Epistemic trust and associations with psychopathology: Validation of the German version of the Epistemic Trust, Mistrust and Credulity-Questionnaire (ETMCQ).

Epistemic trust, defined as trust in socially transmitted knowledge, is discussed as a psychopathological factor in the context of new transdiagnostic approaches for the assessment of mental disorders. The aim of this study is to test the factorial, convergent, and discriminant validity of the German version of the new Epistemic Trust, Mistrust and Credulity-Questionnaire (ETMCQ). Data were collected cross-sectionally from the German-speaking general population (N = 584) and in a second sample of clinical (n = 30) and non-clinical (n = 30) participants.

Real-time prediction of dissolution profiles of coated oral dosage forms.

Optical coherence tomography (OCT) has emerged as an in-line monitoring technique for pharmaceutical coating processes based on a representative number of samples. In this study, an approach was developed to correlate the coating thickness measured in-line via OCT with the resultant tablet dissolution profile. This strategy enables prediction of the dissolution profile of coated oral dosage forms for each individual state of the coating process in real-time.

A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.

Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, NK cells, and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies.

Traumatic childhood experiences and personality functioning: effect of body connection in a cross-sectional German and Chilean sample.

Background: Traumatic childhood experiences are a major risk factor for developing mental disorders later in life. Over the past decade, researchers have begun to investigate the role of early trauma in impairments in personality functioning following the introduction of the Alternative Model of Personality Disorders in Section III of the Diagnostic and Statistical Manual for Mental Disorders 5. Although first studies were able to empirically demonstrate a significant link between early trauma and impairments in personality functioning, only little is known about the underlying mechanisms.

Process analytical technology in Downstream-Processing of Drug Substances- A review.

Process Analytical Technology (PAT) has revolutionized pharmaceutical manufacturing by providing real-time monitoring and control capabilities throughout the production process. This review paper comprehensively examines the application of PAT methodologies specifically in the production of solid active pharmaceutical ingredients (APIs). Beginning with an overview of PAT principles and objectives, the paper explores the integration of advanced analytical techniques such as spectroscopy, imaging modalities and others into solid API substance production processes.

Mediators of outcome in adolescent psychotherapy and their implications for theories and mechanisms of change: a systematic review.

Psychotherapeutic treatment of adolescents requires age-specific approaches and thus plausibly also involves different change mechanisms than adult psychotherapy. To guide further research and improve therapeutic outcomes for adolescents, we reviewed all RCTs investigating mechanisms of change in the psychological treatment of adolescents to identify the most promising age-, disorder- or treatment-specific mediators. Following the preferred reporting items for systematic reviews (PRISMA), 106 studies were included that reported 252 statistical mediation tests assessed with 181 different measures.

Steady-state modeling of a new continuous API dryer: Reduced-order model and investigation of dryer performance.

In the present study, a reduced-order model is proposed to analyze a novel continuous dryer with an application in the pharmaceutical industry. The model was validated using process data from ibuprofen drying test runs, and the results were in good agreement with the experimental data. The test substance was an ibuprofen paste with an initial LOD of up to 30 w%.

Needles to Spheres: Evaluation of inkjet printing as a particle shape enhancement tool.

Active pharmaceutical ingredients (APIs) often reveal shapes challenging to process, e.g. acicular structures, and exhibit reduced bioavailability induced by slow dissolution rate.

Development of a Workflow to Engineer Tailored Microparticles Via Inkjet Printing.

Purpose: New drug development and delivery approaches result in an ever-increasing demand for tailored microparticles with defined sizes and structures. Inkjet printing technologies could be promising new processes to engineer particles with defined characteristics, as they are created to precisely deliver liquid droplets with high uniformity.

Methods: D-mannitol was used as a model compound alone or co-processed with the pore former agent ammonium bicarbonate, and the polymer polyethylene glycol 200.

[The Personality Inventory for ICD-11 (PiCD): Reliability and Validity of the German Version in a Clinical and Non-Clinical Sample].

The 11 version of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) marks a paradigm shift in the diagnosis of personality disorders: In the near future, their classification will no longer be categorical, but dimensional along the severity of personality impairments and optionally regarding the presence of maladaptive personality traits. This study examines the reliability and validity of the German version of the Personality Inventory for ICD-11 (PiCD), a questionnaire designed to assess ICD-11 maladaptive personality domains, in a clinical and nonclinical sample (N=939). The factor structure of the PiCD was examined using Exploratory Factor Analysis (EFA) and showed a tendency for a four-factor model (Negative Affectivity, Dissociality, Detachment, and a bipolar factor Disinhibition-Anankastia).

Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses.

Upregulation of inhibitory receptors, such as lymphocyte activation gene-3 (LAG-3), may limit the antitumor activity of therapeutic antibodies targeting the programmed cell death protein-1 (PD-1) pathway. We describe the binding properties of ezabenlimab, an anti-human PD-1 antibody, and BI 754111, an anti-human LAG-3 antibody, and assess their activity alone and in combination. Ezabenlimab bound with high affinity to human PD-1 (K = 6 nM) and blocked the interaction of PD-1 with PD-L1 and PD-L2.

In-Session-Reflective-Functioning in Anorexia Nervosa: An Analysis of Psychotherapeutic Sessions of the ANTOP Study.

Objective: Previous research suggests that patients with anorexia nervosa (AN) show an impaired capacity to mentalize (reflective functioning, RF). RF is discussed as a possible predictor of outcome in psychotherapeutic processes. The study aimed to explore RF in sessions of patients with AN and its association with outcome and type of treatment.

Reduced vagal activity in borderline personality disorder is unaffected by intranasal oxytocin administration, but predicted by the interaction between childhood trauma and attachment insecurity.

Individuals with borderline personality disorder (BPD) show self-regulatory deficits, associated with reduced heart-rate variability (HRV). However, results on reduced HRV in BPD remain heterogeneous, thus encouraging the search for developmental constructs explaining this heterogeneity. The present study first examined predictors of reduced resting-state HRV in BPD, namely the interaction between self-reported adult attachment insecurity and childhood trauma.

Identity Development and Maladaptive Personality Traits in Young Refugees and First- and Second-Generation Migrants.

Refugees are often exposed to a variety of stressors and traumatic events, posing a significant risk for the development of mental disorders. Young refugees may be particularly at risk because adverse life events affect identity formation, a developmental task that is typically expected in adolescence and emerging adulthood. Trauma and cultural changes may alter identity development, potentially leading to identity diffusion, a core concept of personality disorders.

The PD-L1/4-1BB Bispecific Antibody-Anticalin Fusion Protein PRS-344/S095012 Elicits Strong T-Cell Stimulation in a Tumor-Localized Manner.

Purpose: While patients responding to checkpoint blockade often achieve remarkable clinical responses, there is still significant unmet need due to resistant or refractory tumors. A combination of checkpoint blockade with further T-cell stimulation mediated by 4-1BB agonism may increase response rates and durability of response. A bispecific molecule that blocks the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis and localizes 4-1BB costimulation to a PD-L1-positive (PD-L1+) tumor microenvironment (TME) or tumor draining lymph nodes could maximize antitumor immunity and increase the therapeutic window beyond what has been reported for anti-4-1BB mAbs.

Childhood Traumatic Experiences and Dimensional Models of Personality Disorder in DSM-5 and ICD-11: Opportunities and Challenges.

Purpose Of Review: Childhood trauma is an important risk factor for the development of personality disorders (PDs), yet most research has been devoted to categorical models of personality pathology. Considering the introduction of a dimensional PD model with ICD-11, we review current findings related to various forms of childhood trauma, and PDs, operationalized in the form of personality functioning and maladaptive traits. We focus on the magnitude of associations and examine specific relationships between emotional and physical trauma with areas of personality functioning and single traits.

Barriers to and enablers of attendance at diabetic retinopathy screening experienced by immigrants to Canada from multiple cultural and linguistic minority groups.

Aim: To identify barriers to/enablers of attendance at eye screening among three groups of immigrantsto Canada from cultural/linguistic minority groups living with diabetes.

Methods: Using a patient-oriented research approach leveraging Diabetes Action Canada's patient engagement platform, we interviewed a purposeful sample of people with type 2 diabetes who had immigrated to Canada from: Pakistan (interviews in Urdu), China (interviews in Mandarin) and French-speaking African and Caribbean nations (interviews in French). We collected and analysed data based on the Theoretical Domains Framework covering key modifiable factors that may operate as barriers to or enablers of attending eye screening.

LAG-3 and PD-1+LAG-3 inhibition promote anti-tumor immune responses in human autologous melanoma/T cell co-cultures.

Despite the success of immunotherapy using checkpoint blockade, many patients with solid tumors remain refractory to these treatments. In human cancer, the experimental options to investigate the specific effects of antibodies blocking inhibitory receptors are limited and it is still unclear which cell types are involved. We addressed the question whether the direct interaction between T cells and tumor cells can be enforced through blocking a set of inhibitory receptors including PD-1, TIM-3, BTLA and LAG-3, blocked either individually or in dual combinations with the anti-PD-1 antibody, and to determine the condition that induces maximal T cell function preventing tumor cell proliferation.

Identifying Barriers and Enablers to Attending Diabetic Retinopathy Screening in Immigrants to Canada From Ethnocultural Minority Groups: Protocol for a Qualitative Descriptive Study.

Background: Immigrants to Canada belonging to ethnocultural minority groups are at increased risk of developing diabetes and complications, including diabetic retinopathy, and they are also less likely to be screened and treated. Improved attendance to retinopathy screening (eye tests) has the potential to reduce permanent complications, including blindness.

Objective: This study aims to identify the barriers and enablers of attending diabetic retinopathy screening among ethnocultural minority immigrants living with diabetes in Quebec and Ontario, Canada, to inform the development of a behavior change intervention to improve diabetic retinopathy screening attendance.

[Mentalizing as a Mechanism of Change in the Therapy of Conduct Disorder. A Controlled Case Study].

This controlled case study is dedicated to mentalizing as a mechanism of change in the course of a mentalization-based therapy for the treatment of conduct disorder. Following an introduction to conduct, oppositional defiant disorder and the concept of mentalizing, the case study of a 17-year-old male patient is presented. The patient's mentalizing is measured with the Reflective Functioning Scale and assessed prior to and after treatment as well as in therapy sessions at three time points through the course of therapy.

[Psychometric Evaluation of the German Version of the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1)].

Background: The alternative model for personality disorders of the DSM-5 introduced an evidence-based, dimensional concept for the diagnosis of personality disorders. Criterion A, operationalized with the Level of Personality Functioning Scale, differentiates different levels of impairments in personality functioning. The Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.

PD-1 and LAG-3 Dominate Checkpoint Receptor-Mediated T-cell Inhibition in Renal Cell Carcinoma.

Drugs targeting the programmed cell death protein 1 (PD-1) pathway are approved as therapies for an increasing number of cancer entities, including renal cell carcinoma. Despite a significant increase in overall survival, most treated patients do not show durable clinical responses. A combination of checkpoint inhibitors could provide a promising improvement.