tbuckley/cabot-search huggingface dataset:
Changes in interleukin‐17A, macrophage‐derived chemokine and adiponectin following treatment of psoriasis with calcipotriol plus betamethasone dipropionate aerosol foam: results from the <scp>PSO</scp> ‐ <scp>ABLE</scp> study
Authors: M. Røpke, C. Bulai Livideanu, R. Kaldate, A. Snel, C. Paul
Journal: British Journal of Dermatology (2017)

Psoriasis vulgaris is an immune-mediated disease characterized by skin and systemic inflammation that is associated with an increased risk of comorbidities such as cardiovascular disease. Although typically associated with moderate-to-severe psoriasis, recent data suggests that increased vascular inflammation may occur in patients with milder psoriasis. It has been shown that systemic treatment of psoriasis leads to an improvement in cardiovascular-associated biomarkers, eg adiponectin levels.

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Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants
Authors: Carola Dröge, Michele Bonus, Ulrich Baumann, Caroline Klindt, Elke Lainka, Simone Kathemann, Florian Brinkert, Enke Grabhorn, Eva-Doreen Pfister, Daniel Wenning, Alexander Fichtner, Daniel N. Gotthardt, Karl Heinz Weiss, Patrick McKiernan, Ratna Dua Puri, I.C. Verma, Stefanie Kluge, Holger Gohlke, Lutz Schmitt, Ralf Kubitz, Dieter Häussinger, Verena Keitel
Journal: Journal of Hepatology (2017)
Cancer Project Speeding Along
Authors: Jeff Lyon
Journal: JAMA (2017)

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
Certain about Dying with Uncertainty
Authors: Jeffrey M. Drazen, Maria A. Yialamas
Journal: New England Journal of Medicine (2017)

Mrs. C. said she’d had a good life and if an event came along that was the medical equivalent of a flat tire, we should fix it. But if something required major intervention, she didn’t want it. We didn’t know how hard it would be to keep our part of the bargain.
PTU-002 Does open access influence the citation metrics in gastroenterology journals?
Authors: DS Sanders, N Menic, I Nyamali, JM Punnamkuzhy, P Whelpdale, M Kurien
Journal: Gut (2017)

Introduction  Improving the dissemination and impact of medical research is important, if maximal benefits are to be achieved for patients. To help achieve this goal, researchers are increasingly being asked to make their work open access, or publish in one of the increasing number of open-access journals. The costs associated with open access can be significant, with this financial burden deferred to the submitting research teams. Currently, uncertainty exists as to whether the practice of open access actually adds value to the overall citation metrics. This study addresses this knowledge gap by evaluating outcomes of open access publications in leading gastroenterology journals.  Method  Original research articles published in Gastroenterology, GUT and the American Journal of Gastroenterology (AJG) (2009–2013) were reviewed in October 2016. Publications were examined to determine their status as being open access and to assess their study type (clinical research vs basic science). Publications were then cross referenced with the Web of ScienceTM database to determine overall citation rates. Statistical analyses were performed using contingency tables, using SPSS version 20.0. Chi- sqaured testing was used to assess categorical variables, with a Mann-Whitney U Test (non-parametric testing) used to compare citation rates between open and non-open access publications. p  Results  3057 original research articles were published between Jan 2009-Dec 2013 (Gastroenterology (n=1431), GUT (n=732), AJG (n=894). Of these, 154 (5.0%) were open access publications (Gastroenterology (n=13), GUT (n=70), AJG (n=71). The year of publication did influence the frequency of open access publications x2 (4)=28.7, p  Conclusion  This is the first study to evaluate the citation metrics for open access publications in leading gastroenterology journals. Based on our findings, authors should be encouraged to make their work open access. Given the merits of open access publications both to patients and researchers, questions should be asked as to whether the high costs of making publications open access is really justifiable.  Disclosure of Interest  None Declared
Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients
Authors: Nicholas T. Gimbrone, Bhaswati Sarcar, Edna R. Gordian, Jason I. Rivera, Christian Lopez, Sean J. Yoder, Jamie K. Teer, Eric A. Welsh, Alberto A. Chiappori, Matthew B. Schabath, Gary W. Reuther, Julie Dutil, Miosotis Garcia, Ronald Ventosilla-Villanueva, Luis Vera-Valdivia, Alejandro Yabar-Berrocal, Rodrigo Motta-Guerrero, Pedro G. Santiago-Cardona, Teresita Muñoz-Antonia, W. Douglas Cress
Journal: Journal of Thoracic Oncology (2017)
Temsirolimus in Combination with Three Different Immuno-Chemotherapy Regimens in Relapse and Refractory Mantle Cell Lymphoma, Final Results of the T3 Phase IB Trial of the Lysa Group
Authors: Steven Le Gouill, Krimo Bouabdallah, Barbara Burroni, Thierry Lamy, Remy Gressin, Guillaume Cartron, Catherine Thieblemont, Clémentine Sarkozy, Corinne Haioun, Olivier Casasnovas, Emmanuel Gyan, Olivier Hermine
Journal: Blood (2016)
Validation of the AJCC 8th edition prognostic stage in breast cancer.
Authors: Anna Weiss, Mariana Chavez-Mac Gregor, Daphne Lichtensztajn, Min Yi, Christina A Clarke, Sharon Hermes Giordano, Kelly Hunt, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2017)

e23186 Background: The 8th edition of the AJCC staging manual introduced a prognostic stage incorporating biologic factors. The goal this study was to validate the prognostic stage in a single institution cohort and large population database. Methods: Patients were identified in a prospective institutional database and the California Cancer Registry (CCR). Factors included were T, N, m stage, grade, estrogen receptor, progesterone receptor and HER2 status. Survival was calculated by Kaplan Meier method. Harrell’s concordance index (C index) was used to quantify models’ predictive performance, and Akaike Information Criterion (AIC) to compare model fits. Results: A total of 3,327 Stage I-IIIC breast cancer patients treated 2007-2013 at a single institution with complete clinicopathologic data were identified. Compared to the anatomic stage, the prognostic stage upstaged 29.5% of patients and downstaged 28.1%. Median follow up was 5 yrs. The prognostic staging system’s C index (0.84) and AIC (816.8) reflect a more accurate model predictive of disease specific survival (DSS) (Table) than the anatomic staging (C index 0.74, P &lt; .0001; AIC 1039.8). A total of 49,767 Stage I-IIIC patients diagnosed 2005-2009 with complete data were identified in the CCR. 31.7% of patients were upstaged and 21.1% downstaged. Median follow up was 7.15 years. Prognostic staging performed better (C index 0.81, AIC 65924.1) than anatomic staging (C index 0.77, P &lt; .0001; AIC 66847.7). Conclusions: The newly released 8 th AJCC prognostic staging system, validated in both a single institution and a large population database, provides more accurate prognostic information than the anatomic staging system. [Table: see text]
68Ga-DOTATATE Uptake in Solitary Pancreatic Metastasis From Clear Cell Renal Cancer
Authors: Shankar Vamadevan, Ken Le, Lily Shen, Han Loh, Robert Mansberg
Journal: Clinical Nuclear Medicine (2017)

A 64-year-old man with a lesion of the pancreatic tail was referred for Ga-DOTATATE PET/CT imaging. His medical history included previous metastatic clear cell renal cell cancer. Ga-DOTATATE PET/CT demonstrated increased DOTATATE uptake (SUVmax 10.5) in a pancreatic tail lesion. Histopathology of the resected lesion confirmed clear renal cell cancer metastasis. This case illustrates that clear cell renal cancer metastasis can demonstrate Ga-DOTATATE accumulation.
Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure
Authors: Veena S. Rao, Noah Planavsky, Jennifer S. Hanberg, Tariq Ahmad, Meredith A. Brisco-Bacik, Francis P. Wilson, Daniel Jacoby, Michael Chen, W.H. Wilson Tang, David Z.I. Cherney, David H. Ellison, Jeffrey M. Testani
Journal: Journal of the American Society of Nephrology (2017)

Understanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF ( n =128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine. The mean±SD prediuretic FELi was 16.2%±9.5%, similar to that in a control cohort without HF not receiving diuretics ( n =52; 16.6%±9.2%; P =0.82). Administration of a median of 160 (interquartile range, 40–270) mg intravenous furosemide equivalents increased FELi by 12.6%±10.8% ( P &lt;0.001) but increased FENa by only 4.8%±3.3%. Thus, only 34% (interquartile range, 15.6%–75.7%) of the estimated diuretic-induced sodium release did not undergo distal reabsorption. After controlling for urine diuretic levels, the increase in FELi explained only 6.4% of the increase in FENa ( P =0.002). These data suggest that administration of high-dose loop diuretics to patients with HF yields meaningful increases in sodium exit from the proximal tubule/loop of Henle. However, little of this sodium seems to reach the urine, consistent with findings from animal models that indicate that distal tubular compensatory sodium reabsorption is a primary driver of DR.
<i>miR-99</i> regulates normal and malignant hematopoietic stem cell self-renewal
Authors: Mona Khalaj, Carolien M. Woolthuis, Wenhuo Hu, Benjamin H. Durham, S. Haihua Chu, Sarah Qamar, Scott A. Armstrong, Christopher Y. Park
Journal: The Journal of Experimental Medicine (2017)

The microRNA-99 (miR-99) family comprises a group of broadly conserved microRNAs that are highly expressed in hematopoietic stem cells (HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny. Herein, we show that miR-99 regulates self-renewal in both HSCs and LSCs. miR-99 maintains HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants. Confirming miR-99's role in established AML, miR-99 inhibition induced primary AML patient blasts to undergo differentiation. A forward genetic shRNA library screen revealed Hoxa1 as a critical mediator of miR-99 function in HSC maintenance, and this observation was independently confirmed in both HSCs and LSCs. Together, these studies demonstrate the importance of noncoding RNAs in the regulation of HSC and LSC function and identify miR-99 as a critical regulator of stem cell self-renewal.
How the Real-Life Diagnostic and Therapeutic Approach Changed in the Last Two Decades in the Thrombocythemic Patients with Ph- Negative Myeloproliferative Neoplasm. Report on 2388 Subjects of the Registro Italiano Trombocitemie (RIT)
Authors: Luigi Gugliotta, Alessandra Iurlo, Gabriele Gugliotta, Alessia Tieghi, Lucia Canafoglia, Raffaele Palmieri, Crescenza Pasciolla, Nicola Vianelli, Riccardo Ragionieri, Erminia Rinaldi, Emilio Usala, Giorgio La Nasa, Alessandra Perra, Giuseppe Tagariello, Nilla Maschio, Emma Cacciola, Rossella Rosaria Cacciola, Micaela Bergamaschi, Anna Da Col, Angela Rago, Lorenzo Rizzo, Francesco Spina, Daniele Cattaneo, Daniela Lambertenghi, Aniello Casoria, Maria Langella, Maria Luigia Randi, Elisabetta Cosi, Monica Crugnola, Elena Masselli, Paola Ranalli, Giovanni Garozzo, Katia Codeluppi, Oreste Villani, Grazia Ferrara, Cristina Santoro, Potito Rosario Scalzulli, Manlio Ricciotti, Viviana Appolloni, Anna Candoni, Annalisa Luraschi, Rupoli Serena, Mauro DI Ianni, Giovanni Caocci, Francesco Lanza, Nicola Orofino, Elisa Rumi, Alfredo Dragani, Bruno Martino, Anna Marina Liberati, Umberto Santoro, Alessandro M. Vannucchi
Journal: Blood (2016)
A challenging case of giant biliary stones in a patient with situs inversus totalis: conventional ERCP combined with intraductal cholangioscopy and laser lithotripsy
Authors: Félix Téllez-Ávila, Sandeep Pattel, Gilberto Duarte-Medrano, Marlon Seenath, David Herrera-Mora, Gustavo Lopez-Arce
Journal: Endoscopy (2017)

A 65-year-old man with situs inversus was admitted with jaundice, nausea, and upper abdominal pain. A computed tomography scan confirmed the diagnosis of situs inversus totalis and revealed a large stone in the main bile duct with distal stenosis.
PrEP on demand reduces HIV infections, study finds
Authors: Sophie Cousins
Journal: BMJ (2017)

On demand pre-exposure prophylaxis (PrEP) to prevent HIV infection is highly effective in men who have infrequent sex with men, shows research presented this week at the International AIDS Society’s Conference on HIV Science in Paris, France.

A sub-study of ANRS IPERGAY, a major trial examining the efficacy of on-demand PrEP, found that participants who took fewer than 15 tablets a month—but took one each time they had sex—showed no new HIV infections, compared with six in the placebo arm. The median number of tablets taken each month was 9.5, with a median of five sexual intercourse encounters.

The results, …
T cell population expansion in response to allogeneic cancer vaccine alone (DPV-001) or with granulocyte-macrophage colony-stimulating factor (GM-CSF) or imiquimod (I) for definitively-treated stage III NSCLC patients (pts).
Authors: Bernard A. Fox, Brian C. Boulmay, Rui Li, Kyle T Happel, Christopher Paustian, Tarsem Lal Moudgil, Sachin Puri, Christopher Dubay, Yoshinobu Koguchi, Adi Mehta, Fridtjof Lund-Johansen, Brenda K Fisher, William L Redmond, Carlo Bruno Bifulco, Augusto Ochoa, Hong-Ming Hu, Traci Hilton, Walter John Urba, Rachel E. Sanborn
Journal: Journal of Clinical Oncology (2017)

e14639 Background: The DPV-001 DRibble is a dendritic cell-targeted microvesicle (proteasome blocked autophagosome) vaccine derived from an adenocarcinoma and a mixed histology cell line. It contains multiple TLR agonists and &gt; 130 potential NSCLC antigens, many as prospective altered-peptide ligands. In preclinical studies, DRibble immunotherapy provided significant anti-cancer effects in a dozen models. We hypothesize that DRibble’ vaccination efficacy can be attributed to their capacity to present tumor-derived short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) that are typically not processed and presented by professional antigen presenting cells and against which the host may be less tolerant. Methods: Pts received induction cyclophosphamide, 7 vaccines every 3-weeks, then every 6 weeks x 4 more doses. Pts were randomized to receive DRibble alone (A), or with I (B) or GM-CSF (C). PBMCs /serum were collected at baseline and at each vaccination to assess changes in antibodies (Ab) (ProtoArray and microsphere affinity proteomics), peripheral lymphocyte populations (flow cytometry) and T cell receptor (TCR) repertoires (Adaptive immunoSEQ). Results: 13 pts were enrolled (Arm A: 5; B: 4; C: 4). We previously reported that vaccination induced or increased IgG Ab responses against targets over-expressed by NSCLC. Patients receiving DPV-001 had a significant (p &lt; 0.04) increase in total (CD4 + CD8) TCRs that increased 10 fold over baseline compared to normal controls (independent from trial, n = 3) and the increase in CD4 clones was similar to that seen following ipilimumab (melanoma pts, independent from trial, n = 9). Analysis of a resected metastasis (progressing on treatment), identified brisk infiltration of T cells and tumor that was strongly PD-L1+. Conclusions: Vaccination with DPV-001 expanded populations of T cells over that observed in controls and the increase in CD4 T cells was similar to that observed in patients receiving ipilimumab and may represent vaccine-reactive T cells. Clinical Trial Identifier: NCT01909752, Support: R44 CA121612 Clinical trial information: NCT01909752.
Direct Metabolic Interrogation of Dihydrotestosterone Biosynthesis from Adrenal Precursors in Primary Prostatectomy Tissues
Authors: Charles Dai, Yoon-Mi Chung, Evan Kovac, Ziqi Zhu, Jianneng Li, Cristina Magi-Galluzzi, Andrew J. Stephenson, Eric A. Klein, Nima Sharifi
Journal: Clinical Cancer Research (2017)

Purpose: A major mechanism of castration-resistant prostate cancer (CRPC) involves intratumoral biosynthesis of dihydrotestosterone (DHT) from adrenal precursors. We have previously shown that adrenal-derived androstenedione (AD) is the preferred substrate over testosterone (T) for 5α-reductase expressed in metastatic CRPC, bypassing T as an obligate precursor to DHT. However, the metabolic pathway of adrenal-derived DHT biosynthesis has not been rigorously investigated in the setting of primary disease in the prostate.Experimental Design: Seventeen patients with clinically localized prostate cancer were consented for fresh tissues after radical prostatectomy. Prostate tissues were cultured ex vivo in media spiked with an equimolar mixture of AD and T, and stable isotopic tracing was employed to simultaneously follow the enzymatic conversion of both precursor steroids into nascent metabolites, detected by liquid chromatography-tandem mass spectrometry. CRPC cell line models and xenograft tissues were similarly assayed for comparative analysis. A tritium-labeled steroid radiotracing approach was used to validate our findings.Results: Prostatectomy tissues readily 5α-reduced both T and AD. Furthermore, 5α-reduction of AD was the major directionality of metabolic flux to DHT. However, AD and T were comparably metabolized by 5α-reductase in primary prostate tissues, contrasting the preference exhibited by CRPC in which AD was favored over T. 5α-reductase inhibitors effectively blocked the conversion of AD to DHT.Conclusions: Both AD and T are substrates of 5α-reductase in prostatectomy tissues, resulting in two distinctly nonredundant metabolic pathways to DHT. Furthermore, the transition to CRPC may coincide with a metabolic switch toward AD as the favored substrate. Clin Cancer Res; 23(20); 6351-62. ©2017 AACR.
Increasing Lipolysis and Reducing Atherosclerosis
Authors: Alan R. Tall
Journal: New England Journal of Medicine (2017)

In patients with coronary artery disease, residual cardiovascular risk remains substantial even after levels of low-density lipoprotein (LDL) cholesterol have been effectively lowered by treatment with statins, ezetimibe, or antibodies targeting proprotein convertase subtilisin–kexin type 9 (PCSK9). Many of these patients have elevated levels of triglyceride-rich lipoproteins, often in the context of obesity and insulin resistance. A causal relationship between elevated levels of triglyceride-rich lipoproteins and coronary artery disease has been suggested by mendelian randomization studies in which polymorphisms in genes that are linked to higher levels of triglyceride-rich lipoproteins have also been found to be associated with coronary artery . . .
Insurance retention in adolescent and young adult survivors of malignancies in a vertically integrated health care system.
Authors: Robert Michael Cooper
Journal: Journal of Clinical Oncology (2012)

9588 Background: Adolescents and Young Adults (AYA) with cancer are a unique population of patients. This group is afflicted with a wide range of cancer types. AYA patients often have delays in diagnosis due to issues related to insurance and continuity of care and have less participation clinical trials related to other age groups. Survivors are at risk of late effects of treatment. A vertically integrated health care system with a comprehensive electronic medical record provides an ideal opportunity to care for adolescent and young adult (AYA) cancer survivors and conduct survivorship research. In this system, patients who complete oncology care return to primary medical care but can be tracked in a systematic fashion. Methods: We evaluated the insurance retention of survivors of AYA malignancies by querying the Cancer Registry and identified 13,240 known survivors of malignancies diagnosed within the system between 1990 and 2005. We looked at the percentage of survivors who were still cared for in our system at certain time points after diagnosis. We then reanalyzed the group by ethnicity, disease, and age at diagnosis. Results: The retention rate for all patients was 88% at 1 year, 64 % at 5 years, and 52% at 10 years. The retention rates were similar regardless of ethnicity. When we looked at the influence of age at time of diagnosis we noted that the younger the patients were at diagnosis the lower the percentage of those retaining insurance at the 10 year time point. We analyzed the group by the more common cancers and noted that patients diagnosed with breast cancer had greatest retention at 10 years of 68%. Conclusions: The lengthy insurance retention of adolescent and young adult cancer survivors makes a vertically integrated medical care system an ideal population laboratory for cancer survivorship research in this understudied population of cancer survivors.
60 seconds on . . . Black Wednesday
Authors: Abi Rimmer
Journal: BMJ (2017)

No, you fool—this is Black Wednesday, not Black Friday. It’s the first Wednesday in August, when a new cohort of junior doctors start working at NHS hospitals.

Also known as “the killing season,”1 Black Wednesday is reported in the media every year as a kind of hospital based apocalypse. In 2013, for example, our old friend the Daily Mail …