tbuckley/cabot-search huggingface dataset:
Wheat chromatin architecture is organized in genome territories and transcription factories
Authors: Lorenzo Concia, Alaguraj Veluchamy, Juan S. Ramirez-Prado, Azahara Martin-Ramirez, Ying Huang, Magali Perez, Severine Domenichini, Natalia Y. Rodriguez Granados, Soonkap Kim, Thomas Blein, Susan Duncan, Clement Pichot, Deborah Manza-Mianza, Caroline Juery, Etienne Paux, Graham Moore, Heribert Hirt, Catherine Bergounioux, Martin Crespi, Magdy M. Mahfouz, Abdelhafid Bendahmane, Chang Liu, Anthony Hall, Cécile Raynaud, David Latrasse, Moussa Benhamed
Journal: Genome biology (2020)

Polyploidy is ubiquitous in eukaryotic plant and fungal lineages, and it leads to the co-existence of several copies of similar or related genomes in one nucleus. In plants, polyploidy is considered a major factor in successful domestication. However, polyploidy challenges chromosome folding architecture in the nucleus to establish functional structures.
Rescuing Dicer expression in inflamed colon tissues alleviates colitis and prevents colitis-associated tumorigenesis
Authors: Xiaoli Wu, Xiao Chen, Hui Liu, Zhong-Wei He, Zheng Wang, Lin-Jie Wei, Wei-Yun Wang, Shouhui Zhong, Qin He, Zhechao Zhang, Rongying Ou, Jian Gao, Youchun Lei, Wenjun Yang, Guanbin Song, Yi Jin, Lingli Zhou, Yunsheng Xu, Kai-Fu Tang
Journal: Theranostics (2020)

Chronic inflammation is known to promote carcinogenesis; Dicer heterozygous mice are more likely to develop colitis-associated tumors.This study investigates whether Dicer is downregulated in inflamed colon tissues before malignancy occurs and whether increasing Dicer expression in inflamed colon tissues can alleviate colitis and prevent colitis-associated tumorigenesis.Methods: Gene expression in colon tissues was analyzed by immunohistochemistry, immunoblots, and real-time RT-PCR.Hydrogen peroxide or N-acetyl-L-cysteine was used to induce or alleviate oxidative stress, respectively.Mice were given azoxymethane followed by dextran sulfate sodium to induce colitis and colon tumors.Berberine, anastrozole, or pranoprofen was used to rescue Dicer expression in inflammatory colon tissues.Results: Oxidative stress repressed Dicer expression in inflamed colon tissues by inducing miR-215 expression.Decreased Dicer expression increased DNA damage and cytosolic DNA and promoted interleukin-6 expression upon hydrogen peroxide treatment.Dicer overexpression in inflamed colon tissues alleviated inflammation and repressed colitis-associated carcinogenesis.Furthermore, we found that anastrozole, berberine, and pranoprofen could promote Dicer expression and protect cells from hydrogen peroxide-induced DNA damage, thereby reducing cytosolic DNA and partially repressing interleukin-6 expression upon hydrogen peroxide treatment.Rescuing Dicer expression using anastrozole, berberine, or pranoprofen in inflamed colon tissues alleviated colitis and prevented colitis-associated tumorigenesis.Conclusions: Dicer was downregulated in inflamed colon tissues before malignancy occurred.Decreased Dicer expression further exaggerated inflammation, which may promote carcinogenesis.Anastrozole, berberine, and pranoprofen alleviated colitis and colitis-associated tumorigenesis by Ivyspring
Contemporary Treatment Patterns and Clinical Outcomes of Comorbid Diabetes Mellitus and HFrEF
Authors: Muthiah Vaduganathan, Gregg C. Fonarow, Stephen J. Greene, Adam D. DeVore, Abhishek Kavati, Slaven Sikirica, Nancy M. Albert, Carol I. Duffy, C. Larry Hill, J. Herbert Patterson, John A. Spertus, Laine E. Thomas, Fredonia B. Williams, Adrian F. Hernandez, Javed Butler
Journal: JACC Heart Failure (2020)
<i>Notes from the Field:</i> Cholera Outbreak — Zimbabwe, September 2018–March 2019
Authors: Alison Winstead, Jonathan Strysko, Pryanka Relan, Erin E. Conners, Andrea L. Martinsen, Velma Lopez, Melissa Arons, Kudzai P.E. Masunda, Innocent Mukeredzi, John Manyara, Clemence Duri, Tapfumanei Mashe, Isaac Phiri, Marc Poncin, Nandini Sreenivasan, Rachael D. Aubert, Laurie Fuller, Shirish Balachandra, Eric Mintz, Portia Manangazira
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

A 2018 cholera outbreak in Zimbabwe underscored the importance of community-wide water, sanitation, and hygiene interventions, as well as vaccination and outbreak detection in reducing cholera's impact.
Treatment with abiraterone and enzalutamide does not overcome poor outcome from metastatic castration-resistant prostate cancer in men with the germline homozygous HSD3B1 c.1245C genotype
Authors: C. Lu, A. Terbuch, D. Dolling, J. Yu, H. Wang, Y. Chen, J. Fountain, C. Bertan, A. Sharp, S. Carreira, W.B. Isaacs, E.S. Antonarakis, J.S. De Bono, J. Luo
Journal: Annals of Oncology (2020)
PWE-148 Hepatotoxicity From Anabolic Androgenic Steroids Marketed as Dietary Supplements: Contribution from Atp8B1/Abcb11 Mutations?
Authors: Y Elsherrif, J R Potts, M R Howard, A Barnardo, S Cairns, A S Knisely, S Verma
Journal: Gut (2013)

<h3>Introduction</h3> In the United Kingdom (UK) it is illegal to produce, supply, or possess androgenic anabolic steroids (AAS) with intent. Despite this, non-prescription use of AAS, often marketed as dietary supplements, persists. We encountered drug-induced liver injury (DILI) associated with use of AAS and attempted to elucidate underlying mechanisms. <h3>Methods</h3> We describe two patients with cholestatic DILI following ingestion of the dietary supplement massdrol (“Celtic Dragon”) containing the AAS 2a-17a-dimethyl-etiocholan-3-one,17b-ol. <h3>Results</h3> Two Western European males (aged 25 and 45 years) presented to our institute between July, 2011, and March, 2012, with jaundice and intractable pruritus following use of massdrol acquired from fellow gym users. Screening found no other causes of hepatobiliary disease. Despite significant hyperbilirubinaemia (respective peaks: 614 and 229 µmol/L), peak gamma glutamyl transferase activities were within “normal range”. Besides “bland” intralobular cholestasis, consistent with DILI, liver biopsy in both found deficiency of canalicular expression of the ectoenzymes neutral endopeptidase (CD10), alanyl aminopeptidase (CD13), GGT, and carcinoembryonic antigen (CD66). This suggested generalised abnormality in ectoenzyme trafficking to, or retention within, canalicular membranes, as seen in <i>ATP8B1</i> disease (familial intrahepatic cholestasis 1 [FIC1]). The younger patient showed normal expression of bile salt export pump (BSEP, encoded by <i>ABCB11</i>) and of multidrug resistance protein 3 (MDR3; encoded by <i>ABCB4</i>); in the older BSEP but not MDR3 marking was focally diminished. While this may have been due to AAS-induced inhibition of expression of normal <i>ATP8B1</i>/<i>ABCB11</i>, it also raised the intriguing possibility of mutation in either of these genes – in effect, that AAS exposure had triggered initial episodes of benign recurrent intrahepatic cholestasis type 1/2. On sequencing, <i>ATP8B1</i> was normal in both patients; the younger was heterozygous for the mutation c.2093G &gt; A mutation in <i>ABCB11</i>, a known polymorphism previously encountered in association with intrahepatic cholestasis following antibiotic exposure (personal communication, R Thompson). Morbidity from cholestasis and pruritus was substantial, necessitating use of multiple antipruritic agents and consideration for extracorporal albumin dialysis (<i>MARS</i>). At last follow-up, however, jaundice was resolved in both. <h3>Conclusion</h3> AAS marketed as dietary supplements remain a cause of serious DILI in the UK; underlying mechanisms remain speculative but may include unmasking of genetic cholestatic syndromes. <h3>Disclosure of Interest</h3> None Declared.
GW27-e0576 Relevance of the CYP2C19 Polymorphism for Loading and Maintenance dose of Prasugrel and Clopidogrel Treatment Effect in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention: The PRAISE-GENE Study
Authors: Moo Hyun Kim, Long Zhe Guo, Eun-Seok Shin, Soe Hee Ann, Young-Rak Cho, Jong Sung Park, Kyungil Park, Tae-Ho Park
Journal: Journal of the American College of Cardiology (2016)
Treatment of Glaucoma
Authors: L L Remis, D L Epstein
Journal: Annual Review of Medicine (1984)

In the past five years, new therapeutic modalities have been discovered that have revolutionized the medical and surgical management of glaucoma. New methods of drug delivery have been developed for pilocarpine and epinephrine. Timolol maleate has become the most widely used drug in the treatment of glaucoma since it was approved for general use in 1978. This chapter reviews the pharmacology of the newer antiglaucoma medications and gives a perspective on the role of laser surgery in open-angle glaucoma.
Mobilization of Human Immature Hematopoietic Progenitors after Combinatory Use of Bortezomib and Immunomodulatory Drugs
Authors: Taro Tochigi, Takatoshi Aoki, Yoshikane Kikushige, Tomohiko Kamimura, Takuji Yamauchi, Koji Kato, Katsuto Takenaka, Toshihiro Miyamoto, Koichi Akashi
Journal: Blood (2015)
Proportion of Racial Minority Patients and Patients With Low Socioeconomic Status Cared for by Physician Groups After Joining Accountable Care Organizations
Authors: Jessica T. Lee, Daniel Polsky, Robert Fitzsimmons, Rachel M. Werner
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The incentive structure of accountable care organizations (ACOs) may lead to participating physician groups selecting fewer vulnerable patients. <h3>Objective</h3> To test for changes in the percentage of racial minority patients and patients with low socioeconomic status cared for by physician groups after joining the ACO. <h3>Design, Setting, and Participants</h3> This retrospective cohort consisted of a 15% random sample of Medicare fee-for-service beneficiaries attributed to physician groups from 2010 to 2016. Medicare Shared Savings Program (MSSP) participation was determined using ACO files. Analyses were conducted between January 1, 2019, and February 25, 2020. <h3>Exposures</h3> Using linear probability models, we conducted difference-in-differences analyses based on the year a physician group joined an ACO to estimate changes in vulnerable patients within ACO-participating groups compared with nonparticipating groups. <h3>Main Outcomes and Measures</h3> Whether the patient was black, was dually enrolled in Medicare and Medicaid, and poverty and unemployment rates of the patient’s zip code. <h3>Results</h3> In a cohort of 76 717 physician groups caring for 7 307 130 patients, 16.1% of groups caring for 27.8% of patients participated in an MSSP ACO. Using 2010 characteristics, patients attributed to ACOs from 2012 to 2016, compared with those who were not, were less likely to be black (8.0% [n = 81 698] vs 9.3% [n = 270 924]) or dually enrolled in Medicare and Medicaid (12.8% [n = 130 957] vs 18.2% [n = 528 685]), and lived in zip codes with lower poverty rates (13.8% vs 15.5%); unemployment rates were similar (8.0% vs 8.5%). In the difference-in-differences analysis, there was no statistically significant change associated with ACO participation in the proportions of vulnerable patients attributed to ACO-participating groups compared with nonparticipating groups. After joining an ACO, ACO-participating groups had 0.0 percentage points change (95% CI, −0.1 to 0.1 percentage points;<i>P</i> = .59) for black patients, −0.1 percentage points (95% CI, −0.2 to 0.1 percentage points;<i>P</i> = .32) for patients dually enrolled in Medicare and Medicaid, 0.2 percentage points (95% CI, −3.5 to 4.0 percentage points;<i>P</i> = .91) in poverty rates, and −0.4 percentage points (95% CI, −2.0 to 1.2 percentage points;<i>P</i> = .62) in unemployment rates. <h3>Conclusions and Relevance</h3> In this cohort study, there were no changes in the proportions of vulnerable patients cared for by ACO-participating physician groups after joining an ACO compared with changes among nonparticipating groups.
SEQUIN Multiscale Imaging of Mammalian Central Synapses Reveals Loss of Synaptic Connectivity Resulting from Diffuse Traumatic Brain Injury
Authors: Andrew D. Sauerbeck, Mihika Gangolli, Sydney J. Reitz, Maverick H. Salyards, Samuel H. Kim, Christopher Hemingway, Maud Gratuze, Tejaswi Makkapati, Martin Kerschensteiner, David M. Holtzman, David L. Brody, Terrance T. Kummer
Journal: Neuron (2020)

The brain's complex microconnectivity underlies its computational abilities and vulnerability to injury and disease. It has been challenging to illuminate the features of this synaptic network due to the small size and dense packing of its elements. Here, we describe a rapid, accessible super-resolution imaging and analysis workflow-SEQUIN-that quantifies central synapses in human tissue and animal models, characterizes their nanostructural and molecular features, and enables volumetric imaging of mesoscale synaptic networks without the production of large histological arrays. Using SEQUIN, we identify cortical synapse loss resulting from diffuse traumatic brain injury, a highly prevalent connectional disorder. Similar synapse loss is observed in three murine models of Alzheimer-related neurodegeneration, where SEQUIN mesoscale mapping identifies regional synaptic vulnerability. These results establish an easily implemented and robust nano-to-mesoscale synapse quantification and characterization method. They furthermore identify a shared mechanism-synaptopathy-between Alzheimer neurodegeneration and its best-established epigenetic risk factor, brain trauma.
Developmental Origins of Health and Disease
Authors: Matthew W. Gillman
Journal: JAMA (2007)

At first glance, it may seem implausible that your mother's exposure to stress or toxins while she was pregnant with you, how she fed you when you were an infant, or how fast you grew during childhood can determine your risk for chronic disease as an adult. Mounting evidence, however, indicates that events occurring in the earliest stages of human development — even before birth — may influence the occurrence of diabetes, cardiovascular disease, asthma, cancers, osteoporosis, and neuropsychiatric disorders. More than 40 years ago, Widdowson and McCance1 discovered that rat pups that were undernourished during the three weeks of . . .
Abstract 11746: Direct Comparisons of Left Ventricular Volume and Function by Simultaneous Cardiac Magnetic Resonance Imaging and Gated 13N-ammonia Positron Emission Tomography
Authors: Takatoyo Kiko, Yasuchika Takeishi
Journal: Circulation (2019)

Introduction: Cardiac magnetic resonance imaging (CMR) is a gold standard for evaluating left ventricular (LV) function. ECG-gated 13N-ammonia PET can evaluate not only myocardial perfusion but als...
Covid-19: The time to shield all pregnant frontline workers is now
Authors: Elizabeth B Brickley, Enny S Paixão
Journal: BMJ (2020)

Recent outbreaks of influenza, Ebola, and Zika viruses have taught us that pregnant women are uniquely vulnerable to emerging infectious threats. Let's not fail pregnant frontline workers during the covid-19 pandemic, say <b>Elizabeth B Brickley</b> and <b>Enny S Paixão</b>
Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study
Authors: T. Mok, D.R. Camidge, S.M. Gadgeel, R. Rosell, R. Dziadziuszko, D.-W. Kim, M. Pérol, S.-H.I. Ou, J.S. Ahn, A.T. Shaw, W. Bordogna, V. Smoljanović, M. Hilton, T. Ruf, J. Noé, S. Peters
Journal: Annals of Oncology (2020)

The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019).Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety.Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32-0.58; median PFS 34.8 versus 10.9 months crizotinib]. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46-0.98). The 5-year OS rate was 62.5% (95% CI 54.3-70.8) with alectinib and 45.5% (95% CI 33.6-57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline [HR 0.58 (95% CI 0.34-1.00)] and those without [HR 0.76 (95% CI 0.45-1.26)]. Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed.Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC.NCT02075840.
PTH-074 Smsa score not an independent predictor of outcomes in a large series of endoscopic resections
Authors: Andrew Emmanuel, Shraddha Gulati, Monica Ortenzi, Margaret Burt, Bu Hayee, Amyn Haji
Journal: Endoscopy (2018)

<h3>Introduction</h3> A predictive score to stratify the difficulty of endoscopic resection (ER) of large colorectal superficial neoplastic lesions (CSNL) and predict outcomes would be valuable. The SMSA score assigns a numerical score based on size, morphology, site and ease of access and stratifies lesions into 4 groups of increasing complexity. It has been recommended in several guidelines on colorectal ER and SMSA level 4 is reportedly associated with incomplete resection and increased complications. Despite this, it has not been widely validated in large series of ER for large CSNLs using standardised techniques. We applied the SMSA score to a large series of ER of lesions≥2 cm at a tertiary centre. <h3>Methods</h3> ER of large (≥2 cm) CSNL were included. Surveillance colonoscopy was performed at 3 months and 12 months. SMSA score was calculated and SMSA level 4 compared with level 2–3 for outcomes including failed ER,≥2 ER to achieve clearance, complications and recurrence. Multivariate logistic regression was performed to determine independent predictors of complications and recurrence. <h3>Results</h3> ER was performed for 542 lesions (mean size 53.7 mm). SMSA level 4 was not associated with an increased risk of failed ER (OR 0.06, 95% CI 0.007–0.44, p&lt;0.001) or requirement of ≥2 ER to achieve clearance (OR 3.96, 95% CI 0.49–31.9, p=0.16). Although SMSA level 4 was associated with complications (OR 5.25, 95% CI 1.58–17.5, p=0.002), it was not associated with perforation and a simple assessment of either large lesion size (≥50 mm) or difficult access was similarly associated with complications (OR 4.27, 95% CI 1.47–12.4, p=0.004). Multivariate logistic regression revealed only age (p&lt;0.001), prior heavy manipulation (p=0.03), and ESD/Hybrid ESD (p=0.02) were independently associated with complications but not SMSA level 4 (p=0.06). SMSA level 4 was associated with recurrence (OR 10.8, 95% CI 2.59–45.2, p&lt;0.001), as was either large lesion size or difficult access (OR 6.35, 95% CI 2.47–16.33, p&lt;0.001). On multivariate logistic regression only large size/difficult access (p=0.03) and piecemeal resection (p=0.003) were associated with recurrence but not SMSA level 4. <h3>Conclusion</h3> SMSA level 4 was not associated with failed ER or multiple ERs to achieve clearance. It was not an independent predictor of complications or recurrence on multivariate logistic regression. Although relatively simple, the SMSA score is somewhat difficult to rapidly calculate and stratify lesions. For practical purposes when making a judgement during a procedure, it may be as useful to use a simple assessment of large lesion size or difficulty in accessing the lesion.
Abstract 9142: Performance of Synergraft Decellularized Pulmonary Allografts Compared With Standard Cryopreserved Allografts: Results from Multi-Institutional Data
Authors: Steven Bibevski, David A Wilkinson, Mark Ruzmetov, Randall Fortuna, Mark Turrentine, John W Brown, Richard G Ohye
Journal: Circulation (2012)

Objectives: Cryopreserved pulmonary allografts frequently demonstrate early valve failure and structural degeneration believed to be related in part to an immune response mounted against HLA specific to the transplanted tissue. SynerGraft processing (CryoLife Inc., Kinnesaw, GA) decellularizes the allograft and therefore reduces its immunogenicity. Previous data comparing standard allograft to SynerGraft has been from single institutions and included limited numbers of patients. The purpose of this project was to assess the durability of the SynerGraft-processed allografts compared with standard cryopreserved allografts using data from multiple institutions. Methods: A multi-institutional review was performed of all CryoValves implanted between 2001 and 2010. One hundred sixty-three SynerGraft patients and 124 standard allograft controls were evaluated. Demographics, survival, reintervention, and echocardiographic findings were analyzed. Results: Mean age (months) was 208 ± 198 versus 151 ± 172 (p=N.S.), mean weight (kg) was 45 ± 36 versus 35 ± 33 (p=0.12), and mean valve diameter (mm) was 22.1 ± 5.8 versus 19.5 ± 6.1 (p=&lt;0.05), for SynerGraft and standard allografts, respectively. At a mean echo follow up (months) of 60 ± 34 versus 59 ± 35, mean gradient (mm Hg) was 20.7 ± 15.7 versus 27.3 ± 18.8 mmHg for the (p&lt;0.05). Mean insufficiency grade (0-4) at last follow-up was 1.8 for SynerGraft and 2.3 for standard allograft (p&lt;0.001), and for patients under the age of 24 months was 2.4 for SynerGraft and 3.2 for the standard allograft (p=0.01). By Kaplan-Meier analysis, 8-year freedom from reintervention was 82% for SynerGraft and 60% for the standard allograft (p=0.001). Eight-year freedom from insufficiency was 76% for SynerGraft and 47% for the standard allograft (p&lt;0.001). There was no statistically significant difference in survival. Conclusions: When compared to standard allografts, SynerGrafts demonstrate superior freedom from significant insufficiency and stenosis at a similar follow up period with lower rates of need for reintervention.
The Choice Of Regimens Based On Bortezomib For Patients With Newly Diagnosed Multiple Myeloma
Authors: Li Yang, Jingsong He, Xiaoyan Han, Gaofeng Zheng, Weiyan Zheng, Guoqing Wei, Wenjun Wu, Xiujin Ye, Jimin Shi, Wanzhuo Xie, Li Li, Jie Zhang, Weijia Huang, Yi Zhao, He Huang, Xuejin Zhang, Jiaping Fu, Zhen Cai
Journal: Blood (2013)