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Background The expansion of CAG/CTG repeats in functionally unrelated genes is a causative factor in many inherited neurodegenerative disorders, including Huntington’s disease (HD), spinocerebellar ataxias (SCAs), and myotonic dystrophy type 1 (DM1). Despite many years of research, the mechanism responsible for repeat instability is unknown, and recent findings indicate the key role of DNA repair in this process. The repair of DSBs induced by genome editing tools results in the shortening of long CAG/CTG repeats in yeast models. Understanding this mechanism is the first step in developing a therapeutic strategy based on the controlled shortening of repeats. The aim of this study was to characterize Cas9-induced DSB repair products at the endogenous HTT locus in human cells and to identify factors affecting the formation of specific types of sequences. Results The location of the cleavage site and the surrounding sequence influence the outcome of DNA repair. DSBs within CAG repeats result in shortening of the repeats in frame in ~ 90% of products. The mechanism of this contraction involves MRE11-CTIP and RAD51 activity and DNA end resection. We demonstrated that a DSB located upstream of CAG repeats induces polymerase theta-mediated end joining, resulting in deletion of the entire CAG tract. Furthermore, using proteomic analysis, we identified novel factors that may be involved in CAG sequence repair. Conclusions Our study provides new insights into the complex mechanisms of CRISPR/Cas9-induced shortening of CAG repeats in human cells.

The CRISPR-Cas system has become a cutting-edge technology that revolutionized genome engineering. The use of Cas9 nuclease is currently the method of choice in most tasks requiring a specific DNA modification. The rapid development in the field of CRISPR-Cas is reflected by the constantly expanding ecosystem of computational tools aimed at facilitating experimental design and result analysis. The first group of CRISPR-Cas-related tools that we review is dedicated to aid in guide RNA design by prediction of their efficiency and specificity. The second, relatively new group of tools exploits the observed biases in repair outcomes to predict the results of CRISPR-Cas edits. The third class of tools is developed to assist in the evaluation of the editing outcomes by analysis of the sequencing data. These utilities are accompanied by relevant repositories and databases. Here we present a comprehensive and updated overview of the currently available CRISPR-Cas-related tools, from the perspective of a user who needs a convenient and reliable means to facilitate genome editing experiments at every step, from the guide RNA design to analysis of editing outcomes. Moreover, we discuss the current limitations and challenges that the field must overcome for further improvement in the CRISPR-Cas endeavor.

Expansion of the CAG/CTG repeats in functionally unrelated genes is a causative factor in many inherited neurodegenerative disorders, including Huntington's disease (HD), spinocerebellar ataxias (SCAs) and myotonic dystrophy type 1 (DM1). Despite many years of research, the mechanism responsible for repeat instability is unknown, and recent findings indicate the key role of DNA repair in this process. The repair of DSBs induced by genome editing tools results in the shortening of long CAG repeats in yeast models. Understanding this mechanism is the first step to developing a therapeutic strategy based on controlled shortening of repeats. The aim of this study was to characterize Cas9-induced DSB repair products in the endogenous HTT locus in human cells and to identify factors affecting the formation of specific types of sequences. The location of the cleavage site and the surrounding sequence influence the outcome of DNA repair. DSBs within CAG repeats result in shortening of the repeats in frame in ~90% of products. The mechanism of this contraction involves MRE11-CTIP and RAD51 activity and extensive DNA end resection reaching ~5000 bp. We demonstrated that a DSB located upstream of CAG repeats induces polymerase theta-mediated end joining, resulting in deletion of the entire CAG tract. Furthermore, using unbiased proteomic analysis, we identified novel factors that may be involved in CAG sequence repair.Competing Interest StatementThe authors have declared no competing interest.

The current study assessed the impact of adding wild garlic (Allinum ursinum L.) to the diets of turkeys on the physicochemical and microbiological properties as well as the fatty acid profile and antioxidant potential of thigh muscle. The tested materials were thigh muscle from 40 turkeys (Big-6 type) divided into two groups (P1—control group and P2—sample supplemented with wild garlic at a level of 0.2% in the feed mixture). Measurements of chemical composition, pH, water activity, color, total heme pigments, lipid oxidation, and microbiological analysis (Enterobacteriaceae, E. coli, Salmonella spp., L. monocytogenes) showed that the addition of wild garlic to a turkey diet did not affect thigh meat quality. The effect of adding wild garlic (Allinum ursinum L.) to the diets of turkeys on the antioxidant potential (against the DPPH radical) and fatty acid profile of the thigh muscle was noted. Thigh muscles obtained from turkeys reared in group P2 were characterized by a significantly higher PUFA content compared to meat from the control group. Further studies should consider turkey diet supplementation with a higher level of wild garlic and an in-depth analysis of meat quality.

Background: The COVID-19 pandemic has caused widespread disruptions in oncology care, significantly affecting both the quality of life (QoL) and mental health of cancer patients. This study aimed to evaluate the long-term impacts of the pandemic on oncology patients, focusing on the periods before, during, and after the pandemic. Objective: The objective of this study was to assess the changes in QoL, illness acceptance, and mental health indicators, including the risk of depression, generalized anxiety, elevated stress levels, and post-traumatic stress disorder (PTSD) among oncology patients, comparing these factors across the pre-pandemic, pandemic, and post-pandemic periods. Material and Methods: This study included 2000 oncology patients, divided into three cohorts based on the time of assessment: pre-pandemic (2019, n = 600), during the pandemic (2020–2021, n = 800), and post-pandemic (2023, n = 600). This study included a balanced sample of 52% female and 48% male participants, with a mean age of 58 years (SD = 11.9), representing a wide range of cancer types including breast (25.7%), lung (20.9%), and colorectal cancer (14.8%). Additional demographics showed a mean BMI of 25.8, with varied educational levels, marital statuses, income levels, and lifestyle factors such as smoking and alcohol consumption. QoL was assessed using the EORTC QLQ-C30, while the Hospital Anxiety and Depression Scale (HADS) was used to measure depression and anxiety. The PTSD Checklist for DSM-5 (PCL-5) was used to evaluate PTSD symptoms, and stress levels were measured with the Perceived Stress Scale (PSS). Statistical analyses were conducted using ANOVA and chi-square tests to assess differences between the groups. Results: During the pandemic, the prevalence of depression symptoms rose significantly, from 15% pre-pandemic to 32% (p < 0.001), while the risk of generalized anxiety increased from 18% to 40% (p < 0.001). Stress levels also saw a sharp rise, with 45% of patients reporting elevated stress during the pandemic compared to 22% before (p < 0.001). The rate of PTSD symptoms increased from 10% pre-pandemic to 28% during the pandemic (p < 0.001). QoL scores dropped markedly, with the mean EORTC QLQ-C30 global health status score decreasing by 25% during the pandemic (p < 0.01). Illness acceptance declined, with 60% of patients reporting poor acceptance during the pandemic, compared to 35% before. In the post-pandemic period, a slight improvement was observed across all measures. Depression levels dropped to 28% (p < 0.05 compared to the pandemic period), and anxiety levels decreased to 35% (p < 0.05). Stress and PTSD symptoms also showed modest reductions, with 38% reporting elevated stress and 22% exhibiting PTSD symptoms (p < 0.05). However, these post-pandemic values remained significantly higher than pre-pandemic levels (p < 0.001). QoL improved marginally, with a 10% increase in the global health status score compared to the pandemic period, though it remained lower than pre-pandemic scores (p < 0.05). Conclusions: The COVID-19 pandemic had a profound impact on the mental health and QoL of oncology patients, with significant increases in depression, anxiety, stress, and PTSD symptoms, along with a decrease in QoL and illness acceptance. While post-pandemic recovery trends are apparent, the psychological burden remains elevated compared to pre-pandemic conditions. These findings highlight the need for continued mental health support and interventions for oncology patients, even after the immediate pandemic effects have subsided.

The aim of this study was to create a Polish adaptation of the Tampa Scale of Kinesiophobia considering fatigue, and to verify the usefulness of the scale in the context of pain in cancer patients. The study was conducted at the Breast Cancer Unit, operating at the Greater Poland Cancer Centre, and at the Poznan Centre for Specialist Medical Services in Poznan. After considering the exclusion criteria, 100 people qualified for the interviews for the final study: 50 breast cancer patients and 50 healthy respondents (without cancer). Statistical analysis of the CFA score showed that the chi-square test was not significant (χ2 = 10.243, p = 0.332), indicating an acceptable fit of items across scales. The reliability of the internal consistency of the scales was tested by examining the Cronbach’s alpha scores for each question/statement. The mean values for this indicator were 0.74 for the pain-related scale and 0.84 for the fatigue-related scale. Construct validity was confirmed for the scales; AVE for the pain-related scale was 0.64 and for the fatigue-related scale was 0.68. The results suggest the validity of examining kinesiophobia in the context of pain- and fatigue-related mobility anxiety among breast cancer patients in Poland, and that the Tampa Scale of Kinesiophobia can be adapted for different dimensions of the condition. Both versions of the scale demonstrated adequately prepared parametric constructs, and all correlations showed a statistically significant relationship (p < 0.05). The use of the Tampa Scale of Kinesiophobia in oncology patient studies in Poland may ultimately improve rehabilitation programs and enable the development of strategies to assist patients in supporting treatment to reduce movement anxiety.

Background/Objectives: Physical activity (PA) and exercise have demonstrated numerous benefits for patients with cancer. However, there may be different barriers which vary according to geographical area. The aim of this study was to compare oncologists, PA recommendations, PA patterns and barriers in two different geographical areas. Methods: A total of 254 patients were included, 239 of them women and 15 of them men, while 41.3% of the sample was Polish and 58.7% of the sample Spanish. Results: In terms of differences in time spent on PA per day, the Spanish spent more time walking than the Polish did (p = 0.007). However, no significant differences were found between countries, types or intensity of exercise, and there was a significant relationship between age and type of PA modality (p = 0.002). At the same time, there were different reasons for not practicing PA (p = 0.009). The subsequent analysis showed that younger adults were prone to more vigorous-intensity exercise than the other age groups (p = 0.001, η2 = 0.08). Furthermore, there was a significant difference between age groups, countries and sitting time (p = 0.01), with Polish patients spending more time sitting than Spaniards (p = 0.01, η2 = 0.06). Conclusions: Although PA patterns in the two countries were similar, the main barriers to exercise differed. Therefore, PA programs should be as personalized as possible (taking into account sociodemographic, cultural and climatic characteristics). Ultimately, to improve the quality of life and health of their patients, oncologists should provide those activities that are most beneficial to their patients.

Aim of the study: Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods: Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results: Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved - without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions: Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM.

This paper introduces a novel approach to Dynamic Artificial Neural Networks (D-ANNs) for multi-task demand forecasting called Neuroplastic Multi-Task Network (NMT-Net). Unlike conventional methods focusing on inference-time dynamics or computational efficiency, our proposed method enables structural adaptability of the computational graph during training, inspired by neuroplasticity as seen in biological systems. Each new task triggers a dynamic network adaptation, including similarity-based task identification and selective training of candidate ANN heads, which are then assessed and integrated into the model based on their performance. We evaluated our framework using three real-world multi-task demand forecasting datasets from Kaggle. We demonstrated its superior performance and consistency, achieving lower RMSE and standard deviation compared to traditional baselines and state-of-the-art multi-task learning methods. NMT-Net offers a scalable, adaptable solution for multi-task and continual learning in time series prediction. The complete code for NMT-Net is available from our GitHub repository.

Neurological conditions are the leading cause of ill health worldwide. Here, we show that the neurodevelopmental disorder-associated ubiquitin ligase UBE3C regulates the cellular composition of the murine cerebral cortex and human brain organoids, with its loss favoring neurogenesis and suppressing glial fate. Using genetic complementation, we demonstrate that disease-associated UBE3C mutations alter its autoubiquitination activity and disrupt cortical lamination. Proteomic profiling of UBE3C-deficient forebrains and organoids identifies Cbll1 as a UBE3C substrate, and we show that the UBE3C-Cbll1 duo drives N6-methyladenosine (m6A) mRNA methylation. Hyperactivation of m6A writers in UBE3C-deficient neural progenitors impairs cell cycle exit, a defect reversible in vivo by the METTL3 inhibitor STM2457. Our findings uncover an epiproteomic mechanism controlling m6A-mediated gene expression and define a regulatory axis linking ubiquitin signaling to epitranscriptomic control of neural fate. This work provides a mechanistic framework for understanding neurodevelopmental disorders and highlights potential therapeutic strategies.