model-based model-free

In the realm of medicinal chemistry, the primary objective is to swiftly optimize a multitude of chemical properties of a set of compounds to yield a clinical candidate poised for clinical trials. In recent years, two computational techniques, machine learning (ML) and physics-based methods, have evolved substantially and are now frequently incorporated into the medicinal chemist's toolbox to enhance the efficiency of both hit optimization and candidate design. Both computational methods come with their own set of limitations, and they are often used independently of each other...

BACKGROUND: The aim of the present study was to explore the potential of peripheral immune cells in predicting the response and prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving anti-PD-1 immunotherapy and platinum-based chemotherapy. PARTICIPANTS AND METHODS: We utilized flow cytometry to examine the levels and dynamics of blood immune cells in 79 advanced NSCLC patients treated with the chemoimmunotherapy between December 2019 and January 2022...

BACKGROUND AND AIMS: Mechanical thrombectomy (MT) treatments for pulmonary embolism (PE) have yet to be compared directly. We aimed to determine if patient outcomes varied following treatment of PE with different MT devices. METHODS: All PE encounters with an index treatment of MT between January 2018 and March 2022 were analyzed for in-hospital mortality, discharge to home, and 30-day readmission outcomes in the PINC AI™ Healthcare Database. MT devices used in each encounter were extracted from hospital charge description free-text fields using keyword text and fuzzy matching...

INTRODUCTION: Acupuncture and tuina, acknowledged as ancient and highly efficacious therapeutic modalities within the domain of Traditional Chinese Medicine (TCM), have provided pragmatic treatment pathways for numerous patients. To address the problems of ambiguity in the concept of Traditional Chinese Medicine (TCM) acupuncture and tuina treatment protocols, the lack of accurate quantitative assessment of treatment protocols, and the diversity of TCM systems, we have established a map-filling technique for modern literature to achieve personalized medical recommendations...

AIM: The prognosis of glioma, which is the most common and malignant tumor in the central nervous system, requires the identification of additional markers. MATERIAL AND METHODS: The mRNA expression and clinical data of glioma were downloaded from the TCGA and CGGA databases. Coagulation-related genes were downloaded from the KEGG database. The expression model was constructed using LASSO regression. The GBM data were divided into high and low-risk expression groups based on the median risk score, and the differences in overall survival and progression-free survival between them were calculated...

BACKGROUND: Since 2005, the healthcare system in Ethiopia has implemented policies to promote the provision of free maternal healthcare services. The primary goal of these policies is to enhance the accessibility of maternity care for women from various socioeconomic backgrounds. Additionally, the aim is to increase the utilization of maternity services, such as institutional deliveries, by removing financial obstacles that pregnant women may face. Even though maternity services are free of charge...

BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective...

The widespread use of computers and the Internet has substantially changed the gaming environment during the past ten years. The gambling industry is no longer exclusive to land-based gaming establishments (such as casinos and racetracks). Today, a few keystrokes on a computer are all it takes to access gaming operations. Social media platforms like Facebook, Instagram, Snapchat and various other platforms constitute a particular form of access that has drawn more attention from academics in gambling studies...

Alzheimer's disease (AD) is the most prevalent type of dementia caused by the accumulation of amyloid beta (Aβ) peptides. The extracellular deposition of Aβ peptides in human AD brain causes neuronal death. Therefore, it has been found that Aβ peptide degradation is a possible therapeutic target for AD. CathD has been known to breakdown amyloid beta peptides. However, the structural role of CathD is not yet clear. Hence, for the purpose of gaining a deeper comprehension of the structure of CathD, the present computational investigation was performed using virtual screening technique to predict CathD's active site residues and substrate binding mode...

In this work, the full-potential linearized augmented plane wave method (FP- LAPW) and the modified Becke-Johnson (mBJ) functional with spin-orbit (SO) coupling are used the obtain the structural, optoelectronic and thermoelectric properties of Tl2 O3 under pressure. The results show that Tl2 O3 , as transparent conducting oxide (TCO), is a direct bandgap semiconductor with a band gap of 1.23 eV. The band gap value and the effective mass of electrons increases by increasing pressure. Density of state spectra reveal that the nature of electrons in Tl-6s state in the bottom of conduction band, like free electrons in s state, is responsible for the conducting behavior of Tl2 O3 ...

The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones...

Using Langevin dynamics simulations and a coarse-grained primitive model of electrolytes, we show that the behavior of knotted circular strong polyelectrolytes (PEs) in diluted aqueous solution is largely affected by the diameter of the counterions (CIs), σCI . Indeed, we observe that both gyration radius and knot length vary nonmonotonically with σCI , with both small and bulky CIs favoring knot localization, while medium-sized ones promote delocalized knots. We also show that the conformational change from delocalized to tight knots occurs via the progressive coalescence of the knot's essential crossings...

Vulnerability to adversarial attacks is one of the principal hurdles to the adoption of deep learning in safety-critical applications. Despite significant efforts, both practical and theoretical, training deep learning models robust to adversarial attacks is still an open problem. In this article, we analyse the geometry of adversarial attacks in the over-parameterized limit for Bayesian neural networks (BNNs). We show that, in the limit, vulnerability to gradient-based attacks arises as a result of degeneracy in the data distribution, i...

Hematoxylin and eosin staining can be hazardous, expensive, and prone to error and variability. To circumvent these issues, artificial intelligence/machine learning models such as generative adversarial networks (GANs), are being used to 'virtually' stain unstained tissue images indistinguishable from chemically stained tissue. Frameworks such as deep convolutional GANs (DCGAN) and conditional GANs (CGANs) have successfully generated highly reproducible 'stained' images. However, their utility may be limited by requiring registered, paired images which can be difficult to obtain...

INTRODUCTION: Abemaciclib is an oral inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). Data from the clinical trial monarchE (2023) showed improved survival from invasive disease. The aim of the present article was to conduct an economic assessment of adjuvant treatment with abemaciclib in women with luminal, HER2- and node-positive breast cancer. METHODS: A Markov model was constructed with four mutually exclusive health states (disease-free, local recurrence, distal recurrence and death)...

Sustainable agricultural practices help to manage and use natural resources efficiently. Due to global climate and geospatial land design, soil texture, soil-water content (SWC), and other parameters vary greatly; thus, real time, robust, and accurate soil analytical measurements are difficult to be developed. Conventional statistical analysis tools take longer to analyze and interpret data, which may have delayed a crucial decision. Therefore, this review paper is presented to develop the researcher's insight toward robust, accurate, and quick soil analysis using artificial intelligence (AI), deep learning (DL), and machine learning (ML) platforms to attain robustness in SWC and soil texture analysis...

Molecular generative models have exhibited promising capabilities in designing molecules from scratch with high binding affinities in a predetermined protein pocket, offering potential synergies with traditional structural-based drug design strategy. However, the generative processes of such models are random and the atomic interaction information between ligand and protein are ignored. On the other hand, the ligand has high propensity to bind with residues called hotspots. Hotspot residues contribute to the majority of the binding free energies and have been recognized as appealing targets for designed molecules...

BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets...

One of the prerequisites for successful organ xenotransplantation is a reasonable size match between the porcine organ and the recipient's organ to be replaced. Therefore, the selection of a suitable genetic background of source pigs is important. In this study, we investigated body and organ growth, cardiac function, and genetic diversity of a colony of Auckland Island pigs established at the Center for Innovative Medical Models (CiMM), LMU Munich. Male and female Auckland Island pig kidney cells (selected to be free of porcine endogenous retrovirus C) were imported from New Zealand, and founder animals were established by somatic cell nuclear transfer (SCNT)...

MOTIVATION: Trajectories, which are sequentially measured quantities that form a path, are an important presence in many different fields, from hadronic beams in physics to electrocardiograms in medicine. Trajectory analysis requires the quantification and classification of curves, either by using statistical descriptors or physics-based features. To date, no extensive and user-friendly package for trajectory analysis has been readily available, despite its importance and potential application across various domains...