Type a

Xanthine oxidase (XO) is a key enzyme for the production of uric acid in the human body. XO inhibitors (XOIs) are clinically used for the treatment of hyperuricemia and gout, as they can effectively inhibit the production of uric acid. Previous studies indicated that both indole and isoxazole derivatives have good inhibitory effects against XO. Here, we designed and synthesized a novel series of N-5-(1H-indol-5-yl)isoxazole-3-carboxylic acids according to bioisosteric replacement and hybridization strategies...

BACKGROUND: Bisphenol A (BPA) is an industrial chemical that is commonly found in daily consumer products. BPA is reportedly associated with lung diseases. However, the impact of BPA on pulmonary fibrosis (PF) and its possible mechanisms of action both remain unclear. METHODS: A PF mouse model was induced by bleomycin (BLM). Mouse lung fibroblasts (MLG 2908) and mouse alveolar epithelial cells (MLE-12) were treated with BPA to establish a PF cell model. Tissue staining, CCK-8 assays, western blot experiments and relevant indicator kits were used to detect and evaluate the effect of BPA on PF...

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models...

OBJECTIVE: Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS). METHODS: A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases...

OBJECTIVE: The aim of this study was to provide a quantitative synthesis of the survival outcomes for patients with skull base chordomas, focusing on the role of 1) the extent of resection (gross-total [GTR] vs non-GTR), 2) the type of surgery (primary vs revision), 3) tumor histology, and 4) the different use of adjuvant therapies (proton beam radiotherapy [PBRT], photon radiotherapy [RT], or none). METHODS: A systematic review with a meta-analysis was conducted following the 2020 PRISMA guidelines...

Dancers are susceptible to Relative Energy Deficiency in Sport (REDs), specifically low total body areal bone mineral density (aBMD). Little is known about how dancers' BMD compares to other athletic populations. The objective of this study was to examine the association between participant characteristics and aBMD among female pre-professional dancers compared to other female athletes. 269 females [132 dancers [17.6 (3.2) years] and 137 sport participants [22.8 (2.6) years] were included in this study. aBMD (g/cm2) was estimated using dual X-ray absorptiometry...

Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of cases are considered YAP1/TEAD dependent. Identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs, which may be necessary for YAP1 protein interactions, has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TEAD complex formation and transcriptional activity. We report the discovery and characterization of a novel YAP1/TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TEAD activity...

Speakers with motor speech disorders (MSD) present challenges in speech production, one of them being the difficulty to adapt their speech to different modes. However, it is unclear whether different types of MSD are similarly affected when it comes to adapting their speech to various communication contexts. This study investigates the encoding of speech modes in individuals with AoS following focal brain damage and in individuals with hypokinetic dysarthria (HD) secondary to Parkinson's disease. Participants with mild-to-moderate MSD and their age-matched controls performed a delayed production task of pseudo-words in two speech modes: normal and whispered speech...

PROBLEM: As more states legalize medical aid in dying (MAID), there is an ever-increasing need of physicians trained in this type of end-of-life care. However, resident curricula in MAID have not been previously reported or assessed. The authors describe a residency curriculum in MAID and evaluate the resident outcomes of this program. APPROACH: Since 2018, the Sutter Family Medicine Residency Program in California has offered training in MAID to its residents. Residents attend lectures, evaluate patients for MAID, write prescriptions for aid-in-dying medications, and attend the planned deaths of their patients if desired...

OBJECTIVE: Aim: The aim of the research was to study the features of pancreatic exocrine insufficiency (EPI) in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM) at COVID-19. PATIENTS AND METHODS: Materials and Methods: 72 patients with NAFLD and COVID-19 were examined. The patients have been divided into two groups: group 1 included 42 patients with NAFLD and insulin resistance (IR); group 2 consisted of 30 patients with NAFLD in the combination with type 2 DM...

OBJECTIVE: Aim: To study and analyze the attitude of women of reproductive age to the integrated gynecological care provision by family physicians, their readiness to receive some gynecological services from family physicians, as well as to analyze the level of women's support and readiness for the integrated provision of gynecological care depending on age and level of education. PATIENTS AND METHODS: Materials and Methods: For the survey, anonymous questionnaires containing questions on the attitude of women of reproductive age to the integrated provision of certain types of gynecological care by family physicians were developed...

OBJECTIVE: Aim: Dynamic comparison of the lower limbs length, depending on the type of sport, followed by the construction of a mathematical model for predicting sports abilities. PATIENTS AND METHODS: Materials and Methods: The comparison of the lower limbs length in dynamics was carried out on 132 students of higher education institutions of Bukovyna. While the primary study was carried out during September-October 2021, next study of these same students was conducted in September-October 2022...

OBJECTIVE: Aim: To document the clinical patterns of antibiotic prescriptions in government hospitals, where the majority of physicians possess a degree-based training. PATIENTS AND METHODS: Materials and Methods: A Retrospective cross section study carried out between 1/7/2022 and April 2023 that enrolling 300 patients from governmental hospitals from different provinces of Central and northern Iraq. The research form contained 15 fields divided into three sections...

OBJECTIVE: Aim: To determine the current prevalence of postpartum infections and antimicrobial resistance and antimicrobial resistance of responsible pathogens in Ukraine. PATIENTS AND METHODS: Materials and Methods: Multicenter prospective cohort study was conducted from January 2020 to December 2022 in fifteen hospitals from twelve regions of Ukraine. Definitions of healthcare- associated postpartum infection were adapted from the Centers for Disease Control and Prevention's National Healthcare Safety Network...

Data-independent acquisition has seen breakthroughs that enable comprehensive proteome profiling using short gradients. As the proteome coverage continues to increase, the quality of the data generated becomes much more relevant. Using Spectronaut, we show that the default search parameters can be easily optimized to minimize the occurrence of false positives across different samples. Using an immunological infection model system to demonstrate the impact of adjusting search settings, we analyzed Mus musculus macrophages and compared their proteome to macrophages spiked with Candida albicans ...

Temporal modulations provide a new approach for realizing metamaterials. In this study, through the imposition of uniform temporal modulations, we achieve two types of reciprocal bi-anisotropic metamaterials. Notably, these achievements do not rely on any spatial modulation, preserving inversion symmetry at any instantaneous time. This stands in sharp contrast to the scenario of traditional bi-anisotropic metamaterials, where the disruption of inversion symmetry by spatial arrangements is necessary. Conditions for realizing nonzero bi-anisotropic coupling are discussed and verified through full-wave simulations...

Light-matter interaction between quantum emitters and optical cavities plays a vital role in fundamental quantum photonics and the development of optoelectronics. Resonant metasurfaces are proven to be an efficient platform for tailoring the spontaneous emission (SE) of the emitters. In this work, we study the interplay between quasi-2D perovskites and dielectric TiO2 metasurfaces. The metasurface, functioning as an open cavity, enhances electric fields near its plane, thereby influencing the emissions of the perovskite...

Topological photonic crystals (PCs) provide an effective method for controlling how light propagates and concentrates through their topological states. However, it remains unclear whether topological states can be obtained by combining two different two-dimensional (2D) PCs with topological non-trivial states. In this Letter, two types of 2D Penrose-square (P-S) PCs are proposed. These PCs can generate topological edge states (TESs) and topological corner states (TCSs) within the low-frequency part of the bandgap...

We demonstrate that the temporal contrast of femtosecond light pulses is a critical parameter in laser writing inside transparent dielectrics, allowing different material modifications. In particular, anisotropic nanopores in silica glass are produced by high-contrast of 107 femtosecond Yb:KGW laser pulses rather than low-contrast of 103 Yb fiber laser pulses. The difference originates in the fiber laser storing a third of its energy in a post-pulse of up to 200 ps duration. The absorption of this low-intensity fraction of the pulse by laser-induced transient defects with relatively long lifetime and low excitation energy, such as self-trapped holes, drastically changes the kinetics of energy deposition and the type of material modification...

We numerically analyze two-dimensional photonic crystal (PhC) nanocavities on glass with a thin glass film on top of the structure. We investigated a multistep heterostructure GaAs PhC nanocavity located on glass. We found that covering the structure even with a very thin glass film efficiently suppresses unwanted polarization mode conversion occurring due to the asymmetric refractive index environment around the PhC. We also uncovered that the glass-covered structure can exhibit a higher Q factor than that observed in the structure symmetrically cladded with thick glass...