCA undergo surgery in specialized centers. Despite the challenging surgery and its potential complications, the overall patient satisfaction remains high post- treatment.

An Inexpensive and Quick Method for Genotyping of HLA Variants Included in the Spanish Pharmacogenomic Portfolio of National Health System

The possibility of using the same genotyping technology (TaqMan) for all the genetic tests included in the new Spanish pharmacogenomics portfolio should enable the application of a multigenotyping platform to obtain a whole pharmacogenomics profile. However, HLA-typing is usually performed with other technologies and needs to be adapted to TaqMan assays. Our aim was to establish a set of TaqMan assays for correct typing of HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01. Therefore, we searched for and selected SNVs described in different populations as surrogate markers for these HLA alleles, designed TaqMan assays, and tested in a set of samples with known HLA-A and HLA-B. HLA-A*31:01 was correctly typed with a combination of rs1061235 and rs17179220 (PPV 100%, 95% CI 84.6–100-%; NPV 100%, 95% CI 96.5–100.0%), HLA-B*15:02 with rs10484555 (PPV 100%, 95% CI 69.2–100.0%; NPV 100%, 95% CI 96.8–100.0%) and rs144012689 (PPV 100%, 95% CI 69.2–100.0%; NPV 100%, 95% CI 96.8–100.0%), and HLA-B*57:01 with rs2395029 (PPV 99.5%, 95% CI 72.9–99.3%; NPV 99.5%, 95% CI 98.3–100.0%). HLA-B*58:01 was typed using two allele-specific TaqMan probes mixed with a ß-Globin reference and treated as a genotyping assay (PPV 100.0%, 95% CI 81.5–100.0%; NPV 100%, 95% CI 96.8–100.0%). In conclusion, we demonstrated a clinically useful way to type HLA-A and HLA-B alleles included in the Spanish pharmacogenomics portfolio using TaqMan assays.

Generate fuzzy string-matching to build self attention on Indonesian medical-chatbot

Chatbot is a form of interactive conversation that requires quick and precise answers. The process of identifying answers to users’ questions involves string matching and handling incorrect spelling. Therefore, a system that can independently predict and correct letters is highly necessary. The approach used to address this issue is to enhance the fuzzy string-matching method by incorporating several features for self-attention. The combination of fuzzy string-matching methods employed includes Jaro Winkler distance + Levenshtein Damerau distance and Damerau Levenshtein + Rabin Carp. The reason for using this combination is their ability not only to match strings but also to correct word typing errors. This research contributes by developing a self-attention mechanism through a modified fuzzy string-matching model with enhanced word feature structures. The goal is to utilize this self-attention mechanism in constructing the Indonesian medical bidirectional encoder representations from transformers (IM-BERT). This will serve as a foundation for additional features to provide accurate answers in the Indonesian medical question and answer system, achieving an exact match of 85.7% and an F1-score of 87.6%.

Procedural Motor Memory Deficits in Patients With Long-COVID.

At least 15% of patients who recover from acute severe acute respiratory syndrome coronavirus 2 infection experience lasting symptoms ("Long-COVID") including "brain fog" and deficits in declarative memory. It is not known if Long-COVID affects patients' ability to form and retain procedural motor skill memories. The objective was to determine the ability of patients with Long-COVID to acquire and consolidate a new procedural motor skill over 2 training days. The primary outcome was to determine difference in early learning, measured as the increase in correct sequence typing speed over the initial 11 practice trials of a new skill. The secondary outcomes were initial and final typing speed on days 1 and 2, learning rate, overnight consolidation, and typing accuracy. In this prospective, cross-sectional, online, case-control study, participants learned a sequential motor skill over 2 consecutive days (NCT05746624). Patients with Long-COVID (reporting persistent post-coronavirus disease 2019 [COVID-19] symptoms for more than 4 weeks) were recruited at the NIH. Patients were matched one-to-one by age and sex to controls recruited during the pandemic using a crowd-sourcing platform. Selection criteria included age 18-90 years, English speaking, right-handed, able to type with the left hand, denied active fever or respiratory infection, and no previous task exposure. Data were also compared with an age-matched and sex-matched control group who performed the task online before the COVID-19 pandemic (prepandemic controls). In total, 105 of 236 patients contacted agreed to participate and completed the experiment (mean ± SD age 46 ± 12.8 years, 82% female). Both healthy control groups had 105 participants (mean age 46 ± 13.1 and 46 ± 11.9 years, 82% female). Early learning was comparable across groups (Long-COVID: 0.36 ± 0.24 correct sequences/second, pandemic controls: 0.36 ± 0.53 prepandemic controls: 0.38 ± 0.57, patients vs pandemic controls [CI -0.068 to 0.067], vs prepandemic controls [CI -0.084 to 0.052], and between controls [CI -0.083 to 0.053], p = 0.82). Initial and final typing speeds on days 1 and 2 were slower in patients than controls. Patients with Long-COVID showed a significantly reduced overnight consolidation and a nonsignificant trend to reduced learning rates. Early learning was comparable in patients with Long-COVID and controls. Anomalous initial performance is consistent with executive dysfunction. Reduction in overnight consolidation may relate to deficits in procedural memory formation.

Detection of Weak “B” Phenotype While Resolving an ABO Discrepancy

Quantitative and/or qualitative differences in ABO phenotypes give rise to ABO discrepancies causing difficulties in establishing the accurate phenotype. These discrepant serological reactions result in significant delays in blood bank. The correct typing of the blood group is imperative to prevent ABO incompatibility issues. However, the discrepant results encountered in routine settings are a challenge to immunohematologists. The variants of the ABO occur very rarely particularly true for B subgroups. Here, we present a case study of a healthy blood donor, discrepant results in forward and reverse blood grouping led us to perform adsorption-elution test. The presence of anti-B in the eluate confirmed the presence of weaker variant of B antigen on the surface of red blood cells. Correct identification of blood group is mutually important for donor and recipient to prevent the occurrence of any transfusion reaction. The serologically determined weak B phenotypes, however, require further confirmation through genomic analysis.

PB2155: B-CELL NON-HODGKIN’S LYMPHOMAS ASSOCIATED WITH AMYLOIDOSIS

Background: Different types of B-NHLs (MZL, LPL, B-CLL/SLL, FL, MCL, DLBCL) may show plasmacytic differentiation and may produce AL amyloid locally or as a part of systemic amyloidosis. Case reports of coincidence of B-NHL and non-AL amyloidosis were also reported, therefore correct diagnostic workflow to type amyloid deposits should include three main steps 1. special histological staining (Congo red and/or Saturn red), 2. immunoprofiling and proteomic analysis (LMD-LC/MS). Nomenclature classification distinguishes 36 amyloidogenic proteins and more are expected (ISA 2020). Aims: Analysis of amyloid deposits irrespective of origin and localization is appealing for diagnostic and experimental precising which brings new insights in pathogenesis, classification and correct therapy due to a possibility of combination or hybrid amyloid deposits, and concurrent B-NHL may be detected. Methods: Amyloid deposits were detected in variable FFPE tissues stained with Congo red and/or Saturn red with consequent immunohistochemical analysis (IHC) and proteomic analysis with the use of laser capture microdissection and liquid chromatography/tandem mass spectrometry (LMD-LC/MS/MS). Concurent B-NHLs (excl. multiple myeloma, plasmocytoma and MGUS) were diagnosed due to characteristic morphology (HE, PAS, Giemsa), immunoprofile (primary antibodies with appropriate dilution - CD3, CD5, CD10, CD20, CD21, CD23, CD30, CD138, Bcl-2, Bcl-6, MUM1/IRF4, PAX5, cyclin D1 and/or SOX11, c-Myc, Ki67) and detected clonal rearrangement of IgVH (BIOMED-2). Results: In our file with 329 amyloid positive specimens concurent B-NHLs were found in 14 specimens. 7 specimens were signed as highly suspected for B-NHL with plasmacytic differentiation and immunoglobulin light chain restriction but without evidence of IgVH clonal rearrangement. The most common B-NHL associated with localised amyloidosis was ENMZL MALT-type (10 cases, 1 case with hybrid amyloidosis AL kappa/AH IgG1), in 4 specimens LPL was detected. In all cases with IHC and/or LCM-LC/tandem MS analysis AL type of amyloid was detected including 2 cases with hybrid amyloidosis AL/AH and AL/AApoAIV, and in 1 case local AL amyloid deposition was produced after a therapy for B-NHL. Summary/Conclusion: M-protein produced by B-NHL may be low or high according to a localised or systemic AL involvement resp., localised amyloid deposition is commonly associated with ENMZL MALT-type, both localised and systemic amyloidosis may be found out in LPL. Our category of highly suspected B-NHL with plasmacytic differentiation is literary sign as “AL amyloidosis with a localized B-cell neoplasia of undetermined significance” or as “AL amyloidosis with a an associated predominant kappa or lambda light chain expressing plasma cell population without evidence for clonality”. In our file (7 cases) only kappa/lambda immunohistochemically detected monotypy was recorded without an evidence of IgVH clonal rearrangement (somatic hypermutation of IgVH may be expected). The possibility of senescence evolution in B-NHL after a therapy may also bring local AL deposits (1 case in our cohort). Coincidence or association of non-AL amyloidosis (ATTRwt, ATTRv, AA and other) with B-NHL was described mainly in single case reports and extends the differential diagnosis. In a such cases both methods (IHC and LCM-LC/tandem MS) are suitable for correct amyloid typing, although LMD-LC/tandem MS brought more promising results than IHC.

Defects and countermeasures in laboratory diagnosis of rare IgE multiple myeloma

BackgroundIgE multiple myeloma (MM) is a rare subtype of MM that is easily misdiagnosed. We report a rare case of IgE-MM and investigate the application of the SLiM-CRAB criteria to screen for high-risk smoldering MM (SMM) patients, so as to summarize the causes and methods used to prevent missed diagnosis or misdiagnosis in IgE-MM. MethodsThe serum monoclonal protein (M-protein) classification and IgE quantification was performed and sent to several individual institutions. The results were collected and the causes of IgE detection defects were analyzed. ResultsUpon admission to our hospital, the patient’s serum free kappa light chain was 1069.9 mg/L, free lambda light chain was 9.2 mg/L, and free kappa/lambda ratio was 115.9, which met the SLiM criteria, but without CRAB features. Immunofixation electrophoresis (IF) showed “M-like protein aggregation bands” in all lanes. After pretreatment with 1% β-mercaptoethanol to depolymerize the aggregation of monoclonal protein, the “M-like protein aggregation bands disappeared. The other five institutions did not provide the correct typing results. The quantification of serum IgE was as high as 2.06 × 107 IU/mL, whereas 7 other testing institutions reported IgE levels ranging from 1.0 to 1100 IU/mL. ConclusionHigh-risk biomarkers in SLiM criteria can achieve good therapeutic effects in rare IgE-MM patients. Serum immunofixation performed without antisera against IgE, insufficient identification of the lytic bands produced by high macromolecule aggregation in IF, and the absence of a prozone effect avoidance procedure during IgE quantitative detection are the primary causes of missed diagnosis or misdiagnosis in patients with IgE-MM.

Recommendations for immunocytochemistry in lung cancer typing: An update on a resource-efficient approach with large-scale comparative Bayesian analysis.

The majority of lung cancer cases are of advanced stage and diagnosis is usually made using minimally invasive small biopsies and cytological specimens. The WHO 2015classification recommends limiting immunocytochemistry (ICC) to lung cancer typing and molecular testing drives for personalised therapies. An algorithm using Bayes' theorem could be useful for defining antibody profiles. This study aims to assess the impact of different antibody profiles for cytological samples on the accuracy of lung cancer typing with a large-scale Bayesian analysis. A retrospective examination of 3419 consecutive smears and/or cytospins diagnosed over 2011-2016 found 1960 primary lung cancer tumours: 972 adenocarcinomas (ADC), 256squamous carcinomas (SQC), 268 neuroendocrine tumours (NET), and 464 non-small cell cancer-not otherwise specified (NSCC-NOS). The a priori and a posteriori probabilities, before and after ICC using antibodies singly or in combination, were calculated for different lung cancer types. TTF-1 or CK7 alone improved the a posteriori probabilities of correct cytological typing for ADC to 86.5% and 95.8%, respectively. For SQC, using p40 (∆Np63) or CK5/6 together with CK5/14led to comparable results (78.3% and 90.3%). With synaptophysin or CD56 alone, improvements in a posteriori probabilities to 87.5 and 90.3% for the correct recognition of NET could be achieved. Based on morphological and clinical data, the use of two antibodies appears sufficient for reliable detection of the different lung cancer types. This applies to diagnoses that were finalised following ICC both on a clinical or cytological basis and on a histological basis.

Histologie und Molekularpathologie von Speicheldrüsentumoren

BackgroundSalivary gland tumors are rare but display great morphological heterogeneity with more than 30 entities. Recently, the different tumors have not only been better characterized using conventional histochemical and immunohistochemical methods, but also by molecular means. Hence, so-called driver mutations which play a role in the development of novel molecularly targeted therapies could be identified.ObjectiveThe article aims to show morphological criteria and immunohistochemical characteristics of different tumor entities. Additionally, an overview of tumor-specific genetic aberrations of the most common salivary gland tumors is given.Materials and methodsSamples from daily routine practice are presented with histochemical and immunohistochemical staining. To compile recent molecular findings in salivary gland tumors, a literature review was performed.Results and conclusionFor histopathological diagnosis of differentiated salivary gland tumors, immunohistochemical staining of basal/myoepithelial and luminal/epithelial cells is essential to assess cellular architecture and attribute proliferative activity. Based on correct tumor typing, various molecular parameters can be investigated in order to verify the diagnosis of highly differentiated nonmetastatic tumors. In the case of less differentiated, metastatic cancers, molecular pathology permits identification of potential therapeutic targets. Comprehensive genome profiling should nowadays be applied to highly aggressive salivary gland cancers.

Synthesizing and analyzing long-term monitoring data: A greater sage-grouse case study

Long-term monitoring of natural resources is imperative for increasing the understanding of ecosystem processes, services, and how to manage those ecosystems to maintain or improve function. Challenges with using these data may occur because methods of monitoring changed over time, multiple organizations collect and manage data differently, and monetary resources fluctuate, affecting many aspects of data. Because many species respond to changes in habitat conditions and predator-prey relationships across different spatial scales that span management boundaries, greater efforts for collaborating are essential. We demonstrate the challenges and methods for standardizing greater sage-grouse (Centrocercus urophasianus) long-term monitoring data across the species range in the western United States to inform population modeling needs identified by the Western Association of Fish and Wildlife Agencies. We used automated and repeatable methods of standardizing data via custom open-source software (grsg_lekdb) to improve the scientific integrity of future sage-grouse population assessments within and among states. Data standardization included reconciling uses of different terminology and expunging unusable data, resulting in the removal of 26% of data records due to database insertion errors and modifications to >1 million values to correct formatting and typing errors. Our approaches maximized the inclusion of usable data and identified data that could inform detection probabilities, population trends, and monitoring guidelines. Using sage-grouse databases as an example, we identified the importance of data management and how quality assurance and quality control measures can improve the usefulness of these data for future research needs. Our methods of using informatics and concluding recommendations can support similar endeavors of flora and fauna monitoring programs, whether those efforts are to use existing data or support new monitoring programs.

The Clinical Impact of Proteomics in Amyloid Typing

The Clinical Impact of Proteomics in Amyloid Typing

Lytic lesions of bone: a cytological and histopathological correlative study

Background: Lytic lesions of bone are easier to aspirate and fine needle aspiration cytology aids in an earlier diagnosis. The findings are correlated with radiological findings and subsequent histopathological diagnosis. Sensitivity, specificity, positive and negative predictive value of fine needle aspiration cytology of lytic lesions of bone evaluated.Methods: It was a descriptive study for 2 years. All types of lytic lesions of bone were aspirated with fine needle along with radiological assistance. The cytological diagnosis was correlated with histo pathological diagnosis.Results: A total number of 84 cases were studied with histopathological follow up in 51 cases. FNAC diagnosis was correct in 34 cases. In 8 cases, cytology diagnosis was malignant neoplasm, but correct typing was not possible. In 9 cases cytological diagnosis were inconclusive due to inadequate material. Sensitivity of the test was 70.83%, specificity was 50.12%, positive predictive value was 97.14%, negative predictive value was 6.67% and overall accuracy was 70 .01%.Conclusions: The role of FNAC in diagnosis of bone lesions is both promising and challenging. Because of simplicity, low morbidity and economical benefits, FNAC should be the first step in the diagnosis of bone lesions.

PENGGUNAAN SPELLING CORRECTION DENGAN METODE PETER NORVIG DAN N-GRAM

Typing errors in a document are human errors that are difficult to avoid as a result of which the message to be conveyed is not optimal. Using the Spelling Corrector feature is one way to check typing errors. The Spelling Corrector feature is able to provide only one word suggestion and correct it immediately. The combination of Peter Norvig and Ngram's methods was able to come up with one word suggestion and correct it right away. Both methods of looking for word suggestions use the probability value of the words that appear most frequently in the dictionary. The difference between the two methods is that Peter Norvig uses an algorithm that combines the delete, insert, replace, and transpose processes for the wrong word. Meanwhile, Ngram uses an algorithm that pays attention to the words before and after them based on the sentences in the dictionary. The dictionary used is a dictionary of word lists from KBBI and also a dictionary of sentences taken from several articles on the internet. This combination of methods was tested using 55 documents containing sentences that had one misspelled word. The test results show that the combination of the two methods provides an accuracy rate of 73,684% and a success rate of 37,037% for the total accuracy of this application is 69.09%. These two methods can be used to correct typing errors, although they cannot correct words with an error rate of two or more letters. This is because Peter Norvig was unable to correct a word with a two-letter error rate and needed a good corpus.

A 20-Year Retrospective Analysis of Skin Cancers: Comparison of the First and Second Decades

Objective: The incidence of skin cancer increases day by day depending on environmental factors. Developing diagnostic and pathological methods provide correct typing of skin cancers. Method: This retrospective analysis included patients who presented to and were scheduled for treatment at Sivas Cumhuriyet University Plastic Reconstructive and Aesthetic Surgery Clinic between January 1, 2000 and December 31, 2019 due to skin cancer and carcinoma in situ. The results were divided two groups as first ten years and second ten years. The groups were compared among themself in terms of cancer type, age, gender and localization Results: 619 cases' 652 skin cancer and in situ carcinoma results were detected. When the groups were compared in terms of tumor types detected, there was a significant increase in MM, Bowen's disease, and rare NMSC subtypes other than SCC and BCC in the second decade (p<0.001). Comparison of NMSC and MSC rates between the groups showed that the incidence of MSC had increased significantly from 5.2% to 10% in the past 10 years (p<0,05) Conclusion: Rare Non-melanocytic skin cancer group includes many types of carcinoma, there are various treatment protocols. Furthermore, many members of this group are known to be more aggressive than Basal cell carcinoma and squamous cell carcinoma. There are no consesnsus especially for approaches targeting lymph nodes. Closely following is necessary for early detection of recurrences and metastases.

Imaging Mass Spectrometry Is an Accurate Tool in Differentiating Clear Cell Renal Cell Carcinoma and Chromophobe Renal Cell Carcinoma: A Proof-of-concept Study.

Clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC) are relatively common tumors that can have significant risk for mortality. Treatment and prognostication in renal cell carcinoma (RCC) are dependent upon correct histologic typing. ccRCC and chRCC are generally straightforward to diagnose based on histomorphology alone. However, high-grade ccRCC and chRCC can sometimes resemble each other morphologically, particularly in small biopsies. Multiple immunostains and/or colloidal iron stain are sometimes required to differentiate the two. Imaging mass spectrometry (IMS) allows simultaneous spatial mapping of thousands of biomarkers, using formalin-fixed paraffin-embedded tissue sections. In this study, we evaluate the ability of IMS to differentiate between World Health Organization/International Society for Urological Pathology grade 3 ccRCC and chRCC. IMS spectra from a training set of 14 ccRCC and 13 chRCC were evaluated via support vector machine algorithm with a linear kernel for machine learning, building a classification model. The classification model was applied to a separate validation set of 6 ccRCC and 6 chRCC, with 19 to 20, 150-μm diameter tumor foci in each case sampled by IMS. Most evaluated tumor foci were classified correctly as ccRCC versus chRCC (99% accuracy, kappa=0.98), demonstrating that IMS is an accurate tool in differentiating high-grade ccRCC and chRCC.

Use of non-invasive ventilation in acute respiratory failure due to SARS-CoV-2 pneumonia: typing of patients and choice of respiratory support, the role of internal medicine

The use of non-invasive ventilation (NIV) during de novo acute hypoxemic respiratory failure is not recommended by the guidelines because NIV does not improve the prognosis. With the advent of the new coronavirus, many cases of acute hypoxemic respiratory failure associated with the infection (severe acute respiratory infection) have been observed: data are missing regarding the use of NIV in this particular clinical condition, but a correct typing of patients based on different clinical, pathophysiological and radiological characteristics, could help in prognostic stratification and in the choice of respiratory support (invasive versus non-invasive). During NIV in these patients particular attention is paid to the possibility of environmental dissemination of the virus and consequently adequate technical precautions are taken.

A potential application of height-dependent cloud emission and scattering indices for identifying CrIS clear channels above clouds

Satellite data assimilation of hyperspectral Cross-track Infrared Sounder (CrIS) clear channels in regions with but not affected by low-level clouds requires a set of height-dependent cloud emission and scattering indices (CESIs) that are sensitive to cloud top pressures. In this study, three CESIs are generated by pairing CrIS longwave and shortwave channels at three altitudes around 212 (CESI-5), 452 (CESI-9) and 1085 hPa (CESI-19). The training dataset for CESIs is the European Centre for Medium-Range Weather Forecasting analysis. CESI-5 is strongly (weakly) affected by those ice clouds with cloud-top pressures (CTPs) above (below) ∼300 hPa; CESI-9 is strongly (weakly) affected by those ice clouds with CTPs above (below) ∼600 hPa; and CESI-19 is highly correlated with the ice cloud optical depth (ICOD) obtained from the Atmospheric Infrared Sounder (AIRS) retrieval product. CESIs have latitudinal and scan-dependent biases that need removal. Verified with AIRS ICOD data, CESI-19 is greater than 5 K (6.5 K) if an ice cloud is present. This 5-K threshold gives a probability of correct typing of 85.3% (86.5%), a false alarm rate of 9.5% (5.1%) and a leakage rate of 4.5% (5.0%) during the daytime (nighttime). CESI-5 (CESI-9) is greater than −3 K (−1 K) if an ice cloud is present above 200 hPa (between 200 and 300 hPa). The case of Typhoon Maria (2018) demonstrates the potential of using height-dependent CESIs to identify above-cloud CrIS clear channels.

Approach to the Diagnosis of Amyloidosis.

Amyloidosis is heterogeneous group of disorder characterized by extracellular deposition of misfolded insoluble proteinaceous material with cross beta pleated sheet structure leading to organ dysfunction. This disease is rare and indeed heterogeneous, as it may be hereditary (familial amyloidosis), secondary to spectrum of inflammatory conditions (AA amyloidosis) or member of plasma cell neoplasm family (AL amyloidosis). AL amyloidosis is the most common type of amyloid, however, is rarely accompanied by multiple myeloma or other lymphoproliferative disorder. This disparity in its origin and presentation needs to be addressed by exhaustive battery of investigation tools, to arrive at right diagnosis with correct typing. This is of utmost importance in guiding the treating physicians to choose appropriate therapeutic options. This review deals with diagnostic approach to amyloidosis and its various subtypes.

Automated Reuse of Model Transformations through Typing Requirements Models

Model transformations are key elements of model-driven engineering, where they are used to automate the manipulation of models. However, they are typed with respect to concrete source and target meta-models, making their reuse for other (even similar) meta-models challenging. To improve this situation, we propose capturing the typing requirements for reusing a transformation with other meta-models by the notion of a typing requirements model (TRM). A TRM describes the prerequisites that a model transformation imposes on the source and target meta-models to obtain a correct typing. The key observation is that any meta-model pair that satisfies the TRM is a valid reuse context for the transformation at hand. A TRM is made of two domain requirement models (DRMs) describing the requirements for the source and target meta-models, and a compatibility model expressing dependencies between them. We define a notion of refinement between DRMs and see meta-models as a special case of DRM. We provide a catalogue of valid refinements and describe how to automatically extract a TRM from an ATL transformation. The approach is supported by our tool TOTEM. We report on two experiments—based on transformations developed by third parties and meta-model mutation techniques—validating the correctness and completeness of our TRM extraction procedure and confirming the power of TRMs to encode variability and support flexible reuse.

Highly sensitive parechovirus CODEHOP PCR amplification of the complete VP1 gene for typing directly from clinical specimens and correct typing based on phylogenetic clustering.

Human parechoviruses (HPeVs), particularly type 3, can cause severe neurological disease and neonatal sepsis in infants. HPeV3 lacks the receptor-binding motif arginine-glycine aspartic acid (RGD), and is proposed to use a different receptor associated with severe disease. In contrast, HPeV1, which contains the RGD motif, is associated with mild disease. Rapid characterization of the presence/absence of this motif is essential for understanding their epidemiology and differential disease profiles. Current HPeV typing assays are based on partial capsid genes and often do not encompass the C-terminus where the RGD region is localized/absent. In addition, these assays lack sensitivity to enable characterization within low viral-load samples, such as cerebral spinal fluid. We developed a highly sensitive HPeV CODEHOP PCR, which enables typing of parechoviruses directly from clinical samples while generating a complete VP1 gene, including the C-terminus. The assay was HPeV-specific and has a sensitivity of 6.3 TCID50 ml-1 for HPeV1 and 0.63 TCID50 ml-1 for HPeV3. Analysis of the complete VP1 gene in comparison to partial VP1 fragments generated by previously published PCRs showed homologous clustering for most types. However, phylogenetic analysis of partial VP1 fragments showed incongruent typing based on the 75 % homology classification rule. In particular, the strains designated as type 17 were found to be either type 3 or 4 when using the (near-) complete VP1 fragment. While enabling sensitive characterization of HPeVs directly from clinical samples, the HPeV CODEHOP PCR enables the characterization of RGD and non-RGD strains and correct HPeV typing based on the complete VP1.