Decreasing trend in thyroid cancer incidence: a study from central Italy (2007-2019).

Purpose: Due to overdiagnosis, the incidence of thyroid cancer (TC) has increased in high-income countries, including Italy. Efforts have been made to address this issue since the mid-2010s, but more information is needed about how TC incidence has changed. We aim to examine the trend in TC incidence in the Lazio Region (central Italy) and assess the impact of the 2014 Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) to identify potential changes in TC diagnosis.

A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. However, little is known about PTPN22 posttranslational regulation. Here, we characterize a phosphorylation site at Ser situated C terminal to the catalytic domain of PTPN22 and its roles in altering protein function.

Targeting prostate tumor low-molecular weight tyrosine phosphatase for oxidation-sensitizing therapy.

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the gene-is overexpressed in prostate tumors. We found up-regulated in human prostate tumors and expression inversely correlated with overall survival.

Clustering of phosphatase RPTPα promotes Src signaling and the arthritogenic action of synovial fibroblasts.

Receptor-type protein phosphatase α (RPTPα) promotes fibroblast-dependent arthritis and fibrosis, in part, by enhancing the activation of the kinase SRC. Synovial fibroblasts lining joint tissue mediate inflammation and tissue damage, and their infiltration into adjacent tissues promotes disease progression. RPTPα includes an ectodomain and two intracellular catalytic domains (D1 and D2) and, in cancer cells, undergoes inhibitory homodimerization, which is dependent on a D1 wedge motif.

Macromolecular crowding amplifies allosteric regulation of T-cell protein tyrosine phosphatase.

T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of T-cell receptor and oncogenic receptor tyrosine kinase signaling and implicated in cancer and autoimmune disease. TC-PTP activity is modulated by an intrinsically disordered C-terminal region (IDR) and suppressed in cells under basal conditions. In vitro structural studies have shown that the dynamic reorganization of IDR around the catalytic domain, driven by electrostatic interactions, can lead to TC-PTP activity inhibition; however, the process has not been studied in cells.

Oxidative stress promotes fibrosis in systemic sclerosis through stabilization of a kinase-phosphatase complex.

Systemic sclerosis (SSc) is a fibrotic autoimmune disease characterized by pathogenic activation of fibroblasts enhanced by local oxidative stress. The tyrosine phosphatase PTP4A1 was identified as a critical promoter of TGF-β signaling in SSc. Oxidative stress is known to functionally inactivate tyrosine phosphatases.

[Impact of the COVID-19 epidemic on total and cause-specific mortality in Rome (Italy) in 2020].

Objectives: to estimate the impact of the COVID-19 epidemic on total and cause-specific mortality in people residing and dead in the Municipality of Rome (Italy) in 2020, and to describe the causes of death of subjects with SARS-CoV-2 infection confirmed by molecular test.

Design: descriptive analysis of total and cause-specific mortality in 2020 in Rome and comparison with a reference period (2015-2018 for total mortality and 2018 for cause-specific mortality); descriptive analysis of cause-specific mortality in the cohort of SARS-CoV-2 infected subjects.

Setting And Participants: 27,471 deaths registered in the Lazio mortality-cause Registry, relating to people residing and died in the municipality of Rome in 2020, 2,374 of which died from COVID-19.

[Incidence of cancer among children and adolescents (0-19 years) in Lazio Region (Central Italy), 2009-2015].

Objectives: to investigate, for the first time, the incidence of cancer (years 2009-2015) and geographical distribution among children and adolescents with cancer diagnosis in Lazio Region (Central Italy).

Design: to compute incidence rates of childhood cancers from Lazio Region Childhood Cancer Registry (LRCCR) database, established in 2015, and to compare results with national figures for 2012 provided by the Italian cancer registries network (AIRTUM).

Setting And Participants: all new cases of malignant tumours (behaviour: /3 of ICD-O-3 classification) and all central nervous system tumours were selected, regardless of behaviour (/0, /1, /3) in children and adolescents (0-19 years) registered in the LRCCR data base.

Discovery of Orally Bioavailable Purine-Based Inhibitors of the Low-Molecular-Weight Protein Tyrosine Phosphatase.

Obesity-associated insulin resistance plays a central role in the pathogenesis of type 2 diabetes. A promising approach to decrease insulin resistance in obesity is to inhibit the protein tyrosine phosphatases that negatively regulate insulin receptor signaling. The low-molecular-weight protein tyrosine phosphatase (LMPTP) acts as a critical promoter of insulin resistance in obesity by inhibiting phosphorylation of the liver insulin receptor activation motif.

Real world data to identify target population for new CAR-T therapies.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma often refractory to currently available treatments (immuno-chemotherapy/autologous-stem-cell-transplantation-ASCT). Recently, new cell therapies have been approved for patients failing two conventional treatments, CAR-T (Chimeric-Antigen-Receptor-T-cell), committing payers in planning and implementing their use. We aim to define, using Real World Data (RWD), a reproducible procedure that allows identification of CAR-T target population for DLBCL.

Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal.

Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression.

PTPN22 phosphorylation acts as a molecular rheostat for the inhibition of TCR signaling.

The hematopoietic-specific protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a major autoimmunity risk gene. PTPN22 inhibits T cell activation by dephosphorylating substrates involved in proximal T cell receptor (TCR) signaling. Here, we found by mass spectrometry that PTPN22 was phosphorylated at Ser by PKCα in Jurkat and primary human T cells activated with phorbol ester/ionomycin or antibodies against CD3/CD28.

RPTPα phosphatase activity is allosterically regulated by the membrane-distal catalytic domain.

Receptor-type protein tyrosine phosphatase α (RPTPα) is an important positive regulator of SRC kinase activation and a known promoter of cancer growth, fibrosis, and arthritis. The domain structure of RPTPs comprises an extracellular region, a transmembrane helix, and two tandem intracellular catalytic domains referred to as D1 and D2. The D2 domain of RPTPs is believed to mostly play a regulatory function; however, no regulatory model has been established for RPTPα-D2 or other RPTP-D2 domains.

When social and action spaces diverge: A study in children with typical development and autism.

The space around the body has been defined as action space () and a social space (). Within the current debate about the characteristics of these spaces, here we investigated the functional properties and plasticity of action and social space in developmental age. To these aims, children with typical development and autism spectrum disorders were submitted to Reaching- and Comfort-distance tasks, to assess peripersonal and interpersonal space, respectively.

Reduced expression of phosphatase PTPN2 promotes pathogenic conversion of Tregs in autoimmunity.

Genetic variants at the PTPN2 locus, which encodes the tyrosine phosphatase PTPN2, cause reduced gene expression and are linked to rheumatoid arthritis (RA) and other autoimmune diseases. PTPN2 inhibits signaling through the T cell and cytokine receptors, and loss of PTPN2 promotes T cell expansion and CD4- and CD8-driven autoimmunity. However, it remains unknown whether loss of PTPN2 in FoxP3+ regulatory T cells (Tregs) plays a role in autoimmunity.

PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and internal organs. Protein tyrosine phosphatases have received little attention in the study of SSc or fibrosis. Here, we show that the tyrosine phosphatase PTP4A1 is highly expressed in fibroblasts from patients with SSc.

Structure of anthrax lethal toxin prepore complex suggests a pathway for efficient cell entry.

Anthrax toxin comprises three soluble proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA must be cleaved by host proteases before it oligomerizes and forms a prepore, to which LF and EF bind. After endocytosis of this tripartite complex, the prepore transforms into a narrow transmembrane pore that delivers unfolded LF and EF into the host cytosol.

Arsenic in Drinking Water and Mortality for Cancer and Chronic Diseases in Central Italy, 1990-2010.

Background: In several volcanic areas of Italy, arsenic levels exceed European regulatory limits (10 μg/L in drinking water). There is still uncertainty about health risks from arsenic at low-medium doses (<100 μg/L).

Objectives: A large population-based study using an administrative cohort of residents in the Viterbo province (Central Italy), chronically exposed to low-medium arsenic levels via drinking water, was investigated to evaluate the effects of a lifetime exposure to arsenic on mortality from cancers and chronic diseases.

Personal space regulation in childhood autism spectrum disorders.

People appropriately adjust the distance between themselves and others during social interaction, and they may feel discomfort and move away when another person intrudes on their personal space. In the present study, we investigated personal space in children with persistent difficulties in the domain of social behavior, such as children with autism spectrum disorders (ASD), and in children with typical development (TD). The stop-distance paradigm was used to derive estimates of interpersonal distance, before and after a brief interaction with an unfamiliar adult confederate.

Structure-based design of covalent Siah inhibitors.

The E3 ubiquitin ligase Siah regulates key cellular events that are central to cancer development and progression. A promising route to Siah inhibition is disrupting its interactions with adaptor proteins. However, typical of protein-protein interactions, traditional unbiased approaches to ligand discovery did not produce viable hits against this target, despite considerable effort and a multitude of approaches.

Motor representation of actions in children with autism.

Background: Children with Autistic Spectrum Disorders (ASD) are frequently hampered by motor impairment, with difficulties ranging from imitation of actions to recognition of motor intentions. Such a widespread inefficiency of the motor system is likely to interfere on the ontogeny of both motor planning and understanding of the goals of actions, thus delivering its ultimate effects on the emergence of social cognition.

Methodology/principal Findings: We investigate the organization of action representation in 15 high functioning ASD (mean age: 8.

Safety and effectiveness of transvenous lead extraction in octogenarians.

Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians.

[Effect of misclassification of the place of residence on incidence estimates: the example of child cancer in a local health authority in Rome, Italy].

A study on cancer of the lymphatic and hematopoietic tissue among residents aged 0-14 years was conducted by the Local Health Unit RMD (Rome, Italy; period 2003-09; codes of the International Classification of Diseases, Ninth Revision, Clinical Modification: 200-208). Age and gender Standardized Mortality and Hospitalization Ratios were computed in order to compare observed and expected cases, using municipal rates as reference. Place of residence at the time of admission, as recorded in the Hospital Registry, was compared with the information recorded in the Municipal Registers and the correlation between the two sources was calculated by Cohen's Kappa.

Scared by you: modulation of bodily-self by emotional body-postures in autism.

Objective: Bodily self-recognition is one aspect of our ability to distinguish between self and others and is central to effective socialization. Here we explored the influence of emotional body postures on bodily self-processing in typically developing (TD) as well as in high-functioning ASD children.

Method: Subjects' bodies were photographed while expressing endogenously- (self-generated, Experiment 1) or exogenously-driven body emotions (imitated upon request, Experiment 2).