tbuckley/cabot-search huggingface dataset:
Evaluation and Management Strategies for Per- and Polyfluoroalkyl Substances (PFASs) in Drinking Water Aquifers: Perspectives from Impacted U.S. Northeast Communities
Authors: Jennifer L. Guelfo, Thomas Marlow, David M. Klein, David A. Savitz, Scott Frickel, Michelle Crimi, Eric M. Suuberg
Journal: Environmental Health Perspectives (2018)

Background: Multiple Northeast U.S. communities have discovered per- and polyfluoroalkyl substances (PFASs) in drinking water aquifers in excess of health-based regulatory levels or advisories. Regional stakeholders (consultants, regulators, and others) need technical background and tools to mitigate risks associated with exposure to PFAS-affected groundwater. Objectives: The aim was to identify challenges faced by stakeholders to extend best practices to other regions experiencing PFAS releases and to establish a framework for research strategies and best management practices. Methods and Approach: Management challenges were identified during stakeholder engagement events connecting attendees with PFAS experts in focus areas, including fate/transport, toxicology, and regulation. Review of the literature provided perspective on challenges in all focus areas. Publicly available data were used to characterize sources of PFAS impacts in groundwater and conduct a geospatial case study of potential source locations relative to drinking water aquifers in Rhode Island. Discussion: Challenges in managing PFAS impacts in drinking water arise from the large number of relevant PFASs, unconsolidated information regarding sources, and limited studies on some PFASs. In particular, there is still considerable uncertainty regarding human health impacts of PFASs. Frameworks sequentially evaluating exposure, persistence, and treatability can prioritize PFASs for evaluation of potential human health impacts. A regional case study illustrates how risk-based, geospatial methods can help address knowledge gaps regarding potential sources of PFASs in drinking water aquifers and evaluate risk of exposure. Conclusion: Lessons learned from stakeholder engagement can assist in developing strategies for management of PFASs in other regions. However, current management practices primarily target a subset of PFASs for which in-depth studies are available. Exposure to less-studied, co-occurring PFASs remains largely unaddressed. Frameworks leveraging the current state of science can be applied toward accelerating this process and reducing exposure to total PFASs in drinking water, even as research regarding health effects continues. https://doi.org/10.1289/EHP2727
Food intake and nutritional status of colorectal cancer patients undergoing radio-chemotherapy in Sardjito hospital
Authors: M. Purba, H. Winarti, R. Pangastuti
Journal: Annals of Oncology (2018)

Introduction: Diet has long been thought to have a role in the etiology of colorectal cancer (CRC), particularly when a poor diet is combined with excess calorie intake and weight gain, physical inactivity, and unhealthy practices, such as smoking and consuming a great deal of alcohol. Current knowledge about food consumption patterns indicates that a diet high in vegetables, fruit, and fibre is protective against certain types of cancer, but the evidence that fruit and vegetable consumption is specifically related to a reduced risk of CRC was recently challenged. In an attempt to clarify the relationship between diet and CRC, researchers are examining individual food intake and nutritional status of patients undergoing radio-chemotherapy in Dr Sardjito Hospital. Methods: The study was observational with cross sectional design. The subject of the study is colorectal cancer patients undergoing chemotherapy in the hospital. Total of 181 colorectal patients, men and women aged 21-79 years participated in the study. A measuring instrument used are a semi quantitative food frequency questionnaire, microtoise and weight scales. Analysis of data use univariate, bivariate and multivariate analysis with significant p value < 0.05. Results: This study found that 58% of the subjects are male, 73% anemia, 77% low in body mass index (BMI). Moreover, most of the patient had low consumption in energy, protein, Fe, folic acid, and B12 vitamin (71%, 71%, 79%, 52%, 40% respectively). Mean daily intake for energy is 1254 ±270 kcal, protein 46 ±12 g, Fe 8.9 ±10.7 mg, Folic acid 252±154 mg, B12 vit 8.9±10.7 mg. Subjects with a higher BMI tend to have a higher nutrient intake (p<0.005). There was a significant association between food intake and nutritional status (Risk prevalence 2.11 for energy, and 1.93 for protein with p value <0.05), and 0.65 for Fe, 0.91 for folic acid, 0.53 for B12 vit respectively with p value > 0.05. Conclusion: Most of the patients had a low intake and body mass index. This study found that there was a significant association between food intake and nutritional status.
Insect Retroelements Provide Novel Insights into the Origin of Hepatitis B Viruses
Authors: Zhen Gong, Guan-Zhu Han
Journal: Molecular Biology and Evolution (2018)

The origin of hepadnaviruses (Hepadnaviridae), a group of reverse-transcribing DNA viruses that infect vertebrates, remains mysterious. All the known retrotransposons are only distantly related to hepadnaviruses. Here, we report the discovery of two novel lineages of retroelements, which we designate hepadnavirus-like retroelement (HEART1 and HEART2), within the insect genomes through screening 1, 095 eukaryotic genomes. Both phylogenetic and similarity analyses suggest that the HEART retroelements represent the closest nonviral relatives of hepadnaviruses so far. The discovery of HEART retroelements narrows down the evolutionary gap between hepadnaviruses and retrotransposons and might thus provide unique insights into the origin and evolution of hepadnaviruses.
Longitudinal associations between psychotic experiences and disordered eating behaviours in adolescence: a UK population-based study
Authors: Francesca Solmi, Daniela Melamed, Glyn Lewis, James B Kirkbride
Journal: The Lancet Child & Adolescent Health (2018)

Psychotic experiences might represent non-specific markers of poor mental health in adolescence. However, only a few predominantly cross-sectional studies have tested their association with disordered eating behaviours in adolescent and adult populations. The aim of this study was to explore the association between psychotic experiences at age 13 years, and disordered eating behaviours and body-mass index (BMI) at age 18 years.
NSRG-04. DIAGNOSTIC YIELD AND MORBIDITY AFTER NEURONAVIGATION GUIDED FRAMELESS STEREOTACTIC BIOPSY FOR DEEP SEATED BRAIN TUMOURS IN CHILDREN
Authors: Amit Kanwar, Ian Kamaly
Journal: Neuro-Oncology (2018)

To assess the diagnostic yield and morbidity following Brain Lab guided Brain biopsy for deep seated tumours in the Paediatric Population. Subjects, 14 male and 8 females. Age range 1-15 years, mean 6.73. Patients identified retrospectively from Jan 2008-July 2016. Case notes were reviewed retrospectively. 22 biopsies were performed, all patients had General Anaesthetic Various locations were biopsied including tectum, brainstem and thalamus pineal gland, and hypothalamus and suprasellar region. Various entry points used with various biopsy lengths ranging from 58.6 to 129.2mm, mean 84.13, Standard deviation=17.5, Multiple biopsies were taken ranging in size from 1 to 18mm. 18 done by Consultant, 4 by SPR. All patients had Pre-operative MRI brain Lab; all patients had Post op imaging 21 MRI, 1 CT. In 15 patients radiological diagnosis matched histology. None of the patients had Complications post operatively. Histological diagnosis was obtained in 22 cases (100%) on first biopsy. Brain lab Vario- guided Brain biopsy can be performed safely in deep seated tumour locations in the paediatric population without significant complications and has a high diagnostic yield. (100%).
DIPG-76. PNOC-003: PRECISION MEDICINE TRIAL FOR CHILDREN WITH DIFFUSES INTRINSIC PONTINE GLIOMA: PRELIMINARY EXPERIENCE WITH MULTI-AGENT PERSONALIZED THERAPY RECOMMENDATIONS
Authors: Lindsay Kilburn, John Kuhn, Kellie Nazemi, Annette Molinaro, Winnie Liang, Anu Banerjee, Eugene Hwang, John Crawford, Theodore Nicolaides, Roger Packer, Javad Nazarian, Nalin Gupta, Adam C Resnick, Sara Byron, Michael Berens, Michael Prados, Sabine Mueller
Journal: Neuro-Oncology (2018)

New therapies for children with diffuse intrinsic pontine glioma (DIPG) are greatly needed. Within a prospective multi-center feasibility trial, we evaluated whether genomic profiling (tumor and germline exome sequencing and tumor RNA) could be used to identify targetable events to inform a treatment recommendation from a multidisciplinary tumor board within 21 business days after biopsy recommending up to four FDA approved drugs to start following focal radiotherapy. Agents were prioritized that target DNA alterations and have available pediatric safety and dosing information. Agents were introduced in a sequential manner with close toxicity monitoring when there was limited experience for the combinations. Seventeen patients were enrolled. Fourteen of the 15 eligible patients had complete profiling and generation of a tumor board recommendation. Eight patients followed the treatment recommendation. Panobinostat was used as the backbone of therapy for the majority of patients with histone mutations with a starting dose of 16mg/m2/dose three times a week for 2 weeks followed by a 1-week break with dose escalation as tolerated. Administered doses of panobinostat ranged from 15-37mg/m2/dose with most patients tolerating a 15-24mg/m2 dose for 2–12 cycles of therapy. Several patients remain on study therapy. Additional agents recommended in combination included etoposide, cabozantinib, mebendazole, dabrafenib, trametinib, minocycline, carboplatin, metformin, dasatinib, and everolimus. Therapy has been generally well tolerated without unexpected severe toxicities. Reported grade 3 or greater treatment related toxicities include ALT elevation, mucositis, hypertension, hypertriglyceridemia, and hypokalemia and hematologic toxicities. The study has been expanded to evaluate preliminary efficacy of this approach.
RADI-21. IMAGING CHARACTERISTICS OF BRAF V600E MUTATED PEDIATRIC BRAIN TUMORS
Authors: Nicholas Stence, Jean Mulcahy-Levy, Lindsey Hoffman, Adam Green, David Mirsky, Ilana Neuberger, Laura Fenton, John Maloney, Bette Kleinschmidt-DeMasters, Rajeev Vibhakar, Nicholas Foreman, Kathleen Dorris
Journal: Neuro-Oncology (2018)

Genomic assessment of BRAF V600E has become routine in specific pediatric glioma subtypes in recent years given availability of targeted therapies. Comparison of imaging characteristics of pediatric gliomas with or without the V600E mutation has not been previously reported. Pathology reports of pediatric brain tumors diagnosed from 2010-2017 at a single institution were searched for keywords “V600E” or “VE1” using institutional databases (Nuance mPower, Nuance Communications). Cases where V600E testing was successfully performed and whose pathologic diagnosis was ganglioglioma, pleomorphic xanthoastrocytoma (PXA) or epithelioid glioblastoma were included. Preoperative MRI studies were reviewed by a single neuroradiologist (NVS) for tumor volume, T1 and T2 signal characteristics, cystic or solid components, enhancement, adjacent non-enhancing T2 hyperintensity, hemorrhage, DWI signal and ADC values in solid components, and location. Review of charts and follow-up imaging studies was conducted to evaluate tumor recurrence or progression. Fisher’s exact test was used for categorical data and a two-tailed unpaired t-test was used for continuous data. 30 tumors met pathologic inclusion criteria, including 18 gangliogliomas, 10 PXAs and 2 epithelioid glioblastomas. Average age was 10.6 years (range 0.64-24 years). IHC or molecular analysis identified BRAF V600E in 16 tumors. These tumors were significantly more likely to exhibit hyperintensity on DWI (p=0.009), lower ADC values (p=0.046), and non-enhancing T2 hyperintensity adjacent to solid enhancing components. BRAF V600E mutant tumors demonstrate restricted diffusion, which may indicate differences in cellularity or tumor microarchitecture. Further study with advanced imaging sequences, including MR spectroscopy and perfusion, is needed.
LGG-10. EPIGENETIC/GENETIC/MORPHOLOGIC ANALYSES REVEAL CLINICAL/PROGNOSTIC INSIGHT OF PEDIATRIC LOW GRADE GLIOMAS
Authors: Kohei Fukuoka, Yasin Mamatjan, Ruth Tatevossian, Michal Zapotocky, Scott Ryall, Ana Guerreiro Stucklin, Julie Benett, Betty Luu, Ji Wen, Lili-Naz Hazrati, Norm Laperriere, James Drake, James Rutka, Peter Dirks, Abhaya Kulkarni, Michael Taylor, Ute Bartels, Annie Huang, Kenneth Aldape, Eric Bouffet, Vijay Ramaswamy, David Ellison, Cynthia Hawkins, Uri Tabori
Journal: Neuro-Oncology (2018)

Methylation analysis provides insight into the diagnosis and prognosis of pediatric brain tumors. However, the role of the methylome on pediatric low grade gliomas (PLGG) is still unclear. We performed methylome analysis using the Illumina EPIC array combined with pathologic, molecular and outcome data on 153 well annotated PLGG from both St-Jude and SickKids. For BRAFV600E gliomas, high grade gliomas were also included. Hierarchical clustering and t-Distributed Stochastic Neighbor Embedding (tSNE) plots uncovered multiple factors that influence methylation-based clustering of PLGG. Importantly, tumor location and lymphocyte infiltration influence the cluster more than molecular status or pathology. Methylation data results in helpful information to change the clinical management in 2.2% of tumors but classified tumors incorrectly 4.3%. For BRAF-V600E gliomas (n=81), all tumors with CDKN2A deletion were included in a PXA cluster regardless of the pathology. Gene-ontology analysis shows that the genes with highly methylated promoter regions in the PXA cluster are relevant to central nervous system/cell/tissue differentiation/development. Tumors clustering as PXA (DKFZ classifier) had 78% 5-year overall survival (OS). However, this group could be further stratified into 100% OS for those with low grade histology versus 30% for HGG (p<0.003). The PLGG methylome is affected by multiple non-neoplastic factors and provides information on rare subtypes. Combined molecular and pathological and methylation classification is required to implement this analysis in a clinical setting.
NURS-10. IMPACT OF INTEGRATING PALLIATIVE CARE INTO A NEURO-ONCOLOGY CLINIC
Authors: Lauren Hancock, Deborah Lafond
Journal: Neuro-Oncology (2018)

CNS tumors account for 25% of cancer deaths in children, in the United States. Children have significant morbidities related to treatment. Palliative care (PC) mitigates symptom distress. Three members of the neuro-oncology (NO) team completed primary PC education. A quality improvement project identified barriers and challenges to integrating PC for children with high-risk brain tumors. Subsequently, a PC NP was embedded within the clinic. Metrics including numbers of visits, deaths, hospice referrals and PC involvement greater than 30 days prior to death were followed 1 year pre-implementation and 2 years post, as well as assessing family satisfaction with palliative care involvement. N = 98 children with brain tumors, with 52 deaths. Baseline PC involvement > 30 days prior to death was 52.6 % (N = 10/19). With additional PC training, that increased to 56.3% (N = 9/16) and to 76.4% (N = 13/17) with the addition of a PC NP embedded in the NO clinic. Number of PC visits with NO patients increased steadily over the 3 year period (2015 = 100 visit; 2016 = 172 visits, 2017 = 260 visits). N = 32 (61.5%) were enrolled with home hospice. Parents indicated acceptance of integration of palliative care services throughout the trajectory of disease. Integration of PC services within a NO clinic is feasible and acceptable to both providers and parents and improved care at the time of death.
BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle
Authors: John Wood, Margaret Chui Ling Tse, Xiuying Yang, Daniel Brobst, Zhixue Liu, Brian Pak Shing Pang, Wing Suen Chan, Aung Moe Zaw, Billy K.C. Chow, Keqiang Ye, Chi Wai Lee, Chi Bun Chan
Journal: Metabolism (2018)
Secondary Plastids of Euglenids and Chlorarachniophytes Function with a Mix of Genes of Red and Green Algal Ancestry
Authors: Rafael I Ponce-Toledo, David Moreira, Purificación López-García, Philippe Deschamps
Journal: Molecular Biology and Evolution (2018)

Endosymbiosis has been common all along eukaryotic evolution, providing opportunities for genomic and organellar innovation. Plastids are a prominent example. After the primary endosymbiosis of the cyanobacterial plastid ancestor, photosynthesis spread in many eukaryotic lineages via secondary endosymbioses involving red or green algal endosymbionts and diverse heterotrophic hosts. However, the number of secondary endosymbioses and how they occurred remain poorly understood. In particular, contrasting patterns of endosymbiotic gene transfer have been detected and subjected to various interpretations. In this context, accurate detection of endosymbiotic gene transfers is essential to avoid wrong evolutionary conclusions. We have assembled a strictly selected set of markers that provides robust phylogenomic evidence suggesting that nuclear genes involved in the function and maintenance of green secondary plastids in chlorarachniophytes and euglenids have unexpected mixed red and green algal origins. This mixed ancestry contrasts with the clear red algal origin of most nuclear genes carrying similar functions in secondary algae with red plastids.
Intensive first line FIr-C/FOx-C association of triplet chemotherapy plus cetuximab in RAS wild-type metastatic colorectal cancer patients: Preliminary phase II data and individual limiting toxicity syndromes prediction by pharmacogenomic biomarkers
Authors: G. Bruera, S. Massacese, F. Pepe, U. Malapelle, A. Dal Mas, E. Ciacco, G. Calvisi, P. Marchetti, G. Troncone, M. Simmaco, E. Ricevuto
Journal: Annals of Oncology (2018)

Introduction: Intensive triplet chemotherapy/bevacizumab significantly increased MCRC outcome. Phase II study investigated safety/activity of FIr-C/FOx-C triplet/cetuximab (CET) in first line RAS wild-type and prediction of individual limiting toxicity syndromes by pharmacogenomic biomarkers. Methods: Simon two-step design: p0 70%, p1 85%, power 80%, α 5%, β 20%; projected objective response rate (ORR) I step 14/19. FIr-C/FOx-C: 5-fluorouracil (5-FU) 12h-timed-flat-infusion 900 mg/m2 days (d)1-2,8-9,15-16,22-23; alternating irinotecan (CPT-11) 160 mg/m2 d1,15, oxaliplatin 80 mg/m2 d8,22; CET loading 400 then 250 mg/m2 d1,8,15,22; every 28d. Toxicity, individual limiting toxicity syndromes (LTS) evaluated, compared by chi-square test; activity/efficacy by log-rank. 5-FU/CPT-11 pharmacogenomic biomarkers, 5-FU degradation rate (5-FUDR), SNPs ABCB1, CYP3A4, DYPD, UGT1A1 evaluated in patients with LTS and at recommended dose. Results: Enrolled: 29 patients 80%; G3-4 toxicities: diarrhea 23%, asthenia 15%, vomiting 8%, hypertransaminasemy 8%; LTS 19 patients (65.5%), 83% yE. LTS prevalently multiple (ms) vs single site (59 vs 7% p 0.006). Reduced FUDR 56%, SNPs CYP3A4 22%, UGT1A1 71%, >2 positive pharmacogenomics biomarkers 78% prevalently in patients with gastrointestinal LTS. Conclusion: Intensive first-line FIr-C/FOx-C at recommended doses is tolerable, highly effective in RAS wild-type. Reduced FUDR, CYP3A4, UGT1A1 SNPs may predict individual LTS-ms to select fit patients. Prospective studies personalized by toxicity biomarkers will confirm efficacy.
EMBR-14. RECLASSIFICATION OF CENTRAL NERVOUS SYSTEM PRIMITIVE NEUROECTODERMAL TUMOR (CNS-PNET) INTO ENTITIES REFLECTS OUTCOME: RESULTS FROM THE PROSPECTIVE SJYC07 AND SJMB03 TRIALS
Authors: Anthony Liu, Brent Orr, Tong Lin, Tim Hassall, Daniel C Bowers, Eric Bouffet, Sridharan Gururangan, Paul Fisher, John Crawford, Stewart J Kellie, Murali Chintagumpala, Michael Fisher, Anne Bendel, David Ellison, Giles Robinson, Amar Gajjar
Journal: Neuro-Oncology (2018)

Central nervous system primitive neuroectodermal tumor (CNS-PNET) was removed from the WHO classification after DNA-methylation profiling unveiled its underlying heterogeneity. Here we describe the makeup and outcome of patients histopathologically diagnosed as CNS-PNET treated on 2 multi-center, prospective trials. Patients <3yr received chemotherapy with/without focal irradiation (SJYC07). Patients ≥3yr received risk-adapted craniospinal-irradiation (23.4Gy for localized disease, 36–39.6Gy for metastatic) and chemotherapy (SJMB03). DNA-methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. Fifty-six patients were enrolled (SJYC07=32; SJMB03=24) with median age 2.86yr (range: 0.64–19.47). Sixteen were stratified as high-risk including 10 with metastasis. Histopathological diagnosis upon central review was CNS-PNET (n=34), ETMR (n=17), CNS-neuroblastoma/ganglioneuroblastoma (n=3) and HGNET (n=2). 42/56 cases were methylation-profiled into ETMR (N=13), GBM (N=3), MBgroup3 (N=2), CNS-NB-FOXR2 (N=3), CNS-EFT-CIC (N=1), EPN-RELA (N=1), choroid plexus tumor (pediatric B) (N=1), PBgroupB (N=1), normal tissue (N=3), and “no match” (calibrated scores <0.9) (N=14). Median duration of follow-up was 2.24yr (range: 0.06–12.7). 5yr-OS/PFS in SJMB03-AR and -HR patients were 46.7 ± 12.9%/46.7 ± 12.9% and 33.3 ± 15.7%/33.3 ± 15.7% (OS p=0.503; PFS p=0.494). 5yr-OS/PFS in SJYC07-IR and -HR patients were 46.8 ± 10.6%/44.7 ± 10.4% and 57.1 ± 18.7%/14.3 ± 13.2% respectively (OS p=0.973; PFS p=0.046). Patients methylation-profiled as ETMR/GBM/MB had 5yr-OS/PFS of 24.1 ± 10.4%/14.8 ± 8.9% compared to 90.0 ± 9.5%/80.0 ± 12.6% in the other entities (OS p=0.001; PFS p<0.001). Age, metastasis, extent of surgery and treatment protocol did not significantly impact outcome. Classification by DNA-methylation profiling (p=0.037), histopathological diagnosis (p=0.019) and radiation use (p<0.001) were predictive of PFS. Outcome of pediatric CNS-PNET varied but better conformed to convention when assigned a new entity.