tbuckley/cabot-search huggingface dataset:
Bazam: a rapid method for read extraction and realignment of high-throughput sequencing data
Authors: Simon P. Sadedin, Alicia Oshlack
Journal: Genome biology (2019)

The vast quantities of short-read sequencing data being generated are often exchanged and stored as aligned reads. However, aligned data becomes outdated as new reference genomes and alignment methods become available. Here we describe Bazam, a tool that efficiently extracts the original paired FASTQ from alignment files (BAM or CRAM format) in a format that directly allows efficient realignment. Bazam facilitates up to a 90% reduction in the time for realignment compared to standard methods. Bazam can support selective extraction of read pairs from focused genomic regions for applications such as targeted region analyses, quality control, structural variant calling, and alignment comparisons.
Characteristics, management and outcome of DLBCL patients, presenting with simultaneous systemic and CNS disease at diagnosis: A retrospective multicenter study
Authors: Chava Perry, Sharon Ben Barouch, Neta Goldschmidt, Nadav Sarid, Yair Herishanu, Lev Shvidel, Osnat Bairey, Noa Lavi, Netanel Horowitz, Avraham Avigdor, Eyal Lebel, Orit Sofer, Ron Ram, Irit Avivi
Journal: American Journal of Hematology (2019)

Abstract The incidence of systemic diffuse large B cell lymphoma (DLBCL) concurrently involving the central nervous system (CNS) at diagnosis, is very low and data regarding the clinical course of these patients are scarce. We investigated characteristics, efficacy of treatment regimens including consolidative autologous stem cell transplantation and outcome of patients presenting with concomitant systemic and CNS DLBCL. The records of 44 patients, diagnosed between 2004 and 2017, who fulfilled the inclusion criteria, were retrospectively reviewed. CNS involvement was diagnosed as solely parenchymal in 41%, solely leptomeningeal in 43%, and paranchymal with leptomeningeal in 11% of the patients. Induction regimens were anthracycline‐based combined with high‐dose methotrexate (HD‐MTX) in 80% (n = 35) of patients, anthracycline‐based combined with intrathecal MTX in 3, cytarabine‐based (without antracyclines) in 2, HD‐MTX in 1 and palliative in three. Five of 41 patients treated with chemotherapy died of treatment‐related toxicity, all due to infections. Nineteen patients had consolidative autologous transplantation. Overall response rate following induction was 80% (complete responses 66% and partial responses 15%). All relapses (n = 11) occurred within less than 2 years. Within a median follow‐up of 26.8 months, 3‐years projected overall survival (OS) and progression free survival rates for the entire cohort were 56% ± 8.3 and 42% ± 8.9, respectively. In multivariate analysis, RCHOP‐HD MTX‐based induction [HR = 0.228, (0.054‐0.964)], administration of 3.5 g/m 2 MTX [HR = 0.735 (0.620‐0.871)], and attaining CR following induction [HR = 0.185, (0.051‐0.667)] predicted longer OS. RCHOP‐HD MTX can provide prolonged remissions in DLBCL patients presenting with concomitant systemic and CNS involvement whereas role of autograft remains uncertain.
Abstract 13186: Factor XII Deletion Induces Diverse Phenotypes in Preclinical Inflammation Models
Authors: Eileen Bird, Mary Giancarli, Rongan Zhang, George Psaltis, Debra Search, Patricia Smith, Ricardo Garcia
Journal: Circulation (2013)

Factor XII (FXII) is a member of the intrinsic coagulation pathway and is thought to play key roles in hemostasis, inflammation and immune responses. FXII is implicated in activation of the kallikr...
Determination of cerebrospinal fluid leakage by selective deletion of transferrin glycoform using an immunochromatographic assay
Authors: Jusung Oh, Seok-Joon Kwon, Jonathan S. Dordick, William J. Sonstein, Robert J. Linhardt, Min-Gon Kim
Journal: Theranostics (2019)

Cerebrospinal fluid (CSF) leakage can lead to brain and spine pathologies and there is an urgent need for a rapid diagnostic method for determining CSF leakage.Beta-2 transferrin (β2TF), asialotransferrin, is a specific CSF glycoprotein biomarker used to determine CSF leakage when distinguished from serum sialotransferrin (sTF). Methods:We detected β2TF using an immunochromatographic assay (ICA), which can be potentially developed as a point-of-care (POC) testing platform.Sialic acid-specific lectin selectively captures sTF in multiple deletion lines within an ICA test strip, enabling the detection of β2TF.A sample pre-treatment process efficiently captures excess sTF increasing sensitivity for CSF leakage detection.Results: An optimal cut-off value for determining the presence of CSF in test samples was obtained from receiver operating characteristic (ROC) analysis of the ratio of the test signal intensity and the deletion lines.On 47 clinical samples, ICA test strips discriminated CSF positive from negative samples with statistically significant (positive versus negative t-test; P =0.00027).Additional artificial positive samples, prepared by mixing CSF positive and negative clinical samples, were used as a further challenge.These positive samples were clearly discriminated from the negative samples (mixture versus negative t-test; P =0.00103) and CSF leakage was determined with 97.1% specificity and 96.2% sensitivity.Conclusions: ICA represents a promising approach for POC diagnosis of CSF leakage.While requiring 70 min assay time inconvenient for POC testing, our method was significantly shorter than conventional electrophoresis-based detection methods for β2TF.
Macrophages are the primary effector cells in IL-7-induced arthritis
Authors: Seung-jae Kim, Huan J. Chang, Michael V. Volin, Sadiq Umar, Katrien Van Raemdonck, Aimee Chevalier, Karol Palasiewicz, John W. Christman, Suncica Volkov, Shiva Arami, Mehrdad Maz, Anjali Mehta, Ryan K. Zomorrodi, David A. Fox, Nadera Sweiss, Shiva Shahrara
Journal: Cellular and Molecular Immunology (2019)
Correction: Mutations in GDI1 are responsible for X-linked non-specific mental retardation
Authors: Patrizia D'Adamo, Andrea Menegon, Cristiana Lo Nigro, Marina Grasso, Massimo Gulisano, Filippo Tamanini, Thierry Bienvenu, Agi Gedeon, Ben Oostra, Shih-Kwang Wu, Anurag Tandon, Flavia Valtorta, William Balch, Jamel Chelly, Daniela Toniolo
Journal: Nature Genetics (1998)
PB2389 UNDERDOSING DEFERIPRONE IN TM: MYTH OR REALITY?
Authors: A. Spasiano, A. Meloni, L. Pistoia, G. Roccamo, F. V. Commendatore, S. Pulini, M. Benni, N. Dello Iacono, S. Campisi, M. Allò, A. Vallone, A. Riva, V. Positano, A. Pepe
Journal: HemaSphere (2019)

Background: Data from clinical practice show that some patients with thalassemia major (TM) received underdoses of deferiprone (DFP). Aims: This retrospective real‐life study aimed to investigate the reasons of the underdosing of DFP and to assess if the underdosing could result in an inadequate response. Methods: Among the 1746 TM patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network between 2006 and 2015, we selected the 171 consecutively patients (100 M and 71 F) patients who were treated with DFP dosages&lt;75 mg/Kg/day. Mean age at starting underdosed therapy was 30.95 ± 8.78 years. Heart and liver iron overload were measured by T2∗ Magnetic resonance imaging (MRI) technique. Results: Fifty‐four patients were treated with DFP in monotherapy (60.31 ± 12.82 mg/kg/die for 6.96 ± 0.19 days/week), 87 with combined DFP + deferoxamine (DFO) therapy (52.28 ± 21.29 mg/kg/die for 6.00 ± 1.43 days/week), and 30 with sequential DFO/DFP therapy (60.53 ± 9.75 mg/kg/die for 4.07 ± 0.69 days/week). Table 1 shows the motivations of underdosage, divided by chelation regimens. The most frequent motivation was the weight‐driven adjustment of the dosage, followed by the presence of low ferritin levels and side effects (gastric disturbances = 14/33 pts, increase of transaminases 6/33 pts and neutropenia 5/33). Sixty‐eight patients maintained the same chelation regimen (24 monotherapy, 27 combined and 17 sequential) during the execution of two consecutive MRI scans, performed in a time span of 18 months. At the first MRI 17 patients showed myocardial iron overload (MIO‐global heart T2∗ value&lt;20 ms). In this subgroup there was a significant increase of global heart T2∗ values (12.39 ± 3.77 ms vs 20.43 ± 10.71 ms; P = 0.002) and six (35.3%) patients reached a global heart T2∗ &gt; 20 ms at the second MRI. None of the 51 patients with a normal global heart T2∗ value at the first MRI showed MIO at the second MRI. In the 39 patients with hepatic iron overload (MRI liver iron concentration‐LIC≥3 mg/g dw) at the first MRI, there was not a significant decrease in LIC values, although 7 (17.9%) patients reached a normal value at the second MRI. Out of the 21 patients with a normal LIC value at the first MRI, 5 (17.2%) showed hepatic iron at the second MRI. Summary/Conclusion: In the real world the weight‐driven adjustment of the dosage, low ferritin levels and sides effects were the main causes of the DFP underdosage in TM. DFP dosages&lt;75 mg/Kg/day can be effective in improving myocardial siderosis but do not allow an improvement in terms of hepatic iron. image
Management of Stage II Germ Cell Tumors: Be Sure, Be Patient, Be Safe
Authors: Christian K. Kollmannsberger, Lucia Nappi, Craig Nichols
Journal: Journal of Clinical Oncology (2019)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A healthy 27-year-old man discovered a left testicular mass. Several months later he saw an urologist, who palpated a suspicious mass on the left testicle; an ultrasound confirmed a 2-cm solid mass. Serum tumor marker testing disclosed a slightly elevated alpha-fetoprotein (AFP) of 12.3 µg/L (upper limit of normal, 8.0 µg/L), and a normal β-human chorionic gonadotropin (HCG). Staging imaging with a contrast-enhanced computed tomography (CT) scan of the chest/abdomen/pelvis showed no evidence for retroperitoneal lymphadenopathy or distant metastases. He underwent a left radical orchiectomy, and pathology showed a 1.5-cm mixed germ cell tumor with 85% embryonal, 10% yolk sac tumor, and 5% mature teratoma histologies. Lymphovascular invasion was present. His AFP normalized after surgery. After discussion of management alternatives, he chose active surveillance, but 4 months later a scheduled surveillance CT scan identified a 1.4-cm left para-aortic lymph node just below the left renal hilum (Fig 1). Serum tumor markers remained negative. He returns to discuss his results and potential management options.
THU0344 A PILOT STUDY ASSESSING THE EFFECT OF AIR POLLUTION ON EXTRACELLULAR VESICLES IN SYSTEMIC SCLEROSIS
Authors: Tommaso Schioppo, Mirjam Hoxha, Simona Iodice, Laura Pergoli, Orazio De Lucia, Antonella Murgo, Luca Ferrari, Valentina Bollati, Francesca Ingegnoli
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is a severe autoimmune disease characterized by a progressive multi-organ fibrosis. The identification of specific diagnostic and prognostic biomarkers remains an unmet need. Over the past few years, it has been suggested that extracellular vescicles (EVs) and environmental toxicants, such as particulate matter (PM), may have an important role in the pathogenesis of autoimmune diseases. At present, no data are available on the impact of PM exposure on EVs from patients with SSc. <h3>Objectives</h3> Our aim was to evaluate the effects of PM with aerodynamic diameter ≤ 10 μm (PM<sub>10</sub>) and ≤ 2.5 μm (PM<sub>2.5</sub>) on EVs in SSc and osteoarthritis (OA) as control. <h3>Methods</h3> Plasma EVs were analyzed by Nanosight and flow cytometry after labeling with the following markers: CD14 (monocyte), CD61 (platelet), CD25 (T-reg), human endogenous retrovirus w (HERV-w), human leukocyte antigen G (HLA-G). Demographic and clinical data were collected for each patient. Plasma EV concentrations were measured in SSc and OA patients and were analyzed by generalized linear regression models. Daily PM concentrations, estimated by Regional Environmental Protection Agency at municipality resolution, were used to assign short-term exposure (mean of the 7 days preceding the evaluation) to each study subjects. <h3>Results</h3> 12 consecutive patients with limited cutaneous SSc (11 female, median age 66.8, median disease duration 12.3, 7 anti-centromere positive, median mRSS 3.5) and 12 patients with OA (median age 67.1, median disease duration 9.3, 8 female) were enrolled. The increase of PM<sub>2.5</sub> led to a decrease of HERV-w+ microvesicles (MV) in both SSc (β=-0. 10; p=0. 01) and OA (β=-0. 09; p=0. 01) and of HLA-G+ (β=-0.11; p&lt;0. 01) only in SSc. Similar results were observed analyzing PM<sub>10</sub> exposure. Analysis of EVs concentration according to their dimensions showed a negative association in the size range of exosomes (63-92nm) in SSc compared to OA (p&lt;0. 05) and in the range of MV (230-510 nm) (figure below). Finally, we observed a positive association between HLA-G+ with Erythrocyte Sedimentation Rate (ESR) (β=0.34; p&lt;0.01). <h3>Conclusion</h3> In our study, limited cutaneous SSc showed different EVs concentrations from controls: SSc tends to have less exosomes and more MV than OA. Moreover, environmental stimuli (<i>e.g.</i> PM exposure) are confirmed to be able to influence HERV-w+ MV release both in SSc and controls. Finally, in SSc patients PM exposure could significantly alter the release of HLA-G+ MV that has been correlated to the process of self-tolerance maintenance. Further studies are required to fully unlock the role of PM and EVs in SSc. <h3>Disclosure of Interests</h3> None declared
PB2257 USE OF ARGATROBAN AS AN ANTICOAGULANT TREATMENT ALTERNATIVE IN CRITICAL PATIENTS WITH HEPARIN‐INDUCED THROMBOCYTOPENIA. EXPERIENCE IN A THIRD LEVEL HOSPITAL.
Authors: E. Salvador, M. Villalba, A. García, S. Pinzón, N. Fernández, J. M. Calvo, P. Delgado
Journal: HemaSphere (2019)

Background: Heparin is a widely used drug. The most frequent complication derived from its use is the haemorrhage. However, an uncommon but potentially serious adverse effect is heparin‐induced thrombocytopenia (HIT). The goal of treatment of HIT is to reduce platelet activation and thrombin formation to decrease the risk of thrombosis. Argatroban is the drug of choice in HIT patients as an alternative anticoagulant treatment in critically ill patients with high risk of haemorrhage, postoperative cardiac events or renal failure, since it allows close control of anticoagulation. Aims: To analyze the clinical, laboratory and therapeutic characteristics of patients treated with Argatroban by HIT in our hospital Methods: Retrospective analysis or patients treated with Argatroban for diagnosed HIT during the last year. Results: Four patients have required treatment with Argatroban for HIT since they required maintenance of anticoagulation due to mitral prosthesis, unstable angina, DVT in the right lower extremity and acute ischemia in the left lower extremity. Median age 68 years (43‐79). All of them were diagnosed with HIT according to the 4T score during their admission to the Intensive Care Unit. PF4/Heparin antibody testing was positive in the four patients. The median number of days from the start of Heparin treatment (2 with unfractioned and 2 with low molecular weight) to the onset of thrombocytopenia was 6 days (1‐8). Median platelets at diagnosis were 73x10 9 /L (49‐82). Median number of days from the start of Argatroban to platelet recovery was 6 days (3‐12). Median number of days of treatment with Argatroban was 9.5 days (2‐18). Argatroban dose was adjusted to maintain aPTT at 1.5‐3.0 times baseline. 3 patients presented thrombotic events, 2 directly related to HIT (1 ischemic stroke and 1 acute ischemia of right upper extremity) and 1 with worsening of reperfusion of the limb. 2 patients required amputation of the limb. No adverse events associated with Argatroban, including haemorrhage, were observed. Summary/Conclusion: HIT is a potentially catastrophic complication of heparin treatment which requires urgent detection and treatment with a non‐heparin anticoagulant such as Argatroban should be initiated. Even in critically ill patients, Argatroban anticoagulation improves clinical outcomes in patients who have HIT, without increasing bleeding risk.
WHO drops opioid guidelines after criticism of corporate influence
Authors: Owen Dyer
Journal: BMJ (2019)

The World Health Organization is discarding two opioid guidelines after a report by two members of the US Congress alleged that they were tainted by opioid manufacturers.

The bipartisan report accused the opioid manufacturer Purdue Pharma of working, through its international arm Mundipharma, to expand the indications for chronic opioid use and minimise concerns about risks of addiction.1

Mundipharma paid physician opinion leaders and sponsored “astroturf” patients’ groups (set up by industry bodies) to demand easier access to opioids for pain treatment, the report alleged. Purdue Pharma faces extensive legal action in the US, where it has often been accused of leading a campaign to normalise opioid use.2

WHO responded by saying that …
FRI0206 HYDROXYCHLOROQUINE BLOOD LEVELS PREDICT RETINOPATHY IN SLE
Authors: Michelle A. Petri, LI Jessica, Marwa Elkhalifa, Daniel Goldman, Laurence Magder
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Hydroxychloroquine (HCQ) retinopathy after 10 years or more of use is more frequent than previously appreciated. This led to new ophthalmology guidelines that changed the recommended dosing from 6.5 mg/kg to 5 mg/kg (1). However, it is not clear that the lower dose of hydroxychloroquine will have the same efficacy for SLE activity or the same protective role against cardiovascular risk factors and thrombosis. <h3>Objectives:</h3> We asked whether hydroxychloroquine blood levels could help identify those at greater future risk of retinopathy. <h3>Methods:</h3> We analyzed data on 537 SLE patients from a clinical cohort who had repeated assessments of HCQ blood concentrations, and were evaluated one or more times for retinopathy (300 single retinopathy exam, 149 two and 88 three or more assessments). The patients were 92% female and 42% Caucasian. Hydroxychloroquine blood levels were performed as previously described. In our analysis, HCQ toxicity was defined dichotomously by a retina expert: all those with a value of "No" or "Possible" were categorized as not having HCQ toxicity, and those who had a "Yes" were categorized as having it. Mean and maximum HCQ blood concentration over all cohort visits prior to the final retinopathy assessment were calculated. Risk of HCQ toxicity was then assessed in tertiles defined by these variables. <h3>Results:</h3> <h3>Conclusion:</h3> Our data show that the risk of HCQ retinopathy is higher in men and Caucasians. As expected, it is higher in older patients and with greater duration. We also found that BMI and hypertension were predictive of HCQ retinopathy. For the first time, our data show the utility of HCQ blood levels in predicting retinopathy. This would allow clinicians to either decrease dose or increase monitoring in those with high blood levels. <h3>References:</h3> [1] Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016;123:1386–1394. <h3>Acknowledgement:</h3> The Hopkins Lupus Cohort was funded by NIH Grant R01-AR069572 <h3>Disclosure of Interests:</h3> Michelle A Petri Shareholder of: Pfizer, Merck, Grant/research support from: AstraZeneca, Exagen, Consultant for: Eli Lilly, GSK, Merck EMD Serono, Janssen, Amgen, Novartis, Quintiles, Exagen, Inova Diagnostics, AstraZeneca, Blackrock, Glenmark, UCB, and the Annenberg Center for Health Sciences, Jessica Li: None declared, Marwa Elkhalifa: None declared, Daniel Goldman Shareholder of: Pfizer, Merck, Laurence Magder: None declared
Clust: automatic extraction of optimal co-expressed gene clusters from gene expression data
Authors: Basel Abu-Jamous, Steven Kelly
Journal: Genome biology (2018)

Identifying co-expressed gene clusters can provide evidence for genetic or physical interactions. Thus, co-expression clustering is a routine step in large-scale analyses of gene expression data. We show that commonly used clustering methods produce results that substantially disagree and that do not match the biological expectations of co-expressed gene clusters. We present clust, a method that solves these problems by extracting clusters matching the biological expectations of co-expressed genes and outperforms widely used methods. Additionally, clust can simultaneously cluster multiple datasets, enabling users to leverage the large quantity of public expression data for novel comparative analysis. Clust is available at https://github.com/BaselAbujamous/clust .
Abstract 15929: Cardiosphere-derived Cells From Young Rats Improve Diastolic Function, Exercise Capacity and Age-associated Biomarkers in Senescent Rats
Authors: Lilian Grigorian, Soraya Fereydooni, Weixin Liu, Ryan Middleton, Jae-Hyung Cho, Jackelyn Valle, Antonio Echavez, Eduardo Marbán
Journal: Circulation (2016)

Introduction: Aging is associated with diastolic dysfunction and global functional impairment. Despite its increasing prevalence, age-related diastolic heart failure is refractory to conventional t...
QsRNA-seq: a method for high-throughput profiling and quantifying small RNAs
Authors: Alla Fishman, Dean Light, Ayelet T. Lamm
Journal: Genome biology (2018)

The ability to profile and quantify small non-coding RNAs (sRNAs), specifically microRNAs (miRNAs), using high-throughput sequencing is challenging because of their small size. We developed QsRNA-seq, a method for preparation of sRNA libraries for high-throughput sequencing that overcomes this difficulty by enabling a gel-free separation of fragments shorter than 100 nt that differ only by 20 nt in length. The method allows the use of unique molecular identifiers for quantification and is more amenable to automation than gel-based methods. We show that QsRNA-seq gives very accurate, comprehensive, and reproducible results by looking at miRNAs in Caenorhabditis elegans embryos and larvae.
Small RNAs Reflect Grandparental Environments in Apomictic Dandelion
Authors: Lionel Morgado, Veronica Preite, Carla Oplaat, Sarit Anava, Julie Ferreira de Carvalho, Oded Rechavi, Frank Johannes, Koen J.F. Verhoeven
Journal: Molecular Biology and Evolution (2017)

Plants can show long-term effects of environmental stresses and in some cases a stress "memory" has been reported to persist across generations, potentially mediated by epigenetic mechanisms. However, few documented cases exist of transgenerational effects that persist for multiple generations and it remains unclear if or how epigenetic mechanisms are involved. Here, we show that the composition of small regulatory RNAs in apomictic dandelion lineages reveals a footprint of drought stress and salicylic acid treatment experienced two generations ago. Overall proportions of 21 and 24 nt RNA pools were shifted due to grandparental treatments. While individual genes did not show strong up- or downregulation of associated sRNAs, the subset of genes that showed the strongest shifts in sRNA abundance was significantly enriched for several GO terms including stress-specific functions. This suggests that a stress-induced signal was transmitted across multiple unexposed generations leading to persistent changes in epigenetic gene regulation.