Validation framework for digital measures.

The adoption of digital measures in pharmaceutical research and development (R&D) presents an opportunity to enhance the efficiency and effectiveness of discovering and developing new therapeutics. For clinical measures, the Digital Medicine Society's (DiMe) V3 Framework is a comprehensive validation framework that encompasses verification, analytical validation, and clinical validation. This manuscript describes collaborative efforts to adapt this framework to ensure the reliability and relevance of digital measures for a preclinical context.

Structural and dynamical investigation of glassforming smectogen by X-ray diffraction and infra-red spectroscopy aided by density functional theory calculations.

Molecular arrangement in the chiral smectic phases of the glassforming (S)-4'-(1-methylheptylcarbonyl)biphenyl-4-yl 4-[7-(2,2,3,3,4,4,4-heptafluorobutoxy) heptyl-1-oxy]benzoate is investigated by X-ray diffraction. An increased correlation length of the positional short-range order in the supercooled state agrees with the previous assumption of the hexatic smectic phase. However, the registered X-ray diffraction patterns are not typical for the hexatic phases.

The Use of MPS in Three Rs and Regulatory Applications: Perspectives From Developers on Stakeholder Responsibilities.

Increasing the use of microphysiological systems (MPS) in Three Rs and regulatory applications is a nuanced but important goal, which would also help increase their scientific impact. There are three distinct and important stakeholder groups that each play a unique role in expediting the use of MPS for regulatory purpose - namely, commercial MPS developers, end-users and regulators. Additionally, non-profit organisations, such as the 3Rs Collaborative (3RsC), can help coordinate these efforts.

Exploring allocryptopine as a neuroprotective agent against oxidative stress-induced neural apoptosis via Akt/GSK-3β/tau pathway modulation.

Alzheimer's disease (AD) is characterized by neuronal loss due to hyperphosphorylated proteins induced by oxidative stress. AD remains a formidable challenge in the medical field, as current treatments focusing on single biomarkers have yielded limited success. Hence, there's a burgeoning interest in investigating novel compounds that can target mechanisms, offering alternative therapeutic approaches.

Magnetic structures in RPtIn (R = Tb-Tm) investigated by neutron powder diffraction.

Results of the neutron powder diffraction measurements carried out for RPtIn (R = Tb-Tm) are reported. The compounds crystallize in an orthorhombic crystal structure of the LuNiIn-type with the rare earth atoms occupying three different sublattices. Neutron diffraction data reveal that at low temperatures the rare earth magnetic moments order below the critical temperature equal to 105, 93, 28, 12 and 3.

Digitalization of toxicology: improving preclinical to clinical translation.

Though the portfolio of medicines that are extending and improving the lives of patients continues to grow, drug discovery and development remains a challenging business on its best day. Safety liabilities are a significant contributor to development attrition where the costliest liabilities to both drug developers and patients emerge in late development or post-marketing. Animal studies are an important and influential contributor to the current drug discovery and development paradigm intending to provide evidence that a novel drug candidate can be used safely and effectively in human volunteers and patients.

An organizing framework to break down Western-centric views of knowledge in North-South research.

Unlabelled: Global challenges, such as climate change, persistent poverty, and food insecurity are complex problems. These societal, environmental, and economic challenges cross scientific disciplines, communities, and geographies, requiring interdisciplinary, North-South solutions. Nevertheless, prevailing sustainability science responses are Western-centric.

Normalization of the Suppression Head Impulse Test (SHIMP) and its correlation with the Head Impulse Test (HIMP) in healthy adults.

Objective: In our study, it was aimed to compare vestibulo-ocular reflex (VOR) gain and saccade parameters in HIMP and SHIMP tests between gender, right and left ears, and age groups in healthy adults and to examine the correlation between the tests regarding these parameters.

Methods: The study included a total of 100 healthy participants aged 18-65 and without complaints of hearing loss, dizziness, lightheadedness, and/or imbalance. Participants underwent HIMP and SHIMP tests, respectively.

Toward implementing virtual control groups in nonclinical safety studies.

Historical data from control groups in animal toxicity studies are currently mainly used for comparative purposes to assess validity and robustness of study results. Due to the highly controlled environment in which the studies are performed and the homogeneity of the animal collectives it has been proposed to use the historical data to build so-called virtual control groups, which could partly or entirely replace the concurrent control group. This would constitute a substantial contribution to the reduction of animal use in safety studies.

Crystal and magnetic structures of RNiIn compounds (R = Tb and Ho).

Crystal and magnetic structures of RNiIn (R = Tb and Ho) have been studied using powder neutron diffraction at low temperatures. The compounds crystallize as orthorhombic crystal structures of the MnAlB type. At low temperatures, the magnetic moments localized solely on the rare earth atoms form antiferromagnetic structures.

An AI Approach to Generating MIDD Assets Across the Drug Development Continuum.

Model-informed drug development involves developing and applying exposure-based, biological, and statistical models derived from preclinical and clinical data sources to inform drug development and decision-making. Discrete models are generated from individual experiments resulting in a single model expression that is utilized to inform a single stage-gate decision. Other model types provide a more holistic view of disease biology and potentially disease progression depending on the appropriateness of the underlying data sources for that purpose.

Integrating AI/ML Models for Patient Stratification Leveraging Omics Dataset and Clinical Biomarkers from COVID-19 Patients: A Promising Approach to Personalized Medicine.

The COVID-19 pandemic has presented an unprecedented challenge to the healthcare system. Identifying the genomics and clinical biomarkers for effective patient stratification and management is critical to controlling the spread of the disease. Omics datasets provide a wealth of information that can aid in understanding the underlying molecular mechanisms of COVID-19 and identifying potential biomarkers for patient stratification.

Safety of laparoscopic surgery in the management of endometrioid endometrial cancer.

Background: Laparoscopic surgery has increasingly been preferred in recent years. However, data regarding the safety of laparoscopy in endometrial cancer are not sufficient. The aim of this study was to compare perioperative and oncologic outcomes of laparoscopic and laparotomic staging surgery in patients with endometrioid endometrial cancer and to evaluate the safety and efficacy of laparoscopic surgery in this population.

Investigation of Chiral Smectic Phases and Conformationally Disordered Crystal Phases of the Liquid Crystalline 3F5FPhH6 Compound Partially Fluorinated at the Terminal Chain and Rigid Core.

Complementary methods are applied to investigate the phase transitions and crystallization kinetics of the liquid crystalline compound denoted as 3F5FPhH6. Two crystal phases are confirmed, and one of them is the conformationally disordered (CONDIS) phase. Complexity of the melt crystallization process is revealed by the analysis with Friedman's isoconversional method.

"Expert persuasion" can decrease willingness to pay for sugar-containing food.

Recent studies have revealed types of eating nudges that can steer consumers toward choosing healthier options. However, most of the previously studied interventions target individual decisions and are not directed to changing consumers' underlying perception of unhealthy food. Here, we investigate how a healthy eating call-first-person narrative by a health expert-affects individuals' willingness to pay (WTP) for sugar-free and sugar-containing food products.

A Social Network Analysis of Tweets Related to Mandatory COVID-19 Vaccination in Poland.

Poland's efforts to combat COVID-19 were hindered by endemic vaccination hesitancy and the prevalence of opponents to pandemic restrictions. In this environment, the policy of a COVID-19 vaccination mandate faces strong resistance in the public debate. Exploring the discourse around this resistance could help uncover the motives and develop an understanding of vaccination hesitancy in Poland.

An intermetallic molecular nanomagnet with the lanthanide coordinated only by transition metals.

Magnetic molecules known as molecular nanomagnets (MNMs) may be the key to ultra-high density data storage. Thus, novel strategies on how to design MNMs are desirable. Here, inspired by the hexagonal structure of the hardest intermetallic magnet SmCo, we have synthesized a nanomagnetic molecule where the central lanthanide (Ln) Er is coordinated solely by three transition metal ions (TM) in a perfectly trigonal planar fashion.

Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development.

In drug discovery and development, traditional assessment of human patients and preclinical subjects occurs at limited time points in potentially stressful surroundings (i.e., the clinic or a test arena), which can impact data quality and welfare.

Perspectives on the evaluation and adoption of complex in vitro models in drug development: Workshop with the FDA and the pharmaceutical industry (IQ MPS Affiliate).

Complex in vitro models (CIVM) offer the potential to improve pharmaceutical clinical drug attrition due to safety and/ or efficacy concerns. For this technology to have an impact, the establishment of robust characterization and qualifi­cation plans constructed around specific contexts of use (COU) is required. This article covers the output from a workshop between the Food and Drug Administration (FDA) and Innovation and Quality Microphysiological Systems (IQ MPS) Affiliate.

Organiational Structure and Created Values. Review of Methods of Studying Collective Intelligence in Policymaking.

The domain of policymaking, which used to be limited to small groups of specialists, is now increasingly opening up to the participation of wide collectives, which are not only influencing government decisions, but also enhancing citizen engagement and transparency, improving service delivery and gathering the distributed wisdom of diverse participants. Although collective intelligence has become a more common approach to policymaking, the studies on this subject have not been conducted in a systematic way. Nevertheless, we hypothesized that methods and strategies specific to different types of studies in this field could be identified and analyzed.

In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals.

The aim of this study is to identify potential drug-like molecules against SARS-CoV-2 virus among the natural antiviral compounds published in the Encyclopedia of Traditional Chinese Medicine. To test inhibition capability of these compounds first, we docked them with Spike protein, angiotensin-converting enzyme 2 (ACE2) (PDB ID: 6M0J) and neuropilin 1 (NRP1) (PDB ID: 7JJC) receptors, and found significant docking scores with extra precision up to -11 kcal/mol. Then, their stability in the binding pockets were further evaluated with molecular dynamics simulation.

Prognostic factors of endometrial cancer in elderly patient group and their effects on survival.

Objective: The objective of the study was to investigate the prognostic factors of the elderly group and their effects on survival by examining the histopathological features, surgical treatment protocols, and treatment modalities of patients diagnosed with endometrial cancer (EC).

Methods: The records of 397 EC patients who completed their treatment and follow-up at a single center between 2012 and 2019 were evaluated retrospectively. The patients were evaluated in two groups as <70 years old (n: 301; 75.