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https://www.readbyqxmd.com/read/28422816/why-not-wait-eight-institutions-share-their-experiences-moving-united-states-medical-licensing-examination-step-1-after-core-clinical-clerkships
#1
Michelle Daniel, Amy Fleming, Colleen O'Conner Grochowski, Vicky Harnik, Sibel Klimstra, Gail Morrison, Arnyce Pock, Michael L Schwartz, Sally Santen
The majority of medical students complete the United States Medical Licensing Examination Step 1 after their foundational sciences; however, there are compelling reasons to examine this practice. This article provides the perspectives of eight MD-granting medical schools that have moved Step 1 after the core clerkships, describing their rationale, logistics of the change, outcomes, and lessons learned. The primary reasons these institutions cite for moving Step 1 after clerkships are to foster more enduring and integrated basic science learning connected to clinical care and to better prepare students for the increasingly clinical focus of Step 1...
April 18, 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28415794/micrornas-of-the-mir-17-92-cluster-regulate-multiple-aspects-of-pancreatic-tumor-development-and-progression
#2
Brian Quattrochi, Anushree Gulvady, David R Driscoll, Makoto Sano, David S Klimstra, Christopher E Turner, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398253/t-cell-mediated-immunity-towards-yellow-fever-virus-and-useful-animal-models
#3
REVIEW
Alan M Watson, William B Klimstra
The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus...
April 11, 2017: Viruses
https://www.readbyqxmd.com/read/28288385/alphaviruses-suppress-host-immunity-by-preventing-myeloid-cell-replication-and-antagonizing-innate-immune-responses
#4
REVIEW
Derek W Trobaugh, William B Klimstra
Alphaviruses are medically important mosquito-borne viruses that cause a range of diseases in humans from febrile illness to arthritis or encephalitis. The innate immune response functions to suppress virus replication through upregulation of antiviral molecules and contributes to development of the adaptive immune response. Myeloid cells act as master regulators of virus infection by initiating both the innate and adaptive immune responses. Alphaviruses are capable of antagonizing individual components of these responses to increase replicative fitness in vivo...
March 10, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28184012/chromosome-20q-amplification-defines-a-subtype-of-microsatellite-stable-left-sided-colon-cancers-with-wild-type-ras-raf-and-better-overall-survival
#5
Ryan N Ptashkin, Carlos Pagan, Rona Yaeger, Sumit Middha, Jinru Shia, Kevin P O'Rourke, Michael F Berger, Lu Wang, Robert Cimera, Jiajing Wang, David S Klimstra, Leonard Saltz, Marc Ladanyi, Ahmet Zehir, Jaclyn F Hechtman
Here comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma (CRC) harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced CRC underwent next generation sequencing (NGS) via MSK-IMPACT and a subset of case samples were subjected to high resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) CRC data. Of the CRC patients sequenced (n=401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28094897/cytology-assessment-can-predict-survival-for-patients-with-metastatic-pancreatic-neuroendocrine-neoplasms
#6
Carlie S Sigel, Huimin Guo, Keith M Sigel, Ming Zhang, Natasha Rekhtman, Oscar Lin, David S Klimstra, Achim A Jungbluth, Laura K Tang
BACKGROUND: Histological features and Ki-67 index have known usefulness in predicting prognosis and guiding therapy among patients with metastatic pancreatic neuroendocrine neoplasms. Fine-needle aspiration may offer advantages for Ki-67 assessment because the technique obtains highly cellular, well-preserved specimens with the potential for broader tumor sampling. In the current study, the authors evaluated concordance for grade and differentiation between concurrent core needle biopsy and cytology preparations...
March 2017: Cancer
https://www.readbyqxmd.com/read/28044242/on-the-development-of-harmony-turbulence-and-independence-in-parent-adolescent-relationships-a-five-wave-longitudinal-study
#7
Hana Hadiwijaya, Theo A Klimstra, Jeroen K Vermunt, Susan J T Branje, Wim H J Meeus
The separation-individuation, evolutionary, maturational, and expectancy violation-realignment perspectives propose that the relationship between parents and adolescents deteriorate as adolescents become independent. This study examines the extent to which the development of adolescents' perceived relationship with their parents is consistent with the four perspectives. A latent transition analysis was performed in a two-cohort five-wave longitudinal study design covering ages 12-16 (n = 919, 49.2% female) and 16-20 (n = 392, 56...
January 2, 2017: Journal of Youth and Adolescence
https://www.readbyqxmd.com/read/28034727/diagnosing-colorectal-medullary-carcinoma-interobserver-variability-and-clinicopathological-implications
#8
Lik Hang Lee, Rhonda K Yantiss, Eran Sadot, Bing Ren, Marcela Santos Calvacanti, Jaclyn F Hechtman, Sinisa Ivelja, Be Huynh, Yue Xue, Tatiana Shitilbans, Hamza Guend, Zsofia K Stadler, Martin R Weiser, Efsevia Vakiani, Mithat Gönen, David S Klimstra, Jinru Shia
Colorectal medullary carcinoma, recognized by the World Health Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved prognosis and unique molecular pathogenesis. A fundamental but as yet unaddressed question, however, is whether it can be diagnosed reproducibly. In this study, by analyzing 80 colorectal adenocarcinomas whose dominant growth pattern was solid (thus encompassing medullary carcinoma and its mimics), we provided a detailed description of the morphological spectrum from "classic medullary histology" to nonmedullary poorly differentiated histologies and demonstrated significant overlapping between categories...
April 2017: Human Pathology
https://www.readbyqxmd.com/read/27989642/microrna-regulation-of-rna-virus-replication-and-pathogenesis
#9
REVIEW
Derek W Trobaugh, William B Klimstra
microRNAs (miRNAs) are non-coding RNAs that regulate many processes within a cell by manipulating protein levels through direct binding to mRNA and influencing translation efficiency, or mRNA abundance. Recent evidence demonstrates that miRNAs can also affect RNA virus replication and pathogenesis through direct binding to the RNA virus genome or through virus-mediated changes in the host transcriptome. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27984235/intraductal-tubulopapillary-neoplasm-of-the-pancreas-a-clinicopathologic-and-immunohistochemical-analysis-of-33-cases
#10
Olca Basturk, Volkan Adsay, Gokce Askan, Deepti Dhall, Giuseppe Zamboni, Michio Shimizu, Karina Cymes, Fatima Carneiro, Serdar Balci, Carlie Sigel, Michelle D Reid, Irene Esposito, Helena Baldaia, Peter Allen, Günter Klöppel, David S Klimstra
Intraductal tubulopapillary neoplasm (ITPN) is a relatively recently described member of the pancreatic intraductal neoplasm family. Thus, the literature on its histologic and immunohistochemical features, clinical behavior, and its similarities and differences from other pancreatic neoplasms is limited. Thirty-three cases of ITPN, the largest series to date, were identified. Immunohistochemical labeling for cytokeratins, glycoproteins, pancreatic enzymes, markers for intestinal and neuroendocrine differentiation, and antibodies associated with genetic alterations previously described in pancreatic neoplasms was performed...
March 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27982025/morphological-characterization-of-colorectal-cancers-in-the-cancer-genome-atlas-reveals-distinct-morphology-molecular-associations-clinical-and-biological-implications
#11
Jinru Shia, Nikolaus Schultz, Deborah Kuk, Efsevia Vakiani, Sumit Middha, Neil H Segal, Jaclyn F Hechtman, Michael F Berger, Zsofia K Stadler, Martin R Weiser, Jedd D Wolchok, C Richard Boland, Mithat Gönen, David S Klimstra
The Cancer Genome Atlas data on colorectal carcinoma have provided a comprehensive view of the tumor's genomic alterations and their tumorigenic roles. Tumor morphology, however, has not been fully integrated into the analysis. The aim of this study was to explore relevant associations between tumor morphology and the newly characterized genomic alterations in colorectal carcinoma. Two hundred and seven colorectal carcinomas that had undergone whole-exome sequencing as part of The Cancer Genome Atlas project and had adequate virtual images in the cBioPortal for Cancer Genomics constituted our study population...
April 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27889647/activation-of-wnt-%C3%AE-catenin-signaling-enhances-pancreatic-cancer-development-and-the-malignant-potential-via-up-regulation-of-cyr61
#12
Makoto Sano, David R Driscoll, Wilfredo E DeJesus-Monge, Brian Quattrochi, Victoria A Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S Klimstra, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras(G12D), Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin(S37A) and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development...
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27829276/biliary-carcinomas-pathology-and-the-role-of-dna-mismatch-repair-deficiency
#13
REVIEW
Vitor Werneck Krauss Silva, Gokce Askan, Tanisha D Daniel, Maeve Lowery, David S Klimstra, Ghassan K Abou-Alfa, Jinru Shia
The pathology of biliary carcinomas is diverse with different gross and histological features in tumors arising in the different segments of the biliary system. Various epidemiological risk factors, varied genetic makeup, and tissue microenvironment are contributory factors. As biliary tumors have been shown to be a part of the Lynch syndrome tumor spectrum, it is plausible to speculate that DNA mismatch repair (MMR) deficiency plays a role in biliary tumors. Literature data suggest that DNA MMR deficiency indeed occurs in these tumors, albeit infrequently with the reported frequencies (weighted for sample size) of high level microsatellite instability (MSI) being 5% each for gallbladder carcinoma and carcinoma of extra-hepatic bile ducts, and 10% each for intrahepatic cholangiocarcinoma and ampullary carcinoma...
October 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/27799312/a-role-for-human-skin-mast-cells-in-dengue-virus-infection-and-systemic-spread
#14
Andrea Troupin, Devon Shirley, Berlin Londono-Renteria, Alan M Watson, Cody McHale, Alex Hall, Adam Hartstone-Rose, William B Klimstra, Gregorio Gomez, Tonya M Colpitts
Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27759713/treatment-response-and-outcomes-of-grade-3-pancreatic-neuroendocrine-neoplasms-based-on-morphology-well-differentiated-versus-poorly-differentiated
#15
Nitya Raj, Emily Valentino, Marinela Capanu, Laura H Tang, Olca Basturk, Brian R Untch, Peter J Allen, David S Klimstra, Diane Reidy-Lagunes
OBJECTIVES: Emerging data suggest that not all grade 3 (G3) pancreatic neuroendocrine neoplasms (panNENs) behave the same; tumor differentiation may predict outcome. METHODS: Patients with G3 panNENs treated at our institution between 1999 and 2014 were identified. Demographics, response to therapy, and overall survival were determined. RESULTS: Forty-five patients were identified, 16 with G3 well differentiated pancreatic neuroendocrine tumors (WD-panNETs) and 29 with poorly differentiated neuroendocrine carcinomas (PDNEC)...
March 2017: Pancreas
https://www.readbyqxmd.com/read/27758884/mtorc2-signaling-drives-the-development-and-progression-of-pancreatic-cancer
#16
David R Driscoll, Saadia A Karim, Makoto Sano, David M Gay, Wright Jacob, Jun Yu, Yusuke Mizukami, Aarthi Gopinathan, Duncan I Jodrell, T R Jeffry Evans, Nabeel Bardeesy, Michael N Hall, Brian J Quattrochi, David S Klimstra, Simon T Barry, Owen J Sansom, Brian C Lewis, Jennifer P Morton
mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27685844/circulating-plasma-levels-of-microrna-21-and-microrna-221-are-potential-diagnostic-markers-for-primary-intrahepatic-cholangiocarcinoma
#17
Camilo Correa-Gallego, Danilo Maddalo, Alexandre Doussot, Nancy Kemeny, T Peter Kingham, Peter J Allen, Michael I D'Angelica, Ronald P DeMatteo, Doron Betel, David Klimstra, William R Jarnagin, Andrea Ventura
BACKGROUND: MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. METHODS: Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers...
2016: PloS One
https://www.readbyqxmd.com/read/27664376/p53-and-p16-ink4a-p19-arf-loss-promotes-different-pancreatic-tumor-types-from-pymt-expressing-progenitor-cells
#18
Stephanie Azzopardi, Sharon Pang, David S Klimstra, Yi-Chieh Nancy Du
In human studies and mouse models, the contributions of p53 and p16(Ink4a)/p19(Arf) loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs...
October 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27632170/aedes-aegypti-d7-saliva-protein-inhibits-dengue-virus-infection
#19
Michael J Conway, Berlin Londono-Renteria, Andrea Troupin, Alan M Watson, William B Klimstra, Erol Fikrig, Tonya M Colpitts
Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection...
September 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27591765/distinct-pathways-of-pathogenesis-of-intraductal-oncocytic-papillary-neoplasms-and-intraductal-papillary-mucinous-neoplasms-of-the-pancreas
#20
Olca Basturk, Sun M Chung, Ralph H Hruban, N Volkan Adsay, Gokce Askan, Christine Iacobuzio-Donahue, Serdar Balci, Sui Y Zee, Bahar Memis, Jinru Shia, David S Klimstra
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm (IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas (DAs) and IPMNs (SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as antibodies to mucins and differentiation markers [MUC1/MUC2/MUC5AC/MUC6/CDX2/hepatocyte paraffin-1 (HepPar-1)] was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors...
November 2016: Virchows Archiv: An International Journal of Pathology
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