Miracle-dz/UniFAR-FTUs huggingface dataset:
EPR Studies of Functionally Active, Nitroxide Spin-Labeled Peptide Analogs of the C-terminus of a G-Protein Alpha Subunit

The C-terminal tail of the transducin alpha subunit, Gtα(340–350), is known to bind and stabilize the active conformation of rhodopsin upon photoactivation (R*). Five spin-labeled analogs of Gtα(340–350) demonstrated native-like activity in their ability to bind and stabilize R*. The spin label 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) was employed at interior sites within the peptide, whereas a Proxyl (3-carboxyl-2,2,5,5-tetramethylpyrrolidinyloxy) spin label was employed at the amino terminus of the peptide. Upon binding to R*, the electron paramagnetic resonance spectrum of TOAC343-Gtα(340–350) revealed greater immobilization of the nitroxide when compared to that of the N-terminal modified ProxylGtα(340–350) analog. A double-labeled Proxyl/TOAC348-Gtα(340–350) was examined by DEER spectroscopy to determine the distribution of distances between the two nitroxides in the peptides when in solution and when bound to R*. TOAC and Proxyl spin labels in this GPCR-G-protein αpeptide system provide unique biophysical probes that can be used to explore the structure and conformational changes at the rhodopsin-G-protein interface. Spin-labeled proteins and peptides, as used in EPR studies, provide a dynamic view of biological phenomenon. In site-directed spin labeling (SDSL), nitroxide amino acids are selectively introduced into a peptide or protein, and the electron paramagnetic resonance is analyzed to provide information on sequence-specific secondary and tertiary structure, membrane protein topography and electrostatic potential (1), conformational changes (2), protein dynamics (3), and inter-nitroxide distances (4–7). In most studies, the nitroxide side chain designated R1 has been employed (Figure 1a). Crystallographic (8–11), mutagenic (12,13) and spectral simulation studies (14) revealed that internal motions of the side chain are constrained due to interactions of the disulfide with main-chain atoms. Thus, the dynamics, and hence the EPR spectra, are primarily determined by limited torsional oscillations about two dihedral angles (angles X4 and X5 in Figure 1a). As a result of this constrained motion, the EPR spectrum is highly sensitive to additional backbone #Corresponding authors – GRM, 314-362-1567, no fax, garlandm@gmail.com. #WLH, 310-206-8830, 310-794-2144 (fax), hubbellw@jsei.ucla. edu. *These authors contributed equally to the work. NIH Public Access
Impact of imperfect diagnosis in ME/CFS association studies

The absence of an objective disease biomarker puts studies of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) under the curse of imperfect diagnosis. This problem leads to frequent reports that fail to reproduce prior published studies. To address the impact of imperfect diagnosis on the robustness of studies' conclusions, we conducted a simulation study to quantify the statistical power to detect a disease association with a hypothetical binary factor in the presence of imperfect diagnosis. Using the classical case-control design, studies with sample sizes of less than 500 individuals per group could not reach the target power of at least 80% to detect realistic disease associations. We then recreated serological association studies in which the chance of imperfect diagnosis was combined with the probability of misclassifying a binary factor, as it happens in a typical serological association study. In this case, the target power of 80% could only be achieved for studies with more than 1000 individuals per group. Given the current sample sizes of ME/CFS studies, our results suggest that most studies are likely to be underpowered due to imperfect diagnosis alone. To increase reproducibility across studies, we provided some practical recommendations, such as the use of standard case definitions together with multi-centric study designs, and routine reporting of power calculations under a non-negligible chance of misdiagnosis. Our results can also inform the design of future studies under the assumption of misdiagnosis.
Development of a scoring model for the Sharp/van der Heijde score using convolutional neural networks and its clinical application in predicting radiographic progression using a graph convolutional network

Objective: To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings. Methods: First, we built a rheumatoid arthritis (RA) image database linked to clinical information. We then constructed the prediction model in three steps: orientation, detection, and damage prediction. We assessed whether the SHS generated by our model replicated known findings on the association between radiographic progression and serological markers. Finally, after characterizing the SHSs of 4,264 patients using hierarchical clustering, we constructed a predictive model for joint destruction using a graph convolutional network (GCN). Results: We built a model with an accuracy of 100% in the correction of image orientation using EfficientNet and constructed a model with all predicted joint coordinates within 10 pixels of the correct coordinates using U-Net. In the damage prediction phase, the EfficientNet-based model combined with the modules achieved correlation coefficients of 0.879 for erosion and 0.868 for joint space narrowing between the model and expert, exceeding that of the previous best model. Our model replicated the known finding of erosion progression's association with serologically positive patients. The areas under the curve for predicting finger and wrist erosion in the GCN model were 0.800 and 0.748, respectively. We observed that clusters generated by hierarchical clustering ranking in the top 10 were important features in the GCN for predicting erosion. Conclusion: We constructed a high-performance scoring model for SHSs applicable to clinical research. Our analysis revealed that clusters are important for predicting erosion using the GCN.
Which surface treatment improves the long-term repair bond strength of aged methacrylate-based composite resin restorations? A systematic review and network meta-analysis

This study aimed to investigate the effect of common surface treatments on the long-term repair bond strength of the aged methacrylate-based composite resin restorations. Also, provide their rankings and two-by-two comparison. In-vitro studies evaluating the methacrylate-based composite resins subjected to rigorous aging procedures before and after being repaired with a new composite were included. A frequentist network meta-analysis was carried out using a random-effects model. P-scores were used to rank the efficacy of the surface treatments. Also, the global and node-split inconsistencies were evaluated. Web of Science, PubMed/Medline, Scopus, and Embase databases were searched until November 11, 2021. Application of diamond bur + silane + total-etch adhesive (shear MD 41.12 MPa, 95% CI 29.02 to 53.21, P-score 0.99; tensile MD 29.36 MPa, 95% CI 12.36 to 46.35; P-score 0.69), and air abrasion with silica-coated alumina + silane + total-etch adhesive (shear MD 16.29 MPa, 95% CI 6.54 to 26.05, P-score 0.66; tensile MD 33.86 MPa, 95% CI 16.17 to 51.54; P-score 0.82) produced the highest (micro)tensile and (micro)shear bond strengths compared to abrasive paper, according to two network meta-analyses containing 22 investigations. There has been no variation comparing self- and total-etch adhesives. Further, mechanical surface treatments should be used alongside the chemical adhesive agents to yield stronger bonds. It is possible to achieve acceptable repair bond strength using common dental clinic equipment. Therefore, clinicians could consider repairing old composite resins rather than replacing them.
Alzheimer’s Disease and the β -Amyloid Peptide

Alzheimer’s disease (AD) pathogenesis is widely believed to be driven by the production and deposition of the β -amyloid peptide (A β ). For many years, investigators have been puzzled by the weak to nonexistent correlation between the amount of neuritic plaque pathology in the human brain and the degree of clinical dementia. Recent advances in our understanding of the development of amyloid pathology have helped solve this mystery. Substantial evidence now indicates that the solubility of A β , and the quantity of A β in different pools, may be more closely related to disease state. The composition of these pools of A β reflects different populations of amyloid deposits, and has definite correlates with the clinical status of the patient. Imaging technologies, including new amyloid imaging agents based on the chemical structure of histologic dyes, are now making it possible to track amyloid pathology along with disease progression in the living patient. Interestingly, these approaches indicate that the A β deposited in AD is different from that found in animal models. In general, deposited A β is more easily cleared from the brain in animal models, and does not show the same physical and biochemical characteristics as the amyloid found in AD. This raises important issues regarding the development and testing of future therapeutic agents.
Attenuated brain white matter functional network interactions in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by extensive structural abnormalities in cortical and subcortical brain areas. However, an association between changes in the functional networks in brain white matter (BWM) and Parkinson's symptoms remains unclear. With confirming evidence that resting‐state functional magnetic resonance imaging (rs‐fMRI) of BWM signals can effectively describe neuronal activity, this study investigated the interactions among BWM functional networks in PD relative to healthy controls (HC). Sixty‐eight patients with PD and sixty‐three HC underwent rs‐fMRI. Twelve BWM functional networks were identified by K‐means clustering algorithm, which were further classified as deep, middle, and superficial layers. Network‐level interactions were examined via coefficient Granger causality analysis. Compared with the HC, the patients with PD displayed significantly weaker functional interaction strength within the BWM networks, particularly excitatory influences from the superficial to deep networks. The patients also showed significantly weaker inhibitory influences from the deep to superficial networks. Additionally, the sum of the absolutely positive/negative regression coefficients of the tri‐layered networks in the patients was lower relative to HC (p < .05, corrected for false discovery rate). Moreover, we found the functional interactions involving the deep BWM networks negatively correlated with part III of the Unified Parkinson's Disease Rating Scales and Hamilton Depression Scales. Taken together, we demonstrated attenuated BWM interactions in PD and these abnormalities were associated with clinical motor and nonmotor symptoms. These findings may aid understanding of the neuropathology of PD and its progression throughout the nervous system from the perspective of BWM function.
The role of stereotypical information on medical judgements for black and white patients

THIS ARTICLE USES WORDS OR LANGUAGE THAT IS CONSIDERED PROFANE, VULGAR, OR OFFENSIVE BY SOME READERS. The new generation of direct-acting antivirals has improved dramatically the rates of cure for chronic hepatitis C. Yet, evidence shows that racial groups are deemed more often ineligible for hepatitis C treatment, despite no clinical evidence supporting differential treatment for Black and White patients. One possible explanation has to do with providers’ racial biases. This investigation sought to explore medical students’ racial stereotypes (Study 1, N = 171) and the role of stereotypical cues on perceptions of medical adherence of Black and White patients (Study 2, N = 208). In Study 1, we first sought to identify health-related aspects that are consistently associated with Blacks as part of a stereotype. In Study 2, we experimentally manipulated racial stereotypes identified in Study 1 by asking participants to read a clinical vignette depicting a patient (Black vs. White) and their medical history (cause of exposure to hepatitis C: unprotected sex vs. non-injectable drugs use). The results show that the impact of stereotypicality on patient perceived compliance varies as a function of medical students’ racial prejudice. Implications for further applied health inequalities research and for medical training are discussed.
Antiproliferative efficacy of the antioxidant bioactive compounds of defatted seeds of Azadirachta indica and Momordica charantia against the regulatory function of tumor suppressor gene inducing oral carcinoma

Abstract The present study focuses on the antiproliferative activity of polyphenolic flavonoids found in defatted seeds of Azadirachta indica and Momordica charantia with the regulatory function of tumor suppressor genes inducing Oral Squamous Cell Carcinoma. Polyphenolic flavonoid in extracts was characterized using chromatographic analysis and has confirmed the presence of quercetin, rutin and tannic acid in the extracts of A. indica and M. charantia. According to DPPH assay and reducing power assays, free radical scavenging was found to be high in ethanolic extract of defatted seeds. Antiproliferative efficacies of defatted seed extracts against KB cell line (mouth) were studied by MTT assay and revealed that aqueous extract of defatted seeds of M. charantia has exhibited maximum antiproliferative activity against KB cells. Antioxidant activity of defatted seed extracts were observed on treated KB cells by determining enzymatic activity (SOD, Cat, and GST) and nonenzyme content (GSH and MDA Content). Using the AutoDock tool, quercetin, rutin and tannin acid revealed that mutant p53, TWIST related protein, TGF-β and Snail I have the best binging energy results. MD simulation was observed on best docking results between the molecule and identified flavonoid by Desmond V 5.9 package . This leads to the conclusion that bioactive extracts with antiproliferative activity, antioxidant capacity and polyphenols with binding efficacy against tumor suppressor gene regulatory function could be used as a herbal remedy. Communicated by Ramaswamy H. Sarma
Pareto optimal solution of multiobjective synthesis of robust controllers of multimass electromechanical systems based on multiswarm stochastic multiagent optimization

Purpose. Developed the method for solving the problem of multiobjective synthesis of robust control by multimass electromechanical systems based on the construction of the Pareto optimal solutions using multiswarm stochastic multi-agent optimization of particles swarm, which reduces the time of determining the parameters of robust controls multimass electromechanical systems and satisfy a variety of requirements that apply to the work of such systems in different modes. Methodology. Multiobjective synthesis of robust control of multimass electromechanical systems is reduced to the solution of solving the problem of multiobjective optimization. To correct the above problem solving multiobjective optimization in addition to the vector optimization criteria and constraints must also be aware of the binary preference relations of local solutions against each other. The basis for such a formal approach is to build areas of Pareto-optimal solutions. This approach can significantly narrow down the range of possible solutions of the problem of optimal initial multiobjective optimization and, consequently, reduce the complexity of the person making the decision on the selection of a single version of the optimal solution. Results . The results of the synthesis of multi-criteria electromechanical servo system and a comparison of dynamic characteristics, and it is shown that the use of synthesized robust controllers reduced the error guidance working mechanism and reduced the system sensitivity to changes in the control parameters of the object compared to the existing system with standard controls. Originality. For the first time, based on the construction of the Pareto optimal solutions using a multiswarm stochastic multi-agent optimization particle algorithms improved method for solving formulated multiobjective multiextremal nonlinear programming problem with constraints, to which the problem of multiobjective synthesis of robust controls by multimass electromechanical systems that can significantly reduce the time to solve problems and meet a variety of requirements that apply to the multimass electromechanical systems in different modes. Practical value. Practical recommendations on reasonable selection of the target vector of robust control by multimass electromechanical systems. Results of synthesis of electromechanical servo system shown that the use of synthesized robust controllers reduced the error guidance of working mechanism and reduce the system sensitivity to changes of plant parameters compared to a system with standard controls.
Psychological Factors Predicting Functional Ability and Participation After Hip Fracture.

IMPORTANCE Positive psychological factors have been related to better outcomes among adults with various health conditions. OBJECTIVE To predict functional ability and participation in older adults who had experienced a hip fracture on the basis of data at admission to acute (inpatient) rehabilitation. We measured physical factors, as well as positive and negative psychological factors, at three time points. DESIGN Prospective and cross-sectional cohort study. Data collection occurred during admission, at discharge, and 6 mo after rehabilitation. SETTING Inpatient geriatric rehabilitation center and follow-up at home. PARTICIPANTS Seventy-one older adults (M age = 78.58 yr, SD = 6.09) who had sustained a hip fracture because of a fall and who attended acute rehabilitation; 55 completed follow-up assessments 6 mo after discharge from rehabilitation. MEASURES Participants completed the Adult Hope Scale, Life Orientation Test, Positive Affect Questionnaire, Geriatric Depression Scale (at admission only), hand-grip strength measures, Numeric Pain Rating Scale, and FIM® Motor domain (mFIM) before and after acute rehabilitation and after 6 mo. The Activity Card Sort (ACS) was administered only at follow-up. Outcome measures were the mFIM and ACS. RESULTS At 6-mo follow-up, functional ability was correlated more with optimism than with age, gender, or hand-grip strength measured at admission. Participation was predicted by age, the hope-agency component, and pain in walking at admission; however, the hope-agency component was only marginally significant. At discharge, functional ability was strongly predicted by age, hand-grip strength, and mFIM scores at admission. CONCLUSIONS AND RELEVANCE Optimism and hope played a role in explaining rehabilitation outcomes at 6-mo follow-up. Occupational therapy evaluation should address positive psychological factors, and intervention should aim to strengthen these factors as powerful aids in older adults' recovery from hip fractures. What This Article Adds: This study reflects the philosophy of occupational therapy, which places great emphasis on the connection between clients' mind-body-spirit and their participation in daily life occupations.
Exploring fungal diversity in Antarctic wildlife: isolation and molecular identification of culturable fungi from penguins and pinnipeds

ABSTRACT Aims To survey the diversity of fungal species that may be cultured from Antarctic penguins and pinnipeds, and to test the in vitro susceptibility to triazole drugs of any medically important Aspergillus spp. isolates. Methods During an expedition to Argentinean Antarctic research stations at Potter Peninsula (South Shetland Islands) and Primavera Cape (Antarctic Peninsula) in February 2019, samples (n = 212) were collected from fur seals (Arctocephalus gazella), elephant seals (Mirounga leonine), leopard seals (Hydrurga leptonyx), Weddell seals (Leptonychotes weddellii) and crabeater seals (Lobodon carcinophaga) and gentoo penguins (Pygoscelis papua). Oral, nasal and rectal swabs and skin/hair brushings were collected from pinnipeds, and skin/feather brushings, cloacal swabs and moulted feathers from penguins. Samples were cultured on Sabouraud dextrose agar and/or potato dextrose agar plates and fungal isolates identified by morphological criteria followed by PCR amplification and DNA sequencing. Antifungal susceptibility of Aspergillus spp. isolates to triazoles was tested. Results Fungi from 21 genera were isolated from 121/212 (57.1%) samples obtained from pinnipeds and penguins. Among pinnipeds from Potter Peninsula (fur seals and elephant seals), the most frequent fungal species were Debaryomyces hansenii and Rhodotorula mucilaginosa, isolated from the oral, nasal and/or rectal mucosa, and Antarctomyces psychrotrophicus isolated from the skin/hair of all sampled individuals. Among pinnipeds from Primavera Cape (leopard seals, Weddell seals and crabeater seals), the most frequent fungal species were Naganishia adeliensis and Cryptococcus neoformans var. uniguttulatus, isolated from the nasal/oral mucosa of 4/33 (15.2%) and 5/33 (12.1%) animals, respectively. The most frequently isolated fungal species from gentoo penguins (Potter Peninsula), were Pseudogymnoascus pannorum and A. pyschrotrophicus, which both were isolated from skin/feathers of 7/15 (46.7%) birds, and Thelebolus microsporus, isolated from the cloacal mucosa and skin/feathers of 5/15 (33.3%) and 2/15 (13.3%) birds, respectively. Fungi that are potentially pathogenic to both humans and animals (Aspergillus fumigatus, Asp. flavus, Asp. versicolor, Candida parapsilosis and Microsporum canis) were isolated from 4/38 (10.5%), 1/38 (2.6%), 2/38 (5.3%), 4/38 (10.5%) and 2/38 (5.3%) sampled pinnipeds, respectively. Only non-azole-resistant isolates of Asp. fumigatus and Asp. flavus were identified. Conclusions The fungal biodiversity in Antarctic pinnipeds and gentoo penguins was explored using standard mycological culture followed by PCR and DNA sequencing. The frequency of fungal carriage varied among animal species, sample type and location. This study constitutes an epidemiologic approach to monitoring of these marine animals for emerging fungal pathogens.
Kinematic and dynamic analyses of the front crawl tumble turn in elite female swimmers

Abstract Based on a three-dimensional (3D) underwater analysis, the objective of the present study was to identify the biomechanical variables the most associated with turn times in 10 elite female swimmers. For each participant (95.7 ± 2.6% of the 200 m freestyle world record), the best-time turn (from 3 m in to 3 m out, 2.89 ± 0.08 s) was analysed from a three-dimensional (3D) direct linear transformation kinematical reconstruction and the use of a piezoelectric force platform. Bivariate analysis showed that lateral impulse was linked to turn time (r = -0.76, p = 0.01) as well as horizontal velocities at end of the glide and swim resumption (respectively, 1.88 ± 0.2 m·s−1 and 1.48 ± 0.15 m·s−1; r = -0.67 and -0.68; p < 0.05 for both variables). One variable was considered relevant in the best Lasso (Least Absolute Shrinkage and Selection Operator) model: the lateral impulse (8.8 ± 5.1 N·s) during the placement sub-phase.The best tumble turn times were associated with higher lateral impulse during the placement and faster velocities during the underwater actions. The lateral impulse may reflect the swimmers’ longitudinal rotation which was higher for the fastest swimmers.