Medical Specialties Commons^™

Editorial., Jeffrey C Wang, Jens R Chapman, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.

Mitf Has A Central Role In Regulating Starvation-Induced Autophagy In Melanoma., Katrin Möller, Sara Sigurbjornsdottir, Asgeir O Arnthorsson, Vivian Pogenberg, Ramile Dilshat, Valerie Fock, Solveig H Brynjolfsdottir, Christian Bindesboll, Margret Bessadottir, Helga M Ogmundsdottir, Anne Simonsen, Lionel Larue, Matthias Wilmanns, Vesteinn Thorsson, Eirikur Steingrimsson, Margret H Ogmundsdottir

Articles, Abstracts, and Reports

The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, …

Shared Heritability And Functional Enrichment Across Six Solid Cancers., Xia Jiang, Hilary K Finucane, Fredrick R Schumacher, Stephanie L Schmit, Jonathan P Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B Kuchenbaecker, Joe Dennis, David V Conti, Graham Casey, Mia M Gaudet, Jeroen R Huyghe, Demetrius Albanes, Melinda C Aldrich, Angeline S Andrew, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Natalia N Antonenkova, Susanne M Arnold, Kristan J Aronson, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Jyotsna Batra, Matthias W Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I Berndt, Heike Bickeböller, Stephanie A Bien, Carl Blomqvist, Stefania Boccia, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Hiltrud Brauch, Hermann Brenner, James D Brenton, Mark N Brook, Joan Brunet, Hans Brunnström, Daniel D Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A Caligo, Ian Campbell, Peter T Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L Carvalho, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, Chu Chen, David C Christiani, Kathleen B M Claes, Frank Claessens, Judith Clements, J Margriet Collée, Marcia Cruz Correa, Fergus J Couch, Angela Cox, Julie M Cunningham, Cezary Cybulski, Kamila Czene, Mary B Daly, Anna Defazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L Donovan, Thilo Dörk, Eric J Duell, Alison M Dunning, Miriam Dwek, Diana M Eccles, Christopher K Edlund, Digna R Velez Edwards, Carolina Ellberg, D Gareth Evans, Peter A Fasching, Robert L Ferris, Triantafillos Liloglou, Jane C Figueiredo, Olivia Fletcher, Renée T Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J Gallinger, Patricia A Ganz, Judy Garber, José A García-Sáenz, Simon A Gayther, Graham G Giles, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Ellen L Goode, Marc T Goodman, Gary E Goodman, Kjell Grankvist, Mark H Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C Hamdy, Robert J Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L Hopper, Richard Houlston, Peter J Hulick, David J Hunter, David G Huntsman, Gregory Idos, Evgeny N Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A Jenkins, Mattias Johansson, Mikael Johansson, Esther M John, Amit D Joshi, Radka Kaneva, Beth Y Karlan, Linda E Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S Kibel, Lambertus A Kiemeney, Jeri Kim, Susanne K Kjaer, Julia A Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A Levine, Li Li, Christopher I Li, Annika Lindblom, Noralane M Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley Mcguffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L Milne, Robert J Macinnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, David E Neal, Andrew R Ness, Susan L Neuhausen, Heli Nevanlinna, Polly A Newcomb, Lisa F Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G Nordestgaard, Robert L Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I Olopade, Andrew F Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y Park, Nora Pashayan, Michael T Parsons, Tanja Pejovic, Kathryn L Penney, Wilbert H M Peters, Catherine M Phelan, Amanda I Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J Ramus, Leon Raskin, Gad Rennert, Hedy S Rennert, Elizabeth J Van Rensburg, Marjorie J Riggan, Harvey A Risch, Angela Risch, Monique J Roobol, Barry S Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P Sandler, Elinor J Sawyer, Matthew B Schabath, Johanna Schleutker, Marjanka K Schmidt, V Wendy Setiawan, Hongbing Shen, Erin M Siegel, Weiva Sieh, Christian F Singer, Martha L Slattery, Karina Dalsgaard Sorensen, Melissa C Southey, Amanda B Spurdle, Janet L Stanford, Victoria L Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J Swerdlow, Eloiza H Tajara, Catherine M Tangen, Adonina Tardon, Jack A Taylor, M Dawn Teare, Manuel R Teixeira, Mary Beth Terry, Kathryn L Terry, Stephen N Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E Toland, Diana Torres, Paul A Townsend, Ruth C Travis, Nadine Tung, Shelley S Tworoger, Cornelia M Ulrich, Nawaid Usmani, Celine M Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M Webb, Clarice R Weinberg, Stephanie Weinstein, Mark C Weissler, Jeffrey N Weitzel, Catharine M L West, Emily White, Alice S Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K Zorn, Jacqueline M Lane, Richa Saxena, Duncan Thomas, Rayjean J Hung, Brenda Diergaarde, James Mckay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A Eeles, Georgia Chenevix-Trench, Paul J Brennan, Christopher A Haiman, Jacques Simard, Douglas F Easton, Stephen B Gruber, Paul D P Pharoah, Alkes L Price, Bogdan Pasaniuc, Christopher I Amos, Peter Kraft, Sara Lindström

Articles, Abstracts, and Reports

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r

Static And Dynamic Postural Control Deficits In Aging Fragile X Mental Retardation 1 (Fmr1) Gene Premutation Carriers., Zheng Wang, Pravin Khemani, Lauren M Schmitt, Su Lui, Matthew W Mosconi

Articles, Abstracts, and Reports

BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS.

METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG …

Demethylation By Low-Dose 5-Aza-2'-Deoxycytidine Impairs 3d Melanoma Invasion Partially Through Mir-199a-3p Expression Revealing The Role Of This Mir In Melanoma., Cécile Desjobert, Arnaud Carrier, Audrey Delmas, Diego M Marzese, Antoine Daunay, Florence Busato, Arnaud Pillon, Jörg Tost, Joëlle Riond, Gilles Favre, Chantal Etievant, Paola B Arimondo

Articles, Abstracts, and Reports

BACKGROUND: Efficient treatments against metastatic melanoma dissemination are still lacking. Here, we report that low-cytotoxic concentrations of 5-aza-2'-deoxycytidine, a DNA demethylating agent, prevent in vitro 3D invasiveness of metastatic melanoma cells and reduce lung metastasis formation in vivo.

RESULTS: We unravelled that this beneficial effect is in part due to MIR-199A2 re-expression by promoter demethylation. Alone, this miR showed an anti-invasive and anti-metastatic effect. Throughout integration of micro-RNA target prediction databases with transcriptomic analysis after 5-aza-2'-deoxycytidine treatments, we found that miR-199a-3p downregulates set of genes significantly involved in invasion/migration processes. In addition, analysis of data from melanoma patients showed a …

The Carotid Sinus Nerve And The First English Translation Of Hering's Original Research On This Nerve., Mohammadali M Shoja, Rabjot Rai, Stefan Lachkar, Seleipiri Iboroma Akobo, Emre Yilmaz, Marios Loukas, Emanuela Binello, Mehrnoush Gorjaian, Christoph J Griessenauer, Joe Iwanaga, R Shane Tubbs

Articles, Abstracts, and Reports

This paper provides a brief depiction of the life and achievements of the most iconic experiments of Heinrich Ewald Hering. The authors herein have presented a translation of his paper on the carotid sinus nerve in English; the original paper by Heinrich Ewald Hering, titled "Ueber die Wand des Sinus caroticus als Reizempfänger und den Sinusnerv als zentripetale Bahn für die Sinusreflexe" (1924), provides a detailed account of his experimental process and findings. He recognized that the sinus reflexes are mediated by a branch of the glossopharyngeal nerve (CN IX).

Predicting Adherence To Therapy In Rheumatoid Arthritis, Psoriatic Arthritis Or Ankylosing Spondylitis: A Large Cross-Sectional Study., Josef S Smolen, Dafna Gladman, H Patrick Mcneil, Philip J Mease, Joachim Sieper, Maja Hojnik, Pascal Nurwakagari, John Weinman

Articles, Abstracts, and Reports

Objective: This analysis explored the association of treatment adherence with beliefs about medication, patient demographic and disease characteristics and medication types in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) to develop adherence prediction models.

Methods: The population was a subset from ALIGN, a multicountry, cross-sectional, self-administered survey study in adult patients (n=7328) with six immune-mediated inflammatory diseases who were routinely receiving systemic therapy. Instruments included Beliefs about Medicines Questionnaire (BMQ) and 4-item Morisky Medication Adherence Scale (MMAS-4

Results: A total of 3390 rheumatological patients were analysed (RA, n=1943; PsA, n=635; AS, n=812). Based on the strongest significant …

Erratum: Author Correction: Surgical Standards For Management Of The Axilla In Breast Cancer Clinical Trials With Pathological Complete Response Endpoint., Judy C Boughey, Michael D Alvarado, Rachael B Lancaster, W Fraser Symmans, Rita Mukhtar, Jasmine M Wong, Cheryl A Ewing, David A Potter, Todd M Tuttle, Tina J Hieken, Jodi M Carter, James W Jakub, Henry G Kaplan, Claire L Buchanan, Nora T Jaskowiak, Husain A Sattar, Jeffrey Mueller, Rita Nanda, Claudine J Isaacs, Paula R Pohlmann, Filipa Lynce, Eleni A Tousimis, Jay C Zeck, M Catherine Lee, Julie E Lang, Paulette Mhawech-Fauceglia, Roshni Rao, Bret Taback, Constantine Goodellas, Margaret Chen, Kevin M Kalinsky, Hanina Hibshoosh, Brigid Killelea, Tara Sanft, Gillian L Hirst, Smita Asare, Jeffrey B Matthews, Jane Perlmutter, Laura J Esserman

Articles, Abstracts, and Reports

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

High-Dose Ipilimumab And High-Dose Interleukin-2 For Patients With Advanced Melanoma., Ann W Silk, Howard L Kaufman, Brendan Curti, Janice M Mehnert, Kim Margolin, David Mcdermott, Joseph Clark, Jenna Newman, Praveen K Bommareddy, Lisa Denzin, Saltanat Najmi, Azra Haider, Weichung Shih, Michael P Kane, Andrew Zloza

Articles, Abstracts, and Reports

High-dose ipilimumab (IPI) and high-dose interleukin-2 (IL-2) are approved agents for metastatic melanoma, but the efficacy and safety of the combination are unknown. The objective of this study was to evaluate the feasibility, safety, and efficacy of combination high-dose IPI and high-dose IL-2 in patients with histologically confirmed advanced unresectable stage III and IV melanoma. This Phase II, multicenter, open-label, single-arm trial was conducted in nine patients enrolled between 12/2014 and 12/2015. Subjects were treated with high-dose IPI 10 mg/kg intravenous (IV) every 3 weeks for four doses starting at week 1 and high-dose IL-2 (600,000 IU/kg IV bolus every …

If We Build It They Will Come: Targeting The Immune Response To Breast Cancer., Margaret E Gatti-Mays, Justin M Balko, Sofia R Gameiro, Harry D Bear, Sangeetha Prabhakaran, Jami Fukui, Mary L Disis, Rita Nanda, James L Gulley, Kevin Kalinsky, Houssein Abdul Sater, Joseph A Sparano, David Cescon, David B Page, Heather Mcarthur, Sylvia Adams, Elizabeth A Mittendorf

Articles, Abstracts, and Reports

Historically, breast cancer tumors have been considered immunologically quiescent, with the majority of tumors demonstrating low lymphocyte infiltration, low mutational burden, and modest objective response rates to anti-PD-1/PD-L1 monotherapy. Tumor and immunologic profiling has shed light on potential mechanisms of immune evasion in breast cancer, as well as unique aspects of the tumor microenvironment (TME). These include elements associated with antigen processing and presentation as well as immunosuppressive elements, which may be targeted therapeutically. Examples of such therapeutic strategies include efforts to (1) expand effector T-cells, natural killer (NK) cells and immunostimulatory dendritic cells (DCs), (2) improve antigen presentation, and …

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis., Sean J O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A S Reyes, Jon Gorky, Rajanikanth Vadigepalli, Elisabeth J Van Bockstaele, James S Schwaber

Articles, Abstracts, and Reports

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably

Multicentre Pilot Randomised Clinical Trial Of Early In-Bed Cycle Ergometry With Ventilated Patients., Michelle E Kho, Alexander J Molloy, France J Clarke, Julie C Reid, Margaret S Herridge, Timothy Karachi, Bram Rochwerg, Alison E Fox-Robichaud, Andrew Je Seely, Sunita Mathur, Vincent Lo, Karen Ea Burns, Ian M Ball, Joseph R Pellizzari, Jean-Eric Tarride, Jill C Rudkowski, Karen Koo, Diane Heels-Ansdell, Deborah J Cook

Articles, Abstracts, and Reports

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient's ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients.

Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, …

Prediction Of Cardiovascular Outcomes With Machine Learning Techniques: Application To The Cardiovascular Outcomes In Renal Atherosclerotic Lesions (Coral) Study., Tian Chen, Pamela Brewster, Katherine Tuttle, Lance D Dworkin, William Henrich, Barbara A Greco, Michael Steffes, Sheldon Tobe, Kenneth Jamerson, Karol Pencina, Joseph M Massaro, Ralph B D'Agostino, Donald E Cutlip, Timothy P Murphy, Christopher J Cooper, Joseph I Shapiro

Articles, Abstracts, and Reports

Background: Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study.

Methods: We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according …

Characterizing Whole Brain Temporal Variation Of Functional Connectivity Via Zero And First Order Derivatives Of Sliding Window Correlations., Flor A Espinoza, Victor M Vergara, Eswar Damaraju, Kyle G Henke, Ashkan Faghiri, Jessica A Turner, Aysenil A Belger, Judith M Ford, Sarah C Mcewen, Daniel H Mathalon, Bryon A Mueller, Steven G Potkin, Adrian Preda, Jatin G Vaidya, Theo G M Van Erp, Vince D Calhoun

Articles, Abstracts, and Reports

Brain functional connectivity has been shown to change over time during resting state fMRI experiments. Close examination of temporal changes have revealed a small set of whole-brain connectivity patterns called dynamic states. Dynamic functional network connectivity (dFNC) studies have demonstrated that it is possible to replicate the dynamic states across several resting state experiments. However, estimation of states and their temporal dynamicity still suffers from noisy and imperfect estimations. In regular dFNC implementations, states are estimated by comparing connectivity patterns through the data without considering time, in other words only zero order changes are examined. In this work we propose …

Are There Mortality Risks For Patients With Epilepsy Who Use Cannabis Treatments As Monotherapy?, Devon M Kollmyer, Kyla E Wright, Nicole M Warner, Michael J Doherty

Articles, Abstracts, and Reports

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.

A Microbial-Based Cancer Vaccine For Induction Of Egfrviii-Specific Cd8+ T Cells And Anti-Tumor Immunity., Lauren Zebertavage, Shelly Bambina, Jessica Shugart, Alejandro Alice, Kyra D Zens, Peter Lauer, Bill Hanson, Michael J. Gough, Marka R Crittenden, Keith S Bahjat

Articles, Abstracts, and Reports

Dysregulated signaling via the epidermal growth factor receptor (EGFR)-family is believed to contribute to the progression of a diverse array of cancers. The most common variant of EGFR is EGFRvIII, which results from a consistent and tumor-specific in-frame deletion of exons 2-7 of the EGFR gene. This deletion generates a novel glycine at the junction and leads to constitutive ligand-independent activity. This junction forms a novel shared tumor neo-antigen with demonstrated immunogenicity in both mice and humans. A 21-amino acid peptide spanning the junctional region was selected, and then one or five copies of this 21-AA neo-peptide were incorporated into …

How Might Tissue Glucose Influence Responsive Neurostimulation Detection?, Kyla E Wright, Devon M Kollmyer, Nicole M Warner, Alan M Haltiner, Ryder P Gwinn, Michael J Doherty

Articles, Abstracts, and Reports

No abstract provided.

Participation In An Innovative Patient Support Program Reduces Prescription Abandonment For Adalimumab-Treated Patients In A Commercial Population., Diana Brixner, Manish Mittal, David T Rubin, Philip Mease, Harry H Liu, Matthew Davis, Arijit Ganguli, A Mark Fendrick

Articles, Abstracts, and Reports

Purpose: Nonadherence to indicated therapy reduces treatment effectiveness and may increase cost of care. HUMIRA Complete, a Patient Support Program (PSP), aims to reduce nonadherence in patients prescribed adalimumab (ADA). The objective of this study was to assess the relationship between participation in the PSP and prescription abandonment rates among ADA-treated patients.

Patients and methods: This longitudinal study using patient-level data from AbbVie's PSP linked with medical and pharmacy claims data included patients ≥18 years with an ADA-approved indication, ≥1 pharmacy claim for ADA, and available data ≥3 months before and ≥6 months after the index date (defined as the …

Lipid-Polymer Hybrid Nanoparticles As A Next-Generation Drug Delivery Platform: State Of The Art, Emerging Technologies, And Perspectives., Anubhab Mukherjee, Ariana K Waters, Pranav Kalyan, Achal Singh Achrol, Santosh Kesari, Venkata Yenugonda

Articles, Abstracts, and Reports

Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation core-shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer. Although they have garnered significant interest, they remain not yet widely exploited or ubiquitous. Recently, a fundamental transformation has occurred in the preparation of LPHNPs, characterized by a transition from a two-step to a one-step strategy, involving synchronous self-assembly of polymers and lipids. Owing to its two-in-one structure, this approach is of particular interest as a combinatorial drug delivery platform in oncology. In particular, the outer surface can be decorated in multifarious ways …

An Inflammatory Landscape For Preoperative Neurologic Deficits In Glioblastoma., Amal Katrib, Hyun-Hwan Jeong, Nina L Fransen, Kristin S Henzel, Jeremy A Miller

Articles, Abstracts, and Reports

No abstract provided.

Difficult Conversations., Alison Christy

Articles, Abstracts, and Reports

No abstract provided.

Effect Of Tofacitinib On Patient-Reported Outcomes In Patients With Active Psoriatic Arthritis And An Inadequate Response To Tumour Necrosis Factor Inhibitors In The Phase Iii, Randomised Controlled Trial: Opal Beyond., Vibeke Strand, Kurt De Vlam, Jose A Covarrubias-Cobos, Philip Mease, Dafna D Gladman, Linda Chen, Elizabeth Kudlacz, Joseph Wu, Joseph C Cappelleri, Thijs Hendrikx, Ming-Ann Hsu

Articles, Abstracts, and Reports

Objectives: Tofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). Patient-reported outcomes (PROs) were evaluated in patients with PsA with inadequate responses to tumour necrosis factor inhibitors (TNFi-IR) in a 6-month, phase III randomised controlled trial (OPAL Beyond [NCT01882439]).

Methods: Patients (N=394) received tofacitinib 5 or 10 mg twice daily or placebo (advancing to tofacitinib 5 or 10 mg twice daily at month 3). Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences and scores ≥normative values were determined in Patient Global Assessment of disease activity (PtGA), Pain, Patient …

Ensuring Quality Standards And Reproducible Research For Data Analysis Services In Oncology: A Cooperative Service Model., Frank Emmert-Streib, Matthias Dehmer, Olli Yli-Harja

Articles, Abstracts, and Reports

Modern molecular high-throughput devices, e.g., next-generation sequencing, have transformed medical research. Resulting data sets are usually high-dimensional on a genomic-scale providing multi-factorial information from intertwined molecular and cellular activities of genes and their products. This genomics-revolution installed precision medicine offering breathtaking opportunities for patient's diagnosis and treatment. However, due to the speed of these developments the quality standards of the involved data analyses are lacking behind, as exemplified by the infamous Duke Saga. In this paper, we argue in favor of a two-stage cooperative serve model that couples data generation and data analysis in the most beneficial way from the …

Down Syndrome Associated Moyamoya May Worsen Epilepsy Control And Can Benefit From Surgical Revascularization., Sarah R Garson, Stephen J Monteith, Sheila D Smith, Bart P Keogh, Ryder P Gwinn, Michael J Doherty

Articles, Abstracts, and Reports

Objectives: To examine outcome of bilateral extracranial to intracranial (EC-IC) bypass surgeries for a Down syndrome patient with hard-to-treat epilepsy and moyamoya.

Materials and methods: Superficial temporal arteries were anastamosed using an indirect bypass technique to middle cerebral arteries bilaterally to help limit perfusion deficits and seizure controls.

Results: Two superficial temporal to middle cerebral artery indirect bypass surgeries were performed within 3 months. Post-revascularization improvements included seizure control, gait, perfusion, wakefulness, language and quality of life.

Conclusion: In patients with Down syndrome and moyamoya, improvements in seizure control and quality of life may occur with EC-IC bypass procedures.

Regeneration Enhances Metastasis: A Novel Role For Neurovascular Signaling In Promoting Melanoma Brain Metastasis., Roshini Prakash, Sivan Izraely, Nikita S Thareja, Rex H Lee, Maya Rappaport, Riki Kawaguchi, Orit Sagi-Assif, Shlomit Ben-Menachem, Tsipi Meshel, Michal Machnicki, Shuichi Ohe, Dave S B Hoon, Giovanni Coppola, Isaac P Witz, S Thomas Carmichael

Articles, Abstracts, and Reports

Neural repair after stroke involves initiation of a cellular proliferative program in the form of angiogenesis, neurogenesis, and molecular growth signals in the surrounding tissue elements. This cellular environment constitutes a niche in which regeneration of new blood vessels and new neurons leads to partial tissue repair after stroke. Cancer metastasis has similar proliferative cellular events in the brain and other organs. Do cancer and CNS tissue repair share similar cellular processes? In this study, we identify a novel role of the regenerative neurovascular niche induced by stroke in promoting brain melanoma metastasis through enhancing cellular interactions with surrounding niche …

Glioblastoma Mimicking Viral Encephalitis Responds To Acyclovir: A Case Series And Literature Review., Keenan J Piper, Haidn Foster, Brandon Gabel, Burt Nabors, Charles Cobbs

Articles, Abstracts, and Reports

Viral encephalitis and glioblastoma are both relatively rare conditions with poor prognoses. While the clinical and radiographic presentations of these diseases are often distinctly different, viral encephalitis can sometimes masquerade as glioblastoma. Rarely, glioblastoma can also be misdiagnosed as viral encephalitis. In some cases where a high-grade glioma was initially diagnosed as viral encephalitis, antiviral administration has proven effective for relieving early symptoms. We present three cases in which patients presented with symptoms and radiographic findings suggestive of viral encephalitis and experienced dramatic clinical improvement following treatment with acyclovir, only to later be diagnosed with glioblastoma in the region of …

Serum Amyloid A And Janus Kinase 2 In A Mouse Model Of Diabetic Kidney Disease., Brad P Dieter, Rick L Meek, Robert J Anderberg, Sheryl K Cooney, Jen L Bergin, Hongyu Zhang, Viji Nair, Matthias Kretzler, Frank C Brosius, Katherine Tuttle

Articles, Abstracts, and Reports

BACKGROUND: Serum amyloid A (SAA), a potent inflammatory mediator, and Janus kinase 2 (JAK2), an intracellular signaling kinase, are increased by diabetes. The aims were to elucidate: 1) a JAK2-mediated pathway for increased SAA in the kidneys of diabetic mice; 2) a JAK2-SAA pathway for inflammation in podocytes.

METHODS: Akita diabetic mice (129S6) with podocyte JAK2 overexpression and angiotensin II infusion (4 weeks) were given a JAK1,2 inhibitor (LY03103801, 3 mg/kg/day orally for the last two weeks). Kidneys were immunostained for SAA isoform 3 (SAA3). SAA3 knockout and control mouse podocytes were exposed to advanced glycation end products (AGE) or …

Understanding The Association Between Skin Involvement And Joint Activity In Patients With Psoriatic Arthritis: Experience From The Corrona Registry., Philip Mease, Carol J Etzel, William J Huster, Talia M Muram, April W Armstrong, Jeffrey R Lisse, Sabrina Rebello, Rhiannon Dodge, Mwangi James Murage, Jeffrey D Greenberg, William N Malatestinic

Articles, Abstracts, and Reports

Objective: To compare the characteristics of patients with psoriatic arthritis among patient groups stratified by degree of skin and joint involvement, and to evaluate the relationship between skin severity and joint activity.

Methods: Body surface area (BSA) and Clinical Disease Activity Index (CDAI) at enrolment were analysed. Patient characteristics were stratified by skin severity and joint activity. Baseline patient characteristics, clinical and disease characteristics and patient-reported outcomes were compared. The strength of the relationship of skin severity and joint activity was evaluated using methods for categorical variables (χ

Results: 1542 adult patients in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry enrolled between …

Body Mass Index And Treatment Response To Subcutaneous Abatacept In Patients With Psoriatic Arthritis: A, Iain B Mcinnes, Gianfranco Ferraccioli, Maria-Antonietta D'Agostino, Manuela Le Bars, Subhashis Banerjee, Harris A Ahmad, Yedid Elbez, Philip Mease

Articles, Abstracts, and Reports

Objective: This

Methods: In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly SC abatacept 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients achieving American College of Rheumatology 20% improvement response, Disease Activity Score in 28 joints (DAS28 (C reactive protein (CRP))) ≤3.6 and

Results: Of 212/213 and 210/211 patients with baseline BMI data in the abatacept and placebo groups, respectively, 15% and 19% were underweight/normal, 36% and 27% were overweight, and 49% and 54% were obese. After adjusting for baseline characteristics, there were no significant …

Alkylaminophenol Induces G1/S Phase Cell Cycle Arrest In Glioblastoma Cells Through P53 And Cyclin-Dependent Kinase Signaling Pathway., Phuong Doan, Aliyu Musa, Nuno R Candeias, Frank Emmert-Streib, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. We show here that small molecule 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), a potential anticancer agent, increases the human glioblastoma cell death. Its mechanism of action and the interaction of selective signaling pathways remain elusive. Three structurally related phenolic compounds were tested in multiple glioma cell lines in which the potential activity of the compound, THTMP, was further validated and characterized. Upon prolonged exposer to THTMP, all glioma cell lines undergo p53 and cyclin-dependent kinase mediated cell death with the IC