A Monotonic On-Line Linear Algorithm for Hierarchical Agglomerative Classification

We start from an algorithm for on-line linear hierarchical classification for multidimensional data, using a centroid aggregation criterion. After evoking some real-life on-line settings where it can be used, we analyze it mathematically, in the framework of the Lance–Williams algorithms, proving that it does not have some useful properties: it is not monotonic, nor space-conserving. In order to use its on-line capabilities, we modify it and show that it becomes monotonic. While still not having the internal similarity-external dissimilarity property, the worst case classifications of the new algorithm are correctable with an additional small computational effort, on the overall taking O(n?k) time for n points and k classes. Experimental study confirm the theoretical improvements upon the initial algorithm. A theoretical and experimental comparison to other algorithms from the literature, shows that it is among the fastest and performs well.     

Assessing the Efficiency of Triangular Gold Nanoparticles as NIR Photothermal Agents In Vitro and Melanoma Tumor Model

Photothermal therapy (PTT) is gaining a lot of interest as a cancer treatment option with minimal side effects due to the efficient photothermal agents employed. They are based on nanomaterials that, upon laser irradiation, absorb photon energy and convert it into heat to induce hyperthermia, which destroys the cancer cells. Here, the unique light-to-heat conversion features of three different gold nanotriangular nanoparticles (AuNTs) are evaluated with respect to their absorption properties to select the most efficient nanoheater with the highest potential to operate as an efficient photothermal agent. AuNTs with LSPR response in- and out- of resonance with the 785 nm near-infrared (NIR) excitation wavelength are investigated. Upon 15 min laser exposure, the AuNTs that exhibit a plasmonic response in resonance with the 785 nm laser line show the highest photothermal conversion efficacy of 80%, which correlates with a temperature increase of 22 °C. These photothermal properties are well-preserved in agarose-based skin biological phantoms that mimic the melanoma tumoral tissue and surrounding healthy tissue. Finally, in vitro studies on B16.F10 melanoma cells prove by fluorescence staining and MTT assay that the highest phototoxic effect after NIR laser exposure is induced by AuNTs with LSPR response in resonance with the employed laser line, thus demonstrating their potential implementation as efficient photothermal agents in PTT.     

The Impact of the Azo-Chromophore Sort on the Features of the Supramolecular Azopolyimide Films Desired to Be Used as Substrates for Flexible Electronics

High-performance supramolecular polyimide systems were synthesized via a simple and innovative approach using two types of azo-chromophores, leading to concomitant special properties: high thermostability, the ability to be processed in the form of films with high flexibility, adequate morphological features, and good structuring capacity via phase mask ultraviolet (UV) laser irradiation, induced by the presence of the azo groups (–N=N–). The dimension and the anisotropy degree of the micro/nano patterns obtained on the surface of the flexible films (determined by atomic force microscopy) depend on the azo-dye type used in the supramolecular azopolyimide synthesis, which were higher when the azo-chromophore containing a –cyano group (–C≡N) was used. The molecular dynamics method, an excellent tool for an in-depth examination of the intermolecular interactions, was used to explain the morphological aspects. Energetic, dynamic and structural parameters were calculated for the two systems containing azo-chromophores, as well as for the pristine polymer system. It was highlighted that the van der Waals forces make a major contribution to the intermolecular interactions. The results from the combination of the dynamic analysis and the concentration profile explain the better mobility of the polyimide chains with a maximum content of azo groups in the cis configuration compared to the other systems. Taking all these data into account, the surfaces of the films can be tuned as required for the proposed applications, namely as substrates for flexible electronis.     

Replacing the Burden of the Gluten Free Diet: Then,Now, and the Future

Without a doubt, a majority of diseases are food-pattern-related. However, one disease stands out as an increasingly more common autoimmune-mediated enteropathy triggered by the ingestion of gluten. Celiac disease (CD) is an old disease, with changing clinical patterns, affecting any age, including infancy and adolescence, and becoming more frequent among the elderly. The gluten-free diet (GFD) has been the sole provider of clinical, serological, and histological improvement for patients with CD for more than seven decades. Nowadays, complete avoidance of dietary gluten is rarely possible because of the wide availability of wheat and other processed foods that contain even more gluten, to the detriment of gluten-free products. Undeniably, there is a definite need for replacing the burdensome GFD. An add-on therapy that could control the dietary transgressions and inadvertent gluten consumption that can possibly lead to overt CD should be considered while on GFD. Nevertheless, future drugs should be able to provide patients some freedom to self-manage CD and increase food independence, while actively reducing exposure and mucosal damage and alleviating GI symptoms. Numerous clinical trials assessing different molecules have already been performed with favorable outcomes, and hopefully they will soon be available for patient use.     

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body’s own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016–2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.     

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.     

Correlation between CRISPR Loci Diversity in Three Enterobacterial Taxa

CRISPR-Cas is an adaptive immunity system of prokaryotes, composed of CRISPR arrays and the associated proteins. The successive addition of spacer sequences in the CRISPR array has made the system a valuable molecular marker, with multiple applications. Due to the high degree of polymorphism of the CRISPR loci, their comparison in bacteria from various sources may provide insights into the evolution and spread of the CRISPR-Cas systems. The aim of this study was to establish a correlation between the enterobacterial CRISPR loci, the sequence of direct repeats (DR), and the number of spacer units, along with the geographical origin and collection source. For this purpose, 3474 genomes containing CRISPR loci from the CRISPRCasdb of Salmonella enterica, Escherichia coli, and Klebsiella pneumoniae were analyzed, and the information regarding the isolates was recorded from the NCBI database. The most prevalent was the I-E CRISPR-Cas system in all three studied taxa. E. coli also presents the I-F type, but in a much lesser percentage. The systems found in K. pneumoniae can be classified into I-E and I-E*. The I-E and I-F systems have two CRISPR loci, while I-E* has only one locus upstream of the Cas cluster. PCR primers have been developed in this study for each CRISPR locus. Distinct clustering was not evident, but statistically significant relationships occurred between the different CRISPR loci and the number of spacer units. For each of the queried taxa, the number of spacers was significantly different (p < 0.01) by origin (Africa, Asia, Australia and Oceania, Europe, North America, and South America) but was not linked to the isolation source type (human, animal, plant, food, or laboratory strains).     

Reactive Oxygen Species and Long Non-Coding RNAs,an Unexpected Crossroad in Cancer Cells

Long non-coding RNAs (lncRNA) have recently been identified as key regulators of oxidative stress in several malignancies. The level of reactive oxygen species (ROS) must be constantly regulated to maintain cancer cell proliferation and chemoresistance and to prevent apoptosis. This review will discuss how lncRNAs alter the ROS level in cancer cells. We will first describe the role of lncRNAs in the nuclear factor like 2 (Nrf-2) coordinated antioxidant response of cancer cells. Secondly, we show how lncRNAs can promote the Warburg effect in cancer cells, thus shifting the cancer cell’s “building blocks” towards molecules important in oxidative stress regulation. Lastly, we explain the role that lncRNAs play in ROS-induced cancer cell apoptosis and proliferation.     

Recent Advances on the Roles of PCSK-9 Inhibitors in the Management of Acute Ischemic Stroke Patients

Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence.     

Cardiac Troponin Biosensor Designs: Current Developments and Remaining Challenges

Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.