tbuckley/cabot-search huggingface dataset:
Helen Salisbury: Do we need integration?
Authors: Helen Salisbury
Journal: BMJ (2019)

I recently went to a city-wide integration workshop, involving about 200 people from the new primary care networks. I was hoping to learn about local progress towards an integrated care system, as foretold in the NHS Long Term Plan ,1 but I was disappointed. There seemed to be no big plan. There wasn’t even a small plan, unless our leaders were keeping it to themselves.

Instead, we were seated in multi-professional groups and were asked to talk about our vision for integrated care and what we’d do to bring …
The effect of neoadjuvant chemotherapy on pathologic downstaging and survival for patients with muscle-invasive bladder cancer with mixed histological features.
Authors: James Lin, Dara Denise Holder, Michael Whalen, Gregory Hruby, Guarionex DeCastro, James M. McKiernan
Journal: Journal of Clinical Oncology (2012)

e15019 Background: Urothelial carcinoma of the bladder (UCB) with mixed histological features (MH) is thought to portend a worse prognosis when compared to pure UC, based on reports of decreased survival for pure non-UC tumors. While patients with muscle-invasive UCB have been shown to derive a survival benefit from treatment with neoadjuvant chemotherapy (NC), the response of patients with MH is unclear. We sought to examine the pathologic and clinical outcomes of treatment with NC of patients with MH versus those with pure UC. Methods: Between 1990-2011, 318 patients were identified with clinical stage T2-T4a, N0-Nx, M0-Mx UCB who had either NC (+/- radical cystectomy) (n=67) or radical cystectomy (RC) alone (n=251). Among those given NC, 58% received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and 24% received gemcitabine/cisplatin. 265 patients had pure UC and 53 patients had MH, defined as UC with concomitant squamous or glandular differentiation on final pathology (biopsy histology used if pT0 or RC not performed). Endpoints included downstaging to pT0 and overall survival. Multivariable Cox regression was used to estimate the effect of histological type (MH vs. pure UC) on all-cause mortality within each treatment arm (NC vs. RC only) and to test for treatment-by-histological type interaction. Results: The rate of downstaging to pT0 was significantly higher in NC treated patients (34.3%) compared to those with RC alone (4.4%, p&lt;0.01). When stratified by histology, downstaging to pT0 was not significantly different for those treated with NC (37.0% for pure UC vs. 23.1% for MH, p=0.34). After adjusting for age, pathologic stage, and positive surgical margins on multivariate Cox regression, there was no difference in survival outcome for those with MH vs. pure UC (HR=1.5, p=0.5), nor for those treated with NC vs. RC only (HR=2.8, p=0.1). Conclusions: Prior evidence on the benefits of NC for patients with MH is mixed, but our data suggest that there is improvement in rate of pT0 on final pathology in those treated with NC, regardless of histology. As NC is not detrimental to the overall survival of MH patients, its administration should be continued.
Effects of Aryl Hydrocarbon Receptor Deficiency on PCB-77-Induced Impairment of Glucose Homeostasis during Weight Loss in Male and Female Obese Mice
Authors: Erin N. Jackson, Sean E. Thatcher, Nika Larian, Victoria English, Sony Soman, Andrew J. Morris, Jiaying Weng, Arnold Stromberg, Hollie I. Swanson, Kevin Pearson, Lisa A. Cassis
Journal: Environmental Health Perspectives (2019)

Background: Lipophilic polychlorinated biphenyls (PCBs) accumulate with obesity, but during weight loss, liberated PCBs act as ligands of the aryl hydrocarbon receptor (AhR) to negatively influence health. Previous studies demonstrated that PCB-77 administration to obese male mice impaired glucose tolerance during weight loss. Recent studies indicate higher toxic equivalencies of dioxin-like PCBs in exposed females than males. Objectives: We compared effects of PCB-77 on weight gain or loss and glucose homeostasis in male vs. female mice. We defined effects of AhR deficiency during weight gain or loss in male and female mice exposed to PCB-77. Methods: Study design was vehicle (VEH) or PCB-77 administration while fed a high-fat (HF) diet for 12 wk, followed by weight loss for 4 wk. The following groups were examined: male and female C57BL/6 mice administered VEH or PCB-77, female AhR+/+ and −/− mice administered VEH or PCB-77, and male AhR+/+ and −/− mice administered PCB-77. Glucose tolerance was quantified during weight gain (week 11) and loss (week 15); liver and adipose AhR and IRS2 (insulin receptor substrate 2) mRNA abundance, and PCB-77 concentrations were quantified at week 16. Results: PCB-77 attenuated development of obesity in females but not males. During weight loss, PCB-77 impaired glucose tolerance of males. AhR-deficient females (VEH) were resistant to diet-induced obesity. Compared with VEH-treated mice, HF-fed AhR+/+ females treated with PCB-77 has less weight gain, and AhR−/− females had greater weight gain. During weight loss, AhR−/− females but not AhR−/− males treated with PCB-77 exhibited impaired glucose tolerance. In AhR−/− females administered PCB-77, IRS2 mRNA abundance was lower in adipose tissue compared with VEH-treated mice. Conclusion: Male and female mice responded differently to PCB-77 and AhR deficiency in body weight (BW) regulation and glucose homeostasis. AhR deficiency reversed PCB-77-induced glucose impairment of obese males losing weight but augmented glucose intolerance of females. These results demonstrate sex differences in PCB-77-induced regulation of glucose homeostasis of mice. https://doi.org/10.1289/EHP4133
Abstract 12320: Concomitant Use of Rivaroxaban and CYP3A4/P-gp Interacting Medications is Not Associated With an Increased Risk of Bleeding in Nonvalvular Atrial Fibrillation (NVAF) Patients
Authors: Elmor D Pineda, Joseph A Goble, Kiumars Zolfaghari, Paul J Godley, Gregory J Dehmer, Dustin N Hartzel, Leeann K Webster, Eric A Wright, Jeffrey B Michel
Journal: Circulation (2018)

Introduction: Rivaroxaban is a known substrate of the cytochrome P450 3A4 (CYP3A4) enzyme and the P-glycoprotein (P-gp) efflux transport system. Theoretically, concomitant use of rivaroxaban with m...
Safety and efficacy of focused ultrasound induced blood-brain barrier opening, an integrative review of animal and human studies
Authors: Ying Meng, Christopher B. Pople, Harriet Lea-Banks, Agessandro Abrahao, Benjamin Davidson, Suganth Suppiah, Laura M. Vecchio, Nardin Samuel, Faiza Mahmud, Kullervo Hynynen, Clement Hamani, Nir Lipsman
Journal: Journal of Controlled Release (2019)
Activity of venetoclax-based therapy in <i>TP53</i>-mutated acute myeloid leukemia.
Authors: Mahran Shoukier, Marina Konopleva, Courtney Denton Dinardo, Farhad Ravandi, Michael Andreeff, Guillermo Garcia-Manero, Elias Jabbour, Naval Guastad Daver, Gautam Borthakur, Naveen Pemmaraju, Guillermo Montalban-Bravo, Christopher Brent Benton, Nicholas James Short, Kapil N. Bhalla, Jorge E. Cortes, Hagop M. Kantarjian, Tapan M. Kadia
Journal: Journal of Clinical Oncology (2019)

7034 Background: Mutations in TP53 are associated with low response rates to standard therapy and poor outcomes in patients (pts) with acute myeloid leukemia (AML). Combination therapy with the BCL2 inhibitor venetoclax (VEN) has emerged as an effective treatment option for pts with AML. Methods: We reviewed pts with TP53-mutated AML treated with VEN-based therapy between 2014-2018. Mutation testing was performed using a whole-exome next-generation sequencing panel. We analyzed the characteristics of these pts, responses to therapy, and outcomes. Results: Sixty nine pts with TP53-mutated AML treated with VEN were identified, 36 (52%) in frontline &amp; 33 (48%) in the salvage (R/R) setting (Table). The median follow up was 4.5 [0.5 - 48.5] and 8 [1 - 46.5] months for frontline &amp; R/R pts, respectively. Karyotype was complex in 32 (88%) and 29 (88%) pts in the frontline &amp; R/R cohorts, respectively. In the R/R cohort, the number of median prior treatments was 2 [0 – 8]. VEN was given in combination with: 1) Hypomethylating agents (HMA) (87%), 2) FLAG-Ida (3%), 3) Low dose Ara-C (4%), or 4) CPX-351 (6%). The overall response rate (ORR) was 47% &amp; 24% in frontline and R/R pts, respectively. All 6 pts with negative minimal residual disease (MRD) achieved complete cytogenetic response after taking VEN % remain in complete remission (CR) with a median of 3.4 [1.7-4.7] months. Two pts (both R/R) underwent allogeneic stem cell transplantation. Conclusions: VEN based therapy was associated with similar ORR, but higher CR rates in TP53 mutated AML compared with HMAs alone. Larger studies with longer follow up are needed to determine the role of VEN-based therapy in this difficult subset. Patient characteristics and outcome. [Table: see text]
A Practical, One Clinic Visit, Population Pharmacokinetic (PK) Protocol for Generation of PK Profiles in Subjects with Severe Hemophilia a
Authors: Victor S. Blanchette, Laura Tiseo, David Lillicrap, Shannon Jackson, Massimo Morfini, Vanessa Bouskill, Manuel Carcao, Margaret L. Rand, Derek Stephens, Liane Khoo, Ester Zapotocka, Vladimir Komrska, Jan Blatny
Journal: Blood (2018)
Association of Preterm Birth and Low Birth Weight With Romantic Partnership, Sexual Intercourse, and Parenthood in Adulthood
Authors: Marina Mendonça, Ayten Bilgin, Dieter Wolke
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Social relationships are important determinants of well-being, health, and quality of life. There are conflicting findings regarding the association between preterm birth or low birth weight and experiences of social relationships in adulthood. <h3>Objective</h3> To systematically investigate the association between preterm birth or low birth weight and social outcomes in adulthood. <h3>Data Sources</h3> PubMed, PsycINFO, Web of Science, and Embase were searched for peer-reviewed articles published through August 5, 2018. <h3>Study Selection</h3> Prospective longitudinal and registry studies reporting on selected social outcomes in adults who were born preterm or with low birth weight (mean sample age ≥18 years) compared with control individuals born at term. <h3>Data Extraction and Synthesis</h3> The meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The data were collected and extracted by 2 independent reviewers. Pooled analyses were based on odds ratios (ORs) with 95% confidence intervals and Hedges<i>g</i>, which were meta-analyzed using random-effects models. <h3>Main Outcomes and Measures</h3> Ever being in a romantic partnership, ever having experienced sexual intercourse, parenthood, quality of romantic relationship, and peer social support. <h3>Results</h3> Twenty-one studies were included of the 1829 articles screened. Summary data describing a maximum of 4 423 798 adult participants (179 724 preterm or low birth weight) were analyzed. Adults born preterm or with low birth weight were less likely to have ever experienced a romantic partnership (OR, 0.72; 95% CI, 0.64-0.81), to have had sexual intercourse (OR, 0.43; 95% CI, 0.31-0.61), or to have become parents (OR, 0.77; 95% CI, 0.65-0.91) than adults born full-term. A dose-response association according to degree of prematurity was found for romantic partnership and parenthood. Overall, effect sizes did not differ with age and sex. When adults born preterm or with low birth weight were in a romantic partnership or had friends, the quality of these relationships was not poorer compared with adults born full-term. <h3>Conclusions and Relevance</h3> These findings suggest that adults born preterm or with low birth weight are less likely to experience a romantic partnership, sexual intercourse, or to become parents. However, preterm birth or low birth weight does not seem to impair the quality of relationships with partners and friends. Lack of sexual or partner relationships might increase the risk of decreased well-being and poorer physical and mental health.
HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy
Authors: Emiko Noguchi, Masato Akiyama, Akiko Yagami, Tomomitsu Hirota, Yukinori Okada, Zenichiro Kato, Reiko Kishikawa, Yuma Fukutomi, Michihiro Hide, Eishin Morita, Michiko Aihara, Makiko Hiragun, Yuko Chinuki, Takahiro Okabe, Akiko Ito, Atsuko Adachi, Atsushi Fukunaga, Yumiko Kubota, Toshiyuki Aoki, Youko Aoki, Kazue Nishioka, Tetsuya Adachi, Nobuo Kanazawa, Hitoshi Miyazawa, Hiroyuki Sakai, Takehito Kozuka, Hideo Kitamura, Hideo Hashizume, Chiharu Kanegane, Koji Masuda, Kumiya Sugiyama, Reiko Tokuda, Junichi Furuta, Ikkou Higashimoto, Atsuko Kato, Mariko Seishima, Akihiko Tajiri, Atsuko Tomura, Hiroko Taniguchi, Hiroto Kojima, Hidenori Tanaka, Aiko Sakai, Wataru Morii, Masashi Nakamura, Yoichiro Kamatani, Atsushi Takahashi, Michiaki Kubo, Mayumi Tamari, Hirohisa Saito, Kayoko Matsunaga
Journal: Journal of Allergy and Clinical Immunology (2019)
Cannabis as a Substitute for Opioids
Authors: Charles John Gonzalez, Nicole Quackenbush, Sharon Stancliff
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Frequency and Practice-Level Variation in Inappropriate and Nonrecommended Prasugrel Prescribing
Authors: Ravi S. Hira, Kevin Kennedy, Hani Jneid, Mahboob Alam, Sukhdeep S. Basra, Laura A. Petersen, Christie M. Ballantyne, Vijay Nambi, Paul S. Chan, Salim S. Virani
Journal: Journal of the American College of Cardiology (2014)
Abstract 18920: Post-Translational Modification of Telomeric Repeat-Binding Factor 2 (terf2)-Interacting Protein (terf2ip) Mediates Atherosclerosis (as) via Orchestrating Endothelial Cells (ec) Senescence (sen) and Inflammation
Authors: Nhat Tu Le, Kyung-Sun Heo, Kyung Ae Ko, Tamlyn Thomas, Keigi Fujiwara, Jun-ichi Abe
Journal: Circulation (2016)

Objective: Shortened telomere (TL) provokes EC Sen, which is associated with focalized EC inflammation and plaque formation in the area exposed by disturbed flow (d-flow). Although it is well known...
Molecular identification of basal-like breast cancer through genomic analyses across five cancer types.
Authors: Aleix Prat, Barbara Adamo, Cheng Fan, Maria Vidal, Patricia Galvan, Enriqueta Felip, Jose Maria Del Campo, Josep Tabernero, Javier Cortes
Journal: Journal of Clinical Oncology (2013)

1011 Background: Common molecular alterations in different types of cancer are being identified and these might be successfully targeted regardless of the tumor´s tissue of origin. To better understand the genomic relationships among different types of cancer, we explored global gene expression patterns across breast, lung, ovarian, brain and colorectal cancers. Methods: A unified set of 1,707 samples of 5 human cancer types (breast [n=547], lung [squamous and adenocarcinomas, n=249], ovarian [serous carcinoma, n=489], brain [glioblastoma multiforme, n=202] and colorectal [n=220]) from The Cancer Genome Atlas (TCGA) project was evaluated. All microarrays were performed at the University of North Carolina under the same protocol and platform. All samples provided in each publication of TCGA were used, except for lung adenocarcinomas where we used TCGA public data. Consensus clustering was used to identify molecular entities, and breast cancer intrinsic subtyping was performed using the PAM50 predictor. Results: A total of 6 distinct and robust molecular entities were identified representing tumors from breast luminal/HER2-enriched, breast Basal-like, lung, ovarian, brain and colorectal cancers. Strikingly, 55%, 26%, 16% of Basal-like breast cancers were found to be more similar to squamous cell lung carcinomas, lung adenocarcinomas and ovarian cancers, respectively, compared to breast luminal/HER2-enriched tumors. Breast cancer intrinsic subtyping identified a Basal-like profile in 55% of squamous cell lung cancers, 53% of ovarian cancers and 8% of lung adenocarcinomas. Finally, single genes and gene signatures tracking cancer-related biological processes such as proliferation, angiogenesis and immune activation were found highly expressed in different proportions across the 6 molecular entities. Conclusions: These data suggest that breast tumors of the Basal-like subtype have a distinct cell of origin compared to luminal/HER2-enriched tumors. Clinical trials focusing on tumors with common profiles and/or biomarker expression rather than their tissue of origin are warranted with a special focus on Basal-like breast cancer, squamous cell lung carcinoma and serous ovarian cancer.
miR-34a as hub of T cell regulation networks
Authors: Martin Hart, Barbara Walch-Rückheim, Lena Krammes, Tim Kehl, Stefanie Rheinheimer, Tanja Tänzer, Birgit Glombitza, Martina Sester, Hans-Peter Lenhof, Andreas Keller, Eckart Meese
Journal: Journal for ImmunoTherapy of Cancer (2019)

Micro(mi)RNAs are increasingly recognized as central regulators of immune cell function. While it has been predicted that miRNAs have multiple targets, the majority of these predictions still await experimental confirmation. Here, miR-34a, a well-known tumor suppressor, is analyzed for targeting genes involved in immune system processes of leucocytes. Using an in-silico approach, we combined miRNA target prediction with GeneTrail2, a web tool for Multi-omics enrichment analysis, to identify miR-34a target genes, which are involved in the immune system process subcategory of Gene Ontology. Out of the 193 predicted target genes in this subcategory we experimentally tested 22 target genes and confirmed binding of miR-34a to 14 target genes including VAMP2, IKBKE, MYH9, MARCH8, KLRK1, CD11A, TRAFD1, CCR1, PYDC1, PRF1, PIK3R2, PIK3CD, AP1B1, and ADAM10 by dual luciferase assays. By transfecting Jurkat, primary CD4+ and CD8+ T cells with miR-34a, we demonstrated that ectopic expression of miR-34a leads to reduced levels of endogenous VAMP2 and CD11A, which are central to the analyzed subcategories. Functional downstream analysis of miR-34a over-expression in activated CD8+ T cells exhibits a distinct decrease of PRF1 secretion. By simultaneous targeting of 14 mRNAs miR-34a acts as major hub of T cell regulatory networks suggesting to utilize miR-34a as target of intervention towards a modulation of the immune responsiveness of T-cells in a broad tumor context.
Hematological profile: A prognosis tool in melanoma patients treated with immunotherapy.
Authors: Soraia Lobo Martins, Patrícia Miguel-Semedo, Diogo Alexandre Martins-Branco, Ana Maria Monteiro, Cecilia Melo Alvim Moreira, Helena Pais, Ines Vendrell, Andre Mansinho, Emanuel Jose Gouveia, Maria-Jose Saramago Passos, Luis Costa, Ana Rita Teixeira Sousa
Journal: Journal of Clinical Oncology (2019)

135 Background: Immunotherapy (IO) has changed the disease course of metastatic malignant melanoma (mMM). Prognostic biomarkers are lacking, but high neutrophil-lymphocyte ratio (NLR) has been correlated with poor outcome. Lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR) are also readily available. This study aimed to investigate the prognostic value of NLR, LMR and PLR. Methods: Retrospective cohort of mMM patients (pts) treated with anti PD-1 blockade in 2 centers, between Jan ’13-Aug ’18. Baseline and 6-week (6 w) blood counts were collected. Cut-offs for NLR, LMR and PLR were defined based on literature and ROC curve method. Progression free survival (PFS; primary outcome) and overall survival (OS) were calculated using log rank test. Uni and multivariate analysis were performed using cox-regression model. Results: Baseline characteristics: 83 pts with median age 65.5 years (range 21-90), 77% BRAFwt, 98% PS-ECOG 0-1, 51% LDH &gt;ULN, 5% on steroids. Median NLR 2.7 (IQR 2.1-3.8), LMR 3.1 (2.1-4.3) and PLR 160.8 (98.3-216.4). The majority of pts (65%) were treated with pembrolizumab. With a median follow-up of 6.2 months (m), median PFS was 7.3 m (CI 5.5-9.2) and median OS was 15.9 m (13.4-18.4). In the multivariate model, baseline NLR high (≥3.0) and PLR high (≥180.0) were associated with worse PFS (HR 2.04, CI 1.11-3.77; p=0.02; and HR 2.50, CI 1.37-4.57; p=0.003). Baseline LMR high (≤2.1) was associated with worse PFS (HR 1.886, CI 1.019-3.488; p=0.043) only on the univariate analysis. At 6 w, 16 out of 39 pts with baseline NLR high presented a decrease in NLR. This was associated with better PFS (HR 0.24, CI 0.09-0.62; p=0.003). Inversely, an increase ≥20% in NLR or PLR was associated with progression (HR 3.65, CI 1.99-6.72, p &lt; 0.001; and HR 3.99, CI 2.01-7.91, p &lt; 0.001). Conclusions: Our data showed that NLR and PLR, as surrogates for systemic inflammation, might be used as prognostic biomarkers for melanoma patients treated with IO. Decreasing NLR in pts with previously high NLR, has a 76% risk reduction of progression. In clinically challenging situations, these biomarkers may help the clinician in an earlier therapeutic orientation.
Treatment of calcinosis cutis in systemic sclerosis and dermatomyositis: A review of the literature
Authors: Hélène Traineau, Rohit Aggarwal, Jean-Benoît Monfort, Patricia Senet, Chester V. Oddis, Carlo Chizzolini, Annick Barbaud, Camille Francès, Laurent Arnaud, François Chasset
Journal: Journal of the American Academy of Dermatology (2019)
Expanding Access to Short-Acting Hormonal Contraceptive Methods in the United States
Authors: Daniel Grossman
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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