tbuckley/cabot-search huggingface dataset:
Difference of colorectal cancer microbial community by metagenomics and culture-based methods.
Authors: Dong Ho Lee, Mijin Seol, Yu Ra Lee, Young Soo Park, Cheol Min Shin, Hyuk Yoon, Nayoung Kim, Jae Ho Cho, Dong Jin Song, Kyung Mi Kim
Journal: Journal of Clinical Oncology (2019)

489 Background: Dysbiosis of intestinal microbiota is promoting the development of colorectal cancer (CRC). We confirmed the intestinal microbiota composition from fecal sample of Korean CRC patients. Metagenomic analysis was performed and we isolated single microbes through culture-based method. Methods: CRC fecal samples were collected from 12 individuals. Metagenome Sequencing was based on the 16S rRNA gene amplicon on the Illumina MiSeq platform. The bacteria strains were subcultivated on the agar plate medium in aerobic and anaerobic and further identified by using the 16s rRNA gene sequencing. Results: Bacteria diversity by metagenome analysis was decreased in CRC group compared to control group. In CRC group, relative abundance of Firmicutes and Bacteroidetes were increased while the prevalence of Proteobacteria was decreased. The difference of microbial composition between control and CRC group was found at the genus level. Bacteroides, Parabacteroides of Bacteroidetes have increased and Acinetobacter, Pseudomonas of Proteobacteria have significantly decreased in CRC compared to control group. Using culture method, we isolated diverse bacteria of species level including five strains of Bacteroides; B. ovatus, B. uniformis, B. salyersiae, B. vulgatus and B. xylanisolvens and two strains of Fusobacterium; F. gonidiaformans and F. necrophorum from CRC patients. Conclusions: Metagenome analysis showed the genus Bacteroides, Parabacteroides of the phylum Bacteroidetes has increased and the genus Acinetobacter, Pseudomonas of Proteobacteria decreased in CRC group compared to control group. In addition to, we have isolated various strains associated with CRC by culture-based method.
Absence of Calreticulin Phenocopies Cellular Abnormalities Induced By Calreticulin Exon-9 Mutation in Myeloproliferative Neoplasms
Authors: Laura Calabresi, Manjola Balliu, Niccolò Bartalucci, Simona Salati, Laura Maggi, Francesco Annunziato, Rossella Manfredini, Paola Guglielmelli, Alessandro M. Vannucchi
Journal: Blood (2018)
Abstract 16813: Shared Comorbid Burden and Medication Adherence in Heart Failure Patient-Caregiver Dyads
Authors: Melissa I Owen, Julie Bidwell, Melinda Higgins, Carolyn Reilly, Sandra B Dunbar
Journal: Circulation (2017)

Introduction: Heart failure (HF) medication adherence is an important element of disease management, and HF patients often have caregivers (CGs) that assist with medications. However, many CGs also...
Quantification of human neuromuscular function through optogenetics
Authors: Olaia F. Vila, Sebastien G.M. Uzel, Stephen P. Ma, Damian Williams, Joseph Pak, Roger D. Kamm, Gordana Vunjak-Novakovic
Journal: Theranostics (2019)

The study of human neuromuscular diseases has traditionally been performed in animal models, due to the difficulty of performing studies in human subjects.Despite the unquestioned value of animal models, inter-species differences hamper the translation of these findings to clinical trials.Tissue-engineered models of the neuromuscular junction (NMJ) allow for the recapitulation of the human physiology in tightly controlled in vitro settings.Methods: Here we report the first human patient-specific tissue-engineered model of the neuromuscular junction (NMJ) that combines stem cell technology with tissue engineering, optogenetics, microfabrication and image processing.The combination of custom-made hardware and software allows for repeated, quantitative measurements of NMJ function in a user-independent manner.Results: We demonstrate the utility of this model for basic and translational research by characterizing in real time the functional changes during physiological and pathological processes.Principal Conclusions: This system holds great potential for the study of neuromuscular diseases and drug screening, allowing for the extraction of quantitative functional data from a human, patient-specific system.
A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.
Authors: Carl Christoph Schimanski, Stefan Kasper, Susanna Hegewisch-Becker, Jan Schroeder, Friedrich Overkamp, Frank Kullmann, Wolf Otto Bechstein, Matthias Voehringer, Robert Oellinger, Florian Lordick, Volker Heinemann, Michael Geissler, Armin Schulz-Abelius, Bernhard Linz, Helga Bernhard, Michael R. Schoen, Richard Greil, Victoria Smith-Machnow, Irene Schmidtmann, Markus Hermann Moehler
Journal: Journal of Clinical Oncology (2019)

3537 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m 2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513.
SHP1 Deficiency Is Responsible for the Constitutive Activation of the BCR Pathway in GCB DLBCL
Authors: Binu K Sasi, Sven Turkalj, Hilal Kalkan, Fabiola Porro, Engin Bojnik, Beata Pyrzynska, Abdessamad Zerrouqi, Malgorzata Bobrowicz, Magdalena Winiarska, Valdemar Priebe, Francesco Bertoni, Larry Mansouri, Richard Rosenquist, Dimitar G Efremov
Journal: Blood (2018)
Abstract P2-02-11: Combinational treatment of biguanides and fatty acid β-oxidation inhibitor in triple-negative breast cancers
Authors: JH Park, KH Jung, S Vithayathil, D Jia, BA Kaipparettu
Journal: Cancer Research (2019)

Abstract Among breast cancers (BCs), the driver pathways and therapeutic targets are still poorly understood for triple negative (TN) BCs. Advances in cancer metabolism research over the last decade have enhanced our understanding on metabolic reprogramming in cancer therapy. We have previously shown that metabolic reprogramming to fatty acid β-oxidation (FAO) is a major energy pathway in metastatic TNBC. Moreover, we reported that FAO regulates c-Src, one of the frequently upregulated oncopathways in TNBC via autophosphorylation of Src at Y419. Since FAO inhibitors alone cannot effectively control the tumor progression in TNBC, suitable combination therapies with other metabolic targets are necessary. Recently increasing evidences show that anti-diabetic biguanides have attractive anticancer effect in various cancer types including BC. However, its significance as an anticancer drug is not well established due to parallel metabolic pathways that support tumor growth. Phenformin, a biguanide derivative similar to metformin, has a greater potency than metformin. Like metformin, phenformin also inhibits mitochondrial electron transport chain (ETC) through complex I inhibition. In addition, biguanides lead to the activation of AMPK, which plays a key role in insulin signaling and energy sensing. Importantly, AMPK is an upstream regulator of FAO pathway because it can phosphorylate ACC to activate FAO. Considering the dependency of TNBC to FAO, we evaluated the therapeutic significance of the combination of biguanides(ETC inhibitors) and FAO inhibitors in TNBC progression and metastasis. We hypothesize that blocking both 'arms' of the pathway can provide more pronounced and durable responses in TNBCs. Our different in vitro and in vivo studies using TNBC cell line and PDX models suggest that the combination of both inhibitors can provide better therapeutic significance in metastatic TNBCs. This is a rationale and cost-effective metabolic approach to manage the currently non-targetable metastatic TNBCs. Further investigation into the clinical effectiveness of this combination may provide better treatment opportunities for TNBC patients. Citation Format: Park JH, Jung KH, Vithayathil S, Jia D, Kaipparettu BA. Combinational treatment of biguanides and fatty acid β-oxidation inhibitor in triple-negative breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-02-11.
Quantitative Analysis of MLL Fusion Transcripts By Droplet Digital PCR to Monitor Minimal Residual Disease in MLL-Rearranged Acute Myeloid Leukemia
Authors: Sadia Afrin, Christine RC Zhang, Claus Meyer, Mellissa Maybury, Thy Pham, Nicola Venn, Toby N Trahair, Rosemary Sutton, Rolf Marschalek, Lynn Fink, Andrew S. Moore
Journal: Blood (2018)
The optimal treatment for improving cognitive function in elder people with mild cognitive impairment incorporating Bayesian network meta-analysis and systematic review
Authors: Jing-hong Liang, Wan-ting Shen, Jia-yu Li, Xin-yuan Qu, Jing Li, Rui-xia Jia, Ying-quan Wang, Shan Wang, Rong-kun Wu, Hong-bo Zhang, Lei Hang, Yong Xu, Lu Lin
Journal: Ageing Research Reviews (2019)
Abstract P286: Egg Consumption is Associated With Cardiovascular Disease Risk Factors in the Coronary Artery Risk Development in Young Adults Study
Authors: Katie A Meyer
Journal: Circulation (2017)

Objective: The role of eggs in cardiovascular disease risk remains uncertain. Studies implicate a metabolite of choline , trimethylamine N-oxide (TMAO), in the development of cardiovascular disease (CVD). We tested the association between egg consumption and CVD risk factors over 20 years of follow-up. Methods: Study participants were from the CARDIA Study, a multicenter cohort of black and white Americans established in 1985/86 (baseline n=5,115; ages 18-30). Egg consumption was calculated from reported intake on a diet history at baseline and years 7 and 20 of follow-up. Eggs were categorized as: ≤1.0, 1.1-3.5, 3.6-6.9, and ≥7 per week. CVD risk factors were assessed at each exam, including blood pressure, lipids, and insulin resistance (defined by homeostatic model assessment, HOMA-IR). Multivariable-adjusted fixed effects (within-subject) regression models quantified prospective associations between time-varying egg consumption and CVD risk factors. Results: In the regression (Table), 7+ eggs per week was negatively associated with systolic and diastolic blood pressure and &gt;3.5 eggs per week was positively associated with HDL-C. Total cholesterol and LDL-C were positively associated with low-to-moderate consumption, but not with higher consumption. Conclusion: At higher levels of intake, eggs were negatively associated with blood pressure and positively associated with HDL-C; at low-to-moderate levels, eggs were positively associated with total cholesterol and LDL-C. P
Abstract 10277: Effect of CoQ10 on Contractile Reserve of Hibernating Swine Myocardium Following Bypass Surgery
Authors: Laura Hocum Stone, Cayla Duffy, Tammy A Butterick, Christopher Holley, Melanie Crampton, Herbert B Ward, Corey Swingen, Rosemary F Kelly, Edward O McFalls
Journal: Circulation (2015)

Background: We have previously shown that the recovery of regional function and maximal oxygen consumption in a pig model of hibernating myocardium is incomplete at 4 weeks following bypass surgery (CABG). Because clinical studies suggest a beneficial effect of chronic administration of Coenzyme Q10 (CoQ10) in ischemic heart disease, we tested the benefit of this supplement on contractile reserve, using MRI. Methods: Twelve pigs underwent placement of a constrictor around the LAD artery and had reduced function by MRI at 12 weeks. They then underwent off-pump byass using a left internal mammary artery graft and were allowed to recover. Pigs were given daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo and restudied with MRI at 4 weeks post-CABG. Images were acquired prior to and following CABG with a 3.0-T scanner (Achieva, Philips Medical Systems, Andover MA, USA), with a 4-element phased array coil on the chest and EKG gating. Regional circumferential strain (EC) measures were determined at baseline and at the time of the final study post-CABG, during an infusion of low dose dobutamine. Immediately post-stress, blood samples were obtained for analysis of troponins. Results: One animal did not survive and comparisons are made between the Placebo (N=6) and CoQ10 (N=5) groups. At 12 weeks following instrumentation and just prior to CABG, strain in the LAD region of all animals was lower than the remote regions at rest (-14.27±0.65 versus -15.13±0.69 P&lt;0.05). At 4 weeks post-CABG, baseline strain in placebo and CoQ10 groups was -12.4±1.2 and -13.7±0.8 respectively (NS). In addition to no differences in basal function, there were no intergroup differences in either contractile reserve in the LAD region, as measured by circumferential strain, or cardiac troponin levels post-stress (Figure). In summary, in this model of chronic myocardial ischemia, daily supplementation with CoQ10 did not improve basal function or contractile reserve at 4 weeks following CABG.
Abstract 16502: Effect of Azelnidipine, an Unique Calcium Channel Blocker, and Amlodipine on Sympathetic Nerve Activity in Primary Hypertensive Patient
Authors: Jun-ichiro Inomata, Hisayoshi Murai, Daisuke Kobayashi, Yu Sugiyama, Yoshiteru Sekiguchi, Shigeo Takata, Shuichi Kaneko, Masayuki Takamura
Journal: Circulation (2013)

Purpose: Calcium channel blocker is one of antihypertensive drugs that have strong vasodilatation.However, baroreflex mediated sympathetic activationmight cause adverse effects in hypertensive pati...
Systemic timolol exposure following topical application to infantile hemangiomas
Authors: Beth A. Drolet, Felix Boakye-Agyeman, Barrie Harper, Kristen Holland, Andrew Lewandowski, Nicole Stefanko, Chiara Melloni, Gary Furda, Danny Benjamin, Edmund Capparelli, Gregory L. Kearns, Ian M. Paul, Christoph Hornik, Kelly Wade
Journal: Journal of the American Academy of Dermatology (2019)
Autoimmune Laboratory Testing Practices for Evaluation of Chronic Urticaria
Authors: Michele N. Pham, Shradha Agarwal
Journal: Journal of Allergy and Clinical Immunology (2019)

Current guidelines recommend against autoimmune testing for chronic urticaria (CU) without findings suggestive of autoimmunity. Despite the majority of cases being idiopathic, patients and referring physicians often consult A/I specialists to identify the etiology of disease. Here we describe current autoimmune laboratory testing practices and utility. Retrospective chart review of patients evaluated at an allergy/immunology practice for CU. Autoimmune lab tests, biopsies, and resultant referrals were reviewed. Among 149 patients, autoimmune testing was performed in 81.2% (121) with 43.8% (53) being indicated based upon current autoimmune diagnosis (50.9%), family history of autoimmune disease (41.5%), concerning review of systems (37.7%), or abnormal rash quality (11.3%). The most common tests ordered included TSH (86.0%), C4 (47.9%), TPO (36.4%), and ANA (31.4%). The most frequently abnormal tests were ANA (31.58% 13/38), ESR (20.83% 5/24), SSA (16.7% 1/6), and thyroglobulin (14.0% 6/43). There was no difference between indication for testing versus whether testing was sent overall (OR 0.90, 95%CI 0.39-2.1) or for each individual test. Of the thirty-seven patients with abnormal results- 45.9% resulted in no action, 54.1% were referred for further evaluation. Though those with testing indications, when compared to those without indication, did not have more abnormal results, they had 5 times greater odds of undergoing further intervention (OR 5.38,95% I 2.4-12.2). There was no association between testing indication and the ordering of tests or abnormal results. Routine extensive testing may lead to higher health care related costs without increased clinical benefit.
A Pooled Analysis of Survival By Defibrotide Timing of Initiation in Adults with Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Following Hematopoietic Stem Cell Transplant (HSCT)
Authors: Paul Richardson, Enric Carreras, Antonio Pagliuca, Robert Ryan, William Tappe, Mohamad Mohty
Journal: Blood (2018)
Rapid Genetic Code Evolution in Green Algal Mitochondrial Genomes
Authors: Emmanuel Noutahi, Virginie Calderon, Mathieu Blanchette, Nadia El-Mabrouk, Bernd Franz Lang
Journal: Molecular Biology and Evolution (2019)

Genetic code deviations involving stop codons have been previously reported in mitochondrial genomes of several green plants (Viridiplantae), most notably chlorophyte algae (Chlorophyta). However, as changes in codon recognition from one amino acid to another are more difficult to infer, such changes might have gone unnoticed in particular lineages with high evolutionary rates that are otherwise prone to codon reassignments. To gain further insight into the evolution of the mitochondrial genetic code in green plants, we have conducted an in-depth study across mtDNAs from 51 green plants (32 chlorophytes and 19 streptophytes). Besides confirming known stop-to-sense reassignments, our study documents the first cases of sense-to-sense codon reassignments in Chlorophyta mtDNAs. In several Sphaeropleales, we report the decoding of AGG codons (normally arginine) as alanine, by tRNA(CCU) of various origins that carry the recognition signature for alanine tRNA synthetase. In Chromochloris, we identify tRNA variants decoding AGG as methionine and the synonymous codon CGG as leucine. Finally, we find strong evidence supporting the decoding of AUA codons (normally isoleucine) as methionine in Pycnococcus. Our results rely on a recently developed conceptual framework (CoreTracker) that predicts codon reassignments based on the disparity between DNA sequence (codons) and the derived protein sequence. These predictions are then validated by an evaluation of tRNA phylogeny, to identify the evolution of new tRNAs via gene duplication and loss, and structural modifications that lead to the assignment of new tRNA identities and a change in the genetic code.
Abstract 18882: Intrinsic and Extrinsic Cardiac Nerve Response to Apnea: Role in Atrial Fibrillation
Authors: Liliana Tavares, Moisés Rodríguez-Mañero, Sufen Wang, Miguel Valderrabano
Journal: Circulation (2017)

Introduction: Obstructive sleep apnea is associated with atrial fibrillation. The mechanisms remain poorly understood. Hypothesis: Apnea induces consistent intrinsic and extrinsic cardiac autonomic...
Creator of first gene edited babies faces “stern” punishment
Authors: Owen Dyer
Journal: BMJ (2019)

He Jiankui, the Chinese scientist who rocked the field of genetics when he announced in November that he had created the world’s first gene edited babies,1 will be “sternly dealt with,” said China’s government, which is believed to have been holding him under house arrest for weeks.

The preliminary findings of a report by the Health Commission of China, passed to China’s official news agency Xinhua, seem to confirm that the twin girls whose birth announcement by He caused the uproar do indeed have an artificially altered genome and that the birth of a third child gene edited child is also expected.

Motivated by the pursuit of “personal fame and fortune,” according to Xinhua’s account of the report, He “organized a project team that …
Tissue-Resident T Cells and Other Resident Leukocytes
Authors: David Masopust, Andrew G. Soerens
Journal: Annual Review of Immunology (2019)

Resident memory T (Trm) cells stably occupy tissues and cannot be sampled in superficial venous blood. Trm cells are heterogeneous but collectively constitute the most abundant memory T cell subset. Trm cells form an integral part of the immune sensing network, monitor for local perturbations in homeostasis throughout the body, participate in protection from infection and cancer, and likely promote autoimmunity, allergy, and inflammatory diseases and impede successful transplantation. Thus Trm cells are major candidates for therapeutic manipulation. Here we review CD8
Abstract 04: Racial Disparities in Cardiovascular Health Behaviors are Partially Explained by Socioeconomic, Psychosocial and Environmental Factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Kara M Whitaker, David R Jacobs, Kiarri N Kershaw, John N Booth, David C Goff, Donald M Lloyd-Jones, Ryan T Demmer, Catarina I Kiefe
Journal: Circulation (2017)

Introduction: There are known racial differences in cardiovascular health behaviors, including smoking, physical activity, and diet quality. A better understanding of factors that explain these differences may suggest novel intervention targets for reducing disparities in cardiovascular disease. Objective: To examine whether socioeconomic, psychosocial and environmental factors mediate racial differences in health behaviors. Methods: We studied 3,028 Black or White CARDIA participants who were enrolled at age 18-30 years in 1985-86 and completed the 30 year follow-up visit in 2015-2016. Health behaviors included smoking (current, former ≤ 12 months, never smoker/quit &gt;12 months), physical activity (inactive, active but not meeting guidelines, meeting guidelines), and a surrogate for healthy eating using fast food and sugar-sweetened beverage consumption (frequency per week ≥ 2, some but &lt; 2, none). Each behavior was assigned a value of 0 for poor, 1 for intermediate or 2 for ideal and summed to calculate an overall health behavior score for each participant (range 0-6). The race difference (β) in health behavior score was estimated using linear regression. Formal mediation analyses computed the proportion of the total effect of race on health behavior score explained by socioeconomic, psychosocial, and environmental factors (see Table footnote). Results: Blacks had a lower health behavior score than Whites in crude analyses (mean difference: -1.04, p&lt;0.001). After adjustment for sex, age and field center, socioeconomic factors mediated 50.5% of the association between race and the health behavior score, psychosocial factors 26.8% and environmental factors 9.0% (p&lt;0.05 for all). Joint associations mediated 58.1% of the race-health behavior score association. Conclusions: Observed racial differences in the health behavior score are predominately mediated by socioeconomic factors, which appear to play a stronger explanatory role than psychosocial and environmental factors.