Revealing the Mutually Enhanced Mechanism of Necroptosis and Immunotherapy Induced by Defect Engineering and Piezoelectric Effect.

Owing to low immunogenicity-induced immune escape and short-term circulating immune responses, the efficiency of immunotherapy is unsatisfactory. Therefore, triggering immunogenic cell death and establishing a long-term, mutually reinforced treatment modality are urgent challenges. In this study, ultrathin CaBi2 Nb2 O9 nanosheets with tunable oxygen vacancies (abbreviated as CBNO-OV1) are prepared for synergistic necroptosis and immunotherapy. The optimized vacancy concentration significantly improves the piezoelectric effect under ultrasound irradiation, thereby considerably improving the generation of reactive oxygen species (ROS). Density functional theory shows that oxygen vacancies can improve the efficiency of electron hole separation by suppressing their recombination, thus resulting in enhanced piezocatalytic activity. Moreover, the piezoelectric effect improves the permeability of tumor cell membranes, thus resulting in Ca2+ influx. Additionally, CBNO-OV1 also releases a portion of Ca2+ , which induces necroptosis assisted by explosive ROS. Ribonucleic acid transcription tests suggest the mechanisms associated with immune response activation and necroptosis. More importantly, necroptosis can trigger a significant immune response in vivo, thus activating macrophage M1 polarization through the NF-kappa B pathway and promoting T-cell differentiation.Tumor Necrosis Factor-α differentiated from macrophages conversely promotes necroptosis, thus realizing a mutually enhanced effect. This study demonstrates the feasibility of mutually reinforced necroptosis and immunotherapy for amplifying tumor efficacy.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Psychopathological Risk Assessment in Children with Hyperphenylalaninemia.

BACKGROUND: Phenylketonuria (PKU) is a rare congenital disorder caused by decreased metabolism of phenylalanine determining cerebral impairments. If untreated, PKU might lead to intellectual disability, seizures and behavioral disorders. The aim of this study is to provide a characterization of the psychopathological profile of a pediatric population diagnosed with PKU at newborn screening. METHODS: an accurate neuropsychological evaluation of 23 patients (aged 8-18 years) with hyperphenylalaninemia (defined as experimental group, EG) and in 23 age-matched healthy controls (defined as control group, CG) was performed using the Child and Adolescent Behavior Inventory (CABI) and Self-Administrated Psychiatric Scales for Children and Adolescents (SAFA) questionnaires. RESULTS: the CABI test showed significant differences for the sub-scales related to "Irritable mood", "Oppositional-provocative symptoms" and "ADHD" in the EG compared to CG (p = 0.014, p = 0.032, and p = 0.032, respectively). Patients with hyperphenylalaninemia also presented with significant differences both for anxiety disorder scale and depression scale of SAFA test than controls (p = 0.018 and p = 0.009, respectively). CONCLUSIONS: children and adolescents with early diagnosis of PKU showed a psychopathological risk profile characterized by an increased risk of experiencing symptoms such as mood deflection, anxiety, attention deficit, oppositional defiant behavior, and obsessive traits than healthy peers. Our findings highlighted the need of the inclusion of a neuropsychiatric evaluation in the management of these patients to improve their overall quality of life.

Influence of Mn Ions' Insertion in Pseudo-Tetragonal Phased CaBi4Ti4O15-Based Ceramics for Highly Efficient Energy Storage Devices and High-Temperature Piezoelectric Applications.

In the present era of advanced technology, the surge for suitable multifunctional materials capable of operating above 300 °C has increased for the utilization of high-temperature piezoelectric devices. For this purpose, a pseudo-tetragonal phased CaBi4Ti3.98 (Nb0.5Fe0.5)0.02O15:xwt%MnO2 (CBTNF:xMn), with x = 0-0.20, ceramic system has been engineered for the investigation of structural, ferroelectric, dielectric and high-temperature-dependent piezoelectric properties. XRD analysis confirms that low-content Mn-ion insertion at the lattice sites of CBTNF does not distort the pseudo-tetragonal phase lattice of CBTNF:xMn ceramics, but enhances the functional behavior of the ceramic system, specifically at x = 0.15 wt%Mn. Compared to pure CBT and CBTNF ceramics, CBTNF:0.15Mn has demonstrated a highly dense relative density (~96%), a saturated polarization (PS) of 15.89 µC/cm2, a storage energy density (WST) of ~1.82 J/cm3, an energy-conversion efficiency (ƞ) of ~51% and an upgraded piezoelectric behavior (d33) of 27.1 pC/N at room temperature. Sharp temperature-dependent dielectric constant (εr) peaks display the solid ferroelectric behavior of the CBTNF:0.15Mn sample with a Curie temperature (TC) of 766 °C. The thermally stable piezoelectric performance of the CBTNF:0.15Mn ceramic was observed at 600 °C, with just a 0.8% d33 loss (25 pC/N). The achieved results signify that multi-valence Mn ions have effectively intercalated at the lattice sites of the pseudo-tetragonal phased CBTNF counterpart and enhanced the multifunctional properties of the ceramic system, proving it to be a durable contender for utilization in energy-storage applications and stable high-temperature piezoelectric applications.

Gd/Mn Co-Doped CaBi4Ti4O15 Aurivillius-Phase Ceramics: Structures, Electrical Conduction and Dielectric Relaxation Behaviors.

In this work, Gd/Mn co-doped CaBi4Ti4O15 Aurivillius-type ceramics with the formula of Ca1-xGdxBi4Ti4O15 + xGd/0.2wt%MnCO3 (abbreviated as CBT-xGd/0.2Mn) were prepared by the conventional solid-state reaction route. Firstly, the prepared ceramics were identified as the single CaBi4Ti4O15 phase with orthorhombic symmetry and the change in lattice parameters detected from the Rietveld XRD refinement demonstrated that Gd3+ was successfully substituted for Ca2+ at the A-site. SEM observations further revealed that all samples were composed of the randomly orientated plate-like grains, and the corresponding average grain size gradually decreased with Gd content (x) increasing. For all compositions studied, the frequency independence of conductivity observed above 400 °C showed a nature of ionic conduction behavior, which was predominated by the long-range migration of oxygen vacancies. Based on the correlated barrier hopping (CBH) model, the maximum barrier height WM, the dc conduction activation energy Edc, as well as the hopping conduction activation energy Ep were calculated for the CBT-xGd/0.2Mn ceramics. The composition with x = 0.06 was found to have the highest Edc value of 1.87 eV, as well as the lowest conductivity (1.8 × 10-5 S/m at 600 °C) among these compositions. The electrical modules analysis for this composition further illustrated the degree of interaction between charge carrier ß increases, with an increase in temperature from 500 °C to 600 °C, and then a turn to decrease when the temperature exceeded 600 °C. The value of ß reached a maximum of 0.967 at 600 °C, indicating that the dielectric relaxation behavior at this temperature was closer to the ideal Debye type.

Early Detection of Behavioral and Emotional Problems in School-Aged Children and Adolescents: The Parent Questionnaires.

INTRODUCTION: Early detection of behavioral and emotional problems in children and adolescents is relevant. For this purpose, the use of questionnaires completed by parents is applicable. Parent questionnaires are also useful preliminary support to the clinical investigation. METHODS: Validated tools for the analysis of behavioral and emotional problems suitable for school-age subjects are analyzed in their characteristics and possibilities of use. RESULTS: The following are the main characteristics of the instruments examined. The Child and Adolescent Symptom Inventory 4&5, Parent Checklist (CASI-4&5) and Behavior Assessment System For Children - Parent Rating Scales 2&3 (BASC-2&3) include a high number of questions, with exploration extended to almost all possible pathologies.The Child Behavior Check-List (CBCL) has less items (113), but only 48 refer to DSM pathologies. The use of CASI, BASC and CBCL carries a cost because they are copyrighted.The Pediatric Symptom Checklist (PSC) has 35 items, but only 17 have a reference to 3 clinical areas. The Strength & Difficulties Questionnaire (SDA) is very short (25 items) and concerns only the main externalizing and internalizing disorders. The Child and Adolescent Behavior Inventory (CABI) has 75 items and explores a wide range of psycho-pathological issues, likewise CASI and BASC. PSC, SDA and CABI can be used free of charge. CONCLUSION: The comparison of the characteristics of the aforementioned questionnaires can guide the psychiatrist and the epidemiologist in choosing the most suitable tool for what is proposed to be assessed, in relation to practicability, extension of the areas explored and costs.

Child and Adolescent Behavior Inventory (CABI): Standardization for Age 6-17 Years and First Clinical Application.

BACKGROUND: The Child and Adolescent Behavior Inventory (CABI) is a questionnaire designed to collect information from the parents of children and adolescents, both for the preparation of screening and epidemiological studies and for clinical evaluation. It has been published in CPEMH in 2013, with the first data on 8-10 years old school children. Here we report an extended standardization on a school population 6-17 years old and the first results of the application in a clinical sample. METHODS: Parents, after giving their informed consent, answered to the questionnaire. Complete and reliable data were obtained from the parents of 659 school children and adolescents 6-17 y.o., with a balanced distribution of gender. Moreover, in a population of 84 patients, the results with the CABI were compared with the clinical evaluation and the CBCL. RESULTS: In the school population, scores were different in relation to gender and age. The values of externalizing disorders were higher in males, with the highest values for ADHD in the 6-10 y.o. children. On the contrary, the scores of internalizing disorders and of eating disorders tended to be slightly higher in females. In the clinical population, scores at the CABI were in agreement with the clinical evaluation in 84% cases for depressive symptoms (compared to CBCL 66%), 53% for anxiety symptoms (CBCL 42%) and 87% for ODD (CBCL 69%), differences, however; without statistical significance (chi square). CONCLUSION: The study obtained normative data for the CABI and gave information of the behavioral differences in relation to age and gender of the school population as evaluated by parents/caregivers. Clinically, the CABI provided useful information for the clinical evaluation of the patient, sometimes with better agreement with the final diagnosis compared to the CBCL.

Strain Engineered CaBi2Nb2O9 Thin Films with Enhanced Electrical Properties.

In this work, strain engineered polycrystalline thin films (∼250 nm) of bismuth layer-structured ferroelectric (BLSF) CaBi2Nb2O9 (CBNO) were prepared by using a radio frequency (RF) magnetron sputtering technique. XRD analysis revealed that the films were (200)/(020) and (00l) textured with a large in-plane tensile stress. Cross-sectional TEM analyses confirmed the bismuth layered-structure, as well as crystalline orientations and a strain-controlled growth mode of the grains. Result of a quantitative XPS analysis revealed that the composition of the film is close to the chemical stoichiometry. Excellent electrical properties were achieved in the CBNO films, including a high dielectric constant (∼280 @5 kHz), a small dielectric loss (tgδ ≤ 1.6% up to an applied electric field of ∼1200 kV/cm) and a large polarization (Pr ≈ 14 µC/cm(2) @ 1 kHz).

Child and Adolescent Behavior Inventory (CABI): A New Instrument for Epidemiological Studies and Pre-Clinical Evaluation.

BACKGROUND: Some questionnaires have already been elaborated to collect information from parents of children and adolescents, both as preparation for clinical evaluation and for screening and epidemiological studies. Here a new questionnaire, the CABI, is proposed, and it is validated in a population of 8-10 year-old children. Compared to existing questionnaires, the CABI has been organized so as to be of medium length, with items concerning the most significant symptoms indicated by the DSM-IV-TR for the pertinent disorders, and covering a wider range than existing instruments. There is no charge for its use. METHODS: The answers of the parents of 302 children in the last 3 years of primary school provided the normative data. A discriminant validation was done for internalizing and externalizing disorders and as a comparison with self-administered anxiety and depression scales. Exploratory factor analysis and internal consistency were also performed. RESULTS: Distribution of scores on the main scales in the normal population shows positive skewness, with the most frequent score being zero. A highly discriminant capability was found in regard to the sample of children with internalizing and externalizing disorders, with high correlation with the self-administered anxiety and depression scales. CONCLUSION: The CABI appears to be capable, at least for 8-10 year-old children, of effectively discriminating those with pathological symptoms from those without. Compared with the widely- used CBCL, it has the advantages of a lower number of items, which should facilitate parental collaboration especially in epidemiological studies, and of being free of charge.