Optimization of Transcription Factor-Driven Neuronal Differentiation from Human Induced Pluripotent Stem Cells for Disease Modelling and Drug Screening.

Progress of human brain in vitro models stands as a keystone in neurological and psychiatric research, addressing the limitations posed by species-specific differences in animal models. The generation of human neurons from induced pluripotent stem cells (iPSCs) using transcription factor reprogramming protocols has been shown to reduce heterogeneity and improve consistency across different stem cell lines. Despite notable advancements, the current protocols still exhibit several shortcomings.

Extracellular Vesicles Released by Glioblastoma Cancer Cells Drive Tumor Invasiveness via Connexin-43 Gap Junctions.

Background: Although invasiveness is one of the major determinants of the poor glioblastoma (GBM) outcome, the mechanisms of GBM invasion are only partially understood. Among the intrinsic and environmental processes promoting cell-to-cell interaction processes, eventually driving GBM invasion, we focused on the pro-invasive role played by Extracellular Vesicles (EVs), a heterogeneous group of cell-released membranous structures containing various bioactive cargoes, which can be transferred from donor to recipient cells.

Methods: EVs isolated from patient-derived GBM cell lines and surgical aspirates were assessed for their pro-migratory competence by spheroid migration assays, calcium imaging, and PYK-2/FAK phosphorylation.

Simultaneous Unbinned Differential Cross-Section Measurement of Twenty-Four Z+jets Kinematic Observables with the ATLAS Detector.

Z boson events at the Large Hadron Collider can be selected with high purity and are sensitive to a diverse range of QCD phenomena. As a result, these events are often used to probe the nature of the strong force, improve Monte Carlo event generators, and search for deviations from standard model predictions. All previous measurements of Z boson production characterize the event properties using a small number of observables and present the results as differential cross sections in predetermined bins.

Measurement of multidifferential cross sections for dijet production in proton-proton collisions at .

A measurement of the dijet production cross section is reported based on proton-proton collision data collected in 2016 at by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of up to 36.3 . Jets are reconstructed with the anti- algorithm for distance parameters of and 0.

Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to Parkinson's and Lewy Body diseases: An exploratory study.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) and low alpha (8-10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex.

MINFLUX Nanoscopy: A "Brilliant" Technique Promising Major Breakthrough.

MINFLUX nanoscopy relies on the localization of single fluorophores with expected ~ 2 nm precision in 3D mapping, roughly one order of magnitude better than standard stimulated emission depletion microscopy or stochastic optical reconstruction microscopy. This "brilliant" technique takes advantage of specialized localization principles and algorithms that require only dim fluorescence signals with a minimum flux of photons; hence the name follows. With this level of performance, MINFLUX imaging and tracking should allow for the routine study of biological processes down to the molecular scale, revealing previously unresolved details in cell structures, such as the organization of calcium channels in muscle cells or the clustering of receptors in synapses.

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

Chronic Cough Patient Perspective: questionnaire validation and symptom impact.

Background: Chronic cough (CC) is underevaluated and underreported. The introduction of a tool that is easy to complete, score and interpret and with the psychometric properties requested for use in individual patients could improve clinical practice.

Objective: This cross-sectional study aimed to validate the Chronic Cough Patient Perspective (CCPP) for assessing CC in daily practice.

Artificial intelligence and network science as tools to illustrate academic research evolution in interdisciplinary fields: The case of Italian design.

In this paper, we explore the application of Artificial Intelligence and network science methodologies in characterizing interdisciplinary disciplines, with a specific focus on the field of Italian design, taken as a paradigmatic example. Exploratory data analysis and the study of academic collaboration networks highlight how the field is evolving towards increased collaboration. Text analysis and semantic topic modelling identified the evolution of research interest over time, defining a ranking of pairs of keywords and three prominent research topics: User-Centric Experience Design, Innovative Product Design and Sustainable Service Design.

A Rare Pediatric Giant Cell Tumor of the Clivus Bone, H3.3 p.Gly35Trp-mutated: Case Report and Mini-review of the Literature.

Introduction: Giant cell tumor of bone (GCTB) is a rare, typically benign neoplasm that primarily affects long bones in adults, with clival involvement being extremely rare, particularly in pediatric cases: a mini-review shows a total of 28 described cases, of which only 5 were truly pediatric (within 14 years of age). Surgery is the treatment of choice, and Denosumab is reported to be the most effective drug therapy. To date, the GCTB's molecular hallmark is the somatic mutation p.

Resting-State EEG Alpha Rhythms Are Related to CSF Tau Biomarkers in Prodromal Alzheimer's Disease.

Patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8-12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid-tau biomarkers in ADMCI patients.

Eight quick tips for biologically and medically informed machine learning.

Machine learning has become a powerful tool for computational analysis in the biomedical sciences, with its effectiveness significantly enhanced by integrating domain-specific knowledge. This integration has give rise to informed machine learning, in contrast to studies that lack domain knowledge and treat all variables equally (uninformed machine learning). While the application of informed machine learning to bioinformatics and health informatics datasets has become more seamless, the likelihood of errors has also increased.

A data-driven model of disability progression in progressive multiple sclerosis.

This study applies the Gaussian process progression model, a Bayesian data-driven disease progression model, to analyse the evolution of primary progressive multiple sclerosis. Utilizing data from 1521 primary progressive multiple sclerosis participants collected within the International Progressive Multiple Sclerosis Alliance Project, the analysis includes 18 581 longitudinal time-points (average follow-up time: 28.2 months) of disability assessments including the expanded disability status scale, symbol digit modalities, timed 25-foot-walk, 9-hole-peg test and of MRI metrics such as T1 and T2 lesion volume and normalized brain volume.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Search for Fractionally Charged Particles with CUORE.

The Cryogenic Underground Observatory for Rare Events (CUORE) is a detector array comprised by 988 5  cm×5  cm×5  cm TeO_{2} crystals held below 20 mK, primarily searching for neutrinoless double-beta decay in ^{130}Te. Unprecedented in size among cryogenic calorimetric experiments, CUORE provides a promising setting for the study of exotic throughgoing particles. Using the first tonne year of CUORE's exposure, we perform a search for hypothesized fractionally charged particles (FCPs), which are well-motivated by various standard model extensions and would have suppressed interactions with matter.

The expression of pro-prion, a transmembrane isoform of the prion protein, leads to the constitutive activation of the canonical Wnt/β-catenin pathway to sustain the stem-like phenotype of human glioblastoma cells.

Background: Cellular prion protein (PrP) is a widely expressed membrane-anchored glycoprotein, which has been associated with the development and progression of several types of human malignancies, controlling cancer stem cell activity. However, the different molecular mechanisms regulated by PrP in normal and tumor cells have not been characterized yet.

Methods: To assess the role of PrP in patient-derived glioblastoma stem cell (GSC)-enriched cultures, we generated cell lines in which PrP was either overexpressed or down-regulated and investigated, in 2D and 3D cultures, its role in cell proliferation, migration, and invasion.

Relationship Between Coronary Artery Calcium Score and Vulnerability of Culprit Plaque Assessed by OCT in Patients With Established Coronary Artery Disease.

Background: Coronary artery calcium score (CACS) is widely used for risk stratification. However, in patients with established coronary artery disease, its clinical implication and relationship with plaque vulnerability are unclear. We sought to correlate the CACS and plaque vulnerability assessed by optical coherence tomography.

The Impact of Metaphors on Academic Text Comprehension: The Case of Students With Dyslexia.

Metaphor has long been used by scholars to make concepts more comprehensible. However, this use of figurative language has never been investigated in relation to the way students with dyslexia learn from academic texts. This study aims to assess the impact of metaphors on overall academic text comprehension in university students with and without dyslexia.

Thermodynamic constraints and exact scaling exponents of flocking matter.

We use advances in the formalism of boost agnostic passive fluids to constrain transport in polar active fluids, which are subsequently described by the Toner-Tu equations. Acknowledging that the system fundamentally breaks boost symmetry, we compel what were previously entirely phenomenological parameters in the Toner-Tu model to satisfy precise relationships among themselves. Consequently, we propose a thermodynamic argument to determine the scalings of the transport coefficients under dynamical renormalization group flow given that the scaling of the noise correlator is exact, as has been supported numerically.

NAD+ METABOLISM RESTRICTION BOOSTS HIGH-DOSE MELPHALAN EFFICACY IN PATIENTS WITH MULTIPLE MYELOMA.

Elevated levels of the nicotinamide adenine dinucleotide (NAD+)-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in Multiple Myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials due to the existence of alternative NAD+ production routes utilizing NAD+ precursors other than nicotinamide.