Polyfunctional IL-21 IFNG T follicular helper cells contribute to checkpoint inhibitor diabetes mellitus and can be targeted by JAK inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic beta-islet cell destruction leading to hyperglycemia and life-long insulin dependence.

Growing Role of 3D In Vitro Cell Cultures in the Study of Cellular and Molecular Mechanisms: Short Focus on Breast Cancer, Endometriosis, Liver and Infectious Diseases.

Over the past decade, the development of three-dimensional (3D) models has increased exponentially, facilitating the unravelling of fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues and organs and respond to biochemical and biophysical stimuli under both physiological and pathological conditions. This section presents a concise overview of the most recent updates on the significant contribution of different types of 3D cell cultures including spheroids, organoids and organ-on-chip and bio-printed tissues in advancing our understanding of cellular and molecular mechanisms. The case studies presented include the 3D cultures of breast cancer (BC), endometriosis, the liver microenvironment and infections.

Metastatic squamous cell carcinoma arising from mature teratoma of the ovary: Description of multi-modality treatment including incorporation of adjuvant immunotherapy and maintenance PARP inhibitor therapy.

•Squamous cell carcinoma arising from mature teratoma of the ovary is a rare occurrence without clear agreement regarding optimal treatment.•Multimodality treatment should be considered, particularly for metastatic disease.•Maintenance therapy may be considered.

Surface Properties of a Biocompatible Thermoplastic Polyurethane and Its Anti-Adhesive Effect against and .

Thermoplastic polyurethane (TPU) is a polymer used in a variety of fields, including medical applications. Here, we aimed to verify if the brush and bar coater deposition techniques did not alter TPU properties. The topography of the TPU-modified surfaces was studied via AFM demonstrating no significant differences between brush and bar coater-modified surfaces, compared to the un-modified TPU (TPU Film).

Effect of Low Copper Doping on the Optical, Cytocompatible, Antibacterial, and SARS-CoV-2 Trapping Properties of Calcium Phosphate Glasses.

Calcium phosphate glasses (CPGs) are acquiring great importance in the biomedical field because of their thermomechanical and bioresorbable properties. In this study, optically transparent copper (1 mol %)-doped calcium phosphate glasses (CPGs_Cu) were prepared through the melt-quenching method, and their biocompatibility and antibacterial and antiviral properties were evaluated and compared with undoped CPGs. Biocompatibility was evaluated on murine fibroblast NIH-3T3 cells as a preliminary study of cytocompatibility.

Upgrades of Genetic Programming for Data-Driven Modeling of Time Series.

In many engineering fields and scientific disciplines, the results of experiments are in the form of time series, which can be quite problematic to interpret and model. Genetic programming tools are quite powerful in extracting knowledge from data. In this work, several upgrades and refinements are proposed and tested to improve the explorative capabilities of symbolic regression (SR) via genetic programming (GP) for the investigation of time series, with the objective of extracting mathematical models directly from the available signals.

Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis.

Background: In mouse liver hepatocytes, nearly half of the surface area of every mitochondrion is covered by wrappER, a wrapping-type of ER that is rich in fatty acids and synthesizes lipoproteins (VLDL) (Anastasia et al. in Cell Rep 34:108873, 2021; Hurtley in Science (80- ) 372:142-143, 2021; Ilacqua et al. in J Cell Sci 135:1-11, 2021).

Genetic Determinants of Hydrogen Sulfide Biosynthesis in Fusobacterium nucleatum Are Required for Bacterial Fitness, Antibiotic Sensitivity, and Virulence.

The Gram-negative anaerobe Fusobacterium nucleatum is a major producer of hydrogen sulfide (HS), a volatile sulfur compound that causes halitosis. Here, we dissected the genetic determinants of HS production and its role in bacterial fitness and virulence in this important member of the oral microbiome. F.

Human Protein-l-isoaspartate -Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins.

The spontaneous l-isoaspartate protein modification has been observed to negatively affect protein function. However, this modification can be reversed in many proteins in reactions initiated by the protein-l-isoaspartyl (d-aspartyl) -methyltransferase (PCMT1). It has been hypothesized that an additional mechanism exists in which l-isoaspartate-damaged proteins are recognized and proteolytically degraded.

A Refinement of Recurrence Analysis to Determine the Time Delay of Causality in Presence of External Perturbations.

This article describes a refinement of recurrence analysis to determine the delay in the causal influence between a driver and a target, in the presence of additional perturbations affecting the time series of the response observable. The methodology is based on the definition of a new type of recurrence plots, the Conditional Joint Recurrence plot. The potential of the proposed approach resides in the great flexibility of recurrence plots themselves, which allows extending the technique to more than three quantities.

Data driven theory for knowledge discovery in the exact sciences with applications to thermonuclear fusion.

In recent years, the techniques of the exact sciences have been applied to the analysis of increasingly complex and non-linear systems. The related uncertainties and the large amounts of data available have progressively shown the limits of the traditional hypothesis driven methods, based on first principle theories. Therefore, a new approach of data driven theory formulation has been developed.

Genetic Manipulation and Virulence Assessment of Fusobacterium nucleatum.

Considered a commensal, the Gram-negative anaerobe Fusobacterium nucleatum is a key member of the oral microbiome due to its wide range of interactions with many oral microbes. While the periodontal pathogenic properties of this organism have widely been examined, its connotation with extra-oral infections, including preterm birth and colorectal cancer, has now become apparent. Nonetheless, little is known about the mechanisms of pathogenicity and the associated virulence factors of F.

A comprehensive study of the uncertainties in bolometric tomography on JET using the maximum likelihood method.

Essential physical quantities of magnetically confined plasmas are derived on a routine basis from bolometric reconstructions. In the last few years at the Joint European Torus (JET), the Maximum Likelihood method has demonstrated the capability of providing reliable reconstructions for this class of ill-posed problems. The article is focused on quantifying the effects of important sources of errors, usually underestimated, that can influence both the reconstructions and the derived quantities.

A Model Falsification Approach to Learning in Non-Stationary Environments for Experimental Design.

The application of data driven machine learning and advanced statistical tools to complex physics experiments, such as Magnetic Confinement Nuclear Fusion, can be problematic, due the varying conditions of the systems to be studied. In particular, new experiments have to be planned in unexplored regions of the operational space. As a consequence, care must be taken because the input quantities used to train and test the performance of the analysis tools are not necessarily sampled by the same probability distribution as in the final applications.

A 2-dimensional ratchet model describes assembly initiation of a specialized bacterial cell surface.

Bacterial spores are dormant cells that are encased in a thick protein shell, the "coat," which participates in protecting the organism's DNA from environmental insults. The coat is composed of dozens of proteins that assemble in an orchestrated fashion during sporulation. In , 2 proteins initiate coat assembly: SpoVM, which preferentially binds to micron-scale convex membranes and marks the surface of the developing spore as the site for coat assembly; and SpoIVA, a structural protein recruited by SpoVM that uses ATP hydrolysis to drive its irreversible polymerization around the developing spore.

On the Use of Entropy to Improve Model Selection Criteria.

The most widely used forms of model selection criteria, the Bayesian Information Criterion (BIC) and the Akaike Information Criterion (AIC), are expressed in terms of synthetic indicators of the residual distribution: the variance and the mean-squared error of the residuals respectively. In many applications in science, the noise affecting the data can be expected to have a Gaussian distribution. Therefore, at the same level of variance and mean-squared error, models, whose residuals are more uniformly distributed, should be favoured.

On the Use of Transfer Entropy to Investigate the Time Horizon of Causal Influences between Signals.

Understanding the details of the correlation between time series is an essential step on the route to assessing the causal relation between systems. Traditional statistical indicators, such as the Pearson correlation coefficient and the mutual information, have some significant limitations. More recently, transfer entropy has been proposed as a powerful tool to understand the flow of information between signals.

Maximum likelihood bolometric tomography for the determination of the uncertainties in the radiation emission on JET TOKAMAK.

The total emission of radiation is a crucial quantity to calculate the power balances and to understand the physics of any Tokamak. Bolometric systems are the main tool to measure this important physical quantity through quite sophisticated tomographic inversion methods. On the Joint European Torus, the coverage of the bolometric diagnostic, due to the availability of basically only two projection angles, is quite limited, rendering the inversion a very ill-posed mathematical problem.

Quality of life related factors for parents of children with hearing loss.

Hearing loss among children, particularly those with severe and profound hearing impairment, has an effect on their communication and development, which in turn can have a significant impact on their parents. This study aimed to evaluate the quality of life of parents of children with hearing loss and identify the associated factors. A cross-sectional study was carried out involving parents of children that went through phonoaudiological therapy at a public university clinic in the city of São Paulo.

Public Stigma towards Older Adults with Depression: Findings from the São Paulo-Manaus Elderly in Primary Care Study.

This study investigates three domains of public stigma (perceived negative reactions, perceived discrimination, and dangerousness) against older adults with depression. The sample comprised of older adults registered with primary care clinics (n = 1,291) and primary health care professionals (n = 469) from São Paulo and Manaus, Brazil. Participants read a vignette describing a 70-year-old individual (Mary or John) with a depressive disorder and answered questions measuring stigma.

Anxiety and depressive disorders in elderly with chronic dizziness of vestibular origin.

Introduction: Dizziness is one of the most prevalent symptoms in the elderly. Anxiety and depression are common in dizzy adult patients, but there is scarce information about comorbidity between vestibular disturbances and psychiatric disorders in the aged.

Objective: To assess the prevalence of anxiety and depression disorders in elderly with chronic dizziness of vestibular origin.

Differential characteristics of young and midlife adult users of psychotherapy, psychotropic medications, or both: information from a population representative sample in São Paulo, Brazil.

Objective: While the personal characteristics of users of psychotherapy and/or psychotropic medications have been examined, direct user comparison of these treatment approaches appears to be rare. Our aim is to ascertain extent of receipt of these services, and identify basic distinguishing characteristics of users.

Methods: Information on demographics, lifetime and past 12 month use of mental health services, and presence of common mental disorders (CMD), was gathered in 2002 using a multi-stage sampling procedure that yielded a population-representative, community-resident sample (N = 2000, age 18-65) for São Paulo, Brazil.

Patrolling monocytes control tumor metastasis to the lung.

The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models.

Improved equilibrium reconstructions by advanced statistical weighting of the internal magnetic measurements.

In a Tokamak the configuration of the magnetic fields remains the key element to improve performance and to maximise the scientific exploitation of the device. On the other hand, the quality of the reconstructed fields depends crucially on the measurements available. Traditionally in the least square minimisation phase of the algorithms, used to obtain the magnetic field topology, all the diagnostics are given the same weights, a part from a corrective factor taking into account the error bars.