tbuckley/cabot-search huggingface dataset:
The effect of palbociclib (P) in combination with letrozole (L) on bone metastases in women with ER+/ HER2- metastatic breast cancer (MBC): Subanalysis from a randomized phase II study.
Authors: Richard S. Finn, John Crown, Istvan Lang, Sergey O. Kulyk, Marcus Schmidt, Ravi Patel, Anu Thummala, Igor Bondarenko, Sophia Randolph, Sindy Kim, Xin Huang, Erling Donnelly, Cynthia Huang Bartlett, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2015)

572 Background: Bone metastases (BM) are common in MBC. They are often the first and only site of distance disease. Patients with BM only usually have a protracted clinical course though increased bone pain and fractures can be debilitating. PALOMA-1/TRIO-18 was a randomized Phase II study, comparing P plus L (P+L) vs L alone as first-line treatment of advanced ER+ / HER2- BC. At final analysis, P+L doubled progression-free survival (Finn et al. Lancet Oncol 2015). In this sub-analysis, we evaluated the effects of P+L on bone metastases. Methods: 165 ER+ and HER2- postmenopausal women who were untreated for their ABC were randomized to receive L (2.5 mg/day) (N = 81) or L (2.5 mg/day) plus P (125 mg/day for 3 weeks on/1 week off) (N = 84). The primary endpoint was investigator-assessed PFS. Tumor assessments were performed every 8 weeks and bone scans every 12 weeks. PFS analysis was performed for those patients (pts) with objective progression determined based on the appearance of new bone lesion(s) and/or progression of existing bone non-target lesion(s). Patient reported outcomes (PRO) on pain severity (PS) and pain interference (PI) were assessed with Modified Brief Pain Inventory-Short Form (mBPI-sf). Results: 75% of patients had bone disease at baseline (73% P+L vs. 77% L) and 18% had bone only disease (20% P+L vs. 15% L). Median PFS among pts who had objective PD due to the appearance of new BM and/or objective PD in bone as non-target lesion were 18 m (95% CI 9, 28) for P+L (n = 8) vs. 4 m (95% CI 2, 35) for L (n = 16). Among those patients with bone-only disease at baseline, significant prolongation of PFS (NR P+ L vs 13.3 m L, HR = 0.294, 95% CI 0.092-0.945). Numerical differences in PI and PS scores in favor of P + L over L were observed from the PRO data collected from all randomized pts. Conclusions: Theaddition of P to L demonstrated a significant improvement in PFS. P+L leads to clinically meaningful delays in progression in the bone. Clinical trial information: NCT00721409.
CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms
Authors: Xian-Yang Li, Indrajit Das, Ailin Lepletier, Venkateswar Addala, Tobias Bald, Kimberley Stannard, Deborah Barkauskas, Jing Liu, Amelia Roman Aguilera, Kazuyoshi Takeda, Matthias Braun, Kyohei Nakamura, Sebastien Jacquelin, Steven W. Lane, Michele W.L. Teng, William C. Dougall, Mark J. Smyth
Journal: Journal of Clinical Investigation (2018)

Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) require greater attention. Nectins and nectin-like molecules might be promising targets for immunotherapy, since they play critical roles in cell proliferation and migration and exert immunomodulatory functions in pathophysiological conditions. Here, we show CD155 expression in both malignant cells and tumor-infiltrating myeloid cells in humans and mice. Cd155–/– mice displayed reduced tumor growth and metastasis via DNAM-1 upregulation and enhanced effector function of CD8+ T and NK cells, respectively. CD155-deleted tumor cells also displayed slower tumor growth and reduced metastases, demonstrating the importance of a tumor-intrinsic role of CD155. CD155 absence on host and tumor cells exerted an even greater inhibition of tumor growth and metastasis. Blockade of PD-1 or both PD-1 and CTLA4 was more effective in settings in which CD155 was limiting, suggesting the clinical potential of cotargeting PD-L1 and CD155 function.
Care for Undocumented Immigrants — Rethinking State Flexibility in Medicaid Waivers
Authors: A Taylor Kelley, Renuka Tipirneni
Journal: New England Journal of Medicine (2018)

Interview with Dr. Taylor Kelley on options for states seeking to expand health insurance coverage for undocumented immigrants (08:41)Download Under President Trump, HHS has promised to grant states more flexibility in structuring their Medicaid programs. But in a contentious and uncertain policy environment, states may sense little room to advance policies related to the health of undocumented immigrants.
Multispectral <i>ex vivo</i> photoacoustic imaging of cutaneous melanoma for better selection of the excision margin
Authors: J. Kim, Y.H. Kim, B. Park, H.-M. Seo, C.H. Bang, G.S. Park, Y.M. Park, J.W. Rhie, J.H. Lee, C. Kim
Journal: British Journal of Dermatology (2018)
Publisher Correction: Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
Authors: Etienne Patin, Milena Hasan, Jacob Bergstedt, Vincent Rouilly, Valentina Libri, Alejandra Urrutia, Cécile Alanio, Petar Scepanovic, Christian Hammer, Friederike Jönsson, Benoît Beitz, Hélène Quach, Yoong Wearn Lim, Julie Hunkapiller, Magge Zepeda, Cherie Green, Barbara Piasecka, Claire Leloup, Lars Rogge, François Huetz, Isabelle Peguillet, Olivier Lantz, Magnus Fontes, James P. Di Santo, Stéphanie Thomas, Jacques Fellay, Darragh Duffy, Lluís Quintana-Murci, Matthew L. Albert
Journal: Nature Immunology (2018)
Albumin function in acute-on-chronic liver failure (ACLF): Effect of plasma exchange with albumin 5% (PE-A5%)
Authors: M. Torres, R. Horrillo, N. Afonso, L. Nunez, A.M. Ortiz, A. Pérez, M. Costa, V. Arroyo, J. Fernández, S. Grancha, A. Páez
Journal: Journal of Hepatology (2018)
The Obesity Paradox in Cancer: How Important Is Muscle?
Authors: Elizabeth M. Cespedes Feliciano, Candyce H. Kroenke, Bette J. Caan
Journal: Annual Review of Nutrition (2018)

Although higher body mass index (BMI) increases the incidence of many cancers, BMI can also exhibit a null or U-shaped relationship with survival among patients with existing disease; this association of higher BMI with improved survival is termed the obesity paradox. This review discusses possible explanations for the obesity paradox, the prevalence and consequences of low muscle mass in cancer patients, and future research directions. It is unlikely that methodological biases, such as reverse causality or confounding, fully explain the obesity paradox. Rather, up to a point, higher BMI may truly be associated with longer survival in cancer patients. This is due, in part, to the limitations of BMI, which scales weight to height without delineating adipose tissue distribution or distinguishing between adipose and muscle tissue. Thus, cancer patients with higher BMIs often have higher levels of protective muscle. We assert that more precise measures of body composition are required to clarify the relationship of body size to cancer outcomes, inform clinical decision-making, and help tailor lifestyle interventions.
A Case of Gastric Neuroendocrine Neoplasm with Mixed Grade: a Distinct Type of “High”-grade Well-Differentiated Neuroendocrine Neoplasm
Authors: Elia Guadagno, Gaetano Luglio, Alessandro Iacobelli, Giorgio Borrelli, Antonio Castaldi, Gaetano De Rosa, Marialaura Del Basso De Caro
Journal: Endocrine Pathology (2018)
Suicide: A Silent Contributor to Opioid-Overdose Deaths
Authors: Maria A. Oquendo, Nora D. Volkow
Journal: New England Journal of Medicine (2018)

A Silent Contributor to Opioid-Overdose Deaths Most strategies for reducing opioid-overdose deaths don’t include screening for suicide risk or address tailoring of interventions for suicidal persons. And the inaccuracy of data on the proportion of opioid deaths that are suicides hinders appropriate prevention.
Abstract 12217: A Hierarchical Model for Stage B Heart Failure Screening- Results of a Classification and Regression-Based Decision Tree
Authors: Hong Yang, Kazuaki Negishi, Ying Wang, Mark Nolan, Thomas Marwick
Journal: Circulation (2015)

Purpose: In pts with stage A heart failure (SAHF), the identification of stage B HF relies on echo, but application of this to community based screening is limited by access and cost. We sought to use clinical characteristics and functional capacity to select at risk subjects for echo. Methods: 308 asymptomatic subjects ≥65 years with the presence of ≥ 1 HF risk factor (hypertension, type 2 diabetes, obesity, previous chemotherapy, family history of heart failure and history of cardiac disease but not in HF) were recruited from the local community. All subjects underwent baseline risk quantification using ARIC risk score, functional assessment by 6 minute-walk test (6MW) and a comprehensive echocardiogram including conventional diastology and speckle tracking analysis for global longitudinal strain (GLS) and diastolic strain (DS). New HF was assessed at 14±4 m, based on 3 independent cardiologists using Framingham criteria. A classification and regression-based decision tree (CART) was built using baseline characteristics as independent variables. Results: In the CART model, a 3-level decision tree model was chosen to predict 19 pts (6%) who developed new HF at 1 year. The best predictor was 6MW followed by ARIC risk score (Figure). Using this model, 190 individuals (6MW≤330, or ARIC score&gt;4.75%) were classified as high risk (9.5% events) and 118 (38%) were classified as low risk (0.8% events). GLS, DS and conventional diastolic measures (e’, E/e’) were significantly impaired in the high risk group (Figure). The AUC of the combined CART model with GLS was 0.72 (95% CI: 0.62-0.82, p=0.001) for new HF. Conclusion: Pts with SAHF with low HF risk and preserved exercise capacity have preserved LV function and a low event rate. GLS assessment in SAHF may be considered in pts with &gt;4.75% 4 year risk, or 6MW≤330m.
lkb1 inhibits the hepatic gluconeogenis by impeding the availability of amino acids
Authors: C. Perret, S. Charawi, J. Pierre-Alexandre, Raphaël Denis, T. Massire, B. Sultan, S. Nadia, S. Pierre, S. Mathilde, W. Maud, L. Marjorie, G. François, S. Luquet, P. Bossard
Journal: Journal of Hepatology (2018)
Comparison of event-free survival between DAA and IFN-based antiviral therapy for HCV, adjusted for disease severity
Authors: L. Krassenburg, W.R. Zanjir, F. Georgie, K. Munawar, O. Cerocchi, E. Stotland, J. Lau, H. Janssen, B. Hansen, J. Feld
Journal: Journal of Hepatology (2018)
Antitumor activity of osimertinib in NSCLC harboring EGFR exon 20 insertions.
Authors: Jonathan Riess, Nicolas Floch, Matthew Martin, Jonathon Orme, Anna Staniszewska, Ludovic Menard, Maria Emanuela Cuomo, Daniel O'Neill, Richard Ward, Raymond Finlay, Darren McKerrecher, Mingshan Cheng, Daniel Vang, Rebekah Tsai, Chunting Ye, James G. Keck, David R. Gandara, Philip C. Mack, Darren Cross
Journal: Journal of Clinical Oncology (2017)

9030 Background: EGFR exon 20 insertions (Ex20Ins), the 3 rd most common EGFR activating mutation, are generally unresponsive to 1 st and 2 nd generation EGFR-TKIs. Development of EGFR-TKIs that effectively target NSCLC with Ex20Ins mutations represents a major unmet need. Osimertinib is an EGFR TKI approved for the treatment of advanced NSCLC harboring EGFR T790M, but the potential of osimertinib remains to be fully assessed in patients (pts) with Ex20Ins NSCLC. Methods: CRISPR engineered Ex20Ins cell line xenografts representing the two most common Ex20Ins (D770_N771InsSVD and V769_D770InsASV) and pt derived xenograft (PDX) of 3 EGFR Ex20Ins (V769_D770InsASV, M766_A767insASV, H773_V774insNPH) were used for in vivo experiments. Xenografts were treated by oral gavage with vehicle, erlotinib (50 mg/kg/day) or afatinib (20 mg/kg/day), osimertinib metabolite AZ5104 (50 mg/kg/day) and osimertinib (25 mg/kg/day) and assessed for tumor growth inhibition (TGI). Immunoblotting was performed for EGFR and relevant signaling pathways. A pt from whom the V769_D770InsASV Ex20ins PDX was derived was treated on a UC Davis IRB approved protocol with osimertinib at 160 mg PO once-daily (QD). Results: At completion of treatment, QD administration of osimertinib or AZ5104 induced significant TGI in xenografts across the 4 EGFR Ex20ins tested (range 60-95% TGI, p &lt; 0.001 compared to control for all models) that was superior to either afatinib or erlotinib. Robust decrease in p-EGFR, p-ERK, p-Akt, p-Stat3 was observed with osimertinib treatment. The patient corresponding to the V769_D770InsASV Ex20ins PDX treated with osimertinib exhibited clinical improvement and tumor shrinkage; unfortunately he was found to have interstitial pneumonitis that necessitated drug discontinuation. Conclusions: Osimertinib at clinically representative doses has in vivo activity across multiple EGFR Ex20ins that comprising the most common Ex20ins detected in patients (~50% prevalence); metabolite AZ5104 may contribute to efficacy. Tumor shrinkage was observed in a patient with lung cancer harboring an Ex20ins treated for a limited time with osimertinib. Based on this in vivo xenograft and pt data, osimertinib warrants further study in pts with EGFR Ex20ins NSCLC.
Abstract 20288: Quantification and Z-Score “Normalization” of Regional Myocardial Contractile Data in Ischemic Coronary Artery Disease Patients
Authors: Matthew C Henn, Beckah D Brady, Julia Kar, Brian P Cupps, Kathleen Wallace, Alan C Braverman, Michael K Pasque
Journal: Circulation (2014)

Introduction: Left ventricular (LV) regional contractile information is currently limited to subjective interpretation of low-resolution echocardiography. In order to establish a more specific and standardized form of imaging, this study compared strain patterns in normal patients to patients with coronary artery disease (CAD) using high-resolution contractile data from cardiac MRI. Methods: Sixty normal test subjects underwent cardiac MRI with multiple 3D strain parameters calculated from tissue tag-plane displacement data. 15,300 LV grid points contributed to a normal human strain database. Sixty patients with known CAD underwent cardiac MRI. Normalized z-scores for 3 strain parameters at each of the LV grid-points were calculated by comparing raw strain values to the normal database. The z-scores at each point were then averaged to generate 15,300 normalized strain z-scores. Clinical evidence for prior ischemic events was sought in each patient’s medical record. Results: Multi-parametric strain information was successfully obtained in all 60 CAD patients with post-processing display of “quantified” regional ischemic injury over patient-specific LV geometry. We displayed “normalized” micro-regional contractile function by intuitive z-score color-coding of regions (&lt;1 standard deviation=blue; 1-2=yellow; &gt;2=red) over patient-specific 3D LV geometry (Figure). Clinical evidence for prior ischemic events obtained from echo, viability studies, ECG, and left heart catherization correlated well with regional injury patterns. Conclusions: The quantitative “normalization” of raw patient-specific values by z-score calculation from a normal human strain database can effectively create vivid displays of prior ischemic events. These high-resolution images provide detailed contractile information that may shape a new paradigm in preoperative surgical evaluation prior to revascularization.
Emergence of hepatitis C virus resistance associated variants in patients failing direct acting antivirals by ultra-deep sequencing
Authors: T. Nguyen, S. Akhavan, F. Caby, L. Bonyhay, L. Larrouy, A. Gervais, P. Lebray, T. Poynard, Y. Calmus, A. Simon, M.-A. Valantin, V. Calvez, A.-G. Marcelin, E. Todesco
Journal: Journal of Hepatology (2018)
Sero-prevalence of Hepatitis B surface antigen among 5-7 years old children and their mothers in Cambodia by nationwide multistage stratified random sampling strategy
Authors: J. Tanaka, J.V. Woodring, V. Ork, M. Bunsoth, S. Nagashima, C. Yamamoto, C. Chuon, K. Ko, S. Hossain
Journal: Journal of Hepatology (2018)
Small leucine-rich proteoglycans expression in colorectal cancer: Differences by primary tumor location.
Authors: Maria Del Pilar Solis Hernandez, Natalia Perez Lopez, Yolanda Garcia Mesa, Ivan Fernandez-Vega, Olivia García-Suárez, Victor Lozano Iturbe, Beatriz García, Luis M Quirós
Journal: Journal of Clinical Oncology (2018)

721 Background: SLRP are present in normal and tumor colorectal tissue, with different patterns of expression, being predominant in L CRC. However, due to the small sample the differences observed in survival were no statistically significative. These alterations could be related to interactions at the extracellular matrix level. Further prospective and larger analysis are needed for a better comprehension of tumor microenvironment. Aims: To describe SLRP expression pattern by PTL and survival rate. Methods: 32 tumor specimens and their respective healthy tissue (fresh frozen tissue) from primary tumor surgery from the local biobank: 12 right-sided (R) &amp; 20 left-sided (L) CRC. Transcriptomic approach to analyze SLRP core protein transcriptions using RT-PCR in Those with significative differences were confirmed by immunohistochemistry. Survival analysis was performed using Kaplan-Meier curves and log rank test. Results: Both sides showed BGN 2-fold overexpression (R p = 0.015, L p = 0.001) and OGN decreased 4-3-fold (R p = 0.038, L p &lt; 0.001). PODNL was only expressed in tumor tissue. Additionally, alterations in other 4 genes in L CRC: PODN 2-fold p = 0.003, CHAD 4-fold p = 0.017, DCN 2fold p = 0.047 and PRELP 3-fold p = 0.003. EPYC was only expressed in 50% of L CRC. No difference in ASPN, FMOD, LUM, ECM2, KERA, OMD, TSK. Neither it was in PRELP for L CRC nor EPYC and DCN in R CRC. No expression of OPTC was found. No significative differences in survival were found. Median relapse-free survival (RFS) was 25 months (mo), 10.75 mo R CRC and 19.47mo L CRC. BGN overexpression (44%) was related with worse RFS (14 vs 19mo), better in L CRC (12 vs 19mo). OGN decrease (17%) showed better RFS (40 vs 16mo) favoring L CRC (21 vs 17mo). Overall survival displayed a similar behavior. Conclusions: SLRP are present in normal and tumor colorectal tissue, with different patterns of expression, being predominant in L CRC. However, due to the small sample the differences observed in survival were no statistically significative. These alterations could be related to interactions at the ECM level. Further prospective and larger studies are needed for a better comprehension of tumor microenvironment.
European countries are urged to carry out catch-up campaigns as measles outbreaks continue
Authors: Jacqui Wise
Journal: BMJ (2018)

European countries should carry out vaccination catch-up campaigns targeting teenagers and young people to stem measles outbreaks around the continent, the European Centre for Disease Prevention and Control has said.

The centre’s annual report shows that as many as 80% of teenagers and young adults who contracted measles in 2017 had not been vaccinated.1 A rapid risk assessment by the centre found that unvaccinated healthcare workers were affected in the latest outbreaks.

Mike Catchpole, chief scientist at the centre, told The BMJ , “We are seeing …
Efficacy and safety of 8 weeks of elbasvir/grazoprevir in HCV GT4-infected treatment-naīve participants
Authors: T. Asselah, S. Pol, C. Hezode, V. Loustaud-Ratti, V. Leroy, S.N.S. Ahmed, V. Ozenne, J.-P. Bronowicki, D. Larrey, A. Tran, L. Alric, E. Nguyen-Khac, M. Robertson, G. Hanna, D. Brown, E. Asante-Appiah, S. Ludmerer, M. Su, P. Hwang, S. Klopfer, F. Dutko, A. Guidoum, K. Hagen, B. Haber, R. Talwani, L. Serfaty
Journal: Journal of Hepatology (2018)
Doctors protest against “hostile environment” immigration policy spreading to NHS
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

Philippa Velhinho

Doctors were joined by nurses and the public in Westminster on 2 May to protest against the Home Office’s use of NHS services and staff to help with immigration enforcement.

Their prop was a spoof van, organised by Doctors of the World (DOTW) UK and the campaign organisation 38 Degrees. It parodied the “Go home or face arrest” vans that became synonymous with Theresa’s May “hostile environment” policy in 2013, when she was home secretary—but with a new message: “Doctors acting as border guards? 70 000 doctors and patients say ‘no’ to sharing patient data with the Home Office.”

The message refers to a petition urging NHS Digital and Jeremy Hunt, England’s health and social care …
Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 is a Novel Post-Transcriptional Regulator of Ewing Sarcoma Malignancy
Authors: Caterina Mancarella, Michela Pasello, Selena Ventura, Andrea Grilli, Linda Calzolari, Lisa Toracchio, Pier-Luigi Lollini, Davide Maria Donati, Piero Picci, Stefano Ferrari, Katia Scotlandi
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Large-scale sequencing studies have indicated that besides genomic alterations, the posttranscriptional regulation of gene expression or epigenetic mechanisms largely influences the clinical behavior of Ewing sarcoma. We investigated the significance of the RNA-binding protein IGF2BP3 in the regulation of Ewing sarcoma aggressiveness. Experimental Design: Explorative study was performed in 14 patients with localized Ewing sarcoma using RNA sequencing. Next, 128 patients with localized Ewing sarcoma were divided into two cohorts. In the training set, 29 Ewing sarcoma samples were analyzed using Affymetrix GeneChip arrays. In the validation set, 99 Ewing sarcoma samples were examined using qRT-PCR. Patient-derived cell lines and experimental models were used for functional studies. Results:Univariate and multivariate analyses indicated IGF2BP3 as a potent indicator of poor prognosis. Furthermore, ABCF1 mRNA was identified as a novel partner of IGF2BP3. Functional studies indicated IGF2BP3 as an oncogenic driver and ABCF1 mRNA as a sponge that by binding IGF2BP3, partly repressed its functions. The combined evaluation of IGF2BP3 and ABCF1 could identify different patient outcomes—high IGF2BP3 and low ABCF1 levels indicated poor survival (25%), whereas low IGF2BP3 and high ABCF1 levels indicated favorable survival (85.5%). The bromodomain and extraterminal domain inhibitor (BETi) JQ1 decreased IGF2BP3 expression, modified the expression of its validated targets and inhibited the capability of Ewing sarcoma cells to grow under anchorage-independent conditions. Conclusions: The combined assessment of IGF2BP3 and ABCF1 predicts recurrence in Ewing sarcoma patients. Thus, for patients with high expression of IGF2BP3 and poor probability of survival, the use of BETis should be clinically evaluated. Clin Cancer Res; 24(15); 3704–16. ©2018 AACR.
No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals
Authors: Agnieszka Butwicka, Amir Sariaslan, Henrik Larsson, Jonas Halfvarson, Pär E Myrelid, Ola Olén, Louise Frisen, Paul Lichtenstein, Jonas F Ludvigsson
Journal: Gut (2018)

We read with interest the recently published work in Gut by Imhann et al .1 Although this paper suggests that genetics plays an important role in IBD,1 environmental factors clearly contribute to its aetiology.2 When Ng et al 2 reviewed environmental risk factors for IBD in this journal they noted that urbanisation may be linked to both Crohn’s disease (CD) and ulcerative colitis (UC).

We used Cox regression to estimate the effect of urbanisation and deprivation during childhood on future IBD.

From the Swedish Total Population Register,3 the government agency Statistics Sweden selected all individuals born in Sweden between 1973 and 2013 (n=4 161 280). Among these there …
The bile acid biome and its relationship to the development and severity of alcoholic hepatitis
Authors: P. Puri, F. Mirshahi, S. Liangpunsakul, D. Crabb, V. Shah, G. Gores, P. Kamath, H. Malhi, M. Sikaroodi, S. Raedeva, P. Gillevet, N. Chalasani, A. Sanyal
Journal: Journal of Hepatology (2018)