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https://www.readbyqxmd.com/read/29903845/adiponectin-free-fatty-acids-and-cardiovascular-outcomes-in-patients-with-type-2-diabetes-and-acute-coronary-syndrome
#1
Ilse C Schrieks, Anna Nozza, Barbara E Stähli, John B Buse, Robert R Henry, Klas Malmberg, Bruce Neal, Stephen J Nicholls, Lars Rydén, Linda Mellbin, Anders Svensson, Hans Wedel, Arlette Weichert, A Michael Lincoff, Jean-Claude Tardif, Diederick E Grobbee, Gregory G Schwartz
OBJECTIVE: In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio trial, which compared the PPAR-α/γ agonist aleglitazar with placebo...
June 14, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29802158/nrg1-fusions-in-kras-wild-type-pancreatic-cancer
#2
Christoph Heining, Peter Horak, Sebastian Uhrig, Paula L Codo, Barbara Klink, Barbara Hutter, Martina Fröhlich, David Bonekamp, Daniela Richter, Katja Steiger, Roland Penzel, Volker Endris, Karl Roland Ehrenberg, Stephanie Frank, Kortine Kleinheinz, Umut H Toprak, Matthias Schlesner, Ranadip Mandal, Lothar Schulz, Helmut Lambertz, Sebastian Fetscher, Michael Bitzer, Nisar P Malek, Marius S Horger, Nathalia A Giese, Oliver Strobel, Thilo Hackert, Christoph Springfeld, Lars Feuerbach, Frank Bergmann, Evelin Schröck, Christof von Kalle, Wilko Weichert, Claudia Scholl, Claudia R Ball, Albrecht Stenzinger, Benedikt Brors, Stefan Fröhling, Hanno Glimm
We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 PDAC patients enrolled in a precision oncology program revealed gene fusions amenable to pharmacologic inhibition by small-molecule tyrosine kinase inhibitors in all patients with KRAS wild-type (KRASwt) tumors (4 of 17). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor-mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in two patients with NRG1-rearranged tumors that had proved resistant to standard treatment...
May 25, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29769068/correction-to-microrna-expression-profiling-for-the-prediction-of-resistance-to-neoadjuvant-radiochemotherapy-in-squamous-cell-carcinoma-of-the-esophagus
#3
Julia Slotta-Huspenina, Enken Drecoll, Marcus Feith, Daniel Habermehl, Stephanie E Combs, Wilko Weichert, Marcus Bettstetter, Karen Becker, Rupert Langer
Following publication of the original article [1], the authors reported that for one of the authors, Stephanie E. Combs, the middle name was accidentally omitted. They also reported that for two of the authors, Daniel Habermehl and Stephanie E. Combs, two affiliations were accidentally omitted. In this Correction the incorrect and correct author name are shown and the two omitted affiliations are listed.
May 16, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29755686/transcriptome-based-individualized-therapy-of-refractory-pediatric-sarcomas-feasibility-tolerability-and-efficacy
#4
Bushra Weidenbusch, Günther H S Richter, Marie Sophie Kesper, Monika Guggemoos, Katja Gall, Carolin Prexler, Ilya Kazantsev, Alexandra Sipol, Lars Lindner, Michaela Nathrath, Olaf Witt, Katja Specht, Frigga Beitinger, Carolin Knebel, Stuart Hosie, Rüdiger von Eisenhardt-Rothe, Wilko Weichert, Irene Teichert-von Luettichau, Stefan Burdach
Survival rates of pediatric sarcoma patients stagnated during the last two decades, especially in adolescents and young adults (AYAs). Targeted therapies offer new options in refractory cases. Gene expression profiling provides a robust method to characterize the transcriptome of each patient's tumor and guide the choice of therapy. Twenty patients with refractory pediatric sarcomas (age 8-35 years) were assessed with array profiling: ten had Ewing sarcoma, five osteosarcoma, and five soft tissue sarcoma. Overexpressed genes and deregulated pathways were identified as actionable targets and an individualized combination of targeted therapies was recommended...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755669/a-stitch-in-time-saves-nine-external-quality-assessment-rounds-demonstrate-improved-quality-of-biomarker-analysis-in-lung-cancer
#5
Cleo Keppens, Véronique Tack, Nils 't Hart, Lien Tembuyser, Ales Ryska, Patrick Pauwels, Karen Zwaenepoel, Ed Schuuring, Florian Cabillic, Luigi Tornillo, Arne Warth, Wilko Weichert, Elisabeth Dequeker
Biomarker analysis has become routine practice in the treatment of non-small cell lung cancer (NSCLC). To ensure high quality testing, participation to external quality assessment (EQA) schemes is essential. This article provides a longitudinal overview of the EQA performance for EGFR , ALK , and ROS1 analyses in NSCLC between 2012 and 2015. The four scheme years were organized by the European Society of Pathology according to the ISO 17043 standard. Participants were asked to analyze the provided tissue using their routine procedures...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29729025/anticholinergic-medications-in-patients-admitted-with-cognitive-impairment-or-falls-amici-the-impact-of-hospital-admission-on-anticholinergic-cognitive-medication-burden-results-of-a-multicentre-observational-study
#6
I Weichert, R Romero-Ortuno, J Tolonen, T Soe, C Lebus, S Choudhury, C V Nadarajah, P Nanayakkara, M Orrù, S Di Somma
WHAT IS KNOWN AND OBJECTIVE: Drugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission...
May 4, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29695427/complex-and-dynamic-interactions-between-parvovirus-capsids-transferrin-receptors-and-antibodies-control-cell-infection-and-host-range
#7
Heather M Callaway, Kathrin Welsch, Wendy Weichert, Andrew B Allison, Susan L Hafenstein, Kai Huang, Sho Iketani, Colin R Parrish
Antibody and receptor binding are key virus/host interactions that control host range and determine the success of infection. Canine and feline parvovirus capsids bind the transferrin receptor type-1 (TfR) to enter host cells, and specific structural interactions appear necessary to prepare the stable capsids for infection. Here we define the details of binding, competition, and occupancy of wild-type and mutant parvovirus capsids with purified receptors and antibodies. TfR/capsid binding interactions depended on the TfR species and varied widely, with no direct relationship between binding affinity and infection...
April 25, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29695253/microrna-expression-profiling-for-the-prediction-of-resistance-to-neoadjuvant-radiochemotherapy-in-squamous-cell-carcinoma-of-the-esophagus
#8
Julia Slotta-Huspenina, Enken Drecoll, Marcus Feith, Daniel Habermehl, Stephanie Combs, Wilko Weichert, Marcus Bettstetter, Karen Becker, Rupert Langer
BACKGROUND: MicroRNAs (miRNAs) play an important role in cancer biology. Neoadjuvant radiochemotherapy followed by surgery is a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, a subset of patients do not respond. We evaluated whether miRNA profiles can predict resistance to radiochemotherapy. METHODS: Formalin-fixed, paraffin-embedded pretherapeutic biopsies of patients treated by radiochemotherapy followed by esophagectomy were analyzed...
April 25, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29665323/introducing-a-novel-highly-prognostic-grading-scheme-based-on-tumour-budding-and-cell-nest-size-for-squamous-cell-carcinoma-of-the-uterine-cervix
#9
Moritz Jesinghaus, Johanna Strehl, Melanie Boxberg, Frido Brühl, Adrian Wenzel, Björn Konukiewitz, Anna M Schlitter, Katja Steiger, Arne Warth, Andreas Schnelzer, Marion Kiechle, Matthias W Beckmann, Aurelia Noske, Arndt Hartmann, Grit Mehlhorn, Martin C Koch, Wilko Weichert
A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e...
April 2018: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/29665042/neural-tube-defects-in-embryonic-life-lessons-learned-from-340-early-pregnancy-failures
#10
David R Hartge, Michael Gembicki, Achim Rody, Jan Weichert
OBJECTIVES: The aim of this study was to evaluate the feasibility of sonographic assessment of the embryonic/fetal neural tube in nonviable pregnancies and to determine the defect incidence. METHODS: Prospective analysis of transvaginally acquired 3-dimensional (3D) multiplanar and 3D surface-rendered volume sets of 340 cases of missed abortion between March 2010 and September 2015 was performed. Data regarding karyotype and postmortem examination as well as demographic features and the outcomes of subsequent pregnancies were evaluated...
April 17, 2018: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/29659887/homeostasis-model-assessment-of-insulin-resistance-and-survival-in-patients-with-diabetes-and-acute-coronary-syndrome
#11
Barbara E Stähli, Anna Nozza, Ilse C Schrieks, John B Buse, Klas Malmberg, Linda Mellbin, Bruce Neal, Stephen J Nicholls, Lars Rydén, Anders Svensson, Hans Wedel, Arlette Weichert, A Michael Lincoff, Diederick E Grobbee, Jean-Claude Tardif, Gregory G Schwartz
Purpose: Insulin resistance has been linked to development and progression of atherosclerosis and is present in most patients with type 2 diabetes (T2D). Whether the degree of insulin resistance predicts adverse outcomes in patients with T2D and acute coronary syndrome (ACS) is uncertain. Methods: The AleCardio trial compared the peroxisome proliferator-activated receptor-α/γ agonist aleglitazar with placebo in patients with T2D and recent ACS. In participants not treated with insulin, we determined whether baseline homeostasis model assessment of insulin resistance (HOMA-IR, n=4303) or the change in HOMA-IR on assigned study treatment (n=3568) was related to the risk of death or major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, and stroke) in unadjusted and adjusted models...
April 6, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29656008/identification-of-mirnas-linked-with-the-drought-response-of-tef-eragrostis-tef-zucc-trotter
#12
Federico Martinelli, Gina Cannarozzi, Bipin Balan, Fredy Siegrist, Annett Weichert, Regula Blösch, Zerihun Tadele
Tef [Eragrostis tef (Zucc.) Trotter], a staple food crop in the Horn of Africa and particularly in Ethiopia, has several beneficial agronomical and nutritional properties, including waterlogging and drought tolerance. In this study, we performed microRNA profiling of tef using the Illumina HiSeq 2500 platform, analyzing both shoots and roots of two tef genotypes, one drought-tolerant (Tsedey) and one drought-susceptible (Alba). We obtained more than 10 million filtered reads for each of the 24 sequenced small cDNA libraries...
May 2018: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29603092/microrna-expression-levels-are-altered-in-the-cerebrospinal-fluid-of-patients-with-young-onset-alzheimer-s-disease
#13
Paul M McKeever, Raphael Schneider, Foad Taghdiri, Anna Weichert, Namita Multani, Robert A Brown, Adam L Boxer, Anna Karydas, Bruce Miller, Janice Robertson, Maria Carmela Tartaglia
Clinical diagnosis of Alzheimer's disease (AD) prior to the age of 65 years is classified as young-onset (YOAD), whereas diagnosis after the age of 65 years is considered late-onset (LOAD). Although rare autosomal mutations more commonly associate with YOAD, most YOAD and LOAD cases are sporadic. YOAD and LOAD share amyloid and tau pathology, but many YOAD patients show increased disease severity and rate of progression. The current study examined the microRNA (miRNA) expression profile from exosomes isolated from the cerebrospinal fluid (CSF) of YOAD patients with biomarker-confirmed AD...
March 30, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29599921/a-multicenter-round-robin-test-of-pd-l1-expression-assessment-in-urothelial-bladder-cancer-by-immunohistochemistry-and-rt-qpcr-with-emphasis-on-prognosis-prediction-after-radical-cystectomy
#14
Markus Eckstein, Ralph M Wirtz, Carolin Pfannstil, Sven Wach, Robert Stoehr, Johannes Breyer, Franziska Erlmeier, Cagatay Günes, Katja Nitschke, Wilko Weichert, Wolfgang Otto, Bastian Keck, Sebastian Eidt, Maximilian Burger, Helge Taubert, Bernd Wullich, Christian Bolenz, Arndt Hartmann, Philipp Erben
Background: Immunohistochemical PD-L1 assessment is currently used to identify responders towards checkpoint inhibitors although it is limited by inter-observer effects. Here, we conducted a multi-center round robin test to prove the possibility of assessing the PD-L1 status by gene expression to avoid inter-observer effects. Patients and methods: Gene expression of PD-L1 was analyzed in a total of 294 samples (14 cases non-muscle invasive and muscle-invasive bladder cancer; MIBC) in seven centers by a RT-qPCR kit and compared with immunohistochemical scoring of three pathologists (DAKO, 22c3)...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29596894/pancreatic-neuroendocrine-carcinomas-reveal-a-closer-relationship-to-ductal-adenocarcinomas-than-to-neuroendocrine-tumors-g3
#15
Björn Konukiewitz, Moritz Jesinghaus, Katja Steiger, Anna Melissa Schlitter, Atsuko Kasajima, Bence Sipos, Giuseppe Zamboni, Wilko Weichert, Nicole Pfarr, Günter Klöppel
Pancreatic neuroendocrine carcinoma is a rare aggressive tumor commonly harboring TP53 and RB1 alterations and lacking neuroendocrine related genetic changes such as mutations in MEN1 and ATRX/DAXX. Little is known about its genetic profile with regard to that of pancreatic ductal adenocarcinoma. We therefore conducted a detailed genetic study in 12 pancreatic neuroendocrine carcinomas of large cell (n=9) and small cell type (n=3) using massive parallel sequencing applying a 409 gene panel on an Ion Torrent system...
March 26, 2018: Human Pathology
https://www.readbyqxmd.com/read/29555890/clinical-reasoning-a-42-year-old-man-with-unilateral-leg-weakness
#16
Raphael Schneider, Anna Weichert, Ekaterina Rogaeva, Janice Robertson, Julia Keith, Lorne Zinman
No abstract text is available yet for this article.
March 20, 2018: Neurology
https://www.readbyqxmd.com/read/29546479/advanced-high-grade-serous-ovarian-cancer-inverse-association-of-klk13-and-klk14-mrna-levels-in-tumor-tissue-and-patients-prognosis
#17
Larissa Dettmar, Nancy Ahmed, Matthias Kotzsch, Sandra Diersch, Rudolf Napieralski, Dalila Darmoul, Manfred Schmitt, Wilko Weichert, Marion Kiechle, Julia Dorn, Viktor Magdolen
PURPOSE: Gene expression of a variety of the 15 members of the KLK serine protease family is dysregulated in ovarian cancer. We aimed at determining the clinical relevance of KLK13 and KLK14 mRNA expression in tumor tissues of a homogeneous patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO stage III/IV). METHODS: mRNA expression levels of KLK13 and KLK14 were assessed by quantitative PCR in tumor tissue of 91 patients and related with clinical factors and patients' outcome...
June 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29540682/crystal-structure-of-undecaprenyl-pyrophosphate-phosphatase-and-its-role-in-peptidoglycan-biosynthesis
#18
Meriem El Ghachi, Nicole Howe, Chia-Ying Huang, Vincent Olieric, Rangana Warshamanage, Thierry Touzé, Dietmar Weichert, Phillip J Stansfeld, Meitian Wang, Fred Kerff, Martin Caffrey
As a protective envelope surrounding the bacterial cell, the peptidoglycan sacculus is a site of vulnerability and an antibiotic target. Peptidoglycan components, assembled in the cytoplasm, are shuttled across the membrane in a cycle that uses undecaprenyl-phosphate. A product of peptidoglycan synthesis, undecaprenyl-pyrophosphate, is converted to undecaprenyl-phosphate for reuse in the cycle by the membrane integral pyrophosphatase, BacA. To understand how BacA functions, we determine its crystal structure at 2...
March 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29510988/cross-cohort-analysis-identifies-a-tead4-mycn-positive-feedback-loop-as-the-core-regulatory-element-of-high-risk-neuroblastoma
#19
Presha Rajbhandari, Gonzalo Lopez, Claudia Capdevila, Beatrice Salvatori, Jiyang Yu, Ruth Rodriguez-Barrueco, Daniel Martinez, Mark Yarmarkovich, Nina Weichert-Leahey, Brian J Abraham, Mariano J Alvarez, Archana Iyer, Jo Lynne Harenza, Derek Oldridge, Katleen De Preter, Jan Koster, Shahab Asgharzadeh, Robert C Seeger, Jun S Wei, Javed Khan, Jo Vandesompele, Pieter Mestdagh, Rogier Versteeg, A Thomas Look, Richard A Young, Antonio Iavarone, Anna Lasorella, Jose M Silva, John M Maris, Andrea Califano
High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator proteins that were conserved across independent cohorts...
May 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29497802/tracer-uptake-in-mediastinal-and-paraaortal-thoracic-lymph-nodes-as-a-potential-pitfall-in-image-interpretation-of-psma-ligand-pet-ct
#20
Ali Afshar-Oromieh, Lars Peter Sattler, Katja Steiger, Tim Holland-Letz, Marcelo Livorsi da Cunha, Walter Mier, Oliver Neels, Klaus Kopka, Wilko Weichert, Uwe Haberkorn
PURPOSE: Since the introduction of 68 Ga-PSMA-11 PET/CT for imaging prostate cancer (PC) we have frequently observed mediastinal lymph nodes (LN) showing tracer uptake despite being classified as benign. The aim of this evaluation was to further analyze such LN. METHODS: Two patient groups with biphasic 68 Ga-PSMA-11 PET/CT at 1 h and 3 h p.i. were included in this retrospective evaluation. Group A (n = 38) included patients without LN metastases, and group B (n = 43) patients with LN metastases of PC...
March 1, 2018: European Journal of Nuclear Medicine and Molecular Imaging
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