tbuckley/cabot-search huggingface dataset:
<i>ROS1</i> rearrangement in non-small cell lung cancer (NSCLC): Prognostic and predicitve impact and genetic variability.
Authors: Matthias Scheffler, Anne Maria Schultheis, Cristina Teixido, Sebastian Yves Friedrich Michels, Daniela Morales-Espinosa, Santiago Viteri, Sabine Merkelbach-Bruse, Rieke Fischer, Jana Fassunke, Martin Sebastian, Monika Heidi Serke, Winfried Randerath, Ulrich Gerigk, Yon-Dschun Ko, Stefan Krüger, Roland Schnell, Achim Rothe, Rafael Rosell, Reinhard Büttner, Juergen Wolf
Journal: Journal of Clinical Oncology (2015)

8066 Background: Rearrangements of the ROS1 oncogene occur in about 1-2% of non-small cell lung cancer (NSCLC) patients. While data suggest that the EML4-ALK/MET/ROS1 inhibitor crizotinib is highly effective in these patients, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Methods: 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results: ROS1 status was analyzed in 1035 (91.0%) patients, whereof 19 (1.8%) had ROS1-rearrangement. The median OS of the patients has not been reached yet. Stage IV patients with ROS1-rearrangement had the best OS of all analyzed subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response under chemotherapy. Pemetrexed-containing regimens showed higher response rates than paclitaxel-containing ones (80% vs 17%). Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years (median not reached). Ten patients with ROS1-rearrangement (52.6%) harbored additional genetic aberrations in BRAF, MET, EGFR, MAP2K1, and TP53. Conclusions: ROS1-rearangement is not only a strong predictive marker for response to crizotinib, but also seems to be the best prognostic molecular marker in NSCLC reported so far. In stage IV ROS1-positive patients, response to chemotherapy was remarkable high and overall survival regardless of systemic therapy significantly better compared to other genetically defined subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.
Abstract 345: Dramatic ATP Depletion Without Concomitant Declines in ATP Synthesis Rates Suggests Impaired Energy Metabolism Mechanisms in Adrenergic-Deficient Mouse Embryos
Authors: Jessica N Peoples, Candice Baker, Steven Ebert
Journal: Circulation Research (2015)

High cardiac energy demands increase during embryonic development, requiring oxidative phosphorylation converting ADP to ATP in mitochondria to meet these demands. We have recently shown that adrenergic hormones are required to maintain sufficient cardiac energy metabolism during embryonic development, but the specific mechanism(s) underlying this regulation are not known. Mouse embryos lacking adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to targeted loss of the essential dopamine β-hydroxylase ( Dbh ) gene, have remarkably decreased steady-state ATP/ADP ratios. To determine if ATP synthesis was affected, we examined the rate of ATP formation in adrenergic-deficient and control embryonic hearts. Our rate data have shown that despite &gt; 50-fold decrease of steady-state ATP concentrations in Dbh -/- embryos, the rate of ATP synthesis was not significantly different in adrenergic-competent and deficient embryos. This indicates that respiratory complexes in mitochondria are capable of producing ATP in adrenergic-deficient embryos, and suggest that ATP is either consumed at a faster rate than it is produced or its production is limited in vivo due to limited access to metabolic substrates (“starvation”). These findings reveal new mechanistic insights about how adrenergic hormones regulate energy metabolism during embryonic development.
In Vivo Reflectance Confocal Microscopy for the Diagnosis of Melanoma and Melanotic Macules of the Lip
Authors: Pablo Uribe, Helena Collgros, Richard A. Scolyer, Scott W. Menzies, Pascale Guitera
Journal: JAMA Dermatology (2017)

Benign melanotic macules (MAC) are the most frequent cause of lip pigmentation and sometimes difficult to differentiate from lip melanoma (MEL).To report in vivo reflectance confocal microscopy (RCM) features of normal lips of different phototypes and to identify features that assist in distinguishing MEL from MAC using dermoscopy and RCM.For this retrospective observational study, 2 groups of patients from 2 tertiary referral centers for melanoma (Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia) were recruited between June 2007 and January 2015. Group 1 included patients with normal lips and different phototypes, and Group 2 consisted of patients with MAC and MEL; RCM and dermoscopy were used for lips analysis.Overall, 92 RCM features were correlated with clinical history, dermoscopic images, and histopathology in all patients with MEL and 5 patients with MAC.Images from the vermillion and/or mucosal part of the lip were recorded from 10 patients with clinically normal lips (mean [SD] age, 34.5 [6.1] years), 16 patients with MAC (mean [SD] age, 49.6 [17.9] years), and 5 patients with 6 cases of MEL (1 patient had a recurrent lesion; mean [SD] age, 56.2 [15.5] years). In normal lips, the draped pattern-a previously described MAC RCM feature-was identified in all cases. In MEL, the following findings were frequent and significantly different from MAC: epidermal disarray; pagetoid infiltration of dendritic and/or round cells; a nonspecific architectural pattern at the dermoepidermal junction (DEJ); nonhomogenously distributed papillae; continuous (lentiginous) proliferation of cells with marked atypia at the DEJ, especially in interpapillary spaces; a higher number of dendritic cells (especially roundish); and atypical round cells at the DEJ. The cellular body area of dendritic cells was about the double in MEL compared with MAC. An RCM lip algorithm was developed that provided 100% sensitivity and 88% specificity for the diagnosis of MEL of the vermillion and mucosal part of the lip. With dermoscopy, MAC were correctly classified as benign in 13 of 16 cases (81%) and MEL were classified as equivocal or malignant in 5 of 6 cases (83%).Reflectance confocal microscopy can assist in the differential diagnosis of lip MEL and MAC. An RCM Lip Score that we developed based on study results is proposed and needs to be validated on an independent data set.
Missense variants in Lynch Syndrome genes in endometrial cancer patients characterized by The Cancer Genome Atlas (TCGA) project.
Authors: Christine S. Walsh, Beth Karlan, Dennis Hazelett
Journal: Journal of Clinical Oncology (2015)

1547 Background: We sought to characterize the missense variants in the Lynch Syndrome genes in patients with endometrial cancer that had normal germline DNA characterized by TCGA. Methods: We obtained institutional IRB approval and approval from the National Center for Biotechnology Information Genotypes and Phenotypes Database (NCBI dbGaP) for data access to TCGA data files. We utilized Variant Call Format (VCF) files to annotate germline single nucleotide variants in exomic regions of the Lynch Syndrome genes (MLH1, MSH2, MSH6, PMS2) among 248 patients with endometrial cancer. We used the MetaLR composite score from Annovar, which combines data from SIFT, PolyPhen2, LRT, MutationTaster, MutationAssessor, FATHMM, GERP++, PhyloP and SiPhy for prediction of variant effects on protein function. Results: A total of 120 different missense variants from 248 patients were found in the Lynch Syndrome genes (8 in MLH1, 26 in MSH2, 41 in MSH6, 45 in PMS2). 82 (68%) of these variants were novel and were not annotated in dbSNP or in publically available databases of Lynch Syndrome variants. None of the 120 missense variants were previously reported deleterious mutations known to cause Lynch Syndrome. Eight variants had a MetaLR score of > 0.9, signifying the highest probability of the variant having a deleterious effect. Of these, the top six variants clustered in exon 4 of the PMS2 gene between codons 105 and 116. Other variants with high MetaLR scores clustered in exon 1 of MSH2. Conclusions: We identified a large number of novel missense variants in the MLH1, MSH2, MSH6 and PMS2 genes in patients with endometrial cancer characterized by the TCGA. The variants with the highest probability of having a deleterious effect clustered in exon 4 of PMS2 and exon 1 of MSH2.
Effectiveness of Two Week Rule (TWR) Referral System for Patients with Symptoms of Dyspepsia
Authors: AR Khan, M Riazuddin, K Hafeez, BQ Khan, Z Mahmood
Journal: Endoscopy (2006)

Background: Based on Department of Health (DOH) guidelines to identify suspected upper gastrointestinal cancer cases, Performa is designed for General Practitioners (GP) to refer cases under TWR with symptoms of dyspepsia associated with “alarm symptoms“ (weight loss, vomiting, anaemia, family history of gastric cancer or age over 55 years).
Abstract 1741: Bone Marrow Mononuclear Cell Therapy upon Reperfusion Reduces Myocardial Infarct Size by Activating the PI3K/Akt Survival Pathway
Authors: Mohammed Yasin, Yasunori Shintani, Massimo Collino, Kunihiko Takahashi, Husein Salem, Amar Kapoor, Garry Rucklidge, Ken Suzuki, Christoph Thiemermann
Journal: Circulation (2008)

Cardioprotective molecular mechanisms underlying adult bone marrow progenitor cell therapy have not been fully elucidated. We hypothesized that intravenous bone marrow mononuclear cells (BMMNC) might be: protective when administered upon reperfusion protective by paracrine mechanisms. Freshly isolated 10 million BMMNC, c-Kit + (7 ± 1%, n =10), CD34 + (7 ± 1%, n =10), CD45 + (54 ± 6 %, n = 10), and CD133 + (15 ± 1%, n = 10), were intravenously administered upon reperfusion in a rat model of 25 minutes left anterior descending coronary artery occlusion followed by reperfusion lasting either 2 hours (I/R2h) or 7 days (I/R7D). At the end of I/R2h, BMMNC caused significant reductions in infarct size (BMMNC 33 ± 3 %; control 57 ± 2 %, n = 10, P &lt; 0.01). Following I/R7D, BMMNC caused significant improvements in systolic function (LVEF: BMMNC 71 ± 3 %; control 48 ± 4 %, n = 11, P &lt; 0.0001) and diastolic function (LVEDP: BMMNC 5 ± 2 mmHg; control 15 ± 2 mmHg, n = 9, P &lt; 0.01). Comparable cardioprotection was achieved when BMMNC supernatant was intravenously administered instead of BMMNC. Cardioprotection by BMMNC was associated with Akt phosphorylation, which could be abolished by inhibition of PI3K with LY294002. When compared with controls, proteomics of hearts subjected to I/R2h and treated with BMMNC demonstrated higher expression of the anti-oxidants catalase (3.3 fold), and peroxiredoxin 6 (2.0 fold); heat shock proteins HSP20 (2.9 fold), alpha B crystallin (1.7 fold), HSP72 (2.8 fold), ischemia responsive protein-94 (1.6 fold), and TNF receptor-associated protein 1 (2.3 fold); glycolytic enzymes alpha-enolase (1.6 fold), glyceraldehyde-3-phosphate dehydrogenase (2 fold), and pyruvate kinase (2 fold); and mitochondrial respiratory proteins, aconitase (4.8 fold), ATPase synthase (3.5 fold), citrate synthase (2.5 fold), and voltage-dependent anion-selective channel protein 1 (3.4 fold). In conclusion, intravenous administration of BMMNC upon reperfusion reduced infarct size by activation of the PI3K/Akt survival pathway. Further survival benefits were also demonstrated by up-regulated expression of recognised cardioprotective anti-oxidants, heat shock proteins, and augmented glycolytic mitochondrial bioenergetics.
Spirituality in Dermatology Practice
Authors: Jorge Roman, David J. Elpern
Journal: JAMA Dermatology (2017)

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Advanced gastrointestinal cancer patients' perceptions of prognosis and goals of treatment.
Authors: Areej El-Jawahri, Lara Traeger, Elyse R. Park, Joseph A. Greer, William F. Pirl, Inga Tolin Lennes, Vicki A. Jackson, Emily R. Gallagher, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2012)

6106 Background: Patients with advanced cancer require accurate perception of their illness in order to make informed decisions regarding their care. However, little is known about the accuracy of these patients’ illness and prognostic understanding. The objectives of this study are to 1) examine prognostic understanding in patients with advanced gastrointestinal (GI) cancers, 2) assess patient preferences for prognostic information, and 3) explore associations of perceptions with quality of life (QOL) and mood. Methods: Cross-sectional study of 50 patients within 6-12 weeks post diagnosis of advanced GI cancers (gastric, esophageal, pancreatic, and hepatobiliary). We assessed patients’ perceptions of prognosis with a 15-item questionnaire, the Perception of Treatment and Prognosis Questionnaire. QOL and mood were assessed using the Functional Assessment of Cancer Therapy-General (FACT-G) and hospital anxiety and depression scales (HADS), respectively. Results: We enrolled 50/62 (80%) consecutive eligible patients within an 11-month period. 50% (25/50) of participants responded that the primary goal of their cancer treatment was to “cure their cancer.” Similarly, 54% (27/50) reported that they were “somewhat” to “extremely likely” to be cured from their cancer. Only 22% (10/49) reported having a discussion about their end-of-life care preferences with their oncologist. 76% (38/50) reported wanting to know as many details as possible about their cancer diagnosis and treatment and 64% (32/50) rated this information as “extremely important.” Patients who perceived knowing about their prognosis as “extremely helpful” reported a better QOL (p = 0.009), lower symptoms of anxiety (p = 0.02) and depression (p = 0.02). Conclusions: Although the majority of patients report that they desire detailed information about their prognosis, half incorrectly perceived their cancer as curable and the majority did not discuss their end-of-life care preferences with their oncologist. Patients who found learning about their prognosis to be extremely helpful reported better QOL and mood. Studies of interventions to increase advanced cancer patients’ knowledge of their prognosis and to encourage end-of-life discussions are warranted.
First stage of an on-going phase 2, open label, international, randomized, parallel design study investigating efficacy + safety of GTx-024 for advanced ER+/AR+ breast cancer (BC)
Authors: B. Overmoyer, H.S. Rugo, S. Johnston, J.A. O'Shaughnessy, C. Palmieri, L.S. Schwartzberg, R.P. Taylor, D.C. Young, M.A. Johnston
Journal: Annals of Oncology (2017)
<i>AJRCCM</i>: 100-Y<scp>ear</scp> A<scp>nniversary</scp>.The Shifting Landscape for Lung Cancer: Past, Present, and Future
Authors: Anil Vachani, Lecia V. Sequist, Avrum Spira
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The past century has witnessed a transformative shift in lung cancer from a rare reportable disease to the leading cause of cancer death among men and women worldwide. This historic shift reflects the increase in tobacco consumption worldwide, spurring public health efforts over the past several decades directed at tobacco cessation and control. Although most lung cancers are still diagnosed at a late stage, there have been significant advances in screening high-risk smokers, diagnostic modalities, and chemopreventive approaches. Improvements in surgery and radiation are advancing our ability to manage early-stage disease, particularly among patients considered unfit for traditional open resection. Arguably, the most dramatic progress has occurred on the therapeutic side, with the development of targeted and immune-based therapy over the past decade. This article reviews the major shifts in the lung cancer landscape over the past 100 years. Although many ongoing clinical challenges remain, this review will also highlight emerging molecular and imaging-based approaches that represent opportunities to transform the prevention, early detection, and treatment of lung cancer in the years ahead.
Re: Kenneth A. Iczkowski's Letter to the Editor re: Re: Rodolfo Montironi, Silvia Gasparrini, Roberta Mazzucchelli, et al's Letter to the Editor re: Karim A. Touijer, James A. Eastham. The Sentinel Lymph Node Concept and Novel Approaches in Detecting Lymph Node Metastasis in Prostate Cancer. Eur Urol 2016;70:738–9: Sentinel Lymph Nodes in Adipose Tissue Surrounding the Prostate Gland and Seminal Vesicles as Observed in Virtual Whole-mount Histologic Slides. Eur Urol 2017;71:e73–5
Authors: Rodolfo Montironi, Antonio Lopez-Beltran, Liang Cheng, Silvia Gasparrini, Maria Alessandra Montironi, Francesco Massari, Marina Scarpelli, Francesco Montorsi
Journal: European Urology (2017)
Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis
Authors: Vanessa Clifford, Marc Tebruegge, Christel Zufferey, Susie Germano, Ben Forbes, Lucy Cosentino, Emma McBryde, Damon Eisen, Roy Robins-Browne, Alan Street, Justin Denholm, Nigel Curtis
Journal: Journal of Infection (2017)
Results from short-term CT assessments in patients (pts) with advanced poor performance status non-small cell lung cancer (NSCLC) receiving pemetrexed in a phase II trial
Authors: R. Zinner, R. S. Herbst, F. V. Fossella, F. M. Johnson, D. D. Karp, M. S. Kies, J. V. Heymach, J. S. Price, S. M. Lippman, J. Erasmus
Journal: Journal of Clinical Oncology (2009)

e19069 Background: Early determination of therapeutic failure can potentially spare a pt ineffective and toxic treatment. We previously reported in a retrospective study the use of CT within 4 weeks of initiation of chemotherapy in advanced NSCLC to assess response and progression by RECIST (Bruzzi et al. JTO 2006). Here, we prospectively assess whether CT imaging after the first cycle of pemetrexed in advanced NSCLC has a role in evaluating response and management. Methods: We accrued pts with PS 2 or 3 advanced NSCLC receiving at least one dose of 1 st or 2 nd line pemetrexed. A repeat CT prior to a 2nd course was required. Pts with progression by RECIST were to come off study. CT scans were done using multislice CT technology (GE Lightspeed Plus), and images were reconstructed with slice thicknesses of 3.75mm or less. All images were reviewed using a PACs workstation (Stentor iSite) and measurements were done with electronic calipers. RECIST criteria: progression, an increase in the tumor's longest dimension by 20%, response, a decrease by 30%. Results: Thirty pts had a median age of 68 years (45 - 81). PS 2/3, 1 st /2 nd line, and F/M were 16/14, 17/13, and 12/18 respectively. Pts received 1–8 cycles (median 2). Twelve pts received only 1 course of whom 7 pts had f/u CTs at a median of 20 days (12–25) after 1 st chemo dose. Of these pts, 5/7 had progression by RECIST and the other 2/7 pts had stable disease with 1 pt who came off due to serial PEs and 1 pt who opted off for reasons of travel. Two of the 5 pts who had progression by CT had no detectable change by CXR. Of 5/12 pts treated with only 1 course without f/u CT, 2 pts died, 2 pts had progression by CXR, and 1 pt stopped after treatment for pneumonia. All 18 pts receiving ≥2 cycles had a repeat CT prior to their 2 nd course. Conclusions: The results of this prospective trial support earlier retrospective findings that short-term follow-up using CT in pts with advanced NSCLC can detect tumor progression and impact patient management. We will also present f/u CTs in pts who received ≥ 1course to determine whether early signs of progression predict later RECIST determined progression. [Table: see text]
Endoscopic removal of metal bottle cap from the esophagus
Authors: Lukasz Rojek, Andrzej Jasinski, Krystian Adrych
Journal: Endoscopy (2017)

A 22-year-old man was admitted to the emergency department with dysphagia and chest pain after inadvertently swallowing a metal bottle cap. Two hours earlier he had opened a bottle of cider using his teeth and accidently swallowed the bottle cap with the first sip of cider. After the incident, he was able to swallow fluids and saliva. He had no other previous medical history and no background of psychiatric illness. His vital signs were within normal limits. Physical examination revealed no abnormalities.
Mice deficient in NRROS show abnormal microglial development and neurological disorders
Authors: Kit Wong, Rajkumar Noubade, Paolo Manzanillo, Naruhisa Ota, Oded Foreman, Jason A Hackney, Brad A Friedman, Rajita Pappu, Kimberly Scearce-Levie, Wenjun Ouyang
Journal: Nature Immunology (2017)
The large-balloon occupation technique: a new technique for removing multiple biliary stones from a large-diameter bile duct
Authors: Hiroshi Yamauchi, Mitsuhiro Kida, Kazuho Uehara, Eiji Miyata, Kosuke Okuwaki, Hiroshi Imaizumi, Wasaburo Koizumi
Journal: Endoscopy (2017)

Multiple stones, a periampullary diverticulum, and advanced patient age are factors that contribute to difficulty in stone removal [1]. We were able to completely remove the bile duct stones in a 93-year-old woman with a periampullary diverticulum, multiple stones (about 100), and common bile duct of 35 mm in diameter using the large-balloon occupation technique (LBOT).