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Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7‐AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP‐positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7‐AMkL cell population after 24 h of co‐culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti‐CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio. [ABSTRACT FROM AUTHOR]

Objective: Our primary objective was to describe the baseline characteristics, main reasons for intensive care unit (ICU) admission, and interventions required in the ICU across patients who received CAR-T cell immunotherapy. The secondary objectives were to evaluate different outcomes (ICU mortality) across patients admitted to the ICU after having received CAR-T cell therapy. Materials and Methods. We performed a medical literature review, which included MEDLINE, Embase, and Cochrane Library, of studies published from the inception of the databases until 2022. We conducted a systematic review with meta-analyses of proportions of several studies, including CAR-T cell-treated patients who required ICU admission. Outcomes in the meta-analysis were evaluated using the random-effects model. Results: We included four studies and analyzed several outcomes, including baseline characteristics and ICU-related findings. CAR-T cell recipients admitted to the ICU are predominantly males (62% CI-95% (57–66)). Of the total CAR-T cell recipients, 4% CI-95% (3–5) die in the hospital, and 6% CI-95% (4–9) of those admitted to the ICU subsequently die. One of the main reasons for ICU admission is acute kidney injury (AKI) in 15% CI-95% (10–19) of cases and acute respiratory failure in 10% CI-95% (6–13) of cases. Regarding the interventions initiated in the ICU, 18% CI-95% (13–22) of the CAR-T recipients required invasive mechanical ventilation during their ICU stay, 23% CI-95% (16–30) required infusion of vasoactive drugs, and 1% CI-95% (0.1–3) required renal replacement therapy (RRT). 18% CI-95% (13–22) of the initially discharged patients were readmitted to the ICU within 30 days, and the mean length of hospital stay is 22 days CI-95% (19–25). The results paint a current state of matter in CAR-T cell recipients admitted to the ICU. Conclusions: To better understand immunotherapy-related complications from an ICU standpoint, acknowledge the deteriorating patient on the ward, reduce the ICU admission rate, advance ICU care, and improve the outcomes of these patients, a standard of care and research regarding CAR-T cell-based immunotherapies should be created. Studies that are looking from the perspective of intensive care are highly warranted because the available literature regarding this area is scarce. [ABSTRACT FROM AUTHOR]

The synthesis of cupric oxide (CuO) films on cost-efficient, optical grade borosilicate-crown glass substrates (BK7) via chemical spray pyrolysis (CSP), either in pure form or with a low concentration of Al doping (below 1%), is presented and discussed. As a non-toxic p-type semiconductor, exhibiting monoclinic crystal structure and widely tuneable band gap (Eg), it is used in various applications. The optical properties, morphology and crystalline phases of CuO films are influenced by substrate temperature during thin film growth (annealing) and also by chemical doping very often introduced to modify grain boundary energy. The importance of our research subject is therefore perfectly justified and is essentially based on the fact that the potential fields of application are wide. Thus, herein we emphasize impact of the annealing stage and Al doping upon the structural, optical and electrical properties of the resulting product. Raman spectroscopy analysis confirms the presence of vibrational bands characteristic of a CuO phase, while X-ray diffraction (XRD) confirms the polycrystalline nature of the pure films. The thickness of the CuO films grown at 350 °C over three annealing intervals is proportional to the annealing time, while the crystallite phase in the films is proportional with the annealing temperature. Furthermore, XRD analysis of the Al:CuO films indicates the formation of a monoclinic-type structure (CuO phase) exhibiting a preferred orientation along the (002) plane, together with a significant grain size reduction from ~88 to ~45 nm as Al content increases. The transmittance spectra (between 400 and 800 nm) reveal a decrease in the transmittance from 48% to 15% with as the Al doping ratio increases. Additionally, the bandgap energy of the films is measured, modelled and discussed, using data from an ultraviolet–visible (UV-Vis) spectrophotometer. The calculated Eg is approximately 3.5 eV, which decreases with respect to the increasing annealing temperature, while the electrical resistivity varies from ~19 to ~4.6 kOhm.cm. Finally, perspectives and applications of CuO films are suggested, since the films are found to have a remarkable improvement in their structure and optical properties when doped with Al. [ABSTRACT FROM AUTHOR]

Acquired haemophilia (AH) is a rare disorder characterized by bleeding in patients with no personal or family history of coagulation/clotting‐related diseases. This disease occurs when the immune system, by mistake, generates autoantibodies that target FVIII, causing bleeding. Small RNAs from plasma collected from AH patients (n = 2), mild classical haemophilia (n = 3), severe classical haemophilia (n = 3) and healthy donors (n = 2), for sequencing by Illumina, NextSeq500. Based on bioinformatic analysis, AH patients were compared to all experimental groups and a significant number of altered transcripts were identified with one transcript being modified compared to all groups at fold change level. The Venn diagram shows that haemoglobin subunit alpha 1 was highlighted to be the common upregulated transcript in AH compared to classical haemophilia and healthy patients. Non‐coding RNAs might play a role in AH pathogenesis; however, due to the rarity of HA, the current study needs to be translated on a larger number of AH samples and classical haemophilia samples to generate more solid data that can confirm our findings. [ABSTRACT FROM AUTHOR]

In this first volume, we cover relevant aspects of chemical and physical processes of the production and characterization of magnetic materials in bulk, thin films, nanostructures, and/or nanocomposites, as well as modeling aspects involving such structures. Accordingly, this volume presents eleven original research and review works on the challenges and trends covering fundamental and experimental work, with a special focus on the design, synthesis, and characterization of various types of magnetic materials, and the study of their structure–property relationships. State-of-the-art results on the development of new experimental concepts, leading to the transfer, chemical transformation, and high-resolution patterning of advanced thin films and nanomaterials, and to the design and fabrication of devices, are also presented and discussed. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a plasma cell malignancy that affects an increasing number of patients worldwide. Despite all the efforts to understand its pathogenesis and develop new treatment modalities, MM remains an incurable disease. Novel immunotherapies, such as CAR T cell therapy (CAR) and bispecific T cell engagers (BiTE), are intensively targeting different surface antigens, such as BMCA, SLAMF7 (CS1), GPRC5D, FCRH5 or CD38. However, stem cell transplantation is still indispensable in transplant-eligible patients. Studies suggest that the early use of immunotherapy may improve outcomes significantly. In this review, we summarize the currently available clinical literature on CAR and BiTE in MM. Furthermore, we will compare these two T cell-based immunotherapies and discuss potential therapeutic approaches to promote development of new clinical trials, using T cell-based immunotherapies, even as bridging therapies to a transplant. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and treatment should be initiated as soon as possible. In the current manuscript, we focus on classifying the HLH spectrum, describing the pathophysiology and the tools needed to search for and correctly identify HLH, and the current therapeutic opportunities. We also present the first case of a multiple myeloma patient that developed HLH following therapy with the ixazomib-lenalidomide-dexamethasone protocol. [ABSTRACT FROM AUTHOR]

This joint Special Issue presents modern approaches in the recent advances in stem cell transplantation for the hematological patient, with a special emphasis on progress in conditioning chemotherapy and cellular therapies. The prospect of providing a definitive alternative therapy for various malignancies, rather than conventional chemotherapy management, is indeed clinically, socially, and economically attractive, due to the huge medical, social, and economic burden that a malignancy imposes. Hematological malignancies are considered to be one of the most important causes of mortality and morbidity in the modern world. [Extracted from the article]

Patients with relapsed/refractory acute myeloid leukaemia (AML), ineligible for intensive chemotherapy and allogeneic stem cell transplantation, have a dismal prognosis. For such cases, hypomethylating agents are a viable alternative, but with limited success. Combination chemotherapy using a hypomethylating agent plus another drug would potentially bring forward new alternatives. In the present manuscript, we present the cell and molecular background for a clinical scenario of a 44-year-old patient, diagnosed with high-grade serous ovarian carcinoma, diagnosed, and treated with a synchronous AML. Once the ovarian carcinoma relapsed, maintenance treatment with olaparib was initiated. Concomitantly, the bone marrow aspirate showed 30% myeloid blasts, consistent with a relapse of the underlying haematological disease. Azacytidine 75 mg/m2 treatment was started for seven days. The patient was administered two regimens of azacytidine monotherapy, additional to the olaparib-based maintenance therapy. After the second treatment, the patient presented with leucocytosis and 94% myeloid blasts on the bone marrow smear. Later, the patient unfortunately died. Following this clinical scenario, we reproduced in vitro the combination chemotherapy of azacytidine plus olaparib, to accurately assess the basic mechanisms of leukaemia progression, and resistance to treatment. Combination chemotherapy with drugs that theoretically target both malignancies might potentially be of use. Still, further research, both pre-clinical and clinical, is needed to accurately assess such cases. [ABSTRACT FROM AUTHOR]

This work serves as a roadmap for the development of a Vanadium dioxide (VO2)-Iridium composite based on the self-assembly of closely packed colloidal polystyrene microspheres (Pspheres) coupled with a Pulsed Laser Deposition (PLD) process. The self-assembly of a monolayer of PS is performed on an Al2O3 -c substrate, using an adapted Langmuir-Blodgett (LB) process. Then, on the substrate covered with P-spheres, a 50-nanometer Iridium layer is deposited by PLD. The Iridium deposition is followed by the removal of PS with acetone, revealing an array of triangular shaped metallic elements formed on the underlaying substrate. In a last deposition step, 50-, 100- and 200-nanometer thin films of VO2 are deposited by PLD on top of the substrates covered with the Iridium quasi-triangles, forming a composite. Adapting the size of the P-spheres leads to control of both the size of the Iridium micro-triangle and, consequently, the optical transmittance of the composite. Owing to their shape and size the Iridium micro-triangles exhibit localized surface plasmon resonance (LSPR) characterized by a selective absorption of light. Due to the temperature dependent properties of VO2, the LSPR properties of the composite can be changeable and tunable. [ABSTRACT FROM AUTHOR]