tbuckley/cabot-search huggingface dataset:
Phase 1 positron emission tomography (PET) study of the receptor occupancy of rolapitant, a novel NK-1 receptor antagonist.
Authors: Allen Poma, Jennifer Christensen, Jennifer Davis, Vikram Kansra, Robert E. Martell, Mary Lynne Hedley
Journal: Journal of Clinical Oncology (2014)

e20690 Background: Rolapitant is a potent, highly selective, competitive and long acting NK-1 receptor antagonist in development for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic chemotherapy. NK-1 receptor occupancy (RO) is a critical predictor of delayed efficacy in CINV; therefore, this PET study determined the levels and duration of RO achieved by rolapitant using 11C-GR205171, a radiolabeled tracer NK-1 ligand. Methods: 14 healthy subjects were enrolled into this open-label, single-dose, pharmacodynamic, dose-escalation phase 1 study. Baseline PET scans with the radiotracer 11C-GR205171 alone followed by repeat PET scans 120 hours post administration of rolapitant were performed. Blood samples were collected up to 120 hours following rolapitant administration to determine rolapitant plasma concentration. The Patlak method was used to assess the baseline (uptake of 11C-GR205171) for the regions of interest. Regional occupancies (%) for each individual subject were then calculated as ((Ki'baseline – Ki'blocked) / Ki'baseline) * 100. Results: Oral rolapitant was rapidly absorbed. Exposure, both Cmaxand AUC, increased dose proportionally. NK-1 RO in the cortex was directly related to rolapitant dose and plasma concentration. A PK/PD model based on the sigmoid Emax model demonstrated that rolapitant concentrations above 348 ng/mL, achieved at 120 hours with the 200 mg dose level, corresponded to >90% NK-1 RO. No discontinuations due to adverse event (AE), or serious AEs were reported. Conclusions: Greater than 90% NK-1 RO was maintained up to 5 days following rolapitant administration. This indicates that a single oral 200 mg dose of rolapitant administered prior to chemotherapy may protect a patient for the entire 5-day period during which the patient is at risk of developing CINV. Rolapitant was safe and well tolerated in this study.
P3.02b-116 Molecular Mechanism of Transformation from Adenocarcinoma to Small-Cell Lung Cancer after EGFR-TKI
Authors: Jiefei Han, Qiuyi Zhang, Binchao Wang, Qing Zhou, Lixu Yan, Zhou Zhang, Huajun Chen, Jian Su, Zhi Xie, Feiyu Niu, Yi Long Wu, Shannon Chuai, Jinji Yang, Zhong-Yi Dong
Journal: Journal of Thoracic Oncology (2017)
Risk Factors for Fatal Residential Fires
Authors: Carol W. Runyan, Shrikant I. Bangdiwala, Mary A. Linzer, Jeffrey J. Sacks, John Butts
Journal: New England Journal of Medicine (1992)

Residential fires are the most important cause of fire-related mortality in the United States. Previous research has concentrated on fatal fires in urban areas; considerably less is known about fatal fires in rural areas.
Radiation therapy primes tumors for nanotherapeutic delivery via macrophage-mediated vascular bursts
Authors: Miles A. Miller, Ravi Chandra, Michael F. Cuccarese, Christina Pfirschke, Camilla Engblom, Shawn Stapleton, Utsarga Adhikary, Rainer H. Kohler, James F. Mohan, Mikael J. Pittet, Ralph Weissleder
Journal: Science Translational Medicine (2017)

Radiation therapy enhances nanotherapeutic drug delivery in a tumor-associated macrophage–dependent fashion.
Inflammasomes and IL-1 biology in the pathogenesis of allograft dysfunction
Authors: S. Samuel Weigt, Vyacheslav Palchevskiy, John A. Belperio
Journal: Journal of Clinical Investigation (2017)

Inflammasomes are high-molecular-weight cytosolic complexes that mediate the activation of caspases. There are many inflammasomes, and each is influenced by a unique pattern-recognition receptor response. Two signals are typically involved in the inflammasome pathways. Signal one involves recognition of pathogen-associated molecular patterns (PAMPs), such as LPS or other colonizing/invading microbes, that interact with TLRs, which induce the downstream production of pro-IL-1β. This is followed by signal two, which involves recognition of PAMPs or damage-associated molecular patterns (DAMPs), such as uric acid or ATP, via NLRP3, which leads to caspase-1-dependent cleavage of pro-IL-1β to active IL-1β and pyroptosis. Ultimately, these two signals cause the release of multiple proinflammatory cytokines. Both PAMPs and DAMPs can be liberated by early insults to the allograft, including ischemia/reperfusion injury, infections, and rejection. The consequence of inflammasome activation and IL-1 expression is the upregulation of adhesion molecules and chemokines, which leads to allograft neutrophil sequestration, mononuclear phagocyte recruitment, and T cell activation, all of which are key steps in the continuum from allograft insult to chronic allograft dysfunction.
Global Genomic Analysis of Newly Diagnosed t(4 ;14) Multiple Myeloma Reveals a Specific Mutational Spectrum and Identifies PKD2 As a Potential Therapeutic Target
Authors: Xiu Ly Song, Raphaël Szalat, Alexis Talbot, HaiVu Nguyen, Mehmet K. Samur, David Mosen-Ansorena, Nikhil C. Munshi, Stephane Minvielle, Herve Avet Loiseau, Wendy Cuccuini, Jean-Paul Fermand, Bertrand Arnulf, Jean-Christophe Bories
Journal: Blood (2016)
Are gesture and speech mismatches produced by an integrated gesture-speech system? A more dynamically embodied perspective is needed for understanding gesture-related learning
Authors: Wim T. J. L. Pouw, Tamara van Gog, Rolf A. Zwaan, Fred Paas
Journal: Behavioral and Brain Sciences (2017)

Abstract We observe a tension in the target article as it stresses an integrated gesture-speech system that can nevertheless consist of contradictory representational states, which are reflected by mismatches in gesture and speech or sign. Beyond problems of coherence, this prevents furthering our understanding of gesture-related learning. As a possible antidote, we invite a more dynamically embodied perspective to the stage.
PWE-110 What is the significance of “diminutive” colonic polyps in patients screened for colon cancer after a positive faecal human haemoglobin test (FHH)?: Abstract PWE-110 Table 1
Authors: V Mahesh, A Lim, K Pietris, J Argyrides
Journal: Gut (2012)

<h3>Introduction</h3> By definition “diminutive” colonic polyps are ≤5 mm in size. Improvements in optical imaging modalities and image resolution coupled with increased operator awareness have resulted in a higher detection rates at colonoscopy. Although such polyps are low risk for malignancy, studies suggest that high grade dysplasia may occur up to a rate of 4% in these polyps. There is an ongoing debate regarding the natural history and prognostic relevance of these polyps including suggestions for non-resection/to resect and discard. <h3>Aim</h3> To analyse the significance of “Diminutive” colonic polyps in patients screened for colon cancer after a positive Faecal Human Haemoglobin test. <h3>Methods</h3> Patients referred to a single tertiary institution in South Australia for screening colonoscopy after detection of a positive FHH. All patients referred between 2007 and 2010 were included in this retrospective study. The patients were referred either through the National Bowel Cancer Screening Program (NBCSP) or through GP initiated screening. Polyps were measured after the tissue was placed in formalin (histological size). For each colonoscopy the predetermined aim was to resect all polyps and assess histologically. <h3>Results</h3> A total of 384 patients had colonoscopy. NBCSP referred (n=173, 45%) and GP initiated FOBT (n=211, 55%). 228 M: 156 F with mean age of 61.8±0.6 yrs, 305 polyps in total. Majority of the polyps (57%, n=173) were ≤5 mm compared with 6–9 mm (23%, n=69; p&lt;0.001) and ≥10 mm polyps (21%, n=63; p&lt;0.001). The histological features of the polyps ≤5 mm were predominantly tubular adenomas (TA) (80%, n=86/107), please see Abstract PWE-110 table 1 for rest of histology. Only 38% (n=66) of polyps ≤5 mm were hyperplastic in nature. In polyps ≤5 mm in size, one TA with high grade dysplasia (0.6%) was seen but no carcinoma compared to 11 (3.6%) carcinomas/high grade dyspasia in ≥6 mm size polyps (p&lt;0.001). Three cancers were seen, two in polyps ≥10 mm size and one in the 6–9 mm size. 51% were left sided, 14% were right sided, location not specified in 35%, this difference was not statistically significant. <h3>Conclusion</h3> In patients who are positive for FHH the incidence of diminutive polyps is considerable and importantly there is a significant proportion of adenomatous polyps. Based on these findings we believe that diminutive polyps should be resected, histologically evaluated and followed-up appropriately. <h3>Competing interests</h3> None declared.
Treatment obstacles for metastatic clear cell renal cell carcinoma of Fuhrman grade IV and with sarcomatoid histologies.
Authors: Anna Malgorzata Czarnecka, Agnieszka Gebara-Puchniarz, Anna Nowak-Dement, Beata Miciuk, Wojciech Solarek, Cezary Szczylik
Journal: Journal of Clinical Oncology (2014)

e15604 Background: Sarcomatoid metastatic renal cell carcinoma and RCC Fuhrman grade IV represents an aggressive subset of disease, but a definitive therapeutic strategy in this cases still remain questionable. We seek to define outcomes associated with its therapy with special attention to diagnostic ambiguities and their impact on therapeutic decisions. Methods: The analyzed cohort consisted of patients with ccRCC diagnosed/treated at MIM from Jan 2007 to Jan 2014. Baseline clinical features, detailed radiologic and histologic reports were collected. Patients with mRCC either with sarcomatoid features and/or with Fuhrman grade IV disease were followed. Outcome was assessed by a dedicated radiologist for determination of tumor response, PFS and OS. Survival was estimated with the Kaplan-Meier method, and associations with survival outcome were analyzed with univariable and multivariable Cox regression analyses. All patients treated with sunitinib and pazopanib underwent radical nephrectomy. Results: Among all ccRCC patients treated in MIM 10% were identified to presented sarcomatoid featutes and/or Fuhrman grade IV mRCC. The percentage of sarcomatoid features was in the range from 10% to 90%. Patients were treated with: sunitinib > pazopanib > cytotoxic agents. Partial responses and stable disease were observed, but most patients had progressive disease as their best response or died before first scheduled follow-up. PR/SD were limited to patients who had >50% underlying clear-cell histology in first pathologic reports. Before treatment multiple patients required pathologist's second opinion. Dicrepancy between primary and metastatic tumors was reported. Conclusions: A subset of patients with sarcomatoid variant of ccRCC benefit from TKIs, but most have poor outcome. It is imperative that pathologists reliably report on absence/ presence and the estimated percentage of a coexisting sarcomatoid component. Facing pathologically ambiguous cases additional review including metastasectomy material analysis may enable discrimination between RCC subtypes. Further studies are needed to identify biomarkers defining the optimal therapeutic strategy for this subset of patients.
Dissecting microsatellite instability in colorectal cancer: one size does not fit all
Authors: Robert M. Samstein, Timothy A. Chan
Journal: Genome Medicine (2017)

Microsatellite instability (MSI) marks distinct subsets of tumors in many cancer types and is caused by mutations in genes required for mismatch repair. A recent report analyses the molecular foundations of MSI-positive colorectal cancers and reveals substantial molecular heterogeneity, which might have consequences for the potential use of immunotherapy in MSI-positive cancers. See related research by Sveen et al. 10.1186/s13073-017-0434-0
Heterogeneity of trichoscopy findings in dissecting cellulitis of the scalp: correlation with disease activity and duration
Authors: A.E. Verzì, F. Lacarrubba, G. Micali
Journal: British Journal of Dermatology (2017)

dissecting cellulitis of the scalp (DCS) is a chronic inflammatory condition characterized by recurrent nodules, abscesses and sinus tract formation.1-3 It usually starts as a simple folliculitis with occlusion of follicular openings mainly on the scalp vertex or nape, generally followed by perifollicular pustules and painful firm or fluctuant nodules releasing a purulent discharge, either spontaneously or after a gentle pressure.

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A dissimilar biosimilar? Lichenoid drug eruption induced by an infliximab biosimilar
Authors: N. Gonzalez, P. Patel, G. Han
Journal: British Journal of Dermatology (2017)

Summary The advent of therapeutic antibodies, or biological medications, has transformed the treatment of many inflammatory diseases in dermatology. Recently, the development of biosimilars, biological drugs that are highly similar in quality, safety and efficacy to approved biologics, has changed this landscape. Although biosimilars are not identical to their reference product, they are required to have the same mechanism of action, route of administration, dosage form and strength as the reference product. This also leads to the possibility that subtle differences in the activity of these biosimilars can lead to differing clinical responses. We report the first case of a lichenoid eruption induced by a biosimilar to infliximab after switching from infliximab. Several days after initial infusion of the biosimilar, the patient developed a pruritic papulosquamous eruption that was biopsied to reveal a lichenoid drug eruption. Possible mechanisms for lichenoid drug eruptions as a result of tumour necrosis factor-α inhibitor administration are discussed, along with reasons why such a reaction may occur with a biosimilar but not the original, reference product. This case report calls attention to the unique differences between biosimilars and biological medications that a clinician should consider prior to prescribing these medications.
Abstract 253: Restoring GDF11 to Normal Levels in Old Mice Has no Effect on Cardiac Structure and Function
Authors: Shavonn Smith, Xiaoxiao Zhang, Xiaoying Zhang, Polina Gross, Tim Starosta, Michael Franti, Priyanka Gupta, David Hayes, Maria Myzithras, Jennifer Ahlberg, Xiongwen Chen, Scott MacDonnell, Steven R Houser
Journal: Circulation Research (2015)

Rationale: GDF11 (Growth Differentiation Factor 11) is a member of the TGFβ super family of secreted factors, which play an important role in the regulation of cell processes including proliferation, differentiation, death, adhesion, and migration. Recently it was shown that circulating GDF11 levels fall with aging and this change is associated with pathological cardiac hypertrophy (PCH). Restoring GDF11 to normal levels was shown to rescue PCH. Objective: To determine if we can confirm the hypothesis that correcting the levels of a single factor, GDF11, determines aging related PCH. Methods and Results: We used the study design described by Loffredo et al, 2013. Investigators were blinded to treatment group. 24 month old C57BL/6 male mice were given a daily injection of recombinant GDF11 at 0 .1mg/kg or vehicle for 28 days. GDF11 bioactivity was confirmed in-vitro. After treatment, GDF11 levels were significantly increased but there was no difference in heart weight (HW) to body weight (BW) ratio (4.74 vs 4.70) between GDF11 and vehicle treated old mice. HW/BW ratios of old mice were not different from12 week-old animals (4.56) and the PCH markers ANP and BNP were not different in young verses old mice. Before GDF11 treatment there were no significant differences in ejection fraction (46 versus 46 %), internal ventricular dimensions (4.33 vs 4.28 mm), and septal wall thickness (0.72 versus 0.78 mm) between GDF11 and vehicle treated groups. All structural and functional parameters remained unchanged at 1, 2 and 4 weeks of treatment. Strain analysis showed no significant difference in radial or longitudinal strain. Invasive hemodynamics performed at time of sacrifice also showed no significant differences in max dP/dt (6499.17 vs 6011.95 mmHg/s) or min dP/dt (-6551.73 vs -6214.33 mmHg/s) between GDF11 and vehicle treated animals respectively. Conclusions: There is no significant age-related PCH in C57Bl6 mice. GDF11 injections had no effects on cardiac structure or function in old male C57BL/6 mice. Our results question the idea that there is age-related PCH in disease free C57BL6 mice and question the findings that restoring GDF11 in old mice has any effect on cardiac structure or function.
THE EFFECT OF PREVENTIVE PROGRAM IN DECREASING INJURY INCIDENCE IN GYMNASTIC ATHLETES
Authors: Natalia Bittencourt, Mariana Weschenfelder, Marcela Leite, Gabriela Gonçalves, Rafael Freire, Luciana Mendonça
Journal: British Journal of Sports Medicine (2017)

<h3>Background</h3> Youth gymnastic athletes have high risk for knee, ankle, spine and shoulder injury. Specific preventive programs could reduce injury incidence and sports time loss, which may reflect positively in an athlete9s performance. <h3>Objective</h3> Compare injury incidence rate before and after the implementation of a tailored preventive intervention in youth gymnastic athletes. <h3>Design</h3> Prospective study. <h3>Setting</h3> All athletes were followed-up over a three-year period at Minas Tenis Clube. The tailored preventive intervention was implemented only in the third year. <h3>Patients (or Participants)</h3> 82 female and male gymnastic athletes participated in this study; the mean for age was 10.59±2.69 years; body mass, 33.36 ±12.86 kg; and height 136.99±15.98 cm. <h3>Interventions (or Assessment of Risk Factors)</h3> After a preseason assessment a tailored preventive intervention was developed, including: 1) thoracic spine, shoulder, hip and ankle mobility; 2) core and scapular stabilization; 3) hip external rotation, eccentric lower limb and intrinsic foot muscle strengthening; 4) breathing exercises associated with core muscles. This preventive program was applied four times a week for 20 min supervised by the coaches and two times a week was executed by the sports physiotherapist. <h3>Main Outcome Measurements</h3> Injury incidence rate by 1000 hours of exposure and days of time loss were calculated each year. <h3>Results</h3> during the first two years without preventive intervention the injury incidence was 8.8 and 8 injuries/1000 h, respectively. The third year with preventive intervention had an incidence rate of 3.8 injury/1000 h. The average time loss of the two years was 902 days and in the third year was 345 days. T-test revealed statistical difference pre and post intervention (p&lt;0,02). <h3>Conclusions</h3> This study has shown that a tailored preventive intervention was effective to reduce the injury incidence rate in youth gymnastic athletes.
Evaluation comparative randomisée d'un logiciel d'auto-formation à la dissection sous-muqueuse en France et au Japon
Authors: M Pioche, J Rivory, T Nishizawa, T Uraoka, S Touzet, T Ponchon, N Yahagi
Journal: Endoscopy (2016)

La dissection sous muqueuse endoscopique (ESD) est la technique de référence pour les résections des tumeurs superficielles du tube digestif de plus de 15 mm. Cette technique est difficile, risquée en terme de perforations et demandeuse en temps. Il est difficile de se former sans supervision d'expert et les opérateurs sont souvent obligés d'aller dans des centres experts pour profiter d'un compagnonnage. Il est admis désormais que la formation initiale doit passer par l'animal avec des modèles d'intestin de porc ou de bovin afin d'éviter les perforations lors des premiers cas chez l'humain. Dans le but de développer un programme d'auto-apprentissage, la firme Olympus® en collaboration avec la Keio university et l'hôpital Edouard Herriot ont développé un logiciel d'aide à l'auto-formation expliquant pas à pas les premières étapes et les gestes recommandés pour réséquer correctement et en sécurité les pièces. Ce logiciel explique à chaque étape de la procédure les enjeux et les gestes à réaliser pour allier efficacité, qualité et sécurité. Une étude comparative randomisée a donc été menée en parallèle à Lyon et Tokyo pour mesurer l'impact de ce logiciel sur la courbe d'apprentissage des étudiants comparativement à des films de procédures d'ESD sans explication interactive.
Reliability and validity analyses are essential for questionnaire research
Authors: Hao Xing, Lei Liang, Zhen‐Li Li, Han Zhang, Tian Yang
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. Supported by grants from the National Natural Science Foundation of China (81472284, 81172020, and 81372262). Author names in bold designate shared co‐first authorship. To the Editor: We read with great interest the recent article by Farvardin et al.1 In this research, they carried out a questionnaire survey among patients with cirrhosis in order to find out the role of patient knowledge and attitudes toward hepatocellular carcinoma (HCC) surveillance and patient‐reported barriers in improving surveillance rates. Among all 541 enrolled respondents, nearly 70% were considered as having patient‐reported barriers, which was identified as an independent risk factor for lower HCC surveillance rates by multivariable regression analysis. However, we would like to raise the following comments. As we know, comprehensiveness and reasonability are key elements for designing a high‐quality questionnaire. In general, a questionnaire's reliability and validity analyses are essential for a solid internal consistency and external generalizability of its results. However, the study by Farvardin et al., failed to clearly lay out relevant reliability and validity tests for their self‐regulating questionnaire. In our opinion, it may be a major limitation of this study, which could influence the credibility of its results and the conclusions they drew. As for content, we believe some potentially important items are necessary, which at least include the following: (1) whether the respondents were receiving anticirrhotic treatment and/or antiviral therapy against hepatitis B or C virus—if so, they may undergo higher rates of HCC surveillance by their specialists2—(2) accessibility to medical institutions—easy access is more likely to promote patient compliance with HCC surveillance. In summary, clarification regarding the above‐mentioned omissions would greatly solidify the conclusions of their study.