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Gastro-esophageal reflux disease (GERD) is a pathological entity in which the mixture of gastric contents (with low pH because of the high content of HCl acid) and biliary juice (rich in proteolytic enzymes like pepsin and trypsin) causes lesions on the mucosa lining the esophagus. A higher prevalence of GERD was discovered in patients who had a total laryngectomy. Concerning laryngectomies with tracheo-esophageal speaking valves, it has been demonstrated that GERD is an independent risk factor for failure of this method of speech rehabilitation. The authors performed an analysis of English language articles found following a search of the major medical scientific databases (NCBI®, EMBASE®, Cochrane®) containing the following keyword string: vocal prosthesis, total laryngectomy, GERD, acid reflux, tracheo-esophageal fistula, failure. Studies showed that exposure to the protelolytic enzymes from the reflux juice increases the diameter of the tracheo-esophageal fistula and permits local granulation tissue to form. Progressively, the increasing fistula diameter leads to complications ranging from microaspiration of liquids and saliva to speaking valve expulsion or ingestion and temporary incapacity of oral feeding. Medical therapy in the postoperative period as well as long-term (6 months or more) correction of GERD (PPI therapy, H2 blockers, prokinetics) is also demonstrated to reduce the complication rate in this category of patients. GERD has a high prevalence in the total laryngectomy population of patients and it has multiple etiologic factors. In patients with tracheoesophageal vocal prostheses, GERD causes an increase in the fistula diameter – with important consequences that affect the patient's quality of life - his ability to phonate and his ability to swallow. These complications come with added costs because of the need to more frequently change the vocal prostheses with ones increasing in diameter, as well as multiple hospitalizations (even surgery to recalibrate or close the tracheo-esophageal fistula). Recognizing and treating this condition therefore decreases the risk of complications following vocal prosthesis speech rehabilitation.

RESEARCH AND SCIENCE TODAY is a biannual science journal established in 2011. The journal is an informational platform that publishes assessment articles and the results of various scientific research carried out by academics. We provide the authors with the opportunity to create and/or perfect their science writing skills. Thus, each issue of the journal (two per year and at least two supplements) will contain professional articles from any academic field, authored by domestic and international academics. The goal of this journal is to pass on relevant information to undergraduate, graduate, and post-graduate students as well as to fellow academics and researchers; the topics covered are unlimited, considering its multi-disciplinary profile. Regarding the national and international visibility of Research and Science Today, it is indexed in over 30 international databases (IDB) and is present in over 200 online libraries and catalogues; therefore, anybody can easily consult the articles featured in each issue by accessing the databases or simply the website.

Scoliosis is one of the most frequent spine deformities encountered in children and is regularly discovered after 15 years of age with a girls to boys ratio of 2:1. Vertebral arthrodesis involves both short and long term complications. Neurological complications consist of nerve root injuries, cauda equina or spinal cord deficit. Traction is a good orthopaedic technique of progressive deformity correction which attempts to minimize complications. The purpose of this study is to assess the complications that arise during halo gravity traction and to evaluate the correction of the scoliotic curves under traction. A single centre prospective study was conducted on 19 paediatric patients suffering from scoliosis that were admitted between 2019–2022. Traction-related complications were encountered in 94.7% of patients, with the most frequent being cervical pain (89.5%). It was followed by back pain, in 36.8% of the cases, with just 5.3% of the cases having experienced vertigo or pin displacement. Neurological symptoms were present in 26.3% of the patients and pin pain and pin infection equally affected 26.3% of patients. Even though minor halo related complications are frequent, with proper patient monitoring they can be addressed, thus making traction a safe method for progressive curve correction.

The article presents a study on transmandibular approach for curative surgery patients with T4 tumors of the oral cavity and hypopharynx. Topics discussed include assessment of patients with magnetic resonance imaging and computed tomography, performing dental evaluation for dental extractions, and performance of glosopelvectomy with partial mandibulectomy. Also mentioned are complications of curative surgery including fistulas, necrosis of the cervical soft tissues, and mediastinitis.

This study explores nonlinear development of the magnetized Rayleigh-Taylor instability (RTI) in a prominence-corona transition region. Using a two-fluid model of a partially ionized plasma, we compare RTI simulations for several different magnetic field configurations. We follow prior descriptions of the numerical prominence model (Popescu Braileanu et al. 2021 Astron. Astrophys. , A93 (doi:10.1051/0004-6361/202039053), Popescu Braileanu 646 , A93 (doi:10.1051/0004-6361/202039053), Popescu Braileanu et al. , A181 (doi:10.1051/0004-6361/202140425) and Popescu Braileanu Astron. Astrophys. 650 , A181 (doi:10.1051/0004-6361/202140425) and Popescu Braileanu et al. 2023 Astron. Astrophys. 670 , A31 (doi:10.1051/0004-6361/202142996)) and explore the charged-neutral fluid coupling and plasma heating in a two-dimensional mixing layer for different magnetic field configurations. We also investigate how the shear in magnetic field surrounding a prominence may impact the release of the gravitational potential energy of the prominence material. We show that the flow decoupling is strongest in the plane normal to the direction of the magnetic field, where neutral pressure gradients drive ion-neutral drifts and frictional heating is balanced by adiabatic cooling of the expanding prominence material. We also show that magnetic field within the mixing plane can lead to faster nonlinear release of the gravitational energy driving the RTI, while more efficiently heating the plasma via viscous dissipation of associated plasma flows. We relate the computational results to potential observables by highlighting how integrating over under-resolved two-fluid sub-structure may lead to misinterpretation of observational data. This article is part of the theme issue 'Partially ionized plasma of the solar atmosphere: recent advances and future pathways'.

In this paper, we study the role of radiative cooling (RC) in a two-fluid model consisting of coupled neutrals and charged particles. We first analyse the linearized two-fluid equations where we include radiative losses in the energy equation for the charged particles. In a one-dimensional geometry for parallel propagation and in the limiting cases of weak and strong coupling, it can be shown analytically that the instability conditions for the thermal mode and the sound waves, the isobaric and isentropic criteria, respectively, remain unchanged with respect to one-fluid radiative plasmas. For the parameters considered in this paper, representative for the solar corona, the RC produces growth of the thermal mode and damping of the sound waves. In the weak coupling limit, the growth of the thermal instability and the damping of the sound waves is as derived in Field (Field 1965 Astrophys. J. 142 , 531 (doi:10.1086/148317)) using the charged fluid properties. When neutrals are included and are sufficiently coupled to the charges, the thermal mode growth rate and the wave damping both reduce by the same factor, which depends on the ionization fraction only. For a heating function that is constant in time, we find that the growth of the thermal mode and the damping of the sound waves are slightly larger. The numerical calculation of the eigenvalues of the general system of equations in a three-dimensional geometry confirm the analytic results. We then run two-dimensional fully nonlinear simulations that give consistent results: a higher ionization fraction or lower coupling will increase the growth rate. The magnetic field contribution is negligible in the linear phase. Ionization-recombination effects might play an important role because the RC produces a large range of temperatures in the system. In the numerical simulation, after the first condensation phase, when the minimum temperature is reached, the fraction of neutrals increases four orders of magnitude because of the recombination. This article is part of the theme issue 'Partially ionized plasma of the solar atmosphere: recent advances and future pathways'.

Introduction: Oropharyngeal cancer requires a comprehensive evaluation of treatment options, including surgery, radiation therapy, and chemotherapy. It is crucial to customize these treatments based on the stage of the tumor and the overall health of the patient, enabling personalized or combined approaches. Transoral surgical techniques have regained popularity due to the advancements and limitations of non-surgical strategies. The potential influence of surgical procedures on patients' quality of life highlights the need for careful intervention selection; among them, the transoral approach has proven to be especially beneficial for early-stage oropharyngeal neoplasms., Methods: To explore potential treatments for early-stage oropharyngeal malignancies, this study carefully reviews the literature, using information from papers, current research, and global databases. The review protocol commenced on November 2023. A comprehensive search of the PUBMED database was undertaken, employing pertinent terms associated with oropharyngeal, transoral surgery or radiotherapy, robotic surgery, and chemotherapy., Results: Treating early-stage oropharyngeal neoplasms is particularly intriguing due to the multitude of variables influencing treatment decisions, leading to ongoing debates in specialized literature. Regardless of the chosen approach, maintaining a high quality of life is crucial. To assess this, standardized questionnaires from the European Organization for Research and Treatment of Cancer were employed, revealing superior outcomes for patients solely undergoing surgical intervention. Additionally, in the realm of specialized literature, cases of HPV-positive oropharyngeal neoplasms are recognized for their heightened radiosensitivity and more favorable long-term prognosis., Conclusions: Surgical intervention and radiotherapy are the main treatment options for oropharyngeal cancer, and they can be used separately or together for maximum effectiveness. Amid ongoing discussions, determining the superior effectiveness between the two options continues to be a matter of debate. This study provides a comprehensive analysis, offering valuable perspectives for future discussions. Neoplasm in the oropharynx can be effectively treated using transoral microsurgery.

Multiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosis and management of MM. The main purpose of this study is to determine whether NGS, in addition to cytogenetics, can influence risk stratification and management. Additionally, we aim to establish whether mutational analysis of the CD138 cell population is a suitable option for the characterization of MM compared to the bulk population. Following the separation of the plasma cells harvested from 35 patients newly diagnosed with MM, we performed a FISH analysis to detect the most common chromosomal abnormalities. Consecutively, we used NGS to evaluate NRAS, KRAS, BRAF, and TP53 mutations in plasma cell populations and in bone marrow samples. NGS data showed that sequencing CD138 cells provides a more sensitive approach. We identified several variants in BRAF, KRAS, and TP53 that were not previously associated with MM. Considering that the presence of somatic mutations could influence risk stratification and therapeutic approaches of patients with MM, sensitive detection of these mutations at diagnosis is essential for optimal management of MM.

The Mancha3D code is a versatile tool for numerical simulations of magnetohydrodynamic (MHD) processes in solar/stellar atmospheres. The code includes nonideal physics derived from plasma partial ionization, a realistic equation of state and radiative transfer, which allows performing high-quality realistic simulations of magnetoconvection, as well as idealized simulations of particular processes, such as wave propagation, instabilities or energetic events. The paper summarizes the equations and methods used in the Mancha3D (Multifluid (-purpose -physics -dimensional) Advanced Non-ideal MHD Code for High resolution simulations in Astrophysics 3D) code. It also describes its numerical stability and parallel performance and efficiency. The code is based on a finite difference discretization and a memory-saving Runge-Kutta (RK) scheme. It handles nonideal effects through super-time-stepping and Hall diffusion schemes, and takes into account thermal conduction by solving an additional hyperbolic equation for the heat flux. The code is easily configurable to perform different kinds of simulations. Several examples of the code usage are given. It is demonstrated that splitting variables into equilibrium and perturbation parts is essential for simulations of wave propagation in a static background. A perfectly matched layer (PML) boundary condition built into the code greatly facilitates a nonreflective open boundary implementation. Spatial filtering is an important numerical remedy to eliminate grid-size perturbations enhancing the code stability. Parallel performance analysis reveals that the code is strongly memory bound, which is a natural consequence of the numerical techniques used, such as split variables and PML boundary conditions. Both strong and weak scalings show adequate performance up to several thousands of processors (CPUs)., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Mutations in the receptor tyrosine kinases (RTKs) FLT3 and KIT are frequent and associated with poor outcomes in acute myeloid leukemia (AML). Although selective FLT3 inhibitors (FLT3i) are clinically effective, remissions are short-lived due to secondary resistance characterized by acquired mutations constitutively activating the RAS/MAPK pathway. Hereby, we report the pre-clinical efficacy of co-targeting SHP2, a critical node in MAPK signaling, and BCL2 in RTK-driven AML. The allosteric SHP2 inhibitor RMC-4550 suppresses proliferation of AML cell lines with FLT3 and KIT mutations, including cell lines with acquired resistance to FLT3i. We demonstrate that pharmacologic SHP2 inhibition unveils an Achilles' heel of RTK-driven AML, increasing apoptotic dependency on BCL2 via MAPK-dependent mechanisms, including upregulation of BMF and downregulation of MCL1. Consequently, RMC-4550 and venetoclax are synergistically lethal in AML cell lines and in clinically relevant xenograft models. Our results provide mechanistic rationale and pre-clinical evidence for co-targeting SHP2 and BCL2 in RTK-driven AML., Competing Interests: Declaration of interests C.S. is a former employee and stockholder of Revolution Medicines, Inc., and a current employee and stockholder of BridgeBio Pharma, Inc. B.J.L. is a current employee of Revolution Medicines, Inc. J.A.C. is a current employee of Outpace Bio. S.K.T. reports research funding unrelated to this work from Beam Therapeutics; Kura Oncology; Incyte Corporation; scientific advisory boards for Aleta Biotherapeutics, Kura Oncology, and Syndax Pharmaceuticals; consulting for bluebird bio; and travel support from Amgen. C.C.S. reports research funding from AbbVie, Inc., and Revolution Medicines and has served as an advisory board member for AbbVie, Inc., and Genentech., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Multiple sclerosis (MS) is the leading cause of non-traumatic disability in young adults. New avenues are needed to help predict individuals at risk for developing MS and aid in diagnosis, prognosis, and outcome of therapeutic treatments. Previously, we showed that skin fibroblasts derived from patients with MS have altered signatures of cell stress and bioenergetics, which likely reflects changes in their protein, lipid, and biochemical profiles. Here, we used Fourier transform infrared (FTIR) spectroscopy to determine if the biochemical landscape of MS skin fibroblasts were altered when compared to age- and sex-matched controls (CTRL). More so, we sought to determine if FTIR spectroscopic signatures detected in MS skin fibroblasts are disease specific by comparing them to amyotrophic lateral sclerosis (ALS) skin fibroblasts. Spectral profiling of skin fibroblasts from MS individuals suggests significant alterations in lipid and protein organization and homeostasis, which may be affecting metabolic processes, cellular organization, and oxidation status. Sparse partial least squares-discriminant analysis of spectral profiles show that CTRL skin fibroblasts segregate well from diseased cells and that changes in MS and ALS may be unique. Differential changes in the spectral profile of CTRL, MS, and ALS cells support the development of FTIR spectroscopy to detect biomolecular modifications in patient-derived skin fibroblasts, which may eventually help establish novel peripheral biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wilkins, Gakh, Guo, Popescu, Staff and Lucchinetti.)

Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive blood cancer with a poor prognosis despite intensive chemotherapy or stem cell transplant. Children and adolescents with positive end-of-induction minimal residual disease have an overall survival lower than 30%. However, data regarding therapeutic alternatives for this disease is nearly nonexistent, emphasizing the critical need for new or adjunctive therapies that can improve outcomes. We previously reported on the therapeutic efficacy of venetoclax (ABT-199) in hypodiploid B-lineage ALL but with limitations as monotherapy. In this study, we set out to identify drugs enhancing the anti-leukemic effect of venetoclax in hypodiploid ALL. Using a highthroughput drug screen, we identified dinaciclib, a cyclin-dependent kinase inhibitor that worked synergistically with venetoclax to induce cell death in hypodiploid cell lines. This combination eradicated leukemic blasts within hypodiploid ALL patient-derived xenografts mice with low off-target toxicity. Our findings suggest that dual inhibition of BCL-2 (venetoclax) and CDK9/MCL-1 (dinaciclib) is a promising therapeutic approach in hypodiploid ALL, warranting further investigation to inform clinical trials in this high-risk patient population.

Allosteric SHP2 inhibitors are a novel class of compounds that target hyperactive Ras/Mitogen Activated Protein Kinase (MAPK) signaling. In this issue of JEM, Wei et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221563) report a genome-wide CRISPR/Cas9 knockout screen that uncovered novel mechanisms of adaptive resistance to pharmacologic inhibition of SHP2., (© 2023 Popescu and Shannon.)

Laryngeal cancer is an important oncological entity in which prognosis depends on the establishment of appropriate preventive and diagnostic measures, especially in high-risk populations. We present a retrospective two-year study (January 2021 to December 2022) with 152 patients diagnosed with laryngeal cancer from a tertiary hospital in Romania. The average age of the patients was 62 years old for both sexes, with a range from 44 to 83 years. The most frequent symptom was dysphonia with or without dyspnea in 142 cases (93.42%), followed by dyspnea alone in nine patients (5.92%) and dysphagia in one case (0.66%). Surgical treatment in this study consisted of partial laryngectomy (CO 2 laser transoral tumor ablation, supraglottic horizontal laryngectomy or hemilaryngectomy), or total laryngectomy. The main treatment was total laryngectomy (63%). For the eight patients with initial organ preservation treatment, the average time of recurrence was about two-and-a-half years. For the four patients who underwent a total circular pharyngo-laryngectomy, the upper digestive tract needed to be rebuilt with a salivary bypass tube or with a tubed myocutaneous flap from the major pectoralis muscle. One strong point is characteristic of the study group in gathering patients with advanced stages of laryngeal carcinoma candidates for salvage surgery and extended reconstruction methods. The development of new prevention protocols is mandatory in Eastern European countries.

The objective of the present research was to investigate the psychometric properties and the validity of the student version of the Burnout Assessment Tool (BAT) in a Romanian undergraduate student sample. A sample of undergraduate students (N = 399, 60,70% female) from a Romanian university completed the BAT and other measures used for assessing measurement validity. Confirmatory factor analyses supported the original factor structure of the BAT, and all scales showed good internal consistency. The validity of the BAT scales was supported by their strong associations with measures of depression, anxiety, stress, psychosomatic symptoms, prospective appraisal of future tasks, and coping strategies., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04232-w., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The influence of processing on the martensitic transformation and related magnetic properties of the Ni 55 Fe 18 Nd 2 Ga 25 ferromagnetic shape memory alloy, as bulk and ribbons prepared by the melt spinning method and subjected to different thermal treatments, is investigated. Structural, calorimetric, and magnetic characterizations are performed. Thermal treatment at 1173 K induces a decrease in both the Curie and the martensitic transformation temperatures, while a treatment at 673 K produces the structural ordering of the ribbons, hence an increase in T C . A maximum value of the magnetic entropy variation of -5.41 J/kgK was recorded at 310 K for the as quenched ribbons. The evaluation of the magnetoresistive effect shows a remarkable value of -13.5% at 275 K on the bulk sample, which is much higher than in the ribbons.

Squamous cell carcinoma of the head and neck (HNSCC) is a common malignancy often diagnosed in the advanced stage with a complex negative influence on the patient's quality of life (QoL). Given its multi-modal treatment, the first step is to adequately balance the needs of the patient, and the second step includes the consultations, interventions, and care provided by the medical team, with the purpose of improving the overall management of the HNSCC. Current attempts to develop and validate quality-of-life instruments specific to cancers of the head and neck have been reported, and certain questionnaires are now available. We performed a retrospective study in a tertiary centre, involving 89 patients who survived 3 years after HNSCC surgery. A patient-related outcome measurement was made using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 instruments to assess QoL at admission and 3 years after treatment. The 3-year survivors reported an overall improvement in QoL compared with those in the pre-treatment period. The unique details of head and neck cancer treatments outline the importance of considering the characteristics of the patient population in quality-of-life research and also identify how quality-of-life data can contribute to the care provided by the multi-disciplinary team involved in a patient's follow-up., Competing Interests: The authors declare no conflict of interest.

Aims: To assess the characteristics, management, and survival of patients with multiple native valvular heart disease (VHD)., Methods and Results: Among the 5087 patients with ≥1 severe left-sided native VHD included in the EURObservational VHD II Survey (maximum 3-month recruitment period per centre between January and August 2017 with a 6-month follow-up), 3571 had a single left-sided VHD (Group A, 70.2%), 363 had one severe left-sided VHD with moderate VHD of the other ipsilateral valve (Group B, 7.1%), and 1153 patients (22.7%) had ≥2 severe native VHDs (left-sided and/or tricuspid regurgitation, Group C). Patients with multiple VHD (Groups B and C) were more often women, had greater congestive heart failure (CHF) and comorbidity, higher left atrial volumes and pulmonary pressures, and lower ejection fraction than Group A patients (all P ≤ 0.01). During the index hospitalization, 36.7% of Group A (n = 1312), 26.7% of Group B (n = 97), and 32.7% of Group C (n = 377) underwent valvular intervention (P < 0.001). Six-month survival was better for Group A than for Group B or C (both P < 0.001), even after adjustment for age, sex, body mass index, and Charlson index [hazard ratio (HR) 95% confidence interval (CI) 1.62 (1.10-2.38) vs. Group B and HR 95% CI 1.72 (1.32-2.25) vs. Group C]. Groups B and C had more CHF at 6 months than Group A (both P < 0.001). Factors associated with mortality in Group C were age, CHF, and comorbidity (all P < 0.010)., Conclusion: Multiple VHD is common, encountered in nearly 30% of patients with left-sided native VHD, and associated with greater cardiac damage and leads to higher mortality and more heart failure at 6 months than single VHD, yet with lower rates of surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcripts, and their associations with demyelinating activity, we documented a spectrum of astrocytopathy in addition to complement deposition, microglial reaction, granulocyte infiltration and regenerating activity. Within advanced demyelinating lesions, and in periplaque areas, there was remarkable hypertrophic astrogliosis, more subtle than astrocytic lysis. A degenerative component was suggested by 'dystrophic' morphology, cytoplasmic vacuolation, Rosenthal fibres and associated stress protein markers. The abundance of AQP4 mRNA transcripts in sublytic reactive astrocytes devoid of aquaporin-4 protein supported in vivo restoration following IgG-induced aquaporin-4 endocytosis/degradation. Astrocytic alterations extending beyond demyelinating lesions speak to astrocytopathy being an early and primary event in the evolving neuromyelitis optica lesion. Focal astrocytopathy observed without aquaporin-4 loss or lytic complement component deposition verifies that astrocytic reactions in neuromyelitis optica are not solely dependent on IgG-mediated aquaporin-4 loss or lysis by complement or by IgG-dependent leucocyte mediators. We conclude that neuromyelitis optica reflects a global astrocytopathy, initiated by binding of IgG to aquaporin-4 and not simply definable by demyelination and astrocytic lysis. The spectrum of astrocytic morphological changes in neuromyelitis optica attests to the complexity of factors influencing the range of astrocytic physiological responses to a targeted attack by aquaporin-4-specific IgG. Sublytic astrocytic reactions are no doubt an important determinant of the lesion's evolution and potential for repair. Pharmacological manipulation of the astrocytic stress response may offer new avenues for therapeutic intervention., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a 'sub-proteome', such as the 'metalloproteome', defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α2macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1-1) isoform in 15% of the population., Competing Interests: The authors have declared that no competing interests exist.

The influence of the rapid solidification technique and heat treatment on the martensitic transformation, magnetic properties, thermo- and magnetic induced strain and electrical resistivity is investigated for the Cu doped NiMnGa Heusler-based ferromagnetic shape memory ribbons. The martensitic transformation temperatures are unexpectedly low (below 90 K-which can be attributed to the disordered texture as well as to the uncertainty in the elements substituted by the Cu), preceded by a premartensitic transformation (starting at around 190 K). A thermal treatment slightly increases the transformation as well as the Curie temperatures. Additionally, the thermal treatment promotes a higher magnetization value of the austenite phase and a lower one in the martensite. The shift of the martensitic transformation temperatures induced by the applied magnetic field, quantified from thermo-magnetic and thermo-magnetic induced strain measurements, is measured to have a positive value of about 1 K/T, and is then used to calculate the transformation entropy of the ribbons. The magnetostriction measurements suggest a rotational mechanism in low fields for the thermal treated samples and a saturation tendency at higher magnetic fields, except for the temperatures close to the phase transition temperatures (saturation is not reached at 5 T), where a linear volume magnetostriction cannot be ruled out. Resistivity and magnetoresistance properties have also been measured for all the samples.

This work focuses on the temperature evolution of the martensitic phase ε (hexagonal close packed) induced by the severe plastic deformation via High Speed High Pressure Torsion method in Fe 57 Mn 27 Si 11 Cr 5 (at %) alloy. The iron rich alloy crystalline structure, magnetic and transport properties were investigated on samples subjected to room temperature High Speed High Pressure Torsion incorporating 1.86 degree of deformation and also hot-compression. Thermo-resistivity as well as thermomagnetic measurements indicate an antiferromagnetic behavior with the Néel temperature (T N ) around 244 K, directly related to the austenitic γ-phase. The sudden increase of the resistivity on cooling below the Néel temperature can be explained by an increased phonon-electron interaction. In-situ magnetic and electric transport measurements up to 900 K are equivalent to thermal treatments and lead to the appearance of the bcc-ferrite-like type phase, to the detriment of the ε(hcp) martensite and the γ (fcc) austenite phases.

Composites of magnetite (Fe 3 O 4 ) nanoparticles dispersed in a polydimethylsiloxane (PDMS) matrix were prepared by a molding process. Two types of samples were obtained by free polymerization with randomly dispersed particles and by polymerization in an applied magnetic field. The magnetite nanoparticles were obtained from magnetic micrograins of acicular goethite (α-FeOOH) and spherical hematite (α-Fe 2 O 3 ), as demonstrated by XRD measurements. The evaluation of morphological and compositional properties of the PDMS:Fe 3 O 4 composites, performed by SEM and EDX, showed that the magnetic particles were uniformly distributed in the polymer matrix. Addition of magnetic dispersions promotes an increase of thermal conductivity compared with pristine PDMS, while further orienting the powders in a magnetic field during the polymerization process induces a decrease of the thermal conductivity compared with the un-oriented samples. The shape of the magnetic dispersions is an important factor, acicular dispersions providing a higher value for thermal conductivity compared with classic commercial powders with almost spherical shapes.

Gastrointestinal stromal tumors (GISTs) are the most frequently encountered mesenchymal tumors that develop anywhere along the gastrointestinal (GI) tract, but they account for less than 1% of all GI tumors. However, GISTs can also develop outside the GI tract. They are referred to as extragastrointestinal stromal tumors (EGISTs) and represent around 5-10% of all GISTs. In this latter case, the tumor itself is not connected to the GI tract and can affect the omentum, mesentery, and retroperitoneum. EGISTs can also originate from the pancreas, but they are extremely uncommon. It is estimated that pancreatic EGISTs account for about 5% of all EGISTs, with around 30 cases being reported in the literature so far. The current report presents an extremely rare case of pancreatic EGIST encountered in a 53-year-old woman with no remarkable personal or family medical history. Surgical resection of the pancreatic head tumor through pancreaticoduodenectomy using Whipple procedure combined with negative resection margins and adjuvant Imatinib mesylate treatment led to a favorable postoperative evolution. The follow-up at six months after surgery did not reveal any malignant changes.

This study aims to establish whether the use of biomaterials, particularly polydimethylsiloxane (PDMS), for surgical reconstruction of the esophagus with templates, Montgomery salivary tube, after radical oncology surgery for malignant neoplasia is an optimal choice for patients' safety and for optimal function preservation and organ rehabilitation. Structural analysis by Raman spectrometry and biomechanical properties with dynamic mechanical analysis are performed for fatigue strength and toughness, essential factors in durability of a prosthesis in the reconstruction practice of the esophagus. Nanocomposites with silicone elastomers and nanoparticles used in implantable devices and in reconstruction surgery present risks of infection and fatigue strength when required to perform a mechanical effort for long periods of time. This report takes into account the effect of silver (Ag) nanoparticles on the fatigue strength using polydimethylsiloxane (PDMS) matrix, representative for silicon elastomers used in implantable devices. PDMS with 5% (wt) Ag nanoparticles of 100-150 nm during mechanical fatigue testing at shear strength loses elasticity properties after 400 loading-unloading cycles and up to 15% shear strain. The fatigue strength, toughness, maximum shear strength, as well as clinical properties are key issues in designing Montgomery salivary tube and derivates with appropriate biomechanical behavior for each patient. Prosthesis design needs to indulge both clinical outcomes as well as design methods and research in the field of biomaterials.

The equimolar oxide mixture β-Ga 2 O 3 -α-Fe 2 O 3 was subjected to high-energy ball milling (HEBM) with the aim to obtain the nanoscaled GaFeO 3 ortho-ferrite. X-ray diffraction, 57 Fe Mössbauer spectroscopy, and transmission electron microscopy were used to evidence the phase structure and evolution of the equimolar nano-system β-Ga 2 O 3 -α-Fe 2 O 3 under mechanochemical activation, either as-prepared or followed by subsequent calcination. The mechanical activation was performed for 2 h to 12 h in normal atmosphere. After 12 h of HEBM, only nanoscaled (~20 nm) gallium-doped α-Fe 2 O 3 was obtained. The GaFeO 3 structure was obtained as single phase, merely after calcination at 950 °C for a couple of hours, of the sample being subjected to HEBM for 12 h. This temperature is 450 °C lower than used in the conventional solid phase reaction to obtain gallium orthoferrite. The optical and magnetic properties of representative nanoscaled samples, revealing their multifunctional character, were presented.

Therapy for those with relapsed or refractory acute myeloid leukemia is suboptimal. Studies have suggested that timed sequential salvage combination cytotoxic chemotherapy may have particular utility for that indication. We report here a series of ten such adult patients treated sequentially at a single center with EMA (cytarabine 500 mg/m 2 /day as continuous infusion on days 1-3 and days 8-10, mitoxantrone 12 mg/m 2 /day on days 1-3, and etoposide 200 mg/m 2 /day as continuous infusion on days 8-10). The overall complete remission rate was 40% (including 3 of 4 of those with relapsed disease) but use of this regimen was associated with prolonged cytopenia and a high rate of infectious adverse events. Even with the availability of modern infectious prophylaxis and therapies, the EMA regimen is likely best reserved for those with relapsed disease treated with curative intent prior to an allogeneic hematopoietic cell transplant., Competing Interests: Conflict of Interest: CSH has received laboratory research funding from Merck and Sellas. CL has served on an advisory board for Agios, Daiichi-Sankyo, and Jazz Pharmaceuticals and as a speaker for Astellas and Jazz Pharmaceuticals. All other authors report not relevant conflicts of interest.

Acute myeloid leukemia (AML) is a genetically heterogeneous disease that is characterized by abnormal clonal proliferation of myeloid progenitor cells found predominantly within the bone marrow (BM) and blood. Recent studies suggest that genetic and phenotypic alterations in the BM microenvironment support leukemogenesis and allow leukemic cells to survive and evade chemotherapy-induced death. However, despite substantial evidence indicating the role of tumor-host interactions in AML pathogenesis, little is known about the complex microenvironment of the BM. To address this, we performed novel proteomic profiling of the noncellular compartment of the BM microenvironment in patients with AML (n = 10) and age- and sex-matched healthy control subjects (n = 10) using an aptamer-based, highly multiplexed, affinity proteomics platform (SOMAscan). We show that proteomic assessment of blood or RNA-sequencing of BM are suboptimal alternate screening strategies to determine the true proteomic composition of the extracellular soluble compartment of AML patient BM. Proteomic analysis revealed that 168 proteins significantly differed in abundance, with 91 upregulated and 77 downregulated in leukemic BM. A highly connected signaling network of cytokines and chemokines, including IL-8, was found to be the most prominent proteomic signature associated with AML in the BM microenvironment. We report the first description of significantly elevated levels of the myelosuppressive chemokine CCL23 (myeloid progenitor inhibitory factor-1) in both AML and myelodysplastic syndrome patients and perform functional experiments supportive of a role in the suppression of normal hematopoiesis. This unique paired RNA-sequencing and proteomics data set provides innovative mechanistic insights into AML and healthy aging and should serve as a useful public resource.

Aims: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey., Methods and Results: Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE., Conclusion: EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Dual HIV infections are possible and likely in people who inject drugs (PWID). Thirty-eight newly diagnosed patients, 19 PWID and 19 heterosexually HIV infected were analyzed. V2V3 loop of HIV-1 env gene was sequenced on the NGS platform 454 GSJunior (Roche). HIV-1 dual/multiple infections were identified in five PWID. For three of these patients, the reconstructed variants belonged to pure F1 subtype and CRF14&#95;BG strains according to phylogenetic analysis. New recombinant forms between these parental strains were identified in two PWID samples. NGS data can provide, with the help of phylogenetic analysis, important insights about the intra-host sub-population structure., (Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Unstable isotopes and their capacity to emit ionizing radiation have been employed in clinical practice not only for diagnostic, but also for therapeutic purposes, with significant contribution in several fields of medicine and primarily in the management of oncologic patients. Their efficacy is associated with their ability to provide the targeted delivery of ionizing radiation for a determined duration. These compounds can be used for curative or palliative treatment, as well as for a diagnostic-therapeutic (theranostic) approach. This review summarises the most recent trends in radionuclide treatment for several malignancies, including prostate cancer, neuroendocrine tumours, and hematological and thyroid malignancies, in which radionuclide-based therapies have been employed with high effectiveness.

Aims: This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases., Methods and Results: Demographic data (age, body surface area, blood pressure, and heart rhythm and rate), type (vendor and model) of ultrasound system used and image quality need to be reported. In addition, measurements should be normalized for body size. Reference normal values, derived by ASE/EACVI recommendations, shall always be reported to differentiate normal from pathological conditions. This Expert Consensus document suggests avoiding the surveillance of specific variable using different ultrasound techniques (e.g. in echo labs with high expertise in left ventricular ejection fraction by 3D and not by 2D echocardiography). The report should be also tailored in relation with different cardiac pathologies, quality of images, and needs of the caregivers., Conclusion: The conclusion should be concise reflecting the status of left ventricular structure and function, the presence of left atrial and/or aortic dilation, right ventricular dysfunction, and pulmonary hypertension, leading to an objective communication with the patient health caregiver. Variation over time should be considered carefully, taking always into account the consistency of the parameters used for comparison., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)