Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections.

Glioblastoma is a major unmet clinical need characterized by striking inter- and intra-tumoral heterogeneity and a population of glioblastoma stem cells (GSCs), conferring aggressiveness and therapy resistance. GSCs communicate through a network of tumor-tumor connections (TTCs), including nanotubes and microtubes, promoting tumor progression. However, very little is known about the mechanisms underlying TTC formation and overall GSC morphology.

Electrospun poly(ε-caprolactone)/poly(glycerol sebacate) aligned fibers fabricated with benign solvents for tendon tissue engineering.

The electrospinning technique is a commonly employed approach to fabricate fibers intended for various tissue engineering applications. The aim of this study is to develop a novel strategy for tendon repair through the use of aligned poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) fibers fabricated in benign solvents, and further explore the potential application of PGS in tendon tissue engineering (TTE). The fibers were characterized for their morphological and physicochemical properties; amniotic epithelial stem cells (AECs) were used to assess the fibers teno-inductive and immunomodulatory potential due to their ability to teno-differentiate undergoing first a stepwise epithelial to mesenchymal transition, and due to their documented therapeutic role in tendon regeneration.

An unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function screen of 671 lncRNAs in MM cells and their bortezomib (BZB)-resistant derivative.

Impact of morphological features and chemical composition of tendon biomimetic scaffolds on immune recognition Toll-like receptors.

Tendinopathies are a major worldwide clinical problem. The development of tendon biomimetic scaffolds is considered a promising, therapeutic approach. However, to be clinically effective, scaffolds should avoid immunological recognition.

A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data.

Background: CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias).

[Semaglutide in Chronic Kidney Disease: Great Enthusiasm. But How Does It Work?].

Chronic Kidney Disease (CKD) is a clinical condition characterized by the progressive loss of kidney function. 10% of the world's population is affected by this condition, which represents the fifth leading cause of death globally. Furthermore, CKD is associated with increased risk of fatal and non-fatal cardiovascular events, and progression to end-stage renal disease.

The role of a mindful movement-based program (Movimento Biologico) in health promotion: results of a pre-post intervention study.

Introduction: Mindful movement is a comprehensive approach that integrates various bodily, emotional and cognitive aspects into physical activity, promoting overall well-being. This study assessed the impact of a mindful movement program, known as Movimento Biologico (MB), on participants psychological well-being (PWB), positive mental health (PMH), sense of coherence (SOC), and interoceptive awareness.

Methods: MB program was conducted for students attending the bachelor's degree in Kinesiology and Sport Sciences of University of Perugia over 8 weeks (from October 16 to November 27, 2022).

A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization.

Genetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens.

Benchmark Software and Data for Evaluating CRISPR-Cas9 Experimental Pipelines Through the Assessment of a Calibration Screen.

Genome-wide genetic screens using CRISPR-guide RNA libraries are widely performed in mammalian cells to functionally characterize individual genes and for the discovery of new anticancer therapeutic targets. As the effectiveness of such powerful and precise tools for cancer pharmacogenomics is emerging, tools and methods for their quality assessment are becoming increasingly necessary. Here, we provide an R package and a high-quality reference data set for the assessment of novel experimental pipelines through which a single calibration experiment has been executed: a screen of the HT-29 human colorectal cancer cell line with a commercially available genome-wide library of single-guide RNAs.

RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges because of subsequent waves and long-term consequences of great concern. Here, we chart the molecular basis of COVID-19 pathogenesis by analyzing patients' immune responses at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproducts (RAGE) pathway in monocytes.

Processing and characterization of aligned electrospun gelatin/polycaprolactone nanofiber mats incorporating borate glass (13-93B3) microparticles.

Aligned biodegradable fibers incorporating bioactive glass particles are being highly investigated for tissue engineering applications. In this study, 5, 7 and 10 wt% melt-derived 1393B3 borate glass (BG) microparticles (average size: 3.15 µm) were incorporated in 83 wt% polycaprolactone (PCL) and 17 wt% gelatin (GEL) (83PCL/17GEL) solutions to produce aligned electrospun composite nanofiber mats.

Highlights from the 1st European cancer dependency map symposium and workshop.

The systematic identification of tumour vulnerabilities through perturbational experiments on cancer models, including genome editing and drug screens, is playing a crucial role in combating cancer. This collective effort is known as the Cancer Dependency Map (DepMap). The 1st European Cancer Dependency Map Symposium (EuroDepMap), held in Milan last May, featured talks, a roundtable discussion, and a poster session, showcasing the latest discoveries and future challenges related to the DepMap.

Hybrid Palliation for Hypoplastic Borderline Left Ventricle: One More Chance to Biventricular Repair.

Treatment options for hypoplastic borderline left ventricle (LV) are critically dependent on the development of the LV itself and include different types of univentricular palliation or biventricular repair performed at birth. Since hybrid palliation allows deferring major surgery to 4-6 months, in borderline cases, the decision can be postponed until the LV has expressed its growth potential. We aimed to evaluate anatomic modifications of borderline LV after hybrid palliation.

Synthetic indicators to analyze work-related physical and psychosocial risk factors: evidence from the European Working Conditions Survey.

In modern workplaces, alongside physical, chemical, and biological hazards, other risks are linked to the organisation of work and to the nature of the work itself. This paper investigates the association between workers' well-being and both psychosocial and physical risk factors at work proposing a synthetic measure suitable to generate insights on well-being at work and on individual risk factors. Exploiting data from the European Working Conditions Survey, we select as response variable the "self-assessed health".

An interactive web application for processing, correcting, and visualizing genome-wide pooled CRISPR-Cas9 screens.

A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes arising from copy-number-amplified genomics regions. To solve this issue, we previously developed CRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing false-positive signals while maintaining sensitivity in identifying relevant genetic dependencies.

A heuristic algorithm solving the mutual-exclusivity-sorting problem.

Motivation: Binary (or Boolean) matrices provide a common effective data representation adopted in several domains of computational biology, especially for investigating cancer and other human diseases. For instance, they are used to summarize genetic aberrations-copy number alterations or mutations-observed in cancer patient cohorts, effectively highlighting combinatorial relations among them. One of these is the tendency for two or more genes not to be co-mutated in the same sample or patient, i.

Phenotypic plasticity and genetic control in colorectal cancer evolution.

Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity. The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC).

Reduced gene templates for supervised analysis of scale-limited CRISPR-Cas9 fitness screens.

Pooled genome-wide CRISPR-Cas9 screens are furthering our mechanistic understanding of human biology and have allowed us to identify new oncology therapeutic targets. Scale-limited CRISPR-Cas9 screens-typically employing guide RNA libraries targeting subsets of functionally related genes, biological pathways, or portions of the druggable genome-constitute an optimal setting for investigating narrow hypotheses and are easier to execute on complex models, such as organoids and in vivo models. Different supervised methods are used for computational analysis of genome-wide CRISPR-Cas9 screens; most are not well suited for scale-limited screens, as they require large sets of positive/negative control genes (gene templates) to be included among the screened ones.

Negative-Pressure Wound Therapy for Prevention of Sternal Wound Infection after Adult Cardiac Surgery: Systematic Review and Meta-Analysis.

The results of current studies are not conclusive on the efficacy of incisional negative-pressure wound therapy (NPWT) for the prevention of sternal wound infection (SWI) after adult cardiac surgery. A systematic review of the literature was performed through PubMed, Scopus and Google to identify studies which investigated the efficacy of NPWT to prevent SWI after adult cardiac surgery. Available data were pooled using RevMan and Meta-analyst with random effect models.

Computational estimation of quality and clinical relevance of cancer cell lines.

Immortal cancer cell lines (CCLs) are the most widely used system for investigating cancer biology and for the preclinical development of oncology therapies. Pharmacogenomic and genome-wide editing screenings have facilitated the discovery of clinically relevant gene-drug interactions and novel therapeutic targets via large panels of extensively characterised CCLs. However, tailoring pharmacological strategies in a precision medicine context requires bridging the existing gaps between tumours and in vitro models.