Batrachochytrium salamandrivorans’ Amphibian Host Species and Invasion Range

Batrachochytrium salamandrivorans (Bsal), a species related to the destructive pathogen Batrachochytrium dendrobatidis (Bd), was found and identified in Europe in 2013. Now, a decade later, a large amount of information is available. This includes data from studies in the field, reports of infection in captive amphibians, laboratory studies testing host susceptibility, and data from prospective studies that test for Bsal’s presence in a location. We conducted a systematic review of the published literature and compiled a dataset of Bsal tests. We identified 67 species that have been reported positive for Bsal, 20 of which have a threatened conservation status. The distribution of species that have been found with infection encompasses 69 countries, highlighting the potential threat that Bsal poses. We point out where surveillance to detect Bsal have taken place and highlight areas that have not been well monitored. The large number of host species belonging to the families Plethodontidae and Salamandridae suggests a taxonomic pattern of susceptibility. Our results provide insight into the risk posed by Bsal and identifies vulnerable species and areas where surveillance is needed to fill existing knowledge gaps

Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

Seven percent of renal cell carcinoma (RCC) cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC) and a tubulocystic renal carcinoma (TCRC) in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR) and distal tubule cell (CK19) markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2) of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3) showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted \u3c5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy

Ultrasensitive immuno-detection using viral nanoparticles with modular assembly using genetically-directed biotinylation

We report a novel, modular approach to immuno-detection based on antibody recognition and PCR read-out that employs antibody-conjugated bacteriophage, easily-manipulated nonpathogenic viruses, as affinity agents. Our platform employs phage genetically tagged for in vivo biotinylation during phage maturation that can easily be linked, through avidin, to any biotinylatable affinity agent, including full-length antibodies, peptides, lectins or aptamers. The presence of analyte is reported with high sensitivity through real-time PCR. This approach avoids the need to clone antibody-encoding DNA fragments, allows the use of full-length, high affinity antibodies and, by having DNA reporters naturally encapsulated inside the bacteriophage, greatly reduces nonspecific binding of DNA. We validate the efficacy of this new approach through the detection of VEGF (Vascular Endothelial Growth Factor), a known angiogenic cancer biomarker protein, at attomolar concentrations in bronchoalveolar lavage (BAL) fluid

Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors

<p>Abstract</p> <p>Background</p> <p>Renal epithelial tumors are morphologically, biologically, and clinically heterogeneous. Different morphologic subtypes require specific management due to markedly different prognosis and response to therapy. Each common subtype has characteristic chromosomal gains and losses, including some with prognostic value. However, copy number information has not been readily accessible for clinical purposes and thus has not been routinely used in the diagnostic evaluation of these tumors. This information can be useful for classification of tumors with complex or challenging morphology. 'Virtual karyotypes' generated using SNP arrays can readily detect characteristic chromosomal lesions in paraffin embedded renal tumors and can be used to correctly categorize the common subtypes with performance characteristics that are amenable for routine clinical use.</p> <p>Methods</p> <p>To investigate the use of virtual karyotypes for diagnostically challenging renal epithelial tumors, we evaluated 25 archived renal neoplasms where sub-classification could not be definitively rendered based on morphology and other ancillary studies. We generated virtual karyotypes with the Affymetrix 10 K 2.0 mapping array platform and identified the presence of genomic lesions across all 22 autosomes.</p> <p>Results</p> <p>In 91% of challenging cases the virtual karyotype unambiguously detected the presence or absence of chromosomal aberrations characteristic of one of the common subtypes of renal epithelial tumors, while immunohistochemistry and fluorescent in situ hybridization had no or limited utility in the diagnosis of these tumors.</p> <p>Conclusion</p> <p>These results show that virtual karyotypes generated by SNP arrays can be used as a practical ancillary study for the classification of renal epithelial tumors with complex or ambiguous morphology.</p

Estructuras de datos y algoritmos eficientes para búsquedas web y procesamiento de grandes datos

Desde hace ya un par de décadas, la cantidad de información, las aplicaciones y el número de usuarios digitales crece exponencialmente, formando un ecosistema en el cual se intenta explotar la masividad de los datos y presentan a la comunidad científico/ tecnológica nuevos desafíos. Por ejemplo, los motores de búsqueda para la web son aplicaciones que procesan miles de millones de documentos para responder consultas de los usuarios. Esto genera nuevas necesidades de almacenamiento, procesamiento y búsquedas, expandiendo los límites del trabajo en una sola máquina y unos pocos algoritmos. Las consultas deben responderse en milisegundos, con resultados relevantes, sobre un escenario altamente heterogéneo. Además, el área de “Big Data”, que se aplica a cúmulos de datos que no pueden ser procesados y/o analizados de forma eficaz y eficiente utilizando técnicas tradicionales, aporta nuevos enfoques que complementan la idea anterior. En este proyecto se estudian, proponen, diseñan y evalúan estructuras de datos y algoritmos para soportar búsquedas de escala web y/o analizar datos masivos de forma eficiente.Eje: Bases de Datos y Minería de Datos.Red de Universidades con Carreras en Informátic

Estructuras de datos y algoritmos eficientes para búsquedas web y procesamiento de grandes datos

Desde hace ya un par de décadas, la cantidad de información, las aplicaciones y el número de usuarios digitales crece exponencialmente, formando un ecosistema en el cual se intenta explotar la masividad de los datos y presentan a la comunidad científico/ tecnológica nuevos desafíos. Por ejemplo, los motores de búsqueda para la web son aplicaciones que procesan miles de millones de documentos para responder consultas de los usuarios. Esto genera nuevas necesidades de almacenamiento, procesamiento y búsquedas, expandiendo los límites del trabajo en una sola máquina y unos pocos algoritmos. Las consultas deben responderse en milisegundos, con resultados relevantes, sobre un escenario altamente heterogéneo. Además, el área de “Big Data”, que se aplica a cúmulos de datos que no pueden ser procesados y/o analizados de forma eficaz y eficiente utilizando técnicas tradicionales, aporta nuevos enfoques que complementan la idea anterior. En este proyecto se estudian, proponen, diseñan y evalúan estructuras de datos y algoritmos para soportar búsquedas de escala web y/o analizar datos masivos de forma eficiente.Eje: Bases de Datos y Minería de Datos.Red de Universidades con Carreras en Informátic

Relevance, Pathogenesis, and Testing Algorithm for Mismatch Repair–Defective Colorectal Carcinomas

Loss-of-function defects in DNA mismatch repair (MMR), which manifest as high levels of microsatellite instability (MSI), occur in approximately 15% of all colorectal carcinomas (CRCs). This molecular subset of CRC characterizes patients with better stage-specific prognoses who experience no benefit from 5-fluorouracil chemotherapy. Most MMR-deficient (dMMR) CRCs are sporadic, but 15% to 20% are due to inherited predisposition (Lynch syndrome). High penetrance of CRCs in germline MMR gene mutation carriers emphasizes the importance of accurate diagnosis of Lynch syndrome carriers. Family-based (Amsterdam), patient/family-based (Bethesda), morphology-based, microsatellite-based, and IHC-based screening criteria do not individually detect all germline mutation carriers. These limitations support the use of multiple concurrent tests and the screening of all patients with newly diagnosed CRC. This approach is resource intensive but would increase detection of inherited and de novo germline mutations to guide family screening. Although CRC prognosis and prediction of 5-fluorouracil response are similar in both the Lynch and sporadic dMMR subgroups, these subgroups differ significantly with regard to the implications for family members. We recommend that new CRCs should be classified into sporadic MMR-proficient, sporadic dMMR, or Lynch dMMR subgroups. The concurrent use of MSI testing, MMR protein IHC, and BRAF c.1799T>A mutation analysis would detect almost all dMMR CRCs, would classify 94% of all new CRCs into these MMR subgroups, and would guide secondary molecular testing of the remainder

Estructuras de datos y algoritmos eficientes para búsquedas web y procesamiento de grandes datos

Desde hace ya un par de décadas, la cantidad de información, las aplicaciones y el número de usuarios digitales crece exponencialmente, formando un ecosistema en el cual se intenta explotar la masividad de los datos y presentan a la comunidad científico/ tecnológica nuevos desafíos. Por ejemplo, los motores de búsqueda para la web son aplicaciones que procesan miles de millones de documentos para responder consultas de los usuarios. Esto genera nuevas necesidades de almacenamiento, procesamiento y búsquedas, expandiendo los límites del trabajo en una sola máquina y unos pocos algoritmos. Las consultas deben responderse en milisegundos, con resultados relevantes, sobre un escenario altamente heterogéneo. Además, el área de “Big Data”, que se aplica a cúmulos de datos que no pueden ser procesados y/o analizados de forma eficaz y eficiente utilizando técnicas tradicionales, aporta nuevos enfoques que complementan la idea anterior. En este proyecto se estudian, proponen, diseñan y evalúan estructuras de datos y algoritmos para soportar búsquedas de escala web y/o analizar datos masivos de forma eficiente.Eje: Bases de Datos y Minería de Datos.Red de Universidades con Carreras en Informátic

Relevance, Pathogenesis, and Testing Algorithm for Mismatch Repair–Defective Colorectal Carcinomas A Report of the Association for Molecular Pathology

Loss-of-function defects in DNA mismatch repair (MMR), which manifest as high levels of microsatellite instability (MSI), occur in approximately 15% of all colorectal carcinomas (CRCs). This molecular subset of CRC characterizes patients with better stage-specific prognoses who experience no benefit from 5-fluorouracil chemotherapy. Most MMR-deficient (dMMR) CRCs are sporadic, but 15% to 20% are due to inherited predisposition (Lynch syndrome). High penetrance of CRCs in germline MMR gene mutation carriers emphasizes the importance of accurate diagnosis of Lynch syndrome carriers. Family-based (Amsterdam), patient/family-based (Bethesda), morphology-based, microsatellite-based, and IHC-based screening criteria do not individually detect all germline mutation carriers. These limitations support the use of multiple concurrent tests and the screening of all patients with newly diagnosed CRC. This approach is resource intensive but would increase detection of inherited and de novo germline mutations to guide family screening. Although CRC prognosis and prediction of 5-fluorouracil response are similar in both the Lynch and sporadic dMMR subgroups, these subgroups differ significantly with regard to the implications for family members. We recommend that new CRCs should be classified into sporadic MMR-proficient, sporadic dMMR, or Lynch dMMR subgroups. The concurrent use of MSI testing, MMR protein IHC, and BRAF c.1799T>A mutation analysis would detect almost all dMMR CRCs, would classify 94% of all new CRCs into these MMR subgroups, and would guide secondary molecular testing of the remainder