tbuckley/cabot-search huggingface dataset:
The ‘<i>in vivo</i> lifestyle’ of bile acid 7α-dehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice
Authors: Jason M. Ridlon, Saravanan Devendran, João Mp Alves, Heidi Doden, Patricia G. Wolf, Gabriel V. Pereira, Lindsey Ly, Alyssa Volland, Hajime Takei, Hiroshi Nittono, Tsuyoshi Murai, Takao Kurosawa, George E. Chlipala, Stefan J. Green, Alvaro G. Hernandez, Christopher J. Fields, Christy L. Wright, Genta Kakiyama, Isaac Cann, Purna Kashyap, Vance McCracken, H. Rex Gaskins
Journal: Gut Microbes (2019)

The formation of secondary bile acids by gut microbes is a current topic of considerable biomedical interest. However, a detailed understanding of the biology of anaerobic bacteria in the genus Clostridium that are capable of generating secondary bile acids is lacking. We therefore sought to determine the transcriptional responses of two prominent secondary bile acid producing bacteria, Clostridium hylemonae and Clostridium hiranonis to bile salts (in vitro) and the cecal environment of gnotobiotic mice. The genomes of C. hylemonae DSM 15053 and C. hiranonis DSM 13275 were closed, and found to encode 3,647 genes (3,584 protein-coding) and 2,363 predicted genes (of which 2,239 are protein-coding), respectively, and 1,035 orthologs were shared between C. hylemonae and C. hiranonis. RNA-Seq analysis was performed in growth medium alone, and in the presence of cholic acid (CA) and deoxycholic acid (DCA). Growth with CA resulted in differential expression (>0.58 log2FC; FDR < 0.05) of 197 genes in C. hiranonis and 118 genes in C. hylemonae. The bile acid-inducible operons (bai) from each organism were highly upregulated in the presence of CA but not DCA. We then colonized germ-free mice with human gut bacterial isolates capable of metabolizing taurine-conjugated bile acids. This consortium included bile salt hydrolase-expressing Bacteroides uniformis ATCC 8492, Bacteroides vulgatus ATCC 8482, Parabacteroides distasonis DSM 20701, as well as taurine-respiring Bilophila wadsworthia DSM 11045, and deoxycholic/lithocholic acid generating Clostridium hylemonae DSM 15053 and Clostridium hiranonis DSM 13275. Butyrate and iso-bile acid-forming Blautia producta ATCC 27340 was also included. The Bacteroidetes made up 84.71% of 16S rDNA cecal reads, B. wadsworthia, constituted 14.7%, and the clostridia made up <.75% of 16S rDNA cecal reads. Bile acid metabolomics of the cecum, serum, and liver indicate that the synthetic community were capable of functional bile salt deconjugation, oxidation/isomerization, and 7α-dehydroxylation of bile acids. Cecal metatranscriptome analysis revealed expression of genes involved in metabolism of taurine-conjugated bile acids. The in vivo transcriptomes of C. hylemonae and C. hiranonis suggest fermentation of simple sugars and utilization of amino acids glycine and proline as electron acceptors. Genes predicted to be involved in trimethylamine (TMA) formation were also expressed.
SAT0380 FIBROMYALGIA IS THE STRONGEST NEGATIVE PREDICTOR FOR THE ACHIEVEMENT OF EITHER REMISSION AND MINIMAL DISEASE ACTIVITY IN NAIVE PSORIATIC ARTHRITIS PATIENTS STARTING BIOLOGIC DRUGS
Authors: Florenzo Iannone, Mariangela Nivuori, Giuseppe Lopalco, Maria Grazia Anelli, Laura Coladonato, Gaetana Laselva, Crescenzio Scioscia
Journal: Annals of the Rheumatic Diseases (2019)

Conclusion:In clinical practice, the sDMARD given to the majority of pts is MTX, but its use achieves the recommended treatment target of MDA only in 16.5% of pts.The SC MTX treatment significantly, up to 30%, improves the achievement of MDA.The use of SC MTX could be a therapy optimized option in clinical practice.
Abstract 20399: Trx1 Regulates Nitroso-Redox Balance to Regulate Cell Survival in Cardiomyocytes
Authors: Narayani Nagarajan, Shinichi Oka, Sebastiano Sciarretta, Junichi Sadoshima
Journal: Circulation (2017)

Background: Thioredoxin1 (Trx1) is cardioprotective during ischemia by reducing oxidized proteins through thiol-disulfide exchange reactions. Whether Trx1 also regulates nitrosylation of target pro...
Abstract 16119: Mitochondrial Dysfunction and Autophagy Upregulation Associated Metabolic Remodeling in a Sheep Model of Persistent Atrial Fibrillation
Authors: Qiqiang Jie, Gang Li, Yang Wei, Xiaoyan Liu, Chengyu Wang, Qing Zhang, Lin Wu
Journal: Circulation (2018)

Introduction: The pathogenesis of atrial fibrillation (AF) is unknown. The objective of this study was to determine the metabolic remodeling, and autophagy levels in a sheep model with nonsustained...
PS1288 SAFETY AND UTILIZATION OF MIDLINE CATHETERS VERSUS TUNNELED CENTRAL VENOUS CATHETERS IN THE MANAGEMENT OF ACUTE MYELOID LEUKEMIA PATIENTS: A SINGLE CENTER EXPERIENCE
Authors: H. Gardeney, P. Gallego, J.M. Torregrosa Diaz, E. Cayssials, N. Maillard, B. Rammaert
Journal: HemaSphere (2019)

Background: Tunneled central venous catheters (TCVCs) are used in cancer patients for irritant or vesicant infusions such as chemotherapy or antibiotics. However, they can be associated with significant complications. Midline catheters (MCs) are peripheral intravenous access devices that ends in a large peripheral vein. They are easier to install and which may reduce the need for CVCs. Aims: Therefore, the aim of this study is to assess the rate of adverse events with both kind of catheter, in hospitalized patients for the treatment of acute myeloid leukemia. Methods: We retrospectively compared the use and complications of TCVCs and MCs at our institution between December 2017 and July 2018. Data were collected using electronic medical records. Both devices were used indistinctly among our hospitalized patients for chemotherapy, antibiotics and parenteral nutrition. The following complications were recorded: catheter‐related bloodstream infection (defined as documented bacteriemia and differential time to positivity pointing to TCVC as main source), local signs of infection (such as erythema or inflammation) at insertion site, thrombosis which requires an anticoagulant treatment, extravasation and local bleeding at insertion site. Results: Through this period, 59 chemotherapy episodes were recorded among 36 different patients: 39 of them were performed through TCVC and 20 through MC. As expected duration of the device was shorter for MCs (mean 31days) as they were ablated on discharge, compared to Hickman (51 days) or Port‐à‐cath (48days). Main complications were related to infections, with 17 (43.6%) among TCVCs and 6 (30%) in MCs (p = 0.4). Local signs of infection were also present on 5 (12.8%) of TCVCs. Median aplasia duration (defined as polymorphonuclear neutrophils count in peripheral blood &lt;500/mm3) was 19.0 days [0 to 55 days], with no differences among the groups (18.3 days in MCs vs 19.7 days in TCVCs). No extravasation was found in any group. As expected local bleeding was not observed among MC and only in 3 (7.7%) TCVCs. There is a trend towards more frequent complications (infection, thrombosis and bleeding) were more frequent among TCVCs (n = 32) than among MCs (n = 6; p = 0.08) even when reported to the length of the catheter (0.63 complications/day in TCVCs and 0.19 complications/day in MCs). Summary/Conclusion: MCs insertion ‐quick and easy‐ makes them user‐friendly for hematologists and can be safely used among acute leukemia patients.
Alarmin augments the antitumor immunity of lentiviral vaccine in ectopic, orthotopic and autochthonous hepatocellular carcinoma mice
Authors: Zhili Liu, Zhen Lu, Renwei Jing, Bingfeng Zuo, Xianjun Gao, Gang Han, Han Qi, Li Wu, Yunde Liu, Haifang Yin
Journal: Theranostics (2019)

It is a daunting therapeutic challenge to completely eradicate hepatocellular carcinoma (HCC) from patients. Alpha-fetoprotein (AFP) -based vaccines appear promising, however the efficacy needs to be improved.
AB0231 PAIN THRESHOLD IN RHEUMATOID ARTHRITIS AND ITS RELATED FACTOR
Authors: Aysegul Altun Guvenir, Aslı Calıskan Uckun, Fatmagul Yurdakul, Hatice Bodur
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Pain remains the most important challenge for rheumatoid arthritis (RA) patients. In order to cope with pain in RA, clinicians firstly need to understand the degree of patients'pain. When self reported measures such as visual analog scale were used, inconsistency between clinicians' and patients' ratings of pain was demonstrated (1). As a result, inability to fully assess the pain will cause the inability to fully assess the impact of pain on disease severity. Measuring pressure pain threshold with pressure algometry may provide additional advantages for the evaluation of pain and disease severity when compared with self-reported measures. <h3>Objectives</h3> The aim of this study was to evaluate the pain threshold and to determine the variables associated with pain threshold in the patients with RA. <h3>Methods</h3> The current study included 100 RA patients and 80 age-sex matched controls with non-inflammatory chronic low back pain. Clinical parameters, functional status, disease activity, pain, fatigue, depression, anxiety, pain catastrophizing and laboratory activity of RA patients were recorded. The pressure pain thresholds on the dominant thumb nail bed, trapezius and wrist of the two groups were measured by the algometer. The pain thresholds of the paients with RA and controls were compared. Moreover, the relation between pain threholds and all evaluated parameters in RA patients was analysed. <h3>Results</h3> The mean age of RA patients was 55.93 ± 10.81; the mean age of the controls was 54,50 ± 9,47. The pain thresholds of RA patients and controls were statistically similar in all areas. When the parameters found to be significantly correlated with pain threshold in RA patients were analyzed by regression analysis, depression was the only factor associated with low pain threshold in all areas (Table 1). <h3>Conclusion</h3> We found that depression was the only factor associated with low pain threshold in the patients with RA. The use of pressure algometry in the evaluation of chronic pain could offer an additional method to detect pain/depression overlap. <h3>Reference</h3> [1] Bagnato G, De Andres I, Sorbara S, Verduci E, Corallo G, Ferrera A, et al. Pain threshold and intensity in rheumatic patients: correlations with the Hamilton Depression Rating scale. Clinical rheumatology. 2015;34(3):555-61. <h3>Disclosure of Interests</h3> None declared
AB1262 THE RELATIONSHIP BETWEEN HYPERURICEMIA AND HEART RATE IRREGULARITY, USING DATA FROM THE KOREAN NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2016
Authors: Yeonghee Eun, Eun-Jung Park, Ji-Young Chai, Hoon-Suk Cha, Eun-MI Koh, Hyungjin Kim, Jaejoon Lee
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Hyperuricemia is one of the well-known cardiovascular risk factors. In recent studies, hyperuricemia has been shown to be an independent risk factor for atrial fibrillation, which may be associated with oxidative stress or inflammation. There is still a lack of data on the association of hyperuricemia and arrhythmia other than atrial fibrillation. <h3>Objectives:</h3> In this study, we investigated the relationship between hyperuricemia and heart rate (HR) irregularity using representative sample data of adult Korean. <h3>Methods:</h3> The study included 5870 subjects aged 19 years or older who completed the uric acid measurement in the Korean National Health and Nutrition Examination Survey conducted in 2016. Logistic regression was used to analyze the association between hyperuricemia and HR irregularity identified by the examiner at the time of the survey. <h3>Results:</h3> Subjects with HR irregularity were older, had more smoking and drinking, had a higher prevalence of HTN, and had lower glomerular filtration rate than those with regular heartbeat. In the presence of hyperuricemia, the HR irregularity was three times higher than in the absence (HR 3.65, 95% CI 1.77-7.53, <i>P</i> = 0.0005). The association of HR irregularity and hyperuricemia was significant in most subjects, especially in those older than 65 years, with diabetes and hypertension. <h3>Conclusion:</h3> Hyperuricemia was highly correlated with HR irregularity in adult Korean representative sample data, especially in subjects with conventional cardiovascular risk factors such as old age, hypertension, diabetes mellitus. This study included all subjects who showed HR irregularity at the time of examination, not just atrial fibrillation. Therefore, it is suggested that hyperuricemia may be associated with other arrhythmia as well as atrial fibrillation. Further researches are warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism. <h3> Disclosure of Interests:</h3> None declared
PF192 CLINICAL PROFILE OF POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME IN HAEMATOLOGY PATIENTS AT A TERTIARY CARE CENTRE
Authors: G. Gupta, T. Seth, M. Mahapatra, M. Aggarwal, R. Dhawan
Journal: HemaSphere (2019)

Background: Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible subcortical vasogenic brain edema with acute neurological symptoms in patients of renal failure, hypertension and on cytotoxic drugs. Established diagnostic criteria have been lacking and diagnosis can be made on exclusion based on clinical criteria, serum markers, CSFand imaging. The treatment is symptomatic depending on underlying condition. The overall prognosis is favourable but some patients may have long‐term sequale. Aims: To study the clinico‐radiologic profile and outcomes of PRES in hematological disorders. Methods: We retrospectively reviewed clinical and neuroimaging findings of patients diagnosed with PRES from January 2016 ‐ October 2018. PRES was diagnosed based on clinical signs and MRI findings. Results: There were total of 16 patients diagnosed with PRES. There were 7 females and 9 males with age ranging from 2–25 years. Maximum (12/16) patients were ALL on induction chemotherapy (BFM protocol), rest were AML on consolidation high dose cytarabine (HiDAC), thalassemia post HSCT and aplastic anaemia. None of the patients had prior history of seizures, hypertension or evidence of CNS disease. Most patients had hypertension and generalised tonic clonic seizures (GTCS) as presenting complaints. CSF examination done in all was inconclusive. The most common MRI finding (12/16) was bilateral symmetrical subcortical white matter hyperintensity on T2 and FLAIR images in occipital and parietal lobes. Others had frontal lobe, temporal lobe, thalamus and cerebellar involvement. For management cytotoxic drugs were stopped, antihypertensive (amlodipine, labetalol) and anti‐epileptics were started. Most patients experienced normalisation of blood pressure in an average of 8.6 days (range 4–15 days). Two patients expired during the course due to fungal pneumonia and intra‐cerebral haemorrhage respectively. Patients were continued on antiepileptics for 6–12 months after last seizure episode. Antihypertensives were used for period of one month and then tapered off successfully. Most patients (14/16) were discharged and are under our follow up with no active PRES related complications except one patient who has persistence of neurological deficit in the form of right sided hemiparesis. Summary/Conclusion: Amongst patients with hematological malignancy, PRES is especially seen in ALL where steroids are the backbone of induction chemotherapy. Close blood pressure monitoring in settings of induction chemotherapy and immunosuppressive drugs like calcineurin inhibitors should always be prescribed. Early recognition of PRES may facilitate appropriate treatment in a timely manner, conferring a better prognosis. Future studies should be done to address questions like duration of interruption of drug implicated in PRES, if the implicating drug has to be eliminated permanently, optimal duration of anti‐hypertensives and anti‐epileptics. image
PB1692 G-CSF ACTIVATING P38 MAPK PATHWAY ENHANCES THE ANTI-LEUKEMIC ACTIVITY OF ARSENIC TRIOXIDE IN VITRO THROUGH UP-REGULATING AQP9 EXPRESSION
Authors: A. Wang, J. Wang, X. Li, H. Pu, L. Xu, F. Chen, J. Hou, H. Zhong
Journal: HemaSphere (2019)

Background: Because of relatively lower chemotherapy-related side effects and better tolerance, granulocyte colony-stimulating factor (G-CSF) combining with other low dosage chemotherapeutics has been widely used in elderly acute myeloid leukemia (AML) patients in China. Unfortunately not all patients benefit from this regimen. Therefore, identifying novel treatment protocols with minimal toxicities and overcoming drug resistance remain the most challenging scenarios facing this population of patients. Arsenic trioxide (ATO) shows its effects in acute promyelocytic leukemia treatment and may show promising effects in other subtypes of acute myeloid leukemia. The aquaporin 9 (AQP9) expression on the leukemia membrane limits ATO transporting into the leukemia cells. Therefore, we hypothesize that the combination of ATO and specific factor which may regulate AQP9 expression would increase arsenic-induced cytotoxicity in AML. Aims: To evaluate the feasibility of combining G-CSF and arsenic trioxide in AML and to explore the mechanisms underlying the increased sensitivity of AML cells to ATO induced by G-CSF. Methods: Acute myeloid leukemia HL-60 and THP-1 cells were treated with G-CSF and/or ATO. AQP9 expression was suppressed by culturing these leukemia cells with phloretin. Cell viability, apoptosis and cell cycle distribution of each group were assessed by CCK-8 and flow cytometry respectively. Mechanistic studies were carried out by RT-qPCR and western blotting. Results: Compared with single-agent treatment in HL-60 and THP-1 cells, the combination of G-CSF and arsenic trioxide was associated with decreased cell proliferation and increased apoptosis as well as altered cell cycle distribution. Mechanistically, G-CSF treatment triggered up-regulation of AQP9, which was found to control arsenic transport and might determine ATO sensitivity. G-CSF also increased phosphorylation P38 expression. Furthermore, G-CSF induced AQP9 expression effects can be neutralized by phloretin. Summary/Conclusion: The pretreatment AML cells with G-CSF enhanced ATO anti-leukemic effect. This effect may relate with G-CSF-driven up-regulation of AQP9 expression and may be associated with the activation of P38 MAPK signaling pathway. Our findings suggest that synergistic effects of ATO and G-CSF may provide as a new therapeutic approach for elderly AML patients.
Abstract 16274: A Systems Approach for Noninvasive and Instantaneous Measurement of Left Ventricular End Diastolic Pressure Using Smartphone
Authors: Niema M Pahlevan, Melissa Ramos, Ray V Matthews
Journal: Circulation (2018)

Introduction: The ability to measure left ventricular end-diastolic pressure (LVEDP) noninvasively offers enormous benefit in the management of heart failure (HF) patients. We recently showed that ...
A phase I dose-escalation trial of AEZS-108 in taxane- and castration-resistant prostate cancer (CRPC).
Authors: Jacek K. Pinski, Andrew V. Schally, Denice D Tsao-Wei, Tanya B. Dorff, Susan G. Groshen, Shigang Xiong, David I. Quinn, Yu-Chong Tai, Juergen Engel, Stephen V. Liu
Journal: Journal of Clinical Oncology (2013)

5062 Background: The receptor for luteinizing hormone releasing hormone (LHRH-R) is highly expressed on CRPC cells and is a potential therapeutic target. AEZS-108 is an LHRH-cytotoxic hybrid that covalently couples an LHRH agonist with doxorubicin. We report the completed Phase I trial of AEZS-108 in men with taxane-resistant CRPC. We explored visualization of AEZS-108 internalization into circulating tumor cells (CTCs) exploiting the auto-fluorescence of doxorubicin and also tested LHRH-R expression on CTCs. Methods: This was a dose escalation Phase I trial in men with taxane-resistant CRPC to confirm the dose established in a phase I trial in women. Standard 3+3 design was used with planned expansion at the MTD to ensure 6 patients received 2+ courses without DLT. Eligibility criteria included progression of disease despite prior LHRH agonist and taxane therapy. Patients received AEZS-108 every 21 days until progression or unacceptable toxicity. The primary endpoint was safety. CTCs were captured with a novel slot microfilter and identified by PSA and DAPI staining. AEZS-108 internalization was visualized by fluorescence microscopy. Results: Eighteen men with a median of 2 prior chemotherapy regimens (range 1-5) and a median PSA of 106.4 ng/mL (range 8.4-1624.0) enrolled from November 2010 to August 2012. The dose was escalated from 160 mg/m 2 to 210 mg/m 2 then to 267 mg/m 2 . There were 2 DLTs in the 7 men receiving 267 mg/m 2 (grade 4 neutropenia), prompting de-escalation to 210 mg/m 2 where 1 of 8 men experienced a DLT (grade 4 neutropenic fever), establishing 210 mg/m 2 as the MTD. Significant non-hematologic toxicities included a case of grade 3 nausea. No cardiotoxicity was seen on serial evaluation and 6 patients completed 6 cycles. Internalization of AEZS-108 was consistently visualized in CTCs 1-3 hours after dosing. Maximal PSA response was stable or decreased in 8 of 18 men. Conclusions: The MTD of AEZS-108 in men with taxane-resistant CRPC is 210 mg/m 2 , which is below the MTD reported in women with refractory endometrial, ovarian and breast cancer. The activity of AEZS-108 was promising in this heavily pretreated population. The Phase II portion is currently accruing. Clinical trial information: NCT01240629.