tbuckley/cabot-search huggingface dataset:
Neglected breast cancers in an inner city hospital.
Authors: Sarah Louise Picardo, MinYuen Teo, Jane Sze Yin Sui, Lynda M. O'Riordan, Michael Thomas McCarthy, Deirdre Kelly, Saira Nasim, Desmond N. Carney, Michaela Jane Higgins, Catherine Margaret Kelly, John McCaffrey
Journal: Journal of Clinical Oncology (2015)

e11540 Background: Breast cancer is the most commonly diagnosed malignancy in women. Due to widespread use of mammographic screening and awareness campaigns, under 10% present with metastatic disease. Nevertheless, some women continue to present with advanced neglected breast cancers. We sought to investigate characteristics of these patients in a European inner city hospital setting. Methods: We defined neglected breast cancers as those in which symptoms had been present for at least 3 months and with documented skin changes. Demographic, clinical and pathological data on patients presenting to an inner city hospital in Ireland over a 3 year period were retrospectively identified from a prospectively maintained database. Characteristics of these patients were analysed in order to determine factors contributing to their delayed presentation. Results: Between 2012 and 2014, the total number of newly diagnosed breast cancers was 819. Sixteen women were identified with neglected breast cancers, comprising 2% of the total. Median age of these patients was 59 (range: 29-84). Eight patients reported that symptom duration of over 1 year. 50% of patients had ulcerated/bleeding tumours at presentation. Eleven patients (73%) had tumours measuring > 5cm, of which 10 were ER+. At initial staging, 11 patients had metastatic disease, the majority to bone and non-regional lymph nodes. Three patients received hormonal treatment only, all aged over 80. The majority of patients (75%) had no medical co-morbidities, while only one patient had a psychiatric condition. Socially, 6 women (38%) lived alone, while 8 lived with partners. Of 12 patients aged under 65, 50% were unemployed. Three patients were immigrants from non-English speaking countries. Of the 16 patients in this study, 2 did not attend for follow up, while 3 were either non-compliant with treatment or refused the recommended treatment option. Conclusions: We found that neglected breast cancers represent only a very small proportion of breast cancer patients. Even in an inner city setting, the majority were employed, partnered, and non-immigrant. Most presented with metastatic disease. Further qualitative interview-based studies could identify themes and factors amenable to intervention.
Phase II study of atorvastatin in combination with radiotherapy and temozolomide in patients with glioblastoma.
Authors: Abdullah Khalaf Altwairgi, Waleed Ali Alghareeb, Fouad H AlNajjar, Mohammed Mubasher, Hussain Alhussain, Rasha Mustafa Saleh
Journal: Journal of Clinical Oncology (2014)

TPS2102 Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Despite recent advances in the understanding of the molecular mechanism of tumorigenesis, the outcome remains poor. Atorvastatin is an inhibitor of HMG-CoA reductase, a rate-limiting enzyme in the mevalonate pathway. Preclinical studies have demonstrated pro-apoptotic, anti-proliferative, anti-invasive, and radiosensitizing properties of statins. To date, no prospective studies have addressed the anti-tumor effects of statins in GBM. This trial was designed to determine the efficacy and safety of atorvastatin in combination with radiotherapy and temozolomide (TMZ) in patients with newly diagnosed GBM. Methods: In this open-label, prospective, single-arm, phase II study, eligible patients will receive oral atorvastatin (40 mg/d for 3 weeks and 80 mg/d thereafter) until disease progression or significant toxicity, in combination with standard therapy comprising radiotherapy (60 Gy/30 fractions) and TMZ (75 mg/m2/d) in the 6-wk concurrent phase, then with TMZ (150-200 mg/m2/d on days 1-5 for 6 cycles). The key eligibility criteria includes: adults (≥18 years) with newly diagnosed GBM, who have undergone surgical resection or biopsy, ECOG performance status ≤ 2, adequate organ function, no prior chemotherapy or radiotherapy, stable dose of steroids for ≥14 days prior to registration, and written informed consent. The primary endpoint is progression free survival (PFS) at 6 months (RANO criteria). Secondary endpoints include overall survival (OS), and safety. A minimum of 80% power required at least 32 eligible patients to be enrolled starting January 2014 with a planned interim analysis after the first 15 evaluable patients. Statistical analysis plan includes Kaplan Meir techniques and Cox proportional hazard modeling. Clinical trial information: NCT02029573.
Abstract 12745: Interleukin-4 Promotes Procollagen Type-I Alpha 1 Gene Expression via Activator Protein 1 Activation in Cardiac Fibroblasts
Authors: Hongmei Peng, Min Wu, Edward Peterson, Nour-Eddine Rhaleb
Journal: Circulation (2016)

Interleukin-4 (IL-4) activates the signal transducer and activator of transcription 6 signaling pathway, resulting in the upregulation of procollagen genes and promotion of collagen production in cardiac fibroblasts (CFs). In addition, transcription factors may participate in the transcriptional activation of collagen genes. We hypothesize that IL-4 activates activator protein 1 (AP-1) via c-Jun phosphorylation, promoting transcriptional activation of the procollagen type-I alpha 1 (Col1α1) gene and collagen type-I expression in CFs. Primary mouse CFs were used. Western blot analyses revealed that IL-4 (10 ng/ml) increased phosphorylation of c-Jun, a subunit of AP-1. Additionally, our experiments utilizing electrophoretic mobility shift assay (EMSA) revealed a significant increase in DNA binding activity for AP-1 in IL-4-treated CFs compared to control cells (1.00±0.07 to 2.14±0.38 fold change versus control, p &lt;0.05). Here we aimed to determine whether IL-4-activated AP-1 participates in transcriptional activation of the Col1α1 gene leading to increased collagen type-I expression in CFs. To that end, we blocked AP-1 with shRNA lentiviral particles specific for c-Jun in CFs, detected Col1α1 mRNA by qRT-PCR, and measured collagen type-I by Western blot. We found that IL-4 significantly induced Col1α1 mRNA expression after incubation with control shRNA-transduced cells for 6 hours (1.01±0.01 to 1.52±0.07 fold change versus control, p &lt;0.005), and it increased collagen type-I expression after 24 hours of incubation (1.00±0.01 to 1.95±0.12 fold change versus control, p &lt;0.005). In contrast, IL-4 did not increase mRNA levels of Col1α1 (1.09±0.02 to 0.98±0.03, p &gt;0.05) and the collagen type-I (0.95±0.05 to 1.01±0.10, p &gt;0.05) in c-Jun shRNA-transfected cells. Our data demonstrate that IL-4-activated AP-1, an ubiquitous transcription factor containing phosphorylated c-Jun, enhanced Col1α1 gene expression and collagen type-I expression in CFs. Data generated from this study provides a novel molecular basis for potential treatment of cardiac fibrosis by targeting IL-4-induced signaling in CFs.
APOL1 Genotype and Renal Function of Black Living Donors
Authors: Mona D. Doshi, Mariella Ortigosa-Goggins, Amit X. Garg, Lihua Li, Emilio D. Poggio, Cheryl A. Winkler, Jeffrey B. Kopp
Journal: Journal of the American Society of Nephrology (2018)

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n =19; 14%) or low-risk (one or zero risk alleles; n =117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m 2 ; P =0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m 2 ; P =0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m 2 per year, P =0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline ( P =0.39) or any statistical interaction by APOL1 status ( P =0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.
Study On Asthma Exacerbations In Patients With Asthma And Rhinitis
Authors: Ken Ohta, Hiroshi Tanaka, Yuhji Tohda, Hirotsugu Kohrogi, Kazuo Akiyama, Junichi Chihara, Hiroki Sakakibara, Mitsuru Adachi, Gen Tamura
Journal: Journal of Allergy and Clinical Immunology (2018)
Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease
Authors: Shipra Arya, Anjali Khakharia, Zachary O. Binney, Randall R. DeMartino, Luke P. Brewster, Philip P. Goodney, Peter W.F. Wilson
Journal: Circulation (2018)

Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality.
Abstract 20370: Baseline Consumer Study of Public Awareness About Sudden Cardiac Arrest
Authors: Mary M Newman, Jennifer Chap, Kelly N Sawyer, Youssou Ba, Karen Ba, Rick Chap
Journal: Circulation (2016)

Introduction:  Survival from sudden cardiac arrest (SCA) depends largely on bystander intervention with CPR and automated external defibrillators (AEDs). While several public awareness studies have been conducted, none have examined awareness of SCA relative to other health conditions. A research approach using open-ended responses (unaided awareness) to investigate where SCA fits on the consumer hierarchy of healthcare concerns is needed and may generate deeper insights into public perceptions and knowledge gaps.   Hypothesis:  We hypothesized that gaps in public awareness/ understanding of SCA, CPR and AEDs contribute to consumer apathy.   Methods:  In November 2015, we conducted a quantitative online study of a national representative sample of 999 US respondents, a benchmark sample of 202 respondents from King County (KC), WA, and one-on-one 20-minute interviews with 10 respondents from 6 states in Orlando, FL.   Results:  On an unaided basis, consumers’ top health concerns were cancer (47%), heart disease (46%) and diabetes (34%). No respondents specifically mentioned SCA; only 5% mentioned heart attack. Familiarity with SCA ranked 10 th  out of 13 health conditions shown to respondents. When exposed to a definition of SCA, interest in learning CPR increased from 61 to 80% and interest in learning how to use an AED increased from 33 to 54%. Among 11 statements tested, top motivators to learn CPR/AED were: SCA can happen to anyone, anywhere, anytime—including a loved one (55%), immediate CPR can double or triple survival (52%), and availability of convenient and free CPR/ AED training options (49%). Barriers to action include concern about hurting the victim (42%), lack of confidence/ competence (40%), liability concerns (34%), and belief someone else would be more competent (34%). More than one-third of respondents reported having taken a CPR course. More respondents in the KC sample reported having taken an AED course, compared with the national sample. (17.8 v. 11.8%, p ≤ .05)   Conclusions:  Results suggest that SCA is not on consumers’ radar. When SCA is clearly defined, respondents report they are motivated to learn CPR and how to use an AED. Creating a uniform definition of SCA, written in consumer-friendly language, is recommended.
Interfacial Mineral Fusion and Tubule Entanglement as a Means to Harden a Bone Augmentation Material
Authors: Erik A. B. Hughes, Sophie C. Cox, Megan E. Cooke, Owen G. Davies, Richard L. Williams, Thomas J. Hall, Liam M. Grover
Journal: Advanced Healthcare Materials (2018)

Abstract A new bone augmenting material is reported, which is formed from calcium‐loaded hydrogel‐based spheres. On immersion of these spheres in a physiological medium, they become surrounded with a sheath of precipitate, which ruptures due to a build‐up in osmotic pressure. This results in the formation of mineral tubes that protrude from the sphere surface. When brought into close contact with one another, these spheres become fused through the entanglement and subsequent interstitial mineralization of the mineral tubules. The tubular calcium phosphate induces the expression of osteogenic genes (runt‐related transcription factor 2 (RUNX2), transcription factor SP7 (SP7), collagen type 1 alpha 1 (COL1A1), and bone gamma‐carboxyglutamic acid‐containing protein (BGLAP)) and promotes the formation of mineral nodules in preosteoblast cultures comparable to an apatitic calcium phosphate phase. Furthermore, alkaline phosphatase (ALP) is significantly upregulated in the presence of tubular materials after 10 d in culture compared with control groups ( p &lt; 0.001) and sintered apatite ( p &lt; 0.05). This is the first report of a bioceramic material that is formed in its entirety in situ and is therefore likely to provide a better proxy for biological mineral than other existing synthetic alternatives to bone grafts.
Poly(Lactic‐co‐Glycolic) Acid: Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications (Adv. Healthcare Mater. 1/2018)
Authors: Cláudia Martins, Flávia Sousa, Francisca Araújo, Bruno Sarmento
Journal: Advanced Healthcare Materials (2018)
Abstract P208: The Joint Association of Low Vitamin D and Vitamin K Status with Blood Pressure and Hypertension
Authors: Hanne van Ballegooijen, Ingeborg A Brouwer, Marjolein Visser, Natasja van Schoor, Joline W Beulens
Journal: Circulation (2017)

Introduction: Low vitamin D and vitamin K status are both associated with cardiovascular risk. New evidence from experimental studies on bone health suggest an interaction between vitamin D and K, however a joint association with vascular health outcomes is largely unknown. Hypothesis: We assessed the hypothesis that the combination of low vitamin D and low vitamin K status is associated with higher systolic and diastolic blood pressure in 402 participants and with incident hypertension in 231 participants free of hypertension at baseline. Methods: We used data from a subsample of the Longitudinal Aging Study Amsterdam (LASA), a population-based cohort of Dutch participants 55-65 years. Vitamin D and K status were assessed by measuring 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP). High dp-ucMGP is indicative of a low vitamin K status. Generalized estimating equation and Cox proportional hazard models were used for the association of vitamin D and vitamin K status with blood pressure and incident hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg or using anti-hypertensive medication). Results: During a median follow-up of 6.4 years, 62% of the participants (n=143) developed hypertension. Vitamin D and vitamin K status were categorized in groups: 25(OH)D &lt;50/≥50 mmol/L and median dp-ucMGP &lt;323/≥323pmol/L. The combination of low 25(OH)D &lt;50 nmol/L and high dp-ucMGP ≥323 pmol/L was associated with increased systolic 4.8 mmHg (95% CI 0.1-9.5) and diastolic 3.1 mmHg (0.5-5.7) blood pressure compared to 25(OH)D ≥50 mmol/L and dp-ucMGP &lt;323 pmol/L, after adjusting for age and sex, BMI, alcohol consumption, smoking, education, season of blood collection, total cholesterol and estimated glomerular filtration rate. A similar trend was seen for incident hypertension HR:1.62 (0.96-2.73). Conclusions: The combination of low vitamin D and K status was associated with increased blood pressure and might play a role in the development of hypertension.
Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer
Authors: Rona Yaeger, Walid K. Chatila, Marla D. Lipsyc, Jaclyn F. Hechtman, Andrea Cercek, Francisco Sanchez-Vega, Gowtham Jayakumaran, Sumit Middha, Ahmet Zehir, Mark T.A. Donoghue, Daoqi You, Agnes Viale, Nancy Kemeny, Neil H. Segal, Zsofia K. Stadler, Anna M. Varghese, Ritika Kundra, Jianjiong Gao, Aijazuddin Syed, David M. Hyman, Efsevia Vakiani, Neal Rosen, Barry S. Taylor, Marc Ladanyi, Michael F. Berger, David B. Solit, Jinru Shia, Leonard Saltz, Nikolaus Schultz
Journal: Cancer Cell (2018)
Sex and Race Differences in Lifetime Risk of Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction
Authors: Ambarish Pandey, Wally Omar, Colby Ayers, Michael LaMonte, Liviu Klein, Norrina B. Allen, Lewis H. Kuller, Philip Greenland, Charles B. Eaton, John S. Gottdiener, Donald M. Lloyd-Jones, Jarett D. Berry
Journal: Circulation (2018)

Lifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.Participant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.We included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.Lifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control.
Evolving Recommendations for Scoliosis Screening
Authors: John F. Sarwark, Matthew M. Davis
Journal: JAMA (2018)

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
Counting Calories as an Approach to Achieve Weight Control
Authors: Eve Guth
Journal: JAMA (2018)

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
Essential thrombocythemia treatment algorithm 2018
Authors: Ayalew Tefferi, Alessandro M. Vannucchi, Tiziano Barbui
Journal: Blood Cancer Journal (2018)

Abstract Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e.g., ruxolitinib). Furthermore, the main indication for treatment in ET and PV is to prevent thrombosis and, in that regard, none of the newer drugs have been shown to be superior to the time-tested older drugs (e.g., hydroxyurea). We currently consider three major risk factors for thrombosis (history of thrombosis, JAK2 / MPL mutations, and advanced age), in order to group ET patients into four risk categories: “very low risk” (absence of all three risk factors); “low risk” (presence of JAK2 / MPL mutations); “intermediate-risk” (presence of advanced age); and “high-risk” (presence of thrombosis history or presence of both JAK2 / MPL mutations and advanced age). Herein, we provide a point-of-care treatment algorithm that is risk-adapted and based on evidence and decades of experience.
Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses
Authors: Simone L. Park, Ali Zaid, Jyh Liang Hor, Susan N. Christo, Julia E. Prier, Brooke Davies, Yannick O. Alexandre, Julia L. Gregory, Tiffany A. Russell, Thomas Gebhardt, Francis R. Carbone, David C. Tscharke, William R. Heath, Scott N. Mueller, Laura K. Mackay
Journal: Nature Immunology (2018)
Sympathetic myocardial innervation and prognosis in hypertrophic cardiomyopathy: aprospective , long-term study in a tertiary center.
Authors: Gianfranco Buja, P Zanco, Paola Melacini, L Leoni, Valentina Pescatore, M Bevilacqua, A Gardin, Domenico Corrado, Sabino Iliceto, Gaetano Thiene
Journal: Circulation (2009)