tbuckley/cabot-search huggingface dataset:
PB2313 OCULAR MANIFESTATIONS OF SICKLE CELL DISEASE: A SINGLE CENTRE STUDY
Authors: C. Efobi, O. ejiofor, C. uzozie, A. onyiaorah
Journal: HemaSphere (2019)

Background: Sickle cell disease (SCD) is an inherited haemolytic disorder that affects virtually all body systems including the eye. Ocular complications of SCD could have dire consequences if not detected early. Aims: We aimed at determining the prevalence of ocular complications of SCD in our patients. Methods: This study was carried out on patients attending both the adult and Paediatric Sickle cell clinic at Chukwuemeka Odumegwu Ojukwu teaching Hospital, Akwa, Anambra State, Nigeria, over a 6 month period. A structured questionnaire was administered to consenting patients to determine their sociodemographic variables and other characteristics. Visual acuity was determined with multiple optotype Snellen's chart at 6 metres in natural daylight. Using pen‐torch, the face, external eye examination, anterior segment examination and pupillary reaction to light were assessed. Magnified anterior segment examination was performed with slit‐lamp biomicroscope. All subjects underwent dilated fundoscopy (after instillation of tropicamide 0.5% eye drop) using Welch Allyn indirect ophthalmoscope.Results were analysed using SPSS version 22.0 Inc Chicago Illinois and represented in tables. Statistically significant P value was set at &lt; 0.05 Results: A total of 28 patients with age range of 6‐42 years were seen. 17(60.7%) were males, while 11(39.3%) were females. 8(28.6%) had at least one ocular anomaly comprising of refractory errors 3(10.8%), sickle cell retinopathy 4(14.3%) and glaucoma 2(7.1%). Only 2(7.1%) routinely visit eye clinic. SCD retinopathy was found to increase with age (P value = 0.005) Summary/Conclusion: SCD retinopathy was found more in the older age group despite the small sample size at a prevalence rate of 14.3%. Early initiation of routine ocular examination for SCD patients will be beneficial to avert these complications. More efforts should be made at educating the patients. Larger studies will be required to determine the actual prevalence of ocular anomaly in SCD patients in Anambra State.
Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability
Authors: Lindsay F. Rizzardi, Peter F. Hickey, Varenka Rodriguez DiBlasi, Rakel Tryggvadóttir, Colin M. Callahan, Adrian Idrizi, Kasper D. Hansen, Andrew P. Feinberg
Journal: Nature Neuroscience (2019)
PB2419 PEPTIDE CORRECTION OF OSMOTIC RESISTANCE DISORDERS IN INFLAMMATION
Authors: M. Golubeva, B. Umarova, N. Bondarenko
Journal: HemaSphere (2019)

Background: The development of inflammation is accompanied by a change in the rheology of the blood ‐ an increase in viscosity, aggregation, a decrease in the osmotic resistance of red blood cells, which indicates a change in the structure of their membrane. This leads to a change in the functional properties of red blood cells and impaired microcirculation. The search for new anti‐inflammatory drugs, devoid of side effects is relevant. Promising may be endogenous regulatory peptides of the glyproline family, which have a prophylactic and therapeutic effect in various pathological conditions. Aims: The aim of this study was to investigate changes in the osmotic resistance of erythrocytes in the dynamics of experimental peritonitis with the introduction of the peptide Pro‐Gly‐Pro (PGP). Methods: A pro‐inflammatory agent was used to simulate experimental peritonitis ‐ 40% sodium thioglyaolate solution 4 g/kg, administered intraperitoneally. The erythrocyte osmotic resistance (ORE) was determined 30 minutes, 2 and 18 hours after the induction of inflammation. The evaluation of the wholesale electricity market was carried out to determine the degree of hemolysis in hypotonic solutions of sodium chloride. The light transmittance was recorded on a photoelectrocalorimeter at a wavelength of 580 nm. All experiments were performed in accordance with the ethical principles and regulatory documents recommended by the ESF and the declaration of a humane attitude towards animals. Results: The development of inflammation is accompanied by a decrease in the osmotic resistance of erythrocytes. Statistically significant differences in the wholesale electricity market from control were observed 2 hours after the administration of the thioglycolate. The introduction of PGP peptide at a dose of 3.7 μm/kg before the induction of inflammation reduced pathological changes in the ORE. The percentage of hemolyzed cells decreased, the differences were significant in solutions with salt content of 0.4% and 0.3%. The peptide, introduced against the background of developed inflammation (1 hour and 45 minutes after the introduction of thioglycolate) did not have a corrective effect on the ORE. Summary/Conclusion: The results indicate the ability of PGP to exert a preventive protective effect on the erythrocyte membrane, preventing a decrease in the ORE.
PET imaging of occult tumours by temporal integration of tumour-acidosis signals from pH-sensitive 64Cu-labelled polymers
Authors: Gang Huang, Tian Zhao, Chensu Wang, Kien Nham, Yahong Xiong, Xiaofei Gao, Yihui Wang, Guiyang Hao, Woo-Ping Ge, Xiankai Sun, Baran D. Sumer, Jinming Gao
Journal: Nature Biomedical Engineering (2019)
Analysis of Mir-7 (microRNA-7) Expression in Non-Hodgkin Lymphomas and Its Possible Role in the Regulation of the Transcription Factor KLF4 and YY1
Authors: Mario Morales-Martinez, Gabriel G Vega, Leticia Rocha-Zavaleta, Natividad Neri Munoz, M. J Nambo, Isabel Alvarado, Ivonne Cuadra, Otoniel Martinez-Maza, Sara Huerta-Yepez, Mario Vega
Journal: Blood (2017)
PB2318 DOUBLE HETEROZYGOSITY S/C AT HEMATOLOGY DEPARTMENT ANNABA HOSPITAL ‐ALGERIA
Authors: A. Djenouni, F. Grifi
Journal: HemaSphere (2019)

Background: Major sickle cell disorders account for 95% of the hemoglobinopathies supported at our service; double S/C heterozygosity is infrequent and represents only 6,4%. Aims: The objective of our work is to determine the prevalence and characteristics of acute and chronic complications that occurred in our patients during their follow‐up. Methods: This is a retrospective, descriptive study of 99 patients with double S / C heterozygosity and followed regularly since recruitment until December 2017. The patients benefit from a regular follow‐up, every 04 months with an annual report aimed at detecting the chronic complications. Results: The average age of patients at the time of diagnosis is 21 years, with extremes of [02‐49 years]. The current average age of the cohort is 33 years, with extremes of [13‐66 years] The majority of our patients come from Algerian‐Tunisian border area (79%). During this monitoring, several variously associated complications were collected: The acute complications are dominated by vaso‐occlusive crises in various locations, with exceptionnellent‐required hospitalization; During follow‐up, 32.09% of our patients developed various chronic complications: Summary/Conclusion: Despite of an acute symptomatology low noise from the S/C, chronic complications are frequent, imposing the implementation of a multidisciplinary management strategy at our level. image
Decreased Striatal Vesicular Monoamine Transporter Type 2 Correlates With the Nonmotor Symptoms in Parkinson Disease
Authors: Xinchong Shi, Yan Zhang, Shaohua Xu, Hank F. Kung, Hongwen Qiao, LuLu Jiang, Lin Zhu, Qiyi Guo, Chang Yi, Ganhua Luo, Lei Wu, Zhong Pei, Jian Wang, Xiangsong Zhang, Ling Chen
Journal: Clinical Nuclear Medicine (2019)

Objective Nonmotor symptoms (NMS) are critical players in the patients' quality of life in Parkinson disease (PD). Vesicular monoamine transporter type 2 (VMAT2) has been reported owing to a role in affecting dopamine neurons in the striatum. Therefore, this study set out to characterize the relationship between VMAT2 distribution in the striatum in relation to the NMS in PD. Methods Totally, 21 age-matched normal controls and 37 patients with PD in the moderate stages were included, followed by examination using 18 F-DTBZ ( 18 F-AV133) PET/CT. The specific uptake ratio (SUR) of each striatal subregion was then determined with the occipital cortex as the reference background region. The overall NMSs of each individual patient were evaluated. Finally, the role of the striatal SURs in the clinical symptom scores were evaluated through the application of a Spearman correlation analysis as well as a multivariable stepwise regression analysis. Results Patients with PD, particularly those at a more advanced stage, exhibited a more pronounced reduction in SURs in the bilateral putamen and caudate nucleus ( P &lt; 0.05, vs healthy controls). Meanwhile, patients at more advanced PD stages were found to have significantly worse scores in NMS except cognitive function. The Spearman correlation analysis demonstrated that NMS scores, with the exception of cognition scores, were correlated with striatal SURs ( P &lt; 0.05). Conclusion The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.
Early rise in blood pressure to predict clinical outcomes in metastatic colorectal cancer (mCRC) patients treated with first-line bevacizumab.
Authors: Nazeerahamad N. Upanal, Stephen P. Ackland, Antonino Bonaventura, Patrick McElduff
Journal: Journal of Clinical Oncology (2012)

e14166 Background: Bevacizumab (Bev) induced hypertension (HTN) may be a predictive biomarker of anti-tumor activity in patients with metastatic colorectal cancer (mCRC) . We retrospectively assessed if significant rise in blood pressure (SRBP) [ ≥ 20 mmHg ] or any grade of HTN within first 10 weeks of treatment with bev is associated with improved clinical outcomes. Methods: Retrospective review of all mCRC patients, on or off clinical trial, treated with first line chemotherapy plus Bev (5 mg/kg Q2W or 7.5 mg/kg Q3W) at our institution from 2005-2010 was conducted .BP was measured before each treatment and graded according to CTCAE version 3.0.The median follow-up time of eligible patients was 19.6 months. Results: Of 50 patients eligible for the analysis, 20 patients (40%) developed significant rise in BP or HTN (SRH) whereas 30 patients had no change (NRH). There were no statistical differences between the two groups with respect to age, gender, ECOG status, number of sites of metastases, pre-existing HTN (55% SRH,37% NRH ; P=0.251) and first line chemotherapy regimen. Chemotherapy regimens used in SRH and NRH groups were 5-Fluoropyrimidine based (25% vs 23.3%), irinotecan based (40% vs. 36.7%) and oxaliplatin based (35% vs 30%). Four patients (20%) in the SRH group developed SRBP and other patients in this group developed G1-G3 HTN according to CTCAE v3.0.SRH group had improved median progression free survival (15.8 vs 6.2 months ; p&lt;0.001) and overall survival (25.9 vs. 16 months; p=0.005). Overall response rate was higher in the SRH group (75% vs 26.7%; p=0.001). Conclusions: SRH developing within 10 weeks of commencing first line chemotherapy with bev correlates with improved outcomes in mCRC. These data need confirmation in prospective studies.
PB2133 IMPACT OF THE PRE‐TRANSPLANT INDUCTION (PTI) DURATION ON THE SURVIVAL OF PATIENTS WITH MULTIPLE MYELOMA (MM)
Authors: S. Pereira, L. M. Sarmento, M. Leal Fernandes, R. Brito, A. Monteiro, G. Ferreira, F. Costa, A. Botelho de Sousa
Journal: HemaSphere (2019)

Background: The first‐line strategy consensually accepted as the most effective in MM is a triplet PTI followed by autologous hematopoietic progenitor transplantation (AHPT). The proportion of patients eligible for AHPT has been steadily increasing as its safety and efficacy are documented in older patients. In this context, the duration of PTI gains relevance in real life: the standard recommendation of 3‐4 cycles is defined based on the unproven statement that a longer PTI may have negative effects on patient outcome, a conviction recently denied by the evidence published by Chakraborty et. al . (2018). Additionally, the possibility of prolonging PTI, although potentially associated with undesirable toxicity, may be beneficial in improving response depth prior to AHPT and sustain the response until transplantation is possible according to the transplantation center schedule. Aims: Evaluate the impact of PTI duration on the 3 month (mo)‐CR rate post‐AHPT, on median progression‐free survival (mPFS) and overall survival (OS) in MM patients transplanted at our center over a 12‐year period. Methods Data from 273 MM patients consecutively transplanted after PTI between September 2005 and March 2018 was collected. 104 patients were excluded from the analysis: 75 due to &gt; 12 mo interval from PTI beginning to AHTP, 10 due to &gt; 1 PTI line prior to AHPT and 19 due to missing data. Results: We analyzed 169 patients, median age 61 (30‐73), comparing those treated with PTI up to 4c (n = 70) with those subjected to &gt; 4c (n = 99). The proportion of patients with unfavorable ISS, high‐risk cytogenetics, or that received doublet PTI did not differ among the groups. With a median follow‐up of 40mo, the 3mo CR rate post‐AHPT was similar between the 2 groups (41 vs 51%, p = 0.2) as were the mPFS (37 vs 33mo, p = 0.3) and the 5y OS (68 vs 59%, p = 0.1). We also explored the influence of PTI duration in particular subpopulations: high‐risk cytogenetics; VGPR pre‐AHPT; or treated with doublet PTI (vs triplet). No significant differences were found, except for the mPFS in the subgroup treated with VCD (NA vs 27mo, p = 0.02). Summary/Conclusion: Our results suggest that a prolonged PTI beyond 4c does not improve post‐AHPT outcomes. These findings are similar to those of the Mayo Clinic study. Nevertheless, the conclusion we find most relevant is that a prolonged PTI, which may be required to deepen pre‐AHPT response or to sustain response up to transplantation, is not more deleterious in terms of PFS and OS.
Adeno-Associated Mediated Gene Transfer for Hemophilia B:8 Year Follow up and Impact of Removing "Empty Viral Particles" on Safety and Efficacy of Gene Transfer
Authors: Amit C Nathwani, Ulrike Reiss, Edward Tuddenham, Pratima Chowdary, Jenny McIntosh, Anne Riddell, Jun Pie, Johnny N Mahlangu, Michael Recht, Yu-Min Shen, Kathleen G. Halka, Michael M Meagher, Arthur W. Nienhuis, Andrew M. Davidoff, Sarah Mangles, Chris L Morton, Zhou Junfang, Vlad Calin Radulescu
Journal: Blood (2018)
Abstract 23080: Increased Pulmonary Peripheral (But Not Central) Blood Flow Correlates With Decreased Right Ventricular Volume in Acute Pulmonary Embolism Treated With Ultrasound-Facilitated, Catheter-Directed Fibrinolysis
Authors: Gregory PIAZZA, Farbod N Rahaghi, Samuel Z Goldhaber, Raul S Estepar, Jasleen Minhas, James Ross, George R Washko
Journal: Circulation (2017)

Introduction: Ultrasound-facilitated, catheter-directed fibrinolysis improves right ventricular (RV) function in patients with acute pulmonary embolism (PE). Resolution of central pulmonary arterial thrombotic obstruction has been hypothesized as the principal mechanism for RV recovery. Hypothesis: We postulated that improved peripheral blood flow rather than central blood flow correlates with reversal of RV enlargement due to PE. Methods: Using a 3-dimensional quantitative reconstruction technique that allows resolution of the distal pulmonary arteries, we analyzed the computed tomographic (CT) pulmonary angiograms of 60 submassive and massive PE patients treated with ultrasound-facilitated, catheter-directed, low-dose fibrinolysis. We correlated the change in blood volume of the pulmonary arteries (&lt;10 mm 2 vs. &gt;40 mm 2 cross sectional area) from baseline to 48 ± 6 hours with change in CT-measured RV volume. Results: Forty-five patients demonstrated reduction in RV volume (mean change was -31 ml). Increase in total lung blood volume/lung volume correlated with decreased RV volume/lung volume (R 2 = 0.26). RV volume-to-left ventricular volume ratio decreased by 26% ( Figure, Panel A ). Decreased RV volume correlated with increased blood volume through &lt;10 mm 2 pulmonary arteries (R 2 = 0.28) but not larger pulmonary arteries (&gt; 40 mm 2 ) (R 2 = 0.00003) ( Figure, Panel B1 and B2 ). Conclusion: Total lung blood volume increases following ultrasound-facilitated, catheter-directed fibrinolysis. Increased blood volume through the peripheral, but not central, pulmonary artery vasculature correlates with reduction in RV volume after ultrasound-facilitated catheter-directed fibrinolysis.
Abstract 13719: Delivery of microRNA-145 Restores Coronary Collateral Growth in Metabolic Syndrome Rats
Authors: Rebecca Hutcheson, Erika Smith, Alla Musiyenko, Petra Rocic
Journal: Circulation (2012)

In response to transient, repetitive coronary artery occlusion, small arterioles enlarge into conduit arteries by coronary collateral growth (CCG). In the early stages of CCG, vascular smooth muscl...
Disturbed Eating Behaviors in Adolescents and Emerging Adults With Type 1 Diabetes: A One-Year Prospective Study
Authors: Koen Luyckx, Margaux Verschueren, Nina Palmeroni, Eveline R. Goethals, Ilse Weets, Laurence Claes
Journal: Diabetes Care (2019)

OBJECTIVE Disturbed eating behavior (DEB) is prevalent in youth with type 1 diabetes and is accompanied by an increased risk for complications, morbidity, and mortality. Prospective studies on DEB in the challenging transition to adulthood are scarce. This longitudinal study examined DEB over a 1-year period and investigated the directionality of effects linking DEB to diabetes-specific functioning and depressive symptoms in adolescents and emerging adults. RESEARCH DESIGN AND METHODS Three hundred youth (16–28 years old) with type 1 diabetes participated in a two-wave longitudinal study. Questionnaires measured DEB (Diabetes Eating Problem Survey-Revised [DEPS-R]), self-management, diabetes distress, and depressive symptoms. HbA1c values were obtained from physicians. Mixed ANOVA and cross-lagged analysis were used to examine prospective changes and directionality of effects, respectively. RESULTS Mean DEB remained stable in the total sample, but significant individual differences were observed based on the cutoff score of the DEPS-R: 19% displayed persistent DEB and 8% increased and 7.3% decreased in DEB over time. The remaining individuals scored low on DEB over time. These four groups were differentiated based on insulin restriction, omission, diabetes-specific functioning, and depressive symptoms. Cross-lagged analyses indicated that DEB predicted relative increases in depressive symptoms over time, whereas reciprocal associations with glycemic control were found. CONCLUSIONS This longitudinal study highlights the substantial impact DEB may have in the transition to adulthood, with a substantial portion of youth with type 1 diabetes being at risk for clinical DEB. Prospective pathways linking DEB to functioning were found, emphasizing the clinical relevance of assessing DEB over time.
Response to: ‘SLE-DAS: ready for routine use’ by Mathew et al
Authors: Diogo Jesus, Ana Matos, Carla Henriques, Margherita Zen, Andrea Doria, Luís Sousa Inês
Journal: Annals of the Rheumatic Diseases (2019)

It was with great interest that we read the letter ‘SLE-DAS: Ready for routine use?’ by Mathew and coauthors.1 

Mathew et al commented on our recent article reporting the derivation and validation of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS),2 which demonstrated a much higher sensitivity to change of SLE disease activity, as compared with SLE Disease Activity Index 2000 (SLEDAI-2K).

Mathew et al ’s main concern is in regard of the SLE-DAS scoring of active lupus nephritis (LN). The SLE-DAS renal component is measured continuously, applying a logarithmic scale of proteinuria absolute value (to be scored only if above 500 mg/day and provided it is attributable to active LN). This is very different of the SLEDAI-2K renal component that comprises four dichotomous variables (proteinuria above 500 mg/day, pyuria, haematuria and urinary casts, each one scored solely as present or absent with a weight of 4 points if present and regardless of severity).3 

In the derivation of the SLE-DAS, we modelled the renal component using longitudinal data of real patients with active LN from a large, well-characterised tertiary lupus cohort.4 5 The SLE-DAS with its continuous scoring of the absolute value of proteinuria amends risks of major bias of SLEDAI-2K regarding renal involvement. In patients with active LN, the …
Regularized reconstruction of digital time-of-flight <sup>68</sup>Ga-PSMA-11 PET/CT for the detection of recurrent disease in prostate cancer patients
Authors: Elin Lindström, Irina Velikyan, Naresh Regula, Ali Alhuseinalkhudhur, Anders Sundin, Jens Sörensen, Mark Lubberink
Journal: Theranostics (2019)

Accurate localization of recurrent prostate cancer (PCa) is critical, especially if curative therapy is intended. With the aim to optimize target-to-background uptake ratio in 68Ga-PSMA-11 PET, we investigated the image quality and quantitative measures of regularized reconstruction by block-sequential regularized expectation maximization (BSREM). Methods: The study encompassed retrospective reconstruction and analysis of 20 digital time-of-flight (TOF) PET/CT examinations acquired 60 min post injection of 2 MBq/kg of 68Ga-PSMA-11 in PCa patients with biochemical relapse after primary treatment. Reconstruction by ordered-subsets expectation maximization (OSEM; 3 iterations, 16 subsets, 5 mm gaussian postprocessing filter) and BSREM (β-values of 100-1600) were used, both including TOF and point spread function (PSF) recovery. Background variability (BV) was measured by placing a spherical volume of interest in the right liver lobe and defined as the standard deviation divided by the mean standardized uptake value (SUV). The image quality was evaluated in terms of signal-to-noise ratio (SNR) and signal-to-background ratio (SBR), using SUVmax of the lesions. A visual assessment was performed by four observers. Results: OSEM reconstruction produced images with a BV of 15%, whereas BSREM with a β-value above 300 resulted in lower BVs than OSEM (36% with β 100, 8% with β 1300). Decreasing the acquisition duration from 2 to 1 and 0.5 min per bed position increased BV for both reconstruction methods, although BSREM with β-values equal to or higher than 800 and 1200, respectively, kept the BV below 15%. In comparison of BSREM with OSEM, the mean SNR improved by 25 to 66% with an increasing β-value in the range of 200-1300, whereas the mean SBR decreased with an increasing β-value, ranging from 0 to 125% with a β-value of 100 and 900, respectively. Decreased acquisition duration resulted in β-values of 800 to 1000 and 1200 to 1400 for 1 and 0.5 min per bed position, respectively, producing improved image quality measures compared with OSEM at a full acquisition duration of 2 min per bed position. The observer study showed a slight overall preference for BSREM β 900 although the interobserver variability was high. Conclusion: BSREM image reconstruction with β-values in the range of 400-900 resulted in lower BV and similar or improved SNR and SBR in comparison with OSEM.
Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection
Authors: Chen Yao, Hong-Wei Sun, Neal E. Lacey, Yun Ji, E. Ashley Moseman, Han-Yu Shih, Elisabeth F. Heuston, Martha Kirby, Stacie Anderson, Jun Cheng, Omar Khan, Robin Handon, Julie Reilley, Jessica Fioravanti, Jinhui Hu, Selamawit Gossa, E. John Wherry, Luca Gattinoni, Dorian B. McGavern, John J. O’Shea, Pamela L. Schwartzberg, Tuoqi Wu
Journal: Nature Immunology (2019)