Creation of Scientific Response Documents for Addressing Product Medical Information Inquiries: Mixed Method Approach Using Artificial Intelligence.

Background: Pharmaceutical manufacturers address health care professionals' information needs through scientific response documents (SRDs), offering evidence-based answers to medication and disease state questions. Medical information departments, staffed by medical experts, develop SRDs that provide concise summaries consisting of relevant background information, search strategies, clinical data, and balanced references. With an escalating demand for SRDs and the increasing complexity of therapies, medical information departments are exploring advanced technologies and artificial intelligence (AI) tools like large language models (LLMs) to streamline content development.

Individual vocal identity may be obscured following colony assembly in captive black-capped chickadees.

Black-capped chickadee (Poecile atricapillus) vocalisations remain plastic throughout their lifespans. Although fledglings employ vocal plasticity to refine their vocalisations through the use of tutor mimicry, adults employ vocal plasticity to create unique population dialects. Vocal convergence is one mechanism by which flockmates' vocalisations become increasingly similar to each other and distinct from the calls of other flocks.

Resistify: A Novel NLR Classifier That Reveals Helitron-Associated NLR Expansion in Solanaceae.

Nucleotide-binding domain leucine-rich repeat (NLR) proteins are a key component of the plant innate immune system. In plant genomes, NLRs exhibit considerable presence/absence variation and sequence diversity. Recent advances in sequencing technologies have made the generation of high-quality novel plant genome assemblies considerably more straightforward.

A Novel In Vitro Model of the Bone Marrow Microenvironment in Acute Myeloid Leukemia Identifies CD44 and Focal Adhesion Kinase as Therapeutic Targets to Reverse Cell Adhesion-Mediated Drug Resistance.

Background/objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has therapeutic potential.

The mitochondriotropic antioxidants AntiOxBEN and AntiOxCIN are structurally-similar but differentially alter energy homeostasis in human skin fibroblasts.

Mitochondrial dysfunction and increased reactive oxygen species (ROS) generation play an import role in different human pathologies. In this context, mitochondrial targeting of potentially protective antioxidants by their coupling to the lipophilic triphenylphosphonium cation (TPP) is widely applied. Employing a six‑carbon (C) linker, we recently demonstrated that mitochondria-targeted phenolic antioxidants derived from gallic acid (AntiOxBEN) and caffeic acid (AntiOxCIN) counterbalance oxidative stress in primary human skin fibroblasts by activating ROS-protective mechanisms.

Selective laser sintering for printing bilayer tablets.

In this study Selective Laser Sintering (SLS) was used to produce bilayer tablets containing rosuvastatin and acetylsalicylic acid. Initially, monolithic tablets of each drug were manufactured using different laser intensities in order to identify their impact on the tablet's dissolution, friability and hardness. After the optimization, the final bilayer tablet was fabricated using a new method, that allowed the printing using different powder blends.

Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism Spectrum Disorder.

More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in silico methods to create an ideal (virtual) population of 120,000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use.

The Mechanical and Electrochemical Stability of Trimethysilane Plasma Nanocoatings Deposited onto Cobalt Chromium Cardiovascular Stents.

The objective of this study was to evaluate the coating integrity performance and corrosion protection property of trimethylsilane (TMS) plasma nanocoatings that were directly deposited onto cobalt chromium (CoCr) L605 cardiovascular stents. Hydrophilic surfaces were achieved for the TMS plasma nanocoatings that were deposited onto the coronary stents through NH/O (2:1 molar ratio) plasma post-treatment. With a coating thickness of approximately 20-25 nm, the TMS plasma nanocoatings were highly durable and able to resist delamination and cracking from crimping and expansion by a Model CX with a J-Crimp Station.

Design, synthesis and biological evaluation of glucose metabolism inhibitors as anticancer agents.

Compared to normal cells, tumour cells exhibit an upregulation of glucose transporters and an increased rate of glycolytic activity. In previous research, we successfully identified a promising hit compound BH10 through a rigorous screening process, which demonstrates a potent capacity for inhibiting cancer cell proliferation by targeting glucose metabolism. In the current study, we identify Kelch-like ECH-associated protein 1 (Keap1) as a potential protein target of BH10via avidin pull-down assays with biotinylated-BH10.

The Effects of Long-Term High Fat and/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice.

Background: In MASLD (formerly called NAFLD) mouse models, oversupply of dietary fat and sugar is more lipogenic than either nutrient alone. Fatty acids suppress de novo lipogenesis (DNL) from sugars, while DNL inhibits fatty acid oxidation. How such factors interact to impact hepatic triglyceride levels are incompletely understood.

Patient-specific computational models predict prognosis in B cell lymphoma by quantifying pro-proliferative and anti-apoptotic signatures from genetic sequencing data.

Genetic heterogeneity and co-occurring driver mutations impact clinical outcomes in blood cancers, but predicting the emergent effect of co-occurring mutations that impact multiple complex and interacting signalling networks is challenging. Here, we used mathematical models to predict the impact of co-occurring mutations on cellular signalling and cell fates in diffuse large B cell lymphoma and multiple myeloma. Simulations predicted adverse impact on clinical prognosis when combinations of mutations induced both anti-apoptotic (AA) and pro-proliferative (PP) signalling.

A gene with a thousand alleles: The hyper-variable effectors of plant-parasitic nematodes.

Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the hyper-variable (HYP) effectors of plant-parasitic nematodes.

Characterisation and mapping of a Globodera pallida resistance derived from the wild potato species Solanum spegazzinii.

A new resistance locus acting against the potato cyst nematode Globodera pallida was mapped to chromosome VI in the diploid wild potato species Solanum spegazzinii CPC 7195. The potato cyst nematodes (PCN) Globodera pallida and Globodera rostochiensis are economically important potato pests in almost all regions where potato is grown. One important management strategy involves deployment through introgression breeding into modern cultivars of new sources of naturally occurring resistance from wild potato species.

Determining the Impact of Roller Compaction Processing Conditions on Granulate and API Properties: Impact of Formulation API Load.

Previous work demonstrated that roller compaction of a 40%w/w theophylline-loaded formulation resulted in granulate consisting of un-compacted fractions which were shown to constitute between 34 and 48%v/v of the granulate dependent on processing conditions. The active pharmaceutical ingredient (API) primary particle size within the un-compacted fraction was also shown to have undergone notable size reduction. The aim of the current work was to test the hypothesis that the observations may be more indicative of the relative compactability of the API due to the formulation being above the percolation threshold.

The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits.

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment.

Tail Fan Necrosis syndrome in decapod crustaceans: A review.

Lobsters and crayfish in Australasia can develop a condition known as Tail Fan Necrosis (TFN syndrome). Many attempts have been made to find a primary pathogen or link the syndrome to commercial activities, but a solution remains elusive. TFN syndrome is a 'wicked problem', a problem difficult or impossible to solve because of incomplete and contradictory information forming a matrix of potential outcomes with no simple solution.

Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer.

Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy.

A novel approach to expedite wound healing with plasma brush of cold flame.

Excessive or persistent infection is a major contributing factor in impeding chronic wound healing. Wound bed preparations using antiseptics do not necessarily target the entire bacterial spectrum, and the highly proliferating granulation tissue may be sensitive to the cytotoxic effects, impairing tissue repair. Non-thermal gas atmospheric pressure plasmas are partially ionized gases that contain highly reactive particles while the gas phase remains near room temperature, thus having the capability of accessing small irregular cavities and fissures and killing bacteria because of the diffusive nature of gas phase plasma species that are chemically reactive, providing an ideal approach to topical wound disinfection.

Lamotrigine use and potential for adverse cardiac effects: A retrospective evaluation in a Veteran population.

Objective: To identify the impact of lamotrigine (LTG) on cardiac rhythm and conduction abnormalities for Veterans, an especially vulnerable population.

Background: In October 2020 the US Food and Drug Administration (FDA) added a new warning to the label of lamotrigine (Lamictal™) regarding its potential to cause cardiac rhythm and conduction abnormalities [1]. This warning came following in vitro data which suggested Class IB antiarrhythmic effects occurring at clinically achievable concentrations of lamotrigine [2].

Proteomics Reveals mRNA Regulation and the Action of Annexins in Thyroid Cancer.

Differentiated thyroid cancer is the most common malignancy of the endocrine system. Although most thyroid nodules are benign, given the high incidence of thyroid nodules in the population, it is important to understand the differences between benign and malignant thyroid cancer and the molecular alterations associated with malignancy to improve detection and signal potential diagnostic, prognostic, and therapeutic targets. Proteomics analysis of benign and malignant human thyroid tissue largely revealed changes indicating modifications in RNA regulation, a common cancer characteristic.

Tropical and temperate differences in the trophic structure and aquatic prey use of riparian predators.

The influence of aquatic resource-inputs on terrestrial communities is poorly understood, particularly in the tropics. We used stable isotope analysis of carbon and nitrogen to trace aquatic prey use and quantify the impact on trophic structure in 240 riparian arthropod communities in tropical and temperate forests. Riparian predators consumed more aquatic prey and were more trophically diverse in the tropics than temperate regions, indicating tropical riparian communities are both more reliant on and impacted by aquatic resources than temperate communities.

3D Printing of Personalised Carvedilol Tablets Using Selective Laser Sintering.

Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO laser for the manufacturing of carvedilol personalised dosage forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.

Maintenance lenalidomide in newly diagnosed transplant eligible and non-eligible myeloma patients; profiling second primary malignancies in 4358 patients treated in the Myeloma XI Trial.

Background: Early trials of long-term lenalidomide use reported an increased incidence of second primary malignancy (SPM), including acute myeloid leukaemia and myelodysplastic syndrome. Later, meta-analysis suggested the link to be secondary to lenalidomide in combination with melphalan.

Methods: Myeloma XI is a large, phase III randomised trial in-which lenalidomide was used at induction and maintenance, in transplant eligible (TE) and non-eligible (TNE) newly diagnosed patients (NCT01554852).