Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets.

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138 cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models.

Multi-omics reveal immune microenvironment alterations in multiple myeloma and its precursor stages.

Tumor immune microenvironmental alterations occur early in multiple myeloma (MM) development. In this study, we aim to systematically characterize the tumor immune microenvironment (TME) and the tumor-immune interactions from precursor stages, i.e.

A systematic review and meta-analysis of artificial intelligence versus clinicians for skin cancer diagnosis.

Scientific research of artificial intelligence (AI) in dermatology has increased exponentially. The objective of this study was to perform a systematic review and meta-analysis to evaluate the performance of AI algorithms for skin cancer classification in comparison to clinicians with different levels of expertise. Based on PRISMA guidelines, 3 electronic databases (PubMed, Embase, and Cochrane Library) were screened for relevant articles up to August 2022.

A Risk Stratification System in Myeloma Patients with Autologous Stem Cell Transplantation.

Autologous stem cell transplantation (ASCT) has been a mainstay in myeloma treatment for over three decades, but patient prognosis post-ASCT varies significantly. In a retrospective study of 5259 patients with multiple myeloma (MM) at the University of Arkansas for Medical Sciences undergoing ASCT with a median 57-month follow-up, we divided the dataset into training (70%) and validation (30%) subsets. Employing univariable and multivariable Cox analyses, we systematically assessed 29 clinical variables, identifying crucial adverse prognostic factors, such as extended duration between MM diagnosis and ASCT, elevated serum ferritin, and reduced transferrin levels.

Development and validation of an individualized and weighted Myeloma Prognostic Score System (MPSS) in patients with newly diagnosed multiple myeloma.

Current standard predictive models of disease risk do not adequately account for the heterogeneity of survival outcomes in patients with new-diagnosed multiple myeloma (NDMM). In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM patients and identified the prognostic impact of all features. Using the top-ranked predictive features, a weighted Myeloma Prognostic Score System (MPSS) risk model was formulated and validated to predict overall survival (OS).

Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth.

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse.

BCMA- and CST6-specific CAR T cells lyse multiple myeloma cells and suppress murine osteolytic lesions.

We have previously demonstrated that cystatin E/M (CST6), which is elevated in a subset of patients with multiple myeloma (MM) lacking osteolytic lesions (OLs), suppresses MM bone disease by blocking osteoclast differentiation and function. CST6 is a secreted type 2 cystatin, a cysteine protease inhibitor that regulates lysosomal cysteine proteases and the asparaginyl endopeptidase legumain. Here, we developed B cell maturation antigen (BCMA) CST6 chimeric antigen receptor T cells (CAR-T cells), which lysed MM cells and released CST6 proteins.

Application of R2-ISS risk stratification to patients with multiple myeloma treated with autologous stem cell transplants at UAMS.

The Second Revision of the International Staging System (R2-ISS) was published in 2022 and has been validated in several cohorts of patients with multiple myeloma (MM). In this study, we investigated a total of 860 patients with MM who received an upfront autologous stem cell transplantation between 2001 and 2021. The median age of the patients was 60 years, with a median overall survival (OS) of 123 months and median progression-free survival (PFS) of 70 months.

A gene signature can predict risk of MGUS progressing to multiple myeloma.

Multiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Serum markers are currently used to stratify MGUS patients into clinical risk groups. A molecular signature predicting MGUS progression has not been produced.

Analysis of Plant-Plant Interactions Reveals the Presence of Potent Antileukemic Compounds.

A method to identify anticancer compounds in plants was proposed based on the hypothesis that these compounds are primarily present in plants to provide them with an ecological advantage over neighboring plants and other competitors. According to this view, identifying plants that contain compounds that inhibit or interfere with the development of other plant species may facilitate the discovery of novel anticancer agents. The method was developed and tested using , , , and , which are plant species known to possess compounds with cytotoxic activities.

Identification of hemodynamic biomarkers for bicuspid aortic valve induced aortic dilation using machine learning.

Recent advances in medical imaging have confirmed the presence of altered hemodynamics in bicuspid aortic valve (BAV) patients. Therefore, there is a need for new hemodynamic biomarkers to refine disease monitoring and improve patient risk stratification. This research aims to analyze and extract multiple correlation patterns of hemodynamic parameters from 4D Flow MRI data and find which parameters allow an accurate classification between healthy volunteers (HV) and BAV patients with dilated and non-dilated ascending aorta using machine learning.

Synthesis, Crystallography, and Anti-Leukemic Activity of the Amino Adducts of Dehydroleucodine.

Dehydroleucodine is a bioactive sesquiterpene lactone. Herein, four dehydroleucodine amino derivatives were synthesized using the amines proline, piperidine, morpholine, and tyramine, and spectroscopic methods and single-crystal X-ray diffraction unambiguously established their structures. The cytotoxic activity of these compounds was evaluated against eight acute myeloid leukemia cell lines, and their toxicity to peripheral blood mononuclear cells was also determined.

Characterization of spinal cord damage based on automatic video analysis of froglet swimming.

frogs are a widely used organism to study aspects of modern biology ( Harland and Grainger, 2011). Its central nervous system is particularly interesting, because in certain stages of metamorphosis the spinal cord can regenerate after injury and recover swimming. With this in mind, automatic gait analysis could help evaluate the regenerative performance by means of a method that automatically and quantitatively establishes the degree in froglets' limb movement.

Cranberry A-type proanthocyanidins selectively target acute myeloid leukemia cells.

Most elderly patients affected with acute myeloid leukemia (AML) will relapse and die of their disease even after achieving complete remission, thus emphasizing the urgent need for new therapeutic approaches with minimum toxicity to normal hematopoietic cells. Cranberry (Vaccinium spp.) extracts have exhibited anticancer and chemopreventive properties that have been mostly attributed to A-type proanthocyanidin (A-PAC) compounds.

Palaeopermeability anisotropy and geometrical properties of sealed-microfractures from micro-CT analyses: An open-source implementation.

Fault zone permeability and the real 3D-spatial distribution of the fault-related fracture networks are critical in the assessment of fault zones behavior for fluids. The study of the real 3D-spatial distribution of the microfracture network, using X-ray micro-computed tomography, is a crucial factor to unravel the real structural permeability conditions of a fault-zone. Despite the availability of several commercial software for rock properties estimation from X-ray micro-computed tomography scanning, their high cost and lack of programmability encourage the use of open-source data treatment.

Sister Earth, Our Common Home: Toward a Sustainable, Planet Friendly Approach to Dialysis, a Paradigm of High Technology Medicine.

In our high-technology, highly polluted world, medicine plays an important role balancing saving lives with the expenses of growing amounts of waste products, not only biologically dangerous (the potentially "contaminated" or "hazardous" waste) but also potentially harmful for the planet (nonrecyclable, plastic waste). Dialysis, the prototype of high-technology medicine, is central to these problems, as the present treatment of about 2 million patients produces an enormous quantity of waste (considering hazardous waste only about 2 kg per session, with 160 sessions per year, that is 320 kg per patient, or about 640,000 tons of hazardous waste per year for 2 million patients, roughly corresponding to 6 nuclear aircraft carriers). Furthermore, obsolete dialysis machines, and water treatments are discharged, adding to the "technological waste.

A Method for Automatic Surface Inspection Using a Model-Based 3D Descriptor.

Automatic visual inspection allows for the identification of surface defects in manufactured parts. Nevertheless, when defects are on a sub-millimeter scale, detection and recognition are a challenge. This is particularly true when the defect generates topological deformations that are not shown with strong contrast in the 2D image.

Modeling Search Behaviors during the Acquisition of Expertise in a Sequential Decision-Making Task.

Our daily interaction with the world is plagued of situations in which we develop expertise through self-motivated repetition of the same task. In many of these interactions, and especially when dealing with computer and machine interfaces, we must deal with sequences of decisions and actions. For instance, when drawing cash from an ATM machine, choices are presented in a step-by-step fashion and a specific sequence of choices must be performed in order to produce the expected outcome.

The impact of MEG source reconstruction method on source-space connectivity estimation: A comparison between minimum-norm solution and beamforming.

Despite numerous important contributions, the investigation of brain connectivity with magnetoencephalography (MEG) still faces multiple challenges. One critical aspect of source-level connectivity, largely overlooked in the literature, is the putative effect of the choice of the inverse method on the subsequent cortico-cortical coupling analysis. We set out to investigate the impact of three inverse methods on source coherence detection using simulated MEG data.

MEG Connectivity and Power Detections with Minimum Norm Estimates Require Different Regularization Parameters.

Minimum Norm Estimation (MNE) is an inverse solution method widely used to reconstruct the source time series that underlie magnetoencephalography (MEG) data. MNE addresses the ill-posed nature of MEG source estimation through regularization (e.g.

Olefin metathesis in nano-sized systems.

The interplay between olefin metathesis and dendrimers and other nano systems is addressed in this mini review mostly based on the authors' own contributions over the last decade. Two subjects are presented and discussed: (i) The catalysis of olefin metathesis by dendritic nano-catalysts via either covalent attachment (ROMP) or, more usefully, dendrimer encapsulation - ring closing metathesis (RCM), cross metathesis (CM), enyne metathesis reactions (EYM) - for reactions in water without a co-solvent and (ii) construction and functionalization of dendrimers by CM reactions.