tbuckley/cabot-search huggingface dataset:
CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia
Authors: Julia von Tresckow, Paula Cramer, Jasmin Bahlo, Sandra Robrecht, Petra Langerbeins, Anna-Maria Fink, Othman Al-Sawaf, Thomas Illmer, Holger Klaproth, Sven Estenfelder, Matthias Ritgen, Kirsten Fischer, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Barbara F. Eichhorst, Michael Hallek
Journal: Leukemia (2018)
Harnessing Immune Response to Malignant Lung Nodules. Promise and Challenges
Authors: Ayumu Taguchi, Douglas Arenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

thorough history and physical examination, recognized patterns of HRCT images obtained with proper technique and in both inspiration and exhalation (1), broad serological testing, BAL cellular profile, consultation with a rheumatologist, and an MDD can yield the specific diagnosis of ILD without subjecting patients to the risks of invasive procedures to obtain lung biopsy for diagnostic interventions.
Development of the “Third-Generation” Hybrid Rice in China
Authors: Haiyang Wang, Xing Wang Deng
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Rice is a major cereal crop for China. The development of the “three-line” hybrid rice system based on cytoplasmic male sterility in the 1970s (first-generation) and the “two-line” hybrid rice system based on photoperiod- and thermo-sensitive genic male-sterile lines (second-generation) in the 1980s has contributed significantly to rice yield increase and food security in China. Here we describe the development and implementation of the “third-generation” hybrid rice breeding system that is based on a transgenic approach to propagate and utilize stable recessive nuclear male sterile lines, and as such, the male sterile line and hybrid rice produced using such a system is non-transgenic. Such a system should overcome the intrinsic problems of the “first-generation” and “second-generation” hybrid rice systems and hold great promise to further boost production of hybrid rice and other crops.
Prognostic factors in patients who received surgery for colorectal cancer with peritoneal metastasis.
Authors: Akinobu Furutani, Tomohiro Yamaguchi, Yusuke Kinugasa, Akio Shiomi, Hiroyasu Kagawa, Yushi Yamakawa, Shoichi Manabe, Yusuke Yamaoka, Yusuke Ogi, Yoshinobu Nagasawa, Hitoshi Hino, Shunichiro Kato, Takuya Suzuki, Kakeru Torii, Kohei Koido
Journal: Journal of Clinical Oncology (2018)

574 Background: Peritoneal metastasis (PM) in patients diagnosed with colon cancer is associated with a poor prognosis. We aimed to analyze prognostic factors associated with PM in patients diagnosed with colorectal cancer (CRC). Methods: We evaluated 237 patients who underwent surgery between 2002 and 2016 for CRC with PM. The extent of PM was evaluated using the Peritoneal Cancer Index (PCI). Clinicopathological variables, PCI score, surgical curability, and the administration of postoperative chemotherapy were evaluated. Overall survival was analyzed using the Kaplan-Meier method. Multivariate analysis was performed to assess the prognostic value of these variables, using the Cox regression model. Results: Our patients included 119 men and 118 women with a median age of 64 (range: 21–90) years. The primary tumor sites were the right-sided colon (n = 103), left-sided colon (n = 84), and rectum (n = 50). The median PCI score was 4 (range: 1–30). Synchronous PM was detected at the time of diagnosis of the primary tumor in 165 patients (69.6%). Distant metastases except peritoneal metastases was detected in 137 patients (57.8%). R0 resection was performed in 62 patients (19.0%). Postoperative chemotherapy was performed in 165 patients (69.6%). The median survival time in all patients was 19.4 (range: 0–30) months, and the five-year overall survival rate was 16.3%. Multivariate analysis revealed that PCI ≤ 5 (hazard ratio [HR]: 2.56, 95% confidence interval [CI]: 1.56-4.32, P &lt; 0.01); the absence of distant metastasis, except peritoneal metastasis (HR: 1.65, CI: 1.15-2.40, P &lt; 0.01); R0 resection (HR: 4.21, CI: 2.44-7.50, P &lt; 0.01) affected the survival rate. Conclusions: Our results show that a low PCI, the absence of distant metastasis except peritoneal metastasis, and R0 resection are prognostic factors in patients diagnosed with PM-CRC.
An atlas of genetic influences on osteoporosis in humans and mice
Authors: John A. Morris, John P. Kemp, Scott E. Youlten, Laetitia Laurent, John G. Logan, Ryan C. Chai, Nicholas A. Vulpescu, Vincenzo Forgetta, Aaron Kleinman, Sindhu T. Mohanty, C. Marcelo Sergio, Julian Quinn, Loan Nguyen-Yamamoto, Aimee-Lee Luco, Jinchu Vijay, Marie-Michelle Simon, Albena Pramatarova, Carolina Medina-Gomez, Katerina Trajanoska, Elena J. Ghirardello, Natalie C. Butterfield, Katharine F. Curry, Victoria D. Leitch, Penny C. Sparkes, Anne-Tounsia Adoum, Naila S. Mannan, Davide S. K. Komla-Ebri, Andrea S. Pollard, Hannah F. Dewhurst, Thomas A. D. Hassall, Michael-John G. Beltejar, Douglas J. Adams, Suzanne M. Vaillancourt, Stephen Kaptoge, Paul Baldock, Cyrus Cooper, Jonathan Reeve, Evangelia E. Ntzani, Evangelos Evangelou, Claes Ohlsson, David Karasik, Fernando Rivadeneira, Douglas P. Kiel, Jonathan H. Tobias, Celia L. Gregson, Nicholas C. Harvey, Elin Grundberg, David Goltzman, David J. Adams, Christopher J. Lelliott, David A. Hinds, Cheryl L. Ackert-Bicknell, Yi-Hsiang Hsu, Matthew T. Maurano, Peter I. Croucher, Graham R. Williams, J. H. Duncan Bassett, David M. Evans, J. Brent Richards
Journal: Nature Genetics (2018)
Personalized evidence based medicine: predictive approaches to heterogeneous treatment effects
Authors: David M Kent, Ewout Steyerberg, David van Klaveren
Journal: BMJ (2018)

The use of evidence from clinical trials to support decisions for individual patients is a form of "reference class forecasting": implicit predictions for an individual are made on the basis of outcomes in a reference class of "similar" patients treated with alternative therapies. Evidence based medicine has generally emphasized the broad reference class of patients qualifying for a trial. Yet patients in a trial (and in clinical practice) differ from one another in many ways that can affect the outcome of interest and the potential for benefit. The central goal of personalized medicine, in its various forms, is to narrow the reference class to yield more patient specific effect estimates to support more individualized clinical decision making. This article will review fundamental conceptual problems with the prediction of outcome risk and heterogeneity of treatment effect (HTE), as well as the limitations of conventional (one-variable-at-a-time) subgroup analysis. It will also discuss several regression based approaches to "predictive" heterogeneity of treatment effect analysis, including analyses based on "risk modeling" (such as stratifying trial populations by their risk of the primary outcome or their risk of serious treatment-related harms) and analysis based on "effect modeling" (which incorporates modifiers of relative effect). It will illustrate these approaches with clinical examples and discuss their respective strengths and vulnerabilities.
Secretory Capacity of Pancreatic Beta-Cells Is Enhanced 6 Months After Renal Denervation in Hypertensive Patients
Authors: Christian Ott, Axel Schmid, Felix Mahfoud, Ertan Akarca, Iris Kistner, Tilmann Ditting, Roland Veelken, Michael Böhm, Michael Uder, Roland E. Schmieder
Journal: Journal of the American College of Cardiology (2018)
Abstract MP40: Postprandial Lipemia and the Risk of Coronary Heart Disease and Stroke. The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Dmitry Kats, A. R Sharrett, Vijay Nambi, Gerardo Heiss
Journal: Circulation (2016)

Introduction: Delay in the clearance of circulating triglyceride (TG)-rich lipoproteins from circulation following the consumption of fatty foods is reportedly atherogenic. The literature on the risk of incident cardiovascular events attributed to postprandial lipemia (PPL) is inconclusive, however. Objective: To quantify the degree to which PPL is associated with incident coronary heart disease (CHD) and stroke in Caucasians and African Americans. Methods: Members of the community-based ARIC cohort (n=559) who were free of manifest cardiovascular disease in 1990-1993 (visit 2) participated in a substudy during visit 2 comparing PPL in cases of subclinical atherosclerosis versus controls free of carotid artery atherosclerosis. Postprandial TG, TG-rich lipoprotein triglycerides (TRL-TG), retinyl palmitate (RP), and apolipoprotein B48 to apolipoprotein B100 ratio (apoBR) concentrations were measured from blood samples collected at 0 (fasting), 3.5 and 8 hours after consumption of a fatty meal. The area under the curve (AUC) of the lipid value versus time was calculated for each PPL measure and transformed into weighted standard deviation units. Crude, age-sex adjusted, and fully adjusted associations of risk for validated incident CHD and stroke events (as individual and merged outcomes) by 2013 attributed to each AUC variable were estimated using Cox proportional hazard regression. For fully adjusted models, a stepwise method was applied to select from the following visit 2 covariates: race (Caucasian vs. African American), body mass index (BMI), carotid intima media (IMT), hypertension status, low and high density lipoprotein cholesterols, and cigarette smoking status. Additionally, individual associations of TG, TRL-TG, RP, and apoBR with incident events were evaluated by race and for categories of BMI and IMT. Results: Of 559 individuals without manifest cardiovascular disease in 1990-1993 (visit 2), 127 (23%) developed CHD and 27 (5%) experienced a stroke by 2013. None of the PPL parameters measured at visit 2 were associated (p&gt;0.05) with incident CHD or stroke by 2013 in crude, age-sex adjusted, or fully adjusted models. Similarly, stratified analyses did not identify significant associations between any of the PPL measures and incident events across race, BMI, or IMT subgroups. Conclusion: Extended follow up of a well-characterized, population-based cohort indicates that the extent of postprandial lipemia is not associated with risk of coronary heart disease or stroke.
Human erythrocyte band 3 is a host receptor for Plasmodium falciparum glutamic acid–rich protein
Authors: Haifa Almukadi, Christopher Schwake, Maima M. Kaiser, D. C. Ghislaine Mayer, James Schiemer, Michael R. Baldwin, Shreeya Hegde, Yunzhe Lu, Toshihiko Hanada, Athar H. Chishti
Journal: Blood (2018)
Association Between Early Intravenous Fluids Provided by Paramedics and Subsequent In-Hospital Mortality Among Patients With Sepsis
Authors: Daniel J. Lane, Hannah Wunsch, Refik Saskin, Sheldon Cheskes, Steve Lin, Laurie J. Morrison, Damon C. Scales
Journal: JAMA Network Open (2018)

Early administration of intravenous fluids is recommended for all patients with sepsis, but the association of this treatment with mortality may depend on the patient's initial blood pressure.To test the association between early administration of intravenous fluids by paramedics and in-hospital mortality among patients with sepsis, accounting for patients' initial blood pressure.Cohort study in which multiple analyses were conducted using a 1-year (from April 1, 2015, to March 31, 2016) cohort of 1871 patients with sepsis who were transported to the hospital by paramedics from a large emergency medical services system in Alberta, Canada. Multivariable logistic regression and a propensity-matched analysis adjusting for baseline patient characteristics were used to minimize confounding by indication and test the association between early administration of intravenous fluids by paramedics and in-hospital mortality. Nonparametric additive regression was used to assess the association of early administration of intravenous fluids with prehospital and in-hospital treatment times.Intravenous fluids administered by paramedics at the point of first contact and during transportation to the hospital.The primary outcome was in-hospital mortality. Secondary outcomes included prehospital and emergency department treatment times.A total of 1871 patients with sepsis were identified (955 women and 916 men; median age, 77 years [interquartile range, 64-85 years]), with an overall in-hospital mortality of 28.2% (n = 528). More than half of patients (1015 [54.2%]) received intravenous fluids from paramedics; the median volume provided was 400 mL (interquartile range, 250-500 mL). The association of intravenous fluids with mortality depended on the patient's initial systolic blood pressure (range, 42-222 mm Hg; P < .001 for interaction). For example, in a typical patient with an initial systolic blood pressure of 100 mm Hg, intravenous fluids were associated with decreased mortality (odds ratio, 0.73; 95% CI, 0.56-0.95), but for a typical patient with the median initial systolic blood pressure of 125 mm Hg, intravenous fluids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.81-2.44). Similar results were obtained in the propensity-matched analysis. The administration of intravenous fluids was associated with increased prehospital time compared with patients who did not receive intravenous fluids (median difference, 3.2 minutes; 95% CI, 1.7-4.7 minutes) but was not associated with time to assessment in the emergency department (median difference, 2.4 minutes; 95% CI, -2.4 to 7.3 minutes).Intravenous fluids provided by paramedics were associated with reduced in-hospital mortality for patients with sepsis and hypotension but not for those with a higher initial systolic blood pressure.
Loss of CXCR4 on non-classical monocytes in participants of the Women’s Interagency HIV Study (WIHS) with subclinical atherosclerosis
Authors: Karin A L Mueller, David B Hanna, Erik Ehinger, Xiaonan Xue, Livia Baas, Meinrad P Gawaz, Tobias Geisler, Kathryn Anastos, Mardge H Cohen, Stephen J Gange, Sonya L Heath, Jason M Lazar, Chenglong Liu, Wendy J Mack, Igho Ofotokun, Phyllis C Tien, Howard N Hodis, Alan L Landay, Robert C Kaplan, Klaus Ley
Journal: Cardiovascular Research (2018)

To test whether human immunodeficiency virus (HIV) infection and subclinical cardiovascular disease (sCVD) are associated with expression of CXCR4 and other surface markers on classical, intermediate, and non-classical monocytes in women.
Dissecting the spatial heterogeneity of single CTCs reveals immune evasion through MAX regulated CCL5 overexpression in hepatocellular carcinoma
Authors: Y. Sun, X.-R. Yang, J. Fan
Journal: Annals of Oncology (2018)

Background: The prognosis of hepatocellular carcinoma (HCC) is closely associated with recurrence and metastasis which has been proposed to be initiated by circulating tumor cells (CTCs). Yet, the transcriptomic plasticity and immune evasion mechanism of CTCs during circulation are not well defined. Methods: Blood was drawn from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) of 10 localized HCC patients. Single CTCs were isolated by negative enrichment and robotic micromanipulator, followed by single-cell RNA sequencing (scRNA-seq). After filtering, 113 CTCs with qualified data were subjected to bioinformatics analysis. The scRNA-seq results were further validated in three independent HCC cohorts. Results: Our scRNA-seq data revealed remarkable intra- and inter-vascular heterogeneity among CTCs from four vascular sites. We determined CTC transcriptional dynamics during transportation through consecutive vascular sites and revealed their adaptation mechanisms under biomechanical stress. We further classified CTCs from different vascular sites into two subsets, namely dormant and activated CTCs. Dormant CTCs were associated with a non-cycling state and upregulation of EMT/angiogenic signatures and showed stronger prognostic ability for early relapse than activated CTCs. Furthermore, we discovered an immune escape mechanism by which CTCs recruited regulatory T cells (Tregs) via expression of CCL5, consequently promoting the formation of an immunosuppressive microenvironment favorable for their survival in bloodstream and distant colonization.We proved that MAX, activated through the p38 pathway, was the key transcriptional factor regulating CCL5 overexpression, which was validated by ChIP, luciferase reporter gene and in vitro/vivo knockdown assays. And we further determined that Tregs-derived TGF-β1 can heighten MAX expression, thus amplifying the CCL5 expression. Conclusions: Collectively, our results reveal a previously unappreciated spatial heterogeneity of CTCs and a CTC immune-escape mechanism, which may aid in designing new anti-metastasis therapeutic strategies in HCC. Legal entity responsible for the study: Jia Fan. Funding: The State Key Program of National Natural Science of China. Disclosure: All authors have declared no conflicts of interest.
Utx Insufficiency Cooperates with Braf V600E in the Induction of Myeloma in Mice
Authors: Ola Rizq, Naoya Mimura, Motohiko Oshima, Shuji Momose, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Atsunori Saraya, Tohru Iseki, Emiko Sakaida, Chiaki Nakaseko, Yutaka Okuno, Hiroaki Honda, Jun-ichi Tamaru, Atsushi Iwama
Journal: Blood (2018)
Case 38-2018: A 54-Year-Old Man with New Heart Failure
Authors: Eric M. Isselbacher, Nandini M. Meyersohn, Amy A. Sarma, Amy E. Spooner, Kristen J. Tomaszewski
Journal: New England Journal of Medicine (2018)

A 54-year-old man presented with severe symptoms of heart failure. An evaluation revealed a wide pulse pressure, displaced cardiac impulse, volume overload, and a diastolic murmur. A chest radiograph showed enlargement of the cardiac silhouette. Additional diagnostic tests were performed.
Critical Windows for Associations between Manganese Exposure during Pregnancy and Size at Birth: A Longitudinal Cohort Study in Wuhan, China
Authors: Jie Hu, Chuansha Wu, Tongzhang Zheng, Bin Zhang, Wei Xia, Yang Peng, Wenyu Liu, Minmin Jiang, Simin Liu, Stephen L. Buka, Aifen Zhou, Yiming Zhang, Yangqian Jiang, Chen Hu, Xiaomei Chen, Qiang Zeng, Xi Chen, Bing Xu, Xichi Zhang, Ashley Truong, Kunchong Shi, Zhengmin Qian, Yuanyuan Li, Shunqing Xu
Journal: Environmental Health Perspectives (2018)

Background: Prenatal overexposure to manganese (Mn), an essential micronutrient, is related to impaired fetal growth and development. Fetuses appear to be highly sensitive to Mn during short periods of gestation. However, little is known about the critical windows of susceptibility to Mn for humans. Objectives: Our objective was to estimate trimester-specific associations of exposure to Mn with size at birth. Methods: Urine samples of 3,022 women were collected repeatedly in the first, second, and third trimesters in Wuhan, China. Urinary concentrations of Mn and other toxic metals were measured using an inductively coupled plasma mass spectrometry. Trimester-specific associations of specific gravity–adjusted urinary Mn concentrations with birth weight, birth length, and ponderal index were estimated using multivariable linear regressions with generalized estimating equations. Linear mixed models were applied to evaluate the windows of susceptibility to Mn exposure by comparing the pattern of Mn exposure among newborns with restricted size at birth to those without. Results: When compared with the third quintile of urinary Mn concentrations, both higher and lower quintiles of urinary Mn concentrations in the second and third trimesters were related to reduced birth weight, birth length, and ponderal index. But the observed associations for higher quintiles were stronger and more likely to be statistically significant [e.g., for women who were in the fifth quintile of Mn concentration in the third trimester, the reduction in birth weight was −11.2 (95% CI: −22.2, −0.1) g and in birth length was −0.04 (95% CI: −0.08, 0.00) cm]. Moreover, newborns with restricted size at birth, compared with those without, had higher levels of Mn exposure in the second and third trimesters. Conclusions: This prospective prenatal cohort study revealed an association of exposure to Mn during pregnancy, especially late pregnancy, with restricted size at birth. Replications are needed. https://doi.org/10.1289/EHP3423
It’s time to treat exercise in pregnancy as therapy
Authors: Gregory Davies, Raul Artal
Journal: British Journal of Sports Medicine (2018)

In the November 2018 (http://ow.ly/fpzH30mI7PS) (issue 52.21) and January 2019 (link to issue 53:2 please) issues of the British Journal of Sports Medicine (BJSM) , Dr Davenport and colleagues have published a series of 12 systematic reviews on outcomes related to exercise throughout pregnancy. In this most substantive evaluation of this literature to date, the authors appraised over 27 000 manuscripts and abstracts. The results of their systematic review form the basis of the 2019 Canadian Guideline for Physical Activity throughout Pregnancy.

We commend the author team for being the first to use the Appraisal of Guidelines, Research and Evaluation II methodology, a rigorous and transparent process for guideline development and dissemination.1 The Guideline Consensus Panel represented the fields of exercise physiology, medicine, midwifery, public health, library science, statistics and methodology.

Importantly, the authors were committed to including exercising pregnant women. …
Seeing, acting, and knowing
Authors: Zenon W. Pylyshyn
Journal: Behavioral and Brain Sciences (2001)

The target article proposes that visual experience arises when sensorimotor contingencies are exploited in perception. This novel analysis of visual experience fares no better than the other proposals that the article rightly dismisses, and for the same reasons. Extracting invariants may be needed for recognition, but it is neither necessary nor sufficient for having a visual experience. While the idea that vision involves the active extraction of sensorimotor invariants has merit, it does not replace the need for perceptual representations. Vision is not just for the immediate controlling of action; it is also for finding out about the world, from which inferences may be drawn and beliefs changed.