tbuckley/cabot-search huggingface dataset:
Cavitation of lung metastases induced by regorafenib is associated with radiological response in metastatic colorectal cancer: data from the phase III correct study
Authors: R. Ricotta, S. Ghezzi, A. Verrioli, L. Porcu, C. Cremolini, G. Argiles, A. Adenis, M. Ychou, C. Barone, O. Bouche, Y. Humblet, L. Mineur, A. Sobrero, L. Pietrogiovanna, M. Maiolani, D. Galbiati, F. Tosi, D. Redaelli, A. Grothey
Journal: Annals of Oncology (2015)
Zika Virus as an Emerging Global Pathogen
Authors: J. David Beckham, Daniel M. Pastula, Aaron Massey, Kenneth L. Tyler
Journal: JAMA Neurology (2016)

Zika virus (ZIKV) is an emerging arthropod-borne virus (arbovirus) in the genus Flavivirus that has caused a widespread outbreak of febrile illness, is associated with neurological disease, and has spread across the Pacific to the Americas in a short period.In this review, we discuss what is currently known about ZIKV, neuroimmunologic complications, and the impact on global human health. Zika virus spread across Africa and Asia in part owing to unique genomic evolutionary conditions and pressures resulting in specific human disease manifestations, complications, and pathogenesis. Recent data suggest that acute ZIKV infection in pregnant women may result in acute infection of fetal tissue and brain tissue, causing microcephaly and potentially severe debilitation of the infant or even death of the fetus. Cases of acute ZIKV are also associated with Guillain-Barré syndrome. With the increased number of cases, new complications such as ocular involvement and sexual transmission have been reported.Zika virus is an emerging viral pathogen with significant consequences on human health throughout the world. Ongoing research into this pathogen is urgently needed to produce viable vaccine and therapeutic options.
Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity
Authors: David K. Cole, Anna M. Bulek, Garry Dolton, Andrea J. Schauenberg, Barbara Szomolay, William Rittase, Andrew Trimby, Prithiviraj Jothikumar, Anna Fuller, Ania Skowera, Jamie Rossjohn, Cheng Zhu, John J. Miles, Mark Peakman, Linda Wooldridge, Pierre J. Rizkallah, Andrew K. Sewell
Journal: Journal of Clinical Investigation (2016)

The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key–like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease.
Outcomes and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC).
Authors: Dimitris Ziogas, Kiruthikah Thillai, Dionysios Papadatos-Pastos, Mahfuja Hussain Ruhe Chowdhury, Ippokratis Korantzis, Thubeena Manickavasagar, Abid Suddle, John O'Grady, Nigel Heaton, Paul J. Ross, Debashis Sarker
Journal: Journal of Clinical Oncology (2015)

e15141 Background: HCC is the third commonest malignancy worldwide, with the highest incidence rates in patients over 70 years of age. Although sorafenib is used for patients with advanced HCC, there are concerns about the outcomes and tolerability in this age group. Methods: We conducted a retrospective study of 190 patients treated with sorafenib (177 with sorafenib alone, 13 patients with a combination of sorafenib and erlotinib/placebo within the SEARCH trial). Patient demographics and outcomes were recorded. Results: 190 patients were identified with a median age of 66 (26-87). 111 patients were < 70 years old (yrs) and 79 patients were > 70. 157 patients were male and 33 female. Underlying liver disease in the over 70 group were: non-alcoholic fatty liver disease (N = 21, 26.8%), unknown aetiology (N = 26, 32.9%), alcoholic liver disease (N = 14, 17.7%), hepatitis C (N = 7, 8.9%), hepatitis B (N = 6, 7.6%,) and other (N = 5, 6.3%). In the elderly group, 69 patients were Child-Pugh (CP) A status when starting sorafenib (A5 = 50, A6 = 19) and 10 patients were CP B (B7 = 9, B8 = 1). There was no statistically significant difference in OS between patients over the age of 70 and younger (8.5m for > 70 yrs and 6.7m < 70 yrs p = 0.366, or in PFS [5.3m vs. 4.8m (p = 0.258)]. The ALBI prognostic model using pre-treatment serum albumin and bilirubin was available for 74 patients in the elderly population. There was no difference in OS between patients who had an ALBI score of 1 compared with 2 (ALBI 1 = 9.6m vs. ALBI 2 = 8.1m [p = 0.65]. In terms of safety, there was no significant difference in the frequency of grade 1/2 (63.3% vs. 74.8%, p = 0.109) and grade 3/4 toxicities (20.0% vs. 31.5%, p = 0.066) between the two different age groups ( > 70 vs. ≤ 70 years). The rate of dose reductions were also comparable in both groups (34.2% vs. 31.5%, p = 1.000). Conclusions: Our study suggests that patients aged 70 or older appear to tolerate treatment with sorafenib well with comparable toxicities to those less than 70. We also found no significant differences in survival. With an aging population and increasing incidences of HCC, further prospective evidence is needed to identify safety and survival outcomes in this important group of patients.
Abstract 568: Coronary Artery Plaque Spatial Distribution Matches that of Thrombosis in STEMI, and is Underestimated by Calcified Plaque Segments Alone
Authors: Catherine A Pastorius, Stacia Merkel-Kraus, Jonathan G Schwartz, Robert S Schwartz, Vicki Pink, Gretchen Peichel, John R Lesser, Thomas Knickelbine, Bjorn Flygenring, Terry Longe, sue Duval
Journal: Circulation (2008)

Angiographic studies of ST-elevation myocardial infarction (STEMI) show that occlusive thrombi occur in coronary arteries within the proximal third of each major vessel, within about 35 mm from the ostium. These findings suggest that these high-risk regions are sites of plaque vulnerability. Multidetector CTA (MDCTA) visualizes not only lumen but also calcified and uncalcified coronary plaque. We therefore studied the distribution of coronary plaque in patients to determine plaque distribution to compare result with location of angiographic myocardial infarction thrombus. Methods: 48 outpatients (mean age 57 +− 5) undergoing Dual Source MDCTA (asymptomatic or with atypical symptoms) were studied. Most distal plaque location was measured for ostial-termination distance and composition (calcified/noncalcified) determined by one expert observer using validated, commercial plaque characterization software for lesion location and lesion length. Results: Location of the most distal plaque was as follows, LAD (n=35) 31.8 mm, LCX (n=21) 33.0 mm, and RCA (n=24) 56.0 mm. Mean lesion lengths were LAD 19.4 +− 13.4 mm, LCX 15.1 +− 9.6 and RCA 18.4 +− 9.8 mm. Mean volume (cu mm) for calcified and noncalcified plaque was 130 +− 176 and 204 +− 249 respectively, for a ratio of 0.64. There was no propensity of either calcified or uncalcified plaque to aggregate longitudinally in the arteries. Conclusions: The distribution and location of coronary artery plaque by MDCTA identically matches the known location of coronary artery vulnerability determined by angiographic studies. This finding suggests that STEMI does not occur in distal coronary locations simply because little plaque occurs in these areas. Calcified plaque volume measured in 3-dimensions underestimates total plaque volume by a factor of 2.6. Calcific plaque is thus the ‘tip of the iceberg’.
Problems and considerations in the valid assessment of personality disorders
Authors: J C Perry
Journal: American Journal of Psychiatry (1992)

This article reviews evidence for the reliability and diagnostic concordance of structured-interview and self-report questionnaire methods for the diagnosis of personality disorders. The findings of nine studies that compared two or more axis II diagnostic instruments administered to the same groups of subjects are summarized. Across the eight studies with sufficient data, a summary of the overall diagnostic agreement between any two instruments yielded a low reliability (median kappa = 0.25) for making individual personality disorder diagnoses. Diagnostic concordance was lower between self-report questionnaire and interview methods than between interview methods. Comparing dimensional scores of different methods did not appreciably improve the level of agreement. The author concludes that current methods for making personality disorder diagnoses have high reliability but yield diagnoses that are not significantly comparable across methods beyond chance, which is not scientifically acceptable. Sources for the disagreement include variance due to different raters, interview occasions, data sources (self-report versus observer report), information bases obtained, and instrument sensitivity to state effects (e.g., mood). Serious problems in assessment validity may also arise from the yes/no format, which, despite probes for confirmatory examples, may fail to distinguish adequately between sporadic occurrences and longstanding patterns. Efforts should be made to improve and demonstrate the validity of axis II diagnostic methods. One route to increasing validity is to improve the clinical interview, because personality patterns are best revealed by the recurring patterns one finds when taking a systematic history.
Implementing shared decision making in routine mental health care
Authors: Mike Slade
Journal: World Psychiatry (2017)

Shared decision making (SDM) in mental health care involves clinicians and patients working together to make decisions. The key elements of SDM have been identified, decision support tools have been developed, and SDM has been recommended in mental health at policy level. Yet implementation remains limited. Two justifications are typically advanced in support of SDM. The clinical justification is that SDM leads to improved outcome, yet the available empirical evidence base is inconclusive. The ethical justification is that SDM is a right, but clinicians need to balance the biomedical ethical principles of autonomy and justice with beneficence and non-maleficence. It is argued that SDM is "polyvalent", a sociological concept which describes an idea commanding superficial but not deep agreement between disparate stakeholders. Implementing SDM in routine mental health services is as much a cultural as a technical problem. Three challenges are identified: creating widespread access to high-quality decision support tools; integrating SDM with other recovery-supporting interventions; and responding to cultural changes as patients develop the normal expectations of citizenship. Two approaches which may inform responses in the mental health system to these cultural changes - social marketing and the hospitality industry - are identified.
Ethylene Glycol Monophenyl Ether
Journal: Environmental Health Perspectives (1997)

The disinfectant ethylene glycol monophenyl ether(EPH) features high-efficiency, safety, low toxicity, non-irritation and non-pollution. EPH can be widely used in detergent and cosmetics as disinfectant and preservative due to its special properties in sterilization, anti-microorganism functions to pseudomonas aeruginosa, Gram-positive and Gram-negative bacteria. The effectiveness of adding EPH in detergent and cosmetics used as disinfectant, preservative and deodorant is described in some examples. So far the EPH is still used as an important disinfectant in the cosmetics market in America and in Japan. Recent years, EPH has been used in domestic daily chemicals enterprises.
Il10 Locus As a Biomarker of Melanoma Survival
Authors: J. Rendleman, C. Adaniel, E. Kern, N. Fleming, M. Krogsgaard, D. Polsky, R. Berman, R. Shapiro, A. Pavlick, Y. Shao, I. Osman, T. Kirchhoff
Journal: Annals of Oncology (2014)
Don't Mess With My Smokes: Cigarettes and Freedom
Authors: Luc Bovens
Journal: The American Journal of Bioethics (2016)

Considerations of objective-value freedom and status freedom do impose constraints on policies that restrict access to cigarettes.As to the objective-value freedom, something of value is lost when anti-alcohol policies lead to pub closures interfering with valued life styles, and a similar, though weaker, argument can be made for cigarettes.As to status freedom, non-arbitrariness requires consultation with vulnerable populations to learn what might aid them with smoking cessation.
Utilization of Telemedicine Among Rural Medicare Beneficiaries
Authors: Ateev Mehrotra, Anupam B. Jena, Alisa B. Busch, Jeffrey Souza, Lori Uscher-Pines, Bruce E. Landon
Journal: JAMA (2016)

Utilization of Telemedicine Among Rural Medicare BeneficiariesTelemedicine may increase access and improve quality, particularly in rural areas. 1 Because inadequate reimbursement may limit telemedicine use, 29 states have passed telemedicine parity laws mandating that commercial insurers reimburse telemedicine visits. 2 In contrast, Medicare limits telemedicine reimbursement to select live video encounters with the patient at a clinic or facility in a rural area. 3Federal legislation has been proposed to expand Medicare telemedicine coverage.To inform the debate regarding telemedicine expansion, we describe trends in telemedicine utilization in Medicare from 2004-2013.
Similar savings in non-fundholding practices are not similarly rewarded
Authors: A D Birchall, P W Horsfield, J. Maskery, K L Hambleton, J E Clark
Journal: BMJ (1995)

EDITOR,--As Jon S Dowell and colleagues observe, prescribing in general practice consumes vast quantities of NHS funds,1 and any initiative that reduces this expenditure without adversely affecting patients' care is to be welcomed. Unfortunately, in their enthusiasm to publicise their efforts as a positive benefit stemming from their adoption of fundholding the authors seem to have a poor knowledge and understanding of the …
Antitumor Response of VEGFR2- and VEGFR3-Amplified Angiosarcoma to Pazopanib
Authors: Vinod Ravi, Eric M. Sanford, Wei-Lien Wang, Jeffrey S. Ross, Naveen Ramesh, Andrew Futreal, Shreyaskumar Patel, Phillip J. Stephens, Vincent A. Miller, Siraj M. Ali
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: Angiosarcoma is a malignant neoplastic disease originating from or differentiating toward vascular endothelium, for which systemic pharmacologic treatment has limited durability. The molecular oncogenesis of angiosarcoma is often linked to inappropriate activations of vascular endothelial growth factor receptor (VEGFR) family members, which presents an opportunity for the use of therapy that selectively targets the machinery of vascular signaling. Methods: Hybridization capture of 3,320 exons of 182 cancer-related genes and the introns of 14 genes frequently rearranged in cancer was applied to more than 50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of recurrent angiosarcoma and was sequenced to high, uniform coverage of 939x. Results: The angiosarcoma harbored amplifications of VEGFR2 (KDR) of 8 copies and VEGFR3 (FLT4) of 16 copies. The patient was initially treated with sorafenib, an inhibitor of VEGFR2, and developed progressive disease. The patient then received pazopanib, an inhibitor of VEGFR2 and VEGFR3 and experienced a potent antitumor response resulting in clinically stable disease for 6 months. Conclusions: This exceptional response to pazopanib treatment suggests that a subset of patients with angiosarcoma with genomic alterations in vascular signaling genes may respond well to pazopanib.
Defining the Differentiation Stage of Multiple Myeloma Plasma Cells: Biological and Clinical Significance
Authors: Bruno Paiva, Noemi Puig, María-Belén Vidriales, Norma Carmen Gutierrez, Miguel T Hernandez, Laura Rosiñol, Enrique M Ocio, Albert Oriol, María Asunción Echeveste, Yolanda Gonzalez, Mercedes Gironella, Julio Prieto, Maria Jose Moreno, Pilar Giraldo, Luis Palomera, Intza Aoiz, Joan Blade, Juan José Lahuerta, Maria-Victoria Mateos, Jesus F. San Miguel
Journal: Blood (2014)
Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study
Authors: Simon L F Walsh, Athol U Wells, Sujal R Desai, Venerino Poletti, Sara Piciucchi, Alessandra Dubini, Hilario Nunes, Dominique Valeyre, Pierre Y Brillet, Marianne Kambouchner, António Morais, José M Pereira, Conceição Souto Moura, Jan C Grutters, Daniel A van den Heuvel, Hendrik W van Es, Matthijs F van Oosterhout, Cornelis A Seldenrijk, Elisabeth Bendstrup, Finn Rasmussen, Line B Madsen, Bibek Gooptu, Sabine Pomplun, Hiroyuki Taniguchi, Junya Fukuoka, Takeshi Johkoh, Andrew G Nicholson, Charlie Sayer, Lilian Edmunds, Joseph Jacob, Maria A Kokosi, Jeffrey L Myers, Kevin R Flaherty, David M Hansell
Journal: The Lancet Respiratory Medicine (2016)
Tobacco Smoking Cessation in Adults and Pregnant Women
Authors: Ashley Haddad, Andrew M. Davis
Journal: JAMA (2016)

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High serum TGFα, TNFα and IL6 correlate with abnormal circadian rhythms in patients with metastatic colorectal cancer (MCC)
Authors: P. F. Innominato, T. Rich, J. Boerner, M. C. Mormont, S. Iacobelli, C. Jasmin, F. Lévi
Journal: Journal of Clinical Oncology (2004)

9650 Background: Poor quality of life and poor survival of cancer patients were independently predicted by an alteration of the rest-activity (RA) and/or cortisol circadian rhythms. This disturbance could be mediated by high levels of tumor- or host- derived growth factors, known to modulate circadian clock function.Methods: TGFα, TNFα and IL6 levels were determined with ELISA in sera from 80 MCC patients whose rhythms in RA (wrist actimetry for 3 d) and cortisol (serum drawn at 08:00 and 16:00 ) were prospectively studied (Mormont et al. Clin Cancer Res 2000). The samples were selected from patients having rhythmic (group 1, n=40) or damped (group 2, n=40) RA pattern, as assessed with autocorrelation for a period of 24 h (r24). Groups were compared with Kruskall-Wallis test. Correlations between factor concentrations and circadian parameters were explored with Spearman ρ test.Results: Median RA r24 were 0.56 (range, 0.47 to 0.77) in group 1 and 0.22 (0.03 to 0.35) in group 2 (p < 0.0001). Median cortisol ratio (value at 08:00 / value at 16:00 ± quartile) were 1.72 [1.48 - 1.98] and 1.60 [1.14 - 1.77] respectively (p = 0.031). Median (± quartile) dichotomy index (I<O), an integrated estimate of RA pattern and sleep quality, was 98.5 % [97.0 - 99.7] in group 1 and 91.4 % [82.1 - 96.7] in group 2 (p < 0.0001). TGFα, TNFα and IL6 serum levels (pg/ml) were significantly lower in group 1 as compared to group 2 (Table) and negatively correlated with I<O (r = - 0.45, p < 0.0001; r = -0.27, p = 0.022; r = -0.37, p = 0.001, respectively). IL6 levels were also negatively correlated with cortisol rhythm estimate (r = - 0.31, p = 0.005). Conclusions: Altered circadian function was associated with increased production of cancer-derived growth factors, suggesting a mechanism through which a tumor can promote its own development via the disturbance of host physiology. Supported by: ARTBC; J W Sieg fund. No significant financial relationships to disclose.
Abstract 341: GsMTx4-D is a Cardioprotectant against Myocardial Infarction during Ischemia and Reperfusion
Authors: Ji Li, Jinli Wang, Frederick Sachs, Thomas M Suchyna
Journal: Circulation Research (2014)

Rationale: GsMTx4 peptide is a selective inhibitor of cation selective mechanosensitive ion channels (MSCs) and has helped establish the role of MSCs in cardiac physiology. However, the role of MSCs in ischemic reperfusion injury was unknown. Cation imbalance appears to be a major contributor to ischemic reperfusion injury across multiple systems. MSCs may be significant contributors to the cation overload, and they are likely to be activated in reperfusion due to inhomogeneous local stresses and compromised mechanical support of the sarcolemma. Objective: The aim of this study was to determine if the D enantiomer of GsMTx4 can act as a cardioprotectant during ischemia/reperfusion in mice. Methods and Results: GsMTx4-D pharmacokinetics in the plasma and heart was monitored over 24 hrs using an LCMSMS assay. Ischemia and reperfusion in the mouse heart involved ligating a coronary artery for 20 min followed by release of the ligature. GsMTx4-D was administered by either acute intravenous injection during the ischemic event, or a day prior to the event with two days of intraperitoneal injections, once per day. Dosing of GsMTx4-D was adjusted to achieve tissue concentrations of 1-5 μM. Relative to vehicle injected animals, GsMTx4-D reduced infarct area by &gt;40% for both acute and pretreated animals. Cardiac output was indistinguishable between sham-treated control hearts and GsMTx4-D pretreatment, and arrhythmias were also significantly reduced by intravenous injections of GsMTx4-D. Conclusions: GsMTx4-D is a potent cardioprotectant that decreases infarct area, increases cardiac output and decreases arrhythmias that are caused by ischemia and reperfusion. GsMTx4-D was not toxic and promises to be a useful therapy in reperfusion of the heart and other organs.