Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction Analysis on the SARS-CoV-2 Spike Protein Receptor Binding Domain Using Visualization of the Interfacial Electrostatic Complementarity

Visualization of the interfacial electrostatic complementarity (VIINEC) is a recently developed method for analyzing protein–protein interactions using electrostatic potential (ESP) calculated via the ab initio fragment molecular orbital method. In this Letter, the molecular interactions of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with human angiotensin-converting enzyme 2 (ACE2) and B38 neutralizing antibody were examined as an illustrative application of VIINEC. The results of VIINEC revealed that the E484 of RBD has a role in making a local electrostatic complementary with ACE2 at the protein–protein interface, while it causes a considerable repulsive electrostatic interaction. Furthermore, the calculated ESP map at the interface of the RBD/B38 complex was significantly different from that of the RBD/ACE2 complex, which is discussed herein in association with the mechanism of the specificity of the antibody binding to the target protein.
An inconsistency-based approach for sensing assessment in unknown environments

While exploring an unknown environment, an intelligent agent has only its sensors to guide its actions. Each sensor’s ability to provide accurate information depends on the environment’s characteristics. If the agent does not know these characteristics, how can it determine which sensors to rely on? This problem is exacerbated by sensing anomalies: cases where sensor(s) are working but the readings lead to an incorrect interpretation of the environment, e.g. laser sensors cannot detect glass. This work addresses the following research question: Can an inconsistency-based sensing accuracy indicator, which relies solely on fused sensor readings, be used to detect and characterize sensing anomalies in unknown environments? A novel inconsistency-based approach was investigated for sensing anomaly detection and characterization by a mobile robot using range sensing for mapping. Based on the hypothesis that sensing anomalies manifest as inconsistent sensor readings, the approach employed Dempster-Shafer theory and six metrics from the evidential literature to measure the magnitude of inconsistency. These were applied directly to fused sensor data with a threshold, forming an indicator, used to distinguish minor noise from anomalous readings. Experiments with real sensor data from four indoor and two outdoor environments showed that three of the six evidential inconsistency metrics can partially address the issue of noticing sensing anomalies in unknown environments. Polaroid sonar sensors, SICK laser range finders, and a Canesta range camera were used. Despite extensive training in known environments, the indicators could not reliably detect sensing anomalies, i.e. distinguish them from ordinary noise. However, sensing accuracy could be estimated (correlations with sensor error exceeded 0.8) and regions with suspect readings could be isolated. Trained indicators failed to rank sensors, but improved map quality by resetting suspect regions (up to 57.65%) or guiding sensor selection (up to 75.86%). This work contributes to the robotics and uncertainty in artificial intelligence communities by establishing the use of evidential metrics for adapting a single sensor or identifying the most accurate sensor to optimize the sensing accuracy in unknown environments. Future applications could enable intelligent systems to switch information sources to optimize mission performance and identify the reliability of sources for different environments.
Tunnel Management in Revision Anterior Cruciate Ligament Reconstruction: Current Concepts

Bone tunnel–related complications are frequently encountered during revision anterior cruciate ligament reconstruction (ACLR). Issues with tunnel positioning, enlargement, containment, and hardware interference may complicate surgery and compromise outcomes. As a result, several strategies have emerged to address these issues and optimize results. However, a systematic, unified approach to tunnel pathology in revision ACLR is lacking. The purpose of this review is to highlight the current state of the literature on bone tunnel complications and, although extensive literature on the subject is lacking, present an updated approach to the evaluation and management of tunnel-related issues in revision ACLR.
Developmental Training Model for the Sport Specialized Youth Athlete: A Dynamic Strategy for Individualizing Load-Response During Maturation

Context: Most available data on athletic development training models focus on adult or professional athletes, where increasing workload capacity and performance is a primary goal. Development pathways in youth athletes generally emphasize multisport participation rather than sport specialization to optimize motor skill acquisition and to minimize injury risk. Other models emphasize the need for accumulation of sport- and skill-specific hours to develop elite-level status. Despite recommendations against sport specialization, many youth athletes still specialize and need guidance on training and competition. Medical and sport professionals also recommend progressive, gradual increases in workloads to enhance resilience to the demands of high-level competition. There is no accepted model of risk stratification and return to play for training a specialized youth athlete through periods of injury and maturation. In this review, we present individualized training models for specialized youth athletes that (1) prioritize performance for healthy, resilient youth athletes and (2) are adaptable through vulnerable maturational periods and injury. Evidence Acquisition: Nonsystematic review with critical appraisal of existing literature. Study Design: Clinical review. Level of Evidence: Level 4. Results: A number of factors must be considered when developing training programs for young athletes: (1) the effect of sport specialization on athlete development and injury, (2) biological maturation, (3) motor and coordination deficits in specialized youth athletes, and (4) workload progressions and response to load. Conclusion: Load-sensitive athletes with multiple risk factors may need medical evaluation, frequent monitoring, and a program designed to restore local tissue and sport-specific capacity. Load-naive athletes, who are often skeletally immature, will likely benefit from serial monitoring and should train and compete with caution, while load-tolerant athletes may only need occasional monitoring and progress to optimum loads. Strength of Recommendation Taxonomy (SORT): B.
Computational identification of potential inhibitory compounds in Indian medicinal and aromatic plant species against major pathogenicity determinants of SARS-CoV-2

Abstract SARS-CoV-2 (COVID-19) viral pandemic has been reported across 223 countries and territories. Globalized vaccination programs alongside administration of repurposed drugs will assumingly confer a stronger and longer individual specific immune protection. However, considering possible recurrence of the disease via new variants, a conveniently deliverable phytopharmaceutical drug might be the best option for COVID-19 treatment. In the current study, the efforts have been made to identify potential leads for inhalation therapy as nasal swabs have been reported to transfer viral load prominently. In that direction, 2363 Essential oil (EOs) compounds from Indian medicinal and aromatic plants were screened through docking analysis and potential candidates were shortlisted that can interfere with viral pathogenicity. The main protease (Mpro) of SARS-CoV-2 interacted closely with jatamansin (JM), 6,7-dehydroferruginol (FG) and beta-sitosterol (BS), while Papain-like Protease (PLpro) with friedelane-3-one (F3O) and lantadene D (LD) independently. Reduced Lantadene A (LAR) exhibited preferable interaction with RNA-dependent-RNA-polymerase (RdRp) whereas Lantadene A (LA) with RdRp and spike-glycoprotein (SG-pro) both target proteins. When compared against highest binding affinity conformations of well-known inhibitors of targets, these prioritized compounds conferred superior or comparable SARS-CoV-2 protein inhibition. Additionally, promising results were noted from pharmacokinetics prediction for all shortlisted compounds. Besides, molecular dynamics simulation for 100 ns in two replicates and binding free energy analysis revealed the stability of complexes with optimum compactness. To the best of our knowledge, the current investigation is a unique initial attempt whereby EO compounds have been computationally screened, irrespective of their known medicinal properties to fight COVID-19 infection. Communicated by Ramaswamy H. Sarma
Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.
Biological and methodological complexities of beta‐amyloid peptide: Implications for Alzheimer’s disease research

Although controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid‐beta (Aβ) as the central factor initiating disease onset. In recent years, there has been an increase in emphasis on studying the role of low molecular weight aggregates, such as oligomers, which are suggested to be more neurotoxic than fibrillary Aβ. Other Aβ isoforms, such as truncated Aβ, have also been implicated in disease. However, developing a clear understanding of AD pathogenesis has been hampered by the complexity of Aβ biochemistry in vitro and in vivo. This review explores factors contributing to the lack of consistency in experimental approaches taken to model Aβ aggregation and toxicity and provides an overview of the different techniques available to analyse Aβ, such as electron and atomic force microscopy, nuclear magnetic resonance spectroscopy, dye‐based assays, size exclusion chromatography, mass spectrometry and SDS‐PAGE. The review also explores how different types of Aβ can influence Aβ aggregation and toxicity, leading to variation in experimental outcomes, further highlighting the need for standardisation in Aβ preparations and methods used in current research.
E-GOVERNMENT PORTAL EFFECTIVENESS: MANAGERIAL CONSIDERATIONS FOR DESIGN AND DEVELOPMENT

E-government portals are considered one of the most popular conduits for offering government services, information, and products online. Synonymous to majestic gateways of large buildings, in a literal sense, e-government portals are anchor websites which provide a jurisdictional window to electronic governments by offering a single entry point for the citizen/customer and government employees to access integrated services and information for all of a government’s departments.
Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy

Background and Objectives The mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP). Methods The participants were included from a large Danish cross-sectional clinical study of type 2 diabetes. We diagnosed definite diabetic polyneuropathy using the Toronto criteria and used the Neuropathic Pain Special Interest Group classification for defining P-DPN. We included 60 skin biopsies from patients with diabetic polyneuropathy—30 with P-DPN and 30 with nonpainful diabetic polyneuropathy (NP-DPN)—and 30 biopsies from healthy controls of similar age and sex. The biopsies were stained using PGP 9.5, IbA1, and SP and CGRP primary markers. Results There was increased macrophage density in patients with P-DPN (8.0%) compared with that in patients with NP-DPN (5.1%, p < 0.001), and there was increased macrophage density in patients with NP-DPN (5.1%) compared with that in healthy controls (3.1%, p < 0.001). When controlling for neuropathy severity, body mass index, age, and sex, there was still a difference in macrophage density between patients with P-DPN and patients with NP-DPN. Patients with P-DPN had higher median nerve fiber length density (274.5 and 155 mm−2 for SP and CGRP, respectively) compared with patients with NP-DPN (176 and 121 mm−2 for SP and CGRP, respectively, p = 0.009 and 0.04) and healthy controls (185.5 and 121.5 mm−2 for SP and CGRP, respectively), whereas there was no difference between patients with NP-DPN and controls without diabetes (p = 0.64 and 0.49, respectively). The difference between P-DPN and NP-DPN for SP and CGRP was significant only in female patients, although a trend was seen in male patients. Discussion The findings point to a possible involvement of the innate immune system in the pathogenesis of neuropathic pain in patients with DPN, although markers of activated macrophages were not measured in this study.
Model-based approach to investigate equipment-induced error in pressure-waveform derived hemodynamic measurements

Objective. Advanced hemodynamic monitoring systems have provided less invasive methods for estimating pressure-derived measurements such as pressure-derived cardiac output (CO) measurements. These devices apply algorithms to arterial pressure waveforms recorded via pressure recording components that transmit the pressure signal to a pressure monitor. While standards have been developed for pressure monitoring equipment, it is unclear how the equipment-induced error can affect secondary measurements from pressure waveforms. We propose an approach for modelling different components of a pressure monitoring system and use this model-based approach to investigate the effect of different pressure recording configurations on pressure-derived hemodynamic measurements. Approach. The proposed model-based approach is a three step process. (1) Modelling the response of pressure recording components using bench tests; (2) verifying the identified models through nonparametric equivalence tests; and (3) assessing the effects of pressure recording components on pressure-derived measurements. To delineate the application of this approach, we performed a series of model-based analyses to quantify the combined effect of a wide range of tubing configurations with various damping ratios and natural frequencies and monitors with different bandwidths on pressure waveforms and CO measurements by six pulse contour algorithms. Results. Model-based results show the error in pressure-derived CO measurements because of tubing configurations with different natural frequencies and damping ratios. Tubing configurations with low natural frequencies (<23 Hz) altered characteristics of pressure waveforms in a way that affected the CO measurement, some by as much as 20%. Significance. Our method can serve as a tool to quantify the performance of pressure recording systems with different dynamic properties. This approach can be applied to investigate the effects of physiologic signal recording configurations on various pressure-derived hemodynamic measurements.
Valid Acoustic Models of Cochlear Implants: One Size Does Not Fit All

Supplemental Digital Content is available in the text Hypothesis: This study tests the hypothesis that it is possible to find tone or noise vocoders that sound similar and result in similar speech perception scores to a cochlear implant (CI). This would validate the use of such vocoders as acoustic models of CIs. We further hypothesize that those valid acoustic models will require a personalized amount of frequency mismatch between input filters and output tones or noise bands. Background: Noise or tone vocoders have been used as acoustic models of CIs in hundreds of publications but have never been convincingly validated. Methods: Acoustic models were evaluated by single-sided deaf CI users who compared what they heard with the CI in one ear to what they heard with the acoustic model in the other ear. We evaluated frequency-matched models (both all-channel and 6-channel models, both tone and noise vocoders) as well as self-selected models that included an individualized level of frequency mismatch. Results: Self-selected acoustic models resulted in similar levels of speech perception and similar perceptual quality as the CI. These models also matched the CI in terms of perceived intelligibility, harshness, and pleasantness. Conclusion: Valid acoustic models of CIs exist, but they are different from the models most widely used in the literature. Individual amounts of frequency mismatch may be required to optimize the validity of the model. This may be related to the basalward frequency mismatch experienced by postlingually deaf patients after cochlear implantation.
Manufacturing Capability Evaluation in a Job Shop Production System: A Case Base Approach

Paper analyzes manufacturing capability in job shop environments by evaluating the pattern of decisions using a case study approach. Analytical Hierarchical Process (AHP), a multi criteria decision making (MCDM) method, has been employed which consists of three levels. The overall goal, i.e. manufacturing capability index is placed at level 1 followed by six decision areas at level 2 and thirty three decision criteria at level 3. Structured interview process has been used to collect information about thirty three decision criteria. The data was collected and analyzed for five companies operated in a job shop manufacturing environment. Pattern of decisions that are ideally essential for competitiveness of job shop manufacturing are then compared with the pattern of decisions from the five cases. This approach facilitates the practitioners to indentify the weak decision areas in order to improve the competitiveness in job shop manufacturing.
Effects of Acupuncture and Acupressure on Burnout in Health Care Workers: A Randomized Trial

Background: Health care workers face occupational stressors that may lead to burnout and secondary traumatic stress. Strategies to mitigate the negative psychological impact on frontline workers are urgently needed. Objective: The purpose of this study was to evaluate the effect of auricular acupuncture or acupressure, as compared with ear massage, on anxiety, burnout, and caring capacity in health care workers. Results were stratified on the basis of subject's level of belief in traditional Chinese medicine. Methods: This prospective randomized trial with an open, parallel-group design was conducted at a 334-bed Level II pediatric trauma center. Participants were randomized to one of three groups: (1) auricular acupuncture, (2) auricular seed acupressure, or (3) auricular massage. Interventions were delivered over 3 weeks. Self-reported State-Trait Anxiety Inventory (STAI), Professional Quality of Life (ProQOL), and Caring Ability Inventory (CAI) scores were analyzed using a pre-/posttest design. Univariate analysis, Fisher's exact test, and analysis of variance (ANOVA) were performed to assess group differences. Results: A total of 117 (36%) of 325 eligible participants consented to participate in the study. Seed acupressure treatment (n = 14, 35.9%, one male, 13 females) was associated with a reduction in burnout (ANOVA, p = .04) and secondary traumatic stress (p = .03). This effect remained significant after adjusting for individual pretest scores (ANOVA, p = .05). The studied interventions did not have a significant effect on STAI, ProQOL, or CAI scores. Conclusions: Auricular acupressure is a safe, effective, and practical strategy to reduce burnout and secondary traumatic stress and may support health care workers' ability to develop caring relationships with patients and families.
Repairing Cartilage with Processed Chondrocyte Constructs: A 6-Month Study Using a Porcine Model

Objective Autologous chondrocyte implantation was the first cell-based therapy that used a tissue engineering process to repair cartilage defects. Recently improved approaches and tissue-engineered cell constructs have been developed for growing patient populations. We developed a chondrocyte construct using a collagen gel and sponge scaffold and physicochemical stimuli, implanted with a surgical adhesive. We conducted a proof-of-concept study of these improvements using a cartilage defect model in miniature swine. Design We implanted the autologous chondrocyte constructs into full-thickness chondral defects in the femoral condyle, compared those results with empty and acellular scaffold controls, and compared implantation techniques with adhesive alone and with partial adhesive with suture. Two weeks after the creation of the defects and implantation of the cellular or acellular constructs, we arthroscopically confirmed that the implanted constructs remained at the chondral defects. We evaluated the regenerated tissue macro- and microscopically 6 months after the cell constructs were implanted. The tissues were stained with Safranin-O and evaluated using Sellers’ histology grading system. Results The defects implanted with processed cell constructs and acellular scaffolds were filled with chondrocyte-like round cells and with nearly normal tissue architecture that were significantly greater degree compared to empty defect control. Even with the adhesive alone and with suture alone, the cell construct was composed of the dense cartilaginous matrix that was found in the implantation using both the sutures and the adhesive. Conclusion Implantation of cell constructs promoted regeneration and integration of articular cartilage at chondral defects in swine by 6 months.
Novel Furanyl‐Substituted Isochromanyl Class of Anti‐Inflammatory Turbinochromanone from Brown Seaweed Turbinaria conoides

Organic extract of the brown seaweed Turbinaria conoides (Sargassaceae) was chromatographically fractionated to yield an undescribed furanyl‐substituted isochromanyl metabolite, named as turbinochromanone, which was characterized as methyl 4‐[(3S)‐8‐{[(3R)‐4‐ethyl‐2,3‐dihydrofuran‐3‐yl]methyl}‐1‐oxo‐3,4‐dihydro‐1H‐2‐benzopyran‐3‐yl]butanoate. The isochromanyl derivative possessed comparable attenuation potential against 5‐lipoxygenase (IC50 3.70 μM) with standard 5‐lipoxygenase inhibitor drug zileuton (IC50 2.41 μM). Noticeably, the index of anti‐inflammatory selectivity of turbinochromanone (∼1.7) was considerably greater than that exhibited by the standard agent diclofenac (1.06). Antioxidant properties of turbinochromanone against oxidants (IC50∼24 μM) further supported its potential anti‐inflammatory property. Greater electronic properties (topological polar surface area of 61.8) along with comparatively lesser docking parameters of the studied compound with aminoacyl residues of targeted enzymes (cyclooxygenase‐2 and 5‐lipoxygenase) (binding energy of −11.05 and −9.40 kcal mol−1, respectively) recognized its prospective anti‐inflammatory potential. In an aim to develop seaweed‐based natural anti‐inflammatory leads, the present study isolated turbinochromanone as promising 5‐lipoxygenase and cyclooxygenase‐2 inhibitor, which could be used for pharmaceutical and biotechnological applications.