tbuckley/cabot-search huggingface dataset:
Orally Delivered Antisense Oligodeoxyribonucleotides of TNF‐α via Polysaccharide‐Based Nanocomposites Targeting Intestinal Inflammation
Authors: Bingchao Duan, Mengxia Li, Ying Sun, Siwei Zou, Xiaojuan Xu
Journal: Advanced Healthcare Materials (2019)

Abstract Tumor necrosis factor alpha (TNF‐α) is usually regarded as a potential target for inflammatory bowel disease therapy. Herein, a promising strategy for effective delivery of phosphorothioated antisense oligodeoxyribonucleotide of TNF‐α (PS‐ATNF‐α), targeting the intestinal inflammation based on the interaction of the single chain of triple helical β‐glucan (s‐LNT) with poly‐deoxyadenylic acid [poly(dA)], and the colon‐specific degradation of chitosan‐alginate (CA) hydrogel, is reported. The target gene of PS‐ATNF‐α, with a poly(dA) tail through a disulfide bond (–SS–), interacts with s‐LNT to form a rod‐like nanocomposite of s‐LNT/poly(dA)–SS–PS‐ATNF‐α, which significantly inhibits lipopolysaccharide (LPS)‐induced TNF‐α at the protein level by 38.2% and mRNA level by 48.9% in RAW264.7 macrophages. The nanocomposites carried by the CA hydrogel with the loading amount of 83.5% are then orally administered and specifically released to the inflamed intestine, followed by internalization into intestinal cells such as macrophages, to reduce TNF‐α production by 36.4% and dextran sulfate sodium‐induced inflammation by decreasing myeloperoxidase and malondialdehyde. This study defines a new strategy for the oral delivery of antisense oligonucleotides to attenuate inflammatory response, demonstrating a notable potential for clinical applications in intestine‐inflammation‐targeted therapy.
A New Prediction System for Platelet Recovery after Autologous Stem Cell Transplantation in B-Cell Non-Hodgkin Lymphomas
Authors: Junko Yamaguchi, Yoshiaki Chinen, Hitoji Uchiyama, Nobuhiko Uoshima, Hiroto Kaneko, Mitsushige Nakao, Taku Tsukamoto, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Junya Kuroda
Journal: Blood (2018)
Gastric pH Modulation Increases Risk For Subsequent Prescription Of Anti-allergy Medication: Evidence From A Nationwide Cross-sectional Study
Authors: Erika Jensen-Jarolim, Michael Kundi, Eva Untersmayr, Isabella Pali-Schoell, Berthold Reichardt, Galateja Jordakieva
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 10336: Attenuation of Left Ventricular Fibrosis by Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo Controlled, Double Blind Study
Authors: Yuichi J Shimada, Jonathan J Passeri, Aaron L Baggish, Caitlin O’Callaghan, Patricia A Lowry, Gia Yannekis, Suhny Abbara, Brian B Ghoshhajra, Richard D Rothman, Carolyn Y Ho, James L Januzzi, Christine E Seidman, Michael A Fifer
Journal: Circulation (2013)

Introduction: Despite evidence that left ventricular (LV) hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in hypertrophic cardiomyo...
Abstract 15300: Increase in Comfortable Walking Speed During Hospitalization Predicts the Readmission Due to Decompensated Heart Failure in Elderly Patients With Chronic Heart Failure
Authors: Minoru Tabata, Michitaka Kato, Akiko Akiyama, Shinya Tanaka, Nobuaki Hamazaki, Takashi Masusa
Journal: Circulation (2017)

Background: Patients with chronic heart failure (CHF) are frequently readmitted to the hospital. Walking speed is a clinical measure to assess patients’ exercise capacity and prognosis. However, few reports documented the relations of comfortable walking speed (CWS) during hospitalization to exercise capacity and prognosis. Purpose: This study aimed to investigate whether the increase in comfortable walking speed during hospitalization (ΔCWS) predicted the readmission due to CHF in elderly CHF patients. Methods: Patients who were hospitalized due to decompensated CHF were prospectively followed up for 2 years after hospital discharge. We assessed clinical characteristics including etiology of CHF, brain natriuretic peptide and left ventricular function on admission, and measured patients’ CWS a few days after admission and at discharge. Consequently, we studied 252 patients aged 73.6 ± 8.3 years (164 males and 88 females). Significant factors affecting the readmission and their cut-off values were determi...
Losing Vision and Gaining Perspective
Authors: Bonnielin Swenor
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inactivation of Apoptosis Antagonizing Transcription Factor in tubular epithelial cells induces accumulation of DNA damage and nephronophthisis
Authors: Manaswita Jain, Rainer W.J. Kaiser, Katrin Bohl, Martin Hoehne, Heike Göbel, Malte P. Bartram, Sandra Habbig, Roman-Ulrich Müller, Agnes B. Fogo, Thomas Benzing, Bernhard Schermer, Katja Höpker, Gisela G. Slaats
Journal: Kidney International (2019)
The National Cancer Institute Clinical Trials Planning Meeting for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy
Authors: Susan G Dorsey, Ian R Kleckner, Debra Barton, Karen Mustian, Ann O’Mara, Diane St. Germain, Guido Cavaletti, Suzanne C Danhauer, Dawn L Hershman, Andrea G Hohmann, Ahmet Hoke, Judith O Hopkins, Katherine P Kelly, Charles L Loprinzi, Howard L McLeod, Supriya Mohile, Judith Paice, Julia H Rowland, Daniela Salvemini, Rosalind A Segal, Ellen Lavoie Smith, Worta McCaskill Stevens, Michelle C Janelsins
Journal: JNCI Journal of the National Cancer Institute (2019)

Although recent scientific advances have improved our understanding of basic biological mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN), few interventions are available to prevent or treat CIPN. Although some biological targets from preclinical studies show promise in nonhuman animal models, few targets have been translated to successful clinical trials. To address this problem, the National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee convened a meeting of experts in the CIPN and oncology symptom management fields to participate in a Clinical Trials Planning Meeting (CTPM). Investigators presented data from preclinical and translational studies for possible CIPN interventions; these were evaluated for readiness of randomized clinical trial testing by experts, and recommendations were provided. Breakout sessions were convened to discuss and develop future studies. The CTPM experts concluded that there is compelling evidence to move forward with selected pharmacological and nonpharmacological clinical trials for the prevention and treatment of CIPN. Several key feasibility issues need to be addressed, however. These include identification of optimal outcome measures to define the CIPN phenotype, establishment of parameters that guide the evaluation of clinically meaningful effects, and adoption of approaches for inclusion of translational and biomarker and/or genetic measures. The results of the CTPM provide support for conducting clinical trials that include both pharmacological and nonpharmacological approaches, alone or in combination, with biomarkers, genetics, or other measures designed to inform underlying CIPN mechanisms. Several working groups were formed to design rigorous CIPN clinical trials, the results of which are ongoing.
APOE4-mediated amyloid-β pathology depends on its neuronal receptor LRP1
Authors: Masaya Tachibana, Marie-Louise Holm, Chia-Chen Liu, Mitsuru Shinohara, Tomonori Aikawa, Hiroshi Oue, Yu Yamazaki, Yuka A. Martens, Melissa E. Murray, Patrick M. Sullivan, Kathrin Weyer, Simon Glerup, Dennis W. Dickson, Guojun Bu, Takahisa Kanekiyo
Journal: Journal of Clinical Investigation (2019)

Carrying the ε4 allele of the APOE gene encoding apolipoprotein E (APOE4) markedly increases the risk for late-onset Alzheimer's disease (AD), in which APOE4 exacerbates the brain accumulation and subsequent deposition of amyloid-β (Aβ) peptides. While the LDL receptor-related protein 1 (LRP1) is a major apoE receptor in the brain, we found that its levels are associated with those of insoluble Aβ depending on APOE genotype status in postmortem AD brains. Thus, to determine the functional interaction of apoE4 and LRP1 in brain Aβ metabolism, we crossed neuronal LRP1-knockout mice with amyloid model APP/PS1 mice and APOE3-targeted replacement (APO3-TR) or APOE4-TR mice. Consistent with previous findings, mice expressing apoE4 had increased Aβ deposition and insoluble amounts of Aβ40 and Aβ42 in the hippocampus of APP/PS1 mice compared with those expressing apoE3. Intriguingly, such effects were reversed in the absence of neuronal LRP1. Neuronal LRP1 deficiency also increased detergent-soluble apoE4 levels, which may contribute to the inhibition of Aβ deposition. Together, our results suggest that apoE4 exacerbates Aβ pathology through a mechanism that depends on neuronal LRP1. A better understanding of apoE isoform-specific interaction with their metabolic receptor LRP1 on Aβ metabolism is crucial for defining APOE4-related risk for AD.
Abstract 20432: Soluble Endoglin is an Independent Predictor of Blood Pressure Response to Hemodynamic Stress in Young Adults
Authors: Ashley Verburg, Wilby Williamson, Odaro J Huckstep, Grace Z Yu, Afifah Mohamed, Charlotte Herdman, Polly Whitworth, Paul Leeson, Adam J Lewandowski
Journal: Circulation (2017)

Background: Soluble endoglin (sENG) has been implicated in the abnormal blood pressure response that occurs in mothers who develop preeclampsia on exposure to the hemodynamic stress of pregnancy. E...
Molecular analysis of advanced colorectal cancer in an ethnically diverse patient population at a single institution.
Authors: Nadia Ashai, Mateo Mejia Saldarriaga, Devika Rao, Matthew Stuart, Wei Zhang, Sanjay Goel, Balazs Halmos, Lakshmi Rajdev
Journal: Journal of Clinical Oncology (2019)

702 Background: CRC survival and treatment response differences have been noted across racial and ethnic groups, particularly between Hispanics (HA), non-Hispanic AA (AA), and non-Hispanic Caucasian (CA). We examined if there are differences in molecular drivers between these groups that could explain such differences in our diverse medical center. Methods: We retrospectively examined 361 HA, AA, CA patients at Montefiore Medical Center diagnosed with metastatic CRC (mCRC) from 2007 to 2018. Mismatch repair proficiency (MMR-P), deficiency (MMR-D) was determined by immunohistochemistry. KRAS, NRAS, BRAF were determined by polymerase chain reaction or next generation sequencing. Mutations were then correlated with overall survival (OS). Results: Across subgroups, there was no differences in MMR, KRAS, NRAS, BRAF incidence (Table). Using a univariate analysis, the median survival for RAS mutated (M) patients was 33 months (ms), compared to 69 ms for RAS wild-type (WT, p = 0.01). The median OS for RAS mutated HA patients was 41 ms, compared to 41 ms and 33 ms for CA and AA respectively (p = 0.14). There was also no statistically significant difference between median OS for RAS WT HA patients (69 ms), compared to AA patients (51 ms) and CA (not reached, p = 0.75). Conclusions: In our single institution study, we found no difference in incidence of RAS (KRAS and NRAS), BRAF, MMR amongst HA, AA, and CA. Delivery of uniform care may account for similar OS outcomes in our patient population. RAS WT and M disease had improved OS compared to previously established rates in the literature. Additional studies are needed to evaluate known differences in treatment response and survival in minority populations. [Table: see text]
Author Correction: Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors
Authors: Pakawat Chongsathidkiet, Christina Jackson, Shohei Koyama, Franziska Loebel, Xiuyu Cui, S. Harrison Farber, Karolina Woroniecka, Aladine A. Elsamadicy, Cosette A. Dechant, Hanna R. Kemeny, Luis Sanchez-Perez, Tooba A. Cheema, Nicholas C. Souders, James E. Herndon, Jean-Valery Coumans, Jeffrey I. Everitt, Brian V. Nahed, John H. Sampson, Michael D. Gunn, Robert L. Martuza, Glenn Dranoff, William T. Curry, Peter E. Fecci
Journal: Nature Medicine (2019)
Molecular characterization of AML with <i>RUNX1‐RUNX1T1</i> at diagnosis and relapse reveals net loss of co‐mutations
Authors: Alexander Höllein, Niroshan Nadarajah, Manja Meggendorfer, Sabine Jeromin, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach
Journal: HemaSphere (2019)

AML with RUNX1-RUNX1T1 fusion is a WHO entity with a favorable outcome following intensive chemotherapy. The absence of RUNX1-RUNX1T1 transcripts in remission defines complete molecular response and correlates with a superior survival. However, a significant proportion of patients still relapses and defining molecular risk factors that identify patients at diagnosis or at molecular remission that are at risk of relapse could help tailor treatment strategies for those high risk patients. Here, we analyze a cohort of 94 patients that reach a molecular remission (MR) following intensive treatment and identify 21 patients that relapse despite achieving MR. Using targeted sequencing of 63 genes implicated in hematologic malignancies we show that at diagnosis patients who relapse following MR have a higher burden of co-mutated genes than patients that do not relapse (median = 2 vs median = 0; P = 0.0156). This resulted in a relapse free survival rate of 65% vs 86% at 2 years, respectively (≥1 co-mutation vs no co-mutation, P = 0.02) with a trend for inferior overall survival (n.s.). Applying sensitive sequencing to reassess mutations at relapse in paired samples of 17/21 patients we demonstrate a net loss of co-mutations at relapse: median 2 (range 0-5) vs 1 (0-4) at diagnosis and relapse (P = 0.048). At relapse more patients had no detected co-mutation compared to diagnosis (47% vs 17%, P = 0.034). Co-mutations at diagnosis, therefore, might represent a general susceptibility of the AML clone to acquire mutations and the true nature of 2nd hit mutations that drive leukemia has to be defined for AML with RUNX1-RUNX1T1 fusion.
Abstract 20703: Caloric Restriction Increases the Resistance of Aged Heart to Myocardial Ischemia/Reperfusion Injury via Modulating AMPK-SIRT1 Signaling Pathway
Authors: Zhijia Guo, Thomas Rousselle, Chelsea Luckett, Courtney Cates, Ji Li
Journal: Circulation (2017)

Introduction: Ischemic tolerance of heart decreases with age and many cardio protective interventions including percutaneous coronary intervention (PCI) and post-conditioning are less effective in ...
Clinical impact of preoperative biliary drainage on postoperataive complications in pancreaticoduodenectomy.
Authors: Hirohisa Okabe
Journal: Journal of Clinical Oncology (2019)

302 Background: Biliary drainage is sometimes necessary for patients undergoing pancreaticoduodenectomy (PD) because of tumor invasion to the biliary tract. The current study aims to explore the clinical impact of preoperative biliary drainage (PBD) on postoperative complication in PD. Methods: One hundred sixty-six patients who underwent PD from 2012–2017 were enrolled in this study. Clinical impact of PBD on clinical course was examined. Results: There were 66 patients (40%) undergoing PBD. Patients with PBD showed significantly higher infection rate of bile juice collected at surgery (p &lt; 0.0001) and contamination rate of ascites collected from intraperitoneal drain on postoperative day 3 (POD3) (p &lt; 0.0001) than patients without PBD. Severe postoperative complication (Clavien Dindo ≥ IIIB)was associated with contaminated ascites on POD3 (p = 0.031), but not with PBD. Among patients with PBD, fifty-two patients (79%) received preoperative ERBD. Infection of bile juice at surgery was not associated with the procedure of PBD (ERBD, ENBD or PTCD), but correlated with the duration of drainage. Receiver operating characteristic analysis revealed that patients with PBD for more than 28 days occurs contamination of bile juice at surgery. Among patients with both the contaminated bile juice at operation and the contaminated ascites on POD3 (n = 24), both were consistent in 19 patients (79%). Although Enterococcus faecalis was the most species seen in their bile juice, patients with the contamination of other species of Enterobacter (36%) and Streptococcus (2%) showed higher severe postoperative complication rate than others (p = 0.049). Conclusions: PBD was not directly associated with severe postoperative complication, but the duration of drainage for &gt; 28 days was correlated with contamination of the bile juice. Contaminated ascites on POD3 caused by infectious bile juice at surgery was an only factor associated with severe postoperative complications and therefore needs careful management of the drain removal and selection of antibiotics after surgery.
Computational and comparative molecular docking studies of the interactions of lavendamycin analogues with NAD(P)H:quinone oxidoreductase 1 (NQO1)
Authors: Mary Hassani, David C. Holley, Wen Cai, John M. Gerdes, Mohammad Behforouz, Howard D. Beall
Journal: Cancer Research (2005)

4823  NAD(P)H:quinone oxidoreductase 1 (NQO1) is a homodimeric flavoenzyme containing 273 residues and one molecule of FAD per monomer. This reductase catalyzes a NAD(P)H-dependent two-electron reduction and the bioactivation of many antitumor bioreductive agents. NQO1, expressed at high levels in many human solid tumors, can be used as a unique target for enzyme directed bioreductive cancer drug development. Lavendamycin, a quinolinedione antibiotic with significant antitumor activity, is structurally related to streptonigrin, a good substrate for and efficiently bioactivated by NQO1. Computational molecular modeling studies were performed on two lavendamycin analogues, MB-353 and -323, very good and poor substrates for NQO1, respectively. The molecular docking was performed using the FlexX module of SYBYL6.9.1. The minimized coordinates of the crystal structure of the NQO1 complex with ARH019, an indolequinone, obtained from the Protein Data Bank (ID code: 1H69) was used as a reference structure for docking experiments. The docked conformations of ligands were evaluated using the FlexX and CSCORE modules in SYBYL. CSCORE is the consensus score computed from FlexX, ChemScore, D-Score, G-Score and PMF-Score scoring functions where docked poses are ranked from 1 to 5; where 5 is the best fit to the model. Geometric post-analysis strategies that determine hydrogen-bonding interactions of the ligands with the key residues of the active site (Tyr 126, 128 and His 161), hydride ion transfer from the flavin to the ligands, and the angle between the planes of the ligands and the flavin were performed. Of 30 possible docked conformations of MB-353, 24 poses had orientations similar to the reference ligand (ARH019) and 19 had CSCORE ≥ 4 (4 with CSCORE = 5 and 15 with CSCORE = 4). All of the 19 poses were capable of forming the hydrogen-bonding interactions and hydride ion transfer, and the departure of their planes from an exact aromatic parallel stacking with the flavin closely resembled that of ARH019. However, of 30 possible docked poses of MB-323, no conformation had a CSCORE = 5 and only 4 poses had CSCORE = 4. The remaining poses with CSCOREs of 0 and 1 did not merit further considerations. Also, none of the 30 poses had orientations similar to the reference ligand. Therefore, an increased number of possible conformations of ligand MB-353 with acceptable orientations compared to ligand MB-323 can be considered as a potential contributing factor to substrate specificity. Supported by NIH grants R15 CA78232 and NCRR P20 RR15583.
Incidence patterns of neuroendocrine neoplasms in California.
Authors: Alan Paciorek, Brandon Shih, Meg McKinley, Iona Cheng, Li Zhang, Claire Mulvey, Ann Griffin, Katherine Van Loon, Emily K. Bergsland
Journal: Journal of Clinical Oncology (2019)

242 Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that typically account for &lt; 5% of tumors arising in any organ site. Both the low incidence and heterogeneity contribute to the paucity of epidemiologic data regarding risk factors. However, evidence suggests that incidence rates in the U.S. are rising. We aimed to further characterize the burden of NENs in California. Methods: Using data from the California Cancer Registry (CCR), we identified all newly diagnosed NENs arising from pulmonary (including SCLC) and gastrointestinal (GI) sites from 1992-2015. We estimated age-adjusted incidence rates (AIR) standardized to the 2000 U.S. census population. We calculated annual percent change (APC) in AIRs using Joinpoint regression and compared AIRs by sex, race-ethnicity, primary tumor site, and county of residence categorized as urban, suburban or rural using SEER∗Stat. Results: From 1992-2015, 97,398 NENs were reported, with 40,099 GI (not lung or bronchus). Overall AIR was 12.5 per 100,000 person-years. Most NENs were of pulmonary (AIR 7.6) or colorectal (AIR 1.3) origin. Females had lower AIR with IR ratio (IRR) vs. males (0.80 95% CI 0.79-0.81). However, females had higher rates of gastric (IRR 1.22 95% CI 1.12-1.32) and appendiceal (IRR 1.19 95% CI 1.07-1.33) primaries vs. males. Compared to non-Hispanic (NH) whites, NH blacks had an IRR of 1.06 (95% CI 1.03-1.09), Asian/Pacific Islanders had an IRR of 0.46 (95% CI 0.45-0.48), and Hispanics had an IRR of 0.57 (95% CI 0.56-0.58). For all NEN subtypes, we estimated lower rates for residents of urban counties (IRR 0.83 95% CI 0.80-0.86) and suburban counties (IRR 0.94 95% CI 0.90-0.97) vs. rural counties. However for GI NENs, we estimated higher rates for residents of suburban counties (IRR 1.11 95% CI 1.03-1.18) and urban counties (IRR 1.10 95% CI 1.03-1.18) vs. rural counties. We found that rates of pulmonary NENs decreased since 1992 (APC -2.6), but rates increased in colorectal (APC 3.9) and all other GI primaries (all APCs ≥ 2.8). Conclusions: Based on these results we conclude that incidence rates for GI NENs reported to CCR steadily increased from 1992-2015. Residence in a suburban or urban county was associated with increased incidence of GI NENs. Additional analyses are ongoing.