tbuckley/cabot-search huggingface dataset:
The 76-Gene Signature Defines High-Risk Patients That Benefit from Adjuvant Tamoxifen Therapy.
Authors: Y. Zhang, A. Sieuwerts, M. McGreevy, C. Graham, T. Cufer, A. Paradiso, N. Harbeck, P. Span, D. Hicks, J. Crowe, R. Tubbs, B. Thomas, J. Lyons, F. Sweep, M. Schmitt, F. Schittulli, R. Golouh, D. Talantov, Y. Wang, J. Foekens
Journal: Cancer Research (2009)

Abstract Background: A significant proportion of ER-positive tumors exhibit resistance to endocrine therapy. Clinical studies in LNN/ER+ patients show that the absolute distant disease-free survival benefit of tamoxifen therapy is only about 9%, with a relative benefit of about 30%. These benefits from treatment may, however, differ substantially according to e.g. patient's age and the tumor level of ER and it is therefore of importance to identify biomarkers that allow identification of those breast cancer patients who may actually benefit from adjuvant tamoxifen. This study was to assess the benefit from adjuvant systemic tamoxifen therapy in breast cancer risk groups identified by the previously established prognostic 76-gene signature.Material and Methods: In 300 lymph node-negative (LNN) estrogen receptor-positive (ER+) breast cancer patients (136 treated with adjuvant tamoxifen, 164 having received no systemic adjuvant therapy), distant metastasis-free survival (DMFS) as a function of the 76-gene signature was determined in a multicenter fashion.Results: In 136 tamoxifen-treated patients, the 76-gene signature identified a group of patients with a poor prognosis (hazard ratio (HR), 4.62, P = 0.0248). These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR, 0.52, P = 0.0318) compared with untreated high-risk patients. This represented a 71% increase in relative benefit compared with the 7.2% absolute benefit observed for all 300 patients without using the gene signature. In the low-risk group there was no significant 10-year DMFS benefit of tamoxifen.Discussion: In summary, the 76-gene signature defines high-risk patients who benefit from adjuvant tamoxifen therapy. Although we did not study the value of chemotherapy in this study, low-risk patients identified by the 76-gene signature have a prognosis good enough that chemotherapy would be difficult to justify. The prognosis of these patients is sufficiently good, in fact, that a disease-free benefit for tamoxifen therapy is difficult to prove, though benefits in terms of oco-regional relapse and a reduction in risk for contralateral breast cancer might justify ormonal therapy in these patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2021.
Incidence and predictors of upgrading and upstaging among 10,000 contemporary patients with low-risk prostate cancer.
Authors: Kathryn Tindell Dinh, Brandon Arvin Virgil Mahal, David R. Ziehr, Vinayak Muralidhar, Yu-Wei Chen, Vidya Bhavani Viswanathan, Michelle Daniel Nezolosky, Clair Beard, Toni K. Choueiri, Neil E. Martin, Peter F. Orio, Christopher Sweeney, Quoc-Dien Trinh, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2015)

32 Background: To inform decisions about active surveillance, we determined the incidence of upgrading and upstaging for a contemporary cohort of low-risk prostate cancer patients who received radical prostatectomy and identified clinical predictors of advanced disease. Methods: We studied 10,273 patients in the Surveillance, Epidemiology, and End Result (SEER) database diagnosed with low-risk prostate cancer (cT1c-T2a, PSA&lt;10 ng/mL and Gleason 3+3=6) in 2010-2011. Upgrading was defined as pathologic Gleason score 7-10 and upstaging as pathologic T3-T4/N1 disease. Regression coefficients were used to evaluate the predictive value of clinical factors for upgrading or upstaging. Significant factors were used to develop a risk stratification table to evaluate individual patients. Results: At prostatectomy, 44% of patients were upgraded and 9.7% were upstaged. Multivariable analysis showed age, PSA, and percent total cores positive were associated with advanced disease (all p&lt;0.001). When these variables were dichotomized by the median, age &gt;60 (Adjusted Odds Ratio [AOR] 1.39), PSA&gt;5.0 (AOR 1.28), and &gt;25% total cores positive (AOR 1.76) were significantly associated with upgrading (all p&lt;0.001). Similarly, age&gt;60 (AOR 1.42), PSA&gt;5.0 (AOR 1.44), and &gt;25% total cores positive (AOR 2.26) were associated with upstaging (all p&lt;0.001). Sixty percent of low-risk patients with PSA 7.5-9.9 and &gt;25% total cores positive were upgraded. Conclusions: A significant proportion of low-risk patients eligible for active surveillance were harboring more aggressive or locally-advanced prostate cancer. Age, PSA and percent total cores positive should be used to assess risk of upgrading or upstaging and can guide decisions to pursue further evaluation or treatment. [Table: see text]
Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial
Authors: Helene E Kobbernagel, Frederik F Buchvald, Eric G Haarman, Carmen Casaulta, Samuel A Collins, Claire Hogg, Claudia E Kuehni, Jane S Lucas, Claus E Moser, Alexandra L Quittner, Johanna Raidt, Susanne Rosthøj, Anne L Sørensen, Kim Thomsen, Claudius Werner, Heymut Omran, Kim G Nielsen
Journal: The Lancet Respiratory Medicine (2020)
Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status
Authors: Susan E. McCann, Paola Muti, Dominica Vito, Stephen B. Edge, Maurizio Trevisan, Jo L. Freudenheim
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4015 

A number of epidemiologic studies, including our own, have shown reduced risks of breast cancer associated with higher urinary lignan excretion and higher dietary intakes, the latter especially among premenopausal women. However, only two studies have investigated the relationship between lignans and estrogen receptor (ER) status in breast cancer. We examined the association of dietary lignan intake with ER negative and ER positive breast cancer risk in the Western New York exposures and Breast Cancer Study (WEB Study), a case-control study of 1122 women with primary, incident, histologically confirmed breast cancer and 2036 controls frequency matched to cases on age, race, and county of residence. Diet was assessed with a self-administered 104-item food frequency questionnaire and other relevant data were collected by detailed in-person interviews. Lignans were expressed as the sum of the dietary precursors secoisolariciresinol and matairesinol. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, total energy, and other breast cancer risk factors. Lignan intake was unrelated to ER positive breast cancer in either pre- or postmenopausal women. Among premenopausal women only, those in the highest versus lowest quartile of lignan intake had an approximately 50% reduction in risk of ER negative breast cancer (OR 0.48, 95% CI 0.25-0.95). These results suggest that the observed negative association of lignans with breast cancer may be limited to ER negative tumors.
Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis–Related, Child–Pugh A Cirrhosis
Authors: Eduardo Vilar-Gomez, Luis Calzadilla-Bertot, Vincent Wai-Sun Wong, Marlen Castellanos, Rocio Aller-de la Fuente, Mohammed Eslam, Grace Lai-Hung Wong, Jacob George, Manuel Romero-Gomez, Leon A. Adams
Journal: Clinical Gastroenterology and Hepatology (2020)
SAT0517 MANAGEMENT OF RISK OF VARICELLA INFECTION IN IMMUNOCOMPROMISED CHILDREN: WHAT IS THE EVIDENCE?
Authors: Maria Seago, Kate Armon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Varicella-naive children on methotrexate are at risk of severe infection if they encounter varicella. Current guidance advises that children on low-dose methotrexate can safely receive live vaccines<sup>1</sup>, but management of children on higher doses or combination immunosuppression is challenging as there is no consensus about their management. Acyclovir and varicella-zoster immune globulin (VZIG) are commonly used as post-exposure prophylaxis (PEP). <h3>Objectives</h3> Assess the evidence for use of acyclovir and/or VZIG as PEP in the management of varicella exposure in susceptible children taking methotrexate. <h3>Methods</h3> A literature search using PubMed, the Cochrane Library and EMBASE was conducted from November to December 2017, using the terms methotrexate, immunocompromised, varicella, child, prophylaxis, acyclovir, VZIG and their variations. Only full papers, in English language, studying children were analysed (63 abstracts read for relevance, 28 papers obtained, 11 papers included). <h3>Results</h3> There have been no randomised controlled trials (RCTs) analysing the effectiveness of acyclovir and/or VZIG as PEP in immunocompromised children. The studies that do exist (see table for key publications) are small and uncontrolled and have largely been carried out in oncology rather than rheumatology patients. While they suggest that acyclovir and VZIG are effective at reducing historical infection rates of &gt;70%<sup>1</sup>, a significant proportion of recipients still get varicella. <h3>Conclusion</h3> There is only level 3 evidence for the use of acyclovir and/or VZIG as PEP in susceptible children on methotrexate. The literature indicates acyclovir is more effective, but this is a grade 3 recommendation only. A RCT to compare the effectiveness and acceptability of VZIG and acyclovir is needed, however the difficulty of randomising a cohort of similarly immunocompromised patients should not be underestimated. <h3>References</h3> [1] Public Health England (2017). Contraindications and special considerations: the green book, chapter 6. Immunisation against infectious disease. [2] Evans, et al. (1980). HUMAN ANTI-CHICKENPOX IMMUNOGLOBULIN IN THE PREVENTION OF CHICKENPOX. The Lancet 315(8164):354-356. [3] Zaia, et al. (1983). Evaluation of Varicella-Zoster Immune Globulin: Protection of Immunosuppressed Children after Household Exposure to Varicella. The Journal of Infectious Diseases147(4):737-743. [4] Shinjoh, et al. (2009). Varicella zoster exposure on paediatric wards between 2000 and 2007: safe and effective post-exposure prophylaxis with oral aciclovir. Journal of Hospital Infection72(2):163-168. <h3>Disclosure of Interests</h3> Maria Seago: None declared, Kate Armon Speakers bureau: Abbvie, but the fee was paid into Addenbrookes charitable account
Current smoking is not associated with COVID-19
Authors: Marco Rossato, Lucia Russo, Sara Mazzocut, Angelo Di Vincenzo, Paola Fioretto, Roberto Vettor
Journal: European Respiratory Journal (2020)

<b>Despite the main complications of SARS-CoV-2 infection regard lung involvement, the prevalence of current smoking in COVID-19 patients is very low, thus questioning the role of coexisting active smoking as a risk factor for COVID-19 pneumonia</b>https://bit.ly/3eUnl1R
A comparison of static serial vs continuous ST-segment recovery to predict outcome after lytics for MI
Authors: M.W. Krucoff, C.L. Green, K.M. Trollinger, C.B. Granger, E.M. Ohman, C.M. O'Connor, R.A. Harrington, P.W. Armstrong, M.L. Simoons, E.J. Topol, R.M. Califf
Journal: Journal of the American College of Cardiology (1998)
Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans
Authors: Erik R. Waara, Muhammad N. Iqbal, Ghislaine Robert‐Nicoud, Boubacar Benziane, Helen Vallhov, Agata M. Wasik, Maria Lindgren, Emilia Hagman, Mia Rinde, Natalia Kupferschmidt, Roger Berlin, Eric V. Johnston, Pernilla Danielsson, Tore Bengtsson
Journal: Advanced Healthcare Materials (2020)

Engineered mesoporous silica particles (MSP) are thermally and chemically stable porous materials composed of pure silica and have attracted attention for their potential biomedical applications. Oral intake of engineered MSP is shown to reduce body weight and adipose tissue in mice. Here, clinical data from a first-in-humans study in ten healthy individuals with obesity are reported, demonstrating a reduction in glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol, which are well-established metabolic and cardiovascular risk factors. In vitro investigations demonstrate sequestration of pancreatic α-amylase and lipase in an MSP pore-size dependent manner. Subsequent ex vivo experiments in conditions mimicking intestinal conditions and in vivo experiments in mice show a decrease in enzyme activity upon exposure to the engineered MSP, presumably by the same mechanism. Therefore, it is suggested that tailored MSP act by lowering the digestive enzyme availability in the small intestine, resulting in decreased digestion of macronutrient and leading to reduced caloric uptake. This novel MSP based mechanism-of-action, combined with its excellent safety in man, makes it a promising future agent for prevention and treatment of metabolic diseases.
The Learning Brain: Lessons for Education, Sarah-Jayne Blakemore, Uta Frith. Blackwell (2005), (232 pp.) £50.00/$59.95 (hbk)/£16.99/$24.95 (pbk), ISBN: 1 4051 0622 0 (hbk)/1 4051 2401 6 (pbk)
Authors: Elsbeth Stern
Journal: Trends in Cognitive Sciences (2005)
CSF total and oligomeric α-Synuclein along with TNF-α as risk biomarkers for Parkinson’s disease: a study in LRRK2 mutation carriers
Authors: Nour K. Majbour, Jan O. Aasly, Eldbjørg Hustad, Mercy A. Thomas, Nishant N. Vaikath, Naser Elkum, Wilma D. J. van de Berg, Takahiko Tokuda, Brit Mollenhauer, Henk W. Berendse, Omar M. A. El-Agnaf
Journal: Translational Neurodegeneration (2020)

Abstract Background Asymptomatic carriers of leucine-rich repeat kinase 2 ( LRRK2 ) gene mutations constitute an ideal population for discovering prodromal biomarkers of Parkinson’s disease (PD). In this study, we aim to identify CSF candidate risk biomarkers of PD in individuals with LRRK2 mutation carriers. Methods We measured the levels of CSF total- (t-), oligomeric (o-) and phosphorylated S129 (pS129-) α-syn, total-tau (tTau), phosphorylated threonine 181 tau (pTau), amyloid-beta 40 (Aβ-40), amyloid-beta-42 (Aβ-42) and 40 inflammatory chemokines in symptomatic ( n = 23) and asymptomatic ( n = 51) LRRK2 mutation carriers, subjects with a clinical diagnosis of PD ( n = 60) and age-matched healthy controls ( n = 34). General linear models corrected for age and gender were performed to assess differences in CSF biomarkers between the groups. Markers that varied significantly between the groups were then analyzed using backward-elimination logistic regression analysis to identify an ideal biomarkers panel of prodromal PD. Results Discriminant function analysis revealed low levels of CSF t-α-syn, high levels of CSF o-α-syn and TNF-α best discriminated asymptomatic LRRK2 mutation carriers from both symptomatic PD and healthy controls. Assessing the discriminative power using receiver operating curve analysis, an area under the curve &gt; 0.80 was generated. Conclusions The current study suggests that CSF t-, o-α-syn and TNF-α are candidate risk biomarkers for the detection of PD at the prodromal stage. Our findings also highlight the dynamic interrelationships between CSF proteins and the importance of using a biomarkers’ panel approach for an accurate and timely diagnosis of PD.
Early Interim 18f-FDG PET In Hodgkin's Lymphoma: Evaluation on 304 Patients
Authors: Pier Luigi Zinzani, Luigi Rigacci, Vittorio Stefoni, Alessandro Broccoli, Benedetta Puccini, Letizia Gandolfi, Stefano Fanti, Antonio Castagnoli, Cinzia Pellegrini, Gian Carlo Montini, Federica Quirini, Giulia Antognoli, Luca Vaggelli, Enrico Derenzini, Lisa Argnani, Valentina Ambrosini, Claudio Agostinelli, Stefano A. Pileri, Alberto Bosi, Michele Baccarani
Journal: Blood (2010)
Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT)
Authors: Brian G. M. Durie, Antje Hoering, Rachael Sexton, Muneer H. Abidi, Joshua Epstein, S. Vincent Rajkumar, Angela Dispenzieri, Stephen P. Kahanic, Mohan C. Thakuri, Frederic J. Reu, Christopher M. Reynolds, Robert Z. Orlowski, Bart Barlogie
Journal: Blood Cancer Journal (2020)

Abstract SWOG S0777, a randomized phase III trial, compared bortezomib, lenalidomide and dexamethasone (VRd) with lenalidomide and dexamethasone (Rd). This updated analysis includes 460 patients evaluable for survival endpoints: 225 eligible and analyzable patients were randomized to Rd and 235 to VRd. The 6-month induction was six 28-day cycles of Rd and eight 21-day cycles of VRd followed by Rd maintenance for all patients. Median follow up is 84 months. Median PFS is 41 months for VRd and 29 months for Rd: stratified hazard ratio (96% Wald Confidence Interval) was 0.742 (0.594, 0.928) and one-sided stratified log-rank P -value 0.003. Median OS for VRd is still not reached with median OS for Rd being 69 months: stratified hazard ratio (96% Wald Confidence Interval) was 0.709 (0.543, 0.926) and stratified two-sided P -value was 0.0114. Both PFS and OS were improved with VRd versus Rd adjusting for age ( P -values: 0.013 [PFS]; 0.033 [OS])). Median duration of Rd maintenance was 17.1 months. The addition of bortezomib to lenalidomide dexamethasone for induction therapy results in a statistically significant and clinically meaningful improvement in PFS as well as better OS. VRd continues to represent an appropriate standard of care irrespective of age.
FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation
Authors: Jun Jacob Hu, Xing Liu, Shiyu Xia, Zhibin Zhang, Ying Zhang, Jingxia Zhao, Jianbin Ruan, Xuemei Luo, Xiwen Lou, Yang Bai, Junhong Wang, L. Robert Hollingsworth, Venkat Giri Magupalli, Li Zhao, Hongbo R. Luo, Justin Kim, Judy Lieberman, Hao Wu
Journal: Nature Immunology (2020)
Risk and Resilience in Minority Youth Populations
Authors: Amy K. Marks, G. Alice Woolverton, Cynthia García Coll
Journal: Annual Review of Clinical Psychology (2020)

This review presents current theory and empirical research that address the interplay between risk and resilience processes among minority youth in the United States. To move the clinical sciences forward in their research and treatment approaches to solving minority-majority health and well-being disparities, ecological, intersectional, and emic (within-group) approaches must be adopted. We discuss the consequences of systematic oppression and marginalization for children in the United States, focusing primarily on research regarding xenophobia, discrimination, and racism. Lastly, we provide examples of recent interventions that take emic approaches to closing minority-majority gaps in developmental outcomes.
Early Life Exposure to Perfluoroalkyl Substances (PFAS) and ADHD: A Meta-Analysis of Nine European Population-Based Studies
Authors: Joan Forns, Marc-Andre Verner, Nina Iszatt, Nikola Nowack, Cathrine Carlsen Bach, Martine Vrijheid, Olga Costa, Ainara Andiarena, Eva Sovcikova, Birgit Bjerre Høyer, Jürgen Wittsiepe, Maria-Jose Lopez-Espinosa, Jesus Ibarluzea, Irva Hertz-Picciotto, Gunnar Toft, Hein Stigum, Mònica Guxens, Zeyan Liew, Merete Eggesbø
Journal: Environmental Health Perspectives (2020)

Introduction: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. Objective: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother–child pairs. Methods: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. Results: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. Conclusion: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444
Erythrocytosis with JAK2 GGCC_46/1 haplotype and without JAK2 V617F mutation is associated with CALR rs1049481_G allele
Authors: Luisa Anelli, Paola Orsini, Antonella Zagaria, Angela Minervini, Nicoletta Coccaro, Elisa Parciante, Crescenzio Francesco Minervini, Cosimo Cumbo, Giuseppina Tota, Luciana Impera, Maria Rosa Conserva, Immacolata Redavid, Francesco Tarantini, Alessandra Ricco, Immacolata Attolico, Giorgina Specchia, Francesco Albano
Journal: Leukemia (2020)
18F-FDG PET/CT in Follicular Dendritic Cell Sarcoma With Paraneoplastic Pemphigus as the First Manifestation
Authors: Xueqi Chen, Zhanli Fu, Xing Yang, Qian Li
Journal: Clinical Nuclear Medicine (2020)

Abstract A 48-year-old woman presented with refractory oral ulcers and skin rashes on the palms and trunk, diagnosed as paraneoplastic pemphigus. The chest x-ray revealed a mass in the right lower chest, and the 18 F-FDG PET/CT scan showed the lesion in the right anterior-inferior mediastinum with intense 18 F-FDG uptake, accompanied by right parasternal adenopathy and pleural effusion. The surgical pathology proved a follicular dendritic cell sarcoma, with right parasternal lymph node metastasis.
Elevated Risk of Venous but Not Arterial Thrombosis in Waldenström's Macroglobulinemia and Lymphoplasmacytic Lymphoma
Authors: Malin L Hultcrantz, Ruth M Pfeiffer, Magnus Bjorkholm, Lynn Goldin, Ingemar Turesson, Sam Schulman, Ola Landgren, Sigurdur Y Kristinsson
Journal: Blood (2012)
TCT-321 Invasively Derived Coronary Flow Capacity: Diagnostic Implications of a Cross-modality Physiological Concept
Authors: Tim P. van de Hoef, Mauro Echavarria-Pinto, Martijn A. van Lavieren, M. Meuwissen, Patrick W. Serruys, Javier Escaned, Jan Piek
Journal: Journal of the American College of Cardiology (2014)
The association of frontal fibrosing alopecia with skin and hair care products: A survey-based case series of 56 patients seen at the Mayo Clinic
Authors: Reese L. Imhof, Sydney C. Larkin, Hafsa M. Cantwell, Rochelle R. Torgerson, Stanislav N. Tolkachjov
Journal: Journal of the American Academy of Dermatology (2020)