HyperKAN: Kolmogorov-Arnold Networks make Hyperspectral Image Classificators Smarter

In traditional neural network architectures, a multilayer perceptron (MLP) is typically employed as a classification block following the feature extraction stage. However, the Kolmogorov-Arnold Network (KAN) presents a promising alternative to MLP, offering the potential to enhance prediction accuracy. In this paper, we propose the replacement of linear and convolutional layers of traditional networks with KAN-based counterparts. These modifications allowed us to significantly increase the per-pixel classification accuracy for hyperspectral remote-sensing images. We modified seven different neural network architectures for hyperspectral image classification and observed a substantial improvement in the classification accuracy across all the networks. The architectures considered in the paper include baseline MLP, state-of-the-art 1D (1DCNN) and 3D convolutional (two different 3DCNN, NM3DCNN), and transformer (SSFTT) architectures, as well as newly proposed M1DCNN. The greatest effect was achieved for convolutional networks working exclusively on spectral data, and the best classification quality was achieved using a KAN-based transformer architecture. All the experiments were conducted using seven openly available hyperspectral datasets. Our code is available at https://github.com/f-neumann77/HyperKAN

Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study

Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. Methods In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0–2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60–72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61–72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0–8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2–5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64–0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4–22·8) in the melflufen group and 16·3 months (10·1–23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1–25·6) at a median follow-up of 19·8 months (IQR 12·0–25·0) in the melflufen group and 25·0 months (95% CI 18·1–31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8–23·7; HR 1·10 [95% CI 0·85–1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). Interpretation Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.Oncopeptides ABPeer reviewe

Genetic landscape in Russian patients with familial left ventricular noncompaction

BackgroundLeft ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).MethodsAll index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.ResultsA total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants −8 of 54 (14.8%) −have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 −7.37; p <0.001) per variant after adjustment for sex, age, and family.ConclusionOverall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Influence of the switching frequency of the switch and the amplitude of the reference voltage of a pulsed voltage regulator of the lowering type on its stability

On the basis of classical stability criteria, using the expressions of the transfer function, according to the block diagram, the stability of the impulse controller with feedback is estimated. The influence of the switching frequency of the switch and the amplitude of the reference voltage on the stability of a pulsed voltage regulator of a lowering type with deterministic parameters of the system is analyzed. In accordance with the Nyquist criterion for the transfer function of an open-loop system, both stability and phase stability margins for a closed-loop system can be estimated. When simulating the operation of the device, the phase stability margin was obtained, according to the Nyquist criterion, which is с = Н = 7. An increase in the sawtooth voltage is not a desirable phenomenon, which, although it increases the margin of stability, however, reduces stability. Moreover, the dependence of the ripple, affecting the stability of operation, on the amplitude of the sawtooth voltage is not a predictable value and takes on a random value.</jats:p

AUTOMATED CONTROL SYSTEM FOR STONE CRUSHING PLANT

The issues of automation of production processes are currently not losing their relevance. Many existing devices and systems operate in manual or semi-automatic mode, which leads to known problems. The methods of connecting system elements and the choice of protocols for transmitting signals between them are quite well-established, however, due to the emergence of new devices and communication channels with improved characteristics, the issues of choosing methods and algorithms for the operation of such systems require modification. As a criterion for the quality of the constructed system, an assessment of the reliability of the system is used, provided that the specified time constraints on the performance of the main tasks are met. The elements of novelty of the presented solution are the use of domestically produced equipment at all stages of the system operation, as well as some solutions for the choice of communication channels and signal transmission protocols. Note that the main elements of novelty relate to the software implementation of the system, the description of which is beyond the scope of this article and is planned to be published in a separate work.&#x0D; Purpose. The aim of the work is to develop the structure of an automated control system for a stone crushing plant.&#x0D; Methodology. The work uses the methods of systems analysis, the theory of signal transmission and the theory of algorithms.&#x0D; Results. The use of the presented solution made it possible to implement a simpler and more efficient hardware and software model of the control system, which will reduce the number of failures of various subsystems of the stone crushing plant. In addition, some new features have been introduced, such as the ability to remotely control and receiving data to accounting software.&#x0D; Practical implications. The obtained results are advisable to be applied by production entities carrying out activities, one of the elements of which is the use of crushing plants and complexes.</jats:p

HyperKAN: Kolmogorov–Arnold Networks Make Hyperspectral Image Classifiers Smarter

In traditional neural network designs, a multilayer perceptron (MLP) is typically employed as a classification block following the feature extraction stage. However, the Kolmogorov–Arnold Network (KAN) presents a promising alternative to MLP, offering the potential to enhance prediction accuracy. In this paper, we studied KAN-based networks for pixel-wise classification of hyperspectral images. Initially, we compared baseline MLP and KAN networks with varying numbers of neurons in their hidden layers. Subsequently, we replaced the linear, convolutional, and attention layers of traditional neural networks with their KAN-based counterparts. Specifically, six cutting-edge neural networks were modified, including 1D (1DCNN), 2D (2DCNN), and 3D convolutional networks (two different 3DCNNs, NM3DCNN), as well as transformer (SSFTT). Experiments conducted using seven publicly available hyperspectral datasets demonstrated a substantial improvement in classification accuracy across all the networks. The best classification quality was achieved using a KAN-based transformer architecture

Synthesis, Antimicrobial and Antibiofilm Activities, and Molecular Docking Investigations of 2-(1H-Indol-3-yl)-1H-benzo[d]imidazole Derivatives

The treatment of many bacterial and fungal infections remains a problem due to increasing antibiotic resistance and biofilm formation by pathogens. In the present article, a methodology for the chemoselective synthesis of 2-(1H-indol-3-yl)-1H-benzo[d]imidazole derivatives is presented. We report on the antimicrobial activity of synthesized 2-(1H-indol-3-yl)-1H-benzo[d]imidazoles with significant activity against Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300 (MRSA), Mycobacterium smegmatis (mc(2)155/ATCC 700084), and Candida albicans ATCC 10231. High activity against staphylococci was shown by indolylbenzo[d]imidazoles 3ao and 3aq (minimum inhibitory concentration (MIC) &lt; 1 &micro;g/mL) and 3aa and 3ad (MIC 3.9&ndash;7.8 &micro;g/mL). A low MIC was demonstrated by 2-(1H-indol-3-yl)-1-methyl-1H-benzo[d]imidazole (3ag) against M. smegmatis and against C. albicans (3.9 &micro;g/mL and 3.9 &micro;g/mL, respectively). 2-(5-Bromo-1H-indol-3-yl)-6,7-dimethyl-1H-benzo[d]imidazole (3aq) showed a low MIC of 3.9 &micro;g/mL against C. albicans. Compounds 3aa, 3ad, 3ao, and 3aq exhibited excellent antibiofilm activity, inhibiting biofilm formation and killing cells in mature biofilms. Molecular docking analysis identified three potential interaction models for the investigated compounds, implicating (p)ppGpp synthetases/hydrolases, FtsZ proteins, or pyruvate kinases in their antibacterial action mechanism

Delivery of Functional Exogenous Proteins by Plant Vesicles to Human Cells in Vitro

Abstract Background: Plant-derived extracellular vesicles increasingly gain attention as promising carriers of exogenous bioactive molecules to the human cells. Due to their various edible sources they are distinctly biocompatible, biodegradable and easily available in significant amounts. Methods: In present work, extracellular vesicles from grapefruit juice were isolated by differential centrifugation and characterized in terms of size, quantity, and morphology by nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy, and cryo-electron microscopy (Cryo-EM). In Cryo-EM experiments we have visualized grapefruit vesicles with average size of 41 ± 13 nm, confirmed their round-shaped morphology and estimated the thickness of their lipid bilayer as 5.3 ± 0.8 nm. Results: Using in vitro cell culture models, we have shown that grapefruit-derived extracellular vesicles (GF-EVs) are highly efficient carriers for the delivery of the exogenous Alexa flour 647 labelled BSA and HSP70 proteins into human colon cancer HCT-116 and DLD1 cells. Both proteins when loaded to plant vesicles were captured by human intestinal cells much more efficiently compare to their free state. Additionally, the functional activity of human recombinant HSP70 delivered by GF-EVs in the tissue culture cells has been confirmed. Conclusions: The results clearly indicate the high potential of native plant vesicles for the safe delivery of therapeutic proteins into human cells. Here, we reported the first demonstration of effective loading of natural plant-derived extracellular nanovesicles with exogenous proteins and their successful delivery into human cells.</jats:p

Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro

AbstractPlant-derived extracellular vesicles (EVs) gain more and more attention as promising carriers of exogenous bioactive molecules to the human cells. Derived from various edible sources, these EVs are remarkably biocompatible, biodegradable and highly abundant from plants. In this work, EVs from grapefruit juice were isolated by differential centrifugation followed by characterization of their size, quantity and morphology by nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy and cryo-electron microscopy (Cryo-EM). In Cryo-EM experiments, we visualized grapefruit EVs with the average size of 41 ± 13 nm, confirmed their round-shaped morphology and estimated the thickness of their lipid bilayer as 5.3 ± 0.8 nm. Further, using cell culture models, we have successfully demonstrated that native grapefruit-derived extracellular vesicles (GF-EVs) are highly efficient carriers for the delivery of the exogenous Alexa Fluor 647 labeled bovine serum albumin (BSA) and heat shock protein 70 (HSP70) into both human peripheral blood mononuclear cells and colon cancer cells. Interestingly, loading to plant EVs significantly ameliorated the uptake of exogenous proteins by human cells compared to the same proteins without EVs. Most importantly, we have confirmed the functional activity of human recombinant HSP70 in the colon cancer cell culture upon delivery by GF-EVs. Analysis of the biodistribution of GF-EVs loaded with 125I-labeled BSA in mice demonstrated a significant uptake of the grapefruit-derived extracellular vesicles by the majority of organs. The results of our study indicate that native plant EVs might be safe and effective carriers of exogenous proteins into human cells.</jats:p