tbuckley/cabot-search huggingface dataset:
Compliance and arthralgias in clinical therapy (COMPACT): Assessment of the incidence of arthralgia, therapy costs, and compliance in the first year of adjuvant anastrozole.
Authors: Peyman Hadji, Maria Blettner, Wolfgang W. Bolten, Nadia Harbeck, Hans-Joachim Hindenburg, Christian Jackisch, Peter Klein, Klaus König, Winfried Rief, Diethelm Wallwiener, Silke Zaun, Rolf Kreienberg
Journal: Journal of Clinical Oncology (2012)

e11040^ Background: Aromatase Inhibitors (AI) are well established as adjuvant endocrine treatment for postmenopausal women with HR+ early breast cancer (EBC). However, clinical trial data show higher frequently of arthralgia with AI than tamoxifen. As arthralgia may be greatly influencing compliance to adjuvant therapy, we designed a prospective trial to collect real world data on the effects of AI-associated arthralgia on patient compliance, patient outcomes and treatment costs of arthralgia. Methods: COMPACT is an open, prospective non-interventional study (NCT00857012) assessing the incidence of arthralgia, therapy costs, and compliance within the first year of adjuvant anastrozole (ANA) therapy in postmenopausal patients with HR+ EBC. Patients on adjuvant ANA for 3-6 months were enrolled and stratified by initial adjuvant ANA or switch from tamoxifen. All patients receive regular standardized information about breast cancer from baseline to week 20 to support treatment compliance. Data on demographics, arthralgia, therapy thereof and QoL are collected at baseline, 3, 6 and 9 months. Primary endpoints are scaled data on arthralgia and compliance within the first year of ANA therapy. Secondary endpoints include the incidence of arthralgia, therapy costs, reasons for non-compliance, and influence of arthralgia on clinical outcome. Results: From Apr 2009 to Mar 2011, 2313 patients were enrolled, 2007 on upfront ANA and 306 patients on switch therapy. The mean age was 64.5 years, mean BMI 27.7. Only 16.8% had received HRT prior to their EBC. 41.5% had symptoms relating to skeleton or musculature, and 11.9% stated arthralgia existing prior to ANA. 13.1% reported a worsening of pre-existing arthralgias or new arthralgia after starting ANA. Predictors for non-adherence to AI and scaled data on arthralgia are under analysis. Conclusions: COMPACT aims to provide valid data on AI-associated arthralgia, treatment, treatment costs and compliance to AI. This may help to better inform patients and health care providers about these clinically important issues with the aim to improve adherence to adjuvant ANA, breast cancer outcomes, and therapy costs.
Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice
Authors: Nancy J. Reyes, Chen Yu, Rose Mathew, Carolina M. Kunnen, Joan Kalnitsky, Rachel L. Redfern, Andrea Leonardi, Victor L. Perez, Amanda S. MacLeod, Preeya K. Gupta, Daniel R. Saban
Journal: Science Translational Medicine (2018)

Neutrophils obstruct the meibomian gland in a mouse model of inflammatory eye disease and correlate with disease severity in patients with meibomian gland dysfunction.
Abstract 17177: Crosstalk and Synergism Between Local Brain-derived and Exogenous 17β-Estradiol in Regulating Rapid, Pro-survival Signaling in the Hippocampus Following Global Cerebral Ischemia
Authors: Ruimin Wang, Ratna Vadlamudi, Darrell W BRANN
Journal: Circulation (2015)

Cardiac arrest-induced global cerebral ischemia (GCI) can lead to death of hippocampal CA1 neurons and cognitive impairment. Previous work has shown that the steroid hormone, 17β-estradiol (E2) is strongly neuroprotective against GCI, an effect that involves, in part, rapid signaling via the membrane estrogen receptor, GPR30. To gain greater insight into E2 actions, the current study examined: 1) whether GPR30 expression in the hippocampus changes after CGI, and 2) the role and potential crosstalk/synergism between local (brain-derived) and exogenous E2 in regulation of GPR30 and rapid prosurvival signaling after GCI. GCI was induced in adult ovariectomized female rats by a 4-vessel occlusion model (12-min occlusion). Vehicle or low diestrous levels of E2 were administered chronically by minipump beginning at the time of ovariectomy. The results showed that GPR30 expression in the hippocampal CA1 was unchanged at 3h, but significantly decreased at 1d and 3d after GCI. In contrast, aromatase expression showed an initial decrease at 3h, a rebound at 1day, and a robust elevation at 3 days after CGI. Administration of exogenous E2 increased both GPR30 and aromatase expression at 3h, 1d and 3d after GCI. Interestingly, central administration of the aromatase inhibitor, letrozole or aromatase antisense (AS) oligonucleotides abolished exogenous E2 enhancement of GPR30 and aromatase at 3d after GCI. Furthermore, letrozole and aromatase-AS treatment attenuated exogenous E2-induced phosphorylation/activation of prosurvival ERK1/2 and CREB following GCI, as well as exogenous E2-induced enhanced expression of BDNF, PSD95 and synaptophsin. As a whole, the results suggest that local-derived E2 may help mediate beneficial protective effects of exogenous E2 after GCI to enhance GPR30 expression, increase activation of ERK1/2-CREB-BDNF pro-survival signaling, and improve synaptic function.
Hidradenitis suppurativa treated with secukinumab
Authors: L. Thorlacius, P. Theut Riis, G.B.E. Jemec
Journal: British Journal of Dermatology (2018)

Hidradenitis suppurativa (HS) is a serious skin disease. The cause of HS not known, but it is thought that a disturbance in the immune system's response plays an important role. Studies have found elevated levels of small proteins called cytokines in HS skin. Cytokines are signalling molecules that cells of the immune system use to communicate with each other. Some cytokines cause more inflammation in the skin and others reduce it. IL‐17A is one of the cytokines that cause inflammation, and it was found to be elevated in HS skin. If you remove IL‐17A from the skin tissue, inflammation is reduced and may even disappear. Secukinumab is an antibody that binds and destroys IL‐17A. Because there is a lot of IL‐17A in the skin of HS patients, we have tried this new treatment in a patient with severe disease. Our patient is a 47‐year‐old man, with severe HS. He has been treated for many years and only had temporary benefit from several other treatments that have been tried. We carefully recorded the patient's experience of the treatment, comparing the results at the start of treatment with those after 12 weeks of treatment. After treatment with secukinumab the patient reported fewer boils (going from 23 to 7); less pain (going from 5 to 3 on a ten point scale) and less pain/utility loss/handicap (going from 7 to 4 on a ten point scale). The results may be taken to imply that medications targeting IL‐17A could provide a possible treatment approach for HS in the future.
American Cancer Society Guidelines for the Early Detection of Cancer, 2004
Authors: R. A. Smith, V. Cokkinides, H. J. Eyre
Journal: CA A Cancer Journal for Clinicians (2004)

Each January, the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, including updates, emerging issues that are relevant to screening for cancer, or both. In the spring of 2003, the ACS announced updated guidelines for breast cancer screening, and several other organizations released updated guidelines that we compare with recent ACS updates. Finally, the most recent data pertaining to participation rates in cancer screening are presented by age and sex from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System, as are U.S. maps profiling states based on the proportion of the age-eligible population not recently screened for breast cancer or colorectal cancer.
Inotropic Effects of Glyceryl Trinitrate and Spontaneous NO Donors in the Dog Heart
Authors: BenediktPreckel, GeorgKojda, WolfgangSchlack, DirkEbel, KarinKottenberg, EikeNoack, VolkerThämer
Journal: Circulation (1997)

Background In vitro, NO has a biphasic effect on myocardial inotropy. To determine the inotropic effect of NO in vivo, we investigated the activity of glyceryl trinitrate (GTN) and the NO donors S-nitroso-N-acetyl-d,l-penicillamine (SNAP) and sodium-(2)-1-(N,N-diethyl-amino)-diazen-1-ium-1,2-diolat (DEA/NO) in dogs. Methods and Results Eight anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressures (tip manometers) and coronary flow (ultrasonic flow probes). Regional myocardial function was assessed by sonomicrometry as systolic wall thickening (sWT), mean systolic thickening velocity (Vs), and regional myocardial stroke work index (RSW). GTN, SNAP, and DEA/NO were infused into the left anterior descending coronary artery (LAD) to achieve defined coronary plasma concentrations of GTN, SNAP (both 10 to 100 μmol/L), and DEA/NO (2 to 20 μmol/L). All drugs increased LAD flow and myocardial contractile function in the LAD-dependent myocardium within the first 120 s...
3D‐Plotted Beta‐Tricalcium Phosphate Scaffolds with Smaller Pore Sizes Improve In Vivo Bone Regeneration and Biomechanical Properties in a Critical‐Sized Calvarial Defect Rat Model
Authors: Jingjing Diao, Jun OuYang, Ting Deng, Xiao Liu, Yanting Feng, Naru Zhao, Chuanbin Mao, Yingjun Wang
Journal: Advanced Healthcare Materials (2018)

Abstract Due to the difficulty in fabricating bioceramic scaffolds with smaller pore sizes by the current 3D printing technique, the effect of smaller pore sizes (below 400 µm) of 3D printed bioceramic scaffolds on the bone regeneration and biomechanical behavior is never studied. Herein beta‐tricalcium phosphate (β‐TCP) scaffolds with interconnected smaller pores of three different sizes (100, 250, and 400 µm) are fabricated by 3D plotting. The resultant scaffolds are then implanted into rat critical‐sized calvarial defects without any seeded cells. A custom‐designed device is developed to investigate the biomechanical properties of the scaffolds after surgical implantation for 4, 8, and 12 weeks. The scaffolds with the 100 µm pore size are found to present the highest maximum load and stiffness, comparable to those of the autogenous bone, after being implanted for 12 weeks. Micro‐computed tomography (micro‐CT) and histological analysis further indicate that the scaffolds with the 100 µm pore size achieve the highest percentage of new bone ingrowth, which correlates to their best in vivo biomechanical properties. This study demonstrates that tailoring the pore size of β‐TCP scaffolds to a smaller range by 3D‐plotting can be a facile and efficient approach to enhanced bone regeneration and biomechanical behaviors in bone repair.
Direct Evidence of Nonuniform Distribution of Vagal Effects on Dog Atria
Authors: Ishioninomiya
Journal: Circulation Research (1966)

The duration of the monophasic action potential (APD), the interval between atrial beats and the delay time between excitation of the right and left atria of dogs were measured, using coaxial suction electrodes, before and during vagal stimulation. The effect of vagal stimulation on the degree of shortening of APD varied at different recording sites in the atrium, the shortening being more pronounced in the right than in the left atrium. Threshold and rate of recovery after cessation of stimulation varied throughout the atrium. The results indicate that the vagal effect is nonuniformly distributed over the atrium. The time difference between excitation of the right and left atria increased with vagal stimulation under the present experimental condition, suggesting that a reduction of synchrony of excitation occurred in the atrial myocardial fibers as a whole. The same conclusion was derived from analysis of the pattern of the P wave before and during vagal stimulation.
Bone Marrow–Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages
Authors: HiroshiIwata, IchiroManabe, KatsuhitoFujiu, TetsufumiYamamoto, NorifumiTakeda, KoseiEguchi, AkikoFuruya, MakotoKuro-o, MasatakaSata, RyozoNagai
Journal: Circulation (2010)

Background—It has been proposed that bone marrow–derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow–derived “SM cell–like” cells. Methods and Results—Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SM α-actin, we demonstrated that although some bone marrow–derived cells express SM α-actin in the wire injury–induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC+ bone marrow–derived cells were found in vascular lesions in apolipoprotein E−/−mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow–derived SM α-actin+ cells were also CD115+CD11b+F4/80+Ly-6C+, which is the surface phenotype of inflammatory monocytes. Moreover, adoptively tr...
Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial
Authors: Amit M Oza, Ursula A Matulonis, Susanne Malander, Stacie Hudgens, Jalid Sehouli, Josep M del Campo, Dominique Berton-Rigaud, Susana Banerjee, Giovanni Scambia, Jonathan S Berek, Bente Lund, Anna V Tinker, Felix Hilpert, Isabel Palacio Vázquez, Véronique D'Hondt, Benedict Benigno, Diane Provencher, Joseph Buscema, Shefali Agarwal, Mansoor R Mirza
Journal: The Lancet Oncology (2018)
Biocompatible semiconducting polymer nanoparticles as robust photoacoustic and photothermal agents revealing the effects of chemical structure on high photothermal conversion efficiency
Authors: Jinfeng Zhang, Jing Chen, Jingkun Ren, Weisheng Guo, Xianlei Li, Rui Chen, Jipsa Chelora, Xiao Cui, Yingpeng Wan, Xing-Jie Liang, Yuying Hao, Chun-Sing Lee
Journal: Biomaterials (2018)
Artemisia pollen is the main vector for airborne endotoxin
Authors: Jose Oteros, Elke Bartusel, Francesca Alessandrini, Andrés Núñez, Diego A. Moreno, Heidrun Behrendt, Carsten Schmidt-Weber, Claudia Traidl-Hoffmann, Jeroen Buters
Journal: Journal of Allergy and Clinical Immunology (2018)
Algorithm to detect in situ melanomas
Authors: S. Borsari, R. Pampena, E. Benati, C. Bombonato, K. Athanassios, E. Moscarella, A. Lallas, G. Argenziano, G. Pellacani, C. Longo
Journal: British Journal of Dermatology (2018)

In situ melanoma (MIS) is the very early stage of a skin tumour called melanoma. In recent decades, the incidence rate for melanoma has increased by 2.6% per year and MIS is the main diagnosis responsible for this increase. It is important to recognize MIS, since in this phase (called the intraepidermal phase) cancer cells don't have the opportunity to spread anywhere in the body. Since MIS can be challenging to distinguish from benign (harmless) pigmented lesions, such as normal moles, this study, from Reggio Emilia, Italy, looked at two ways of diagnosing skin cancers that are non‐invasive (meaning they don't require any surgery), called reflectance confocal microscopy (RCM) and dermoscopy, to see if their use can help detect intraepidermal melanomas. Dermoscopy is a cheap, 20‐year‐old method used worldwide, in which doctors use a handheld device called a dermatoscope to look at the skin magnified by about ten times, allowing them to see things that would not be visible to the naked eye. RCM is a more recent technique, but not so readily available, that creates a grey‐scale image of a section of the skin, allowing doctors to see abnormalities, magnified by about 500 times. The authors analysed images of 120 MIS and 213 nevi (moles) using dermoscopy and RCM, which allowed them to identify several features related to MIS diagnosis (RCM aspects of intraepidermal melanoma were not yet well‐known). These features were then combined in a multi‐step diagnostic algorithm which is able to aid the physician to decide if a given pigmented lesion is an early melanoma or not (a score ≥2 signifies melanoma) with a very low margin of error. This new diagnostic algorithm, which is easy to apply, could become helpful in doctors’ clinics.
Breast cancer in older women.
Authors: David B. Pearlstone, Tyler Stewart, Ashkan Afshari, Lyly Nguyen, Rosemary Garofalo
Journal: Journal of Clinical Oncology (2012)

1132 Background: Recent guidelines recommend minimizing breast cancer screening for women over the age of 75. This study examines the presentation and outcome of older patients with breast cancer to determine if increasing screening among older patients may result in better outcomes. Methods: A prospective database at Hackensack University Medical Center was queried for all patients with breast cancer diagnosed between 1/1/2006 and 1/1/2011. Numerical values compared by Student’s t -test; categorical values by Fisher exact test. Median time to events determined by Kaplan-Meier; outcomes compared by log-rank test. Results: 2200 patients were identified (&gt; 75 years, n=335, &lt; 75 years, n=1865). Among the older cohort, mean age was 81 +/- 4 years (range: 75 – 101); mean tumor size was 2.3 +/- 0.1 cm (range: .1 – 12). Most tumors were invasive and localized (in-situ: 12.7%, localized: 57.3%, node positive: 24.0%, metastatic: 5.8%) and most commonly ductal histology (ductal: 77.0%; lobular: 16.6%, mixed:6.2%). Only 10.0% of patients with invasive disease and 29.2% with positive nodes received systemic therapy; 90.2% underwent surgical resection. Disease-free and overall 5 year survival was 54.9% and 62.9% (in-situ: 82.2%; localized: 67.1%; node positive: 57%; metastatic 22%). Older patients had larger tumors (2.30 +/- .11 v. 1.91 +/- .04 cm; p&lt;0.001), more locally advanced (T4) disease (6.7% v. 1.7%, p&lt;.001), more invasive disease (89% v. 84%, p&lt;.01). Older patients had less positive family history (21.7% v. 37.3%, p&lt;.0001). There was no difference between the groups in race, presentation with stage IV disease, tumor grade, lymphovascular invasion, histologic subtype, triple negativity, or nodal positivity. Overall and disease free five year survival were significantly worse for older patients (OS: 90.2% v. 63.9%, p&lt; .0001; DFS: 80.9% v. 54.9%, p&lt;.0001). Conclusions: Breast cancer among older women leads to worse outcomes compared to younger patients, regardless of histology, invasiveness of disease, hormonal status, nodal status or tumor grade. Older women present with more invasive disease, larger tumors and more locally advanced disease, despite having less family history. This implies that continued screening beyond age 75 may lead to less advanced presentation and better outcomes.
SP0098 Hot session: immune related adverse events from checkpoint inhibitor therapy
Authors: L. Calabrese
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Advances in cancer immunotherapy have made it now one of the cornerstones of care for patients with malignancies. Much of these advances have come through the development of checkpoint inhibitors which target negative regulatory signals in the adaptive immune response leading to re-invigoration of cell mediated immunity which had become suppressed or exhausted within the tumoral environment. With such reinvigorated immune response a collateral effect has been the development of autoimmune and or autoinflammatory complications (known as immune related adverse events or irAEs) seen in virtually every organ system. Among these are rheumatic complications estimated to observe in 4%–7% of the exposed population and often requiring acute and chronic immunosuppression to adequately manage. Numerous rheumatic irAEs have been reported the most common of which is inflammatory arthritis as well as myositis, PMR, vasculitis and sicca and others. Rheumatologists are now increasingly seeing such patients as the proliferation of checkpoint therapy increases (three are estimated to be several hundred thousand patients on such therapy in the US with another 1 00 000 patients in varying clinical trial of cancer immunotherapeutics). irAEs in general have been posited to be the potential Achilles heel of cancer immunotherapy. Rheumatologist will be increasing called upon to take key roles in the management of irAEs with a broad spectrum of immunosuppressive and targeted therapies. <h3>Disclosure of Interest</h3> None declared
A pragmatist philosophy of psychological science and its implications for replication
Authors: Ana Gantman, Robin Gomila, Joel E. Martinez, J. Nathan Matias, Elizabeth Levy Paluck, Jordan Starck, Sherry Wu, Nechumi Yaffe
Journal: Behavioral and Brain Sciences (2018)

Abstract A pragmatist philosophy of psychological science offers to the direct replication debate concrete recommendations and novel benefits that are not discussed in Zwaan et al. This philosophy guides our work as field experimentalists interested in behavioral measurement. Furthermore, all psychologists can relate to its ultimate aim set out by William James: to study mental processes that provide explanations for why people behave as they do in the world.
Criminalising HIV transmission is counterproductive and should stop, experts say
Authors: Richard Hurley
Journal: BMJ (2018)

Twenty experts in AIDS research, epidemiology, and care have said in a joint statement that evidence does not support using laws to criminalise the transmission of HIV.

“In many cases, these misconceived laws exacerbate the spread of HIV by driving people living with, and at risk of, infection away from treatment services,” said Linda-Gail Bekker, one of the authors of the statement and professor of medicine at the Desmond Tutu HIV Foundation in Cape Town.

“HIV criminalisation laws are ineffective, unwarranted, and discriminatory,” she said at the International AIDS Conference in Amsterdam on 25 July.

The statement was published in the Journal of the International AIDS Society .1 It said that, “Limited understanding of current HIV science reinforces stigma and may lead to miscarriages of justice.”

At …