tbuckley/cabot-search huggingface dataset:
Toward an Emerging Paradigm for Understanding Attention-Deficit/Hyperactivity Disorder and Other Neurodevelopmental, Mental, and Behavioral Disorders
Authors: Joel T. Nigg
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
An assessment of <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> testing prior to 1<sup>st</sup> line of therapy among mCRC patients treated at community cancer centers in the United States.
Authors: Ana Florea, Tamer Garawin, Laura Sangaré, Michael Anthony Kelsh, Kimberly Lowe
Journal: Journal of Clinical Oncology (2018)

678 Background: We sought to determine the proportion of patients with mCRC in the United States who were tested for KRAS, NRAS, and BRAF mutational status before any 1 st line of therapy. Patient demographics that may influence testing, and the turnaround time between key events associated with biomarker testing and utilization of biomarker results were also assessed. Methods: The study utilized the Oncology Services Comprehensive Electronic Records (OSCER) 2.0 dataset, provided by Flatiron Health, which includes mCRC patients from community cancer centers across the United States. Biomarker results are recorded in the Flatiron Electronic Health Record when available. The proportion of patients tested or not tested for KRAS, NRAS, and BRAF mutational status before 1 st line of therapy between 2013 and 2017 was calculated, as were the differences in the patient demographics. The median number of days between the date of tissue collection, the date the tissue was received by the laboratory, and the date the oncologist received the test results was calculated. Results: Of the 13,437 patients included in the analysis, the proportion of patients who were tested prior to 1 st line of therapy was as follows: KRAS, 30.8%,; NRAS, 9.9%; BRAF, 11.5%. Age, insurance type, race, and presence of liver metastases were all statistically significant factors that influenced testing. Specifically, younger, commercially-insured, Caucasian patients, and those who had liver metastases were more likely to be tested. For KRAS testing, the median time between tissue collection and tissue received by the laboratory was 26 days. Receipt of the results by the oncologist took an additional median number of 27 days. Conclusions: This study found that the testing rate for these key mCRC biomarkers was less than 31% and that the median number of days to assess biomarker results was 26. Further studies conducted in various settings, such as academic cancer clinics, are needed to investigate this low proportion of testing and long time to assess results.
Green beards and signaling: Why morality is not indispensable
Authors: Toby Handfield, John Thrasher, Julian García
Journal: Behavioral and Brain Sciences (2018)

We argue that although objectivist moral attitudes may facilitate cooperation, they are not necessary for the high levels of cooperation in humans. This is implied by evolutionary models that articulate a mechanism underlying Stanford's account, and is also suggested by the ability of merely conventional social norms to explain extreme human behaviors.
Management of Multiple Myeloma
Authors: Shaji K. Kumar
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as “preferred,” “other,” and “useful in certain circumstances.” For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy. Double (tandem) ASCT may benefit patients with high-risk cytogenetics, such as 17p deletion. Lenalidomide maintenance is the standard posttransplant approach and results in improved progression-free and overall survivals. For relapsed disease, a host of new agents have been shown to improve outcomes, mostly in combination with bortezomib or lenalidomide, but their selection depends largely on response and tolerability to prior therapies. </section>
Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015
Authors: Kamilla Laut, Leah Shepherd, Roxana Radoi, Igor Karpov, Milosz Parczewski, Cristina Mussini, Fernando Maltez, Marcelo Losso, Nikoloz Chkhartishvili, Hila Elinav, Helen Kovari, Anders Blaxhult, Robert Zangerle, Tatiana Trofimova, Malgorzata Inglot, Kai Zilmer, Elena Kuzovatova, Thérèse Staub, Dorthe Raben, Jens Lundgren, Amanda Mocroft, Ole Kirk
Journal: Eurosurveillance (2018)

Background: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. Aim: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA &lt; 500 copies/mL) across Europe and explored temporal trends. Methods: In three cross-sectional analyses in 2004–05, 2009–10 and 2014–15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression. Results: Overall, the percentage of people on ART increased from 2004–05 (67.8%) to 2014–15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004–05, 87.7% in 2014–15). However, the rate of improvement over time varied significantly between regions (p &lt; 0.01). In 2014–15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014–15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13–0.21) in Eastern Europe. Conclusions: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.
Mathematical Modeling Predicts Response to Chemotherapy and Drug Combinations in Ovarian Cancer
Authors: Emilia Kozłowska, Anniina Färkkilä, Tuulia Vallius, Olli Carpén, Jukka Kemppainen, Seija Grénman, Rainer Lehtonen, Johanna Hynninen, Sakari Hietanen, Sampsa Hautaniemi
Journal: Cancer Research (2018)

Abstract Platinum-based chemotherapy constitutes the backbone of clinical care in advanced solid cancers such as high-grade serous ovarian cancer (HGSOC) and has prolonged survival of millions of patients with cancer. Most of these patients, however, become resistant to chemotherapy, which generally leads to a fatal refractory disease. We present a comprehensive stochastic mathematical model and simulator approach to describe platinum resistance and standard-of-care (SOC) therapy in HGSOC. We used pre- and posttreatment clinical data, including 18F-FDG-PET/CT images, to reliably estimate the model parameters and simulate “virtual patients with HGSOC.” Treatment responses of the virtual patients generated by our mathematical model were indistinguishable from real-life patients with HGSOC. We demonstrated the utility of our approach by evaluating the survival benefit of combination therapies that contain up to six drugs targeting platinum resistance mechanisms. Several resistance mechanisms were already active at diagnosis, but combining SOC with a drug that targets the most dominant resistance subpopulation resulted in a significant survival benefit. This work provides a theoretical basis for a cancer treatment paradigm in which maximizing platinum's killing effect on cancer cells requires overcoming resistance mechanisms with targeted drugs. This freely available mathematical model and simulation framework enable rapid and rigorous evaluation of the benefit of a targeted drug or combination therapy in virtual patients before clinical trials, which facilitates translating preclinical findings into clinical practice. Significance: These findings present a comprehensive mathematical model for platinum resistance and standard-of-care therapy in a solid cancer, allowing virtual evaluation of novel therapy regimens. Cancer Res; 78(14); 4036–44. ©2018 AACR.
Divergent topological networks in Alzheimer’s disease: a diffusion kurtosis imaging analysis
Authors: Jia-Xing Cheng, Hong-Ying Zhang, Zheng-Kun Peng, Yao Xu, Hui Tang, Jing-Tao Wu, Jun Xu
Journal: Translational Neurodegeneration (2018)

Brain consists of plenty of complicated cytoarchitecture. Gaussian-model based diffusion tensor imaging (DTI) is far from satisfactory interpretation of the structural complexity. Diffusion kurtosis imaging (DKI) is a tool to determine brain non-Gaussian diffusion properties. We investigated the network properties of DKI parameters in the whole brain using graph theory and further detected the alterations of the DKI networks in Alzheimer's disease (AD). Magnetic resonance DKI scanning was performed on 21 AD patients and 19 controls. Brain networks were constructed by the correlation matrices of 90 regions and analyzed through graph theoretical approaches. We found small world characteristics of DKI networks not only in the normal subjects but also in the AD patients; Grey matter networks of AD patients tended to be a less optimized network. Moreover, the divergent small world network features were shown in the AD white matter networks, which demonstrated increased shortest paths and decreased global efficiency with fiber tractography but decreased shortest paths and increased global efficiency with other DKI metrics. In addition, AD patients showed reduced nodal centrality predominantly in the default mode network areas. Finally, the DKI networks were more closely associated with cognitive impairment than the DTI networks. Our results suggest that DKI might be superior to DTI and could serve as a novel approach to understand the pathogenic mechanisms in neurodegenerative diseases.
Polyp burden in Lynch syndrome patients ascertained via multigene panel testing.
Authors: Maegan Roberts, Megan L. Marshall, Erica M Webb, Anna K. McGill, Lisa R. Susswein, Zhixiong Xu, Rachel T. Klein, Kathleen S. Hruska
Journal: Journal of Clinical Oncology (2018)

596 Background: Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is a hereditary colorectal cancer syndrome thought to present with few or no polyps. It has been suggested that the majority of LS patients with colon polyps will develop 1-9 cumulative adenomatous polyps in their lifetime, while approximately 10% will develop ≥10. Our aim was to describe polyp burden in a cohort of LS patients who were ascertained via multi-gene cancer panel testing. Methods: We retrospectively reviewed the personal history for all individuals with a pathogenic or likely pathogenic variant (collectively, PV) in MLH1, MSH2 (including 3’ EPCAM deletions), MSH6, or PMS2. Individuals with more than one PV in a LS-associated or other gene were excluded. All polyp data was obtained from provided test requisition forms and/or pathology reports. Results: A total of 131 individuals reported to have colon polyps were molecularly confirmed as having LS. Of these individuals, 55% (72/131) reported a history of colorectal cancer. Overall, polyp burden was reported as follows: 83% (109/131) with 1-10 polyps, 13% (17/131) with 10-19 polyps, and 4% (5/131) with 20-50 polyps. Of the 5 individuals reporting 20-50 polyps, the average was 31.2 polyps (range 21-50). Adenomatous pathology was reported for one or more polyps in 69% (91/131) of individuals. When limited to those with adenomatous polyps, 85% (77/91) reported 1-10 polyps, 11% (10/91) reported 10-19 polyps, and 4% (4/91) reported 20-50 polyps. When breaking down by presence and absence of colorectal cancer, 18% (13/72) and 15% (9/59), respectively, reported a polyp burden ≥10. Overall, 17% (22/131) of all LS patients reported ≥10 polyps. Conclusions: Similar to previously published data, the majority of LS patients with colon polyps report a polyp burden of &lt; 10. However, our data suggest that the proportion of LS patients with a polyp burden of ≥10 may be higher than previously reported (17% vs. 10%) stressing the importance of including the LS-associated genes for these patients. While LS has historically been referred to as a “non-polyposis” syndrome, a subset of patients actually present with an attenuated polyposis-like phenotype.
Reply to Yuqi Xia, Weimin Yu, and Fan Cheng's Letter to the Editor re: Ryan Swearingen, Akshay Sood, Rabii Madi, et al. Zero-fragment Nephrolithotomy: A Multi-center Evaluation of Robotic Pyelolithotomy and Nephrolithotomy for Treating Renal Stones. Eur Urol 2017;72:1014–21
Authors: Akshay Sood, Khurshid R. Ghani, Ashok K. Hemal
Journal: European Urology (2018)
Do we really externalize or objectivize moral demands?
Authors: Stephen Stich
Journal: Behavioral and Brain Sciences (2018)

Abstract Stanford's goal is to explain the uniquely human tendency to externalize or objectify “distinctively moral” demands, norms, and obligations. I maintain that there is no clear phenomenon to explain. Stanford's account of which norms are distinctively moral relies on Turiel's problematic work. Stanford's justification of the claim that we “objectify” moral demands ignores recent studies indicating that often we do not.
<i>NRG1</i> Fusions in <i>KRAS</i> Wild-Type Pancreatic Cancer
Authors: Christoph Heining, Peter Horak, Sebastian Uhrig, Paula L. Codo, Barbara Klink, Barbara Hutter, Martina Fröhlich, David Bonekamp, Daniela Richter, Katja Steiger, Roland Penzel, Volker Endris, Karl Roland Ehrenberg, Stephanie Frank, Kortine Kleinheinz, Umut H. Toprak, Matthias Schlesner, Ranadip Mandal, Lothar Schulz, Helmut Lambertz, Sebastian Fetscher, Michael Bitzer, Nisar P. Malek, Marius Horger, Nathalia A. Giese, Oliver Strobel, Thilo Hackert, Christoph Springfeld, Lars Feuerbach, Frank Bergmann, Evelin Schröck, Christof von Kalle, Wilko Weichert, Claudia Scholl, Claudia R. Ball, Albrecht Stenzinger, Benedikt Brors, Stefan Fröhling, Hanno Glimm
Journal: Cancer Discovery (2018)

Abstract We used whole-genome and transcriptome sequencing to identify clinically actionable genomic alterations in young adults with pancreatic ductal adenocarcinoma (PDAC). Molecular characterization of 17 patients with PDAC enrolled in a precision oncology program revealed gene fusions amenable to pharmacologic inhibition by small-molecule tyrosine kinase inhibitors in all patients with KRAS wild-type (KRASWT) tumors (4 of 17). These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberrant ERBB receptor–mediated signaling, and pharmacologic ERBB inhibition resulted in clinical improvement and remission of liver metastases in 2 patients with NRG1-rearranged tumors that had proved resistant to standard treatment. Our findings demonstrate that systematic screening of KRASWT tumors for oncogenic fusion genes will substantially improve the therapeutic prospects for a sizeable fraction of patients with PDAC. Significance: Advanced PDAC is a malignancy with few treatment options that lacks molecular mechanism-based therapies. Our study uncovers recurrent gene rearrangements such as NRG1 fusions as disease-driving events in KRASwt tumors, thereby providing novel insights into oncogenic signaling and new therapeutic options in this entity. Cancer Discov; 8(9); 1087–95. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1047
Mental Disorders, Antidepressants, and Type 2 Diabetes
Authors: Rodrigo B. Mansur, Roger S. McIntyre, Elisa Brietzke
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
Time-to-Event Bayesian Optimal Interval Design to Accelerate Phase I Trials
Authors: Ying Yuan, Ruitao Lin, Daniel Li, Lei Nie, Katherine E. Warren
Journal: Clinical Cancer Research (2018)

Late-onset toxicity is common for novel molecularly targeted agents and immunotherapy. It causes major logistic difficulty for existing adaptive phase I trial designs, which require the observance of toxicity early enough to apply dose-escalation rules for new patients. The same logistic difficulty arises when the accrual is rapid. We propose the time-to-event Bayesian optimal interval (TITE-BOIN) design to accelerate phase I trials by allowing for real-time dose assignment decisions for new patients while some enrolled patients' toxicity data are still pending. Similar to the rolling six design, the TITE-BOIN dose-escalation/deescalation rule can be tabulated before the trial begins, making it transparent and simple to implement, but is more flexible in choosing the target dose-limiting toxicity (DLT) rate and has higher accuracy to identify the MTD. Compared with the more complicated model-based time-to-event continuous reassessment method (TITE-CRM), the TITE-BOIN has comparable accuracy to identify the MTD but is simpler to implement with substantially better overdose control. As the TITE-CRM is more aggressive in dose escalation, it is less likely to underdose patients. When there are no pending data, the TITE-BOIN seamlessly reduces to the BOIN design. Numerical studies show that the TITE-BOIN design supports continuous accrual without sacrificing patient safety or the accuracy of identifying the MTD, and therefore has great potential to accelerate early-phase drug development. Clin Cancer Res; 24(20); 4921-30. ©2018 AACR.
Host characteristics and dynamics of Staphylococcus aureus colonization in patients with moderate-to-severe psoriasis before and after treatment: A prospective cohort study
Authors: Su-Hsun Liu, Hsiao-Yun Yu, Ya-Ching Chang, Rosaline Chung-Yee Hui, Yhu-Chering Huang, Yu-Huei Huang
Journal: Journal of the American Academy of Dermatology (2018)
Alopecia areata: a review of disease pathogenesis
Authors: F. Rajabi, L.A. Drake, M.M. Senna, N. Rezaei
Journal: British Journal of Dermatology (2018)

Alopecia areata is a disorder that results in nonscarring hair loss. The psychological impact can be significant, leading to feelings of depression and social isolation. Objectives In this article, we seek to review the pathophysiological mechanisms proposed in recent years in a narrative fashion. We searched MEDLINE and Scopus for articles related to alopecia areata, with a particular emphasis on its pathogenesis. The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. Some believe that a stressed hair follicle environment triggers antigen presentation, while others blame a dysregulation in the central immune system entangling the follicles. Evidence for the latter theory is provided by animal studies, as well investigations around the AIRE gene. Different immune‐cell lines including plasmacytoid dendritic cells, natural killer cells and T cells, along with key molecules such as interferon‐γ, interleukin‐15, MICA and NKG2D, have been identified as contributing to the autoimmune process. Alopecia areata remains incurable, although it has been studied for years. Available treatment options at best are beneficial for milder cases, and the rate of relapse is high. Understanding the exact mechanisms of hair loss in alopecia areata is therefore of utmost importance to help identify potential therapeutic targets.
Meningioma transcription factors link cell lineage with systemic metabolic cues
Authors: Ziming Du, Ryan Brewster, Parker H Merrill, Juliann Chmielecki, Josh Francis, Ayal Aizer, Malak Abedalthagafi, Lynette M Sholl, Lars Geffers, Brian Alexander, Sandro Santagata
Journal: Neuro-Oncology (2018)

Tumor cells recapitulate cell-lineage transcriptional programs that are characteristic of normal tissues from which they arise. It is unclear why such lineage programs are fatefully maintained in tumors and if they contribute to cell proliferation and viability. Here, we used the most common brain tumor, meningioma, which is strongly associated with female sex and high body mass index (BMI), as a model system to address these questions. We screened expression profiling data to identify the transcription factor (TF) genes which are highly enriched in meningioma, and characterized the expression pattern of those TFs and downstream genes in clinical meningioma samples as well as normal brain tissues. Meningioma patient-derived cell lines (PDCLs) were used for further validation and characterization. We identified 8 TFs highly enriched in meningioma. Expression of these TFs, which included sine oculis homeobox 1 (SIX1), readily distinguished meningiomas from other primary brain tumors and was maintained in PDCLs and even in pulmonary meningothelial nodules. In meningioma PDCLs, SIX1 and its coactivator eyes absent 2 (EYA2) supported the expression of the leptin receptor (LEPR), the cell-surface receptor for leptin (LEP), the adipose-specific hormone that is high in women and in individuals with high BMI. Notably, these transcriptional regulatory factors, LEPR and LEP, both contributed to support meningioma PDCLs proliferation and survival, elucidating a survival dependency on both a core transcriptional program and a metabolic cell-surface receptor. These findings provide one rationale for why lineage TF expression is maintained in meningioma and for the epidemiological association of female sex and obesity with meningioma risk.