Durvalumab, Tremelimumab, and Platinum Chemotherapy in Mutation-Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE).

Introduction: -mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs).

Methods: Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance.

Predictive value of CT-based and AI-reconstructed 3D-TAPSE in patients undergoing transcatheter tricuspid valve repair.

Background: The tricuspid annular plane systolic excursion (TAPSE) assessed by echocardiography has failed in predicting outcomes in patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). Considering the complex shape of the tricuspid annulus and right ventricle, as well as the difficult echocardiographic image acquisition of the right heart, cardiac computed tomography (CT) might be superior for the analysis of the annular excursion. Thus, this study aimed to analyze whether CT-captured TAPSE provides additional value in predicting outcomes after TTVI.

Theta transcranial alternating current stimulation over the prefrontal cortex enhances theta power and working memory performance.

Introduction: Transcranial alternating current stimulation (tACS) is a promising tool for modulating brain oscillations. This study investigated whether 5 Hz tACS could modulate neural oscillations in the prefrontal cortex and how this modulation impacts performance in working memory (WM) tasks.

Method: In two sessions, 28 healthy participants received 5 Hz tACS or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC) while performing tasks with high and low WM loads.

Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus.

Infections impacting the central nervous system (CNS) constitute a substantial predisposing factor for the emergence of epileptic seizures. Given that epilepsy conventionally correlates with hippocampal sclerosis and neuronal degeneration, a potentially innovative avenue for therapeutic intervention involves fostering adult neurogenesis, a process primarily occurring within the subgranular zone of the dentate gyrus (DG) through the differentiation of neural stem cells (NSC). While experimental seizures induced by chemoconvulsants or electrical stimulation transiently enhance neurogenesis, the effects of encephalitis and the resultant virus-induced seizures remain inadequately understood.

How To Correct Erroneous Symmetry-Breaking in Coarse-Grained Constant-pH Simulations.

The constant-pH Monte Carlo method is a popular algorithm to study acid-base equilibria in coarse-grained simulations of charge regulating soft matter systems including weak polyelectrolytes and proteins. However, the method suffers from systematic errors in simulations with explicit ions, which lead to a symmetry-breaking between chemically equivalent implementations of the acid-base equilibrium. Here, we show that this artifact of the algorithm can be corrected a-posteriori by simply shifting the pH-scale.

Be Aware of Transient Dissolution Processes in CoO Acidic Oxygen Evolution Reaction Electrocatalysts.

Recently, cobalt-based oxides have received considerable attention as an alternative to expensive and scarce iridium for catalyzing the oxygen evolution reaction (OER) under acidic conditions. Although the reported materials demonstrate promising durability, they are not entirely intact, calling for fundamental research efforts to understand the processes governing the degradation of such catalysts. To this end, this work studies the dissolution mechanism of a model CoO porous catalyst under different electrochemical conditions using online inductively coupled plasma mass spectrometry (online ICP-MS), identical location scanning transmission electron microscopy (IL-STEM), and differential electrochemical mass spectrometry (DEMS).

Active control over exploration improves memory in toddlers.

Across two experiments, we implemented a novel gaze-contingent eye-tracking paradigm to investigate the early emergence of memory benefits from active control over exploration and to examine how exploratory behaviours affect memory formation in early development. Toddlers (experiment 1: = 36, 18-36 months; experiment 2: = 41, 23-36 months) were either allowed to actively control their exploration (active condition) or presented with the same information that they could only passively observe (passive condition in experiment 1; yoked condition in experiment 2). They were then tested in a preferential-looking paradigm in which familiar versus novel stimuli were presented in pairs.

Social vocalizations indicate behavioural type in bats.

Vocalizations play a crucial role in the social systems of many animals and may inadvertently reveal behavioural characteristics of the sender. Bats, the second largest mammalian order, rely extensively on vocalizations owing to their nocturnal lifestyle and complex social systems, making them ideal for studying links between vocalizations and consistent behavioural traits. In this study, we developed a new testing regime to investigate whether consistent individual vocalization differences in nectarivorous bats are associated with specific behavioural types.

Volitional spatial attention is lateralized in crows.

Like humans and many other animal species, birds exhibit left-right asymmetries in certain behaviours due to differences in hemispheric brain functions. While the lateralization of sensory and motor functions is well established in birds, the potential lateralization of high-level executive control functions, such as volitional attention, remains unknown. Here, we demonstrate that carrion crows exhibit more pronounced volitional (endogenous) attention for stimuli monocularly viewed with the left eye and thus in the left visual hemifield.

The promise of community-driven preprints in ecology and evolution.

Publishing preprints is quickly becoming commonplace in ecology and evolutionary biology. Preprints can facilitate the rapid sharing of scientific knowledge establishing precedence and enabling feedback from the research community before peer review. Yet, significant barriers to preprint use exist, including language barriers, a lack of understanding about the benefits of preprints and a lack of diversity in the types of research outputs accepted (e.

Social learning preserves both useful and useless theories by canalizing learners' exploration.

In many domains, learning from others is crucial for leveraging cumulative cultural knowledge, which encapsulates the efforts of successive generations of innovators. However, anecdotal and experimental evidence suggests that reliance on social information can reduce the exploration of the problem space. Here, we experimentally investigate the extent to which cultural transmission fosters the persistence of arbitrary solutions in a context where participants are incentivized to improve a physical system across multiple trials.

A Game of Life with dormancy.

The factors contributing to the persistence and stability of life are fundamental for understanding complex living systems. Organisms are commonly challenged by harsh and fluctuating environments that are suboptimal for growth and reproduction, which can lead to extinction. Many species contend with unfavourable and noisy conditions by entering a reversible state of reduced metabolic activity, a phenomenon known as dormancy.

Rationale and design of the FAIR-HF2-DZHK05 trial: Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure.

Aims: While it is widely accepted that intravenous (IV) iron improves functional capacity, symptoms, and cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) diagnosed with iron deficiency (ID), three recently published cardiovascular outcome trials (AFFIRM-AHF, IRONMAN and HEART-FID) of IV iron supplementation in HF failed to demonstrate a significant benefit on their respective primary endpoints. Dosing of IV iron after the initial correction of baseline ID - by design or as a result of trial circumstances - was relatively low (i.e.

Spaced Transcranial Direct Current Stimulation for Major Depression.

Objective: This study investigated spaced transcranial direct current stimulation for major depressive disorder, focusing on feasibility.

Methods: In a prospective open-label study, 30 participants with major depressive disorder were enrolled to receive a 50-session transcranial direct current stimulation (tDCS) treatment over 2 weeks. The feasibility, safety, tolerability, and preliminary therapeutic effects of this tDCS protocol were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and 1-week and 4-week follow-ups, as well as with the 6-item HAM-D (HAM-D-6) daily during treatment.

Improving the Long-term Enantioselectivity of a Silicon-Carbon Bond-Forming Enzyme.

Enantioselectivity is a key advantage of enzymatic catalysis. Understanding the most important factors influencing enantioselectivity necessitates thorough investigation for each specific enzyme. In this study, we explore various approaches to optimize reaction conditions for organosilicon production using an immobilized Cytochrome C recently tailored via directed evolution.

Room Temperature Ethene to Propene (ETP) Tandem Catalysis using Single Crystalline Solid-State Molecular Pre-Catalysts.

A tandem catalytic ensemble of solid-state molecular organometallic (SMOM) crystalline pre-catalysts are deployed under batch or flow conditions for the ethene to propene process (ETP). These catalysts operate at ambient temperature and low pressure, via sequential ethene dimerization, butenes isomerization and cross-metathesis. Under flow conditions the on-stream ethene conversion (55%), initial propene selectivity (92%), stability (71% selectivity after 7 hrs) and low temperature/pressures are competitive with the best-in-class heterogenous systems, marking a new, in crystallo, approach to ETP.

The Electrochemical Iodination of Electron-Deficient Arenes.

The iodination of electron-deficient arenes and heteroarenes is a long-standing problem in organic synthesis. Herein we describe the electrochemical iodination in nitromethane with BuNI as iodine source and supporting electrolyte under Lewis acid-free conditions in the presence of small amounts of chloride anions. The electrochemically generated reagent could be applied for the iodination of halogenated arenes, aromatic aldehydes, acids, esters, ketones, as well as nitroarenes to afford the products in good to excellent yields.

Diagnosis, Classifications and Treatment of Os Odontoideum: WFNS Spine Committee Recommendations.

Study Design: A systematic literature review and consensus using Delphi method.

Objective: The aim was to formulate consensus recommendations regarding the natural history, diagnosis, classification and optimal treatment of Os Odontoideum with global applicability.

Summary Of Background: Os odontoideum (OO) is a rare anomaly of the cranio-vertebral junction (CVJ).

Lignin-Based Mucus-Mimicking Antiviral Hydrogels with Enzyme Stability and Tunable Porosity.

Mucus is a complex hydrogel that acts as a defensive and protective barrier in various parts of the human body. The rise in the level of viral infections has underscored the importance of advancing research into mucus-mimicking hydrogels for the efficient design of antiviral agents. Herein, we demonstrate the gram-scale synthesis of biocompatible, lignin-based virus-binding inhibitors that reduce waste and ensure long-term availability.

Use of Resonant Acoustic Fields as Atmospheric-Pressure Ion Gates.

Ion optics are crucial for spectrometric methods such as mass spectrometry (MS) and ion mobility spectrometry (IMS). Among the wide selection of ion optics, temporal ion gates are of particular importance for time-of-flight MS (TOF-MS) and drift-tube IMS. Commonly implemented as electrostatic ion gates, these optics offer a rapid, efficient means to block ion beams and form discrete ion packets for subsequent analysis.

Molecular screening of Babesia, Hepatozoon, and Theileria (Apicomplexa: Piroplasmida) in ticks (Acari: Ixodidae) infesting farm ruminants in Peninsular Malaysia.

Ticks are obligate hematophagous arachnids that feed on both humans and animals. Despite the extensive research on detection of bacteria in ixodid ticks in Malaysia, there remains limited knowledge about the detection of protozoa in these ectoparasites, especially in those that feed on farm ruminants. In this study, 1,241 ticks belonging to four species (Rhipicephalus microplus, R.

IQ Survey Results on Current Industry Practices-Part 1: Immunogenicity Risk Assessment.

An immunogenicity risk assessment (IRA) is a relatively new expectation of health authorities that is increasingly incorporated into the drug development process across the pharmaceutical/biotech industry. The guiding principle for an IRA includes a comprehensive evaluation of product- and patient-related factors that may influence the immunogenic potential of a biotherapeutic drug and a potential action plan. The Immunogenicity Working Group from the IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices for conducting IRAs and relevant aspects of bioanalysis.

Head-to-Head Comparison Between [68Ga]Ga-DOTA.SA.FAPi And [18F]F-FDG PET/CT Imaging in Patients With Sarcoma.

Purpose: This study aimed to compare the diagnostic efficacy of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT for detecting primary and metastatic lesions in sarcoma patients.

Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).

Clinical Presentation and Course of Pulmonary Involvement in Chronic Nonbacterial Osteomyelitis.

Objective: Pulmonary involvement in chronic nonbacterial osteomyelitis (CNO) is rare. Limited awareness results in diagnostic challenges, especially because malignancy or infection needs to be considered.

Methods: Based on a survey shared among centers participating in the Kerndokumentation Deutsches Rheumaforschungszentrum (Germany), this study investigated clinical and imaging presentations, demographic features, treatment response and outcomes of pulmonary involvement in CNO (pCNO).