Screening Of Interactions Research Articles

Abstract 15539: Outcomes of a Multidisciplinary Approach to Management of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Background: Mavacamten treats obstructive hypertrophic cardiomyopathy in adults, improving symptoms and functional capacity. Its complex management process involves frequent echocardiograms, dose adjustments based on Valsalva left ventricular outflow tract (VLVOT) gradient changes, and screening for drug interactions. The high cost of mavacamten poses a financial burden to patients, and the management process lacks adequate simplification. Real-world workflow descriptions are needed for successful patient outcomes. Methods: We retrospectively analyzed patients prescribed mavacamten from May 2022 to May 2023 through a multidisciplinary workflow. Patients were referred to a pharmacist after an initial clinic visit with a cardiologist. Pharmacists counseled patients, enrolled them in the online Risk Evaluation and Mitigation Strategies program, and facilitated enrollment in the manufacturer's patient support program for cost reduction options and prior authorization. Echocardiogram dates were determined using a calculator created by the authors and coordinated with the echocardiography staff. Pharmacists adjusted doses based on finalized echocardiogram reports. Outcomes included ejection fraction (EF), LVOT, and VLVOT which were analyzed using a generalized linear mixed model controlling for time. Additional outcomes were out-of-pocket cost, time to approval, and time to first dispense. Results: Among 34 patients considered, 21 received mavacamten. Reasons for non-receipt included cost (6 patients), unwillingness to follow-up (4 patients), drug interactions (1 patient), absence of mavacamten on insurance formulary (1 patient), and awaiting insurance approval (1 patient). Patients on mavacamten received therapy for 2-48 weeks. They experienced significant decreases in average LVOT (P<0.001) and VLVOT (P<0.001) over time. Average EF showed a non-significant decrease (P=0.097), with one patient recovering from a decline below 50% upon discontinuing mavacamten. Conclusion: Mavacamten faces barriers such as echocardiogram follow-up, complex dosing, drug interaction screening, and cost. However, the described workflow effectively addresses many of these barriers, serving as a template for mavacamten management.

RETRACTED ARTICLE: Optimized design and application research of smart interactive screen for wireless networks based on federated learning

The rapid development of infinite networks and information technology has promoted the wide deployment and rapid growth of intelligent interactive devices. However, at the same time, touch interaction technology also faces many challenges such as lack of precision. This study combines federated learning with LayerGesture technology to optimize and design a touch interaction system with higher interaction accuracy and applies it to practice. The analysis results show that with the increase in the number of iterations of the federated model, the accuracy of the human–computer recognition interaction and the amount of information contained in it increases, and the accuracy curve reaches stability at about 2800 times and is at the optimal interaction adaptation. At this point, the loss function also decreases gradually, while the loss factor tends to 0, which verifies the stability of the optimized model. According to the participants’ interaction experience and experimental results, the optimized LayerGesture technique of the federated learning model has an average correctness rate of 90.4% and the lowest average selection time, while the average selection time of LayerGesture in the interaction area at the edge of the screen is 2510 ms and the average correctness rate is 93.60%, which is better than the Shift technique. In addition, the subjective survey results indicated that more participants favored the optimized LayerGesture technique. In summary, this paper’s joint learning algorithm contributes to the recognition effectiveness and efficiency of intelligent interactive systems.

Identification of IL-8 in CSF as a potential biomarker in sepsis-associated encephalopathy

BackgroundSepsis-associated encephalopathy (SAE) is frequently present at the acute and chronic phase of sepsis, which is characterized by delirium, coma, and cognitive dysfunction. Despite the increased morbidity and mortality of SAE, the pathogenesis of SAE remains unclear. This study aims to discover the potential biomarkers, so as to clear the pathogenesis potentially contributing to the development of SAE and provide new therapeutic strategies for the treatment of SAE. MethodsThe GSE135838 dataset was obtained from the Gene Expression Omnibus (GEO) database and utilized for analysis the differentially expressed genes (DEGs). The DEGs were analyzed by limma package of R language and the extracellular protein-differentially expressed genes (EP-DEGs) were screened by the Human Protein Atlas (HPA) and UniProt database. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein–protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the cerebrospinal fluid (CSF) of SAE patients and non-sepsis patients with critical illness. ROC curve was used to evaluate the diagnostic of SAE. ResultsWe screened 82 EP-DEGs from DEGs. EP-DEGs were enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway and NOD-like receptor signaling pathway. We identified 2 key extracellular proteins IL-1B and IL-8. We clinically verified that IL-6 and IL-8 levels were increased in CSF of SAE patients and CSF IL-8 (AUC = 0.882, 95 % CI = 0.775–0.988) had a higher accuracy in the diagnosis of SAE than CSF IL-6 (AUC = 0.824, 95 % CI = 0.686–0.961). Furthermore, we found that the IL-8 levels in CSF might not associated with Glasgow Coma Scale (GCS) scores of SAE patients. ConclusionIL-8 may be the key extracellular cytokine in the pathogenesis of SAE. Bioinformatics methods were used to explore the biomarkers of SAE and validated the results in clinical samples. Our findings indicate that the IL-8 in CSF might be the potential diagnostic biomarker and therapeutic target in SAE.

Exploration of Simiao-Yongan Decoction on knee osteoarthritis based on network pharmacology and molecular docking.

Use network pharmacology combined with molecular docking to study the effects of Simiao-Yongan Decoction (SMYAD) intervenes in Knee Osteoarthritis (KOA) related targets and signaling pathways, and explores the molecular mechanism of SMYAD in treating KOA. The active ingredients and targets of SMYAD, which concluded 4 traditional Chinese medicines, were screened in TCMSP, and the related gene targets of KOA were screened in the disease databases GeneCards, MalaCards, DisGeNET, and Comparative Toxicogenomics Database, and their intersection data were obtained after integration. And used Cytoscape 3.9.1, the software topologies the network diagram of "compound-drug-active ingredient-target protein-disease." Obtains the protein-protein interaction network diagram through STRING, and enriches and analyzes the obtained core targets. Carry out molecular docking matching verification on the main active ingredients and key targets of the drug. 106 active ingredients and 175 targets were screened from SMYAD to intervene in KOA, 36 core targets were obtained through protein-protein interaction screening, and 10 key targets played an important role. The enrichment results showed that the biological process of gene ontology mainly involved positive regulation of gene expression, negative regulation of apoptosis process, and positive regulation of apoptosis process. KEGG signaling pathway mainly involves AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, hypoxia-inducible factor-1 signaling pathway, IL-17 signaling pathway. The pathway of Reactome mainly involves interleukin-4 and interleukin-13 signaling, cytokine signaling in immune system, immune system, apoptosis. Molecular docking showed that the mainly effective components of SMYAD can fully combine with TNF, IL1B, IL6, and CASP3. The results show that the main active ingredients and potential mechanism of action of SMYAD in the treatment of KOA have the characteristics of multiple targets and multiple pathways, which provides ideas and basis for further in-depth exploration of its specific mechanism.

THU502 CYR61, A Member Of The CCN Protein Family, Regulates IGF1 In Metastatic Prostate Cancer

Abstract Disclosure: G.L. Ortiz Hernandez: None. M. Walker: None. L. Woods-Burnham: None. R.A. Kittles: None. C.A. Casiano: None. S.L. Neuhausen: None. The cysteine-rich angiogenic inducer 61 (CYR61) is a member of the cellular communication network (CCN) protein family that can be induced by growth factors. CYR61-specific functions are dependent on cellular context. In prostate cancer (PCa), CYR61 contributes to cell growth and survival through its interactions with extracellular ligands, such as integrins avb3 and a6b4, in the extracellular matrix space. Interestingly, CYR61 contains an insulin-like growth factor-binding protein domain suggesting that it may interact with insulin-like growth factor-1 (IGF1). High serum levels of IGF1 are directly linked to PCa development and recently have been studied as a predictor of metastatic disease. Given the important roles that IGF1 and CYR61 play in PCa and their potential interaction, it is critical to investigate their molecular interplay. We hypothesize that the interaction of CYR61 and IGF1 contributes to aggressive tumor properties (e.g., proliferation, tumorsphere formation) in PCa. Using immunoblotting, we demonstrated that CYR61 is upregulated in the androgen receptor-negative and glucocorticoid receptor-positive (AR-/GR+) metastatic cell line, PC3, and downregulated in the docetaxel-resistant cell line PC3-DR. Furthermore, optimized knockdown of CYR61 using siRNA significantly reduced PC3 cell proliferation, viability, and prostasphere formation. To examine the underlying mechanisms associated with IGF1 signaling, we assessed the activation of the PI3/Akt and MAPK pathways in PC3 cells with CYR61 silenced. CYR61 siRNA-mediated knockdown decreased activation of the PI3/Akt pathway but did not alter the MAPK pathway. We also initiated studies to determine the co-localization of CYR61 and IGF1 using immunofluorescence microscopy (IF). Based on the initial IF observations, we will proceed to examine if their interaction is primarily intra- or extra-cellular and whether interactions differ based on AR signaling. Using both PC3 and MDA-PCa-2b, which is AR+/GR+, we will co-immunoprecipitate CYR61 with IGF1 to assess intracellular interactions and use the AVidity-based EXtracellular Interaction Screen (AVEXIS) system for extracellular interactions. The correlation between PCa aggressiveness and circulating levels of CYR61 and IGF1 is poorly studied. Therefore, our goal is to establish the contribution of CYR61-IGF1 protein-protein interaction to PCa cell proliferation and tumor aggressiveness. Presentation: Thursday, June 15, 2023

Relationship Between Speech Delay and Smart Media in Children: A Systematic Review.

The increasing prevalence of smart media usage among children has raised concerns about its potential impact on various aspects of child development. One such area of worry is speech delay, as early language acquisition is critical for cognitive, social, and educational development. The purpose of this systematic review was to investigate and synthesize available research data in order to determine the association between speech delay and the usage of smart media in children. To perform this systematic review, a thorough literature search was conducted using relevant keywords in electronic databases, such as PubMed, Scopus, PsycINFO, Google Scholar, Web of Science, and Embase. We included studies published during the last 10 years investigating the impact of smart media on children's speech delay using various research designs. The findings showed that extended exposure to electronic media for children was negatively associated with expressive vocabulary and language skills in children, in addition to decreased language scores and speech delays. Educational apps and shared media engagement with parents correlated with stronger language skills.The introduction of smart devices at a later stage of development (24 months of age and older) was associated with positive language development, whereas early introductionwas associated with speech delay. However, six-month abstinence from devices led to speech improvement in the affected children. These findings highlight the need to balance interactive screen time and other forms of interaction to enhance speech development.

Creation of a High-Throughput Microfluidic Platform for Single-Cell Transcriptome Sequencing of Cell-Cell Interactions.

Cell-cell interaction is one of themajor modalities for transmitting information between cells and activating the effects of functional cells. However, the construction of high-throughput analysis technologies from cell omics focusing on the impact of interactions of functional cells on targets has been relatively unexplored. Here, they propose a droplet-based microfluidicplatform for cell-cell interaction sequencing (c-c-seq) and screening in vitro to address this challenge. A class of interacting cells is pre-labeled using cell molecular tags, and additional single-cell sequencing reagents are introduced to quickly form functional droplet mixes. Lastly, gene expression analysis is used to deduce the impact of the interaction, while molecular sequence tracing identifies the type of interaction. Research into the active effect between antigen-presenting cells and T cells, one of the most common cell-to-cell interactions, is crucial for the advancement of cancer therapy, particularly T cell receptor-engineered Tcell therapy. As it allows for high throughput, this platform is superior to well plates as a research platform for cell-to-cell interactions. When combined with the next generation of sequencing, the platform may be able to more accurately evaluate interactions between epitopes and receptors and verify their functional relevance.

Screening the Drug-Drug Interactions Between Antimicrobials and Other Prescribed Medications Using Google Bard and Lexicomp® Online™ Database.

Aim This study aimed tocritically appraise the drug-drug interaction (DDI) screening performance of Google Bard (Google AI, Mountain View, California, United States) by comparing it with the authorized Lexicomp® Online™ database (Wolters Kluwer Health, Philadelphia, Pennsylvania, United States). Methods This cross-sectional study was conducted between April 2023 and August 2023, and enrolled 414 prescriptions that had been collected randomly between April 2023 and June 2023. These prescriptions were processed individually by Lexicomp online and Google Bard to screen for DDIs between antimicrobials and other prescribed medications. Results The total number of DDIs based on Lexicomp and Google Bard were 90 and 68, respectively. Cohen's Kappa (κ) values showed that there was a nil to slight agreement between Lexicomp and Google Bard regarding the DDI risk rating (κ=0.01). Regarding the severity rate, there was a slight agreement between them (κ=0.02), but in terms of reliability rate, there was no agreement (κ =-0.02). Conclusion This study unveiled differences between Lexicomp and Google Bard regarding their DDI identification, severity rating, and reliability rates. It is fundamental to consider that both tools have their strengths and weaknesses and, therefore, should not be individually depended on for final clinical decisions. However, Lexicomp can be considered authoritative in screening DDIs, but Google Bard currently lacks the necessary precision and reliability for conducting such screenings.

Valproate regulates inositol synthesis by reducing expression of myo-inositol-3-phosphate synthase

Inositol depletion is a hypothesized mechanism of action of mood stabilization drugs used in the treatment of bipolar disorder. It was previously reported that the mood stabilizer valproate (VPA) increased phosphorylation of myo-inositol-3-phosphate synthases (MIPS), the rate limiting enzyme of inositol synthesis. Phosphosites were identified and examination of site-directed mutants suggested that phosphorylation leads to decreased enzymatic activity. In this study, we examined the extent of MIPS phosphorylation in response to VPA and used two interaction screens to identify protein kinases that interact with MIPS. Using an epitope tagged MIPS construct, we determined the fraction of phosphorylated MIPS to be very low (less than 2% of total), and we could not detect phosphorylation of untagged MIPS in response to VPA. In vitro analyses of phosphorylation revealed that putative protein kinases, PKC and CKII, have low specificity toward MIPS. These findings suggest that VPA likely depletes inositol via a mechanism other than MIPS phosphorylation. Consistent with this, mRNA levels of the MIPS-encoding gene INO1 and MIPS protein levels were significantly reduced during the mid-log growth phase in response to VPA treatment. These findings suggest that the mechanism whereby VPA causes inositol depletion is by reducing expression of the rate-limiting enzyme MIPS.

Analysis of potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis by bioinformatics

AbstractBackgroundAnkylosing spondylitis (AS) is a disabling chronic inflammatory disease. Mechanisms of ferroptosis in AS remain unclear. Using bioinformatics analysis, we aimed to identify key molecules involved in ferroptosis, provide potential therapeutic targets for AS, and further explore mechanisms of ferroptosis in AS.MethodsGSE25101 was downloaded from the Gene Expression Omnibus and intersected with a ferroptosis gene dataset. The ferroptosis‐relate differentially‐expressed genes were further subjected to functional enrichment analysis, protein interaction network analysis, and gene‐miRNA interaction network analysis, from which potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis were screened.ResultsA total of 20 differentially expressed genes were screened, most of which are involved in phosphoinositide 3 kinase‐Akt or mitogen‐activated protein kinase (MAPK) signaling pathways or the endoplasmic reticulum stress response. The following target genes were identified through protein‐protein interaction network analysis and screening of key modules constructed from genes associated with PI3K‐Akt and MAPK signaling pathways: TP53, PTEN, TLR4, HSPB1, DDIT3, and XBP1. In addition, PI3K‐Akt and MAPK signaling were associated with oxidative stress, which may play a role in AS pathological ossification related to ferroptosis. Only hsa‐miR‐205‐5p was found to target at least two genes by gene‐miRNA interaction network analysis.ConclusionsFuture therapeutic drug development may intervene by modulating MAPK or PI3K‐Akt signaling pathways rather than directly affecting the interleukin 17 pathway. hsa‐miR‐205‐5p may be a potential novel biomarker for AS.

Community-Based Research: Interviewing Older People in Community Pharmacies.

Objective Community pharmacists play an important role in providing many essential services to older adult patients. This study aimed to assess participants' awareness and utilization of current services provided by the community pharmacy and to identify preferences for innovative strategies and services related to healthy aging. Design This is community-based research using interviews with older people in community pharmacies. Student pharmacists performed the interviews, asking 11 questions developed by the research team. The interview questions included services currently provided by the community pharmacy to determine patient awareness and use. Setting One-on-one structured interviews with participants 50 years of age and older were conducted at community pharmacies in Arizona. Results A total of 53 older people (54.7% female) participated, with most patients knowledgeable about current pharmacy services and 69.7% using at least one service. When asked if they would participate in innovative services, more than half of those interviewed (56.6%) were interested in medication side effect screening and education, and 54.7% would want to participate in medication review with drug interaction screening. Almost half were interested in lifestyle education for healthy aging in nutrition and physical activities (49.1%) and medication disposal (47.2%). Most participants preferred to communicate in person with their pharmacists, but some showed interest in mobile phone texts and calls. Conclusion Community pharmacies may be a viable setting to provide novel services to promote healthy aging among older people, particularly medication side effect and drug interaction screenings and education.

(Invited) Unraveling Electron-Phonon Coupling in 2D Materials in Momentum and Time with Ultrafast Electron Diffuse Scattering (UEDS)

The nature of the couplings within and between lattice and charge degrees of freedom is central to an understanding of electrical and heat transport in materials. These interactions are essential to phenomena as diverse as superconductivity, charge density waves and carrier mobility in semiconductors and metals. Despite their fundamental role, detailed momentum-dependent information on the strength of electron-phonon coupling (EPC) and phonon-phonon coupling (PPC) across the entire Brillouin zone has proved to be very difficult to obtain.I will describe an emerging pump-probe technique, ultrafast electron diffuse scattering (UEDS), that provides such information from the perspective of the phonon system directly. Recent examples of the application of UEDS to layered (2D) materials will be the focus. First, in the thermoelectric material SnSe – a strongly polar semiconductor – we directly observe the phonon dressing processes that yield carrier localization and polaron formation with UEDS. In SnSe these phonon dressing dynamics are profoundly bimodal, with the fast (300 fs) process associated with the formation of a quasi-1D lattice distortion and a relatively large polaron and the slower (4 ps, an order of magnitude slower timescale) process associated with small polaron formation. The observations in SnSe are consistent with electron and hole polarons being different sizes, or the process of polaron formation being instrincially bimodal for both carriers in a manner reminiscent of Lars Onsager’s inverse snowball effect. Second, the extension of UEDS to a MoS2 monolayer heterostructure will be demonstrated. These results reveal substrate dielectric screening of the electron-phonon interaction within the monolayer as well as the monomentum-dependent carrier-phonon equilibration. These results are compared directly against ab-initio simulations of these processes Figure 1

Effect of transition metals doping in magnetic properties of Fe3Se4

We report density functional theory (DFT) study of the magnetic properties of Fe3Se4 doped with transition metals, TM (Co, Cr, Ni and Mn), where TM ions are doped in Fe sites to yield Fe2.5(TM)0.5Se4. Screening of the exchange coupling interaction and magnetization modifications were performed upon the substitution of Fe by transition metals at various Fe sites in the Fe3Se4 structure. Our study reveals that doping of Fe3Se4 with TM elements at Fe sites does not remove antiferromagnetic (AFM) coupling across layers, thus, not increasing the magnetization. This coupling is exhibited by elements with more than half-filled electron shell, i.e. Fe is such an element. Moreover, the exchange coupling between layers of Fe increases strongly as function of interlayer spacing (c lattice parameter) for both pristine and TM-doped Fe3Se4, while the magnetizations of Fe3Se4 alloys do not change significantly.

Differential Gene Expression Profiles and Pathways Highlight the Role of Osteoimmunology in Neurofibromatosis Type 1-Related Dystrophic Scoliosis With Osteopenia.

Microarray approach and integrated gene network analysis. To explore the differential genetic expression profile, Gene Ontology terms, and Kyoto Encyclopedia of Genes and Genomes pathways in human trabecular bone (HTB)-derived cells of dystrophic scoliosis secondary to neurofibromatosis type 1 (DS-NF1) and compare these to normal controls. The pathogenesis of DS-NF1 and the accompanying generalized osteopenia remain unclear. We hypothesized that HTBs may play a significant role in the etiology and pathogenesis of DS-NF1. Microarray analysis was used to identify differentially expressed genes of HTBs from patients with DS-NF1 compared with those from healthy individuals. Functional and pathway enrichment analysis were implemented through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway database. Then, the "search tool for the retrieval of interacting genes/proteins" database, Cytoscape, and "Molecular Complex Detection" were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Pathway enrichment analysis was further performed for hub genes and gene clusters identified through module analysis. Six potential crucial genes were selected for validation by reverse transcription polymerase chain reaction. Bioinformatic analysis revealed that there are 401 previously unrecognized differentially expressed genes (238 up and 163 downregulated genes) in HTBs from patients with DS-NF1, and they were mainly enriched in terms of immune response, type-I interferon (IFN) signaling, TNF signaling pathway and etinoic acid inducible gene I-like receptor signaling pathway. Five hub genes, including signal transducer and activator of transcription 1, 2'-5'-oligoadenylate synthetase-like, IFN induced with helicase C domain 1, IFN regulatory factor 7, and MX dynamin-like GTPase 1 were identified through PPI network, which were mainly enriched in terms of Jak-STAT and etinoic acid inducible gene I-like receptor signaling pathway. An independently dysregulated protein cluster containing CCL2, CXCL1, CXCL3, CX3CL1, TLR1 , and CXCL12 was also identified through the PPI network. This indicated that the upper abnormally expressed genes may play essential roles in DS-NF1 pathogenesis and accompanied osteopenia. Six key genes were identified in the progression of DS-NF1-related osteopenia. Immune response might play a key role in the progression of osteopenia, whereas a CXCL12 -mediated osteogenic effect might play a protective role.

In silico protein interaction screening uncovers DONSON's role in replication initiation.

CDC45-MCM2-7-GINS (CMG) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit "pre-loading complex" (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a vertebrate pre-LC containing GINS, TOPBP1, and DNA pol ε. Our evidence suggests that DONSON docks the pre-LC onto MCM2-7, delivering GINS to its binding site in CMG. A patient-derived DONSON mutation compromises CMG assembly and recapitulates microcephalic dwarfism in mice. These results unify our understanding of eukaryotic replication initiation, implicate defective CMG assembly in microcephalic dwarfism, and illustrate how in silico protein-protein interaction screening accelerates mechanistic discovery.

TDP-1 and FUST-1 co-inhibit exon inclusion and control fertility together with transcriptional regulation.

Gene expression is a multistep process and crosstalk among regulatory layers plays an important role in coordinating gene expression. To identify functionally relevant gene expression coordination, we performed a systematic reverse-genetic interaction screen in C. elegans, combining RNA binding protein (RBP) and transcription factor (TF) mutants to generate over 100 RBP;TF double mutants. We identified many unexpected double mutant phenotypes, including two strong genetic interactions between the ALS-related RBPs, fust-1 and tdp-1, and the homeodomain TF ceh-14. Losing any one of these genes alone has no effect on the health of the organism. However, fust-1;ceh-14 and tdp-1;ceh-14 double mutants both exhibit strong temperature-sensitive fertility defects. Both double mutants exhibit defects in gonad morphology, sperm function, and oocyte function. RNA-Seq analysis of double mutants identifies ceh-14 as the main controller of transcript levels, while fust-1 and tdp-1 control splicing through a shared role in exon inhibition. A skipped exon in the polyglutamine-repeat protein pqn-41 is aberrantly included in tdp-1 mutants, and genetically forcing this exon to be skipped in tdp-1;ceh-14 double mutants rescues their fertility. Together our findings identify a novel shared physiological role for fust-1 and tdp-1 in promoting C. elegans fertility and a shared molecular role in exon inhibition.

A precision medicine approach to personalized prescribing using genetic and nongenetic factors for clinical decision-making

Screening potential drug–drug interactions, drug–gene interactions, contraindications, and other factors is crucial in clinical practice. However, implementing these screening concepts in real-world settings poses challenges. This work proposes an approach towards precision medicine that combines genetic and nongenetic factors to facilitate clinical decision-making. The approach focuses on raising the performance of four potential interaction screenings in the prescribing process, including drug–drug interactions, drug–gene interactions, drug–herb interactions, drug–social lifestyle interactions, and two potential considerations for patients with liver or renal impairment. The work describes the design of a curated knowledge-based model called the knowledge model for potential interaction and consideration screening, the screening logic for both the detection module and inference module, and the personalized prescribing report. Three case studies have demonstrated the proof-of-concept and effectiveness of this approach. The proposed approach aims to reduce decision-making processes for healthcare professionals, reduce medication-related harm, and enhance treatment effectiveness. Additionally, the recommendation with a semantic network is suggested to assist in risk–benefit analysis when health professionals plan therapeutic interventions with new medicines that have insufficient evidence to establish explicit recommendations. This approach offers a promising solution to implementing precision medicine in clinical practice.

FORMATION OF PROFESSIONAL COMPETENCE OF HIGER MEDICAL EDUCATION STUDENTS USING INTEGRATED AND BINARY LESSONS IN TEACHING CLINICAL DISCIPLINES

The mission of higher education institution is to support teachers in the development of pedagogical skills. This is especially relevant for the teaching staff of medical educational institutions, where it is necessary to master the method of teaching the discipline and the educational process itself, since the vast majority of teachers do not have special education.
 The purpose of the study was to outline the advantages of conducting integrated and binary classes in the teaching of the discipline "Neurology" with the aim of forming the professional competence of students.
 Materials and methods. Analysis of scientific and methodical literature and generalization of own practical experience of conducting classes were used in the study.
 Results. Topics from the "General Neurology" module include knowledge of topical neurology: the principles of the structure and functioning of all parts of the nervous system, so the built-in interactive anatomical atlas allows students of higher medical education to improve their knowledge of human anatomy online. SECTRA anatomical tables have large interactive screens with an indication system that provides interaction with images of the human body obtained by computer or magnetic resonance imaging. Classes are conducted by two teachers, whose task is to present the studied material from different points of view: anatomical approach and clinical thinking. A significant role is played by the psychological and methodical compatibility of the teachers preparing the binary class. In the process of preparation, teachers analyze the actual material on the topic, determine the motivation of the researched topic, take into account the scope and level of students' knowledge of the disciplines, identify interdisciplinary connections between the studied disciplines, choose the most rational form of the lesson. In our own experience, the inclusion of such technologies in the educational process is an important step that expands the possibilities of assimilation of information for those seeking education. The use of this high-tech equipment in combination with clinical understanding of pathological processes significantly increases the effectiveness of providing educational services to students of higher medical education.
 Conclusion. Binary classes held jointly by the teachers of the Department of Nervous Diseases and the Department of Anatomy with Clinical Anatomy and Operative Surgery of the Poltava State Medical University showed that they are of great interest to both students and teachers. Such experience contributes to a deeper and better assimilation of educational material compared to traditional forms.

Gate-tunable resistance drops related to local superconducting gaps in thin TaS2 layers on SrTiO3 substrates

Strontium titanate [SrTiO3 (STO)], a perovskite oxide with an extremely high gate-tunable dielectric constant (ε) due to quantum paraelectric phases, is attracting considerable attention for yielding various physical phenomena when two-dimensional (2D) layers are integrated. Superconductivity is such a typical phenomenon. However, the influence of the STO substrates on enhancing transition temperatures (Tc) for (atomically) thin 2D flakes attached to them has been rarely investigated. Here, we report gate-tunable and gradual four-terminal resistance drops with critical onset T (TCR) and scanning tunneling spectroscopy (STS) spectra in devices comprising thin TaS2 flakes attached on monolayer hexagonal boron nitride (hBN) spacer/STO substrates. Observation of STS spectra confirms the presence of local superconducting gaps Δ (∼1.5 meV) with transition T (TΔC) three-times higher than previous reports of Tc under absent pressure and strong position dependence of Δ. Depending on Δ on back gate voltages (Vbg) and magnetic fields, there is a strong correlation between TCR and the onset Tc of superconductivity, implying an enhancement of approximately five times compared with the previous highest-onset Tc values without pressure as the applied Vbg increases. The high onset Tc and Δ are discussed based on screening of the long-range Coulomb interaction (CI) due to the high-ε of SrTiO3, while the short-ranged CI remains strong in the 2D limit, causing the superconductivity. Using a monolayer hBN/SrTiO3 substrate with Vbg opens doors to Tc enhancement in thin superconducting layers integrated on it and wide application due to the solid-state high-ε substrates.

Scattering evidence of positional charge correlations in polyelectrolyte complexes

Polyelectrolyte complexation plays an important role in materials science and biology. The internal structure of the resultant polyelectrolyte complex (PEC) phase dictates properties such as physical state, response to external stimuli, and dynamics. Small-angle scattering experiments with X-rays and neutrons have revealed structural similarities between PECs and semidilute solutions of neutral polymers, where the total scattering function exhibits an Ornstein-Zernike form. In spite of consensus among different theoretical predictions, the existence of positional correlations between polyanion and polycation charges has not been confirmed experimentally. Here, we present small-angle neutron scattering profiles where the polycation scattering length density is matched to that of the solvent to extract positional correlations among anionic monomers. The polyanion scattering functions exhibit a peak at the inverse polymer screening radius of Coulomb interactions, q* ≈ 0.2 Å-1. This peak, attributed to Coulomb repulsions between the fragments of polyanions and their attractions to polycations, is even more pronounced in the calculated charge scattering function that quantifies positional correlations of all polymer charges within the PEC. Screening of electrostatic interactions by adding salt leads to the gradual disappearance of this correlation peak, and the scattering functions regain an Ornstein-Zernike form. Experimental scattering results are consistent with those calculated from the random phase approximation, a scaling analysis, and molecular simulations.