Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of autologous stem cell transplantation in multiple myeloma.

Patients undergoing autologous stem cell transplantation (auto-SCT) face elevated risks of infections. Additionally, patients colonized in the gastrointestinal tract with antibiotic-resistant bacteria (ARB) are at higher risk of infection with ARB and other infections. Therefore, patients colonized with ARB before auto-SCT should present with an exceptionally high incidence of infections.

Thermal and Structural Analysis of a High-Entropy CrMnFeCoNiP Alloy-Influence of Cooling Rates on Phase Transformations.

This study investigates the influence of cooling rates on the microstructure and phase transformations of the high-entropy alloy CrMnFeCoNiP. The alloy was synthesized via arc melting and subjected to three cooling conditions: slow cooling (52 K/s), accelerated cooling after a short electric arc pulse (3018 K/s), and rapid quenching (10⁵-10⁶ K/s) using the melt-spinning method. The microstructures were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Mössbauer spectroscopy.

One-Pot Telescoping -Transfer and Trifluoromethylation for the Synthesis of 2-CFS-Imidazoles with -Oxides as Convenient Precursors.

Readily available 2-unsubstituted imidazole -oxides were examined as starting materials for the preparation of fully substituted 1,4,5-aryl/alkyl 2-trifluoromethylsulfanyl-imidazoles. Whereas activation of the -oxide function followed by attempted nucleophilic addition of the SCF was in vain, the alternative approach involving "sulfur transfer reaction" and subsequent electrophilic trifluoromethylation with Togni reagent provided target products in high yield via a one-pot procedure. The structure of representative enantiomerically pure imidazol-2-yl trifluoromethyl sulfide was confirmed by X-ray analysis.

The Concept of Creating Digital Twins of Bridges Using Load Tests.

The paper sheds light on the process of creating and validating the digital twin of bridges, emphasizing the crucial role of load testing, BIM models, and FEM models. At first, the paper presents a comprehensive definition of the digital twin concept, outlining its core principles and features. Then, the framework for implementing the digital twin concept in bridge facilities is discussed, highlighting its potential applications and benefits.

Automation of structural health monitoring (SHM) system of a bridge using BIMification approach and BIM-based finite element model development.

This research focuses on the automation of an existing structural health monitoring system of a bridge using the BIMification approach. This process starts with the Finite Element Analysis (FEA) of an existing bridge for the numerical calculations of static and dynamic parameters. The validation of the FE model and existing SHM system was carried out by the field load testing (Static and dynamic) of the bridge.

Oligoclonal gammopathy: An analysis of 253 cases.

Background: Oligoclonal gammopathy (OG) is a rare disorder of the lymphoid system that is characterized by the presence of at least 2 distinct monoclonal proteins in a patient's serum or urine. The biological and clinical characteristics of this disease are as yet poorly understood.

Objectives: The study aimed to assess whether there are significant differences between patients with OG regarding the developmental history (i.

One-Pot Synthesis of 1-Aryl-3-trifluoromethylpyrazoles Using Nitrile Imines and Mercaptoacetaldehyde As a Surrogate of Acetylene.

A synthetically useful approach for one-pot preparation of 1-aryl-3-trifluoromethylpyrazoles using in situ generated nitrile imines and mercaptoacetaldehyde applied as 1 equiv of acetylene is presented. This protocol comprises (3 + 3)-annulation of the mentioned reagents to form 5,6-dihydro-5-hydroxy-4-1,3,4-thiadiazine, followed by cascade dehydration/ring contraction reactions with -TsCl. In addition, representative nonfluorinated analogues functionalized with Ph, Ac, and COEt groups at the C(3)-position of the pyrazole ring were also prepared by the devised method.

Regioselective [3 + 2] cycloaddition of di/trifluoromethylated hydrazonoyl chlorides with fluorinated nitroalkenes: a facile access to 3-di/trifluoroalkyl-5-fluoropyrazoles.

Herein we describe the base-mediated [3 + 2] cycloaddition reaction of di/trifluoromethylated hydrazonoyl chlorides with fluorinated nitroalkenes. The reaction protocol provides a direct and facile strategy for the dual incorporation of a fluorine atom and fluoroalkyl group into pyrazole cores, thus allowing rapid access to a wide variety of densely functionalized 3-di/trifluoroalkyl-5-fluoropyrazoles in generally high yields with excellent regioselectivities. Furthermore, several drug-like 3-di/trifluoroalkyl-5-fluoropyrazoles have been synthesized, demonstrating potent inhibitory activities against cyclooxygenase 2 (COX-2).

Trifluoromethylated 4,5-Dihydro-1,2,4-triazin-6(1)-ones via (3+3)-Annulation of Nitrile Imines with α-Amino Esters.

The synthesis of two series of monocyclic and bicyclic trifluoromethylated 4,5-dihydro-1,2,4-triazin-6(1)-one derivatives based on (3+3)-annulation of methyl esters derived from natural α-amino acids with in situ generated trifluoroacetonitrile imines has been described. The devised protocol is characterized by a wide scope, easily accessible substrates, remarkable functional group tolerance, and high chemical yield. In reactions with chiral starting materials, no racemization at the stereogenic centers was observed and the respective enantiomerically pure products were obtained.

Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines.

A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring.

Next generations of CAR-T cells - new therapeutic opportunities in hematology?

In recent years, the introduction of chimeric antigen receptor (CAR) T-cell therapies into clinics has been a breakthrough in treating relapsed or refractory malignancies in hematology and oncology. To date, Food and Drug Administration (FDA) has approved six CAR-T therapies for specific non-Hodgkin lymphomas, B-cell acute lymphoblastic leukemia, and multiple myeloma. All registered treatments and most clinical trials are based on so-called 2nd generation CARs, which consist of an extracellular antigen-binding region, one costimulatory domain, and a CD3z signaling domain.

Thermal Energy Analysis of Projectiles during Ricochetting Using a Thermal Camera.

This paper presents the results of a study of the hazards of ground ignition and/or explosion when various small-calibre projectiles struck various solid materials placed on a test stand in environments at risk of ignition (fire) or explosion (ricochets and projectile penetration of obstacles). For projectile ricochetting tests, the following were used: an armour plate, concrete, sidewalk and granite slabs, etc., and various small-calibre projectiles: 7.

Fluorinated Analogues of Lepidilines A and C: Synthesis and Screening of Their Anticancer and Antiviral Activity.

Starting with fluorinated benzylamines, a series of 2-unsubstituted imidazole -oxides was prepared and subsequently deoxygenated in order to prepare the corresponding imidazoles. The latter were treated with benzyl halides yielding imidazolium salts, which are considered fluorinated analogues of naturally occurring imidazolium alkaloids known as lepidilines A and C. A second series of oxa-lepidiline analogues was obtained by -benzylation of the initially synthetized imidazole -oxides.

The Role of Fecal Microbiota Transplantation in the Treatment of Acute Graft-versus-Host Disease.

The number of allogeneic hematopoietic stem cell transplantations conducted worldwide is constantly rising. Together with that, the absolute number of complications after the procedure is increasing, with graft-versus-host disease (GvHD) being one of the most common. The standard treatment is steroid administration, but only 40-60% of patients will respond to the therapy and some others will be steroid-dependent.

The Role of the Crosstalk Between Gut Microbiota and Immune Cells in the Pathogenesis and Treatment of Multiple Myeloma.

Around 10% of all hematologic malignancies are classified as multiple myeloma (MM), the second most common malignancy within that group. Although massive progress in developing of new drugs against MM has been made in recent years, MM is still an incurable disease, and every patient eventually has relapse refractory to any known treatment. That is why further and non-conventional research elucidating the role of new factors in MM pathogenesis is needed, facilitating discoveries of the new drugs.

Trifluoromethylated Pyrazoles via Sequential (3 + 2)-Cycloaddition of Fluorinated Nitrile Imines with Chalcones and Solvent-Dependent Deacylative Oxidation Reactions.

A general approach for preparation of two types of polyfunctionalized 3-trifluoromethylpyrazoles is reported. The protocol comprises (3 + 2)-cycloaddition of the generated trifluoroacetonitrile imines with enones leading to -configured 5-acyl-pyrazolines in a fully regio- and diastereoselective manner. Initially formed cycloadducts were aromatized by treatment with manganese dioxide.

Synthesis and Cytotoxic Activity of Lepidilines A-D: Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones.

A straightforward access to 2-unsubstituted imidazole -oxides with subsequent deoxygenation by treatment with Raney-nickel followed by -benzylation opens up a convenient route to lepidilines A and C. Both imidazolium salts were used to generate in situ the corresponding imidazol-2-ylidenes, which smoothly reacted with elemental sulfur, yielding imidazole-2-thiones. These reactions were performed either under classical conditions in pyridine solutions or mechanochemically using solid CsCO as a base.

Ice-cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the most frequent adverse events of high-dose conditioning chemotherapy with melphalan prior to autologous hematopoietic stem cell transplantation (AHSCT). It significantly reduces the patients' quality of life. One of the preventive strategies for OM is cryotherapy.

The Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias.

In response to emerging discoveries, questions are mounting as to what factors are responsible for the progression of plasma cell dyscrasias and what determines responsiveness to treatment in individual patients. Recent findings have shown close interaction between the gut microbiota and multiple myeloma cells. For instance, that malignant cells shape the composition of the gut microbiota.

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines.

In-situ-generated -aryl nitrile imines derived from trifluoroacetonitrile efficiently react with polycyclic 1,4-quinones, yielding fused pyrazole derivatives as the exclusive products. The reactions proceed via the initially formed [3 + 2]-cycloadducts, which undergo spontaneous aerial oxidation to give aromatized heterocyclic products. Only for 2,3,5,6-tetramethyl-1,4-benzoquinone, the expected [3 + 2]-cycloadduct exhibited fair stability and could be isolated in moderate yield (53%).

Perspectives for the Use of CAR-T Cells for the Treatment of Multiple Myeloma.

During recent years considerable progress has been made in the treatment of multiple myeloma. However, despite the current improvements in the prognosis of this malignancy, it always ends with relapse, and therefore new therapy approaches for destroying resistant cancer cells are needed. Presently, there is great hope being placed in the use of immunotherapy against refractory/relapsed multiple myeloma which is unresponsive to any other currently known drugs.