bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2216 ARTERIAL AND VENOUS THROMBOSIS IN TREATED PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS
Authors: Boban A. , Perić M. Morić , Zekanović I. , Horvat I. , Antolić M. Radić , Rončević P. , Zupančić‐Šalek S. , Serventi‐Seiwerth R. , Kinda S. Bašić , Vrhovac R. , Duraković N. , Perić Z. , Sertić D. , Mikulić M. , Pulanić D. , Aurer I. 
Published: June 2019

Background:Cardiovascular and thromboembolic events are the leading causes of morbidity and mortality for patients with myeloproliferative disorders (MPN).Aims:This retrospective study aimed to evaluate the incidence and the risk factors for the arterial and venous thrombosis in treated patients with MPN.Methods:The study included 329 adult MPN patients, 184 (56%) female, treated at University Hospital Center Zagreb, Department of Internal medicine, Division of Hematology and Zadar General Hospital, Hematology Unit. Patients were aged 24‐85 years (median 68), and were diagnosed as having essential thrombocythemia (ET) (n = 149, 45%), polycythaemia vera (PV)(n = 94, 29%), primary myelofibrosis (PMF)(n = 69, 21%) and unclassifiable MPN (n = 17, 5%). Diagnosis were made according to the 2008 WHO Classification. JAK‐2 mutation status was either established or revised in our center, but was unknown in 55 (17%) patients. Data about treatment and cardiovascular and thromboembolic incidents was retrieved from medical records.Results:Forty patients (12%) developed thrombosis after median of 36 (range 1‐240) months from the time of diagnosis. Fifteen (5%) patients developed venous thrombosis, twenty‐four (7%) arterial, while one (0,3%) patient both type of thrombosis. Regarding the disease type, thrombosis was described in 16 patients with ET (11%), 18 with PV (19%) and 6 with PMF (8%). The risk of thrombosis was the highest in patients with previous thrombotic events, but did not correlate with the type of therapy (cytoreductive and/or antiagreggation) nor the JAK‐2 status.Summary/Conclusion:The risk of both arterial and venous thrombosis was found to be increased in patients with MPN even after introducing appropriate treatment. The highest risk of post treatment thrombosis was found in patients with previously diagnosed thrombotic events.
PB2231 THE MYELOPROLIFERATIVE NEOPLASMS UNCLASSIFIABLE. OUR EXPERIENCE
Authors: Accurso V. , Santoro M. , Contrino A. D. , Sardo M. , Perez A. , Di Piazza F. , Florena A. M. , Russo A. , Siragusa S. 
Published: June 2019

Background:According to the WHO classification, the designation of myeloproliferative neoplasms unclassifiable (MPN‐U) should be used for cases with clinical, morphologic, and molecular features of MPN failing to meet the diagnostic criteria of a specific entity. Reported incidence of MPN‐U varies significantly in different studies with a range up to > 20%. However, most studies show an incidence of 10–15% or even less. When the 2016 WHO criteria have been applied, the incidence is reduced to <5%.Aims:In this report we study the clinical and laboratory characteristics of 31 consecutive cases of unclassifiable myeloproliferative disease afferent to the center for myeloproliferative diseases of our Hematology Unit.Methods:From 2010 to 2018 our center has collected 508 cases of Philadelphia‐negative Myeloproliferative Neoplasms (MPNs). Data from these patients were collected in a specific database and analysed with simple statistic tools.Results:Among these 508 patients, 31 (6.2%) had a diagnosis of MPN‐U, 16 male and 14 female. Median age at diagnosis was 60.9 years. 22/31 (70.9%) were JAK2 V617F positive, 3/31 were CALR mutated (0.96%), 2/31 (0.64%) MPL mutated and 6/31 (19.3%) resulted as triple negative (TN) for driver mutations. Data from the other groups of MPNs (PV, ET, overtMF and preMF) were analised as well and compared to the ones from the MPN‐U group.Summary/Conclusion:Chronic myeloproliferative diseases unclassifiable (MPN‐U) represent the 6.2% of the cases relating to our center. No significant difference at diagnosis has been highlighted regarding sex, age and mutational status between MPN‐U and MPN classified according to WHO 2016. The exact incidence of MPN‐U is unknown. It is probable that frequency varies significantly according to the experience of the diagnostician and the specific classification system and criteria used. It is possible that careful use of the WHO 2016 classification may significantly reduce the frequency of MPN‐U.
PB2439 CAN THROMBOELASTOGRAPHY (TEG) EFFECTIVELY EVALUATE COAGULATION BALANCE IN PATIENTS WITH ACUTE LEUKAEMIA UNDER CHEMOTHERAPY?
Authors: Raso S. , Napolitano M. , Mancuso S. , Santoro M. , Carlisi M. , Tarantino G. , Franco G. , Lipari M. G. , Siragusa S. 
Published: June 2019

Background:Clinical course of AL may be complicated by thrombosis o major bleeding. Basal coagulation tests and platelet count (PLT) alone have been shown to not adequately identify thrombotic or risk.Aims:prospective study investigates the role of TEG, in patients with AL for predicting bleeding or thrombosis either at the presentation o during chemotherapy (CHT).Methods:This prospective study was conducted on 11 consecutive patients (PTs) with AL. Assessment of blood count cell (CBC) and conventional coagulation tests (CCT),PT,a‐PTT,DD,FBGandTEG(TEG®5000, Thromboelastograph Haemostasis System) were collected at the diagnosis and during 1 st cycle of CHT. TEG parameters R‐time(min), a‐angle(°), K‐time(min), MA (maximum amplitude) (mm) were recorded and normal ranges were considered as R 9‐27, K 2‐9, a‐angle 22‐58, MA 44‐64.Results:Overall, 8 PTs with AML and 3 with ALL were evaluated with a median age of 54 y (range 18 –80). CHT administered were intensive in all but 2 PTs, treated with hypomethylating agent (HP). CCTs resulted normal in all cases with the exception of DD levels that were increased. 6 patients developed blood cloting disorders on CHT:3 thrombotic events [1 portal vein thrombosis,1 thrombosis of the lower limbs, 1 myocardial infarction]; 3 haemorrhages [2 of urinary tract (WHO grade 2) and 1 of central nervous system (WHO grade 3)]. TEG assay at diagnosis resulted normal in 9 patients. In PTs with thrombosis, TEG resulted markedly shortened, with an increased rate of a‐angle and a higher MA, when compared to bleeding PTs and to aymptomatic PTs(Table 1).TEG in PTs receiving HP showed no significant alterations, also in presence of thrombocytopenia.Summary/Conclusion:In our cohort, TEG showed a hypercoagulable state, characterized by a reduction of R value during CHT in PTs with thrombosis. MA and a‐angle resulted increased, compared to diagnosis, only in patients with thrombosis, while they were decreased in all the other PTs. These results were no in relationship to PLT or FBG levels. Our findings suggest that TEG may be useful to identify PTs with AL at higher thrombotic risk.image
Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China
Authors: Wang Margaret Z. , Feng Rui-mei , Wang Shaoming , Duan Xian-zhi , Li Dong , Zhang Xun , Mu Rong , Qiao Youlin , Smith Jennifer S. 
Published: June 2019

Background
World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other.

Methods
We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff.

Results
CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+.

Conclusions
When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.
Ecological pressures and the contrasting scaling of metabolism and body shape in coexisting taxa: cephalopods versus teleost fish
Authors: Tan Hanrong , Hirst Andrew G. , Glazier Douglas S. , Atkinson David 
Published: June 2019

Metabolic rates are fundamental to many biological processes, and commonly scale with body size with an exponent (bR) between 2/3 and 1 for reasons still debated. According to the ‘metabolic-level boundaries hypothesis',bRdepends on the metabolic level (LR). We test this prediction and show that across cephalopod species intraspecificbRcorrelates positively with not onlyLRbut also the scaling of body surface area with body mass. Cephalopod species with highLRmaintain near constant mass-specific metabolic rates, growth and probably inner-mantle surface area for exchange of respiratory gases or wastes throughout their lives. By contrast, teleost fish show a negative correlation betweenbRandLR. We hypothesize that this striking taxonomic difference arises because both resource supply and demand scale differently in fish and cephalopods, as a result of contrasting mortality and energetic pressures, likely related to different locomotion costs and predation pressure. Cephalopods with highLRexhibit relatively steep scaling of growth, locomotion, and resource-exchange surface area, made possible by body-shape shifting. We suggest that differences in lifestyle, growth and body shape with changing water depth may be useful for predicting contrasting metabolic scaling for coexisting animals of similar sizes.This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
Integrating within-species variation in thermal physiology into climate change ecology
Authors: Bennett Scott , Duarte Carlos M. , Marbà Núria , Wernberg Thomas 
Published: June 2019

Accurately forecasting the response of global biota to warming is a fundamental challenge for ecology in the Anthropocene. Within-species variation in thermal sensitivity, caused by phenotypic plasticity and local adaptation of thermal limits, is often overlooked in assessments of species responses to warming. Despite this, implicit assumptions of thermal niche conservatism or adaptation and plasticity at the species level permeate the literature with potentially important implications for predictions of warming impacts at the population level. Here we review how these attributes interact with the spatial and temporal context of ocean warming to influence the vulnerability of marine organisms. We identify a broad spectrum of thermal sensitivities among marine organisms, particularly in central and cool-edge populations of species distributions. These are characterized by generally low sensitivity in organisms with conserved thermal niches, to high sensitivity for organisms with locally adapted thermal niches. Important differences in thermal sensitivity among marine taxa suggest that warming could adversely affect benthic primary producers sooner than less vulnerable higher trophic groups. Embracing the spatial, temporal and biological context of within-species variation in thermal physiology helps explain observed impacts of ocean warming and can improve forecasts of climate change vulnerability in marine systems.This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection
Authors: Colson Philippe , Dhiver Catherine , Tamalet Catherine , Delerce Jeremy , Glazunova Olga O. , Gaudin Maxime , Levasseur Anthony , Raoult Didier 
Published: June 2019

ABSTRACTStrategies to cure HIV-infected patients by virus-targeting drugs have failed to date. We identified a HIV-1-seropositive woman who spontaneously suppressed HIV replication and had normal CD4-cell counts, no HIV disease, no replication-competent virus and no cell HIV DNA detected with a routine assay. We suspected that dramatic HIV DNA degradation occurred postinfection. We performed multiple nested-PCRs followed by Sanger sequencing and applied a multiplex-PCR approach. Furthermore, we implemented a new technique based on two hybridization steps on beads prior to next-generation sequencing that removed human DNA then retrieved integrated HIV sequences with HIV-specific probes. We assembled ≈45% of the HIV genome and further analyzed the G-to-A mutations putatively generated by cellular APOBEC3 enzymes that can change tryptophan codons into stop codons. We found more G-to-A mutations in the HIV DNA from the woman than in that of her contaminator. Moreover, 74% of the tryptophan codons were changed to stop codons (25%) or were deleted as a possible consequence of gene inactivation. Finally, we found that this woman’s cells remained HIV-susceptible in vitro. Our findings show that she does not exhibit innate HIV resistance but has been cured of it by extrinsic factors, a plausible candidate for which is the gut microbiota.
PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers – first-in-human results
Authors: Kossatz Susanne , Pirovano Giacomo , De Souza França Paula Demétrio , Strome Arianna L. , Sunny Sumsum P. , Zanoni Daniella Karassawa , Mauguen Audrey , Carney Brandon , Brand Christian , Shah Veer , Ramanajinappa Ravindra D. , Hedne Naveen , Birur Praveen , Sihag Smita , Ghossein Ronald A. , Gönen Mithat , Strome Marshall , Suresh Amritha , Molena Daniela , Kuriakose Moni A. , Patel Snehal G. , Reiner Thomas 
Published: June 2019

AbstractMajor determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.
Combining weather patterns and cycles of population susceptibility to forecast dengue fever epidemic years in Brazil: a dynamic, ensemble learning approach
Authors: McGough Sarah F. , Clemente Cesar L. , Kutz J. Nathan , Santillana Mauricio 
Published: June 2019

AbstractTransmission of dengue fever depends on a complex interplay of human, climate, and mosquito dynamics, which often change in time and space. It is well known that disease dynamics are highly influenced by a population’s susceptibility to infection and microclimates, small-area climatic conditions which create environments favorable for the breeding and survival of the mosquito vector. Here, we present a novel machine learning dengue forecasting approach, which, dynamically in time and adaptively in space, identifies local patterns in weather and population susceptibility to make epidemic predictions at the city-level in Brazil, months ahead of the occurrence of disease outbreaks. Weather-based predictions are improved when information on population susceptibility is incorporated, indicating that immunity is an important predictor neglected by most dengue forecast models. Given the generalizability of our methodology, it may prove valuable for public-health decision making aimed at mitigating the effects of seasonal dengue outbreaks in locations globally.
flowEMMi: An automated model-based clustering tool for microbial cytometric data
Authors: Ludwig Joachim , zu Siederdissen Christian Höner , Liu Zishu , Stadler Peter F , Müller Susann 
Published: June 2019

AbstractBackgroundFlow cytometry (FCM) is a powerful single-cell based measurement method to ascertain multidimensional optical properties of millions of cells. FCM is widely used in medical diagnostics and health research. There is also a broad range of applications in the analysis of complex microbial communities. The main concern in microbial community analyses is to track the dynamics of microbial subcommunities. So far, this can be achieved with the help of time-consuming manual clustering procedures that require extensive user-dependent input. In addition, several tools have recently been developed by using different approaches which, however, focus mainly on the clustering of medical FCM data or of microbial samples with a well-known background, while much less work has been done on high-throughput, online algorithms for two-channel FCM.ResultsWe bridge this gap with flowEMMi, a model-based clustering tool based on multivariate Gaussian mixture models with subsampling and foreground/background separation. These extensions provide a fast and accurate identification of cell clusters in FCM data, in particular for microbial community FCM data that are often affected by irrelevant information like technical noise, beads or cell debris. flowEMMi outperforms other available tools with regard to running time and information content of the clustering results and provides near-online results and optional heuristics to reduce the running-time further.ConclusionsflowEMMi is a useful tool for the automated cluster analysis of microbial FCM data. It overcomes the user-dependent and time-consuming manual clustering procedure and provides consistent results with ancillary information and statistical proof.
Spectral Hallmark of Auditory-Tactile Interactions in the Mouse Somatosensory Cortex
Authors: Zhang Manning , Kwon Sung Eun , Ben-Johny Manu , O’Connor Daniel H. , Issa John B. 
Published: June 2019

ABSTRACTTo synthesize a coherent representation of the external world, the brain must integrate inputs across stimulus modalities. Yet the mechanistic basis of this computation at the level of neuronal populations remains obscure. Here, we investigate tactile-auditory integration using two-photon Ca2+ imaging in the mouse primary (S1) and secondary (S2) somatosensory cortices. Pairing sound with whisker stimulation modulates tactile responses in both S1 and S2, with the most prominent modulation being robust inhibition in S2. The degree of inhibition depends on tactile stimulation frequency, with lower frequency responses the most severely attenuated. Alongside these neurons, we identify sound-selective neurons in S2 whose responses are inhibited by high tactile frequencies. These results are consistent with a hypothesized local mutually-inhibitory S2 circuit that spectrally selects tactile versus auditory inputs. Our findings enrich mechanistic understanding of multisensory integration and suggest a key role for S2 in combining auditory and tactile information.
A Novel PHOX/CD38/MCOLN1/TFEB Axis Important For Macrophage Activation During Bacterial Phagocytosis
Authors: Najibi Mehran , Moreau Joseph A. , Honwad Havisha H. , Irazoqui Javier E. 
Published: June 2019

AbstractMacrophages are a key and heterogenous class of phagocytic cells of the innate immune system, which act as sentinels in peripheral tissues and are mobilized during infection. Macrophage activation in the presence of bacterial cells and molecules entails specific and complex programs of gene expression. How such triggers elicit the gene expression programs is incompletely understood. We previously discovered that transcription factor TFEB is a key contributor to macrophage activation during bacterial phagocytosis. However, the mechanism linking phagocytosis of bacterial cells to TFEB activation remained unknown. In this article, we describe a previously unknown pathway that links phagocytosis with the activation of TFEB and related transcription factor TFE3 in macrophages. We find that phagocytosis of bacterial cells causes an NADPH oxidase (PHOX)-dependent oxidative burst, which activates enzyme CD38 and generates NAADP in the maturing phagosome. Phago-lysosome fusion brings Ca2+ channel TRPML1/MCOLN1 in contact with NAADP, causing Ca2+ efflux from the lysosome, calcineurin activation, and TFEB nuclear import. This drives TFEB-dependent expression of important pro-inflammatory cytokines, such as IL-1α, IL-1β, and IL-6. Thus, our findings reveal that TFEB activation is a key regulatory event for the activation of macrophages. These findings have important implications for infections, cancer, obesity, and atherosclerosis.