tbuckley/cabot-search huggingface dataset:
Pollutants and Insecticides Drive Local Adaptation in African Malaria Mosquitoes
Authors: Colince Kamdem, Caroline Fouet, Stephanie Gamez, Bradley J. White
Journal: Molecular Biology and Evolution (2017)

The Anopheles gambiae complex contains a number of highly anthropophilic mosquito species that have acquired exceptional ability to thrive in complex human habitats. Thus, examining the evolutionary history of this Afrotropical mosquito may yield vital information on the selective processes that occurred during the adaptation to human-dominated environments. We performed reduced representation sequencing on 941 mosquitoes of the Anopheles gambiae complex collected across four ecogeographic zones in Cameroon. We find evidence for genetic and geographic subdivision within An. coluzzii and An. gambiae sensu stricto—the two most significant malaria vectors in the region. Importantly, in both species, rural and urban populations are genetically differentiated. Genome scans reveal pervasive signatures of selection centered on genes involved in xenobiotic resistance. Notably, a selective sweep containing detoxification enzymes is prominent in urban mosquitoes that exploit polluted breeding sites. Overall, our study suggests that recent anthropogenic environmental modifications and widespread use of insecticides are driving population differentiation and local adaptation in vectors with potentially significant consequences for malaria epidemiology.
A one-step specific assay for continuous detection of sirtuin 2 activity
Authors: Qi Dai, Zhihua Zheng, Fan Xia, Peiqing Liu, Min Li
Journal: Acta Pharmaceutica Sinica B (2019)

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases with diverse physiological functions. A variety of small molecules have been developed to interrogate the physiological function of SIRTs. Therefore, it is desirable to establish efficient and convenient assays to screen SIRTs modulators. In this study, we designed a series of fluorescent nonapeptide probes derived from substrates of SIRT1-SIRT3. Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore, which makes this system free of lysine-recognizing protease. Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1-SIRT3 and SIRT6, it was confirmed that this assessment system was the most suitable for SIRT2 activity detection. Thus, SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide. Finally, two specific and efficient fluorescent probes for SIRT2, ne-D9 and ne-K4a, were developed. Evaluation of the results revealed that ne-K4a based assay was more suitable for modulators screening in vitro, while the other specific substrate ne-D9 was stable in cell lysate and could detect the activity of SIRT2 in the same. In summary, this study presents a novel strategy for detecting SIRT2 activity in vitro and in cell lysate.
Abstract 17603: Optimal Biomarkers for Predicting Incident Coronary Events in Patients With Established Coronary Artery Diseases
Authors: Yuen Kwun Wong, Chole Y Cheung, Ka Wing Au, Sherry Hong, Chi Ho Lee, Jo Jo S Hai, Kui Kai Lau, Tai Hing Lam, Pak Chung Sham, Aimin Xu, Karen S Lam, Hung Fat Tse
Journal: Circulation (2016)

Background: Numerous biomarkers have been proposed as potential risk markers for cardiovascular disease (CVD), nevertheless, there is no data on head-to-head comparison among them, and whether the ...
Abstract 39: Adequate Tidal Volumes and Improved Survival With Continuous Chest Compressions and Synchronized Ventilation (10:1)
Authors: Daniel Davis, Rebecca Sell, Anush Minokadeh, James Dunford
Journal: Circulation (2010)

Background: Compression pauses are recommended with non-invasive ventilation during cardiac arrest to allow adequate tidal volume (VT) and minimize gastric insufflation. These pauses are associated...
AB1303 FUNCTIONAL AND PROFESSIONAL OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Soumaya Boussaid, Takoua Aissaoui, Sonia Rekik, Samia Jemmali, Houda Ajlani, Hela Sahli, Elhem Cheour, Mohamed El Euch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatism in adults. It affects the synovial membrane, evolves by outbreaks and can lead to joint destruction. It generates a physical disability that causes an impairment of quality of life and professional activity. <h3>Objectives:</h3> To study the socio-demographic, clinical and professional characteristics of patients and to assess the impact of RA on quality of life and professional activity. <h3>Methods:</h3> We conducted a retrospective, descriptive study on patients' files, followed at the rheumatology department of LA RABTA university hospital, for RA aver a period of ten years. The target population was patients having a professional activity at the time of the discovery of the disease. We assessed disease activity by the Disease Activity Score DAS28-CRP, work impact by the "Work Productivity and Activity Impairment" questionnaire (WPAI:RA) and quality of life by the Health Assessment Questionnaire (HAQ). The data was entered into an excel table and analyzed using SPSS software version 19.0. In all statistical tests, the significance level was set at 0.05. <h3>Results:</h3> We collected 25 cases of RA. Mean age was 50.36 ± 8.28 years with a sex ratio of 1.08. The mean age of RA was 9.8 years and the mean age of onset was 40.56 ± 9.84 years. The study population occupied a manual job in 84% of cases. The average professional seniority was 21.76 ± 12.83 years. Patients reported having stopped work because of their illness in 44% of cases. The mean of DAS28-CRP was 4.32 ± 1.57, 72% of the study population had moderate to severe RA activity. The mean HAQ was 1.38 ± 0.69 with 76% of cases suffering from "moderate to severe" or "severe to very severe disability". The evaluation of the work productivity and activity impairment by the WPAI:RA questionnaire objectified an absenteeism of 30.7 ± 9.4%, a presenteeism of 46.7 ± 26.4%, a work productivity loss of 60.4 ± 33.8% and an activity impairment of 57.2 ± 25.4%. A positive and statistically significant correlation was noted between the results of WPAI and HAQ, between the results of WPAI (except absenteeism) and DAS286CRP and between HAQ and DAS28-CRP. <h3>Conclusion:</h3> RA causes a significant functional disability that affects the professional activity and quality of life of patients. Early diagnosis and treatment of this disease can slow the progression o the disease. Occupational medicine plays an important role in the early detection and maintenance of employees with RA at work. <h3>Disclosure of Interests:</h3> None declared
PB1966 HYPERVITAMINOSIS B12 MEDIATED BY INMUNE COMPLEXES IN PATIENTS WITH VITAMIN B12 DEFIENCY, VALUE OF HOMOCYSTEIN AND METHYLMALONIC ACID ASSESSMENT
Authors: Campo M.A. Legarda, S. Payán-Pernía, J. Sánchez García, A. Pérez Cases, N. Cerdá Gordillo, M.P. Sardá, E. Zapico, A.F. Remacha Sevilla
Journal: HemaSphere (2019)

Background: Although high serum levels of vitamin B12 (B12) are most frequently due to supplementation, they have also been related to multiple conditions such as hematological malignancies, solid tumours, renal failure or liver disease. However, it has been described that some patients have spurious high B12 levels due to the presence of immune complexes that interfere with immunoassays. Aims: To evaluate the possibility of B12 deficiency in patients with high B12 levels due to immune complexes. Methods: A retrospective search covering 24 months was conducted. High serum B12 levels were defined as levels above our reference range: 150-650 pmol/L. Incubation with polyethylene glycol (PEG) was used to evaluate the presence of spurious high B12 levels due to immune complexes, as we previously described1. Existence of immune complexes was assumed in those cases with high serum B12 levels and a subsequent threefold decreased after incubation with PEG. B12 metabolites homocysteine (HCY) and methylmalonic acid (MMA) were evaluated to rule out a B12 deficiency. Results: Incubation with PEG was conducted in 196 patients. A threefold or greater decrease was observed in 57 (29%) cases. HCY was assessed in 19 of them and MMA, in 9 (table 1). HCY was high (>15,5 μmol) in 5 patients, high levels of MMA (>0,4 μmol/L) was associated in 3 of them. One additional patient had normal HCY levels but increased MMA levels. None of these patients had a folate deficiency, although 2 of them had a renal failure that may explain the HCY and MMA results.Summary/Conclusion: There may be a vitamin B12 deficiency even when serum levels are high. Such discordance may be due to immune complexes producing a false negative result. Our study suggests that metabolites assessment should be considered in all cases with vitamin B12-PEG <300 pmol/L.
Oral Ulcer—A Disabling Manifestation in a Patient With Lipoid Proteinosis
Authors: Javier Sabater-Abad, María Matellanes-Palacios, Virginia Pont-Sanjuan, Javier Miquel-Miquel, Pedro Navarro-Conde, Enrique Gimeno-Carpio
Journal: JAMA Dermatology (2019)

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Ultra-deep amplicon sequencing to identify actionable mutations in matched plasma/tumor specimens from 44 patients with colorectal cancer of UICC stage III and IV.
Authors: Paulina Pechanska, Matthias Pross, Cornelia Radke, Frank Marusch, Hartmut Lobeck, Joerg Bunse, Gerald Niedobitek, Rene Mantke, Roland Pauli, Jörg Pertschy, Hartwig Kosmehl, Steffen Weise, Cornelia Tennstedt-Schenk, Bernd Hinzmann, Hans-Peter Adams, Andre Rosenthal
Journal: Journal of Clinical Oncology (2013)

3634 Background: Circulating cell-free DNA (cf-DNA) isolated from plasma samples of cancer patients (pts) is a promising source for noninvasive examination of tumor-specific mutation patterns. We examined the efficiency of ultra-deep amplicon sequencing (UDAS) of cf-DNA isolated from plasma and tumor DNA isolated from matched primary tumor tissue of pts with colorectal cancer (CRC). Methods: Blood was drawn prior to surgery from 44 pts: 20 male, 24 female; 44-79 years of age (median: 67.5); 11 stage III, 33 stage IV; 36 colon, 8 rectum tumors; no neo-adjuvant therapy. Cf-DNA was isolated from 2 ml of EDTA plasma. UDAS was applied to 72 DNA samples (44 plasma, 28 matched snap-frozen primary tumors) using the MiSeq platform (Illumina). A panel of 49 highly multiplexed amplicons was designed (Life Technologies) representing 9 cancer genes frequently mutated in CRC. For 16 primary tumors the mutation profile was determined using the TruSeq Amplicon Cancer Panel (Illumina). Results: Median cf-DNA yield was 310 ng / 2 ml plasma (1ng – 6.600 ng). There was no significant relation between cf-DNA yield and any clinical characteristic. Median amplicon coverage was 20.162 reads per bp (2.913 - 115.782). 33/49 amplicons (67%) had a coverage of &gt; 10.000 reads. Altogether 61 high quality COSMIC-cited mutations were confirmed in plasma of 29/44 (66%) pts: 24/33 (73%) pts in stage IV, 5/11 (45%) pts in stage III. Confirmed mutations are: APC-17; BRAF-2, FBXW7-1, KRAS-15, NRAS-1, PIK3CA-4, SMAD4-2, and TP53-19 mutations. No high quality mutations were found in CTNNB1 and HRAS. Moreover two pts exhibited four high quality plasma mutations which were not detected in the matched primary tumor: APC (R216X), KRAS (Q61K), and SMAD4 (D355E); PIK3CA (E545K). Conclusions: Ultra deep amplicon sequencing is suitable to detect mutations in plasma samples of CRC pts with a high concordance to matched primary tumors. The concordance rate can be further increased by extending the spectrum of analyzed mutations or by the enrichment of cf-DNA tumor copies. This method could be applied to detect and monitor metastasis thus opening a new paradigm for the selection of pts for targeted therapies.
THU0485 EFFICACY OF EXTRACORPOREAL SHOCK-WAVE THERAPY IN THE TREATMENT OF SHOULDER CALCIFIC TENDINITIS IN INSUFFICIENT RESPONDERS TO LOCAL STEROID INJECTION THERAPY: A RETROSPECTIVE ANALYSIS
Authors: Meryem Yilmaz Kaysin, Feyza Unlu Ozkan, Aktas Ilknur, Pinar Akpinar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Calcific tendinitis (CT) results from the deposition of calcium hydroxyapatite crystals in periarticular muscular attachments, and most commonly affects the tendons of the shoulder (1). Extracorporeal shock wave therapy (ESWT) is based on the use of shock waves, and used for pain reduction and tissue healing (2). <h3>Objectives:</h3> The aim of this analysis is to demonstrate the effects of ESWT in patients with shoulder CT with inefficient response to local steroid injection. <h3>Methods:</h3> 2-year data of shoulder outpatient clinic were scanned. 10 patients with shoulder calcific tendinitis without satisfying response to local steroid injection (less than 50% decrease in pain-visual analogue scale (VAS) score) who were treated with ESWT were reviewed. <h3>Results:</h3> 10 patients (9 women, 1 man) fulfilled the inclusion criteria. The mean patient age was 51.3 years (range, 32-70 years) and body mass index was 26.2 kg/m2. The affected shoulder was left in 6 (60%) patients and right in 4 (40%). The calcific tendinitis involved the dominant side in 5 (50%) patients and non-dominant side in other 5 (50%). All patients had one peritendinous local steroid injection-2 ml 2% prilocain and 1 ml steroid (5 mg of betamethasone dipropionate &amp;plus; 2 mg betamethasone sodium phosphate). Mean time from symptom onset to the ESWT treatment was 3.5 weeks (range, 2-6 weeks). Mean VAS score was 9 and Shoulder Disability Index (SDI) score was 84.4 before ESWT treatment. ESWT system Elmed-Vibrolith ver.3.0 was used in the treatments, each treatment consisted 2000 shocks with a frequency of 150 shocks a minute with maximum tolerable energy density (range, 3.2-3.4 bar). Mean ESWT session was 3.3 (8 patients had 3, 1 patient had 4 and 1 patient had 5 sessions of treatment). Mean post-treatment VAS score was 4.2 (53.3% decrease) and SDI score was 43.8 (48.1% decrease) which were evaluated after the last ESWT session. <h3>Conclusion:</h3> With its good tolerance and safety, ESWT might be an alternative treatment method for calcific tendinitis of the shoulder. Although limited number of patients, we hope that this study might give rise to future randomized-controlled studies about the efficacy of ESWT in acute-subacute shoulder calcific tendinitis. <h3>References:</h3> [1] Holt, P. D., &amp; Keats, T. E. (1993). Calcific tendinitis: a review of the usual and unusual. Skeletal radiology, 22(1), 1-9.&nbsp; [2] Cosentino, R., Selvi, E., De Stefano, R., Frati, E., Manca, S., Hammoud, M., &amp; Marcolongo, R. (2004). Extracorporeal shock wave therapy for chronic calcific tendinitis of the shoulder. Clinical rheumatology, 23(5), 475-477. <h3>Disclosure of Interests:</h3> None declared
Abstract 15262: Antiplatelet Activity and Clinical Outcomes on CYP3A4-metabolized Statin in Percutaneous Coronary Intervention
Authors: Jin sup Park, Kwang Soo Cha, Jong Hyun Choi, Bowon Kim, Hye Won Lee, Jun-Hyok Oh, Han Cheol Lee, Taek Jong Hong, Hyo-Soo Kim
Journal: Circulation (2015)

Introduction: Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel metabolism to active metabolite. Recent studies suggest that CYP 3A4-metabolized statins attenuate the anti-aggregatory effect of clopidogrel. Hypothesis: We sought to assess the antiplatelet activity of a CYP 3A4 metabolized statin and its association with clinical outcomes during dual antiplatelet therapy following percutaneous coronary intervention (PCI). Methods: Among 3,755 patients enrolled the HOST-ASSURE trial, 1,187 patients with both baseline and 1-month platelet reactivity unit (PRU) values assessed by VerifyNow P2Y12 assay were assigned to the CYP 3A4-metabolized statin group (n=725) or non-CYP 3A4-metabolized statin group (n=462) according to type of statins used. The co-primary outcome were the differences between baseline and 1-month follow-up of PRU value and the composite of cardiovascular death, recurrent MI, including stent thrombosis, any revascularization and cerebrovascular accident (CVA) during the follow-up period. We compared the outcomes between groups both in the propensity adjusted and matched cohorts. Results: Mean difference of PRU values was not significant in the CYP 3A4-metabolized statin group (mean difference: -4±84, p=0.367) and was significant in the non-CYP 3A4-metabolized statin group (mean difference: -12±69, p=0.006) both in the propensity score adjusted and matched cohorts. Patients with high PRU value at baseline, irrespective of the type of used statins, were associated with a significant reduction in mean difference of PRU values both in the propensity score adjusted (mean difference: -53.35, p&lt;0.001) and matched cohort (mean difference: -41.57, p&lt;0.001). The composite of clinical events did not differ between groups both in the propensity score adjusted (hazard ratio [HR] 0.962, 95% confidence interval [CI] 0.621-1.489, p=0.861) and matched (HR 0.902, 95% CI 0.554-1.468, p=0.678) cohorts. Conclusions: This study showed that a CYP 3A4-metabolized statin slightly reduces antiplatelet activity of clopidogrel during dual antiplatelet therapy but did not increase clinical events in patients following PCI.
Targeting mitochondrial dynamics by regulating Mfn2 for therapeutic intervention in diabetic cardiomyopathy
Authors: Lang Hu, Mingge Ding, Daishi Tang, Erhe Gao, Congye Li, Kaiyan Wang, Bingchao Qi, Jihuan Qiu, Huishou Zhao, Pan Chang, Feng Fu, Yan Li
Journal: Theranostics (2019)

Increasing evidence has implicated the important role of mitochondrial pathology in diabetic cardiomyopathy (DCM), while the underlying mechanism remains largely unclear. The aim of this study was to investigate the role of mitochondrial dynamics in the pathogenesis of DCM and its underlying mechanisms. Methods: Obese diabetic (db/db) and lean control (db/+) mice were used in this study. Mitochondrial dynamics were analyzed by transmission electron microscopy in vivo and by confocal microscopy in vitro. Results: Diabetic hearts from 12-week-old db/db mice showed excessive mitochondrial fission and significant reduced expression of Mfn2, while there was no significant alteration or slight change in the expression of other dynamic-related proteins. Reconstitution of Mfn2 in diabetic hearts inhibited mitochondrial fission and prevented the progression of DCM. In an in-vitro study, cardiomyocytes cultured in high-glucose and high-fat (HG/HF) medium showed excessive mitochondrial fission and decreased Mfn2 expression. Reconstitution of Mfn2 restored mitochondrial membrane potential, suppressed mitochondrial oxidative stress and improved mitochondrial function in HG/HF-treated cardiomyocytes through promoting mitochondrial fusion. In addition, the down-regulation of Mfn2 expression in HG/HF-treated cardiomyocytes was induced by reduced expression of PPARα, which positively regulated the expression of Mfn2 by directly binding to its promoter. Conclusion: Our study provides the first evidence that imbalanced mitochondrial dynamics induced by down-regulated Mfn2 contributes to the development of DCM. Targeting mitochondrial dynamics by regulating Mfn2 might be a potential therapeutic strategy for DCM.
Cognitive Decline Before and After Incident Coronary Events
Authors: Wuxiang Xie, Fanfan Zheng, Li Yan, Baoliang Zhong
Journal: Journal of the American College of Cardiology (2019)

Previous studies have suggested that coronary heart disease (CHD) may be associated with accelerated cognitive decline. However, the temporal pattern of cognitive decline before and after incident CHD remains largely unknown. The purpose of this study was to determine the cognitive trajectory before and after incident CHD diagnosis in a national representative cohort age ≥50 years. This study included 7,888 participants (mean age 62.1 ± 10.2 years) with no history of stroke or incident stroke during follow-up from the English Longitudinal Study of Ageing. Participants underwent a cognitive assessment at baseline (wave 1, 2002 to 2003), and at least 1 other time point (from wave 2 [2004 to 2005] to wave 8 [2016 to 2017]). Incident CHD was identified as a diagnosis of myocardial infarction and/or angina during follow-up. Incident CHD was associated with accelerated cognitive decline during a median follow-up of 12 years. The annual rate of cognitive decline before CHD diagnosis among individuals who experienced incident CHD was similar to that of participants who remained CHD-free throughout follow-up. No short-term cognitive decline was observed in participants with CHD diagnosis after the event. In the years following CHD diagnosis, global cognition, verbal memory, and temporal orientation scores declined significantly faster than they did before the event, after multivariable adjustment. Sensitivity analyses yielded similar results. Incident CHD is associated with accelerated cognitive decline after, but not before, the event. Attention should be drawn to the long-term cognitive deterioration related to CHD. Careful monitoring of cognitive function is warranted in CHD patients in the years following the event.