tbuckley/cabot-search huggingface dataset:
Biomarkers to evaluate distress in cancer patients.
Authors: Elise Labbe-Coldsmith, Thomas Wayne Butler, Paige Naylor, Ileana Aragon
Journal: Journal of Clinical Oncology (2017)

251 Background: Self-report assessments of stress are a popular, but limiting practice, particularly for underserved populations that may struggle with poor psychological insight and illiteracy. Assessment of stress via biomarkers may be a more inclusive approach to stress assessment for patients with cancer. However, as the rise in popularity regarding biomarker function as outcome data has risen, so to have questions regarding the validity of this endeavor. The current study aimed to explore the convergent validity of inflammatory biomarkers (C-Reactive Protein; CRP, Interleukin 6; IL-6, and Cortisol) while also exploring predictors of stress (e.g., sex, race, marital status) in an underserved, diverse cancer population. Methods: Upon IRB approval, patients ( N = 37) were consented and contributed plasma and serum for the examination of biomarkers (CRP, IL-6, and Cortisol). Next, patients completed the Calgary Symptoms of Stress Inventory (CSOSI; Carlson &amp; Thomas, 2007) to assess for biopsychosocial stress levels. The C-SOSI produces one total score and eight subscales measuring physiological, psychological, and social domains of stress. Results: The mean age of patients was 59.6 ( SD= 13.3) and 56.8% were women. The majority of participants identified as White (56.8%), and a wide variety of cancer types was represented. Biomarkers were analyzed via Quantikine ELISA kits. Correlational analyses revealed that certain subscales showed a positive relationship via medium sized significant correlations. Aside from the Anger subscale, only the physiological subscales were correlated with the biomarkers. The Anger subscale was significantly correlated with Cortisol ( r = .348, p = .035), as was Muscle Tension ( r = .341, p = .039), and Upper Respiratory ( r = .382, p = .02). While Cardiopulmonary Arousal was correlated with CRP ( r = .437, p = .007) and IL-6 ( r = .340, p = .04). Interestingly, IL-6 and CRP were correlated, however, Cortisol was not correlated with IL-6 or CRP. Additional analyses demonstrated significant differences for stress between men and women, which will be discussed. Conclusions: It appears that the biomarkers capture physiological aspects of stress, which may serve in screening patients for psychological intervention.
Reticular Hyperpigmented Eruption in a Young Woman
Authors: Paul M. Hoesly, Mark A. Cappel
Journal: JAMA Dermatology (2017)

A woman in her 20s was seen with a 6-year history of recurrent, pruritic skin eruptions involving the middle and lower back. Physical examination showed several discrete, erythematous, scaly papules admixed with light brown reticulated macules and patches. What is your diagnosis?
111In-DTPA-Octreotide SPECT (OctreoScan) Uptake in Metastatic Renal Cell Carcinoma to the Pancreas
Authors: Kenneth Chan, Tu Vinh Luong, Shaunak Navalkissoor
Journal: Clinical Nuclear Medicine (2017)

We report a case of late presentation of metastatic renal cell carcinoma (RCC) demonstrating intense In-DTPA-octreotide uptake in pancreas without recurrence at the primary site. Immunohistochemistry study revealed somatostatin receptor subtype 2 of metastatic RCC preferentially expressed on tumor endothelial cells. The typical hypervascular features of RCC with intense homogeneous contrast enhancement in the arterial phase on CT should raise the possibility of metastatic RCC. This case illustrates that RCC can demonstrate high octreotide uptake in abdominal metastases.
Implementation of the EULAR cardiovascular risk management guideline in patients with rheumatoid arthritis: results of a successful collaboration between primary and secondary care
Authors: Julia M Weijers, Sanne A A Rongen-van Dartel, Dan M G M F Hoevenaars, Max Rubens, Marlies E J L Hulscher, Piet L C M van Riel
Journal: Annals of the Rheumatic Diseases (2017)

The updated European League Against Rheumatism (EULAR) guideline recommends cardiovascular disease (CVD) risk assessment at least once every 5 years in all patients with rheumatoid arthritis (RA). This viewpoint starts with a literature overview of studies that investigated the level of CVD risk factor (CVD-RF) screening in patients with RA in general practices or in outpatient clinics. These studies indicate that CVD-RF screening in patients with RA is marginally applied in clinical practice, in primary as well as secondary care. Therefore, the second part of this viewpoint describes an example of the successful implementation of the EULAR cardiovascular disease risk management (CVRM) guideline in patients with RA in a region in the south of the Netherlands where rheumatologists and general practitioners (GPs) closely collaborate to manage the cardiovascular risk of patients with RA. The different components of this collaboration and the responsibilities of respectively primary and secondary care professionals are described. Within this collaboration, lipid profile was used as an indicator to assess whether CVD-RF screening was performed in the previous 5 years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined in the previous 5 years. As part of routine quality control, a reminder was sent to the GP in case a patient with RA was not screened. After sending the reminder letter, in 88% of all patients with RA, CVD risk assessment was performed. This collaboration can be seen as good practice to provide care in line with the EULAR guideline.
Molecular photoprotection of human keratinocytes <i>in vitro</i> by the naturally occurring mycosporine-like amino acid palythine
Authors: K.P. Lawrence, R. Gacesa, P.F. Long, A.R. Young
Journal: British Journal of Dermatology (2017)

Solar ultraviolet radiation (UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage; however, most formulations contain organic and inorganic UVR filters that are nonbiodegradable and can damage fragile marine ecosystems. Mycosporine‐like amino acids (MAAs) are natural UVR‐absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow‐water habitats. To determine if palythine, a photostable model MAA, could offer protection against a range of UVR‐induced damage biomarkers that are important in skin cancer and photoageing. HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of end points including cell viability, DNA damage (nonspecific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The antioxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays. Palythine offered statistically significant protection (P < 0·005) against all end points tested even at extremely low concentrations (0·3% w/v). Additionally, palythine was found to be a potent antioxidant, reducing oxidatively generated stress, even when added after exposure. Palythine is an extremely effective multifunctional photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to currently approved UVR filters.
Human-Specific Mutations and Positively Selected Sites in MARCO Confer Functional Changes
Authors: Kyle E Novakowski, Nicholas V L Yap, Charles Yin, Kaori Sakamoto, Bryan Heit, G Brian Golding, Dawn M E Bowdish
Journal: Molecular Biology and Evolution (2017)

Macrophage Receptor with COllagenous structure (MARCO) is a class A scavenger receptor that binds, phagocytoses, and modifies inflammatory responses to bacterial pathogens. Multiple candidate gene approach studies have shown that polymorphisms in MARCO are associated with susceptibility or resistance to Mycobacterium tuberculosis infection, but how these variants alter function is not known. To complement candidate gene approach studies, we previously used phylogenetic analyses to identify a residue, glutamine 452 (Q452), within the ligand-binding Scavenger Receptor Cysteine Rich domain as undergoing positive selection in humans. Herein, we show that Q452 is found in Denisovans, Neanderthals, and extant humans, but all other nonprimate, terrestrial, and aquatic mammals possess an aspartic acid (D452) residue. Further analysis of hominoid sequences of MARCO identified an additional human-specific mutation, phenylalanine 282 (F282), within the collagenous domain. We show that residue 282 is polymorphic in humans, but only 17% of individuals (rs6761637) possess the ancestral serine residue at position 282. We show that rs6761637 is in linkage disequilibrium with MARCO polymorphisms that have been previously linked to susceptibility to pulmonary tuberculosis. To assess the functional importance of sites Q452 and F282 in humans, we cloned the ancestral residues and loss-of-function mutations and investigated the role of these residues in binding and internalizing polystyrene microspheres and Escherichia coli. Herein, we show that the residues at sites 452 and 282 enhance receptor function.
Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection
Authors: Chien-Chia Chen, Eric Pouliquen, Alexis Broisat, Francesco Andreata, Maud Racapé, Patrick Bruneval, Laurence Kessler, Mitra Ahmadi, Sandrine Bacot, Carole Saison-Delaplace, Marina Marcaud, Jean-Paul Duong Van Huyen, Alexandre Loupy, Jean Villard, Sandrine Demuylder-Mischler, Thierry Berney, Emmanuel Morelon, Meng-Kun Tsai, Marie-Nathalie Kolopp-Sarda, Alice Koenig, Virginie Mathias, Stéphanie Ducreux, Catherine Ghezzi, Valerie Dubois, Antonino Nicoletti, Thierry Defrance, Olivier Thaunat
Journal: Journal of Clinical Investigation (2017)

Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies.
El objetivo de la eliminación del sarampión en 2010: la necesidad de encontrar grupos de riesgo específicos
Authors: J. S. Spika
Journal: Eurosurveillance (2006)

En la region Europea de la Organizacion Mundial de la Salud (OMS) se realizaron progresos importantes estos ultimos anos hacia el objetivo de eliminar el sarampion y la rubeola en 2010. Tales objetivos fueron definidos en 2005 por la Oficina Regional Europea de la OMS tras la aprobacion de la Resolucion EUR/RC55/R7 [1,2]. En 2005, 28 (54%) de los 52 Estados miembros de la OMS declaraban una incidencia del sarampion inferior a 1 por millon (un indicador que sirve para medir el estatus de eliminacion del sarampion) y en 2006, 50 (el 96%) habian introducido la vacuna de la rubeola en sus programas nacionales. En 2002, los estados miembros empezaron la notificacion mensual a la OMS de los casos de sarampion por edad y estatus vacunal [3]. La declaracion basada en los casos individuales se implemento en 2003. El numero de paises que declararon datos individuales aumento de uno en 2003 a 23 en 2006. Desde 2006, los paises deben notificar mensualmente los casos de rubeola (agregados o individualizados). Tambien se reforzo la red de laboratorios de sarampion y rubeola de la region Europea de la OMS por medio de evaluaciones regulares de los laboratorios y pruebas de eficacia, y a traves de reuniones entre varios paises miembros.
Thyrotoxicosis with Heart Block
Authors: V Vassiliou
Journal: Journal of the Royal Society of Medicine (2001)

Dr Faizel Osman and colleagues (July 2001 JRSM, pp. 346-348) present two cases of thyrotoxicosis with heart block. For the second patient, who responded well only to steroid therapy, they raise the question whether the triad of thyrotoxicosis, heart block and raised erythrocyte sedimentation rate could be due to a single autoimmune disease; yet they do not say whether this was investigated or not.
BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment
Authors: Yueye Huang, Shen Qu, Guangwu Zhu, Fei Wang, Rengyun Liu, Xiaopei Shen, David Viola, Rossella Elisei, Efisio Puxeddu, Laura Fugazzola, Carla Colombo, Barbara Jarzab, Agnieszka Czarniecka, Alfred K Lam, Caterina Mian, Federica Vianello, Linwah Yip, Garcilaso Riesco-Eizaguirre, Pilar Santisteban, Christine J O’Neill, Mark S Sywak, Roderick Clifton-Bligh, Bela Bendlova, Vlasta Sýkorová, Mingzhao Xing
Journal: JNCI Journal of the National Cancer Institute (2017)

Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined.
Extreme exploitation in Southeast Asia waters: Challenges in progressing towards universal health coverage for migrant workers
Authors: Rapeepong Suphanchaimat, Nareerut Pudpong, Viroj Tangcharoensathien
Journal: PLoS Medicine (2017)

Labour exploitation and enslavement of sea workers have caught significant political attention in many Southeast Asian countries in recent years.These human rights violations are complicated by human trafficking syndicates, economic disparities between countries in the region, weak rule of law, inadequate labour inspection and protections, poor access to healthcare, and corruption.• Although some Southeast Asian nations attempt to protect the health and well-being of "everyone" on their soil by introducing health insurance policies, there remain unsolved implementation challenges.• Effectively combating extreme labour exploitation requires a collective effort from all concerned stakeholders, seamless collaboration across countries, and long-term comprehensive mechanisms to prevent further abusive treatments; this is particularly relevant with a highly mobile population like migrant seafarers.
General Anesthesia Inhibits the Activity of the “Glymphatic System”
Authors: Clement Gakuba, Thomas Gaberel, Suzanne Goursaud, Jennifer Bourges, Camille Di Palma, Aurélien Quenault, Sara Martinez de Lizarrondo, Denis Vivien, Maxime Gauberti
Journal: Theranostics (2017)

INTRODUCTION:According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF).Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space.Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation.METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS:In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation.Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia.This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane).These results were consistent across the different anesthesia regimens and imaging modalities.Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice.CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness.General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.
Deep learning analysis of the myocardium in coronary CT angiography for identification of patients with functionally significant coronary artery stenosis
Authors: Majd Zreik, Nikolas Lessmann, Robbert W. van Hamersvelt, Jelmer M. Wolterink, Michiel Voskuil, Max A. Viergever, Tim Leiner, Ivana Išgum
Journal: Medical Image Analysis (2017)
Abstract 24082: A Combined Basic Science and PopulationScience Approach Demonstrating the Potential for Simvastatin to MitigateCardiovascular Disease after Lower Hemi Body Radiotherapy
Authors: Jessica Olson, Reiauna Taylor, Rodney Sparapani, Marek Lenarczyk, John Baker
Journal: Circulation (2017)

Radiation is a cornerstone of successful cancer treatment, with one-half to two-thirds of all patients receiving radiotherapy. Survivors of cancer treated with radiation are at increased risk for cardiovascular disease (CVD). Understanding how radiation causes CVD will allow development of novel therapies. Irradiation of the lower hemi body, but not the upper hemi body, with 10 Gy in rats increases risk factors for CVD and results in cardiac fibrosis quantitatively similar to total body irradiation, suggesting radiation injury to the heart can be indirect. Simvastatin, an inhibitor of liver cholesterol synthesis administered continuously to rats (10 mg/kg/day) after 10 Gy lower hemi body irradiation mitigated against increased blood cholesterol and cardiac fibrosis. These findings indicate simvastatin limits transmission of a signal from the lower hemi body that decreases risk for and occurrence of CVD independent of any direct exposure of the heart to radiation. Bivariate examination of 3,607 patients following therapeutic lower hemi body irradiation using Chi-square, Wilcoxon rank-sum and t-tests was used to examine risk factors for CVD in patients diagnosed with congestive heart failure, myocardial infarction, atrial fibrillation, and cardiomyopathy before 80 years of age. We found that 47.4% of patients age 70-80 developed CVD compared to 29.7% who received simvastatin (p= &lt; 0.001, n = 293 and 361, respectively). Patients who were male, overweight, smokers, and had a diagnosis of chronic kidney disease and diabetes also had significantly higher risk of CVD. Race and hypertension were not indicative of increased risk for CVD. These clinical findings, taken together with the results from our animal studies, support a new research paradigm where radiation-induced heart disease can be indirect, with abdominal organs exporting factors that cause CVD. Simvastatin can be developed to mitigate and treat CVD after therapeutic radiation.
HBsAg quantification in HBeAg negative cirrhosis on nucleoside/nucleotide analogue (NA) and risk of development of HCC
Authors: F. Bronte, D. Ferraro, V. Calvaruso, G. Pecoraro, S. Sferrazza, M. Augugliaro, N. Destri, A. Craxi, V. Di Marco
Journal: Hepatology (2013)
Abstract 16105: Long Non-coding RNA TYKRIL Regulates Pericyte Survival in the Cardiovascular and Central Nervous System in vivo in a p53 Dependent Manner
Authors: Christoph M Zehendner, Serge C Thal, Astrid Werner, Jes-Niels Boeckel, Florian Bischoff, David John, Tyler Weirick, Nicolas Jaé, Shemsi Demolli, Regina Hummel, Katharina Michalik, Benjamin Meder, Hugo A Katus, Jan Haas, Wei Chen, Shizuka Uchida, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2016)

Background:  Vessel maturation is dependent on platelet derived growth factor (PDGF), which signals via tyrosine kinase receptors and facilitates recruitment of pericytes. Long noncoding RNAs (lncRNAs) regulate endothelial and smooth muscle cell properties, but their role in pericyte function is unclear.   Hypothesis:  Here we assessed the hypothesis that lncRNA TYKRIL (Tyrosin kinase receptor inducing lncRNA) regulates pericyte survival.   Results and Discussion:  Using RNA sequencing, we identify the hypoxia induced lncRNA TYKRIL as a species conserved lncRNA which regulates pericyte survival in vitro and in vivo. Using RNA immunoprecipitation (RIP) we demonstrate that TYKRIL binds to p53 (TYKRIL enrichment fold change (FC) 2.7±0.27 vs Ctrl. P  TYKRIL loss fostered p53-p300 interaction in proximity ligation assays (3.57±0.5 FC vs Ctrl., P  Targeting the murine TYKRIL orthologue in the CNS in vivo by LNA GapmeRs resulted in pericyte loss in the cerebral cortex (0.4±0.09 FC vs. Ctrl, P   Conclusion:  Here, we identify the lncRNA TYKRIL as a p53 decoy molecule that represses p53 activation, thereby regulating pericyte survival in vitro and in vivo. Our results identify TYKRIL as a regulator of pericyte function, which may enable to develop novel concepts for pro- or anti-angiogenic therapies in cardiovascular disease and malignancy.
The Promise and Challenges of CAR-T Gene Therapy
Authors: Bridget M. Kuehn
Journal: JAMA (2017)

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