tbuckley/cabot-search huggingface dataset:
Melanomas of the head-and-neck skin with mutation BRAF-V600K or BRAF-V600R define a melanoma subtype with particular clinical features.
Authors: Hans Starz, Justin Moody, Julia Welzel, Christian J Haas
Journal: Journal of Clinical Oncology (2013)

9098 Background: “Malignant melanoma” is a melting pot of diverse melanocytic tumor entities, which arise in different organs under varying pathogenetic circumstances. Chronic sun exposure is a major factor for the development of cutaneous melanomas of the head-and-neck (HN) region. Methods: 131 patients with metastatic cutaneous melanomas were included in a monocentric retrospective study. The HN skin was the primary tumor site in 41 patients. The mutational hotspots of BRAF and NRAS were analysed by Sanger sequencing. In BRAF and NRAS wildtype cases, additionally exons 11, 13 and 17 of the KIT gene were investigated. HN patients with the mutations BRAF-V600K or BRAF-V600R were defined as group A (n = 11), those with other mutations or wildtype as group B (n = 30). A and B were compared with regard to the emergence of different categories of metastases, using the Kaplan-Meier method and log rank tests. The average follow-up time was 50 months. Results: BRAF-V600K occurred in 10 of the 41 HN patients and in 2 of the 90 non-HN patients (p = 0.003 by T-test), BRAF-V600R in 1 HN and in 1 non-HN patient. KIT mutations were restricted to 2 HN patients. Inversely, NRAS mutations were rare in the HN (3 of 41) versus the non-HN (26 of 90) cohort (p = 0.001). Lymphatic metastasis became apparent in each of the 11 group A patients not later than 35 months after the diagnosis of the respective primary melanoma. 5 out of the 8 group A patients, who underwent sentinel node biopsies (SNB), had nodal micrometastases. During follow-up, regional nodal macrometastases emerged earlier and at a higher rate in group A compared to B (p = 0.044 by log rank test). The same applied even more significantly for satellite/intransit metastases (p = 0.002), whereas for distant metastasis no significant difference was found. Conclusions: BRAF-V600K/R mutations in HN melanomas define a distinct melanoma subtype with an especially high risk of lymphatic metastasis. Clinical implications may be mutation analyses already for primary HN melanomas, and SNB even for thin melanomas of this subtype. Extra-guidelines should be considered for the monitoring of these patients. Special attention to this subgroup is also necessary in clinical trials.
Platelets: inflammatory effector cells in the conflagration of cystic fibrosis lung disease
Authors: Guy A. Zimmerman
Journal: Journal of Clinical Investigation (2020)

Cystic fibrosis (CF) is a multisystem disorder, but progressive inflammatory lung disease causes the greatest burden of morbidity and death. Recent translational and mechanistic studies of samples from patients, and observations in animal models, indicate that platelets may drive lung injury and contribute to dysregulated host defense in CF lung disease. In this issue of the JCI, Ortiz-Muñoz and Yu et al. explored the role that the cystic fibrosis transmembrane conductance regulator (CFTR) plays in platelet-related inflammation. The authors used mouse and human model systems to show that CFTR dysfunction in platelets increased calcium entry though the transient receptor potential cation channel 6 (TRPC6), causing hyperactivation and consequent experimental lung inflammation. The study persuasively suggests that platelets are critical thromboinflammatory effector cells in CF lung disease. In the context of platelet-related organ injury seen in a variety of other diseases and syndromes, platelets may also contribute to nonpulmonary manifestations and comorbidities of CF.
Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study
Authors: Simon Husby, Francesco Favero, Christian Nielsen, Betina S. Sørensen, John Bæch, Kathrine Grell, Jakob W. Hansen, Francisco G. Rodriguez-Gonzalez, Eva K. Haastrup, Anne Fischer-Nielsen, Pernille Andersen, Bente Arboe, Susanne G. Sækmose, Per B. Hansen, Ilse Christiansen, Erik Clasen-Linde, Lene Meldgaard, Lene H. Ebbesen, Erik K. Segel, Pär Josefsson, Michael Thorsgaard, Tarec C. El-Galaly, Peter Brown, Joachim Weischenfeldt, Thomas S. Larsen, Kirsten Grønbæk
Journal: Leukemia (2020)
PROSPECTIVE ECHOCARDIOGRAPHY AND MAGNETIC RESONANCE IMAGING VALIDATION STUDY OF A GEOMETRIC MODEL FOR CALCULATING LEFT VENTRICULAR EJECTION FRACTION FROM STRAIN IN VALVULAR HEART DISEASE
Authors: Tom Kai Ming Wang, Zoran Popovic, Scott D. Flamm, Richard A. Grimm, L. Leonardo Rodriguez, Michael Bolen, Laurie Ann Moennich, Kathryn Rutkowski, Brian P. Griffin, Deborah Kwon
Journal: Journal of the American College of Cardiology (2020)
Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association
Authors: Mina K. Chung, Lee L. Eckhardt, Lin Y. Chen, Haitham M. Ahmed, Rakesh Gopinathannair, José A. Joglar, Peter A. Noseworthy, Quinn R. Pack, Prashanthan Sanders, Kevin M. Trulock
Journal: Circulation (2020)

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with substantial morbidity, mortality, and healthcare use. Great strides have been made in stroke prevention and rhythm control strategies, yet reducing the incidence of AF has been slowed by the increasing incidence and prevalence of AF risk factors, including obesity, physical inactivity, sleep apnea, diabetes mellitus, hypertension, and other modifiable lifestyle-related factors. Fortunately, many of these AF drivers are potentially reversible, and emerging evidence supports that addressing these modifiable risks may be effective for primary and secondary AF prevention. A structured, protocol-driven multidisciplinary approach to integrate lifestyle and risk factor management as an integral part of AF management may help in the prevention and treatment of AF. However, this aspect of AF management is currently underrecognized, underused, and understudied. The purpose of this American Heart Association scientific statement is to review the association of modifiable risk factors with AF and the effects of risk factor intervention. Implementation strategies, care pathways, and educational links for achieving impactful weight reduction, increased physical activity, and risk factor modification are included. Implications for clinical practice, gaps in knowledge, and future directions for the research community are highlighted.
PRE-IMPLANT LEFT VENTRICULAR SIZE BEST PREDICTS POOR CARDIAC POWER INDEX IN PATIENTS WITH HM3 SUPPORT
Authors: Varinder Randhawa, Edward Soltesz, Qiuqing Wang, Katherine Wolski, Michael Z.Y. Tong, Shinya Unai, Tiffany Buda, Randall C. Starling, Wai Hong Wilson Tang, Jerry D. Estep
Journal: Journal of the American College of Cardiology (2020)
再生不良性貧血を持つ小児の免疫抑制療法への良好な反応が予測できないHLA-DR15、マイナーPNHクローンまたは再生不良性貧血関連自己抗体の存在 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Yagasaki H, Yoshida N, Hirano N, Nishio N, Wang Y, Takahashi Y, Kojima S
Journal: Blood (2006)
mRNA expression of signal transducer and activator of transcription (STAT5), disheveled-3 (Dvl-3) and dicer in early-stage non-small-cell lung cancer (NSCLC)
Authors: F. Cecere, R. Rosell, M. Taron, A. Ceribelli, M. Milella, P. Mendez, M. Cuello, P. Visca, F. Facciolo, F. Cognetti
Journal: Journal of Clinical Oncology (2006)

17038 Background: STAT5 plays a role in angiogenesis and metastasis. Activation of STAT5 occurs through dysregulation of growth factor receptor tyrosine kinases (TK) (including EGFR TK mutations), non-receptor TKs or Janus kinases. Dvl-3, a critical mediator of the Wingless-type (Wnt) signaling pathway, contributes to self-renewal of stem cells. Dicer has a key role in processing microRNAs required for stem cell regulation. We assessed mRNA expression of STAT5, Dvl-3 and Dicer in early-stage NSCLC. Methods: cDNA was derived from paraffin-embedded primary tumors of 47 surgically resected, early-stage NSCLC patients. Real-time quantitative reverse transcriptase PCR was used to measure STAT5, Dvl-3 and Dicer mRNA levels relative to the internal reference gene β-actin. Results: Median expression levels were: STAT5, 0.66 (0.15–6.03); Dvl-3, 3.69 (1.02–25.83); Dicer, 4.53 (1.22–21.96). STAT5 levels for squamous cell carcinoma (SCC) were 0.57 vs 0.89 for non-SCC (P=0.01), while Dicer levels were higher in SCC (4.25) than in non-SCC (2.60) (P = 0.01). A strong correlation between the levels of Dvl-3 and Dicer was found (rho = 0.49; P &lt; 0.001). 90% of females had low Dicer mRNA levels (P = 0.01). No other correlation between mRNA levels and patient characteristics was found. Conclusions: High levels of Dvl-3 are associated with SCC. The close correlation between Dvl-3 and Dicer levels may indicate that Dicer could process a class of microRNA that activates the Wnt pathway. In non-SCC, overexpression of STAT5 could be involved in tumor angiogenesis. These 3 transcripts could be potential predictors of metastasis and ideal targets for individualized treatment. No significant financial relationships to disclose.
Circulating endothelial cells and serum caspase-cleaved CK18 to predict for response and survival in non-small cell lung cancer patients receiving endostatin and paclitaxel-carboplatin combined chemotherapy.
Authors: Tianqing Chu, Hao Ding, Aiqin Gu, Jun Pei, Baohui Han, Weidong Du
Journal: Journal of Clinical Oncology (2012)

e18088 Background: Combinations of anti-angiogenic drugs with chemotherapeutics are widely used for cancers control. Whether can better efficacy of such a combinated modality be achieved and predicted earlier is a great challenge. Circulating endothelial cells (CECs) and cytokeratins (CKs) might have a role in tumour angiogenesis and in tumour cell death. Measurement of CECs and CKs in the blood of patients with tumors could be a simple, non-invasive approach to monitor or predict responses and survival to treatment. Methods: One hundred and seven patients with primary advanced non-small cell lung cancer (NSCLC) were enrolled, randomly assigned to either the endostatin treatment group (paclitaxel+ carboplatin+ endostatin) or the control group (paclitaxel+carboplatin). CEC count and serum CK8, caspase-cleaved CK18 (ccCK18) and uncleaved CK18 (CK18) were measured in the 107 subjects at before treatment (baseline), week 3, and week 6 of treatment, respectively. Results: Higher baseline CEC count was observed in patients with good tumor response (p=0.002 for all the 107 patents; p=0.000 in the treatment group). When compared with the baseline level, after 6 weeks therapy in the endostatin group, CECs decreased significantly (p=0.000), but the CKs levels increased. The increased levels of ccCK18 and CK18 at week 6 reached significance in the treatment group (p=0.001 and p=0.048, respectively). Tumor response showed strong correlation with the reduction extent of CECs (p=0.000) and the increase value of ccCK18 (p=0.040) after endostatin therapy. The best cut-off values of the changes of CECs and ccCK18 for prediction of survival were designed being 0.58/ul and 19.6ng/ml, respectively. Furthermore, obvious reduction of CECs and more rise of ccCK18 significantly correlated with the longer median survival (p= 0.013 and p = 0.016 for PFS, p = 0.009 and p=0.012 for OS, respectively). Conclusions: CECs and CKs would be the impressive biomarkers to explore for selecting NSCLC patients who might benefit from endostain in combination with paclitaxel plus carboplatin treatment.
NOT ALL BEST LAID PLANS GO AWRY: THE BENEFIT OF COMPLEX PRENATAL PLANNING IN A RARE CASE OF CARDIAC HEMANGIOMA
Authors: Megan Childress, Samyr Elbadri, Robert Egerman, Himesh Vyas, Connie Nixon, Mark Bleiweis, Jennifer Co-Vu
Journal: Journal of the American College of Cardiology (2020)
PERICARDIAL TAMPONADE IN TYPE A ACUTE AORTIC DISSECTION
Authors: Dan Gilon, Arturo Evangelista-Masip, Derek Brinster, Anthony Estrera, Eduardo Bossone, Mark Peterson, Edward P. Chen, Raffi Bekeredjian, Daniel G. Montgomery, Marc Schermerhorn, Roland Van Kimmenade, Firas F. Mussa, Kim Eagle, Christoph Nienaber, Nilto De Oliveira, Amit Korach, Eric M. Isselbacher
Journal: Journal of the American College of Cardiology (2020)
Primary localized gastrointestinal stromal tumors (GIST) of the duodenum: Final results of a French Sarcoma Group (FSG) retrospective review of 110 patients (pts).
Authors: Thanh Khoa Huynh, Philippe A Cassier, Jean Baptiste Bachet, Eveline Boucher, Olivier Bouche, Axel Le Cesne, Bruno Landi, Julien Mancini, Frederic Marchal, Jacques-Olivier Bay, François Bertucci, Jean-Philippe Spano, Antoine Italiano, Olivier Collard, Loic Chaigneau, Nicolas Isambert, Valerie Lebrun-Ly, Jean-Yves Blay, Florence Duffaud
Journal: Journal of Clinical Oncology (2012)

10078 Background: Duodenal GISTs represent 3-5% of all GISTs with limited understanding of patient outcomes from small series. We conducted a retrospective analysis of primary localized duodenal GISTs over the past 18 years. Methods: Pts were identified in two ways: a group of 101 pts reported via survey from 20 FSG centers, and a group of 9 pts enrolled in the BFR14 trial. Results: Pts were:55 females, 55 males, with a median age of 57 years (30-84), and median ECOG 0 (0-3). Abdominal pain, anemia, and GI bleeding were the most common symptoms. Tumors (T) originated mainly in D2 (41%), or D3 (27%), with a median size of 5 cm (1.5-30). All pts except four had resection of the primary T. Surgical procedures were: local resection (LR) [segmental duodenectomy (n=31), wedge local resection (n=31), local excision (n=6)], and duodenopancreatectomy (DP, n=20). Resections were R0 in 84 pts (79%), R1 in 6 pts (6%). T characteristics included: KIT+ (n=100), CD34 + (n= 54), mitoses/50 HPF ≤ 5 (n= 70), or &gt; 5 (n=24), Miettinen low-risk (n=37), and high-risk (n=19), necrosis (n=29), spindle cell (n=84). Genotype was evaluated in 36 cases: KIT exon 11 mutant (n=30), no mutation (n=4), and KIT exon 9 mutant (n=2). 12 pts received neoadjuvant imatinib (IM) therapy resulting in 6 PR, 3 SD, 1 PD. 17 pts received adjuvant IM therapy. With a median FU of 32 months (1-250), 95 pts (86%) are alive. Twenty-eight (26%) pts relapsed: 6 LR, and 26 metastases. The 4-year OS and EFS rates were 89.5% and 68.2 %. The 6-year OS and EFS rates were 89.5% and 36.5%. Univariate analysis showed that: age and ECOG PS have an impact on OS (p= 0.008, p &lt;0.001), necrosis, spindle-cell type, T size, mitoses/50 HPF, and Miettinen risk were predictive of relapse (p&lt; 0.001). In multivariate analysis tumor size and mitoses/ 50 HPF only were predictive of relapse (p&lt; 0.001). Conclusions: Pts with resected duodenal GIST have a reasonably favourable prognosis. LR rather than DP should be pursued if possible to preserve optimal pancreas function. Neoadjuvant IM may potentially allow a proportion of patients requiring DP to undergo LR. Adjuvant IM should be systematically discussed with a patient based on the individual-risk of recurrence.
Suicide Attempts Among LVAD Recipients
Authors: Marion Charton, Erwan Flécher, Christophe Leclercq, Clément Delmas, Camille Dambrin, Céline Goeminne, André Vincentelli, Magali Michel, Laurence Lehelias, Constance Verdonk, Marylou Para, Matteo Pozzi, Jean-François Obadia, Aude Boignard, Olivier Chavanon, Laurent Barandon, Karine Nubret, Michel Kindo, Tam Hoang Minh, Philippe Gaudard, Edeline Pelcé, Vlad Gariboldi, Pierre-Yves Litzler, Frédéric Anselme, Gerard Babatasi, Annette Belin, Fabien Garnier, Marie Bielefeld, David Hamon, Nicolas Lellouche, Thierry Bourguignon, Thibaud Genet, Romain Eschalier, Nicolas D’Ostrevy, Marie-Cécile Bories, Jérôme Jouan, Fabrice Vanhuyse, Hugues Blangy, Julie Doucerain, Raphael P. Martins, Vincent Galand
Journal: Circulation (2020)
ASSOCIATION OF HDL SUBCLASSES WITH BASELINE CORONARY PLAQUE BURDEN BY CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY (CCTA) FROM EVAPORATE (EFFECT OF VASCEPA ON IMPROVING CORONARY ATHEROSCLEROSIS IN PEOPLE WITH HIGH TRIGLYCERIDES TAKING STATIN THERAPY) TRIAL
Authors: Suvasini Lakshmanan, Chandana Shekar, Suraj Dahal, Afiachukwu Onuegbu, April Kinninger, Andrew Cai, Divya Birudaraju, Lavanya Cherukuri, Ilana Golub, Vahid Rezvanizadeh, Christopher Dailing, Ferdinand Flores, Sajad Hamal, Sion K. Roy, John Nelson, Matthew J. Budoff
Journal: Journal of the American College of Cardiology (2020)
Donald West: criminologist who served as president of the Society for Psychical Research and whose work contributed to the decriminalisation of homosexuality
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Credit: Institute of Criminology, Cambridge

Donald West, the pioneering criminologist and clinical scientist whose early work contributed to the decriminalisation of homosexuality and who attended the UK’s last witchcraft trial, has died peacefully at the age of 95.

Born in the Liverpool docklands, the only child of John West, who worked for the Cunard shipping company, and his wife Jessie, who had worked in a cake shop, Donald James West experienced an isolated childhood and a puritanical home life that left him, as he later wrote, with persisting shyness and feelings of inadequacy. The family moved to Crosby, where he won a scholarship to Merchant Taylor’s secondary school, close to his home, where he shone at science.

He read medicine at the University of Liverpool. While a student he forged friendships, read works on psychology and psychoanalysis, developed an interest in the psychic, and started attending seances in Liverpool. He qualified as a doctor in 1947. During the second world war he joined the Officers’ Training Corps, but saw no active military action.

His first academic work was as the research officer of the Society for Psychical Research (SPR) in London, where his commitment to rigorous and impartial examination of claims of paranormal phenomena eventually led to discontent among less sceptical members of the society. He was advised to seek other employment. He retained his links with the SPR throughout his life, however, joining its governing body, serving three terms as president, and publishing several books on the subject, including …
Role of the urologist in whether locoregional prostate cancer patients consult with a radiation oncologist.
Authors: Ruben G. W. Quek, Kevin C. Ward, Viraj A. Master, Chun Chieh Lin, Katherine S. Virgo, Kenneth M. Portier, Joseph Lipscomb
Journal: Journal of Clinical Oncology (2013)

e16029 Background: Multiple treatment options exist for prostate cancer patients, and therapeutic recommendations may differ depending on characteristics of the specialist consulted. The clinical judgment of specialists can play a critical role in the initial treatment choice, especially in cases where there is no professional consensus regarding the optimal treatment strategy. We examined the association between prostate cancer patients’ urologists’ practice affiliation with medical schools on the likelihood the patient would consult a radiation oncologist. Methods: Using the Surveillance, Epidemiology and End Results – Medicare linked database and the American Medical Association Physician Masterfile, we conducted a retrospective cohort study of 39,915 patients aged 66 years or older who were diagnosed between 2004 - 2007 with locoregional prostate cancer, and the 2,404 urologists who performed the diagnostic biopsies. Multilevel regression analysis was used to evaluate the influence of patients’ urologists’ practice affiliations with medical schools on the patients’ consultation with a radiation oncologist within 9 months of diagnosis. Results: Overall, 25,110 (62.9%) patients consulted with a radiation oncologist. After adjusting for patient, tumor and urologist characteristics, patients who saw urologists practicing within non-institutional settings were significantly more likely to consult with a radiation oncologist (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.05-1.34, p = 0.006) when compared to those who saw urologists practicing within settings with a major medical school affiliation. In addition, patients who saw urologists ≥ 58 years old were significantly more likely to consult with a radiation oncologist (OR, 1.71; 95% CI, 1.16-2.50, p = 0.006) when compared to those who saw urologists &lt; 43 years old. Conclusions: Locoregional prostate cancer patients who received their diagnostic biopsy by urologists practicing in non-institutional settings and those who saw older urologists were significantly more likely to eventually consult with a radiation oncologist. This may have implications on which patient eventually receives radiation as initial therapy.
Protein network mapping of platinum-resistant and poor-survival ovarian cancer.
Authors: Maria Isabella Sereni, Elisa Baldelli, Guido Gambara, Laura Zanotti, Elisabetta Bandiera, Eliana Bignotti, Francesco Meani, Antonella Ravaggi, Roberto Angioli, Lance A. Liotta, Sergio L. Pecorelli, Emanuel Petricoin, Mariaelena Pierobon
Journal: Journal of Clinical Oncology (2013)

5560 Background: Epithelial ovarian carcinoma (EOC) is the fifth leading cause of tumor related death in the female population, with only 30% of patients alive at 5 years after diagnosis. Platinum resistance is a major cause of treatment failure. The aim of the study was to perform broad-scale drug target activation mapping of EOC to identify new druggable targets for personalized therapy. Methods: 72 ovarian primary lesions collected from chemo-naïve EOC patients were analyzed. Highly enriched tumor epithelial cells were isolated by laser capture microdissection, lysed and subjected to reverse phase protein microarray analysis for multiplexed protein pathway activation mapping. The activation/phosphorylation level of 156 key signaling proteins was analysed. Based on the disease-free interval to platinum therapy, 61 stage II-IV patients were segregated into platinum-resistant (&lt;6 months), platinum-sensitive (6-12 months), and platinum-supersensitive disease (&gt;12 months). One-way analysis of variance was used to detect significant differences among the three groups in the drug target activation profile. Results: Expression of the drug target PDGF Receptor β and activation of ErbB2/HER2 (Y1248) were significantly higher in patients with resistant disease compared to sensitive groups (respectively, p 0.0033 and p 0.0134), while the expression of Estrogen receptor α was greater in the supersensitive group (p 0.0295). Moreover, overall survival analysis including all stages revealed that the expression level of Cox2 is significantly higher in patients with shorter survival (HR: 2.48, p 0.0179). Conclusions: Functional drug target activation mapping revealed the unique signaling architecture of platinum-resistant EOC. If confirmed in independent study sets, these results suggest that the utilization of drugs targeting PDGF Receptor β and ErbB2/HER2 could be evaluated in platinum resistant EOC and/or in combination with platinum therapy in order to overcome acquired resistance. Finally, this study indicates that Cox2 may play an important role in aggressive EOC, and that the addition of Cox-inhibitors to standard of care could be rationally evaluated as a novel therapeutic regimen for ovarian cancer.
Carnelian uncovers hidden functional patterns across diverse study populations from whole metagenome sequencing reads
Authors: Sumaiya Nazeen, Yun William Yu, Bonnie Berger
Journal: Genome biology (2020)

Abstract Microbial populations exhibit functional changes in response to different ambient environments. Although whole metagenome sequencing promises enough raw data to study those changes, existing tools are limited in their ability to directly compare microbial metabolic function across samples and studies. We introduce Carnelian, an end-to-end pipeline for metabolic functional profiling uniquely suited to finding functional trends across diverse datasets. Carnelian is able to find shared metabolic pathways, concordant functional dysbioses, and distinguish Enzyme Commission (EC) terms missed by existing methodologies. We demonstrate Carnelian’s effectiveness on type 2 diabetes, Crohn’s disease, Parkinson’s disease, and industrialized and non-industrialized gut microbiome cohorts.