Miracle-dz/UniFAR-FTUs huggingface dataset:
A feasibility and phase II study of the hu14.18-IL2 immunocytokine in combination with GM-CSF and isotretinoin in patients with recurrent or refractory neuroblastoma: A Children’s Oncology Group study.

10017 Background: Combining anti-GD2 (disialoganglioside) monoclonal antibody with GM-CSF, IL2 and isotretinoin is now standard of care for high-risk neuroblastoma (NB) minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in NB and is more effective in NB-bearing mice than antibody and cytokine given separately. We therefore evaluated the safety, tolerability and anti-tumor activity of hu14.18-IL2 given with GM-CSF and isotretinoin in a schedule similar to current MRD therapy. Methods: Hu14.18-IL2 was given at the phase II dose (12 mg/m2) on days 4-6 of a 28 day cycle with GM-CSF (250 μg/m2/dose, days 1-2, 8-14) and isotretinoin (160 mg/m2/day, days 11-25). Tolerability was determined based on the number of patients who developed an unacceptable toxicity (required pressor support or intubation). Response was evaluated every 2 cycles for patients with disease measurable by standard radiologic criteria (stratum 1), and for patients wit.
Estimating 
γγ
 absorption for ultrahigh-energy photons with lepton and hadron production

Surprisingly, the contribution to the cosmic opacity to UHE ($E>10^{18} \, \rm eV$) $\gamma$-rays has been systematically computed so far for the $\gamma \gamma \to e^+e^-$ and $\gamma \gamma \to e^+ e^- e^+ e^-$ processes alone. We go a step further by systematically evaluating the additional opacity brought about by other leptons and hadrons. We find that the dominant channels are those leading to the production of $\mu^{\pm}$ and hadrons (mainly $\pi^{\pm}$, $\pi^0$, $K^{\pm}$, $K^0$, $\eta$). For nearly the GZK radius, the photon survival probability becomes smaller by about a factor of two with respect to current estimates.
Innovative Wood Surface Treatments Based on Nanotechnology

This work reviewed innovative wood surface treatments based on nanotechnology. It is well documented in the literature that the cell walls of wood present significant porosity; this porosity is on a molecular scale. The main reason for the use of nanotechnology in wood science and technology is the unique characteristic of nano-based materials to effectively penetrate deeply into wood substrates, which, in turns, results in the alteration of their surface chemistry. This subsequently causes an improvement in wood properties. Any potential change in the wood properties due to treatment with nanomaterials is based on the higher interfacial area which is developed due to the treatment. This occurs because the number of particles is significantly reduced to the nanoscale. The nanomaterials improve the properties of wood as a raw material and alter its original features to a limited extent. However, their potential impact on both health and the environment should be addressed by applying tools such as life-cycle assessments. This will avoid mistakes being made in which new technologies are released on the market prior to an impact assessment having been carried out.
Specificity and effector functions of non-neutralizing gB-specific monoclonal antibodies isolated from healthy individuals with human cytomegalovirus infection

Human cytomegalovirus (HCMV) is the most common congenital infection, and the leading nongenetic cause of sensorineural hearing loss (SNHL) in newborns globally. A gB subunit vaccine administered with adjuvent MF59 (gB/MF59) is the most efficacious tested to-date, achieving 50% efficacy in preventing infection of HCMV-seronegative mothers. We recently discovered that gB/MF59 vaccination elicited primarily non-neutralizing antibody responses, that HCMV strains acquired by vaccinees more often included strains with gB genotypes that are distinct from the vaccine antigen, and that protection against HCMV acquisition correlated with ability of vaccine-elicited antibodies to bind to membrane associated gB. Thus, we hypothesized that gB-specific non-neutralizing antibody binding breadth and function are dependent on their epitope and genotype specificity as well as their ability to interact with membrane-associated gB. Twenty-four gB-specific monoclonal antibodies (mAbs) isolated from naturally HCMV-infected individuals were mapped for gB domain specificity by binding antibody multiplex assay (BAMA) and for genotype preference binding to membrane-associated gB presented on transfected cells. We defined their non-neutralizing functions including antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC). The isolated gB-specific non-neutralizing mAbs were primarily specific for Domain II and linear antigenic domain 2 site 2 (AD2). We observed variability in mAb gB genotype binding preference, with increased binding to gB genotypes 2 and 4. Functional studies identified two gB-specific mAbs that facilitate ADCP and have binding specificities of AD2 and Domain II. This investigation provides novel understanding on the impact of gB domain specificity and antigenic variability on gB-specific non-neutralizing antibody responses. Importance HCMV is the most common congenital infection worldwide, but development of a successful vaccine remains elusive. gB-specific non-neutralizing mAbs, represent a distinct anti-HCMV Ab subset implicated in the protection against primary infection during numerous phase-II gB/MF59 vaccine trials. By studying non-neutralizing gB-specific mAbs from naturally infected individuals, this study provides novel characterization of binding site specificity, genotypic preference, and effector cell functions mediated by mAbs elicited in natural infection. We found that a panel of twenty-four gB-specific non-neutralizing mAbs bind across multiple regions of the gB protein, traditionally through to be targeted by neutralizing mAbs only, and bind differently to gB depending if the protein is soluble versus embedded in a membrane. This investigation provides novel insight into the gB-specific binding characteristics and effector cell functions mediated by non-neutralizing gB-specific mAbs elicited through natural infection, providing new endpoints for future vaccine development.
Patient satisfaction with participation in phase II/III NCCTG clinical trials: Was it worth it? (N0392).

6133 Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%).
Obstructive and Promotive Factors for Access to School and Learning in Primary School in Zambia

This study was as a part of a research project for the Development of the Inclusive Education System Model for Learning Improvement in Developing Countries for the Centre for the Study of International Cooperation at Hiroshima University, funded by the 2015-2018 Grant for Global Sustainability (GGS) of the United Nations University, and the Grant-in-Aid for JSPS Fellows Grant Number 16J03585.
Multi-focus image fusion with Siamese self-attention network

Recently, convolutional neural networks (CNNs) have achieved impressive progress in multi-focus image fusion (MFF). However, it always fails to capture sufficient discrimination features due to the local receptive field limitations of the convolutional operator, restricting most current CNN-based methods’ performance. To address this issue, by leveraging self-attention (SA) mechanism, the authors propose Siamese SA network (SSAN) for MFF. Specifically, two kinds of SA modules, position SA (PSA) and channel SA (CSA) are utilised to model the long-range dependencies across focused and defocused regions in the multi-focus image, alleviating the local receptive field limitations of convolution operators in CNN. To search a better feature representation of the input image for MFF, the captured features obtained by PSA and CSA are further merged through a learnable 1 × 1 convolution operator. The whole pipeline is in a Siamese network fashion to reduce the complexity. After training, the authors SSAN can accomplish well the fusion task with no post-processing. Experiments demonstrate that their approach outperforms other current state-of-the-art methods, not only in subjective visual perception but also in the quantitative assessment.
AN EMPIRICAL ANALYSIS OF CORPORATE CAPITAL STRUCTURE AND FINANCIAL PERFORMANCE OF LISTED CONGLOMERATES IN NIGERIA

The relationship between capital structure and firms’ financial performance has attracted the attention of many researchers both locally and globally. The paucity of empirical evidence from Nigeria in this regard, especially on Nigerian conglomerate firms, portends the need for further research. Against this backdrop, the study investigated the impact of capital structure on the financial performance of listed conglomerates in Nigerian using descriptive statistics, pairwise correlation and panel data regression technique to analyze the secondary data extracted from the annual reports and accounts of the six (6) selected conglomerates for the period 2008 to 2017. The study found that financial leverage proxy by total debt ratio, long-term debt ratio and short-term debt ratio have significant impact on the selected firms’ financial performance proxy by return on assets, except debt to equity ratio that reveals an insignificant impact on return assets (ROA). Firm size and growth also reported a significant effect on the financial performance of the selected firms. The findings is in tandem with the proposition of the agency cost theory in the Nigeria settings but with caution considering the facts that firms in Nigeria were largely finance through short term debt obligation as against long term debt funding that was presumed in the agency cost theoretical proposition. It is therefore recommended that managers of companies should be guided when seeking credit advances from the financial market as it is important when considering the appropriate capital mix that optimize firm value.
FANCA and contribution of studies from Asian populations to the understanding of fanca mediated Fanconi anemia

measures. cellular processes resulting in individual differences in the FA phenotypes. Hematological disorders especially FA has very devastating impact on individuals and societies. Their consequences have significant public health issues with socioeconomic impact in the developing countries. Thus, sporadic and familial cases with inherited FA need to be actively recruited to facilitate molecular characterization in inbred Asian populations to establish molecular genetics diagnostic strategies for timely detection and treatment as well as prenatal and premarital screening to overcome disease burden on societies and health care system. Nevertheless, such studies will lead to a better understanding of disease phenotypes and precise role of FANCA in normal and mutated cells. The FANCA-null mice provide an excellent experimental model for such studies to exploit and elucidate further FANCA functions. Ideally, update of international Fanconi Anemia registries/ databases and their access to retrieve data would greatly improve our understanding about the phenotype and genotype of FA patients. This access would also facilitate clinicians to select suitable strategies for multi-site therapeutic trials on a cohort of individuals. This study emphasizes regional and global epidemiological and molecular genetic studies especially from less developed regions and formulation of standard criteria/strategies of FA diagnosis. We anticipate that data presented in this review will increase awareness and motivate further research on FANCA as well as lethal FA. , ,
Comparison of tumor invasion depth in rectal cancer between rectal MR imaging with pathology and preoperative CT colonography with pathology

Poster: "ECR 2015 / C-0811 / Comparison of tumor invasion depth in rectal cancer between rectal MR imaging with pathology and preoperative CT colonography with pathology" by: "M. Suzuki, H. Kanazawa, K. Utano, S. Kijima, T. Sasaki, Y. Miyakura, H. Horie, H. Sugimoto; Shimotsuke/JP"
Decay Properties Of Multilinear Oscillatory Integrals

DECAY PROPERTIES OF MULTILINEAR OSCILLATORY INTEGRALS Zhen Zeng Philip T. Gressman In this thesis, we study the following multilinear oscillatory integral introduced by Christ, Li, Tao and Thiele [7] Iλ(f1, .fn) = ∫ Rm e (x) n ∏ j=1 fj(πj(x))η(x)dx, (0.0.1) where P : R → R is a real-valued measurable function, η is a compactly supported smooth cutoff function. Each πj is a surjective linear transformation from R to Rj , where 1 ≤ kj ≤ m− 1. Each fj : Rj → C is a locally integrable function with respect to Lebesgue measure on Rj . In Chapter 2, we first introduce the nondegeneracy degree along with the nondegeneracy norm defined in [7] to characterize the nondegeneracy condition of the phase function. In the same chapter, we will summarize some powerful tools that can help to simplify the problem and introduce the idea of a special geometric structure called “separation”. There are three results in this thesis. The first proves trilinear oscillatory integrals with nondegenerate polynomial phase always have the decay property. The second one extends the one-dimensional case whose phase function has large non-
Fonsecaea pedrosoi Conidia and Hyphae Activate Neutrophils Distinctly: Requirement of TLR-2 and TLR-4 in Neutrophil Effector Functions

Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus Fonsecaea pedrosoi. The infection is characterized by erythaematous papules and the histological sections demonstrating an external layer of fibrous tissue and an internal layer of thick granulomatous inflammatory tissue containing mainly macrophages and neutrophils. Several groups have been studying the roles of the innate and adaptive immune systems in F. pedrosoi infection; however, few studies have focused on the role of neutrophils in this infection. In the current study, we verified the importance of murine neutrophils in the killing of F. pedrosoi conidia and hyphae. We demonstrate that phagocytosis and reactive oxygen species during infection with conidia are TLR-2 and TLR-4-dependent and are essentials for conidial killing. Meanwhile, hyphal killing occurs by NETs formation, in a TLR-2, TLR-4 and ROS-independent manner. In vivo experiments showed that TLR-2 and TLR-4 are also important in Chromoblastomycosis infection. TLR-2KO and TLR-4KO animals had lower levels of MIP-2 and KC chemokines and impaired neutrophil migration to the infected site. These animals also had higher fungal loads during infection with F. pedrosoi conidia, confirming that TLR-2 and TLR-4 are essential receptors for F. pedrosoi recognition and immune system activation. Therefore, this study demonstrated for the first time that neutrophils activation during F. pedrosoi is conidial or hyphal-specific, with TLR-2 and TLR-4 being essential during conidial infection but unnecessary for hyphal killing by neutrophils Author Summary Chromoblastomycosis (CBM) is a chronic and progressive subcutaneous mycosis that affects mainly low-income individuals, such as farm workers. CBM have been diagnosed all over the world, but the majority of cases were diagnosed in tropical and subtropical climate countries. The treatment is difficult and involves the combination of antifungal prescriptions, cryo/heat-therapy and, in some cases, surgery to remove all the infected tissue. The treatment is long (at least 6 months) and expensive, leading to a high rate of treatment dropout and disease relapse. However, the understanding of pathogen-host interaction is far from being elucitaded. Our understanding is that this pathogen-host interaction in CBM needs to be uncovered so a different and more effective treatment could be proposed to help those patients that are struggling against this chronic infection. Therefore, our study shed a light in neutrophils and innate immune response against this fungal infection, showing the neutrophils capacity to kill Fonsecaea pedrosoi conidia and hifa, showing the importance of toll-like receptors 2 and 4 in the neutrophil fungicidal capacity against F. pedrosoi conidia but not hyphae. Therefore this work help to the better understanding of how our organism fights back in the CBM infection.
Ca2+ signalling and its consequences in the mousespinal cord dorsal horn under chronic pain

Chronic pain represents one major health problem of today’s global society. Some treatments fail and still many aspects of chronic pain development and maintenance are unknown. Here, we present new insights into the Ca2+ signalling behaviour of acute slices of murine spinal cord dorsal horn astrocytes and parvalbumin(PV)-positive neurons. To our knowledge we showed here for the first time that stimulation of preferred fibre classes from the dorsal root evokes Ca2+ signalling in the cytosol and nucleus of astrocytes and the cytosol of PV-neurons. In addition, we detected a decrease of these evoked Ca2+ signals under neuropathic pain conditions when stimulated with Aβ- or Aδ-fibre preferred frequencies. We did not observe differences under chronic inflammatory pain conditions, neither in astrocytes nor in PV-positive neurons. Further investigation showed that the Ca2+ signalling dependent immediate early gene Npas4 was reduced 3 days after neuropathic pain induction and that overexpression of NPAS4 in spinal dorsal horn neurons in vivo, leads to a rescue of mechanical but not thermal hypersensitivity. These findings suggest an important role of the Ca2+ signalling behaviour of astrocytes in response to Aβ- and Aδ-fibre stimulation under neuropathic pain under the tested conditions. Especially because of the occurrence of Ca2+ signalling in the astrocytic nucleus, we propose a similar gene regulation function as in neurons, which probably induce plasticity changes in astrocytes. This might be due to adaption to the neuronal activity required to transmit signals from the periphery to the brain, which is possibly disturbed under chronic pain conditions. Thus, the purpose of astrocytes to support those changes in pain conditions would also require changes in signalling behaviour. In addition we hypothesize an important role of NPAS4 regulation in the spinal cord dorsal horn under neuropathic pain conditions, primarily to control the inhibition of pain stimuli.
Efficient fabrication of a pre-invasive breast cancer model via double emulsification of Matrigel

• A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers.
Why, When and How We Propose Withdrawal Insulin Treatment in Type 2 Insulin Resistant Diabetes

Insulin treatment is the choice in insulinopenic diabetic patients, in order to prevent or delay microvascular lesions, related to hyperglycaemia. However in insulin resistant type 2 diabetes, the improvement in glycaemic control with insulin, is not without side effects, especially weight gain and hypoglycaemia. Many retrospective or case-control studies of insulin treatment have reported a higher prevalence of CVD in insulin-treated patients. However, many of these patients started insulin therapy in relation to different clinical settings, following this treatment for years. In clinical practice, the physician needs a protocol to assess the possible withdrawal of insulin in some of them.
Oscillatory processes during the aggregation and the fragmentation of the amyloid fibrils.

The objective of this thesis is to study the physical process of protein aggregation and fragmentation. More specifically, oscillatory kinetic phenomena are identified during this process and are the subject of an in-depth analysis. The process of protein aggregation and fragmentation is intimately linked to the contraction and development of a vast class of incurable neurodegenerative diseases, amyloid diseases. Our work focuses on prion diseases, a subcategory of amyloid diseases, caused by the misfolding of protein conformation and the aggregation of these misfolded proteins into fibrils. First, our study focuses on experimental static light scattering data (SLS). The signals obtained correspond approximately to the second moment of the size distribution of amyloid fibrils in vitro and therefore provide information on the evolution of the size distribution over time. We note damped oscillations at specific locations on the signals. These oscillations highlight the presence of complex, underlying kinetic phenomena during protein aggregation/ fragmentation processes. The analysis of SLS signals leads us to build a parametric characterization of oscillations in the frequency domain (Fourier domain). We propose a numerical procedure to obtain these parameters. Then, we build a statistical test of hypotheses. We thus obtain a p-value that allows us to quantitatively assert the presence of oscillations in the experimental signals. In a second step, we introduce and mathematically analyze a kinetic model of proteins capable of generating oscillations. The model is a variant of the polymerization/depolymerization system and considers two species of monomers: a pathological monomer that polymerizes and a healthy monomer that depolymerizes. Unlike traditional models, depolymerization is catalytic and non-linear and an exchange phenomenon occurs between the two species of monomers and polymers. The model combines a Lotka-Volterra system for monomers with a growth/fragmentation system: Becker-Doring in the discrete size setting, Lifshitz-Slyozov in the continuous size setting. In the discrete size model, the oscillations are damped and under certain conditions we prove the exponential convergence towards a stationary state. While in the continuous model, the system oscillates perpetually or converges to a Dirac depending on the shape of the reaction coefficients. By complexifying the model, in particular by integrating other species of polymers and kinetic reactions, it is possible to achieve a realistic modelling of protein kinetic processes. The mathematical study of these models leads to new interesting problems, improves and clarifies the understanding of the underlying physical phenomena.