tbuckley/cabot-search huggingface dataset:
How did that individual make that perceptual decision?
Authors: David A. Booth
Journal: Behavioral and Brain Sciences (2018)

Suboptimality of decision making needs no explanation. High-level accounts of suboptimality in diverse tasks cannot add up to a mechanistic theory of perceptual decision making. Mental processes operate on the contents of information brought by the experimenter and the participant to the task, not on the amount of information in the stimuli without regard to physical and social context.
Synthesis of enantiopure <sup>18</sup>F-trifluoromethyl cysteine as a structure-mimetic amino acid tracer for glioma imaging
Authors: Shaoyu Liu, Hui Ma, Zhanwen Zhang, Liping Lin, Gongjun Yuan, Xiaolan Tang, Dahong Nie, Shende Jiang, Guang Yang, Ganghua Tang
Journal: Theranostics (2019)

Although 11C-labelled sulfur-containing amino acids (SAAs) including L-methyl-[11C]methionine and S-[11C]-methyl-L-cysteine, are attractive tracers for glioma positron emission tomography (PET) imaging, their applications are limited by the short half-life of the radionuclide 11C (t1/2 = 20.4 min). However, development of 18F-labelled SAAs (18F, t1/2 = 109.8 min) without significant structural changes or relying on prosthetic groups remains to be a great challenge due to the absence of adequate space for chemical modification. Methods: We herein present 18F-trifluoromethylated D- and L-cysteines which were designed by replacing the methyl group with 18F-trifluoromethyl group using a structure-based bioisosterism strategy. These two enantiomers were synthesized stereoselectively from serine-derived cyclic sulfamidates via a nucleophilic 18F-trifluoromethylthiolation reaction followed by a deprotection reaction. Furthermore, we conducted preliminary in vitro and in vivo studies to investigate the feasibility of using 18F-trifluoromethylated cysteines as PET tracers for glioma imaging. Results: The two-step radiosynthesis provided the desired products in excellent enantiopurity (ee > 99%) with 14% ± 3% of radiochemical yield. In vitro cell study demonstrated that both enantiomers were taken up efficiently by C6 tumor cells and were mainly transported by systems L and ASC. Among them, the D-enantiomer exhibited relatively good stability and high tumor-specific accumulation in the animal studies. Conclusion: Our findings indicate that 18F-trifluoromethylated D-cysteine, a new SAA tracer, may be a potential candidate for glioma imaging. Taken together, our study represents a first step toward developing 18F-trifluoromethylated cysteines as structure-mimetic tracers for PET tumor imaging.
Polygenic Risk Score in Follicular Lymphoma Risk and Prognosis in a Population-Based Case-Control Study in Los Angeles County
Authors: Charlie Zhong, Jianning Luo, Chun R Chao, Susan Neuhausen, Joo Y. Song, Dennis D. Weisenburger, Leslie Bernstein, Wendy Cozen, Sophia S. Wang
Journal: Blood (2018)
Increasing Utilization and Excellent Initial Outcomes Following Liver Transplant of Hepatitis C Virus (HCV)‐Viremic Donors Into HCV‐Negative Recipients: Outcomes Following Liver Transplant of HCV‐Viremic Donors
Authors: Thomas G. Cotter, Sonali Paul, Burhaneddin Sandıkçı, Thomas Couri, Adam S. Bodzin, Ester C. Little, Vinay Sundaram, Michael Charlton
Journal: Hepatology (2019)

Direct‐acting antiviral (DAA) therapy has altered the frequency and outcome of liver transplantation (LT) for hepatitis C virus (HCV). The high efficacy and tolerability of DAA therapy has also created a rationale for utilizing HCV‐viremic (HCV‐RNA–positive) donors, including into HCV‐negative recipients. We examined trends in frequency of organ utilization and graft survival in recipients of HCV‐viremic donors (HCV‐RNA positive as measured by nucleic acid testing [NAT]). Data were collected from the Scientific Registry of Transplant Recipients (SRTR) on adult patients who underwent a primary, single‐organ, deceased donor LT from January 1, 2008 to January 31, 2018. Outcomes of HCV‐negative transplant recipients (R – ) who received an allograft from donors who were HCV‐RNA positive (DNAT + ) were compared to outcomes for R – patients who received organs from donors who were HCV‐RNA negative (DNAT – ). There were 11,270 DNAT – /R – ; 4,748 DNAT – /R + ; 87 DNAT + /R – ; and 753 DNAT + /R + patients, with 2‐year graft survival similar across all groups: DNAT – /R – 88%; DNAT – /R + 88%; DNAT + /R – 86%; and DNAT + /R + 90%. Additionally, there were 2,635 LTs using HCV antibody‐positive donors (DAb + ): 2,378 DAb + /R + and 257 DAb + /R – . The annual number of DAb + /R – transplants increased from seven in 2008 to 107 in 2017. In the post‐DAA era, graft survival improved for all recipients, with 3‐year survival of DAb + /R – patients and DAb + /R + patients increasing to 88% from 79% and to 85% from 78%, respectively. Conclusion: The post‐DAA era has seen increased utilization of HCV‐viremic donor livers, including HCV‐viremic livers into HCV‐negative recipients. Early graft outcomes are similar to those of HCV‐negative recipients. These results support utilization of HCV‐viremic organs in selected recipients both with and without HCV infection.
Abstract 11779: The Acceleration Sugar Score -a New Way to Track Changes in Sugar Intake
Authors: Wanda Firth, Bernice Pancura, Maureen Tilley, Mark Rogers, Simon Bacon, Darren Warburton, Paul Oh, Nick Giacomantonio
Journal: Circulation (2017)

Background: Evidence is building about the risks associated with excess sugar consumption, particularly in combination with highly processed foods. We hypothesized that a transition of eating behav...
Response to Open Peer Commentaries on “A Radical Approach to Ebola: Saving Humans and Other Animals”
Authors: Sarah J. L. Edwards, Charles H. Norell, Phyllis Illari, Brendan Clarke, Carolyn P. Neuhaus
Journal: The American Journal of Bioethics (2019)

We thank all our commentators for engaging so encouragingly with a proposal that many would regard as simply too radical to consider seriously pursing in practice. In the spirit of encouraging furt...
Predicting imminent disease progression in advanced colorectal cancer by a machine-learning algorithm.
Authors: Yuri Kogan, Shmuel Shannon, Eldad Taub, Marina Kleiman, Moran Elishmereni, Zvia Agur
Journal: Journal of Clinical Oncology (2019)

645 Background: In advanced cancers, predicting disease progression just before its clinical manifestation enables an earlier switch to the next treatment line, preventing deterioration in the patient's state and potentially improving survival. Yet, given the ambiguity of current tumor markers in alerting to progression, physicians are unable to forecast this key event. We developed a diagnostic algorithm for announcing an approaching disease progression in late-stage colorectal cancer (CRC) patients by processing continuous carcinoembryonic antigen (CEA) input. Methods: Longitudinally measured CEA data of advanced CRC patients treated by standard 1 st line chemotherapies, collected from 2 clinical trials (projectdatasphere.org), served for algorithm development by machine-learning and training assisted by receiver-operating-characteristic (ROC) analysis and correlation tests. Performance was validated by cross-validation techniques. Results: CEA and response evaluations of 489 CRC patients (median follow-up time: 168 days) were processed by the algorithm, predicting disease progression with 57% sensitivity (100/175 progression events) and 88% specificity (21/175 false positives). Positive and negative predictive values, accuracy and Cohen’s kappa were 64%, 84%, 79% and 0.46, respectively. The algorithm’s predictive power was superior to that of standard statistical analyses of these CEA data (e.g., ROC). Conclusions: Our study offers a new approach to using tumor markers as prognosticators. The algorithm-amplified ability of CEA to predict progression in CRC complements our recent findings in lung cancer, where integration of CEA and 4 other markers provided 66% sensitivity in predicting progression, surpassing the low capacity of each separate marker. Conceivably, future algorithm-integration of multiple markers in CRC may also exceed the limited signal of a single marker. Clinical use of our algorithm, amplifying weak marker signals of imminent progression, should allow physicians to reliably harness tumor markers for improving treatment and potentially extending survival in cancer patients.
The impact of multidisciplinary team (MDT) management on outcome of hepatic resection in liver-limited colorectal metastases.
Authors: Salvatore Corallo, Maria Alessandra Calegari, Ina Valeria Zurlo, Silvio Marchesani, Armando Orlandi, Vincenzo Dadduzio, Brunella Di Stefano, Floriana Camarda, Carmela Di Dio, Giovanna Garufi, Brunella Barbaro, Maria Vellone, Francesco Ardito, Felice Giuliante, Carmelo Pozzo, Alessandra Cassano, Carlo Antonio Barone, Emilio Bria, Michele Basso
Journal: Journal of Clinical Oncology (2019)

671 Background: Hepatic resection is the gold standard treatment for pts with liver-limited mCRC with 5- and 10-yrs survival rates reaching up to 60% and 20%. Although multidisciplinary team (MDT) management might ensure a more accurate assessment of pts and a faster referral to surgeons, reports discussing the impact of MDTs on survival are controversial and to date there are no strong evidences supporting routinely MDT discussion. The aim of this study was to evaluate the benefit of MDT management in pts with liver-limited mCRC in our single institution experience. Methods: Clinical records of pts with liver-limited mCRC who underwent radical surgery at Fondazione Policlinico “A. Gemelli” - IRCCS from Jan-2006 to Dec-2016 were retrospectively analyzed. The objective of the analysis was to compare survivals of pts managed within our MDT (MDT cohort) to those of pts referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Primary endpoints were DFS and OS. Differences in baseline characteristics and in post-operative morbidity were evaluated. Results: Of the 619 pts analyzed, 230 were included in the MDT cohort and 389 in the non-MDT cohort. No significant difference between the two groups was found in terms of DFS (12vs11 m; p 0.09) and OS (55vs51 m; p 0.68). Concerning baseline characteristics, in the MDT cohort compared to non-MDT cohort there was a statistically higher number of median metastases (4.5vs2.6; p &lt; 0.0001) and a higher rate of synchronous metastases (61.7vs39.3%; p &lt; 0.001). Despite pre-operative CT rate was higher in the MDT group (75.8vs70.7%), the median duration of CT before surgery was significantly lower in MDT pts (7 vs 8 cycle; p &lt; 0.001). Moreover, post-operative morbidity was significantly lower in the MDT cohort (6.2vs19.2%; p &lt; 0.00001). Conclusions: Our study does not demonstrate a survival benefit from MDT management of pts with liver limited mCRC. However, the analysis shows that MDT assessment allows to consider eligible for surgery pts with a more advanced disease. Moreover, MDT discussion seems to reduce the median duration of pre-operative CT with a consequent lower rate of post-operative morbidities. Our data warrant prospective validation.
Clinical outcomes in patients undergoing multiple self-expandable metallic stent placement by stent in stent technique for malignant gastric outlet obstruction.
Authors: Jinwon MO, Jie-Hyun Kim, Seung Yong Shin, Da Hyun Jung, Jae Jun Park, Young Hoon Youn, Hyojin Park
Journal: Journal of Clinical Oncology (2019)

88 Background: Self-expandable metallic stent (SEMS) placement is widely used for relieving the obstructive symptoms of malignant gastric outlet obstruction (MGOO). The aims were to evaluate the efficacy and safety of multiple gastroduodenal stent placement by stent in stent technique and identify predictive factors about stent patency. Methods: We retrospectively analyzed data from 170 patients with GOO receiving SEMS by stent in stent technique from July 2006 to July 2018. Among them, 90 patients had been treated with gastroduodenal SEMS placement for MGOO. Technical and clinical success rates were evaluated. And, clinical outcomes with predictors of stent patency were also analyzed. Results: Among the subjects, 34.4% were treated with secondary SEMS placement, and 9.7% were treated with third SEMS placement because of the previous stent dysfunction. The median stent patency time was 15.7 weeks (range 0-89) in the first SEMS, 10.4 weeks (range 0-44) in the second SEMS, and 11.3 weeks (range 1-29) in the third SEMS. The technical and clinical success rate were 100% and 97.8% in the first SEMS, 100% and 90.3% in the second SEMS, 100% and 100% in the third SEMS. In multivariable analysis, the first SEMS placement of covered type including Comvi stent was correlated with prolonged stent patency (OR 4.549, P = 0.001). And both chemotherapy after the first SEMS placement (OR 8.248, P = 0.006) and chemotherapy after the second SEMS placement (OR 7.467, P = 0.003) were correlated with prolonged stent patency. Serious complications such as gastrointestinal hemorrhage or perforation did not occur in any patient. Conclusions: Secondary and third gastroduodenal SEMS placement by stent in stent technique is a safe and effective treatment for the first stent dysfunction in MGOO. The stent placement of covered type and chemotherapy after stent placement is the predictor of stent patency. Keywords: Malignant gastric outlet obstruction, Self-expandable metallic stent, Stent in stent technique, Stent patency, Predictive factor
Correction: Neoadjuvant Trials in ER+ Breast Cancer: A Tool for Acceleration of Drug Development and Discovery
Authors: Angel L. Guerrero-Zotano, Carlos L. Arteaga
Journal: Cancer Discovery (2019)

In the original version of this article (1), the stated disclosure of the author Carlos L. Arteaga is incorrect. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Regulation of globin-heme balance in Diamond-Blackfan anemia by HSP70/GATA1
Authors: Sarah Rio, Marc Gastou, Narjesse Karboul, Raphaёl Derman, Thunwarat Suriyun, Hana Manceau, Thierry Leblanc, Jamel El Benna, Caroline Schmitt, Slim Azouzi, Jérome Larghéro, Zoubida Karim, Alejandra Macias-Garcia, Jane-Jane Chen, Olivier Hermine, Geneviève Courtois, Hervé Puy, Laurent Gouya, Narla Mohandas, Lydie Da Costa
Journal: Blood (2019)
The combination of the changes and the value of neutrophil-to-lymphocyte ratio is useful for prediction of response for advanced gastric cancer treated with nivolumab: A multicenter retrospective study.
Authors: Takatsugu Ogata, Hironaga Satake, Misato Ogata, Kentaro Inoue, Madoka Hamada, Hisateru Yasui, Yukimasa Hatachi
Journal: Journal of Clinical Oncology (2019)

150 Background: The ATTRACTION-2 study showed that nivolumab is effective in treating advanced gastric cancer (AGC). Many studies have examined the effectiveness of predictive factors. We previously suggested that neutrophil-to-lymphocyte ratio (NLR) was associated with progression-free survival (PFS) and overall survival. The objective of this study was to determine the effectiveness of the changes of NLR for AGC treated with nivolumab. Methods: Data on patients with AGC treated with nivolumab from November 2014 to December 2017 were collected at two centers. NLRs were calculated before the first cycle (NLR pre ) and 2 weeks after the first cycle (NLR post ) of nivolumab, and the changes in NLR (cNLR) was calculated by NLR post /NLR pre . The association of NLR pre and cNLR with the disease control rate (DCR) and PFS were assessed. Results: Forty-one patients (pts), with the median age of 64 years, were enrolled. Twenty-seven pts were men and 14 were women. Regarding ECOG PS, 34 pts had scores of 0-1 and 7 had a score of 2. The median NLR pre , NLR post , and cNLR were 2.01 (range, 0.79–18.4), 2.76 (1.27–12.3), and 1.22 (0.16–5.20), respectively. With a median follow-up period of 6.1 months, DCR was 34.1% (complete response [CR], 1 pt; partial response [PR] 3 pts, stable disease [SD], 10 pts). Patients were divided into 3 classes: 8 in Class I (NLRpre≤5 and cNLR≤ 1); 17 in Class II (NLR pre ≤ 5 and 1 &lt; cNLR≤ 2); and 16 in Class III (NLR pre &gt; 5 or cNLR &gt; 2). There were 8 pts, 17 pts, and 16 pts in Class I, II, and III, respectively. DCRs of Class I, II, and III was 87.5% (CR, 1 pt; PR, 2 pts; SD 4 pts), 29.4% (PR, 1 pts; SD 4 pts), and 12.5% (SD 2 pts), respectively. The median PFS was 2.0 months (mo), and it was longer in Class I than in Classes II+III (5.6 vs. 1.4 mo; p = 0.017) and shorter in Class III than in Classes I+II (3.1 vs. 1.3 mo; p = 0.008). The median PFS was 2.0 months (mo). The median PFS was longer in Class I compared with in Class II+III (5.6 vs 1.4 mo; p = 0.017). The median PFS was shorter in Class III compared with in Class I+II (3.1 vs 1.3 mo; p = 0.008). Conclusions: The combined use of NLR pre and cNLR seemed to be effective in predicting the response of AGC to nivolumab.
Physician Sexual Assault: The Moral Imperative for Gender Equity in Medicine
Authors: Alyssa M. Burgart
Journal: The American Journal of Bioethics (2019)

Prepare to cringe as you read this issue’s article entitled “Serious Ethical Violations in Medicine” by DuBois, Anderson, and colleagues (DuBois et al. 2019). In their analysis of 280 physician mis...
Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis in ischemia/reperfusion injury
Authors: Chiara Poluzzi, Madalina-Viviana Nastase, Jinyang Zeng-Brouwers, Heiko Roedig, Louise Tzung-Harn Hsieh, Jonas B. Michaelis, Eva Miriam Buhl, Flavia Rezende, Yosif Manavski, André Bleich, Peter Boor, Ralf P. Brandes, Josef Pfeilschifter, Ernst H.K. Stelzer, Christian Münch, Ivan Dikic, Christian Brandts, Renato V. Iozzo, Malgorzata Wygrecka, Liliana Schaefer
Journal: Kidney International (2019)
Abstract 247: The Endothelial Transcription Factor GATA2 Prevents the Development of Heart Failure During Pressure Overload Through Suppression of the Two Secreted Long Non-coding RNAs GADLOR1 and 2
Authors: Natali Froese, Malgorzata Szaroszyk, Badder Kattih, Mortimer Korf-Klingebiel, Sally A. Camper, Jeffery D Molkentin, Kai C Wollert, Johann Bauersachs, Jörg Heineke
Journal: Circulation Research (2017)

Capillary endothelial cells influence myocardial growth and function during pathological stress by releasing paracrine factors. We found that the transcription factor GATA2 is suppressed in cardiac endothelial cells by mechanical stimuli, and that GATA2 is downregulated in human failing hearts. To investigate the functional consequence of reduced endothelial GATA2 expression, we exposed endothelial cell specific, inducible GATA2 knock-out (G2-EC-KO) or wild-type (WT) mice to pressure overload through transverse aortic constriction (TAC). G2-EC-KO mice developed aggravated heart failure after TAC, but not enhanced fibrosis or capillary rarefaction. Investigation of stress signaling pathways revealed a prominent activation of p38 MAP kinases and Akt in cardiomyocytes after TAC only in WT mice, but not in G2-EC-KO mice, which in addition exerted increased calcineurin/NFAT activation. Transcriptional profiling revealed a strong upregulation of two distinct previously unknown long non-coding (lnc) RNAs in cardiac endothelial cells from G2-EC-KO mice, which we termed GADLOR1 and GADLOR2 and which were also induced in human failing hearts. Both RNAs were also induced in cultured cardiac endothelial cells in vitro after ablation of GATA2 and were found to be secreted within extracellular vesicles. Isolated cardiomyocytes incubated with extracellular vesicles from GATA2 depleted endothelial cells efficiently incorporated GADLOR1 and 2. Uptake of GADLORs by cardiomyocytes led to a profound reduction of p38 MAPK and Akt activation. Proteomic screening revealed that GADLOR1/2 bind the Ras-like protein TC21 in cardiomyocytes and block downstream signaling by preventing TC21 binding to its target PI3K. Application of both lncRNAs to the mouse myocardium by exosomal gene-transfer triggered aggravated cardiac dysfunction and disturbed stress signaling, while in turn inhibition of GADLOR1/2 by specific GapmeRs rescued stress signaling and cardiac dysfunction in G2-EC-KO mice during TAC. In summary, GATA2 protects the heart during pressure overload by suppressing the endothelial release of two long non-coding RNAs, which interfere with stress signaling in cardiomyocytes and ultimately induce heart failure.
The non-transcriptional activity of IRF3 modulates hepatic immune cell populations in acute-on-chronic ethanol administration in mice
Authors: Carlos Sanz-Garcia, Kyle L. Poulsen, Damien Bellos, Han Wang, Megan R. McMullen, Xiaoxia Li, Saurabh Chattopadhyay, Ganes Sen, Laura E. Nagy
Journal: Journal of Hepatology (2019)
Potentially avoidable acute care use among patients receiving oxaliplatin.
Authors: Eric Roeland, Thomas William LeBlanc, Kathryn Jean Ruddy, Rebecca Anne Clark-Snow, Gary Binder, William L. Bailey, Ravi C. Potluri, Luke M. Schmerold, Eros Papademetriou, Rudolph M. Navari
Journal: Journal of Clinical Oncology (2019)

651 Background: Oxaliplatin (OX), used primarily in gastrointestinal cancers, is considered moderately emetogenic while multiple guidelines classify carboplatin and cisplatin as highly emetogenic chemotherapy (HEC). The new oncology outcome measure (OP-35) from the US Centers for Medicare and Medicaid Services (CMS) deems 30-day post-chemotherapy inpatient (IP) and emergency room (ED) events “potentially avoidable” if involving nausea or emesis (NV) or any of eight other toxicities. We lack data comparing avoidable IP/ED and NV events for OX relative to platinums classified as HEC. Methods: We assessed OX, cisplatin, and carboplatin courses of therapy from 4Q 2012 to 1Q 2018 using the IBM Watson Explorys database. We identified IP/ED and OP-35 toxicities (anemia, dehydration, diarrhea, fever, NV, neutropenia, pain, pneumonia, or sepsis) by diagnosis and procedure codes, and stratified results by sex and age &lt; 70 (median age at diagnosis for colorectal cancer). An IP/ED event could involve ≥ 1 OP-35 toxicity. We also evaluated a FOLFIRINOX subgroup (receiving irinotecan ≤ 3 days after OX). Results: In sum, we identified 4,231 OX courses (382 FOLFIRINOX) (Table). OP-35 toxicities occurred in 75% of IP/ED events; of these, 34% OX and 42% FOLFIRINOX involved NV. Rates of IP/ED, IP/ED OP-35-defined toxicity, and NV after OX were consistent with cisplatin and carboplatin. Among patients receiving OX, women age &lt; 70 (n = 1388) had higher NV rates vs. others (p &lt; 0.001). Conclusions: Roughly one-third of patients receiving OX experienced IP/ED events ≤ 30 days post chemotherapy. Most involved ≥ 1 of 10 OP-35 toxicities, meeting CMS’ criteria as potentially avoidable acute care. OX IP/ED rates and NV rates were similar to other platinums and were worse among women age &lt; 70, suggesting more aggressive antiemetic prophylaxis should be evaluated. [Table: see text]
The NUP98-HOXD13 fusion oncogene induces thymocyte self-renewal via Lmo2/Lyl1
Authors: Benjamin J. Shields, Christopher I. Slape, Ngoc Vo, Jacob T. Jackson, Adriana Pliego-Zamora, Hansini Ranasinghe, Wei Shi, David J. Curtis, Matthew P. McCormack
Journal: Leukemia (2019)