dataesr/scientific-paragraphs-categorization huggingface dataset:
The current proposal is to apply a comprehensive omics strategy to improve our understanding of normal myeloid differentiation and innate immune defense at a systemic level and how genetic aberrations cause perturbations of normal cellular activities, resulting in myeloid disease phenotypes. Given this, the proposal will combine omics technologies and comprehensive cell sorting to generate a state-ofthe art reference omics data set of prospectively purified human bone marrow populations representing successive stages of myeloid differentiation (i. e. HSCs, myeloid progenitors, and mature myeloid cells) in healthy subjects. The resultant data set will improve our understanding of how dynamic regulatory networks control cell fate and function during normal myeloid differentiation and immune defense.
Moreover, the research community will be able to match the resultant normal reference omics data set with omics data sets of sorted bone marrow populations from patients with myeloid diseases harboring defined genetic aberrations. This strategy will allow a standardized omics data set comparison of normal and disease states, which will unravel how specific genetic aberrations in patients promote aberrant cellular activities (e. g. signaling, proliferation, metabolism, apoptosis, etc. ) underlying the phenotype of specific myeloid diseases. Significantly, comprehensive data mining of the normal "reference" and patient omics data sets will allow us to identify novel diagnostic markers, as well as targets for therapeutic interventions, and ultimately improve treat-ment and clinical outcome of patients suffering from AML, MPNs, and other myeloid diseases.
5. Establishment of a European core bioinformatics group for concerted processing and analysis of omics data in order to generate a "reference" omics data set of normal myeloid differentiation. Ideally, the bioinformatics group will also assist European clinicians with standardized comparison of the obtained reference omics data set and omics data sets of patients enrolled in clinical trials. In addition, the bioinformatics group will develop an open-access web-based platform allowing researchers worldwide to download and match omics data from patients with myeloid diseases for comparison with the reference omics data set.
92 The validation of these techniques will require the integration of longitudinal standardized data, as well as uniform criteria for diagnosis and outcome that can be applied in the clinical setting. Better integration of basic and clinical research will also be crucial. Salient features of that integration should include the following: 1. Where possible, consent should be obtained for the procurement and storage of use of excess tissue from lymph node biopsies and normal tissue at the time of presentation and at each subsequent disease relapse for research purposes in order to investigate the molecular biology of these diseases. 2. A biobank of biopsies linked to the clinical database should be available, with protocols for standardized sampling and storage procedures adapted to genomics and functional assays (including live cells), which would form the basis of correlative and biomarker studies.
Of particular importance would be the banking of longitudinal samples from patients at diagnosis and at subsequent relapses and transformation to the nature of relapsing disease. 3. A database (a co-ordinated pan-European registry) that can be accessed by all research partners, containing the biological and clinical information collected for each participating patient, should be made available. 4. Uncovering the molecular mechanisms involved in FL, especially in its early stages  [90] [91] [92]  and the processes involved in transformation, should be a common goal. 88 A key issue would be performing both genetic and microenvironment analyses on longitudinal and/or paired FL biopsies to obtain an integrated view on bidirectional dependency. 5. Robust biomarkers (both prognostic and predictive) should be developed, reflecting the molecular biology of the disease and the impact of the immune microenvironment for disease development and treatment outcome.
These improvements are particularly relevant given that they were achieved in the setting of rare disorders where there are innate difficulties in making progress. The database of the WPSAA of the European Group for Blood and Marrow Transplant (EBMT) contains data on more than 11,000 patients with different subtypes of BMFs, thereby providing a unique opportunity for investigating many different critical aspects of these diseases. The WPSAA of the EBMT continues to run a multinational database to collect data from all European BMFs; the aim is to combine this retrospective work with prospective studies to address further improvements in the complex treatment of these disorders.
European research contributions Researchers from Europe identified 15 novel genes responsible for ITs and seven genes causing IPFDs. Through the construction of patient databases, European groups have provided a thorough definition of the mutation spectrum, clinical features, and genotype/phenotype correlations of some disorders, including MYH9-related disease, Bernard-Soulier syndrome, Glanzmann thrombasthenia, Wiskott-Aldrich syndrome/X-linked thrombocytopenia, and thrombocytopenia 2. European researchers have provided effective tools to standardize the diagnosis of both ITs and IPFDs; European networks have developed methodologies that combine phenotyping of IPFDs and application of next generation sequencing (NGS) to unravel the genetic complexity of these diseases. 196, 212, 213 By using in vitro models of megakaryopoiesis or animal models, European investigators identified the pathogenesis of several ITs and IPFDs, including congenital amegakaryocytic thrombocytopenia, disorders deriving from FLI1 or RUNX1 haploinsufficiency, and thrombocytopenia 2.
Finally, the best management of impaired platelet function and number needs to be established by prospective, European collaborative studies. Another issue to be developed is the role of platelets in liver regeneration and fibrosis. Drug-induced platelet dysfunction in patients undergoing surgery: clinical relevance and treatment. The relevance of drug-induced platelet dysfunction in patients undergoing surgery and of its management may initially be evaluated by a large European retrospective survey assessing the relationship between pre-surgical drug intake and surgical bleeding. Previous experience from the EHA-SWG shows that surveys, although based retrospectively on clinical records, may provide clinically relevant information when the database obtained is sufficiently large. The survey will analyze different drug treatments and various types of surgery, classified as major or minor and by organs/systems.
The diagnosis and study of rare bleeding disorders, including those involving blood platelets, will greatly benefit from the introduction of next generation sequencing (NGS) technology. 246 To take full advantage of this, a stable and sustainable database of genetic variation in hemostatic genes is required. There is also a need for standardization of clinical reporting of genetic test results for hemostatic disorders to have long-term stability of reference sequences to avoid confusion about "versioning" of DNA sequences, and the locus reference genomic sequences aim to achieve this. VT: high-throughput genotyping technologies in the framework of genome-wide association studies have led to the identification of at least eight new loci associated with the risk of first VT. 247 However, the currently known genetic factors explain only approximately 5% of VT heritability.
European research contributions Major steps toward questioning the evidence base for use of blood were established in Europe, beginning with descriptive data by the Sanguis Study Group, which in 1994 reported large differences between hospitals and clinical teams in the use of RBC transfusions (and other blood products) for the same surgical procedures with no clear clinical explanation. Many  Outcome Survey has collected transfusion and outcome data from large numbers of patient transfusion episodes from many centers across Europe. According to reports from the European Blood Alliance, although average RBC use per 1000 inhabitants in Europe is substantially lower than in the US, large variations in usage rates are still reported between European countries, and audits indicate greater than 15% inappropriate use.
Proposed research for the Roadmap Clinical studies on appropriate use/linking to ongoing studies and patient input: the aforementioned European Transfusion Practice and Outcome Survey on blood usage for surgical interventions in Europe still has no counterpart for (onco) hematologic diseases. There is an opportunity to explore current hospital databases to characterize blood use in (onco) hematology and hemoglobinopathy, to generate key base-line information on blood usage practice. Incorporation of data collection for transfusion usage and bleeding outcome in hemato-oncology trials should be encouraged. Policies to enhance patient engagement, for instance in transfusion-dependent myelodysplasia, are required. This could be achieved by introduction of patient-reported outcomes related to physical activity, well-being, and quality of life (QoL) as part of post-transfusion follow up.
Proposed research for the Roadmap Therapeutic apheresis: there remains an ongoing need to contribute to evidence base indications for therapeutic apheresis. Given the orphan character of diseases this requires broad collaboration with all involved institutes in Europe and the establishment of European databases in conjunction with the scientific societies of various medical disciplines. Stem cell donation by autologous, related, and unrelated donors: for stem cell donation, the establishment of a global standardized system for related donor care comparable to unrelated volunteer donors is in progress. This initiative is a joint effort of the World Marrow Donor Association and EBMT, resulting from the establishment of an EBMT board committee on donor follow up (2012) with one of the goals to set up a donor follow-up registry for all EBMT related and unrelated stem cell donors and to provide the possibility for systematically collecting adverse events and longer follow up for family donors.
HLA-net aims at networking researchers in bone marrow transplantation (BMT), epidemiology, and population genetics to improve the molecular characterization of genetic HLA diversity of human populations with an impact on both public health and fundamental research (Allele Frequency Net Database). A European subgroup of the Allele Frequency Net Database (EUROSTAM/HLA-net) is setting up an HLA allele frequency database to enable renal transplantation in highly sensitized patients on the basis of acceptable HLA mismatches. 305 The European platelet immunology working party contributed insight in fetal alloimmune thrombocytopenia. 306 Unraveling the minor histocompatibility antigens aims at dissecting the T-cell immunity causing graft-versus-host disease (GvHD) and graft-versus-tumor effect (see Section 9).
2. Call for standardized diagnostic tests to be established to allow universal diagnostic criteria to be set and commercial assays or protocols to set up services. 3. Large interindividual variabilities of antifungal drug levels are observed in children. Pharmacokinetic/pharmacodynamic data are limited in this group and are warranted for prompt informed adjustment of dosing, allowing optimal treatment with these potentially lethal infections. 4. Optimal duration of antifungal treatment is ill defined, as is subsequent secondary prophylaxis. Surveillance of infections post HSCT: PID patients preparing for HSCT are screened for blood, respiratory, and gut pathogens. Although reasonably controlled pre-HSCT, these pathogens can cause significant problems as the child progresses through HSCT with the conditioning and immunosuppressive regimens.
Acknowledgments The authors wish to thank all who contributed to the creation of this document. Freiburg, Germany),  Hartmut Goldschmidt  ( Universitätsklinikum Heidelberg, Heidelberg, Germany ),  Antonio Palumbo  ( Università degli Studi di Torino, Turin, Italy ),  Evangelos Terpos  ( National and Kapodistrian University of Athens, Athens, Greece ).
In several beyond the standard model scenarios, vectorlike quarks are considered partners of the top and bottom quarks  [16]. Both the charged-current  [17]  and the flavor changing neutral current (FCNC)  [18, 19]  decay processes are allowed. The ratio of the predicted rates depends on the model: in some models the FCNC process dominates  [20] ; in others the two modes are comparable in rate. This paper describes the search for a vectorlike B quark of electric charge -1/3, using data recorded by the CMS experiment from proton-proton collisions at a center-of-mass energy of 8 TeV at the CERN LHC in 2012. It is assumed that B quark-antiquark pairs are produced strongly for B quark masses within the range of this search, which extends to 1 TeV. The B quark may decay either via the charged-current process B → tW or via the FCNC processes B → bZ and B → bH.
However, residual correlation between the two variables is present and must be taken into account in the background estimation procedure. The correlation is measured from data using an alternative set of control regions defined using the following criteria: (i) N jets = 1 or N jets > 1 and (ii) 0. 244 < b-tagging discriminator < 0. 679 or b-tagging discriminator < 0. 244 for the leading jet. This classification divides the N jets vs the b-tagging discriminator plane into four regions, labeled I, J, K, and L, as shown in Fig. 5. These four regions are completely contained within the previously defined regions A and C. The ratio C = N J N K /N I N L is equal to 1 if N jets and the b-tagging discriminator variables are perfectly uncorrelated, and is used to quantify the degree of correlation between the two.
7. Off-shell photon conversions can produce a lepton with very low p T that will not pass the selection criteria or will not be reconstructed. Drell-Yan processes with such conversions can lead to a significant background for the three-lepton category. A measurement of the extrapolation factors for photon conversions to electrons or muons is performed using data events. We measure the extrapolation factors in a control region devoid of signal events, with low H T and E T /. The ratio of the number of events with |M( + -± ) -M(Z)| < 15 GeV or |M( + -± ) -M(Z)| < 15 GeV to the number of events with |M( + -γ) -M(Z)| < 15 GeV defines the extrapolation factor, which is 2. 1 ± 0. 3% (0. 7 ± 0. 1%) for electrons (muons). The measured extrapolation factors are then used to estimate the background in the signal region from the observed number of +γ events in the search region.
In order to estimate background from jets producing misidentified light-lepton candidates that appear to be prompt and isolated, we use data events containing two reconstructed leptons and an additional isolated track. This contribution is then scaled by an extrapolation factor relating isolated tracks to lepton candidates from jets. This light-lepton extrapolation factor is measured in control samples where no signal is expected, such as in the low-E T / or low-H T regions. We measure the extrapolation factor between isolated tracks and electron (muon) candidates to be 0. 7 ± 0. 2% (0. 6 ± 0. 2%), using a data sample dominated by Z+jets. The contribution from backgrounds containing a misidentified third lepton is determined by multiplying the number of events containing isolated tracks in the sample with two leptons by the light-lepton extrapolation factor.
Summary A search for pair production of the B quark with vectorlike couplings to W, Z, and Higgs bosons has been performed, using data recorded by the CMS experiment from proton-proton collisions at a center-of-mass energy of 8 TeV at the CERN LHC in 2012. This hypothesized particle could decay in one of three ways: to tW, bZ, or bH. The search is performed using five distinct topologies to maintain sensitivity to each of these decay modes. The topologies included in this search are the lepton+jets final state, both the opposite-sign and same-sign lepton pair final states, the three or more leptons final state, and finally the all-hadronic final state targeting Higgs boson decays to pairs of bottom quarks. No evidence for the production of B quarks in any topology is found, and limits are set on the B quark-antiquark pair-production cross section.
Materials and Methods Participants Sixteen adults (11 female; aged between 19 and 81 years) who had undergone CI surgery (Digisonic SP; Oticon Medical, Vallauris, France) participated in this study. All were native speakers of French with post-lingual deafness onset and had used the implant for at least 10 months prior to the experiment. No specific inclusion criteria were defined, particularly in terms of etiology or duration of deafness and the time since implantation. This approach provided us access to a wide range of word recognition performances. Demographic data are presented in Table  1. This study and all experimental procedures were approved by the Institutional Review Board at the University Hospital in Nice. Each participant provided written consent and the study and all experimental procedures were approved by the South Mediterranean V Ethical Review Board (Comité de Protection des Personnes Sud Méditérrannée V, authorization n°1 2,075).
Measurement of speech recognition performance without lip reading Speech recognition was assessed using a vowel-consonant-vowel (VCV), 16-alternatives forced-choice logatome test ran in quiet. VCVs were extracted from standardized lists recorded on a CD (Listes de logatomes de Dodelé, Collège National d'Audioprothèse, Paris, France) and embedded in an ad-hoc developed Matlab1 (The MathWorks, Natick, Mass. , United-States) program. Only consonant comprehension was tested, to both increase the difficulty of the test and increase the matching between the speech perception evaluation and the frequency areas tested by the eABR (from 1,107 Hz to 4,883 Hz). All patients were tested four times on each 16 stimuli, with a random selection, for a total of 64 trials. Stimuli were delivered through a loudspeaker placed approximately one meter in front of the patient.
Electrical Auditory Brainstem Response (eABR) measurements EABRs were recorded using surface electrodes that were placed on the forehead (+), the lower part of the chin (-), and the contralateral mastoid (common). Each testing session lasted three to four hours, including breaks. During the recordings, participants were encouraged to relax during the recording sessions to limit artifacts due to muscle activity. The full-scale range used for eABR recording was set to 100 μV using the ABR recording system Centor USB (Racia-Alvar1). Responses were filtered using a wideband (1. 6-3. 6 kHz) analog bandpass filter. The averaging involved 1,500 sweeps. To estimate and confirm reproducibility, eABRs were recorded twice, reported data correspond to the first recording obtained for each participant.
07, 2013, Addinsoft, Inc. , Brooklyn, NY, USA), which matched the model Eq (1): MIC ¼ 1 þ 2:8e À0:04ðVCVscoreÀ6:25Þ ð1Þ In (1), MIC being the MIC value and VCV score the percentage of correct responses obtained with the speech perception test. The resulting function was mapped on the individual data as shown in Fig 3. The fact that the data are well explained by an exponential decay points to an interesting property of our dataset. As the speech score increases from low to medium values, (in our experiment for participants 10-CM with 12. 5% to 6-MJ with 37. 5% recognition score (triangles in Fig  3 ) the MIC value decreases exponentially from high values around 3. 5 to around 1. 5. This is suggesting that the participants with very low speech score (<40% VCV recognition score closed-set in quiet) in general have high MIC values while patients with higher speech recognition score (>47.
Discussion The substantial variability in functional results with CIs, combined with a lack of reliable prognostic factors, limit the individual optimization of this neural prosthesis. We have developed a prognostic test that uses eABRs to measure global electrical and neural interactions at the level of the electrode array. It assesses the biological capacity of the patients to use several information channels supplied by the implant and can explain a substantial amount of the interindividual variability found in speech perception scores among CI patients. We also observed that the speech perception data were well explained by an exponential decrease of the electrical interactions as evaluated by the MIC. Given the number of participants included in the present study it was however not possible to reach significance when studying the difference between lowand high-speech proficient participants, this limit of the current project suggests the interest of running a large multicentric study involving a larger population of CI patients in order to confirm and extend the present observations.
, 1998). These hydrological and biogeochemical studies helped re-envision the watershed concept as a temporally dynamic network of vertical, lateral, and longitudinal exchanges, rather than discrete compartments or flowpaths. The 21st century has seen a continuation of the methodological convergence of catchment hydrology and biogeochemistry  (Godsey et al. , 2009; Oldham et al. , 2013; Zarnetske et al. , 2012). Specifically, two technological advances have strongly influenced the creation and testing of ecological and hydrological theory: 1. Hydrological and biogeochemical models have become vastly more powerful and complex  (Davies et al. , 2013; McDonnell et al. , 2007; McDonnell and Beven, 2014) , and 2. High frequency datasets of hydrological and biogeochemical parameters have come online thanks to advances in remote and environmental sensors  (Kirchner et al.
, 2004; Krause et al. , 2015; McKnight et al. , 2015). Increased computing power has allowed the development of bottomup, mechanistic models that simulate chemical reactions and water exchange based on realistic physics and biology  (Beven and Freer, 2001; Frei et al. , 2012; Trauth et al. , 2014; Young, 2003). At the same time, more extensive and intensive datasets have allowed the development of top-down, black-box models based on empirical or theoretical relationships between catchment characteristics and biogeochemistry  (Godsey et al. , 2010; Jasechko et al. , 2016; Kirchner, 2016b). While there has been a lively discussion of the merits and drawbacks of these approaches, developing models that are simultaneously physically realistic and capable of prediction remains difficult  (Beven and Freer, 2001; Dooge, 1986; Ehret et al.
, 2013). While extracellular eDNA has primarily been used for species detection in freshwater environments  (Ficetola et al. , 2008; Vorkapic et al. , 2016) , it also has potential as a hydrologic tracer, with eDNA from lacustrine invertebrates used to trace lake water up to 10 km from its source  (Deiner and Altermatt, 2014). Tracer sDNA is produced by automatic oligonucleotide synthesis and is normally short (less than 100 nucleotides), which allows approximately limitless unique sequences (4 nucleotides 100 = 1. 61 × 10 60 ). Stop codons distinguish the sDNA from eDNA, and injected sDNA is analyzed by quantitative polymerase chain reaction with custom primers. sDNA has been used to trace sediment transport when bound with montmorillonite Fig. 6. A meta-analysis including unpublished data of δ 13 C values observed in streams and rivers across the globe for dissolved inorganic carbon (DIC), particulate inorganic carbon (PIC), dissolved organic carbon (DOC), and dissolved CO 2.