Generative AI: driving productivity and scientific breakthroughs in pharmaceutical R&D.

The rapid advancement of generative artificial intelligence (AI) is reshaping pharmaceutical research and development (R&D), offering opportunities across drug discovery and development. Generative AI (GenAI) enhances productivity by enabling virtual assistants, which help automate routine tasks. It advances novel small-molecule drug design and drives new machine learning (ML) applications through synthetic data generation.

Target-based drug discovery: Applications of fluorescence techniques in high throughput and fragment-based screening.

Target-based discovery of first-in-class therapeutics demands an in-depth understanding of the molecular mechanisms underlying human diseases. Precise measurements of cellular and biochemical activities are critical to gain mechanistic knowledge of biomolecules and their altered function in disease conditions. Such measurements enable the development of intervention strategies for preventing or treating diseases by modulation of desired molecular processes.

Can I Leave? Perspectives on Parental Leave and Parenthood in Medical Training Among Program Directors and Trainees in Oncologic Specialties.

Peak fertility commonly occurs during medical training, and delaying parenthood can complicate pregnancies. Trainee parental leave policies are varied and lack transparency. Research on the impacts of parenthood on trainee education is limited.

Assessment of the Efficacy of Tranexamic Acid Solution 5% in the Treatment of Melasma in Patients of South Asian Descent.

Melasma is a common dermatologic condition affecting all skin types. Increasing rates of melasma warrant identification of a reliable topical treatment. In recent years, off-label tranexamic acid (TA) has emerged as a potential treatment of melasma.

Evaluating Implementation Costs of an Enhanced Recovery After Surgery (ERAS) Protocol in Colorectal Surgery: A Systematic Review.

Background: Enhanced recovery after surgery (ERAS) protocols have been well documented in the current literature to improve healthcare outcomes by decreasing length of stay, resource utilization, and morbidity without increasing readmission rates or complications. This subsequently leads to a net decrease in hospital costs. However, the initial costs of implementing such a program have not been well described, which is crucial information for hospitals with less resources.

Characterization of a mGluR5 Knockout Rat Model with Hallmarks of Fragile X Syndrome.

The number of reported cases of neurodevelopmental disorders has increased significantly in the last few decades, but the etiology of these diseases remains poorly understood. There is evidence of a fundamental link between genetic abnormalities and symptoms of autism spectrum disorders (ASDs), and the most common monogenetic inheritable form of ASDs is Fragile X Syndrome (FXS). Previous studies indicate that FXS is linked to glutamate signaling regulation by the G-protein-coupled metabotropic glutamate receptor 5 (mGluR5), which has been shown to have a regulatory role in neuroinflammation.

Impact of Age on Surgical Outcomes Following Mandible Fracture Repair.

Objectives: Open repair of mandibular fractures are frequently performed surgical procedures. Increasing rates of such fractures are seen in older adults following falls. This study assesses the impact of older age on early complications following mandible fracture repair.

Clinical outcomes in a U.S. registration study of a new EDOF intraocular lens with a nondiffractive design.

Purpose: To evaluate the effectiveness and safety of the DFT015 intraocular lens (IOL) (AcrySof IQ Vivity Extended Vision) compared with an aspheric monofocal control IOL (AcrySof IQ model SN60WF).

Setting: 11 investigation sites in the U.S.

Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART).

Background: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk.

A Rare Variant of Guillain-Barre Syndrome Following Ad26.COV2.S Vaccination.

Efforts to combat the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) range from adequate diagnostic testing and contract tracing to vaccination for the prevention of coronavirus disease 2019 (COVID-19). In the United States alone, three vaccinations have been authorized for emergency use (EUA) or approved to prevent COVID-19. The Ad26.

Multicountry clinical outcomes of a new nondiffractive presbyopia-correcting IOL.

Purpose: To evaluate the effectiveness and safety of a new presbyopia-correcting intraocular lens (IOL) with a nondiffractive design, DFT015, compared with an aspheric monofocal IOL, SN60WF.

Setting: 19 investigational sites in 4 countries: Australia, Canada, Spain, and the United Kingdom.

Design: Prospective, randomized, parallel-group, controlled, assessor- and patient-masked clinical study.

Dual impedance cardiography: An inexpensive and reliable method to assess arterial stiffness.

Pulse wave velocity (PWV) is a common measure of arterial stiffness. Non-invasive methods to measure PWV are widely used in biomedical studies of aging and cardiovascular disease, but they are rarely used in psychophysiology. Barriers to wider use include the prohibitive costs of specialized equipment and need for trained technicians (e.

Visual Demand and Acuity Reserve of Chinese versus English Newspapers.

Significance: This study suggests that Chinese newspaper characters are more legible than English newspaper letters. Characters in Chinese newspapers have higher acuity reserve than English newspapers.

Purpose: The purpose of this study was to evaluate visual demand and acuity reserve for Chinese newspapers in comparison with published data on U.

Extending flow cytometry sample stability by freezing lysed whole blood for clinical monitoring of Treg.

A major challenge for flow cytometry assays supporting clinical trials is postcollection sample stability. Here we present an approach that could mitigate the stability issue while preserving sample integrity and cellular markers, especially when enumerating rare populations such as Tregs. Stability was evaluated using whole blood stored at room temperature and lysed whole blood stored at -80°C.

Radiation-induced ovarian follicle loss occurs without overt stromal changes.

Radiation damage due to total body irradiation (TBI) or targeted abdominal radiation can deplete ovarian follicles and accelerate reproductive aging. We characterized a mouse model of low-dose TBI to investigate how radiation affects the follicular and stromal compartments of the ovary. A single TBI dose of either 0.

Targeting Phosphopeptide Recognition by the Human BRCA1 Tandem BRCT Domain to Interrupt BRCA1-Dependent Signaling.

Intracellular signals triggered by DNA breakage flow through proteins containing BRCT (BRCA1 C-terminal) domains. This family, comprising 23 conserved phosphopeptide-binding modules in man, is inaccessible to small-molecule chemical inhibitors. Here, we develop Bractoppin, a drug-like inhibitor of phosphopeptide recognition by the human BRCA1 tandem (t)BRCT domain, which selectively inhibits substrate binding with nanomolar potency in vitro.

Age-associated dysregulation of protein metabolism in the mammalian oocyte.

Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA-Seq on individual growing follicles from reproductively young and old mice to identify age-dependent functions in oocytes.

Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes.

Background: Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes.

Immune response to a model shared placenta/tumor-associated antigen reduces cancer risk in parous mice.

During human pregnancy, paternally inherited antigens expressed by the fetal-placental unit can elicit expansion of antigen-specific CD8+ T cells. These cells can persist for years as memory T cells, but their effects on long-term maternal health are unknown. Shared placenta/tumor-associated antigens are expressed by placenta and tumors, but are minimally expressed or absent in normal adult tissues.

Reproductive age-associated fibrosis in the stroma of the mammalian ovary.

Under normal physiological conditions, tissue remodeling in response to injury leads to tissue regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis - or the excess accumulation of ECM - can disrupt tissue architecture and function. Several organs, including the heart, lung and kidney, exhibit age-associated fibrosis.