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1.
Cell ; 175(3): 796-808.e14, 2018 10 18.
Article in English | MEDLINE | ID: mdl-30340043

ABSTRACT

During cell division, mitotic motors organize microtubules in the bipolar spindle into either polar arrays at the spindle poles or a "nematic" network of aligned microtubules at the spindle center. The reasons for the distinct self-organizing capacities of dynamic microtubules and different motors are not understood. Using in vitro reconstitution experiments and computer simulations, we show that the human mitotic motors kinesin-5 KIF11 and kinesin-14 HSET, despite opposite directionalities, can both organize dynamic microtubules into either polar or nematic networks. We show that in addition to the motor properties the natural asymmetry between microtubule plus- and minus-end growth critically contributes to the organizational potential of the motors. We identify two control parameters that capture system composition and kinetic properties and predict the outcome of microtubule network organization. These results elucidate a fundamental design principle of spindle bipolarity and establish general rules for active filament network organization.


Subject(s)
Kinesins/metabolism , Microtubules/metabolism , Molecular Dynamics Simulation , Spindle Apparatus/metabolism , Animals , Humans , Kinesins/chemistry , Microtubules/chemistry , Sf9 Cells , Spindle Apparatus/chemistry , Spodoptera
2.
J Neurosci ; 44(26)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38744531

ABSTRACT

The neurophysiological effects of spinal cord stimulation (SCS) for chronic pain are poorly understood, resulting in inefficient failure-prone programming protocols and inadequate pain relief. Nonetheless, novel stimulation patterns are regularly introduced and adopted clinically. Traditionally, paresthetic sensation is considered necessary for pain relief, although novel paradigms provide analgesia without paresthesia. However, like pain relief, the neurophysiological underpinnings of SCS-induced paresthesia are unknown. Here, we paired biophysical modeling with clinical paresthesia thresholds (of both sexes) to investigate how stimulation frequency affects the neural response to SCS relevant to paresthesia and analgesia. Specifically, we modeled the dorsal column (DC) axonal response, dorsal column nucleus (DCN) synaptic transmission, conduction failure within DC fiber collaterals, and dorsal horn network output. Importantly, we found that high-frequency stimulation reduces DC fiber activation thresholds, which in turn accurately predicts clinical paresthesia perception thresholds. Furthermore, we show that high-frequency SCS produces asynchronous DC fiber spiking and ultimately asynchronous DCN output, offering a plausible biophysical basis for why high-frequency SCS is less comfortable and produces qualitatively different sensation than low-frequency stimulation. Finally, we demonstrate that the model dorsal horn network output is sensitive to SCS-inherent variations in spike timing, which could contribute to heterogeneous pain relief across patients. Importantly, we show that model DC fiber collaterals cannot reliably follow high-frequency stimulation, strongly affecting the network output and typically producing antinociceptive effects at high frequencies. Altogether, these findings clarify how SCS affects the nervous system and provide insight into the biophysics of paresthesia generation and pain relief.


Subject(s)
Paresthesia , Spinal Cord Stimulation , Spinal Cord Stimulation/methods , Humans , Paresthesia/physiopathology , Paresthesia/therapy , Male , Female , Adult , Pain Management/methods , Models, Neurological , Middle Aged , Spinal Cord/physiology , Spinal Cord/physiopathology
3.
Clin Infect Dis ; 78(1): 133-143, 2024 01 25.
Article in English | MEDLINE | ID: mdl-37724763

ABSTRACT

BACKGROUND: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure. METHODS: We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over 2 years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation. RESULTS: Observing TPT and placebo recipients for 2 years as in a typical trial, MDR/RR-TPT was measured to prevent 72% (interquartile range, 45%-100%) of incident MDR/RR-TB among recipients; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT decreased to 54 with 13-18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario. CONCLUSIONS: If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB-including the large effect of increased active TB detection among MDR/RR-TB contacts-could be much greater than suggested by trial outcomes alone.


Subject(s)
Rifampin , Tuberculosis, Multidrug-Resistant , Humans , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/prevention & control , Contact Tracing , Family Characteristics , India/epidemiology , Antitubercular Agents/therapeutic use
4.
Mol Biol Evol ; 40(5)2023 05 02.
Article in English | MEDLINE | ID: mdl-37116207

ABSTRACT

Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by a higher catalytic activity at low temperature than their mesophilic orthologs and are also usually found to be more thermolabile. Computer simulations of the catalytic reactions have been shown to be a very powerful tool for analyzing the structural and energetic origins of these effects. Here, we examine the cold adaptation of lactate dehydrogenases from two Antarctic and sub-Antarctic fish species using this approach and compare our results with those obtained for the orthologous dogfish enzyme. Direct calculations of thermodynamic activation parameters show that the cold-adapted fish enzymes are characterized by a lower activation enthalpy and a more negative entropy term. This appears to be a universal feature of psychrophilic enzymes, and it is found to originate from a higher flexibility of certain parts of the protein surface. We also carry out free energy simulations that address the differences in thermal stability and substrate binding affinity between the two cold-adapted enzymes, which only differ by a single mutation. These calculations capture the effects previously seen in in vitro studies and provide straightforward explanations of these experimental results.


Subject(s)
Cold Temperature , Lactate Dehydrogenases , Animals , Computer Simulation , Catalysis , Thermodynamics , Fishes/genetics , Enzyme Stability , Adaptation, Physiological/physiology
5.
Am J Physiol Heart Circ Physiol ; 326(5): H1146-H1154, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38488520

ABSTRACT

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising tool to study arrhythmia-related factors, but the variability of action potential (AP) recordings from these cells limits their use as an in vitro model. In this study, we use recently published brief (10 s), dynamic voltage-clamp (VC) data to provide mechanistic insights into the ionic currents contributing to AP heterogeneity; we call this approach rapid ionic current phenotyping (RICP). Features of this VC data were correlated to AP recordings from the same cells, and we used computational models to generate mechanistic insights into cellular heterogeneity. This analysis uncovered several interesting links between AP morphology and ionic current density: both L-type calcium and sodium currents contribute to upstroke velocity, rapid delayed rectifier K+ current is the main determinant of the maximal diastolic potential, and an outward current in the activation range of slow delayed rectifier K+ is the main determinant of AP duration. Our analysis also identified an outward current in several cells at 6 mV that is not reproduced by iPSC-CM mathematical models but contributes to determining AP duration. RICP can be used to explain how cell-to-cell variability in ionic currents gives rise to AP heterogeneity. Because of its brief duration (10 s) and ease of data interpretation, we recommend the use of RICP for single-cell patch-clamp experiments that include the acquisition of APs.NEW & NOTEWORTHY We present rapid ionic current phenotyping (RICP), a current quantification approach based on an optimized voltage-clamp protocol. The method captures a rich snapshot of the ionic current dynamics, providing quantitative information about multiple currents (e.g., ICa,L, IKr) in the same cell. The protocol helped to identify key ionic determinants of cellular action potential heterogeneity in iPSC-CMs. This included unexpected results, such as the critical role of IKr in establishing the maximum diastolic potential.


Subject(s)
Induced Pluripotent Stem Cells , Myocytes, Cardiac , Humans , Myocytes, Cardiac/metabolism , Action Potentials/physiology , Arrhythmias, Cardiac/metabolism , Ion Transport
6.
Electrophoresis ; 45(7-8): 618-638, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38115749

ABSTRACT

The mobilization step in a two-step capillary isoelectric focusing protocol is discussed by means of dynamic computer simulation data for systems without and with spacer compounds that establish their zones at the beginning and end of the focusing column. After focusing in an electroosmosis-free environment (first step), mobilization (second step) can be induced electrophoretically, by the application of a hydrodynamic flow, or by a combination of both means. Dynamic simulations provide insight into the complexity of the various modes of electrophoretic mobilization and dispersion associated with hydrodynamic mobilization. The data are discussed together with the relevant literature.


Subject(s)
Capillary Isoelectric Focusing , Computer Simulation , Electrophoresis, Capillary , Capillary Isoelectric Focusing/methods , Electrophoresis, Capillary/methods , Hydrodynamics
7.
Eur Radiol ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546790

ABSTRACT

OBJECTIVES: Evaluate microcalcification detectability in digital breast tomosynthesis (DBT) and synthetic 2D mammography (SM) for different acquisition setups using a virtual imaging trial (VIT) approach. MATERIALS AND METHODS: Medio-lateral oblique (MLO) DBT acquisitions on eight patients were performed at twice the automatic exposure controlled (AEC) dose. The noise was added to the projections to simulate a given dose trajectory. Virtual microcalcification models were added to a given projection set using an in-house VIT framework. Three setups were evaluated: (1) standard acquisition with 25 projections at AEC dose, (2) 25 projections with a convex dose distribution, and (3) sparse setup with 13 projections, every second one over the angular range. The total scan dose and angular range remained constant. DBT volume reconstruction and synthetic mammography image generation were performed using a Siemens prototype algorithm. Lesion detectability was assessed through a Jackknife-alternative free-response receiver operating characteristic (JAFROC) study with six observers. RESULTS: For DBT, the area under the curve (AUC) was 0.97 ± 0.01 for the standard, 0.95 ± 0.02 for the convex, and 0.89 ± 0.03 for the sparse setup. There was no significant difference between standard and convex dose distributions (p = 0.309). Sparse projections significantly reduced detectability (p = 0.001). Synthetic images had a higher AUC with the convex setup, though not significantly (p = 0.435). DBT required four times more reading time than synthetic mammography. DISCUSSION: A convex setup did not significantly improve detectability in DBT compared to the standard setup. Synthetic images exhibited a non-significant increase in detectability with the convex setup. Sparse setup significantly reduced detectability in both DBT and synthetic mammography. CLINICAL RELEVANCE STATEMENT: This virtual imaging trial study allowed the design and efficient testing of different dose distribution trajectories with real mammography images, using a dose-neutral protocol. KEY POINTS: • In DBT, a convex dose distribution did not increase the detectability of microcalcifications compared to the current standard setup but increased detectability for the SM images. • A sparse setup decreased microcalcification detectability in both DBT and SM images compared to the convex and current clinical setups. • Optimal microcalcification cluster detection in the system studied was achieved using either the standard or convex dose setting, with the default number of projections.

8.
RNA Biol ; 21(1): 17-31, 2024 Jan.
Article in English | MEDLINE | ID: mdl-39016036

ABSTRACT

It is likely that an RNA world existed in early life, when RNA played both the roles of the genome and functional molecules, thereby undergoing Darwinian evolution. However, even with only one type of polymer, it seems quite necessary to introduce a labour division concerning these two roles because folding is required for functional molecules (ribozymes) but unfavourable for the genome (as a template in replication). Notably, while ribozymes tend to have adopted a linear form for folding without constraints, a circular form, which might have been topologically hindered in folding, seems more suitable for an RNA template. Another advantage of involving a circular genome could have been to resist RNA's end-degradation. Here, we explore the scenario of a circular RNA genome plus linear ribozyme(s) at the precellular stage of the RNA world through computer modelling. The results suggest that a one-gene scene could have been 'maintained', albeit with rather a low efficiency for the circular genome to produce the ribozyme, which required precise chain-break or chain-synthesis. This strict requirement may have been relieved by introducing a 'noncoding' sequence into the genome, which had the potential to derive a second gene through mutation. A two-gene scene may have 'run well' with the two corresponding ribozymes promoting the replication of the circular genome from different respects. Circular genomes with more genes might have arisen later in RNA-based protocells. Therefore, circular genomes, which are common in the modern living world, may have had their 'root' at the very beginning of life.


Subject(s)
RNA, Catalytic , RNA, Circular , RNA , RNA, Circular/genetics , RNA, Catalytic/genetics , RNA, Catalytic/metabolism , RNA/genetics , RNA/metabolism , Nucleic Acid Conformation , Evolution, Molecular , Genome , Computer Simulation , Origin of Life
9.
Bioorg Chem ; 149: 107503, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823312

ABSTRACT

Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (Ka) for the LDH-rutin system was 2.692 ± 0.015 × 104 M-1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel ß-sheet, and ß-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin.


Subject(s)
L-Lactate Dehydrogenase , Rutin , Rutin/chemistry , Rutin/pharmacology , Rutin/metabolism , L-Lactate Dehydrogenase/antagonists & inhibitors , L-Lactate Dehydrogenase/metabolism , L-Lactate Dehydrogenase/chemistry , Humans , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Molecular Structure , Structure-Activity Relationship , Dose-Response Relationship, Drug , Molecular Docking Simulation , Computer Simulation , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
10.
BMC Health Serv Res ; 24(1): 708, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840245

ABSTRACT

BACKGROUND: Intensive Care Unit (ICU) capacity management is essential to provide high-quality healthcare for critically ill patients. Yet, consensus on the most favorable ICU design is lacking, especially whether ICUs should deliver dedicated or non-dedicated care. The decision for dedicated or non-dedicated ICU design considers a trade-off in the degree of specialization for individual patient care and efficient use of resources for society. We aim to share insights of a model simulating capacity effects for different ICU designs. Upon request, this simulation model is available for other ICUs. METHODS: A discrete event simulation model was developed and used, to study the hypothetical performance of a large University Hospital ICU on occupancy, rejection, and rescheduling rates for a dedicated and non-dedicated ICU design in four different scenarios. These scenarios either simulate the base-case situation of the local ICU, varying bed capacity levels, potential effects of reduced length of stay for a dedicated design and unexpected increased inflow of unplanned patients. RESULTS: The simulation model provided insights to foresee effects of capacity choices that should be made. The non-dedicated ICU design outperformed the dedicated ICU design in terms of efficient use of scarce resources. CONCLUSIONS: The choice to use dedicated ICUs does not only affect the clinical outcome, but also rejection- rescheduling and occupancy rates. Our analysis of a large university hospital demonstrates how such a model can support decision making on ICU design, in conjunction with other operation characteristics such as staffing and quality management.


Subject(s)
Intensive Care Units , Quality Improvement , Intensive Care Units/organization & administration , Humans , Computer Simulation , Hospitals, University , Length of Stay/statistics & numerical data , Decision Making , Decision Making, Organizational
11.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article in English | MEDLINE | ID: mdl-34526387

ABSTRACT

T cell activation is initiated by T cell receptor (TCR) phosphorylation. This requires the local depletion of large receptor-type phosphatases from "close contacts" formed when T cells interact with surfaces presenting agonistic TCR ligands, but exactly how the ligands potentiate signaling is unclear. It has been proposed that TCR ligands could enhance receptor phosphorylation and signaling just by holding TCRs in phosphatase-depleted close contacts, but this has not been directly tested. We devised simple methods to move the TCR in and out of close contacts formed by T cells interacting with supported lipid bilayers (SLBs) and to slow the receptor's diffusion in the contacts, using a series of anti-CD3ε Fab- and ligand-based adducts of the receptor. TCRs engaging a Fab extended with the large extracellular region of CD45 were excluded from contacts and produced no signaling. Conversely, allowing the extended Fab to become tethered to the SLB trapped the TCR in the close contacts, leading to very strong signaling. Importantly, attaching untethered anti-CD3ε Fab or peptide/MHC ligands, each of which were largely inactive in solution but both of which reduced TCR diffusion in close contacts approximately fivefold, also initiated signaling during cell/SLB contact. Our findings indicate that holding TCRs in close contacts or simply slowing their diffusion in phosphatase-depleted regions of the cell surface suffices to initiate signaling, effects we could reproduce in single-particle stochastic simulations. Our study shows that the TCR is preconfigured for signaling in a way that allows it to be triggered by ligands acting simply as receptor "traps."


Subject(s)
Cell Communication , Cell Membrane/metabolism , Lipid Bilayers/metabolism , Lymphocyte Activation , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/metabolism , Humans , Ligands , Phosphorylation , T-Lymphocytes/cytology
12.
Risk Anal ; 44(4): 850-867, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37573254

ABSTRACT

In the United States, assistance from the Department of Housing and Urban Development (HUD) plays an essential role in supporting the postdisaster recovery of states with unmet housing needs. HUD requires data on unmet needs to appropriate recovery funds. Ground truth data are not available for months after a disaster, however, so HUD uses a simplified approach to estimate unmet housing needs. State authorities argue that HUD's simplified approach underestimates the state's needs. This article presents a methodology to estimate postdisaster unmet housing needs that is accurate and relies only on data obtained shortly after a disaster. Data on the number of damaged buildings are combined with models for expected repair costs. Statistical models for aid distributed by the Federal Emergency Management Agency (FEMA) and the Small Business Administration (SBA) are then developed and used to forecast funding provided by those agencies. With these forecasts, the unmet need to be funded by HUD is estimated. The approach can be used for multiple states and hazard types. As validation, the proposed methodology is used to estimate the unmet housing needs following disasters that struck California in 2017. California authorities suggest that HUD's methodology underestimated the state's needs by a factor of 20. Conversely, the proposed methodology can replicate the estimates by the state authorities and provide accounts of losses, the amount of funding from FEMA and SBA, and the total unmet housing needs without requiring data unavailable shortly after a disaster. Thus, the proposed methodology can help improve HUD's funding appropriation without delays.


Subject(s)
Disasters , Wildfires , United States , Housing , California , Costs and Cost Analysis
13.
Clin Oral Investig ; 28(2): 148, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38353803

ABSTRACT

OBJECTIVES: The present study aimed to determine in silico toxicity predictions of test compounds from hydraulic calcium silicate-based sealers (HCSBS) and AH Plus and computationally simulate the interaction between these substances and mediators of periapical inflammation via molecular docking. MATERIALS AND METHODS: All chemical information of the test compounds was obtained from the PubChem site. Predictions for bioavailability and toxicity analyses were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the Autodock4 AMDock v.1.5.2 program to analyse interactions between proteins (IL-1ß, IL-6, IL-8, IL-10 and TNF-α) and ligands (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate) to establish the affinity and bonding mode between systems. RESULTS: Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favourable molecular docking. However, the ligands bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. CONCLUSION: In silico predictions and molecular docking pointed the higher toxicity and greater interaction with mediators of periapical inflammation of the main test compounds from AH Plus compared to those from HCSBS. CLINICAL RELEVANCE: This is the first in silico study involving endodontic materials and may serve as the basis for further research that can generate more data, producing knowledge on the interference of each chemical compound in the composition of different root canal sealers.


Subject(s)
Benzhydryl Compounds , Benzylamines , Calcium Compounds , Epoxy Resins , Phenols , Root Canal Filling Materials , Silicates , Humans , Epoxy Resins/toxicity , Molecular Docking Simulation , Inflammation , Root Canal Filling Materials/toxicity
14.
Sensors (Basel) ; 24(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38276386

ABSTRACT

The paper introduces a step-down converter that exhibits a static conversion ratio of cubic nature, providing an output voltage which is much closer to the input voltage, and at the same duty cycle, compared to a wide class of one-transistor buck-type topologies. Although the proposed topology contains many components, its control is still simple, as it employs only one transistor. A dc analysis is performed, the semiconductor stresses are derived in terms of input and output voltages and output power, revealing that the semiconductor voltage stresses remain acceptable and anyway lower than in other cubic buck topology. All detailed design equations are provided. The state-space approach is used to analyze the converter in the presence of conduction losses and a procedure for calculating the individual power dissipation is provided. The feasibility of the proposed cubic buck topology is first validated by computer simulation and finally confirmed by an experimental 12 V-10 W prototype.

15.
Surg Innov ; 31(1): 82-91, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37916497

ABSTRACT

Learning surgical skills require critical visual-spatial motor skills. Current learning methods employ costly and limited in-person teaching in addition to supplementation by videos, textbooks, and cadaveric labs. Increasingly limited healthcare resources and in-person training has led to growing concerns for skills acquisition of trainees. Recent Mixed Reality (MR) devices offer an attractive solution to these resource barriers by providing three-dimensional holographic representations of reality that mimic in-person experiences in a portable, individualized, and cost-effective form. We developed and evaluated two holographic MR models to explore the feasibility of visual-spatial motor skill acquisition from a technical development, learning, and usability perspective. In our first, a pair of holographic hands were created and projected in front of the trainee, and participants were evaluated on their ability to learn complex hand motions in comparison to traditional methods of video and apprenticeship-based learning. The second model displayed a 3D holographic model of the middle and inner ear with labeled anatomical structures which users could explore and user experience feedback was obtained. Our studies demonstrated that scores between MR and apprenticeship learning were comparable. All felt MR was an effective learning tool and most noted that the MR models were better than existing didactic methods of learning. Identified advantages of MR included the ability to provide true 3D spatial representation, improved visualization of smaller structures in detail by upscaling the models, and improved interactivity. Our results demonstrate that holographic learning is able to mimic in-person learning for visual-spatial motor skills and could be a new effective form of self-directed apprenticeship learning.


Subject(s)
Augmented Reality , Humans , Motor Skills , Mentors , Feedback
16.
Aesthetic Plast Surg ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38777929

ABSTRACT

BACKGROUND: The increasing demand and changing trends in rhinoplasty surgery emphasize the need for effective doctor-patient communication, for which Artificial Intelligence (AI) could be a valuable tool in managing patient expectations during pre-operative consultations. OBJECTIVE: To develop an AI-based model to simulate realistic postoperative rhinoplasty outcomes. METHODS: We trained a Generative Adversarial Network (GAN) using 3,030 rhinoplasty patients' pre- and postoperative images. One-hundred-one study participants were presented with 30 pre-rhinoplasty patient photographs followed by an image set consisting of the real postoperative versus the GAN-generated image and asked to identify the GAN-generated image. RESULTS: The study sample (48 males, 53 females, mean age of 31.6 ± 9.0 years) correctly identified the GAN-generated images with an accuracy of 52.5 ± 14.3%. Male study participants were more likely to identify the AI-generated images compared with female study participants (55.4% versus 49.6%; p = 0.042). CONCLUSION: We presented a GAN-based simulator for rhinoplasty outcomes which used pre-operative patient images to predict accurate representations that were not perceived as different from real postoperative outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

17.
Int J Mol Sci ; 25(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38999936

ABSTRACT

The surface functionalization of polymer-mediated drug/gene delivery holds immense potential for disease therapy. However, the design principles underlying the surface functionalization of polymers remain elusive. In this study, we employed computer simulations to demonstrate how the stiffness, length, density, and distribution of polymer ligands influence their penetration ability across the cell membrane. Our simulations revealed that the stiffness of polymer ligands affects their ability to transport cargo across the membrane. Increasing the stiffness of polymer ligands can promote their delivery across the membrane, particularly for larger cargoes. Furthermore, appropriately increasing the length of polymer ligands can be more conducive to assisting cargo to enter the lower layer of the membrane. Additionally, the distribution of polymer ligands on the surface of the cargo also plays a crucial role in its transport. Specifically, the one-fourth mode and stripy mode distributions of polymer ligands exhibited higher penetration ability, assisting cargoes in penetrating the membrane. These findings provide biomimetic inspiration for designing high-efficiency functionalization polymer ligands for drug/gene delivery.


Subject(s)
Polymers , Polymers/chemistry , Ligands , Transcytosis , Drug Carriers/chemistry , Cell Membrane/metabolism , Gene Transfer Techniques , Drug Delivery Systems , Computer Simulation , Humans
18.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731918

ABSTRACT

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.


Subject(s)
Computer Simulation , Obesity , Humans , Obesity/drug therapy , Obesity/metabolism , Animals , Molecular Docking Simulation , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use , Lipase/metabolism , Lipase/antagonists & inhibitors , Molecular Targeted Therapy/methods
19.
HNO ; 72(5): 357-366, 2024 May.
Article in German | MEDLINE | ID: mdl-38324064

ABSTRACT

BACKGROUND: Technological change in healthcare and the digital transformation of teaching require innovations in student teaching in medicine. New technologies are needed to enable the delivery and use of diverse teaching and learning formats by educational institutions independent of time and place. The aim of this study is to analyze the effectiveness of different multidimensional formats in student teaching in surgical ENT medical anatomy. MATERIALS AND METHODS: During the summer semester 2022 and winter semester 2022/2023, the digital teaching and learning program was expanded by testing different visualization formats (3D glasses, cardboards, or VR glasses) with students in the context of a highly standardized surgical procedure, namely cochlear implantation. A pre- and post-intervention knowledge assessment was carried out in all groups, followed by an evaluation. RESULTS: Of 183 students, 91 students fully participated in the study. The post-intervention knowledge assessment showed a significant increase in correct answers regardless of visualization format. In a direct comparison, the operating room (OR) group answered correctly significantly more often than the cardboard group (p = 0.0424). The majority of students would like to see 3D teaching as an integral part of the teaching program (87.9%) and more streaming of live surgeries (93.4%). They see the use of the various technologies as a very good addition to conventional surgical teaching (72.5%), as good visualization (89%) increases retention (74.7%) and motivation (81.3%). CONCLUSION: Application and use of new visualization technologies in everyday clinical practice is a promising approach to expanding student training. Mobile, interactive, and personalized technical formats can be adapted to the learning behavior of students. Last but not least, the use of new media influences learning motivation. An expansion of digital teaching and learning formats can be expressly recommended on the basis of this study.


Subject(s)
Computer-Assisted Instruction , Curriculum , Otolaryngology , Otolaryngology/education , Germany , Computer-Assisted Instruction/methods , Humans , Male , Female , Students, Medical , Educational Measurement , Anatomy/education , Young Adult , Teaching , Adult
20.
HNO ; 72(Suppl 1): 56-62, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37812257

ABSTRACT

BACKGROUND: One of the main treatment goals in cochlear implant (CI) patients is to improve speech perception. One of the target parameters is speech intelligibility in quiet. However, treatment results show a high variability, which has not been sufficiently explained so far. The aim of this noninterventional retrospective study was to elucidate this variability using a selected population of patients in whom etiology was not expected to have a negative impact on postoperative speech intelligibility. MATERIALS AND METHODS: Audiometric findings of the CI follow-up of 28 adult patients after 6 months of CI experience were evaluated. These were related to the preoperative audiometric examination and evaluated with respect to a recently published predictive model for the postoperative monosyllabic score. RESULTS: Inclusion of postoperative categorical loudness scaling and hearing loss for Freiburg numbers in the model explained 55% of the variability in fitting outcomes with respect to monosyllabic word recognition. CONCLUSION: The results of this study suggest that much of the cause of variability in fitting outcomes can be captured by systematic postoperative audiometric checks. Immediate conclusions for CI system fitting adjustments may be drawn from these results. However, the extent to which these are accepted by individual patients and thus lead to an improvement in outcome must be subject of further studies, preferably prospective.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Humans , Retrospective Studies , Prospective Studies , Cochlear Implantation/methods , Audiometry
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