Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.

Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression.

Treatment Strategies' Impact on Progression-Free Survival According to RMST Function in Metastatic Colorectal Cancer Patients: A Retrospective Study from Romania.

This retrospective study investigates the impact of various treatment strategies on progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), a significant global health issue. We employed the restricted mean survival time (RMST) to evaluate how different treatments affect PFS over a defined period. The study included 225 patients with mCRC who were treated between 2015 and 2023 at the Oncology Department of Colțea Clinical Hospital in Bucharest.

A unifying modelling of multiple land degradation pathways in Europe.

Land degradation is a complex socio-environmental threat, which generally occurs as multiple concurrent pathways that remain largely unexplored in Europe. Here we present an unprecedented analysis of land multi-degradation in 40 continental countries, using twelve dataset-based processes that were modelled as land degradation convergence and combination pathways in Europe's agricultural (and arable) environments. Using a Land Multi-degradation Index, we find that up to 27%, 35% and 22% of continental agricultural (~2 million km) and arable (~1.

SecMet-FISH: labeling, visualization, and enumeration of secondary metabolite producing microorganisms.

Our understanding of the role of secondary metabolites in microbial communities is challenged by intrinsic limitations of culturing bacteria under laboratory conditions and hence cultivation independent approaches are needed. Here, we present a protocol termed Secondary Metabolite FISH (SecMet-FISH), combining advantages of gene-targeted fluorescence in situ hybridization (geneFISH) with in-solution methods (in-solution FISH) to detect and quantify cells based on their genetic capacity to produce secondary metabolites. The approach capitalizes on the conserved nature of biosynthetic gene clusters (BGCs) encoding adenylation (AD) and ketosynthase (KS) domains, and thus selectively targets the genetic basis of non-ribosomal peptide and polyketide biosynthesis.

A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease.

The Huntington's disease mutation is a CAG repeat expansion in the huntingtin gene that results in an expanded polyglutamine tract in the huntingtin protein. The CAG repeat is unstable and expansions of hundreds of CAGs have been detected in Huntington's disease post-mortem brains. The age of disease onset can be predicted partially from the length of the CAG repeat as measured in blood.

Translatable plasma and CSF biomarkers for use in mouse models of Huntington's disease.

Huntington's disease is an inherited neurodegenerative disorder for which a wide range of disease-modifying therapies are in development and the availability of biomarkers to monitor treatment response is essential for the success of clinical trials. Baseline levels of neurofilament light chain in CSF and plasma have been shown to be effective in predicting clinical disease status, subsequent clinical progression and brain atrophy. The identification of further sensitive prognostic fluid biomarkers is an active research area, and total-Tau and levels have been shown to be increased in CSF from Huntington's disease mutation carriers.

Correlations between Demographic, Clinical, and Paraclinical Variables and Outcomes in Patients with KRAS-Mutant or KRAS Wild-Type Metastatic Colorectal Cancer-A Retrospective Study from a Tertiary-Level Center in Romania.

Colorectal cancer (CRC) is a significant global public health concern and its characteristics in Eastern Europe are underexplored. In this retrospective study, data of 225 patients with metastatic colorectal cancer (mCRC) from the Colțea Clinical Hospital's Oncology Department in Bucharest were analyzed between 2015 and 2023. They were divided into two groups based on the presence of KRAS mutation.

Restricted Mean Survival Time-Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors?

Background: Lung cancer (LC) is the first and most lethal cancer in the world; identifying new methods to treat it, such as immune checkpoint inhibitors (ICIs), is needed. ICIs treatment is very effective, but it comes bundled with a series of immune-related adverse events (irAEs). Restricted mean survival time (RMST) is an alternative tool for assessing the patients' survival when the proportional hazard assumption (PH) fails.

Machine learning-based prediction and assessment of recent dynamics of forest net primary productivity in Romania.

While the analysis of spatio-temporal changes in the net primary productivity (NPP) of forests can provide critical information on carbon cycle and climate change, these ecological trends have remained unclear in many countries worldwide, including Romania. By using complex (satellite, forest and climate) data, many sophisticated (machine learning) algorithms and some widely applied (the Mann-Kendall test and Sen's slope estimator) statistical procedures, this study investigates, for the first time, recent forest NPP trends (1987-2018) that occurred in Romania, in relation to climate change that affected the country over the past decades. Following the modelling, mapping and assessment of NPP dynamics, results showed almost exclusively positive trends for this ecological parameter, which accounts for ∼99% of all forest NPP changes that occurred throughout the country, after 1987.

The impact of RAS mutation on the treatment strategy of colorectal cancer.

Kirsten rat sarcoma (KRAS) is the most frequently mutated oncogene in colorectal cancer, being present in 30% of patients with localized disease and in almost half of the patients that develop metastatic disease. While the development of chemotherapy doublets and targeted therapy have improved survival in recent years, KRAS mutation still has a controversial role regarding its prognostic and predictive value both in the adjuvant and in the metastatic setting. The impact of KRAS mutation on treatment strategy remains to be better defined.

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis.

Barriers and Facilitators of Romanian HPV (Human Papillomavirus) Vaccination.

Background: Many countries had initial success with HPV vaccination campaigns worldwide. The HPV vaccine coverage during the COVID-19 pandemic dropped consistently. The aim of our research is to assess the barriers and facilitators of the current Romanian HPV vaccination campaign.

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish () and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains.

Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six and three species (PROBIO) might re-establish the optimal internal parameters.

Aspects Regarding the Influence of Obesity on the Molecular Characteristics of Breast Tumors.

The influence of excess adipose tissue on the evolution and prognosis of breast cancer has been evaluated in numerous papers over the years. The ways in which obesity can influence the development, progression, and prognosis of this neoplasia are complex and requires the design of new studies, both clinical and preclinical. The aim of this study is to highlight a possible correlation between obesity-specific tumor microenvironment markers (adipokine or leptin) and the different histological subtypes and aggressive characteristics of breast tumors.

Correlation Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Programmed Death-Ligand 1 Expression as Prognostic Markers in Non-Small Cell Lung Cancer.

Background The neutrophil-to-lymphocyte ratio (NLR) at baseline treatment is an important marker of systemic inflammation, which is correlated with survival benefits in lung, breast, ovarian, bladder, and colorectal cancer. Programmed death-ligand 1 (PD-L1) expression is a biomarker with discording results regarding survival benefits in lung cancer. In our research, we studied the relationship between these two markers in patients with lung cancer.

Assessing Anti-Social and Aggressive Behavior in a Zebrafish () Model of Parkinson's Disease Chronically Exposed to Rotenone.

Background: Rotenone (ROT) is currently being used in various research fields, especially neuroscience. Separated from other neurotoxins, ROT induces a Parkinson’s disease (PD)-related phenotype that mimics the associated clinical spectrum by directly entering the central nervous system (CNS). It easily crosses through the blood−brain barrier (BBB) and accumulates in mitochondria.

Level of education, background and clinical stage as prognostic factors according to RMST function in patients with early and locally advanced breast cancer: a single institution experience from Romania.

Background And Aims: Our aim is to examine the relationship between the level of education, background, tumor size and lymph node status on the treatment outcome in a group of patients with early and locally advanced breast cancer (BC) by using the restricted mean survival time (RMST), which summarizes treatment effects in terms of event-free time over a fixed period of time.

Methods: We evaluated the prognostic values in 143 patients treated for early BC at Elias University Emergency Hospital, Bucharest, Romania and followed up for a maximum of 36 months. The protocol was amended to include the levels of education (gymnasium, high school, or university), the background (urban or rural) and the clinical stage (primary tumor (T) and regional nodes (N)).

COVID-19 Parental Vaccine Hesitancy in Romania: Nationwide Cross-Sectional Study.

Background: COVID-19 vaccination started in Romania in December 2020. Child vaccination started in 2021 with children aged 12-15 years in August. For children aged 5-11 years, vaccination started in January 2022.

Preliminary Data on Gastrointestinal Deficiencies Incidence and the Prevalence of Anxiety During the COVID-19 Pandemic Among the Medical Workers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious new β-coronavirus that primarily affects the lungs. Because of its unprecedented spread, in a relatively short interval, it is declared a global pandemic. Binding to the angiotensin-converting enzyme 2 receptors, SARS-CoV-2 is easily disseminated through air.

The Possible Role of BB536 and HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson's Disease.

Background: As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson's disease. The latest reports have indeed revealed that rotenone promotes Parkinson's in humans, but studies aiming to show congruent effects in zebrafish () are lacking.

Prevention and Harm Reduction Interventions for Adult Gambling at the Local Level: An Umbrella Review of Empirical Evidence.

Concerns about negative consequences of gambling diffusion are increasing. Prevention and harm reduction strategies play a crucial role in reducing gambling supply and harms. This study aims to conduct an umbrella review of the effectiveness of gambling preventive and harm reduction strategies, which can be implemented at a local level and targeted at adults.

The importance of androgen receptors in breast cancer.

Background And Aim: Breast cancer (BC) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. For the breast malignant tumors there are numerous targeted therapies, depending on the receptors expressed. Regulating the process of epithelial-mesenchyme transcription, the steroid nuclear receptors are important in invasion and progression of BC cells.