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https://www.readbyqxmd.com/read/28719467/pan-trk-immunohistochemistry-is-an-efficient-and-reliable-screen-for-the-detection-of-ntrk-fusions
#1
Jaclyn F Hechtman, Ryma Benayed, David M Hyman, Alexander Drilon, Ahmet Zehir, Denise Frosina, Maria E Arcila, Snjezana Dogan, David S Klimstra, Marc Ladanyi, Achim A Jungbluth
Activating neurotrophic tyrosine receptor kinase (NTRK) fusions, typically detected using nucleic-acid based assays, are highly targetable and define certain tumors. Here, we explore the utility of pan-TRK immunohistochemistry (IHC) to detect NTRK fusions. NTRK rearrangements were detected prospectively using MSK-IMPACT, a DNA-based next-generation sequencing assay. Transcription of novel NTRK rearrangements into potentially functional fusion transcripts was assessed via Archer Dx fusion assay. Pan-Trk IHC testing with mAb EPR17341 was performed on all NTRK rearranged cases and 20 cases negative for NTRK fusions on Archer...
July 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28686653/ribbon-scanning-confocal-for-high-speed-high-resolution-volume-imaging-of-brain
#2
Alan M Watson, Annika H Rose, Gregory A Gibson, Christina L Gardner, Chengqun Sun, Douglas S Reed, L K Metthew Lam, Claudette M St Croix, Peter L Strick, William B Klimstra, Simon C Watkins
Whole-brain imaging is becoming a fundamental means of experimental insight; however, achieving subcellular resolution imagery in a reasonable time window has not been possible. We describe the first application of multicolor ribbon scanning confocal methods to collect high-resolution volume images of chemically cleared brains. We demonstrate that ribbon scanning collects images over ten times faster than conventional high speed confocal systems but with equivalent spectral and spatial resolution. Further, using this technology, we reconstruct large volumes of mouse brain infected with encephalitic alphaviruses and demonstrate that regions of the brain with abundant viral replication were inaccessible to vascular perfusion...
2017: PloS One
https://www.readbyqxmd.com/read/28650392/o6-methylguanine-dna-methyltransferase-status-does-not-predict-response-or-resistance-to-alkylating-agents-in-well-differentiated-pancreatic-neuroendocrine-tumors
#3
Nitya Raj, David S Klimstra, Natally Horvat, Liying Zhang, Joanne F Chou, Marinela Capanu, Olca Basturk, Richard Kinh Gian Do, Peter J Allen, Diane Reidy-Lagunes
OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing...
June 22, 2017: Pancreas
https://www.readbyqxmd.com/read/28609363/o6-methylguanine-dna-methyltransferase-status-does-not-predict-response-or-resistance-to-alkylating-agents-in-well-differentiated-pancreatic-neuroendocrine-tumors
#4
Nitya Raj, David S Klimstra, Natally Horvat, Liying Zhang, Joanne F Chou, Marinela Capanu, Olca Basturk, Richard Kinh Gian Do, Peter J Allen, Diane Reidy-Lagunes
OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28581654/daily-dynamics-of-adolescent-mood-and-identity
#5
Theo A Klimstra, Peter Kuppens, Koen Luyckx, Susan Branje, William W Hale, Annerieke Oosterwegel, Hans M Koot, Wim H J Meeus
Important linkages between daily mood and identity formation have been theorized, but have not been empirically tested as of yet. This study provided a first examination of these linkages within individuals (N = 392; 55.1% boys; Mage at T1 = 13.24, SD = 0.44) across 15 series of 5 days distributed over 5 years. Results revealed negative within-time associations of educational and relational commitment with negative mood. Negative mood was positively associated with educational in-depth exploration and educational and interpersonal reconsideration...
September 2016: Journal of Research on Adolescence: the Official Journal of the Society for Research on Adolescence
https://www.readbyqxmd.com/read/28572718/longitudinal-associations-between-parental-bonding-parenting-stress-and-executive-functioning-in-toddlerhood
#6
Evi S A de Cock, Jens Henrichs, Theo A Klimstra, A Janneke B M Maas, Charlotte M J M Vreeswijk, Wim H J Meeus, Hedwig J A van Bakel
Early executive functioning is an important predictor for future development of children's cognitive skills and behavioral outcomes. Parenting behavior has proven to be a key environmental determinant of child executive functioning. However, the association of parental affect and cognitions directed to the child with child executive functioning has been understudied. Therefore, in the present study we examine the associations between parental bonding (i.e., the affective tie from parent to child), parenting stress, and child executive functioning...
2017: Journal of Child and Family Studies
https://www.readbyqxmd.com/read/28565933/comparing-executive-function-evoked-hemodynamic-response-and-gait-as-predictors-of-variations-in-mobility-for-older-adults
#7
Drew W R Halliday, Sandra R Hundza, Mauricio A Garcia-Barrera, Marc Klimstra, Drew Commandeur, Timothy V Lukyn, Robert S Stawski, Stuart W S MacDonald
OBJECTIVE: Falls represent a major concern for older adults and may serve as clinically salient index events for those presenting in the prodromal stages of mild cognitive impairment. Declines in executive function performance and in gait consistency have shown promise in predicting fall risk; however, associated neurophysiological underpinnings have received less attention. In this study, we used a multimodal approach to assess fall risk in a group of older adults with and without a previous fall history...
May 31, 2017: Journal of Clinical and Experimental Neuropsychology
https://www.readbyqxmd.com/read/28498280/immunohistochemical-characterization-of-the-origins-of-metastatic-well-differentiated-neuroendocrine-tumors-to-the-liver
#8
Zhaohai Yang, David S Klimstra, Ralph H Hruban, Laura H Tang
Metastatic neoplasms of unknown primary site pose a major challenge to patient management. As targeted therapies are now being tailored to neuroendocrine tumors (NETs) of different primary sites, identifying the origin of metastatic NETs has become increasingly important. Compared with more extensive efforts on metastatic adenocarcinomas of unknown primary, the literature on metastatic NETs (often to the liver) is relatively sparse and most studies are based on primary tumors. We sought to study metastatic well-differentiated NETs to the liver to identify markers that predict the site of origin...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28487016/the-expression-level-of-c19mc-mirnas-in-early-pregnancy-and-in-response-to-viral-infection
#9
Tina M F Dumont, Jean-Francois Mouillet, Avaraham Bayer, Christina L Gardner, William B Klimstra, Dana G Wolf, Simcha Yagel, Fabiola Balmir, Anna Binstock, Joseph S Sanfilippo, Carolyn B Coyne, Jacob C Larkin, Yoel Sadovsky
INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR...
May 2017: Placenta
https://www.readbyqxmd.com/read/28486549/genome-and-transcriptome-profiling-of-fibrolamellar-hepatocellular-carcinoma-demonstrates-p53-and-igf2bp1-dysregulation
#10
Eric C Sorenson, Raya Khanin, Zubin M Bamboat, Michael J Cavnar, Teresa S Kim, Eran Sadot, Shan Zeng, Jonathan B Greer, Adrian M Seifert, Noah A Cohen, Megan H Crawley, Benjamin L Green, David S Klimstra, Ronald P DeMatteo
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of HCC that most frequently affects young adults. Because of its rarity and an absence of preclinical models, our understanding of FL-HCC is limited. Our objective was to analyze chromosomal alterations and dysregulated gene expression in tumor specimens collected at a single center during two decades of experience with FL-HCC. We analyzed 38 specimens from 26 patients by array comparative genomic hybridiziation (aCGH) and 35 specimens from 15 patients by transcriptome sequencing (RNA-seq)...
2017: PloS One
https://www.readbyqxmd.com/read/28485185/exploring-the-ecological-validity-and-variability-of-a-10-min-bout-of-wheeling
#11
Megan K MacGillivray, Tania Lam, Marc Klimstra, E Paul Zehr, Bonita J Sawatzky
PURPOSE: To determine the ecological validity of using able-bodied participants to perform a 10-min wheeling trial by (1) evaluating changes in biomechanics over the trial in manual wheelchair users and able-bodied participants naïve to wheeling and (2) describing differences in changes and variability between groups. MATERIALS AND METHODS: Manual wheelchair users (n = 7, 2-27 years' experience) and able-bodied participants (n = 11) wheeled for 10 min...
May 9, 2017: Disability and Rehabilitation. Assistive Technology
https://www.readbyqxmd.com/read/28481359/mutational-landscape-of-metastatic-cancer-revealed-from-prospective-clinical-sequencing-of-10-000-patients
#12
Ahmet Zehir, Ryma Benayed, Ronak H Shah, Aijazuddin Syed, Sumit Middha, Hyunjae R Kim, Preethi Srinivasan, Jianjiong Gao, Debyani Chakravarty, Sean M Devlin, Matthew D Hellmann, David A Barron, Alison M Schram, Meera Hameed, Snjezana Dogan, Dara S Ross, Jaclyn F Hechtman, Deborah F DeLair, JinJuan Yao, Diana L Mandelker, Donavan T Cheng, Raghu Chandramohan, Abhinita S Mohanty, Ryan N Ptashkin, Gowtham Jayakumaran, Meera Prasad, Mustafa H Syed, Anoop Balakrishnan Rema, Zhen Y Liu, Khedoudja Nafa, Laetitia Borsu, Justyna Sadowska, Jacklyn Casanova, Ruben Bacares, Iwona J Kiecka, Anna Razumova, Julie B Son, Lisa Stewart, Tessara Baldi, Kerry A Mullaney, Hikmat Al-Ahmadie, Efsevia Vakiani, Adam A Abeshouse, Alexander V Penson, Philip Jonsson, Niedzica Camacho, Matthew T Chang, Helen H Won, Benjamin E Gross, Ritika Kundra, Zachary J Heins, Hsiao-Wei Chen, Sarah Phillips, Hongxin Zhang, Jiaojiao Wang, Angelica Ochoa, Jonathan Wills, Michael Eubank, Stacy B Thomas, Stuart M Gardos, Dalicia N Reales, Jesse Galle, Robert Durany, Roy Cambria, Wassim Abida, Andrea Cercek, Darren R Feldman, Mrinal M Gounder, A Ari Hakimi, James J Harding, Gopa Iyer, Yelena Y Janjigian, Emmet J Jordan, Ciara M Kelly, Maeve A Lowery, Luc G T Morris, Antonio M Omuro, Nitya Raj, Pedram Razavi, Alexander N Shoushtari, Neerav Shukla, Tara E Soumerai, Anna M Varghese, Rona Yaeger, Jonathan Coleman, Bernard Bochner, Gregory J Riely, Leonard B Saltz, Howard I Scher, Paul J Sabbatini, Mark E Robson, David S Klimstra, Barry S Taylor, Jose Baselga, Nikolaus Schultz, David M Hyman, Maria E Arcila, David B Solit, Marc Ladanyi, Michael F Berger
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28468884/antibody-preparations-from-human-transchromosomic-cows-exhibit-prophylactic-and-therapeutic-efficacy-against-venezuelan-equine-encephalitis-virus
#13
Christina L Gardner, Chengqun Sun, Thomas Luke, Kanakatte Raviprakash, Hua Wu, Jin-An Jiao, Eddie Sullivan, Douglas S Reed, Kate D Ryman, William B Klimstra
Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity rates in humans. In addition to natural outbreaks, there is the potential for exposure to VEEV via aerosolized virus particles. There are currently no FDA-licensed vaccines or antiviral therapies for VEEV. Passive immunotherapy is an approved method used to protect individuals against several pathogens and toxins. Human polyclonal antibodies (PAbs) are ideal, but this is dependent upon serum from convalescent human donors, which is in limited supply...
July 15, 2017: Journal of Virology
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
#14
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
#15
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...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398253/t-cell-mediated-immunity-towards-yellow-fever-virus-and-useful-animal-models
#16
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
#17
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
#18
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 harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced colorectal carcinoma underwent next-generation sequencing via MSK-IMPACT, and a subset of case samples was subjected to high-resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) colorectal carcinoma data. Of the colorectal carcinoma patients sequenced (n = 401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28094897/cytology-assessment-can-predict-survival-for-patients-with-metastatic-pancreatic-neuroendocrine-neoplasms
#19
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
#20
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...
August 2017: Journal of Youth and Adolescence
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