The state of the art in secondary pharmacology and its impact on the safety of new medicines.

Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities has become standard practice in pharmaceutical research and development, and regulatory agencies are increasingly requesting data on activity against targets with recognized adverse effect relationships. However, the screening strategies and target panels used by pharmaceutical companies may vary substantially. To help identify commonalities and differences, as well as to highlight opportunities for further optimization of secondary pharmacology assessment, we conducted a broad-ranging survey across 18 companies under the auspices of the DruSafe leadership group of the International Consortium for Innovation and Quality in Pharmaceutical Development.

The Silent Treatment?: Changes in patient emotional expression after silence.

Psychotherapy can be an emotionally laden conversation, where both verbal and non-verbal interventions may impact the therapeutic process. Prior research has postulated mixed results in how clients emotionally react following a silence after the therapist is finished talking, potentially due to studying a limited range of silences with primarily qualitative and self-report methodologies. A quantitative exploration may illuminate new findings.

Mel frequency spectral domain defenses against adversarial attacks on speech recognition systems.

Automatic speech recognition (ASR) systems are vulnerable to adversarial attacks due to their reliance on machine learning models. Many of the defenses explored for defending ASR systems simply adapt defense approaches developed for the image domain. This paper explores speech-specific defenses in the feature domain and introduces a defense method called mel domain noise flooding (MDNF).

Enhanced photo-fenton and photoelectrochemical activities in nitrogen doped brownmillerite KBiFeO.

Visible-light-driven photo-fenton-like catalytic activity and photoelectrochemical (PEC) performance of nitrogen-doped brownmillerite KBiFeO (KBFO) are investigated. The effective optical bandgap of KBFO reduces from 1.67 to 1.

Rheumatoid arthritis patients treated with Janus kinase inhibitors show reduced humoral immune responses following BNT162b2 vaccination.

Objectives: The mRNA-based COVID-19 vaccines are now employed globally and have shown high efficacy in preventing SARS-CoV-2 infection. However, less is known about the vaccine efficacy in immune-suppressed individuals. This study sought to explore whether humoral immunity to the COVID-19 vaccine BNT162b2 is altered in RA patients treated with Janus kinase inhibitors by analysing their antibodies titre, neutralization activity and B cell responses.

The association between elevated serum interleukin-22 and the clinical diagnosis of axial spondyloarthritis: A retrospective study.

Objective: There is an unmet need for a reliable biomarker for the differentiation of axial spondyloarthritis (AxSpA) from its mimickers. Serum levels of interleukin-22 (IL-22) have previously been found to be significantly elevated in patients with AxSpA compared with healthy individuals or persons with osteoarthritis.

Methods: Consecutive patients with established or suspected AxSpA were enrolled.

g-CN/CaFeO heterostructures for enhanced photocatalytic degradation of organic effluents under sunlight.

g-CN/CaFeO heterostructures were successfully prepared by incorporating g-CN into CaFeO (CFO). As prepared g-CN/CFO heterostructures were initially utilized to photodegrade organic effluent Methylene blue (MB) for optimization of photodegradation performance. 50% g-CN content in CFO composition showed an enhanced photodegradation efficiency (~ 96%) over g-CN (48.

Automated evaluation of psychotherapy skills using speech and language technologies.

With the growing prevalence of psychological interventions, it is vital to have measures which rate the effectiveness of psychological care to assist in training, supervision, and quality assurance of services. Traditionally, quality assessment is addressed by human raters who evaluate recorded sessions along specific dimensions, often codified through constructs relevant to the approach and domain. This is, however, a cost-prohibitive and time-consuming method that leads to poor feasibility and limited use in real-world settings.

Electrochemical synthesis of isobenzofuran-1-imines using oxidative halocyclization of o-alkynylbenzamides.

Electrochemical oxidative 5-exo-dig-oxo-halocyclization of o-alkynylbenzamides was achieved using readily available NaX (X = Cl, Br and I) salts under mild reaction conditions. The use of a cheap and highly stable sodium halide as a halide ion source is impressive for the synthesis of a variety of halogenated isobenzofuran-1-imines. This electrochemical protocol shows regioselectivity and excellent conversion to isobenzofuran-1-imines in good yields without the use of stoichiometric amounts of oxidants and transition metal catalysts.

Meta-learning with Latent Space Clustering in Generative Adversarial Network for Speaker Diarization.

The performance of most speaker diarization systems with x-vector embeddings is both vulnerable to noisy environments and lacks domain robustness. Earlier work on speaker diarization using generative adversarial network (GAN) with an encoder network (ClusterGAN) to project input x-vectors into a latent space has shown promising performance on meeting data. In this paper, we extend the ClusterGAN network to improve diarization robustness and enable rapid generalization across various challenging domains.

Time for a Fully Integrated Nonclinical-Clinical Risk Assessment to Streamline QT Prolongation Liability Determinations: A Pharma Industry Perspective.

Defining an appropriate and efficient assessment of drug-induced corrected QT interval (QTc) prolongation (a surrogate marker of torsades de pointes arrhythmia) remains a concern of drug developers and regulators worldwide. In use for over 15 years, the nonclinical International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) S7B and clinical ICH E14 guidances describe three core assays (S7B: in vitro hERG current & in vivo QTc studies; E14: thorough QT study) that are used to assess the potential of drugs to cause delayed ventricular repolarization. Incorporating these assays during nonclinical or human testing of novel compounds has led to a low prevalence of QTc-prolonging drugs in clinical trials and no new drugs having been removed from the marketplace due to unexpected QTc prolongation.

Efficacy of a fasting-mimicking diet in functional therapy for depression: A randomised controlled pilot trial.

Objective: This randomized controlled trial examined the efficacy of adding a fasting-mimicking diet to a structured psychotherapy protocol for treating depression.

Design: Of 20 patients with depression, 10 were randomly assigned to psychotherapy and dieting (i.e.

Nitrogen Incorporated Photoactive Brownmillerite CaFeO for Energy and Environmental Applications.

CaFeO (CFO) is a potentially viable material for alternate energy applications. Incorporation of nitrogen in CaFeO (CFO-N) lattice modifies the optical and electronic properties to its advantage. Here, the electronic band structures of CFO and CFO-N were probed using Ultraviolet photoelectron spectroscopy (UPS) and UV-Visible spectroscopy.

Improved performance of dye-sensitized solar cells upon sintering of a PEDOT cathode at various temperatures.

Poly(3,4-ethylenedioxythiophene) (PEDOT) thin films have attracted considerable attention as cathodes for dye-sensitized solar cells (DSSCs) due to their air-stable, light-weight and conductive nature. To demonstrate their thermal stability as cathodes, PEDOT thin films coated electrochemical polymerization on fluorine doped tin oxide (FTO) plates were sintered at different temperatures (50, 100, 150, 200, and 300 °C) for 1 h and a comparison was made with the as-prepared PEDOT thin films. We observed a negative temperature coefficient effect up to 200 °C along with lower surface roughness upon increasing the sintering temperature.

The impact of technical and clinical factors on fecal microbiota transfer outcomes for the treatment of recurrent infections in Germany.

Introduction: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany.

Ultrafine particles in airways: a novel marker of COPD exacerbation risk and inflammatory status.

Purpose: Ultrafine particles (UFP) are toxic due to their small size and penetration into deeper lung compartments. We aimed to evaluate the exhaled breath condensate (EBC)-UFP content as a reflection of inflammation and oxidative stress status in COPD patients and as an exacerbation risk marker.

Methods: EBC was collected by conventional methods.

The association between semaphorin 3A levels and gluten-free diet in patients with celiac disease.

Celiac disease (CD) is an inflammatory disease affecting the small intestine. We aim to assess serum level and expression of semaphorin 3A (Sema3A) on T regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac patients, 13 celiac patients on a gluten-free diet and 16 healthy controls included in the study.

The Expansion of CD25 high IL-10 high FoxP3 high B Regulatory Cells Is in Association with SLE Disease Activity.

B regulatory cells (Bregs) belong to a subgroup of activated B cells tasked with maintaining self-tolerance and preventing autoimmunity. While sharing similar regulatory mechanisms such as IL-10 dependency, they also defer in exhibiting their suppressive effects by expressing Fas-Ligand, TGF-beta, and PDL-1. In this study we show, for the first time, the expansion of CD25(high)FoxP3(high) Bregs in systemic lupus erythematosus (SLE) patients compared to healthy individuals (18.

Immunization of pregnant women against pertussis: the effect of timing on antibody avidity.

Background: The Centers for Disease Control and Prevention recommend tetanus-diphteria-acellular pertussis (Tdap) immunization during pregnancy, preferably at 27-36 weeks gestation.

Aims: First, to assess the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) for newborns of women immunized with Tdap during late pregnancy as compared to unimmunized women. Second, to assess whether there is a preferential period of gestational Tdap immunization that provides the highest RAI of umbilical cord IgG to PT.

The induction of breast milk pertussis specific antibodies following gestational tetanus-diphtheria-acellular pertussis vaccination.

Background: Center for Disease Control and Prevention recommends vaccination of pregnant women with tetanus-diphtheria-acellular pertussis (Tdap).

Aim: To measure pertussis specific antibodies, total protein and their ratio in breast milk following gestational Tdap vaccination.

Methods: Women who received Tdap after the 20th week of pregnancy were recruited and unvaccinated women served as controls.

A regulatory role for CD72 expression on B cells in systemic lupus erythematosus.

Background: B regulatory cells and their regulatory products/markers, such us semaphorin 3A (sema3A) and its receptor NP-1, FcγIIB, IL-10, and others, act at the very base of self-tolerance, maintenance, and prevention of autoimmune disease development.

Objectives: The aim of the present study was to assess the involvement of CD72, a regulatory receptor on B cells, in systemic lupus erythematosus (SLE). In addition, the potential of soluble sema3A in enhancing the expression of CD72 on B cells of SLE patients was investigated.

Increased Toll-like receptor 9 expression by B cells from inflammatory bowel disease patients.

Background: Toll-like receptors (TLRs) are important mediators of the innate immune response. Our aim was to evaluate TLR9 expression in peripheral B cells, taken from inflammatory bowel disease (IBD) patients before and after anti-inflammatory treatment. Nineteen patients with IBD (12-crohn's disease, 7-ulcerative colitis) and 18 healthy controls were included in the study.