tbuckley/cabot-search huggingface dataset:
Nomogram for predicting overall survival (OS) in patients (pts) treated with liposomal irinotecan (nal-IRI) ± 5-fluorouracil/leucovorin (5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy in NAPOLI-1.
Authors: Andrea Wang-Gillam, Richard Hubner, Beloo Mirakhur, Floris A de Jong, Bruce Belanger, Li-Tzong Chen
Journal: Journal of Clinical Oncology (2018)

459 Background: Results from NAPOLI-1 (NCT01494506), a phase 3 study in pts with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in OS (primary endpoint), progression-free survival, and objective response rate with nal-IRI+5-FU/LV vs 5-FU/LV. The MPACT study reported a nomogram to predict OS using baseline pt variables in previously untreated mPDAC. We conducted an exploratory post hoc analysis of NAPOLI-1 variables to develop a nomogram to predict OS in the post-gemcitabine setting. Methods: In NAPOLI-1, pts were randomized to receive nal-IRI 80 mg/m2 q2w + 5-FU/LV, nal-IRI 100 mg/m2 q3w, or 5-FU/LV. Univariate and multivariate analyses determined factors significantly predictive of OS. A multivariable Cox model was created using these factors to develop a nomogram that assigned points equal to the weighted sum of relative significance of each variable. Predictive accuracy of the nomogram as measured by the concordance index (c-index) was evaluated by internal bootstrap validation. Results: Data from the 417-pt univariate analysis and 399-pt multivariate analysis (18 pts excluded for missing baseline data) were used. Eight of 21 variables were retained in the multivariate analysis (p &lt; 0.01 except BMI [p=0.08]). Conclusions: In NAPOLI-1, predictors of OS were nal-IRI+5-FU/LV treatment, KPS, NLR, albumin level, baseline CA19-9, stage 4 at diagnosis, BMI, and presence of liver metastasis. The nomogram, which will distinguish between risk groups and may aid in clinical decision making, will be presented in the poster. Clinical trial information: NCT01494506. [Table: see text]
Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques
Authors: Maud Mavigner, Jessica Raper, Zsofia Kovacs-Balint, Sanjeev Gumber, Justin T. O’Neal, Siddhartha K. Bhaumik, Xiaodong Zhang, Jakob Habib, Cameron Mattingly, Circe E. McDonald, Victoria Avanzato, Mark W. Burke, Diogo M. Magnani, Varian K. Bailey, David I. Watkins, Thomas H. Vanderford, Damien Fair, Eric Earl, Eric Feczko, Martin Styner, Sherrie M. Jean, Joyce K. Cohen, Guido Silvestri, R. Paul Johnson, David H. O’Connor, Jens Wrammert, Mehul S. Suthar, Mar M. Sanchez, Maria C. Alvarado, Ann Chahroudi
Journal: Science Translational Medicine (2018)

Zika virus infection early after birth has deleterious effects on the developing brain and long-term behavioral changes in rhesus macaques.
From Crowdsourcing to Extreme Citizen Science: Participatory Research for Environmental Health
Authors: P.B. English, M.J. Richardson, C. Garzón-Galvis
Journal: Annual Review of Public Health (2018)

Environmental health issues are becoming more challenging, and addressing them requires new approaches to research design and decision-making processes. Participatory research approaches, in which researchers and communities are involved in all aspects of a research study, can improve study outcomes and foster greater data accessibility and utility as well as increase public transparency. Here we review varied concepts of participatory research, describe how it complements and overlaps with community engagement and environmental justice, examine its intersection with emerging environmental sensor technologies, and discuss the strengths and limitations of participatory research. Although participatory research includes methodological challenges, such as biases in data collection and data quality, it has been found to increase the relevance of research questions, result in better knowledge production, and impact health policies. Improved research partnerships among government agencies, academia, and communities can increase scientific rigor, build community capacity, and produce sustainable outcomes.
Active Surveillance for Localized Renal Masses: Tumor Growth, Delayed Intervention Rates, and &gt;5-yr Clinical Outcomes
Authors: Andrew G. McIntosh, Benjamin T. Ristau, Karen Ruth, Rachel Jennings, Eric Ross, Marc C. Smaldone, David Y.T. Chen, Rosalia Viterbo, Richard E. Greenberg, Alexander Kutikov, Robert G. Uzzo
Journal: European Urology (2018)
Mobile Sensing in Environmental Health and Neighborhood Research
Authors: Basile Chaix
Journal: Annual Review of Public Health (2018)

Public health research has witnessed a rapid development in the use of location, environmental, behavioral, and biophysical sensors that provide high-resolution objective time-stamped data. This burgeoning field is stimulated by the development of novel multisensor devices that collect data for an increasing number of channels and algorithms that predict relevant dimensions from one or several data channels. Global positioning system (GPS) tracking, which enables geographic momentary assessment, permits researchers to assess multiplace personal exposure areas and the algorithm-based identification of trips and places visited, eventually validated and complemented using a GPS-based mobility survey. These methods open a new space-time perspective that considers the full dynamic of residential and nonresidential momentary exposures; spatially and temporally disaggregates the behavioral and health outcomes, thus replacing them in their immediate environmental context; investigates complex time sequences; explores the interplay among individual, environmental, and situational predictors; performs life-segment analyses considering infraindividual statistical units using case-crossover models; and derives recommendations for just-in-time interventions.
The relationship between dose to skeletal muscle area ratio and gemcitabine nab-paclitaxel toxicity in pancreatic ductal adenocarcinoma.
Authors: Rachel Wong, Julia Freckelton, Daniel Croagh, Darcy Quinn Holt, Adrian Fox, Margaret Lee, Gregory Thomas Moore
Journal: Journal of Clinical Oncology (2018)

492 Background: Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity is less than that associated with other combination metastatic regimens (FOLFIRINOX), but it is still associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. Methods: This study involved two sites and included patients who had received Gem-Nab-P between January 2013 and March 2017. A review of medical records was used to identify demographic, disease and first-cycle treatment information. Chemotherapy toxicity was defined as grade 3 or 4 adverse events using the National Cancer Institute Common Toxicity Criteria Adverse Events manual v4.0. Body composition analysis was performed on computed tomography scans at spinal level L3, using SliceOmatic software. SPSS software was used to for all statistical analysis, with a p value of &lt; 0.05 considered significant. Results: We identified 52 patients treated with first-line Gem-Nab-P for PDAC. Median age was 65 years (57-73) and 24 (47%) were male. Median BMI at commencement of Gem-Nab-P was 24.7 kg/m 2 (21.3-27.4) and 38 (58%) of the patients were myopenic before starting chemotherapy. Fourteen (27%) patients experienced toxicity during the first cycle of chemotherapy. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median SkMA to those who did not (128.6 cm 2 vs. 111.4 cm 2 , p= 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm 2 vs. 14.4 mg/cm 2 , p=0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm 2 vs. 1.8 mg/cm 2 , p=0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm 2 vs. 2.9 mg/cm 2 , p=0.9) between the patients that experienced first cycle toxicity versus those that did not. Conclusions: This study suggests that a pancreatic cancer patient’s skeletal muscle area is unlikely to be a useful addition to conventional body surface area in the dosing of first line Gem-Nab-P, to reduce first-cycle toxicity.
Abstract P158: Lipid Management Challenges in Different Clinical Settings
Authors: Landai Nguyen, Mazen Omar, Bassam A Omar, G. Mustafa Awan, Christopher Malozzi
Journal: Circulation (2018)

Background: Availability of lipid profile during a patient’s clinic encounter can improve decision-making in regards to therapy, and help achieve therapeutic goals. Methods: Encounters from 2 clinics run by one cardiologist; a University-based clinic and a Veterans Administration (VA) clinic were compared for availability of cholesterol profiles and level of cholesterol control in patients with coronary disease. Results: There were 93 out of 300 encounters (31%) with documented coronary disease (CAD) in the University clinic and 77 out of 134 encounters (57%) in the VA clinic. University patients with CAD had 61% (57/93) lipid documentation during their encounters, while VA patients had 99% (76/77) documentation. The average total cholesterol and LDL for University patients was 179 ± 42 mg/dL and 111 ± 35 mg/dL respectively, compared with 154 ± 38 mg/dL and 93 ± 35 mg/dL for the VA patients respectively (P &lt; 0.01 for each category). Only 39% (22/57) of the University-based patients achieved LDL &lt; 100 mg/dL, compared with 66% (51/77) of VA patients. Blood pressures, which were consistently documented every clinic visit in both clinics, averaged 128/76 mmHg in the University clinic compared with 131/75 mmHg in the VA clinic, with no statistically significant difference. Conclusion: Better control of cholesterol levels is seen in the VA-based clinic compared with the University-based clinic. This may partially be explained by the availability of laboratory results through a unified computer system, allowing more prompt decision-making with regards to medication changes and intensified dietary counseling during the clinic encounter. This may not be always available in other settings where laboratory tests are performed by a different provider utilizing a different reporting system which may not be readily shared or available to the treating cardiologist. Other factors could include variable compliance with laboratory appointments and access to medications. Our findings support establishing means for cardiologists to have access to patients’ laboratory results during their encounter to help more efficient decision making.
Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic cell transplantation (ALLIVE): a prospective, multicentre, observational trial
Authors: Martin Wermke, Julia Eckoldt, Katharina S Götze, Stefan A Klein, Gesine Bug, Liesbeth C de Wreede, Michael Kramer, Friedrich Stölzel, Malte von Bonin, Johannes Schetelig, Michael Laniado, Verena Plodeck, Wolf-Karsten Hofmann, Gerhard Ehninger, Martin Bornhäuser, Dominik Wolf, Igor Theurl, Uwe Platzbecker
Journal: The Lancet Haematology (2018)
Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft Injury
Authors: Line Heylen, Bernard Thienpont, Maarten Naesens, Pieter Busschaert, Jeroen Depreeuw, Dominiek Smeets, Ina Jochmans, Diethard Monbaliu, Jacques Pirenne, Evelyne Lerut, Bart Ghesquiere, Dirk Kuypers, Diether Lambrechts, Ben Sprangers
Journal: Journal of the American Society of Nephrology (2018)

Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury. Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n =13), after implantation and reperfusion (postischemia; n =13), and at 3 or 12 months after transplant ( n =5 each); a cross-sectional cohort with preimplantation biopsy specimens ( n =82); and a cross-sectional cohort with postreperfusion biopsy specimens ( n =46). Results Analysis of the paired preischemia and postischemia specimens revealed that methylation increased drastically in all allografts on ischemia. Hypermethylation was caused by loss of 5-hydroxymethylcytosine, the product of TET activity, and it was stable 1 year after transplant. In the preimplantation cohort, CpG hypermethylation directly correlated with ischemia time and for some CpGs, increased 2.6% per additional hour of ischemia. Hypermethylation preferentially affected and reduced the expression of genes involved in suppressing kidney injury and fibrosis. Moreover, CpG hypermethylation in preimplantation specimens predicted chronic injury, particularly fibrosis and glomerulosclerosis, 1 year after transplant. This finding was validated in the independent postreperfusion cohort, in which hypermethylation also predicted reduced allograft function 1 year after transplant, outperforming established clinical variables. Conclusions We highlight a novel epigenetic basis for ischemia-induced chronic allograft injury with biomarker potential.
Epigenetic prediction of complex traits and death
Authors: Daniel L. McCartney, Robert F. Hillary, Anna J. Stevenson, Stuart J. Ritchie, Rosie M. Walker, Qian Zhang, Stewart W. Morris, Mairead L. Bermingham, Archie Campbell, Alison D. Murray, Heather C. Whalley, Catharine R. Gale, David J. Porteous, Chris S. Haley, Allan F. McRae, Naomi R. Wray, Peter M. Visscher, Andrew M. McIntosh, Kathryn L. Evans, Ian J. Deary, Riccardo E. Marioni
Journal: Genome biology (2018)

Genome-wide DNA methylation (DNAm) profiling has allowed for the development of molecular predictors for a multitude of traits and diseases. Such predictors may be more accurate than the self-reported phenotypes and could have clinical applications. Here, penalized regression models are used to develop DNAm predictors for ten modifiable health and lifestyle factors in a cohort of 5087 individuals. Using an independent test cohort comprising 895 individuals, the proportion of phenotypic variance explained in each trait is examined for DNAm-based and genetic predictors. Receiver operator characteristic curves are generated to investigate the predictive performance of DNAm-based predictors, using dichotomized phenotypes. The relationship between DNAm scores and all-cause mortality (n = 212 events) is assessed via Cox proportional hazards models. DNAm predictors for smoking, alcohol, education, and waist-to-hip ratio are shown to predict mortality in multivariate models. The predictors show moderate discrimination of obesity, alcohol consumption, and HDL cholesterol. There is excellent discrimination of current smoking status, poorer discrimination of college-educated individuals and those with high total cholesterol, LDL with remnant cholesterol, and total:HDL cholesterol ratios. DNAm predictors correlate with lifestyle factors that are associated with health and mortality. They may supplement DNAm-based predictors of age to identify the lifestyle profiles of individuals and predict disease risk.
Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU
Authors: Russell R. Miller, Bert K. Lopansri, John P. Burke, Mitchell Levy, Steven Opal, Richard E. Rothman, Franco R. D’Alessio, Venkataramana K. Sidhaye, Neil R. Aggarwal, Robert Balk, Jared A. Greenberg, Mark Yoder, Gourang Patel, Emily Gilbert, Majid Afshar, Jorge P. Parada, Greg S. Martin, Annette M. Esper, Jordan A. Kempker, Mangala Narasimhan, Adey Tsegaye, Stella Hahn, Paul Mayo, Tom van der Poll, Marcus J. Schultz, Brendon P. Scicluna, Peter Klein Klouwenberg, Antony Rapisarda, Therese A. Seldon, Leo C. McHugh, Thomas D. Yager, Silvia Cermelli, Dayle Sampson, Victoria Rothwell, Richard Newman, Shruti Bhide, Brian A. Fox, James T. Kirk, Krupa Navalkar, Roy F. Davis, Roslyn A. Brandon, Richard B. Brandon
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility.Objectives: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults.Methods: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands (www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts.Measurements and Main Results: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82–0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0–10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity.Conclusions: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation.Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502)
Frank Eyvind Hytten
Authors: John Davison
Journal: BMJ (2018)

Frank Eyvind Hytten was a pioneer of physiological research in pregnancy and lactation and a key contributor to the promotion of scientific attitudes and improved research and clinical practice in obstetrics. Frank was born in Hobart, Tasmania, Australia, but his family moved to Sydney during his childhood. He started his qualified career in Sydney with residencies in obstetrics and gynaecology, followed by the award of a prestigious three year Walter and Eliza Hall travelling research fellowship to study research methods abroad. This enabled him to spend time in Aberdeen and Boston (USA), returning to Sydney for the final year. His interests were initially in the newborn, focusing on lactation and breastfeeding. When he returned to Aberdeen in the early 1950s, this research continued, but by the time (1954) he had joined the permanent scientific staff of Sir Dugald Baird’s Medical Research Council (MRC) Obstetric Medicine Research Unit (OMRU), what he referred to as his “meandering trail career path” had led him to focus on maternal physiology in pregnancy, a much neglected research area. Perhaps it was no coincidence that the term “obstetric medicine” had already been coined, with the acronym OMRU becoming famous worldwide.

It was while Frank was in Aberdeen that he and Isabella Leitch (an animal nutritionist) undertook a systematic search and analysis of the literature, which led in 1964 to publication of the 1first edition of their classic book The Physiology of Human Pregnancy . This substantial volume (a “bible” to many) was recognised as a model of scholarship, and its content, style, analysis, and predictions eclipsed all previous publications. The concepts set out by Hytten and Leitch may have been the first guides to rigorous investigation of human pregnancy. A major message was that gestational maternal physiological changes were to benefit the fetus not the mother, …
156P ASTRIS, a real-world study with osimertinib in patients with non-small cell lung cancer (NSCLC) EGFR T790M mutated: Characteristics and diagnostic methods used for patients included in Spain
Authors: D. Vicente Baz, A. Paredes Lario, M.T. Moran Bueno, B. Massuti Sureda, N. Reguard, R. Álvarez, A. Insa Molla, O. Juan, G. Marquez, M. Provencio Pulla
Journal: Journal of Thoracic Oncology (2018)
Decision making in clinical stage I (CSI) testicular cancer (TC).
Authors: Giovannella Palmieri, Lucia Nappi, Caterina Condello, Luigi Formisano, Piera Federico, Pasquale Rescigno, Giuseppe Di Lorenzo, Elide Matano, Sabino De Placido, Vincenzo Damiano
Journal: Journal of Clinical Oncology (2012)

e15034 Background: Optimal management of CSI seminomatous (S) and nonseminomatous (NS) TC is an open question. Quality of life and patient preferences are the principal end-points for the best treatment choice. Multidisciplinary approach is required for CSI TC patients to allow an individualized treatment with a patient-centered approach and an active participation in decisions. The “shared decision making” (SDM) is the prevailing approach because patients together with clinicians arrive at a mutually agreed-on choice. We have a project concerning the involvement of patients with CSI TC in the SDM. Methods: We used some key points of SDM: define the problem; treatment options; discuss pros/cons; clarify patient preferences; clarify the patient’s understanding. Educational material are offered to patients. From 2005 to 2012, 32 patients with CSI TC were evaluated. For each patient some clinical and socio-demographic features, type of treatment chosen and some sequel related to treatment were analyzed. Results: Patients characteristics are reported in the table. 4 S patients chose surveillance, 10 chemotherapy and 6 radiotherapy. 2 NS patients chose surveillance, 9 chemotherapy. 4 relapsed: 1 S patient after 13 months from chemotherapy and 1 during the surveillance after 24 months. 2 NS patients relapsed after 12 and 18 months both during the surveillance. All relapsed patients received chemotherapy. Metabolic alterations were analyzed. 1 S patient treated with chemotherapy had a cardiovascular accident. Conclusions: We observed an high gap between surveillance and the active treatments: there is no best choice for every one so we should improve decision-making process and decision aids into the management of CSI patients with TC. [Table: see text]