tbuckley/cabot-search huggingface dataset:
Mental health in adult AD
Authors: J.I. Silverberg, J.M. Gelfand, D.J. Margolis, M. Boguniewicz, L. Fonacier, M.H. Grayson, P.Y. Ong, Z.C. Chiesa Fuxench, E.L. Simpson
Journal: British Journal of Dermatology (2019)

Atopic dermatitis, also known simply as eczema, is a long‐term skin condition that causes an itchy rash. Scratching can cause skin to weep, crust, become infected and become thicker. 16.5 million adults in the USA suffer from atopic dermatitis, with 6.6 million reporting moderate to severe symptoms. Those with more severe disease have been found to have worse quality of life and increased risk of depression and anxiety. This US‐based study looked at 2893 adults to see if having atopic dermatitis, and how severe it is, affects the likelihood of also having anxiety or depression. Information was collected by sending out a survey. Modified UK diagnostic criteria were used to screen for patients with atopic dermatitis. Disease severity was self‐reported by patients using tools such as the Patient‐Orientated Eczema Measure and Dermatology Life Quality Index. The Hospital Anxiety and Depression Scale (HADS) was used for measuring anxiety and depression. 602 adults had atopic dermatitis. They had higher HADS scores (meaning higher levels of anxiety and depression) than the 2291 adults without atopic dermatitis. There were more adults with atopic dermatitis who also had a formal diagnosis of anxiety or depression than those without atopic dermatitis. However, many atopic dermatitis patients with high HADS scores had no formal diagnosis of anxiety or depression. Furthermore, patients with more severe atopic dermatitis had higher HADS scores than those with milder disease. The conclusion is that atopic dermatitis increases the likelihood of having anxiety and depression, especially if one has severe disease. This may go undiagnosed.
Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone in Patients With Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma
Authors: Oscar Arrieta, Feliciano Barrón, Miguel-Ángel Salinas Padilla, Alejandro Avilés-Salas, Laura Alejandra Ramírez-Tirado, Manuel Jesús Arguelles Jiménez, Edgar Vergara, Zyanya Lucia Zatarain-Barrón, Norma Hernández-Pedro, Andrés F. Cardona, Graciela Cruz-Rico, Pedro Barrios-Bernal, Masao Yamamoto Ramos, Rafael Rosell
Journal: JAMA Oncology (2019)

Metformin hydrochloride is emerging as a repurposed anticancer drug. Preclinical and retrospective studies have shown that it improves outcomes across a wide variety of neoplasms, including lung cancer. Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).To assess the progression-free survival (PFS) in patients with advanced lung adenocarcinoma who received treatment with EGFR-TKIs plus metformin compared with those who received EGFR-TKIs alone.Open-label, randomized, phase 2 trial conducted at the Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. Eligible patients were 18 years or older, had histologically confirmed stage IIIB-IV lung adenocarcinoma with an activating EGFR mutation.Patients were randomly allocated to receive EGFR-TKIs (erlotinib hydrochloride, afatinib dimaleate, or gefitinib at standard dosage) plus metformin hydrochloride (500 mg twice a day) or EGFR-TKIs alone. Treatment was continued until occurrence of intolerable toxic effects or withdrawal of consent.The primary outcome was PFS in the intent-to-treat population. Secondary outcomes included objective response rate, disease control rate, overall survival (OS), and safety.Between March 31, 2016, and December 31, 2017, a total of 139 patients (mean [SD] age, 59.4 [12.0] years; 65.5% female) were randomly assigned to receive EGFR-TKIs (n = 70) or EGFR-TKIs plus metformin (n = 69). The median PFS was significantly longer in the EGFR-TKIs plus metformin group (13.1; 95% CI, 9.8-16.3 months) compared with the EGFR-TKIs group (9.9; 95% CI, 7.5-12.2 months) (hazard ratio, 0.60; 95% CI, 0.40-0.94; P = .03). The median OS was also significantly longer for patients receiving the combination therapy (31.7; 95% CI, 20.5-42.8 vs 17.5; 95% CI, 11.4-23.7 months; P = .02).To our knowledge, this is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS. These results justify the design of a phase 3, placebo-controlled study.ClinicalTrials.gov identifier: NCT03071705.
P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients
Authors: A E Danyeli, C B Akyerli, A Dinçer, E Coşgun, U Abacıoğlu, M Pamir, K Özduman
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.
Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia
Authors: Paula Río, Susana Navarro, Wei Wang, Rebeca Sánchez-Domínguez, Roser M. Pujol, José C. Segovia, Massimo Bogliolo, Eva Merino, Ning Wu, Rocío Salgado, María L. Lamana, Rosa M. Yañez, José A. Casado, Yari Giménez, Francisco J. Román-Rodríguez, Lara Álvarez, Omaira Alberquilla, Anna Raimbault, Guillermo Guenechea, M. Luz Lozano, Laura Cerrato, Miriam Hernando, Eva Gálvez, Raquel Hladun, Irina Giralt, Jordi Barquinero, Anne Galy, Nagore García de Andoín, Ricardo López, Albert Catalá, Jonathan D. Schwartz, Jordi Surrallés, Jean Soulier, Manfred Schmidt, Cristina Díaz de Heredia, Julián Sevilla, Juan A. Bueren
Journal: Nature Medicine (2019)
Characterizing Covariant Trajectories of Individuals at Clinical High Risk for Psychosis Across Symptomatic and Functional Domains
Authors: Dana M. Allswede, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Daniel H. Mathalon, Thomas McGlashan, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Scott W. Woods, Tyrone D. Cannon
Journal: American Journal of Psychiatry (2019)

The authors sought to characterize differences in outcomes among help-seeking individuals at clinical high risk for psychosis by identifying covariant longitudinal patterns of symptoms and functioning.
Gambling related harm: we lack longitudinal data
Authors: Stephanie Bramley, Jill Manthorpe, Caroline Norrie
Journal: BMJ (2019)

Gambling related harm seems to be a surprise to UK parliamentarians, NHS bodies, and even the Gambling Commission.1 But soon we might be overloaded with reports.

Already this year there have been three UK consultations about different aspects of gambling—online gambling,2 the prospect of longitudinal research into gambling related harm (NatCen Social Research, personal communication, 2019), and a new national strategy to reduce gambling related harm.3 Two other consultations are now closed—gambling …
Occult tumor cells in peritoneal lavage in pancreatic carcinoma patients.
Authors: Josef Srovnal, Andrea Benedikova, Roman Havlik, Dusan Klos, Martin Lovecek, Dana Cahova, Bohuslav Melichar, Marian Hajduch
Journal: Journal of Clinical Oncology (2012)

e14556 Background: Pancreatic carcinoma is one of the most aggressive malignancies with a poor prognosis. Assessment of occult tumor cells could prevent aggressive surgery in patients with metastatic spread. The aim of this study was to investigate the prognostic significance of occult tumor cells in peritoneal lavage of patients with pancreatic carcinoma. Methods: This was a prospective study to assess the presence of occult tumor cells in peritoneal lavage of 96 pancreatic carcinoma patients at the time of surgery using real-time RT-PCR for carcinoembryonic antigen (CEA), epidermal growth factor receptor 1 (EGFR1) and human telomerase (hTERT). Gene expression of tested markers was correlated with clinical/pathological characteristics using Kruskal-Wallis Anova and Mann-Whitney tests. Kaplan-Meier methods and Gehan-Wilcoxon tests were used for overall survival analyses. Results: Overall, 65 of 96 (69.9%) pancreatic carcinoma patients died, the overall survival median was 10.3 months. A significant association between CEA expression in peritoneal lavage and the clinical stage was found (p&lt;0.03). In addition, patients with high grade tumors had significantly higher expression of EGFR in peritoneal lavage compared to patients with low grade tumors (p&lt;0.04). The patients with the presence of occult cancer cells detected in the peritoneal lavage using CEA and/or EGFR had significantly shorter overall survival (p&lt;0.001; HR=2.14 [95% CI: 1.30-3.55]) with overall survival median 6.8 months. Conclusions: These data demonstrate that the presence of occult tumor cells in peritoneal lavage is a negative prognostic factor in pancreatic carcinoma patients. Occult tumor cells detection using PCR based methods can identify patients with advanced disease for whom radical surgery is of no benefit. Prospective studies should confirm usefulness of this method for the selection of patients for radical surgery. Acknowledgements: Supported by grants IGA MZ NS 9937‑4, MPOTIP FR-TI1/525, IGA UP LF_2011_018 and CZ.1.05/2.1.00/01.0030.
P14.52 Differential methylation of a single CpG site in the CD95 ligand promoter affects gene activity and correlates with invasiveness of glioma cells
Authors: C Merz, J Sykora, A Krendyukov, B Wiestler, C Gieffers, W Wick
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND CD95 ligand (TNFSF6/APO-1L/FASLG) is a member of the Tumour Necrosis Factor Super Family (TNF-SF). Binding of the CD95 ligand (CD95L) to CD95 expressed on intrinsically apoptosis-resistant cancer cells like glioblastoma, triggers intracellular signal transduction resulting in increased tumour growth and invasiveness. A phase II clinical trial in patients with recurrent glioblastoma (NCT01071837) treated by Asunercept (a recombinant glycosylated fusion protein, which selectively binds and inhibits CD95L activity) was followed by a genome-wide assessment of DNA methylation. Here, a CpG-site (designated CpG2) within the CD95L-promotor was identified, exhibiting differential methylation between Asunercept responders (PFS&gt;5 months) and non-responders (PFS &lt; 2 months) with a significant survival benefit achieved in Asunercept treated patients with low CpG2 methylation (HR 0.34, p = 0.025). METHODS AND RESULTS We have performed in vitro studies to establish a link between the CpG2 methylation status and cellular characteristics of glioblastoma cell lines. A 3-dimensional spheroid invasion assay showed that highly methylated glioma cells like T98G did not grow and invade the surrounding matrix as aggressively compared to spheroids formed from low methylated glioma cells, e.g. U87-MG. Invasive growth of U87-MG spheroids in these assays was suppressed in the presence of Asunercept. A 1 kb fragment of the T98G CD95L promoter was subsequently cloned into a CpG-free reporter gene plasmid. Luciferase-based reporter gene assays of in vitro methylated and unmethylated plasmids in transfected HEK cells indicate that the CD95L promoter, despite the observed sparseness of CpG sites, is at least partially regulated by its methylation level. Furthermore, mutational disruption of the CpG2 site completely silenced reporter gene activity in vitro, which insinuates that both methylation level and gene promoter sequence are involved in regulation of the CD95L gene. CONCLUSION In essence, the level of CpG2 methylation correlates to aggressiveness of glioma derived cancer spheroids in vitro, and methylation of the CD95L promoter in glioblastoma tissue from patients might warrant use as a potential biomarker predicting response to therapy with Asunercept. We are currently developing a specific and sensitive assay to quantify CpG2 methylation considered as a companion diagnostic for further clinical studies.
P04.13 Prognostic role of single stranded DNA binding protein 2 in IDH wild type lower grade glioma
Authors: Y Chai, W Liu, L Hu, Y Zhang, P Liang
Journal: Neuro-Oncology (2019)

Abstract Comprehensive and integrative characterizations of genomic analysis including somatic alterations and molecular subtypes of glioma have been established. However, diffuse gliomas (World Health Organization grades II and III, hereafter referred to collectively as lower-grade gliomas,LGG) consist of highly variable clinical behaviors, leading to emerging studies to identify prognostic factors. Through comparative analyses of 516 cases of primary LGG patients from The Cancer Genome Atlas (TCGA) dataset, we reported that the expression level and methylation level of SSBP2 (encoding single stranded DNA-binding protein 2) gene vary among LGG patients and SSBP2 expression or gene body methylation can be served as prognostic biomarkers for LGG survival. Cox regression results confirmed that SSBP2 as an independent predictor of survival in LGG, with a cox coefficient of 0.534 indicating a worse prognosis. Furthermore, lower-grade glioma was statistically ranked first among 21 different cancer types according to the FDR correction. We further investigated the combination of SSBP2 with other known genetic prognostic factors(IDH mutation and 1p19q co-deletion) of LGG. By matching gene expression profile of LGG patients, IDH-mutant gliomas had decreased expression of SSBP2 compared with IDH-wildtype gliomas and 1p19q intact gliomas had increased expression of SSBP2 compared with 1p19q codeletion gliomas. Moreover, we found that the combination of IDH or 1p19q status with SSBP2 identified LGG subsets with significantly diverse survival effects. Patients with low SSBP2 expression had significantly better 5-, 10-, and 15-year OS in IDH wild type, but not in the cohorts of IDH mutant. Our findings offer an explanation for the specificity of SSBP2 effect on survival rate in IDH wild type LGG patients.
Proteomics Analysis of Lipid Droplets from the Oleaginous Alga <i>Chromochloris Zofingiensis</i> Reveals Novel Proteins for Lipid Metabolism
Authors: Xiaofei Wang, Hehong Wei, Xuemei Mao, Jin Liu
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Chromochloris zofingiensis represents an industrially relevant and unique green alga, given its capability of synthesizing triacylglycerol (TAG) and astaxanthin simultaneously for storage in lipid droplets (LDs). To further decipher lipid metabolism, the nitrogen deprivation (ND)-induced LDs from C. zofingiensis were isolated, purified, and subjected to proteomic analysis. Intriguingly, many C. zofingiensis LD proteins had no orthologs present in LD proteome of the model alga Chlamydomonas reinhardtii. Seven novel LD proteins (i.e., two functionally unknown proteins, two caleosins, two lipases, and one l-gulonolactone oxidase) and the major LD protein (MLDP), which were all transcriptionally up-regulated by ND, were selected for further investigation. Heterologous expression in yeast demonstrated that all tested LD proteins were localized to LDs and all except the two functionally unknown proteins enabled yeast to produce more TAG. MLDP could restore the phenotype of mldp mutant strain and enhance TAG synthesis in wild-type strain of C. reinhardtii. Although MLDP and caleosins had a comparable abundance in LDs, they responded distinctly to ND at the transcriptional level. The two lipases, instead of functioning as TAG lipases, likely recycled polar lipids to support TAG synthesis. For the first time, we reported that l-gulonolactone oxidase was abundant in LDs and facilitated TAG accumulation. Moreover, we also proposed a novel working model for C. zofingiensis LDs. Taken together, our work unravels the unique characteristics of C. zofingiensis LDs and provides insights into algal LD biogenesis and TAG synthesis, which would facilitate genetic engineering of this alga for TAG improvement.
Outcome of patients with refractory malignant peripheral nerve sheath tumors (MPNST) enrolled on phase 2 trials.
Authors: Srivandana Akshintala, Nicole C. Mallory, Yao Lu, Karla V. Ballman, AeRang Kim
Journal: Journal of Clinical Oncology (2019)

e22534 Background: Multiple phase 2 trials using objective radiographic response rates (ORR) as end point have shown negative results in MPNST. Alternative endpoints such as progression free survival (PFS) may be more appropriate for identifying active agents. PFS from prior trials can provide a historical baseline for future single arm phase 2 trials in this rare disease. Methods: Outcomes of patients with recurrent or unresectable MPNST enrolled on one of five negative phase 2 trials (SARC001, 002, 009, 016, and 023) conducted by the Sarcoma Alliance for Research through Collaboration (SARC) from Nov 2001 – Mar 2016 were retrospectively analyzed to calculate PFS. PFS from SARC006, the phase 2 trial of upfront chemotherapy in newly diagnosed patients with unresectable or metastatic MPNST, was analyzed separately. The impact of neurofibromatosis type 1 (NF1) status, tumor location, metastatic involvement, and prior therapy on PFS was evaluated. Results: Sixty-four patients (29 male, median age 39 years (range 15-81)) with MPNST were enrolled on one of five trials of primarily single agent or combined targeted therapy that were determined to be inactive. Primary endpoint was ORR per RECIST, WHO, or Choi criteria. Patients had received a median of 1 (range 0-5) prior systemic therapies and majority had received prior surgery (77%) and radiation (61%), and had metastatic disease (73%) at enrollment. Median PFS was 1.77 months (95% CI 1.61-3.45), and PFS at 4 months was 16%. Greater number of prior systemic therapies was associated with worse PFS (univariate hazard ratio 1.31, 95% CI 1.03-1.68, p = 0.03). There was no significant difference in PFS based on treatment trial, response criteria, NF1 status, presence of metastatic disease, disease site at enrollment, and prior surgery or radiation. PFS at 4 months was 94% in 40 patients enrolled on SARC006 trial, none of whom had received prior systemic or radiation therapy. Conclusions: PFS in patients with recurrent/refractory MPNST enrolled on phase 2 trials is poor and the number of prior regimens may impact PFS. Our data provides a historical baseline PFS that can be used as a comparator in future single arm phase 2 trials in refractory and upfront MPNST patients.
Correction to: Spatial chromatin architecture alteration by structural variations in human genomes at the population scale
Authors: Michal Sadowski, Agnieszka Kraft, Przemyslaw Szalaj, Michal Wlasnowolski, Zhonghui Tang, Yijun Ruan, Dariusz Plewczynski
Journal: Genome biology (2019)

Following publication of the original article [1], it was noticed that the incorrect Fig. 2 and Fig. 3. were processed during production. It was also noticed that Fig. 4a was processed with a superfluous "1e7" symbol in the upper right corner.
10-Year Survival After FFR-Guided Strategy in Isolated Proximal Left Anterior Descending Coronary Stenosis
Authors: Anastasios Milkas, Oscar Leonel Rueda-Ochoa, Stephane Fournier, Olivier Muller, Frank Van Rooij, Oscar Horacio Franco, Carlos Collet, Emanuele Barbato, Maryam Kavousi, Bernard De Bruyne
Journal: Journal of the American College of Cardiology (2019)
Reanalysis of Data Comparing Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non–Small Cell Lung Cancer
Authors: Guosheng Yin, Chenyang Zhang
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal