tbuckley/cabot-search huggingface dataset:
High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation
Authors: Kento Kitada, Steffen Daub, Yahua Zhang, Janet D. Klein, Daisuke Nakano, Tetyana Pedchenko, Louise Lantier, Lauren M. LaRocque, Adriana Marton, Patrick Neubert, Agnes Schröder, Natalia Rakova, Jonathan Jantsch, Anna E. Dikalova, Sergey I. Dikalov, David G. Harrison, Dominik N. Müller, Akira Nishiyama, Manfred Rauh, Raymond C. Harris, Friedrich C. Luft, David H. Wasserman, Jeff M. Sands, Jens Titze
Journal: Journal of Clinical Investigation (2017)

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter–driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.
Achieving the Promise of Price Transparency
Authors: Anna D. Sinaiko, Alyna T. Chien
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Sleep problems in toddlers are linked to touch screen use, survey finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Using touch screen devices has been linked with sleep problems in infants and toddlers in a survey of parents reported in Scientific Reports , a journal from the Nature Research group.1 One experimental psychologist warned, however, that the results should be interpreted with extreme caution.

The online survey was administered to 715 parents of toddlers aged 6 months to 3 years in the UK. Parents were asked how long their child spends using a portable touch screen device on a typical day as well time spent watching television. They were also asked about the average duration of …
Molecular profiling to identify genetic heterogeneity in synchronous and asynchronous breast cancers.
Authors: Windy Marie Dean-Colomb, Clayton Yates, Sandeep K. Reddy, Joyce O'Shaughnessy, Sherri Z. Millis
Journal: Journal of Clinical Oncology (2015)

558 Background: Histologic heterogeneity of tumors is well documented; however, the molecular heterogeneity is not well understood, especially relative to driver mutations within clonal populations and their prognostic and predictive value. Methods: Molecular profiling of breast cancers (BCs) at a single institution were analyzed for differences in clonal populations within the same breast, bilateral synchronous BCs, and/or within primary and paired locally recurrent or metastatic tumors. Gene alterations (GAs) were identified by next generation sequencing (NGS). GAs were compared in 9 synchronous BCs and 48 primary/recurrent paired BCs. Estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), were evaluated by immunohistochemistry (IHC). HER2 was evaluated by IHC and in situ hybridization (ISH). Results: We identified GAs in 11 of 57 cases (19%); 2 were bilateral and 9 were paired primary/recurrent BCs. The 11 cases included 1 primary, 1 primary/locally recurrent, and 9 primary/metastatic pairs. ER, PR, and HER2 status differed in 9 cases (16%), while AR status differed only in 3 (5%).16% 13/57 were negative for ER, PR, and HER2 (triple negative [TN]); of 9 TN BCs with GAs in paired primary/recurrent BCs, 6 of 9 (67%) were TN on both primary and recurrent disease (p = 0.0135). TP53 GAs were identified in 5 of the 11 cases (including the 2 synchronous), PIK3CA GAs were identified in 4 (1 synchronous), and PTEN GAs were identified in 3 (1 synchronous) cases. Other genes in which GAs appeared in only one of the pairs included CDH1 (synchronous), cMET and KRAS (Primary/recurrent pair). Of the 2 synchronously profiled cases, 1 had 2 and 1 had 3 different GAs in the bilateral BCs, and 2 GAs in both BCs. In the primary/metastatic pairs, all discordant GAs were wild type in the primary and pathogenic in the metastasis. Conclusions: We identified that common GAs differ in both synchronous primary BCs and in paired primary/metastatic tissues. Such discordance could influence treatment recommendations. These findings highlight the molecular evolution of BC and the importance of evaluating predictive markers of treatment benefit both in synchronous and metastatic BCs.
TCTAP A-087 Angioscopic Comparison of First Generation Sirolimus-eluting Stent and Second Generation Zotarolimus-eluting Stent Beyond One Year
Authors: Takuya Tsujimura, Takayuki Ishihara, Osamu Iida, Shin Okamoto, Kiyonori Nanto, Shota Okuno, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2017)
Matching NLR Immune Receptors to Autoimmunity in camta3 Mutants Using Antimorphic NLR Alleles
Authors: Signe Lolle, Christiaan Greeff, Klaus Petersen, Milena Roux, Michael Krogh Jensen, Simon Bressendorff, Eleazar Rodriguez, Kenneth Sømark, John Mundy, Morten Petersen
Journal: Cell Host & Microbe (2017)
An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses
Authors: David J. Holthausen, Song Hee Lee, Vineeth TV Kumar, Nicole M. Bouvier, Florian Krammer, Ali H. Ellebedy, Jens Wrammert, Anice C. Lowen, Sanil George, Madhavan Radhakrishna Pillai, Joshy Jacob
Journal: Immunity (2017)
Thoughts and Response to Authority-Perpetrated, Discriminatory, and Race-Based Violence
Authors: Kimlin Tam Ashing, Marva L. Lewis, Valencia P. Walker
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
TCTAP A-167 Percutaneous Transvenous Mitral Commissurotomy in Patients with Calcific Mitral Stenosis: Immediate and In-hospital Clinical, Echocardiographic and Hemodynamic Outcome
Authors: Toufiqur Rahman, Afzalur Rahman, Abdullah Al Shafi Majumder, AKM Monwarul Islam
Journal: Journal of the American College of Cardiology (2017)
Validation of a genomic-clinical classifier for predicting clinical progression in high-risk prostate cancer.
Authors: Christine Buerki, Anirban Pradip Mitra, Peter C. Black, Mercedeh Ghadessi, Eric J. Bergstralh, Nicholas Erho, Rachel Carlson, Anamaria Crisan, Thomas Sierocinski, Benedikt Zimmermann, Zaid Haddad, Ismael A. Vergara, Karla V. Ballman, George G. Klee, Stephanie Fink, Thomas M. Kollmeyer, Timothy J. Triche, Elai Davicioni, R. Jeffrey Karnes, Robert B. Jenkins
Journal: Journal of Clinical Oncology (2012)

4565 Background: The efficient delivery of adjuvant therapy after radical prostatectomy (RP) in patients with prostate cancer is limited by the lack of biomarkers, beyond clinicopathologic factors, that are able to assess the risk of clinically significant disease progression. Previously, routine FFPE patient specimens from the Mayo Clinic Radical Prostatectomy Registry with long term follow-up were selected to develop a genomic classifier (GC) to predict clinical progression. Here, we present the validation of a GC in a cohort of patients at high risk of disease progression. Methods: A case-cohort study of high-risk RP patients from the Mayo Clinic (N=219) was used to validate the genomic classifier (GC) for predicting clinical progression (defined by positive bone or CT scan post-RP). Its performance was compared to a multivariable clinical classifier (CC) and a genomic-clinical classifier (GCC) which combines GC with established clinicopathologic variables. Concordance index, Cox modeling and decision curve analysis were used to compare the different models. Results: GC and GCC were predictive of clinical progression in the high-risk cohort with c-indices of 0.79 and 0.82, respectively, compared to the clinical classifier (0.70). Multivariable survival analysis showed that the majority of prognostic information of GCC came from the GC with a minor contribution from Gleason score. Decision curve analysis showed that GCC had a higher overall net benefit compared to CC over a wide range of ‘decision-to-treat’ thresholds for the risk of progression. Conclusions: In this high-risk cohort, GC and GCC classifiers showed improved performance over CC in prediction of clinical progression. GC is an independent prognostic factor in this cohort and captures the majority of prognostic information. GC and GCC’s prognostic performance and their usefulness in guiding decision-making in the adjuvant setting after RP need further testing in studies of additional prostate cancer risk groups.
Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study
Authors: Carlos A Celis-Morales, Donald M Lyall, Paul Welsh, Jana Anderson, Lewis Steell, Yibing Guo, Reno Maldonado, Daniel F Mackay, Jill P Pell, Naveed Sattar, Jason M R Gill
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality. <b>Design</b>&nbsp;Prospective population based study. <b>Setting</b>&nbsp;UK Biobank. <b>Participants</b>&nbsp;263 450 participants (106 674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The exposure variable was the mode of transport used (walking, cycling, mixed mode <i>v</i> non-active (car or public transport)) to commute to and from work on a typical day. <b>Main outcome measures</b>&nbsp;Incident (fatal and non-fatal) CVD and cancer, and deaths from CVD, cancer, or any causes. <b>Results</b>&nbsp;2430 participants died (496 were related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In maximally adjusted models, commuting by cycle and by mixed mode including cycling were associated with lower risk of all cause mortality (cycling hazard ratio 0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76, 0.58 to 1.00, P&lt;0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P&lt;0.001; mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling 0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P&lt;0.001). Commuting by cycling and walking were associated with a lower risk of CVD incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99, P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45 to 0.91, P=0.01). No statistically significant associations were observed for walking commuting and all cause mortality or cancer outcomes. Mixed mode commuting including walking was not noticeably associated with any of the measured outcomes. <b>Conclusions</b>&nbsp;Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic conditions.
Impact of the delivery of adjuvant anthracycline-based nontaxane chemotherapy schedules on the outcome of breast cancer patients: Results from a retrospective database analysis.
Authors: Isabel Chirivella, Begona Bermejo, Amelia Insa, Jose Alejandro Perez-Fidalgo, Ana Magro, Susana Rosello Keranen, Paloma Martin, Ana Bosch, Ana Lluch
Journal: Journal of Clinical Oncology (2012)

1074 Background: A dose-response effect has previously been observed with CMF and anthracycline-based schedules. The objective of this post-hoc analysis was to give additional information on the impact of chemotherapy delivery on patients’ outcome. Methods: Selection criteria were to have early breast cancer (stage I-IIIA) from Jan 1980 to Dec 2000, to undergo surgery as primary treatment and to receive an anthracycline-based non-taxane schedule in the adjuvant setting. G-CSF support was not given to any patient. Chemotherapy delivery was assessed based on ≥ 2 vs. &lt; 2 delayed cycles, ≥ 15 vs. &lt;15 delayed days and &lt; 85% vs. ≥ 85% of the relative dose intensity (RDI) given. Patients’ outcomes were assessed based on 5- and 10-year disease-free survival (DFS) and overall survival (OS) rates. Results: 793 breast cancer patients with a median age of 51 years (21-79) were analyzed of whom 27% had stage IIIA and 23% had stage I disease. As shown in the table, 5- and 10-year rates of DFS and OS significantly improved when adjuvant chemotherapy was optimally delivered. Conclusions: The dose-response effect is a key factor that should be taken into account when an anthracycline-based non-taxane chemotherapy is administered in the adjuvant setting. Delays and/or reductions of chemotherapy should be avoided in order to achieve the maximal benefit for the patient. This study was partially funded by Amgen SA. [Table: see text]
Impact of neoadjuvant therapy on breast conservation rates in triple-negative and HER2-positive breast cancer: Combined results of CALGB 40603 and 40601 (Alliance).
Authors: Mehra Golshan, Constance T. Cirrincione, Lisa A. Carey, William M. Sikov, Donald A. Berry, Harold J. Burstein, Beth Overmoyer, Norah Lynn Henry, George Somlo, Elisa R. Port, Eric P. Winer, Clifford A. Hudis, David W. Ollila
Journal: Journal of Clinical Oncology (2015)

1007 Background: Neoadjuvant therapy (NAT) improves breast conserving therapy (BCT) rates, but the extent by tumor subtype is unknown. To quantify this effect for triple-negative breast cancer (TNBC) and HER2-positive breast cancer (HER2+ BC), we reviewed surgical outcomes from CALGB 40603, a randomized phase II trial of weekly paclitaxel (P) +/- carboplatin (Cb) followed by doxorubicin + cyclophosphamide (AC) +/- bevacizumab (B) for stage (stg) II-III TNBC, and CALGB 40601, a randomized phase III trial of paclitaxel (P)+ HER2 blockade with trastuzumab (P+H), lapatinib (P+L) or both (P+H+L) for stg II-III HER2+ BC, by requiring surgeons to prospectively evaluate BCT eligibility before and after NAT. Methods: Patients (pts) with stg II-III TNBC (n = 404) were randomized in CALGB 40603. Pts with stg II-III HER2+ BC (n = 292) were randomized in CALGB 40601. The treating surgeon assessed BCT candidacy based on clinico-radiographic criteria before and after NAT. Subsequent surgical management was at surgeon and patient discretion. We determined (1) conversion rate from BCT-ineligible to BCT-eligible and vice-versa, and (2) rate of successful BCT, as defined by tumor-free surgical margins. Results: Pre- and post-treatment surgical assessments were received for 94% of 742 pts treated in the two trials. Of 696 evaluable pts, 340 (49%) were considered BCT candidates prior to NAT. Of these, 310 (91%) remained BCT eligible after NAT; BCT was successful in 209/232 (90%) in whom it was attempted. Of 356 pts (51%) considered BCT ineligible prior to NAT, 151(42%) converted to BCT eligible; BCT was successful in 87/102(85%) in whom it was attempted. The rates were similar across the two studies. Results will be broken down by treatment arm. Of 461 pts judged BCT candidates post NAT, 127(28%) chose mastectomy with no attempt at BCT. Conclusions: We present the largest combined prospective analysis of NAT trials showing a BCT-ineligible to BCT-eligible conversion rate of 42% in both TNBC and HER2+ BC subtypes. BCT was successful in approximately 88% of pts who chose this approach; however, a substantial fraction of BCT-eligible pts opted for mastectomy. Clinical trial information: NCT00861705.
An Unusual Case of Syringocystadenocarcinoma Papilliferum In Situ With Macular Amyloidosis
Authors: Saurabh Singh, Geeti Khullar, Tarun Sharma, Poonam Elhence
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Prognostic and predictive significance of 5-fluorouracil metabolic enzymes in colorectal cancer
Authors: R. C. Soong, N. Shah, M. Salto-Tellez, H. C. Han, S. S. Ng, N. Zeps, D. Joseph, R. B. Diasio, B. J. Iacopetta
Journal: Journal of Clinical Oncology (2006)

2021 Background: Low levels of the 5-Fluorouracil (5-FU) metabolic enzymes, thymidylate synthase (TS), dihydropyrimdine dehydrogenase (DPD) and thymidine phosphorylase (TP) are linked to improved survival in colorectal cancer (CRC) patients receiving 5-FU chemotherapy. However, whether they are prognostic (related to tumor biology) or predictive (drug sensitivity) indicators is not clarified. This study aimed to (1) discriminate the prognostic and predictive significance of TS, DPD and TP and (2) ascertain the clinical and molecular subtype associations of the proteins in a large sample series. Methods: Tissue arrays containing sections from 956 stage 2/3 CRC cases were stained immunohistochemically for TS, DPD and TP. Associations with clinical and molecular characteristics and survival according to treatment status were assessed by Kruskall-Wallis and Kaplan-Meier analysis. Results: Low TS levels were associated with late stage, proximal tumor location and absence of microsatellite instability, low DPD with younger age and late stage and low TP with proximal tumor location. Low levels of all three enzymes associated with absence of tumor infiltrating lymphocytes. There were no associations with gender, grade or ras and p53 mutation. In stage 2 patients treated by surgery alone, those with low DPD levels had a worse survival than those with high levels (p&lt;0.01). Stage 3 patients treated with chemotherapy had a better survival than those without in subgroups of patients with low TS (p=0.05), DPD (p&lt;0.01) and TP (p=0.03) but not high levels of the proteins. Conclusions: Our results suggest the improved outcome of 5FU-treated patients with low tumor TS, DPD and TP levels may be due primarily to a benefit from adjuvant treatment rather than a favorable prognosis. TS, DPD and TP levels may be useful indicators for identifying CRC patients likely to benefit from 5-FU treatment. No significant financial relationships to disclose.
Synergistic Therapeutic Efficacy of Combined JAK1/2, Pan-PIM, and CDK4/6 Inhibition in Myeloproliferative Neoplasms
Authors: Raajit K. Rampal, Pinzon-Ortiz Maria, Hanasoge Somasundara Amritha Varshini, Ross L. Levine, Alex Cao
Journal: Blood (2016)
Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors
Authors: Tyrel T. Smith, Howell F. Moffett, Sirkka B. Stephan, Cary F. Opel, Amy G. Dumigan, Xiuyun Jiang, Venu G. Pillarisetty, Smitha P. S. Pillai, K. Dane Wittrup, Matthias T. Stephan
Journal: Journal of Clinical Investigation (2017)

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.