tbuckley/cabot-search huggingface dataset:
Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation
Authors: Scott D. Solomon, Brian Claggett, Milton Packer, Akshay Desai, Michael R. Zile, Karl Swedberg, Jean Rouleau, Victor Shi, Martin Lefkowitz, John J.V. McMurray
Journal: JACC Heart Failure (2016)

This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability. Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation. Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]). Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality. Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)
Gene Editing: Powerful New Tools for Nephrology Research and Therapy
Authors: Ayano Miyagi, Aiwu Lu, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2016)

Biologic research is experiencing a transformation brought about by the ability of programmable nucleases to manipulate the genome. In the recently developed CRISPR/Cas system, short RNA sequences guide the endonuclease Cas9 to any location in the genome, causing a DNA double–strand break (DSB). Repair of DSBs allows the introduction of targeted genetic manipulations with high precision. Cas9–mediated gene editing is simple, scalable, and rapid, and it can be applied to virtually any organism. Here, we summarize the development of modern gene editing techniques and the biology of DSB repair on which these techniques are based. We discuss technical points in applying this technology and review its use in model organisms. Finally, we describe prospects for the use of gene editing to treat human genetic diseases. This technology offers tremendous promise for equipping the nephrology research community to better model and ultimately, treat kidney diseases.
Collaborative RISC-Score Database: Creation of an International Database for Retroviral Integration Analysis.
Authors: Stephanie Laufs, Frank Giordano, Daniel Lauterborn, K. Zsuzsanna Nagy, Kurt Fellernberg, Agnes Hotz-Wagenblatt, Guillermo Guenechea, Boris Fehse, Juan B. Bueren, Axel Zander, Cynthia E. Dunbar, W. Jens Zeller, Stefan Fruehauf
Journal: Blood (2004)
Systemic antitumor effect and clinical response in a phase 2 trial of intratumoral electroporation of plasmid interleukin-12 in patients with advanced melanoma.
Authors: Adil Daud, Alain Patrick Algazi, Michelle T. Ashworth, Lawrence Fong, Jera Lewis, Stephen E Chan, Michael Buljan, Manuel Alberto Molina, Kathryn Toshimi Takamura, Tuan Tu Diep, Richard Heller, Robert H Pierce, Shailender Bhatia
Journal: Journal of Clinical Oncology (2014)

9025^ Background: Interleukin-12 (IL-12) promotes anti-tumor activity through multiple mechanisms, including augmentation of adaptive and innate immune responses. Intratumoral (IT) delivery of IL-12 via electroporation (EP) avoids systemic toxicity while promoting systemic antitumor immunity. This phase 2 study explores the systemic efficacy, clinical response and safety of IT plasmid IL-12 injection (pIL-12) followed by EP in patients (pts) with advanced melanoma. Methods: This single-arm, open-label phase 2 study plans to enroll 30 pts with in-transit or M1a melanoma. One treatment cycle consists of IT pIL-12-EP on days 1, 5, 8 in up to four lesions per cycle. A maximum of four cycles at 12-week intervals are allowed. ORR was assessed by a modification of RECIST for cutaneous lesions with restaging performed every 12 weeks. The primary endpoint is best ORR within 24 weeks of first treatment. Pre- and post-treatment tumor biopsies were obtained in all patients. Ongoing analyses to assess safety and emerging efficacy data are being utilized to inform future studies. Results: 29 pts have been enrolled and have received at least one treatment cycle. The ORR is 33% (9/27), with 11% CR (3/27). Regression of non-injected lesions was seen in 62% (13/21) of pts with evaluable lesions. Transient pain (56.5%) and inflammation (17.4%) at the treatment site were the most common grade 1/2 drug-related adverse events (AEs), with no grade 3/4 drug-related AEs. Exploratory analyses indicate a doubling of intratumoral NK cells from pre-treatment through day 11 and at day 39, and increased frequency in activated circulating NK cells. Conclusions: Local treatment with pIL-12-EP is well tolerated without severe systemic side effects. Regression of treated and non-treated tumors suggests successful induction of systemic anti-tumor response. Local and systemic increases in NK cells are consistent with the expected pharmacodynamic effect of IL-12. Based on these data, an expansion protocol to evaluate increased treatment frequency is planned for melanoma patients. Clinical trial information: NCT01502293.
A Novel C5 Complement Inhibitor Protects Against Sepsis-Induced Activation of Complement, Coagulation and Inflammation and Provides Survival Benefit in E. coli Sepsis
Authors: Ravi Keshari, Robert Silasi-Mansat, Narcis I. Popescu, Hala Chaaban, Cristina Lupu, Steven J DeMarco, Florea Lupu
Journal: Blood (2014)
Unusual Appearance for Urinary Bladder Obstruction Detected With 99mTc-MDP Bone Scintigraphy
Authors: Chadwick L. Wright, Akash Sharma
Journal: Clinical Nuclear Medicine (2015)

Unanticipated but clinically significant nonosseous findings can be detected during routine bone scintigraphy. We present a case of an 83-year-old man who presented with a pathologic fracture of the right femur. Whole-body bone scintigraphy for osseous staging revealed intense radiotracer accumulation in the kidneys and ureters but no activity within the urinary bladder. The patient had not voided for 14 hours. A Foley catheter was inserted, and more than 2000 mL of urine was drained, most consistent with urinary bladder obstruction. Subsequent repeat images demonstrated marked reduction of the renal and ureteral activity with trace activity in the urinary bladder.
The Danger of Not Treating Parkinson Disease Psychosis—Reply
Authors: Daniel Weintraub, Helen C. Kales, Connie Marras
Journal: JAMA Neurology (2016)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
The Reliability of Frozen Section Diagnosis
Authors: S H Torp, F J Skjørten
Journal: New England Journal of Medicine (1929)

We undertook a retrospective study of 594 consecutive diagnosis by frozen section. Clinically important discrepancies were found between the frozen section and final diagnoses in 18 (3%), and unimportant discrepancies in 35 (6%). The reasons for the discrepancies were misinterpretation in 22 (41%), the presence of focal lesions in 29 (55%), and technical errors in 2 (4%). There were 4 false positive and 18 false negative diagnoses, giving a sensitivity of 93% and a specificity of 99%. Diagnoses from frozen sections were deferred in 40 cases (7%). These results are in accordance with those of similar studies, and confirm that frozen section is a highly accurate, but not infallible, method of rapid histological diagnosis.
Diffuse Idiopathic Skeletal Hyperostosis Is Associated with Lower Lung Volumes in Current and Former Smokers
Authors: Sytse F. Oudkerk, Constantinus F. Buckens, Willem P. T. M. Mali, Harry J. De Koning, F. Cumhur Öner, Rozemarijn Vliegenthart, Esther Pompe, Jan-Willem J. Lammers, Firdaus A. A. Mohamed Hoesein, Jorrit-Jan Verlaan, Pim A. de Jong
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
FEC 60 adjuvant chemotherapy (ACT) in breast cancer (BC) patients (Pts): 5-year and 10-year follow-up results of a Brazilian single center institution
Authors: F. Moura Silva, M. T. Laloni, C. Tosello, A. P. A. P. Bertozzi, M. P. Carvalho, J. C. G. S. Góes
Journal: Journal of Clinical Oncology (2004)

835 Background: To evaluate the influence and the efficacy of the Epirubicin as a part of the FEC60 ACT in operable node positive breast cancer patients in a Brazilian single-center. Methods: We verified retrospectively our experience with FEC 60 as ACT in pre and postmenopausal, node positive, clinical staging II and III women patients with BC. Pts were submitted after surgery to receive Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 every 28 days for 6 cycles. Pts who were ER+ and/or PR+ received Tamoxifen (TMX) 20 mg/day for 5 years after AC. Radiotherapy was also offered at the end of ACT if indicated. All patients were evaluated in terms of 5 year (y) Disease Free Survival (DFS) and Overall Survival (OS). A part of these pts could also be evaluated to 10 year DFS and OS. The most common toxicities (acute and chronic) and metastatic sites will also be reported. Results: Between July 1983 and October 1998 a total of 799 patients (ranging from 22 to 77 years old –median 37.79) were encountered and all of them were evaluated to 5 year (y) DFS and 5 y OS. 335 pts were assessed to 10y DFS and 10y OS. Approximately 63% of these patients received adjuvant TMX. Pts in pre and postmenopausal represented 61% and 39% respectively. The 5y DFS was 54% and the 5y OS after a minimal follow-up of 62.58 months (mo) was 70.9%.The 10y DFS was 47% and the 10y OS after a minimal follow-up of 122.98 mo was 53%. Conclusions: Our 5y follow-up results are similar to those found in randomized studies reported in the literature (NCI-C Ma-5; ICCG; FASG-05) despite of the ACT interval greater than 21 days. Our results also demonstrated that polychemotherapy regimens with Epirubicin are active and well tolerated in the adjuvant treatment for Breast Cancer. Nevertheless, the randomized studies indicate that the greatest anticancer effect of Epirubicin requires doses ranging from 100 to 120 mg/m2. No significant financial relationships to disclose.
Acetazolamide and Invasive Mechanical Ventilation for Patients With COPD—Reply
Authors: Christophe Faisy, Nicholas Heming
Journal: JAMA (2016)

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
Interferons: present and future use in cancer therapy.
Authors: H M Golomb
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.2.123 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2418165 Interferons: present and future use in cancer therapy. H M GolombxH M GolombSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.2.123 First Page PDF © 1986 by American Society of Clinical Oncology
BMA annual meeting: Doctors oppose EU and UK signing transatlantic trade agreement
Authors: Abi Rimmer
Journal: BMJ (2016)

Doctors have said that the European Union and the United Kingdom should not sign the Transatlantic Trade and Investment Partnership (TTIP).

Delegates at the BMA’s annual representatives meeting in Belfast on 20 June voted in favour of a motion saying that the EU (if the UK voted to remain in the EU in the referendum on Thursday 23 June) or the UK (if the referendum resulted in the UK leaving the EU) “should not sign TTIP.” The agreement, which is supposed to promote trade and economic growth, would reduce regulatory barriers to big business, …
Cost-effectiveness analysis of VEGF-A testing to predict response to bevacizumab (BEV) as a component of neo-adjuvant therapy of early HER-2 negative breast cancer
Authors: P.R. Blank, S. Loibl, B.K. Linderholm, S. Caramuta, V. Nekljudova, T.D. Szucs, J. Van Stiphout, Z. Ademi, G. von Minckwitz, M. Schwenkglenks
Journal: Annals of Oncology (2015)
Endoscopic treatment of recurrent sigmoid volvulus with colopexy assisted by T-fasteners and colostomy
Authors: Antonio López-Serrano, Christian Amurrio, Jaime Hervás, Patricia Latorre, Inmaculada Ortiz, Ana Polanco, Eduardo Moreno-Osset
Journal: Endoscopy (2016)

T-fasteners have been used successfully for percutaneous endoscopic sigmoidopexy [1]; however, peritonitis may develop after percutaneous endoscopic sigmoidostomy [2]. We present a patient with recurrent sigmoid volvulus who was treated endoscopically by sigmoidopexy assisted by T-fasteners and sigmoidostomy.
“Unloading shoes” are no better than walking shoes for knee osteoarthritis, trial finds
Authors: Jacqui Wise
Journal: BMJ (2016)

New walking shoes seem to be as effective as specially designed “unloading” shoes for patients with knee osteoarthritis, a randomised controlled trial published in the Annals of Internal Medicine has found.1

Unloading shoes have modified, stiffer soles designed to reposition the foot and reduce the load on the knee. Clinical guidelines for knee osteoarthritis recommend appropriate footwear alongside exercise and weight loss. However, little evidence exists from clinical trials to …
Evaluation of Data Relating Human Leukemia and Ionizing Radiation
Authors: A. W. Kimball
Journal: JNCI Journal of the National Cancer Institute (1958)

The central argument of this paper is a discussion of the statistical reliability of existing data relating human leukemia and ionizing radiation. Conclusions reached by some observers, partly on the basis of statistical techniques having questionable applicability, reveal a confidence in the accuracy of estimated leukemia rates that is difficult to justify. Several sources of error are outlined in detail, and their effect on the use of certain standard statistical methods is illustrated. The conclusion is reached that available data are insufficient to support any conclusion about the shape of the dose-response curve, particularly in the low-dose region.
G‐protein‐coupled bile acid receptor plays a key role in bile acid metabolism and fasting‐induced hepatic steatosis in mice
Authors: Ajay C. Donepudi, Shannon Boehme, Feng Li, John Y.L. Chiang
Journal: Hepatology (2016)

Bile acids are signaling molecules that play a critical role in regulation of hepatic metabolic homeostasis by activating nuclear farnesoid X receptor (Fxr) and membrane G-protein-coupled receptor (Takeda G-protein-coupled receptor 5; Tgr5). The role of FXR in regulation of bile acid synthesis and hepatic metabolism has been studied extensively. However, the role of TGR5 in hepatic metabolism has not been explored. The liver plays a central role in lipid metabolism, and impaired response to fasting and feeding contributes to steatosis and nonalcoholic fatty liver and obesity. We have performed a detailed analysis of gallbladder bile acid and lipid metabolism in Tgr5-/- mice in both free-fed and fasted conditions. Lipid profiles of serum, liver and adipose tissues, bile acid composition, energy metabolism, and messenger RNA and protein expression of the genes involved in lipid metabolism were analyzed. Results showed that deficiency of the Tgr5 gene in mice alleviated fasting-induced hepatic lipid accumulation. Expression of liver oxysterol 7α-hydroxylase in the alternative bile acid synthesis pathway was reduced. Analysis of gallbladder bile acid composition showed marked increase of taurocholic acid and decrease of tauro-α and β-muricholic acid in Tgr5-/- mice. Tgr5-/- mice had increased hepatic fatty acid oxidation rate and decreased hepatic fatty acid uptake. Interestingly, fasting induction of fibroblast growth factor 21 in liver was attenuated. In addition, fasted Tgr5-/- mice had increased activation of hepatic growth hormone-signal transducer and activator of transcription 5 (GH-Stat5) signaling compared to wild-type mice.TGR5 may play a role in determining bile acid composition and in fasting-induced hepatic steatosis through a novel mechanism involving activation of the GH-Stat5 signaling pathway. (Hepatology 2017;65:813-827).
Glucose Metabolism of Tumors Induced by Rous Sarcoma Virus. II. Isotope Studies of Alternate Pathways&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: James Ashmore, George Weber, Gouri Banerjee, William C. Love
Journal: JNCI Journal of the National Cancer Institute (1961)

Slices of Rous sarcoma virus-induced tumors were incubated with glucose-l-C14, glucose-6-C14, and pyruvate-2-C14 for the study of the intermediary metabolic pathways of this tumor. Glucose was readily metabolized and the rate of utilization was increased with rising concentration of the substrate. Preferential oxidation of carbon-1 of glucose was observed, which indicated operation of the direct oxidative pathway of glucose-6-phosphate in this tissue. The maximum contribution of this route did not exceed 4 percent of the glucose used. Incorporation into protein accounted for 1 to 2 percent of the glucose uptake. The Rous tumor utilized labeled pyruvate and approximately 15 percent was accounted for as C14O2. No significant incorporation of labeled carbon from pyruvate into tissue glycogen was observed.
Whole-Exome Sequencing in Two Extreme Phenotypes of Response to VEGF-Targeted Therapies in Patients With Metastatic Clear Cell Renal Cell Carcinoma
Authors: Andre P. Fay, Guillermo de Velasco, Thai H. Ho, Eliezer M. Van Allen, Bradley Murray, Laurence Albiges, Sabina Signoretti, A. Ari Hakimi, Melissa L. Stanton, Joaquim Bellmunt, David F. McDermott, Michael B. Atkins, Levi A. Garraway, David J. Kwiatkowski, Toni K. Choueiri
Journal: Journal of the National Comprehensive Cancer Network (2016)

Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)–targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC). Patients with mRCC who had received first-line sunitinib or pazopanib and were in 2 extreme phenotypes of response were identified. Extreme responders (ERs) were defined as those with partial response or complete response for 3 or more years (n=13) and primary refractory patients (PRPs) were defined as those with progressive disease within the first 3 months of therapy (n=14). International Metastatic RCC Database Consortium prognostic scores were not significantly different between the groups (P=.67). Considering the genes known to be mutated in RCC at significant frequency, PBRM1 mutations were identified in 7 ERs (54%) versus 1 PRP (7%) (P=.01). In addition, mutations in TP53 (n=4) were found only in PRPs (P=.09). Our data suggest that mutations in some genes in RCC may impact response to VEGF-TT.
Platelet monoamine oxidase activity and genetic vulnerability to schizophrenia
Authors: M Baron, M Levitt, R Gruen, J Kane, L Asnis
Journal: American Journal of Psychiatry (1984)

Platelet monoamine oxidase (MAO) activity, determined in 102 patients with chronic schizophrenia, 223 first-degree relatives, and 88 normal control subjects, was shown to be a heritable and stable trait and was significantly lower in patients than in normal control subjects. Within families, MAO activity distinguished ill from well relatives. However, the considerable overlap in enzyme activity between affected and unaffected individuals limits the usefulness of low MAO activity as a major risk factor in schizophrenia.
Heterogeneity of the HIV epidemic in agrarian, trading, and fishing communities in Rakai, Uganda: an observational epidemiological study
Authors: Larry W Chang, Mary K Grabowski, Robert Ssekubugu, Fred Nalugoda, Godfrey Kigozi, Betty Nantume, Justin Lessler, Sean M Moore, Thomas C Quinn, Steven J Reynolds, Ronald H Gray, David Serwadda, Maria J Wawer
Journal: The Lancet HIV (2016)