IDH2 Inhibitors Gain a Wildcard Status in the Cancer Therapeutics Competition.

The metabolic reprogramming characteristic of cancer cells, including the Warburg effect, has long been recognized as a hallmark of malignancy. This commentary explores three recent investigations focusing on the role of wild-type IDH2 in cancer and immune cell function. The first publication identifies wild-type IDH2 as a crucial factor in the survival of triple-negative breast cancer (TNBC) cells, with its inhibition leading to disrupted energy metabolism, reduced tumor growth, and enhanced apoptosis.

An integrated machine-learning model to predict nucleosome architecture.

We demonstrate that nucleosomes placed in the gene body can be accurately located from signal decay theory assuming two emitters located at the beginning and at the end of genes. These generated wave signals can be in phase (leading to well defined nucleosome arrays) or in antiphase (leading to fuzzy nucleosome architectures). We found that the first (+1) and the last (-last) nucleosomes are contiguous to regions signaled by transcription factor binding sites and unusual DNA physical properties that hinder nucleosome wrapping.

Scuba diving-related fatalities in the Philippines from 2008 to 2022 as reported in online news media.

The present study aims to investigate the demographics and characteristics of scuba diving fatalities in the Philippines which can help in the identification of local trends and ultimately in the development of appropriate preventive measures. Data on scuba diving-related fatalities in the Philippines from 2008 to 2022 were manually retrieved from online news media sources. Information on age, sex, nationality, certification, purpose, and causative factors, whenever possible were collected and analysed.

Cognitive Patterns and Problematic Use of Video Games in Adolescents: A Cluster Analysis.

Background: Video game playing (VGP) is an increasingly common leisure activity among children and adolescents, although in some cases, it is accompanied by problems due to misuse.

Method: A sample of 2884 children and adolescents aged between 12 and 20, representative of the Community of Madrid (Spain), were studied using a cluster analysis to explore the existence of cognitive patterns associated with engagement, attitudes, and concurrent cognitions. We also explored the relationship between these patterns and problematic VGP, using the 2173 gamers as a reference.

Video Game Playing and Internet Gaming Disorder: A Profile of Young Adolescents.

In recent times, growing concern has arisen regarding the utilization of technology, video games, and the emergence of internet gaming disorder (IGD), particularly among young adolescents. This worry arises from the ambiguity in distinguishing between "normal" and "problematic" video game behavior, despite efforts to establish clear criteria for defining both. The goal of this study is to outline distinct profiles of adolescent video game players and identify variables associated with their gaming practices that correlate with problematic gaming.

Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy, accounting for approximately 1% of all cancers. Despite recent advances in the treatment of MM, due to the introduction of proteasome inhibitors (PIs) such as bortezomib (BTZ) and carfilzomib (CFZ), relapses and disease progression remain common. Therefore, a major challenge is the development of novel therapeutic approaches to overcome drug resistance, improve patient outcomes, and broaden PIs applicability to other pathologies.

Diagnosis, management and impact of painful diabetic peripheral neuropathy: A patient survey in four European countries.

Aims: The aim of this study was to assess patient perspectives and experiences of the impact of neuropathic pain, painful diabetic neuropathy (pDPN) diagnosis and treatment, and the patient-healthcare professional (HCP) relationship.

Methods: We conducted a quantitative online survey in Germany, the Netherlands, Spain, and the UK among adults with diabetes who responded "yes" to at least four of ten questions of in the Douleur Neuropathique en 4 Questions (DN4) questionnaire.

Results: Of 3626 respondents, 576 met the eligibility criteria.

Phosphorylated histone variant γH2Av is associated with chromatin insulators in Drosophila.

Chromatin insulators are responsible for orchestrating long-range interactions between enhancers and promoters throughout the genome and align with the boundaries of Topologically Associating Domains (TADs). Here, we demonstrate an association between gypsy insulator proteins and the phosphorylated histone variant H2Av (γH2Av), normally a marker of DNA double strand breaks. Gypsy insulator components colocalize with γH2Av throughout the genome, in polytene chromosomes and in diploid cells in which Chromatin IP data shows it is enriched at TAD boundaries.

<i>Drosophila</i> insulator proteins exhibit in vivo liquid-liquid phase separation properties.

Mounting evidence implicates liquid-liquid phase separation (LLPS), the condensation of biomolecules into liquid-like droplets in the formation and dissolution of membraneless intracellular organelles (MLOs). Cells use MLOs or condensates for various biological processes, including emergency signaling and spatiotemporal control over steady-state biochemical reactions and heterochromatin formation. Insulator proteins are architectural elements involved in establishing independent domains of transcriptional activity within eukaryotic genomes.

A Drosophila insulator interacting protein suppresses enhancer-blocking function and modulates replication timing.

Insulators play important roles in genome structure and function in eukaryotes. Interactions between a DNA binding insulator protein and its interacting partner proteins define the properties of each insulator site. The different roles of insulator protein partners in the Drosophila genome and how they confer functional specificity remain poorly understood.

The Impact of the HydroxyMethylCytosine epigenetic signature on DNA structure and function.

We present a comprehensive, experimental and theoretical study of the impact of 5-hydroxymethylation of DNA cytosine. Using molecular dynamics, biophysical experiments and NMR spectroscopy, we found that Ten-Eleven translocation (TET) dioxygenases generate an epigenetic variant with structural and physical properties similar to those of 5-methylcytosine. Experiments and simulations demonstrate that 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) generally lead to stiffer DNA than normal cytosine, with poorer circularization efficiencies and lower ability to form nucleosomes.

Integration of in vitro allergy test results and ratio analysis for the diagnosis and treatment of allergic patients (INTEGRA).

The introduction of molecular diagnosis into routine clinical practice has substantially improved the diagnosis and management of allergic patients by allowing clinicians to precisely identify the allergenic molecule responsible for immunoglobulin E (IgE)-mediated allergies. However, it can be challenging to accurately interpret the results of molecular assays, partly due to the limited evidence base. In this context, a panel of experts with extensive experience in interpreting in vitro measures of total and serum specific IgE reviewed the available scientific evidence.

Phenotypic and Genetic Comparison of a Plant-Internalized and an Animal-Isolated Choleraesuis Strain.

Contamination of fresh produce with human pathogens poses an important risk for consumers, especially after raw consumption. Moreover, if microorganisms are internalized, no removal by means of further hygienic measures would be possible. Human pathogenic bacteria identified in these food items are mostly of human or animal origin and an adaptation to this new niche and particularly for internalization would be presumed.

Impact of DNA methylation on 3D genome structure.

Determining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization.

Implicit detection of user handedness in touchscreen devices through interaction analysis.

Mobile devices now rival desktop computers as the most popular devices for web surfing and E-commerce. As screen sizes of mobile devices continue to get larger, operating smartphones with a single-hand becomes increasingly difficult. Automatic operating hand detection would enable E-commerce applications to adapt their interfaces to better suit their user's handedness interaction requirements.

Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) common language definition of gout.

Objective: To develop a Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) common language definition of gout, with the goal of increasing public understanding and awareness, and ensure consistent and understandable messages about gout.

Methods: A G-CAN working group that included patients, physicians and nongovernmental organisation (NGO) representatives was formed to develop a common language definition of gout for use with the public, media, healthcare providers and stakeholders. A literature search and interviews with patients, healthcare workers and stakeholders informed development of the definition.

Real-Time PCR Method Combined with a Matrix Lysis Procedure for the Quantification of in Meat Products.

In this study a real-time PCR method has been developed for the specific quantification of the foodborne pathogen on meat products through the gene . The PCR was combined with a matrix lysis that allowed the obtaining of the microorganisms without sample dilution and the elimination the PCR inhibitors from dry-cured ham. The qPCR method calibration curve had an efficiency of 100.

The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.

Multiple myeloma is a malignancy of terminally differentiated plasma cells, characterized by an extreme genetic heterogeneity that poses great challenges for its successful treatment. Due to antibody overproduction, MM cells depend on the precise regulation of the protein degradation systems. Despite the success of PIs in MM treatment, resistance and adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise.

A Specialized Therapeutic Approach to Chronic Urticaria Refractory to H1-Antihistamines Improves Disease Burden: The Spanish AWARE Experience.

Objective: During its first year, the AWARE study assessed disease activity, patient quality of life (QOL), and treatment patterns in chronic urticaria (CU) refractory to H1-antihistamines (H1-AH) in clinical practice.

Methods: We performed an observational, prospective (24 months), international, multicenter study. The inclusion criteria were age ≥18 years and H1-AH-refractory CU (>2 months).

Quantitative Interspecific Approach to the Stylosphere: Patterns of Bacteria and Fungi Abundance on Passerine Bird Feathers.

Feathers are the habitat of a myriad of organisms, from fungi and bacteria to lice and mites. Although most studies focus on specific taxa and their interaction with the bird host, anecdotal data glimpse feathers as holders of a system with its own ecology, what we call here the stylosphere. A major gap in our knowledge of the stylosphere is the ecology of the total abundance of microorganisms, being also rare to find studies that analyze abundance of more than one group of microorganisms at the bird interspecific level.

Advertising Games of Chance in Adolescents and Young Adults in Spain.

Gambling advertising can influence attitudes and gaming behavior of adolescents and young adults (A&Y). To study the effect of advertising on the attitudes and gaming behavior of a sample of 2887 Spanish A&Y (12-22 years old), by means of a self-report assessment. On average, participants show a weak effect of advertising, however there are great variations, estimating that 11% of A&Y acknowledge being influenced by advertising and 5% recognize being severely affected.

Mutations in the insulator protein Suppressor of Hairy wing induce genome instability.

Insulator proteins orchestrate the three-dimensional organization of the genome. Insulators function by facilitating communications between regulatory sequences and gene promoters, allowing accurate gene transcription regulation during embryo development and cell differentiation. However, the role of insulator proteins beyond genome organization and transcription regulation remains unclear.