tbuckley/cabot-search huggingface dataset:
Gene Editing: A New Tool for Viral Disease
Authors: Edward M. Kennedy, Bryan R. Cullen
Journal: Annual Review of Medicine (2016)

The emergence of the CRISPR/Cas system of antiviral adaptive immunity in bacteria as a facile system for gene editing in mammalian cells may well lead to gene editing becoming a novel treatment for a range of human diseases, especially those caused by deleterious germline mutations. Another potential target for gene editing are DNA viruses that cause chronic pathogenic diseases that cannot be cured by using currently available drugs. We review the current state of this field and discuss the potential advantages and problems with using a gene editing approach as a treatment for diseases caused by DNA viruses.
Case 28-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Denise J. Strieder, Gerald Nash
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 48-year-old woman was admitted to the hospital because of dyspnea.She had been well until three years previously, when she began to experience mild exertional dyspnea; a physician found hypertension and prescribed furosemide. Six months before admission the dyspnea increased in severity. Two months before entry there was the onset of occasional dyspnea at rest, associated with an intermittent low-grade fever and a nonproductive cough. Her physician reported that her blood pressure was normal, and furosemide was omitted. One month later the dyspnea at rest became persistent, and she ceased work and remained in bed at . . .
Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials.
Authors: Olivia Pagani, Meredith M. Regan, Barbara Walley, Gini F. Fleming, Marco Colleoni, Istvan Lang, Henry Leonidas Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Herve R. Bonnefoi, Silvana Martino, Charles E. Geyer, Manuela Rabaglio-Poretti, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis
Journal: Journal of Clinical Oncology (2014)

LBA1 Background: Adjuvant endocrine therapy with AI vs T improves outcomes in postmenopausal HR+ BC. TEXT and SOFT were designed to test whether adjuvant AI improves outcomes in premenopausal women with HR+ BC treated with OFS (AI question) and to determine the value of OFS in women who remain premenopausal and are suitable for adjuvant T (OFS question). Methods: TEXT and SOFT, randomized phase 3 trials, enrolled 5,738 premenopausal women with HR+ early BC from Nov03 to Apr11 (2672 TEXT; 3066 SOFT). TEXT randomized women within 12wk of surgery to 5y E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5y E+OFS vs T+OFS vs T alone, either within 12wk of surgery if no CT planned, or within 8mo of completing (neo)adjuvant CT. OFS was by choice of 5y triptorelin, oophorectomy, or ovarian irradiation. The primary endpoint is disease-free survival (DFS: randomization until invasive local, regional, distant recurrence, or contralateral breast; 2nd malignancy; death). Due to low event rates, protocol amendments in 2011 changed the analysis plans to answer the AI question (E+OFS vs T+OFS) by joint analysis of TEXT and SOFT. By Q3’2013 with &gt;5y median follow-up, 436 DFS events were projected, providing 84% power for HR=0.75 with E+OFS vs T+OFS (stratified logrank 2-sided α=0.05). Results: At 5.7y median follow-up, 514 (11%) DFS events were reported in the ITT population comparing E+OFS (n=2346) vs T+OFS (n=2344). Patients assigned E+OFS had significantly reduced DFS hazard (HR=0.72; 95% CI, 0.60-0.86; P=0.0002) vs T+OFS; 5y DFS was 91.1% vs 87.3%. Reductions were similar for secondary endpoints of BC-free interval (HR=0.66 (0.55-0.80) 5y BCFI 92.8% vs 88.8%) and distant recurrence-free interval (HR=0.78 (0.62-0.97)), though not overall survival (HR=1.14 (0.86-1.51)) at this early follow-up (194 (4%) deaths). Grade 3-4 targeted AEs were reported in 31% E+OFS vs 29% T+OFS patients. Conclusion: In premenopausal women with HR+ BC, adjuvant treatment with E+OFS significantly reduced the risk of recurrence compared to T+OFS. Clinical trial information: NCT00066703 / NCT00066690 .
CATCH: A randomized trial comparing tinzaparin versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients.
Authors: Agnes Y. Lee, Rupert Bauersachs, Mette S. Janas, Mikala F. Jarner, Pieter W Kamphuisen, Guy Meyer, Luis Paz-Ares, Alok A. Khorana
Journal: Journal of Clinical Oncology (2012)

TPS9149^ Background: VTE is a major cause of morbidity and mortality in cancer patients. LMWHs have been shown to be superior to warfarin in one randomized study, but adequately powered confirmatory studies have not been conducted and warfarin continues to be widely used for treatment of cancer-associated VTE. Methods: We are conducting an open-label, randomized trial of tinzaparin versus warfarin in 900 patients with active cancer and symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Tinzaparin is given at full treatment doses (175 IU/kg once daily) for 6 months in the experimental arm and initial tinzaparin treatment for 5-10 days followed by dose-adjusted warfarin (target INR 2.0-3.0) is given for 6 months in the control arm. The primary composite outcome is time to recurrent VTE event, including incidentally diagnosed VTE and fatal PE. Baseline characteristics will be analysed for their ability to predict the risk for recurrent VTE or bleeding. In particular, the parameters of the Khorana scale and Wells rule will be tested for their usefulness in predicting recurrent VTE. Predictive biomarkers will be tested including D-dimer and Tissue Factor. Assessment of post-thrombotic syndrome (PTS), quality of life and healthcare resource utilization will also be performed. The trial is recruiting in &gt; 160 sites in &gt;25 countries in 4 continents (NCT01130025). As of Jan 2012, 135 sites were activated for study enrolment and 228 patients have been enrolled. We anticipate completion of enrolment in Jan 2013. The results obtained from this study will add significantly to the knowledge on the efficacy, safety and cost-effectiveness of LMWH to prevent recurrent VTE. Important prospective data on the clinical significance of incidental VTE in patients with active cancer will be generated, and analyses of risk stratification parameters will add important information that may help to further tailor therapy. The study of PTS, which has not previously been done in this selected patient population, will add to the evidence that tinzaparin significantly reduces the incidence of PTS and leg ulcers (Hull et al, Am J Med 2009;122:762-9).
Lenalidomide Inhibits Proliferation Of Chronic Lymphocytic Leukemia Cells Via a Cereblon/p21WAF1/Cip1-Dependent Mechanism
Authors: Jessie-Farah Fecteau, Laura G Corral, Diahnn Futalan, Svetlana Gaidarova, Ila Bharati, Brian Cathers, Emanuela M. Ghia, Maria Schwaederlé, Antonia Lopez-Girona, Davorka Messmer, Thomas J. Kipps
Journal: Blood (2013)
A Highly Sensitive Molecular Detection Platform for Robust and Facile Diagnosis of Middle East Respiratory Syndrome (MERS) Corona Virus
Authors: Il Young Jung, Jae Bem You, Bo Ram Choi, Ji Su Kim, Hyun Kyung Lee, Bora Jang, Han Saem Jeong, Kyuri Lee, Sung Gap Im, Hyukjin Lee
Journal: Advanced Healthcare Materials (2016)

Trail polymerization enables a significant enhancement of the DhITACT system. DhITACT-Trail (DNA hydrogel formation by isothermal amplification of complementary targets trail polymerization) offers a robust diagnosis of target RNA strands in pseudo-serum specimen. This system requires minimum liquid handling as compared to conventional analysis. In addition, a definitive diagnostic result can be achieved within 30 min by an optical detection. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
P2-014: Single nucleotide polymorphisms of Pim-1 in Korean lung cancer patients
Authors: Jun Seok Jung, Sle Gi Lo Han, Uk Hyun Jo, Won Beak Yoo, Hyo Seon Choi, Jae Sook Sung, Hyo Jung Lee, Jae Won Lee, Jun Suk Kim, Yeul Hong Kim
Journal: Journal of Thoracic Oncology (2007)
miRNA analysis between malignant and benign tissue and circulating exosomes (CE) in patients (pts) with tongue squamous cell carcinoma.
Authors: Guilherme Rabinowits, Ludmila Flores, Anne M. O'Neill, Kristen Stevenson, Irene M. Ghobrial, Victoria Vergara, Vickie Y Jo, Sigitas Jonas Verselis, Nicole Grace Chau, Jochen H. Lorch, Robert I. Haddad
Journal: Journal of Clinical Oncology (2013)

6088 Background: The identification of a specific miRNA pattern in HNSCC is challenging given the heterogeneity of this disease and different methodologies used in prior studies. Here we chose to group pts according to primary tumor location and used Nanostring as a larger miRNA platform. Methods: CE-miRNA was isolated from 500ul of plasma collected in Heparin/EDTA tubes. Samples were pretreated with Pacific Hemostasis Thromboplastin D. Supernatant was treated with ExoQuick. Exosomal pellet was resuspended in 1ml of QIAzol Lysis Reagent. Formalin fixed paraffin embedded (FFPE) samples were deparaffinized and digested with proteinase K. miRNA from plasma and FFPE were isolated with miRNeasy Mini Kit. Samples were processed by Nanostring Technology. In this analysis, only tongue cancer pts were selected due to availability of paired tumor and benign tissue miRNA in conjunction with CE from the same pts and others with tongue cancer. Results: 21 HNSCC pts and 32 age-matched controls have enrolled to date. For homogeneity we analyzed only patients with tongue cancer (n=9): 8 males, median age 55.5 years (range 24-64), all had stage IVA tongue cancer (6 base of tongue), 6 HPV/p16 positive. Nine pts received chemoradiation; 4 also had surgery; 8 had clinical and radiological complete response. Of the 800 miRNAs tested 62 were overexpressed and 15 were suppressed in the tumor compared to benign tissue in the same pts. Of those overexpressed and suppressed in tumor tissue, 4 (miR23a-3p; miR150-5p; miR199a-5p; miR203) had a post/pre treatment average ratio (PPTAR) less than 1, while 4 (miR720; miR1253; miR145-5p; miR1283) had PPTAR greater than 1, respectively on CE of pts. miR150-5p was suppressed and miR1283, miR145-5p and miR1253 were overexpressed on CE of control samples compared to pre treatment samples of pts. Conclusions: Of the 800 miRNAs, 8 appear to correlate with treatment response. The average levels of 4 of those miRNA mirror the average levels of tumor tissue miRNA and is in an inverse relationship with benign tissue and control blood samples, suggesting this may be a unique signature for tongue cancer. This observation needs to be validated in larger studies.
Submucosal tunneling endoscopic resection for multiple esophageal leiomyomas
Authors: Yuyong Tan, Changmei Hu, Yuqian Zhou, Yi Chu, Jirong Huo, Deliang Liu
Journal: Endoscopy (2016)

A 61-year-old man presented for treatment of esophageal submucosal tumors (SMTs). The SMTs had been found 1 month previously at his local hospital during a health examination. Upon presentation, his physical examination and laboratory tests were unremarkable. Esophagogastroduodenoscopy (EGD) revealed two protruded lesions in the middle of the esophagus ([Fig. 1]; [Video 1]). Endoscopic ultrasonography (EUS) revealed that the tumors were originating from the muscularis propria layer ([Fig. 2]). Computed omography (CT) also showed the lesions in the mid-esophagus, which were suspected to be benign tumors ([Fig. 3]; [Video 2]).
Feasibility and Safety of RNA-transfected CD20-specific Chimeric Antigen Receptor T Cells in Dogs with Spontaneous B Cell Lymphoma
Authors: M Kazim Panjwani, Jenessa B Smith, Keith Schutsky, Josephine Gnanandarajah, Colleen M O'Connor, Daniel J Powell, Nicola J Mason
Journal: Molecular Therapy (2016)

Preclinical murine models of chimeric antigen receptor (CAR) T cell therapy are widely applied, but are greatly limited by their inability to model the complex human tumor microenvironment and adequately predict safety and efficacy in patients. We therefore sought to develop a system that would enable us to evaluate CAR T cell therapies in dogs with spontaneous cancers. We developed an expansion methodology that yields large numbers of canine T cells from normal or lymphoma-diseased dogs. mRNA electroporation was utilized to express a first-generation canine CD20-specific CAR in expanded T cells. The canine CD20 (cCD20) CAR expression was efficient and transient, and electroporated T cells exhibited antigen-specific interferon-gamma (IFN-γ) secretion and lysed cCD20+ targets. In a first-in-canine study, autologous cCD20-ζ CAR T cells were administered to a dog with relapsed B cell lymphoma. Treatment was well tolerated and led to a modest, but transient, antitumor activity, suggesting that stable CAR expression will be necessary for durable clinical remissions. Our study establishes the methodologies necessary to evaluate CAR T cell therapy in dogs with spontaneous malignancies and lays the foundation for use of outbred canine cancer patients to evaluate the safety and efficacy of next-generation CAR therapies and their optimization prior to translation into humans.
AT <sub>2</sub> Receptor Activation Prevents Sodium Retention and Reduces Blood Pressure in Angiotensin II–Dependent Hypertension
Authors: Brandon A. Kemp, Nancy L. Howell, Susanna R. Keller, John J. Gildea, Shetal H. Padia, Robert M. Carey
Journal: Circulation Research (2016)

Compound 21 (C-21) is a highly selective nonpeptide angiotensin AT2 receptor (AT2R) agonist.To test the hypothesis that chronic AT2R activation with C-21 induces natriuresis via an action at the renal proximal tubule (RPT) and lowers blood pressure (BP) in experimental angiotensin II (Ang II)-dependent hypertension.In rats, Ang II infusion increased both sodium (Na(+)) retention and BP on day 1, and BP remained elevated throughout the 7-day infusion period. Either intrarenal or systemic administration of C-21 prevented Ang II-mediated Na(+) retention on day 1, induced continuously negative cumulative Na(+) balance compared with Ang II alone, and reduced BP chronically. The effects of C-21 are likely to be mediated by action on the RPT as acute systemic C-21-induced natriuresis was additive to that induced by chlorothiazide and amiloride. At 24 hours of Ang II infusion, AT2R activation with C-21, both intrarenally and systemically, translocated AT2Rs from intracellular sites to the apical plasma membranes of RPT cells without altering the total cellular pool of AT2Rs and internalized/inactivated major RPT Na(+) transporters Na(+)-H(+)-exchanger-3 and Na(+)/K(+)ATPase. C-21 lowered BP to a similar degree whether administered before or subsequent to the establishment of Ang II-dependent hypertension.Chronic AT2R activation initiates and sustains receptor translocation to RPT apical plasma membranes, internalizes/inactivates Na(+)-H(+)-exchanger-3 and Na(+)/K(+)ATPase, prevents Na(+) retention resulting in negative cumulative Na(+) balance, and lowers BP in experimental Ang II-induced hypertension. Acting uniquely at the RPT, C-21 is a promising candidate for the treatment of hypertension and Na(+)-retaining states in humans.
Imaging of Esophageal Lymph Node Metastases by Desorption Electrospray Ionization Mass Spectrometry
Authors: Nima Abbassi-Ghadi, Ottmar Golf, Sacheen Kumar, Stefan Antonowicz, James S. McKenzie, Juzheng Huang, Nicole Strittmatter, Hiromi Kudo, Emrys A. Jones, Kirill Veselkov, Robert Goldin, Zoltan Takats, George B. Hanna
Journal: Cancer Research (2016)

Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intraobserver variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes (LN) and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were coregistered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within LNs. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched IHC images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign LN tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 89.5%, 100%, 100%, and 97.2%, respectively, when compared with gold-standard IHC. DESI-MSI has the potential to be a diagnostic tool for perioperative identification of LNM and compares favorably with techniques currently used by histopathology experts. Cancer Res; 76(19); 5647-56. ©2016 AACR.
P0904 : RG-101, A novel GalNAc-conjugated inhibitor of microrna-122, demonstrates significant viral load reduction and reduces liver steatosis in human hepatocyte chimeric mice infected with genotype 1A or hard-to-treat genotype 3A Hepatitis C Virus (HCV)
Authors: S. Neben, K. Liu, J. Tay, N. Chau, Y. Morikawa, B. Bhat, N.W. Gibson
Journal: Journal of Hepatology (2015)
Parent-of-origin-specific signatures of de novo mutations
Authors: Jakob M Goldmann, Wendy S W Wong, Michele Pinelli, Terry Farrah, Dale Bodian, Anna B Stittrich, Gustavo Glusman, Lisenka E L M Vissers, Alexander Hoischen, Jared C Roach, Joseph G Vockley, Joris A Veltman, Benjamin D Solomon, Christian Gilissen, John E Niederhuber
Journal: Nature Genetics (2016)
The Intracellular Distribution of Cathepsin, Benzoylarginine Amidase and Leucine Amidase Activities in Normal Rat Tissues and Primary Rat Hepatoma
Authors: Maver, Mary E., Greco, Antoinette E.
Journal: JNCI Journal of the National Cancer Institute (1951)

Journal Article The Intracellular Distribution of Cathepsin, Benzoylarginine Amidase and Leucine Amidase Activities in Normal Rat Tissues and Primary Rat Hepatoma Get access Mary E. Maver, Mary E. Maver National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Antoinette E. Greco Antoinette E. Greco National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 1, August 1951, Pages 37–48, https://doi.org/10.1093/jnci/12.1.37 Published: 01 August 1951 Article history Received: 27 March 1951 Published: 01 August 1951
GUIDELINES Management of hip fracture in adults: summary of NICE guidance
Authors: Saoussen Ftouh, Antonia Morga, Cameron Swift
Journal: BMJ (2011)

This is one of a series of BMI summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists. Further information about the guidance, a list of members of the guideline development group, and the supportingevidence statements are in the full version on bmj.com. Hip fracture resulting from a fall from standing height or lower in people with osteoporosis or osteopenia (fragil ity fracture) is major, growing health problem associated with population ageing. It has an annual UK incidence of 70-75 000, with a medical and social care cost of about £2bn (€2.3bn; $3.3bn),' and one month and one year mortality of about 10% and 30% respectively2 (usually resulting from comorbidity rather than from the fracture itself). A compre hensive multidisciplinary approach, avoidance of delay, and continuity of management are needed from presentation to follow-up, including after transition from hospital back into the community. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of hip fracture.3 The recommen dations are for all adults but are based on surgical, anaes thetic, and orthogeriatric evidence and expertise acquired among older patients (the group in whom hip fracture is most common). Prevention of hip fracture is covered by other NICE guidance (on falls and osteoporosis5').
Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers
Authors: Laura Breda, Irene Motta, Silvia Lourenco, Chiara Gemmo, Wulan Deng, Jeremy W. Rupon, Osheiza Y. Abdulmalik, Deepa Manwani, Gerd A. Blobel, Stefano Rivella
Journal: Blood (2016)
The value of secondary pathology review.
Authors: Lavinia P Middleton, Tinisha L. Mayo, Tracy E. Spinks, Richard Cheney, Peiguo Chu, Harry S. Cooper, Suzanne Dintzis, Hormoz Ehya, Christopher D. Fletcher, Amy Gerwirtz, Anthony Martin Magliocco, Sue Ellen Martin, Andrew E. Rosenberg, Andy Sherrod, Lee K Tan, Brent L. Wood, Ronald Stewart Walters
Journal: Journal of Clinical Oncology (2016)

6 Background: Improving the value of cancer care is a major focus for the Alliance of Dedicated Cancer Centers (ADCC). Looking to align with the Institute of Medicine’s (IOM) initiative to “Develop and deploy approaches to identify, learn from, and reduce diagnostic errors and near misses in clinical practice,” the ADCC implemented a study to examine the clinical impact of expert secondary pathology review. The goal of this project was to: 1) demonstrate the value of secondary review of outside pathological specimens by ADCC subspecialty pathologists in identifying significant errors that can potentially impact treatment; and 2) create an opportunity to improve patient cancer care. Methods: All consult slides from patients referred to each ADCC center were reviewed by designated pathologists. Patient-level data for original and revised diagnoses were collected for two months in 2014. Discrepancies were classified as: 1) major - diagnosis changes treatment or surveillance; or, 2) minor - diagnosis does not change affect treatment or surveillance. To verify these assessments, disease-specific, multi-center teams of clinical experts reviewed each discrepant case and provided treatment recommendations for the original and revised diagnoses. Results: A total of 13,109 cases were collected across all ADCC centers and the discrepancy rate was 11% (1,488/1309); 3% (359/13,109) were major and 9% (1,129/13,109) were minor. The most common discrepancy was reclassification of the neoplasm cell type. The highest discrepancy rate was shown in the neuro-oncology and head and neck cases, with a 7% and 4% major discrepancy rate respectively. Conclusions: We identified an overall discrepancy rate of 11%, with 3% of cases leading to a change in treatment or surveillance. This demonstrates the importance of expert pathology review and that secondary pathology review can significantly improve clinical outcomes through precise and accurate pathological diagnoses. As indicated in the recent IOM report, this project further demonstrates that “diagnostic errors may cause harm to patients by preventing or delaying appropriate treatment, providing unnecessary or harmful treatment, or resulting in psychological or financial repercussions.”