tbuckley/cabot-search huggingface dataset:
Retrospective analysis of clinical characteristics of mCRC patients receiving three or more lines of chemotherapy.
Authors: Pilar Garcia Alfonso, Íñigo Martínez Delfrade, Javier Soto Alsar, Marianela Bringas Beranek, Natalia Gutiérrez Alonso, Laura Ortega, Gabriela Torres, Andres J. Muñoz Martín, Montserrat Blanco-Codesido, Aitana Calvo, Miguel Martin
Journal: Journal of Clinical Oncology (2019)

682 Background: Prognostic and predictive factors are becoming more important in mCRC patients, and may have an impact in overall survival and in the number of lines of chemotherapy that a patient can receive. Methods: We conducted a retrospective analysis of 334 patients with mCRC. We analyzed the clinical characteristics of 113 (33.8%) mCRC patients who received ≥3 lines of chemotherapy. We apply the statistical test Chi square in order to identify significant association. Results: Several characteristics were significantly associated with receiving ≥ 3 lines of chemotherapy (n = 113): age &lt; 80 years (n = 93, OR = 3.07, p = 0.001), ECOG 0-1 (n = 98, OR = 3.21, p = 0.055), primary tumor resection (n = 62, OR = 2.36, p = 0.000) and resection of metastases (n = 56, OR = 2.07, p = 0.002). Partial or complete response rate in the first line of chemotherapy was also significantly associated with receiving ≥ 3 lines of treatment (n = 65, p = 0.011). Tumor mutational status was analyzed in 333 patients: KRAS mutation was detected in 163 over 333 patients genotyped (48.9%), NRAS in 25/206 (12.1%), BRAF in 15/217 (6.9%) and PI3K in 31/213 (14.5%). In the group of patients receiving ≥ 3 lines of chemotherapy (n = 113): KRAS mutation was found in 60/113 patients (53.1%), NRAS in 5/77 (6.5 %), BRAF in 5/84 (5.9%) and PI3K in 8/80 (11.1%). Tumor mutations were not significantly associated with ≥ 3 lines of chemotherapy. No significant association was found between sex, tumor location (right [n = 33, 29.2%] or left [n = 76, 73%]), liver or lung isolated metastases and 3 or later lines of chemotherapy. We also performed in our database a survival analysis in the 334 patients: those who received ≥3 lines of chemotherapy had significantly higher survival rates (median OS 18 m in the group of &lt; 3 lines of treatment vs. 37.2 m in the group of ≥ 3 lines of chemotherapy, HR = 1,6; CI 95% 1,2-2.1; p &lt; 0,001). Conclusions: This retrospective analysis showed that mCRC patients with &lt; 80 years, ECOG 0-1, primary tumor and or metastases resected and those with complete or partial response in the first line of treatment have a higher probability of receiving ≥ 3 lines of chemotherapy. [Table: see text]
Case of IgG4-associated sclerosing cholangitis with normal serum IgG4 concentration, diagnosed by anti-laminin 511-E8 antibody: a novel autoantibody in patients with autoimmune pancreatitis
Authors: Yukari Kato, Keishiro Azuma, Hitoshi Someda, Masahiro Shiokawa, Tsutomu Chiba
Journal: Gut (2019)

We read with great interest the article by Hubers et al published in Gut .1 They identified annexin A11 as an autoantigen in IgG4-associated cholangitis (IAC) and autoimmune pancreatitis (AIP), which is targeted by IgG4 and IgG1 antibodies in the sera of IAC/AIP patients.1 Notably, they reported that none of the 20 patients tested for primary sclerosing cholangitis (PSC) had anti-annexin A11 antibodies. Thus, the measurement of these antibodies  is helpful in differentiating IAC from PSC. In addition to the anti-annexin A11 antibodies, we recently reported another autoantibody, anti-laminin 511-E8 antibody, in patients with AIP.2 Here, we show a case of IAC/AIP with a normal serum IgG4 concentration and no infiltration of IgG4 plasma cells in the biliary duct, whose diagnosis was made by measuring the anti-laminin 511-E8 antibody. 

A 57-year-old man visited our hospital in 2005 for swelling of pancreas. Contrast-enhanced CT and …
Evaluation of the allergenic activity of the Glutathione Transferase from Blomia tropicalis (Blo t 8) in a mouse model of airway inflammation
Authors: Juana Bustillo, Ronald Regino, Sandra M. Coronado, Ines Benedetti, Lars Pedersen, Geoffrey A. Mueller, Josefina Zakzuk, Luis Caraballo
Journal: Journal of Allergy and Clinical Immunology (2019)
Clinical effect and cost-effectiveness of incorporation of point-of-care assays into early infant HIV diagnosis programmes in Zimbabwe: a modelling study
Authors: Simone C Frank, Jennifer Cohn, Lorna Dunning, Emma Sacks, Rochelle P Walensky, Sushant Mukherjee, Caitlin M Dugdale, Esther Turunga, Kenneth A Freedberg, Andrea L Ciaranello
Journal: The Lancet HIV (2019)
A Thousand Blessings
Authors: Richard B. Weinberg
Journal: Annals of Internal Medicine (2019)

On Being a Doctor5 February 2019A Thousand BlessingsRichard B. Weinberg, MDRichard B. Weinberg, MDWake Forest School of Medicine, Winston Salem, North Carolina (R.B.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-1604 Audio Reading - “A Thousand Blessings” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Thousand Blessings," by R.B. Weinberg. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Some days I don't know why I even became a doctor!”Aaron Jacobs was an excellent physician, perhaps one of our brightest. He was knowledgeable, dedicated, and hard working. But he was also high-strung and susceptible to bouts of dark pessimism. If presented with the proverbial glass half full, Dr. Jacobs would immediately start to worry about how long it would be before someone knocked it over on the floor and he would have to clean it up. As his outpatient clinic preceptor, I considered it my task not so much to instruct him on the latest treatment guidelines (which ... Author, Article, and Disclosure InformationAffiliations: Wake Forest School of Medicine, Winston Salem, North Carolina (R.B.W.)Corresponding Author: Richard B. Weinberg, MD, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “A Thousand Blessings” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Thousand Blessings," by R.B. Weinberg. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 5 February 2019Volume 170, Issue 3Page: 207-208KeywordsComputersGratitudeHepatitis AHepatitis CInfectious diseasesIntensive care unitsJewish peopleOutpatient clinicsPatientsTreatment guidelines ePublished: 5 February 2019 Issue Published: 5 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Systemic chemo (CTX) plus surgery and intraperitoneal (IP) CTX for patients (pts) with gastric cancer (GC) and peritoneal carcinomatosis (PC).
Authors: Megan Greally, Vivian E. Strong, Sam S. Yoon, Joanne F. Chou, Marinela Capanu, David Paul Kelsen, Yelena Yuriy Janjigian, David H. Ilson, Geoffrey Yuyat Ku
Journal: Journal of Clinical Oncology (2019)

117 Background: The role of IP CTX in pts with GC and PC is unclear. The PHOENIX-GC phase III study (J Clin Oncol 2018;35:1922) did not show overall survival (OS) benefit for IP CTX plus systemic CTX while a retrospective French study suggested benefit for IP CTX and cytoreductive surgery (J Clin Oncol 36:8 [abstr]). Prolonged survival may be possible in pts with chemosensitive disease (dz). Methods: We reviewed GC pts diagnosed with PC (+ve cytology and/or gross dz) at diagnostic laparoscopy (DL). We identified pts treated with gastrectomy and IP floxuridine 1,000mg/ m 2 /leucovorin 240 mg/m 2 ×3d q14d and pts who had CTX alone. Pts with visible dz on imaging were excluded. Progression-free survival (PFS) and OS were calculated from surgery date and estimated using Kaplan-Methods in surgery + IP CTX pts. Pt characteristics were compared using Fisher’s exact test and Wilcoxon Rank-Sum tests. Results: From 2000-2017, 18 pts had surgery + IP CTX (IP); 45 pts received CTX alone. Median age was 50 in IP pts and 65 in CTX only pts (p = 0.002); 94% of IP pts were ECOG PS 0/1 vs. 78% in CTX only pts (p = 0.16). 56% and 67% of pts had gross dz at DL in IP and CTX only pts respectively; remaining pts had +ve cytology only. IP pts received CTX (72% 5-FU/platinum based) for a median 3.3 months before repeat DL. 14/18 pts cleared dz; four pts with residual dz (1 +ve cytology only) had gross dz at baseline. Fourteen pts had R0 resection; 83% of tumors were ypT3-4N+. 4 pts had R1 resection; three had residual gross PC at DL. Pts received IP CTX for a median of 1 month post surgery. Median PFS and OS were 12.4 and 23 months respectively in surgery + IP CTX pts. While there was no difference in PFS in pts with -ve vs. persistently +ve cytology at repeat DL following CTX (15.5 vs. 4.7 months, p = 0.3), median OS was improved in pts who cleared cytology (29 vs. 8 months, p = 0.01). Median PFS and OS were 7 and 13.5 months respectively in CTX only pts. Conclusions: Surgery and IP CTX may have a role in highly select pts with GC and +ve cytology or small-volume gross dz. While survival was encouraging, no pt had OS &gt; 5 years. Surgery and IP CTX may be considered in pts who have a -ve repeat DL after initial CTX. Survival in CTX only pts is comparable with stage IV pts enrolled on clinical trials.
Self-sacrifice for a cause: The role of ideas and beliefs in motivating human conflict
Authors: Jeremy Ginges, Crystal Shackleford
Journal: Behavioral and Brain Sciences (2018)

The role of ideas and beliefs is generally underplayed in Whitehouse's account. However, just as people may feel that their identity is fused with a collective, they may also feel that their identity is fused with an idea (god, history, justice), which can motivate the same type of behaviors that Whitehouse seeks to explain.
Duohexabody-CD37, a Novel Bispecific Antibody with a Hexamerization-Enhancing Mutation Targeting CD37, Demonstrates Superior Complement-Dependent Cytotoxicity in Preclinical B-Cell Malignancy Models
Authors: Simone C. Oostindie, Hilma J. Van Der Horst, Marije B. Overdijk, Kristin Strumane, Sandra Verploegen, Margaret A. Lindorfer, Erica M. Cook, Martine E.D. Chamuleau, Tuna Mutis, Janine Schuurman, A. Kate Sasser, Ronald P. Taylor, Paul W. H. I. Parren, Frank J. Beurskens, Esther C. W. Breij
Journal: Blood (2018)
Korea Brain Initiative: Emerging Issues and Institutionalization of Neuroethics
Authors: Sung-Jin Jeong, In Young Lee, Bang Ook Jun, Young-Joon Ryu, Jeong-woo Sohn, Sung-Phil Kim, Choong-Wan Woo, Ja Wook Koo, Il-Joo Cho, Uhtaek Oh, Kyungjin Kim, Pann-Ghill Suh
Journal: Neuron (2019)

Neuroscience research has become a national priority for the Korean government. Korean scholars have dedicated interest in the societal ramifications of neurotechnologies; neuroethics is an integral component of the Korea Brain Initiative and to the formation of its growing neuroscience community. Neuroscience research has become a national priority for the Korean government. Korean scholars have dedicated interest in the societal ramifications of neurotechnologies; neuroethics is an integral component of the Korea Brain Initiative and to the formation of its growing neuroscience community.
Abstract B071: Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer
Authors: Andreas Josefsson, Karin Larsson, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén
Journal: Cancer Research (2018)

Abstract Background: Circulating tumor cells (CTC) are promising biomarkers in advanced prostate cancer. Since they are seeded from metastases, they may also serve as liquid biopsies for skeletal metastases that are difficult to sample. The aim of the present study was to evaluate to which extent CTCs reflect the phenotype of skeletal metastases, and thereby their potential to serve as a clinical tool in individualizing treatment of metastatic prostate cancer. Materials and Method: CTC and tissue from skeletal metastases were sampled from 22 patients (8 GnRH-naïve and 14 castration-resistant) during surgery for spinal cord compression symptoms. CTCs were sampled prior to removal of metastatic tissue, and isolated with AdnaTest ProstateCancerSelect/Detect (Qiagen). Resulting cDNA was preamplified in a multiplex reaction and analyzed for expression of 37 genes related to prostate cancer progression and metastasis with qPCR. RNA was extracted from the metastatic tissue with RNeasy Plus Universal Mini kit (Qiagen), and gene expression was assessed in the same way as for CTCs. EPCAM expression level was used as internal control to enable normalization to epithelial content (CTCs or tumor tissue) of the samples. Correlation of detected signals between matched CTC and tissue was calculated with Pearson correlations. Results: 12 of the 37 genes displayed expression patterns that were correlating in paired CTC and metastatic samples. Using this subset of genes, the metastases could be grouped similarly to when all 37 genes were included in hierarchical clustering analyses. Using a smaller subset of genes and patients, defined by gene detection frequency in CTC samples, hierarchical clustering of gene expression in CTCs could group the patients similar to when expression data from the metastases were used. In addition, a subset of genes discriminating GnRH-naïve from castration-resistant metastases could be analyzed in CTCs, where it, to a large extent, could identify the same groups of patients. Conclusion: This study shows that gene expression patterns in CTCs can reflect those of metastases. However, careful selection of the genes to include is important. In addition, insufficient detection sensitivity in CTC analyses limits the range of the genes to be analyzed with current methodology. Taken together, the results imply that CTC phenotyping is a promising tool for individualized therapy in metastatic prostate cancer. Citation Format: Andreas Josefsson, Karin Larsson, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén. Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B071.
Immunomodulatory Effects of Pevonedistat, a NEDD8-Activating Enzyme (NAE) Inhibitor, in Chronic Lymphocytic Leukemia (CLL)
Authors: Scott R Best, Adam Kittai, Taylor Rowland, Nur Bruss, Stephen E Spurgeon, Allison Berger, Amy Moran, Alexey V Danilov
Journal: Blood (2018)
Suggestion of new nomogram including inflammatory marker for predicting invasive carcinoma in intraductal papillary mucinous neoplasm of the pancreas.
Authors: In Woong Han
Journal: Journal of Clinical Oncology (2019)

204 Background: Previous studies have analyzed that inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI), associated with the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). This study aimed to evaluate the correlation between the inflammatory markers and the invasive carcinoma in IPMN and propose a nomogram including inflammatory markers for predicting invasive IPMN. Methods: From 1995 to 2016, total 468 patients who underwent surgical resection at four institutions for histologically confirmed IPMN and the data were reviewed retrospectively. The patients with history of pancreatitis, other malignancies and without CA19-9 data or lymphocyte counts were excluded, the study cohort consisted of 365 patients. Variables with P &lt; 0.05 in risk factor analysis were included in the nomogram. Results: Of 365 patients, 98 (26.8%) patients had invasive IPMN. In univariate analysis, high body mass index (BMI) ( P = 0.037), pre-operative bilirubin level ( P = 0.001), CA19-9 ( P &lt; 0.001), NLR ( P = 0.019), PLR ( P = 0.002), ALI ( P = 0.001), main duct type (P &lt; 0.001), the presence of solid portion ( P &lt; 0.001) and tumor size (P = 0.086) were identified as risk factors for invasive IPMN. In multivariate analysis, pre-operative bilirubin level (P = 0.003), CA19-9 (P = 0.002), main duct type (P = 0.034) and the presence of solid portion (P &lt; 0.001) were independent predictive markers for invasive IPMN. The nomogram was developed including all factors of risk factor analysis. Conclusions: The inflammatory markers were the risk factors for the presence of IPMN-associated invasive carcinoma. This nomogram may be useful in identifying patients with IPMN at risk of malignancy and for selecting which patients should undergo surgery. Further validation studies are needed to assess the predictive ability of nomogram including inflammatory markers.
Hypertrophic cardiomyopathy mutations in <i>MYBPC3</i> dysregulate myosin
Authors: Christopher N. Toepfer, Hiroko Wakimoto, Amanda C. Garfinkel, Barbara McDonough, Dan Liao, Jianming Jiang, Angela C. Tai, Joshua M. Gorham, Ida G. Lunde, Mingyue Lun, Thomas L. Lynch, James W. McNamara, Sakthivel Sadayappan, Charles S. Redwood, Hugh C. Watkins, Jonathan G. Seidman, Christine E. Seidman
Journal: Science Translational Medicine (2019)

Mutations in MYBPC3 disrupt myosin states of relaxation, and manipulating myosin therapeutically abates the effects of MYBPC3 mutations.
Interventions to Prevent Perinatal Depression
Authors: Elizabeth O’Connor, Caitlyn A. Senger, Michelle L. Henninger, Erin Coppola, Bradley N. Gaynes
Journal: JAMA (2019)

<h3>Importance</h3> Depression during pregnancy and the postpartum period is relatively common and can have adverse effects on both mother and child. <h3>Objective</h3> To systematically review benefits and harms of primary care–relevant interventions to prevent perinatal depression, a major or minor depressive episode during pregnancy or up to 1 year after childbirth, to inform the US Preventive Services Task Force. <h3>Data Sources</h3> MEDLINE, PubMED (for publisher-supplied records only), PsycINFO, and the Cochrane Central Register of Controlled Trials; surveillance through December 5, 2018. <h3>Study Selection</h3> Randomized clinical trials (RCTs) and nonrandomized controlled intervention studies of interventions (eg, behavior-based, antidepressants, dietary supplements) to prevent perinatal depression in general populations of pregnant and postpartum individuals or in those at increased risk of perinatal depression. Large cohort studies were considered for harms of antidepressant use only. <h3>Data Extraction and Synthesis</h3> Two investigators independently reviewed abstracts and full-text articles and quality rated included studies. Random-effects meta-analysis was used to estimate the benefits of the interventions. <h3>Main Outcomes and Measures</h3> Depression status; depression symptoms; maternal, infant, and child health outcomes. <h3>Results</h3> Fifty studies (N = 22 385) that met inclusion criteria were identified. Counseling interventions were the most widely studied interventions. Compared with controls, counseling interventions were associated with a lower likelihood of onset of perinatal depression (pooled risk ratio [RR], 0.61 [95% CI, 0.47-0.78]; 17 RCTs [n = 3094];<i>I</i><sup>2</sup> = 39.0%). The absolute difference in the risk of perinatal depression ranged from 1.3% greater reduction in the control group to 31.8% greater reduction in the intervention group. Health system interventions showed a benefit in 3 studies (n = 5321) and had a pooled effect size similar to that of the counseling interventions, but the pooled effect was not statistically significant using a method appropriate for pooling a small number of studies (restricted maximum likelihood RR, 0.58 [95% CI, 0.22-1.53]; n = 4738;<i>I</i><sup>2</sup> = 66.3%; absolute risk reduction range, −3.1% to −13.1%). None of the behavior-based interventions reported on harms directly. A smaller percentage of participants prescribed sertraline had a depression recurrence compared with those prescribed placebo (7% vs 50%,<i>P</i> = .04) at 20 weeks postpartum in 1 very small RCT (n = 22 analyzed) but with an increased risk of adverse effects to the mother. <h3>Conclusions and Relevance</h3> Counseling interventions can be effective in preventing perinatal depression, although most evidence was limited to women at increased risk for perinatal depression. A variety of other intervention approaches provided some evidence of effectiveness but lacked a robust evidence base and need further research.
Abstract 20334: Thromboembolic Risk of Imaging-Confirmed Coronary Artery Disease Without Myocardial Infarction in Patients With Non-Valvular Atrial Fibrillation
Authors: Min Soo Cho, Kyusup Lee, Kee-Joon Choi, Ungjeong Do, Yu-na Kim, Jongmin Hwang, Jun Kim, Gi-Byoung Nam, You-Ho Kim
Journal: Circulation (2017)

Introduction: Diagnosis of obstructive coronary artery disease (CAD) is increasing with the evolution of coronary imaging. However, implication of CAD without clinical manifestation of MI (non-MI C...
Effect of curcumin-nanoemulsion associated with photodynamic therapy in HPV-16 E6 positive vulvar carcinoma cell lines
Authors: Marilia F. Calmon, Caroline M. Bonfim, Leticia F. Monteleoni, Natalia M. Candido, Silvana M. Quintana, Patricia P. S. Melli, Fernando L. Primo, Camila F. Adamantino, Tedesco C. Antonio, Paula Rahal
Journal: Clinical Cancer Research (2018)