New insights in uranium bioremediation by cytochromes of the bacterium G. uraniireducens.

The bacterium Geotalea uraniireducens, commonly found in uranium-contaminated environments, plays a key role in bioremediation strategies by converting the soluble hexavalent form of uranium (U) into less soluble forms (e.g. U.

Interpersonal counselling for adolescent depression delivered by youth mental health workers without core professional training: the ICALM feasibility RCT.

Background: As milder cases of adolescent depression do not meet treatment thresholds for specialist mental health services, young people often receive support from non-qualified professionals in third-sector/voluntary agencies. Early psychological interventions to meet growing demand with limited resources are crucial.

Objectives: The study aimed to explore the effectiveness and cost effectiveness of interpersonal counselling for adolescents by (1) assessing the feasibility and acceptability of trial procedures; (2) exploring the delivery of, and differences between, interpersonal counselling for adolescents and treatment as usual; (3) evaluating the extent of contamination of the control arm and if it should be mitigated against in a future trial; and (4) investigating whether the interval estimate of benefit of interpersonal counselling for adolescents over treatment as usual in depression post treatment includes a clinically significant effect.

Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRASG12C.

Approved inhibitors of KRASG12C prevent oncogenic activation by sequestering the inactive, GDP-bound (OFF) form rather than directly binding and inhibiting the active, GTP-bound (ON) form. This approach provides no direct target coverage of the active protein. Expectedly, adaptive resistance to KRASG12C (OFF)-only inhibitors is observed in association with increased expression and activity of KRASG12C(ON).

Clinical Pharmacology of Cytokine Release Syndrome with T-cell Engaging Bispecific Antibodies: Current Insights and Drug Development Strategies.

Cytokine release syndrome (CRS) is a common acute toxicity in T-cell therapies, including T-cell engaging bispecific antibodies (T-BiSp). Effective CRS management and prevention is crucial in T-BiSp development. Required hospitalization for 7 of the 9 approved T-BiSp and the need for clinical intervention in severe cases highlight the importance of mitigation strategies to reduce healthcare burden and improve patient outcome.

Foxn3 is part of a transcriptional network that regulates cilia genes in the developing mouse retina.

The forkhead transcription factor Foxn3 is a transcriptional repressor. Analysis of embryonic retinas from mice with a targeted disruption of the Foxn3 gene revealed upregulation of numerous genes linked to cilia structure or assembly. Foxj1, a forkhead transcription factor required for motile cilia, was upregulated, along with multiple target genes of Foxj1.

PBBM Considerations for Base Models, Model Validation, and Application Steps: Workshop Summary Report.

The proceedings from the 30th August 2023 (Day 2) of the workshop "Physiologically Based Biopharmaceutics Models (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives" are provided herein. Day 2 covered PBBM case studies from six regulatory authorities which provided considerations for model verification, validation, and application based on the context of use (COU) of the model. PBBM case studies to define critical material attribute (CMA) specification settings, such as active pharmaceutical ingredient (API) particle size distributions (PSDs) were shared.

A Novel Step-Up Dosage Regimen for Enhancing the Benefit-to-Risk Ratio of Mosunetuzumab in Relapsed or Refractory Follicular Lymphoma.

Mosunetuzumab, a T-cell engaging bispecific antibody targeting CD20xCD3, is approved for treating relapsed/refractory follicular lymphoma. This research supports the approved intravenous clinical dose regimen, summarizing the exposure-response relationships for clinical safety and efficacy. A population pharmacokinetic model and E logistic regression exposure-response models for safety and efficacy were developed using data from 439 patients with relapsed/refractory non-Hodgkin lymphoma and 159 patients with relapsed/refractory follicular lymphoma, respectively, from a Phase I/II study (NCT02500407).

Enantiopure molecules form apparently racemic monolayers of chiral cyclic pentamers.

Ultra-high vacuum scanning tunneling microscopy (UHV-STM) was used to investigate two related molecules pulse-deposited onto Au(111) surfaces: indoline-2-carboxylic acid and proline (pyrrolidine-2-carboxylic acid). Indoline-2-carboxylic acid and proline form both dimers and -symmetric "pinwheel" pentamers. Enantiomerically pure -(-)-indoline-2-carboxylic acid and -proline were used, and the pentamer structures observed for both were chiral.

Quantitative NMR Analysis of Marine Macroalgae for AGE Inhibition by Methylglyoxal Scavenging.

Reactive carbonyl species (RCS) induce a fundamental form of biological stress that has driven the evolution of diverse mechanisms for minimizing its impact on organismal health. The complications that accompany uncontrolled hyperglycemia exemplify the health implications when RCS stress exceeds the body's capacity to prevent the excessive formation of advanced glycation end-products. Presented here is a novel quantitative NMR (qNMR) technique for evaluating scavengers of the prominent sugar-derived carbonyl methylglyoxal (MGO).

The clinical and cost effectiveness of internet-delivered self-help Acceptance and Commitment Therapy for family carers of people with dementia (iACT4CARERS): Study protocol for a randomised controlled trial with ethnically diverse family carers.

Background: Following the successful completion of feasibility and acceptability studies of internet-delivered self-help Acceptance and Commitment Therapy for family carers of people with dementia (iACT4CARERS), a full-scale randomised controlled trial (RCT) evaluating its clinical and cost effectiveness will be conducted. This paper describes the design and protocol for a multi-site, parallel, single-blind, 2-arm RCT evaluating the clinical and cost effectiveness of iACT4CARERS plus treatment-as-usual (TAU) in comparison to TAU alone for reducing anxiety in family carers of people with dementia.

Methods: 496 family carers aged ≥18 years, who are caring for a person with dementia, will be recruited from national healthcare services, general practices and community groups in England.

Evaluating the correspondence between the EQ-5D-5L and disease severity and quality of life in adults and adolescents with cystic fibrosis.

Background: The EQ-5D is the recommended measure to capture health-related quality of life (HRQoL), recognised for use in health technology appraisal bodies. In order to assess whether it is appropriate to use the EQ-5D for making decisions about the cost-utility of treatments in cystic fibrosis (CF), this study assesses the performance of the EQ-5D-5L in adults and adolescents with CF.

Method: This was a cross-sectional observational survey study of patients with CF attending a single large CF centre.

A realist evaluation of prospective entrustment decisions in paediatric residency clinical competency committees.

Purpose: Making entrustment decisions (granting more responsibility, advancement and graduation) are important actions in medical training that pose risks to trainees and patients if not done well. A previous realist synthesis of the existing literature revealed that clinical competency committees (CCCs) do not typically make deliberate entrustment decisions, instead defaulting to the promotion and graduation of trainees in the absence of red flags. This study sought further understanding of these areas through empirical data.

Three-dimensional stem cell models of mammalian gastrulation.

Gastrulation is a key milestone in the development of an organism. It is a period of cell proliferation and coordinated cellular rearrangement, that creates an outline of the body plan. Our current understanding of mammalian gastrulation has been improved by embryo culture, but there are still many open questions that are difficult to address because of the intrauterine development of the embryos and the low number of specimens.

Synthesis of pyridyl functionalized 3-pyrrolyl BODIPY based fluoroprobes and application towards highly selective detection of picric acid.

A series of pyridyl-coupled 3-pyrrolyl BODIPY fluoroprobes were synthesized by varying the position of the pyridyl/-methylated pyridyl group at the α-/-position of the 3-pyrrolyl BODIPY scaffold and thoroughly characterized by HRMS and 1D/2D NMR techniques. Our studies indicated that only the water-soluble -methylated -pyridyl 3-pyrrolyl BODIPY among various pyridyl-coupled 3-pyrrolyl BODIPYs synthesized here showed an effective and exclusive sensing for picric acid (HPA). The -methylated -pyridyl 3-pyrrolyl BODIPY rapidly detects HPA in an aqueous medium with exceptional selectivity, sensitivity (LOD = 7.

A Reduced-Symmetry PdL Cage from a Heterotopic Dipyridyl Ligand.

Two dipyridyl ligands, and , have been used in combination with palladium(II) in the construction of metallosupramolecular species that show anion-dependent behavior in solution. A rare example of a low-symmetry () lantern-type cage is formed in one instance, [Pd(L)], while the isomeric ligand yields a larger double-walled square complex, [Pd(L)]. [Pd(L)](NO) was isolated in crystalline form revealing two anions within the interior of the -symmetry cage.