Miracle-dz/UniFAR-FTUs huggingface dataset:
Reliability of Ayurvedic Diagnosis for Knee Osteoarthritis Patients: A Nested Diagnostic Study Within a Randomized Controlled Trial

Abstract Background: Ayurveda is a traditional Indian system of medicine. The customized Ayurvedic approach consists of a combination of several diagnostic procedures and subsequent individualized therapeutic interventions. Evaluation of inter-rater reliability (IRR) of Ayurvedic diagnoses has rarely been performed. The aim of this study was to evaluate IRR of Ayurvedic diagnosis for patients with knee osteoarthritis. Methods: A diagnostic reliability study of 30 patients and 4 Ayurvedic experts was nested in a randomized controlled trial. Patients were diagnosed in a sequential order by all experts utilizing a semistructured patient history form. A nominal group technique as consensus procedure was performed to reach agreement on the items to be diagnosed. An IRR analysis using Fleiss' and Cohen's kappa statistics was performed to determine a chance-corrected measure of agreement among raters. Results: One hundred and twenty different ratings and 30 consensus ratings were performed and analyzed. While high percentages of agreement for main diagnostic entities and the final Ayurveda diagnosis (95% consensus agreement on main diagnosis) could be observed, this was not reflected in the corresponding kappa values, which largely yielded fair-to-poor inter-rater agreement kappas for central diagnostic aspects such as prakriti and agni (κ values between 0 and 0.4). Notably, agreement on disease-related entities was better than that on constitutional entities. Conclusions: This is the first diagnostic study embedded in a clinical trial on patients with knee osteoarthritis utilizing a multimodality whole systems approach. Results showed a contrast between the high agreement of the consented final diagnosis and disagreement on certain diagnostic details. Future diagnostic studies should have larger sample sizes and a methodology more tailored to the specificities of traditional whole systems of medicine. Equal emphasis will need to be placed on all core diagnostic components of Ayurveda, both constitutional and disease specific, using detailed structured history taking forms.
Resveratrol and Its Human Metabolites—Effects on Metabolic Health and Obesity

Resveratrol is one of the most widely studied polyphenols and it has been assigned a plethora of metabolic effects with potential health benefits. Given its low bioavailability and extensive metabolism, clinical studies using resveratrol have not always replicated in vitro observations. In this review, we discuss human metabolism and biotransformation of resveratrol, and reported molecular mechanisms of action, within the context of metabolic health and obesity. Resveratrol has been described as mimicking caloric restriction, leading to improved exercise performance and insulin sensitivity (increasing energy expenditure), as well as having a body fat-lowering effect by inhibiting adipogenesis, and increasing lipid mobilization in adipose tissue. These multi-organ effects place resveratrol as an anti-obesity bioactive of potential therapeutic use.
Relevance of Pituitary Gland Magnetic Resonance Imaging Results with Clinical and Laboratory Findings in Growth Hormone Deficiency

Background The present study investigated the relationship between detection of organic pathologies with magnetic resonance imaging of the pituitary gland, clinical and laboratory findings, and treatment response. Material/Methods The study included a total of 183 patients who had isolated growth hormone deficiency, received at least 1 year of treatment, returned regularly for follow-ups, and whose pituitary magnetic resonance images were available. The patients were divided into 2 groups: those with and without pathological evidence with magnetic resonance imaging. Clinical and laboratory features and treatment responses were compared between patients with and without pathological evidence with magnetic resonance imaging. Results Of the 183 patients, 105 were females and 78 were males, and 114 patients (62.2%) were prepubertal and 69 patients (37.8%) were pubertal. Their mean age was 10.01±3.25 years (1–17.6 years). Pituitary images of 153 (83.6%) patients were normal. Of the patients with detected pathologies (16.4%), 19 (10,4%) had pituitary hypoplasia, 5 (2.7%) had partial empty sella, 3 (1.7%) had ectopic neurohypophysis and 3 (1.7%) had empty sella, pineal, and arachnoid cyst. A statistically significant increase was observed in the height increase rate after treatment compared to before treatment in both groups (p<0.001). However, the group with pathology had a statistically significant (p=0. 007) post-treatment increase height rate. Although in the group with pathology there was a lower L-DOPA and clonidine peak GH response, there was not any statistically significant difference between the 2 groups (p=0.051, p=0.113). Pituitary gland length was also shorter in the group with pathology compared to the group without pathology (P<0.001). Conclusions Magnetic resonance imaging is a useful tool in assessing GH deficiency pathogenesis and in predicting treatment response.
Steroid pretreatment of organ donors does not impact on early rejection and long‐term kidney allograft survival: Results from a multicenter randomized, controlled trial

Steroid pretreatment of deceased donors reduces inflammation in allografts and is recommended by organ procurement guidelines. The impact on long‐term graft outcome, however, remains elusive. In this multicenter randomized controlled trial, 306 deceased donors providing organs for 455 renal transplant recipients were randomized to 1000 mg of methylprednisolone or placebo prior to organ procurement (ISRCTN78828338). The incidence of biopsy‐confirmed rejection (Banff>1) at 3 months was 23 (10%) in the steroid group and 26 (12%) in the placebo group (P = .468). Five‐year functional graft survival was 84% and 82% for the steroid group and placebo group, respectively (P‐value = .941). The hazard ratio of functional graft loss was 0.90 (95% confidence interval 0.57‐1.42, P = .638) for steroid vs placebo in a multivariate Cox model. We did not observe effect modification by any of the predictors of graft survival and treatment modality. A robust sandwich estimate was used to account for paired grafts of some donors. The mean estimated GFR at 5 years was 47 mL/min per 1.73 m2 in the steroid group and 48 mL/min per 1.73 m2 in the placebo group (P = .756). We conclude that steroid pretreatment does not impact on long‐term graft survival. In a donor population with higher risk of delayed graft function, however, repetitive and higher doses of steroid treatment may result in different findings.
‘Absent’ pulmonary valve with intact ventricular septum mimicking tricuspid valve atresia: Prenatal diagnosis and postnatal course

Absent pulmonary valve syndrome is a rare congenital heart disease characterized by absent or rudimentary pulmonary valve leaflets and hypoplastic pulmonary annulus. The most common variant, associated with tetralogy of Fallot, implies dilatation of pulmonary branches and usually absent ductus arteriosus. Rarely, absent pulmonary valve occurs with intact ventricular septum: pulmonary branches are normally sized or mildly dilated and ductus arteriosus is usually patent. The rarest type is associated with intact ventricular septum and tricuspid atresia. A close connection has been raised between pulmonary regurgitation and development of tricuspid valve. We describe a case of prenatal diagnosed absent pulmonary valve with intact ventricular septum and patent ductus arteriosus in which severe pulmonary regurgitation caused reversible functional atresia of tricuspid valve. Postnatally, satisfactory biventricular circulation was obtained with inotropic support for a few days while ductus arteriosus closed spontaneously. At a 3‐year follow up the child is asymptomatic without therapy.
Effects of medial collateral ligament release, limb correction, and soft tissue laxity on knee joint contact force distribution after medial opening wedge high tibial osteotomy: a computational study

Abstract In this study, the effects of medial collateral ligament (MCL) release and the limb correction strategies with pre-existing MCL laxity on tibiofemoral contact force distribution after high tibial osteotomy (HTO) were investigated. The medial and lateral contact forces of the knee were quantified during simulated standing using computational modeling techniques. MCL slackness had a primary influence on contact force distribution of the knee, while there was little effect of simulated limb correction. Anterior and middle bundle release, which involved the partial release of two-thirds of the superficial MCL, was shown to be an optimal surgical method in HTO, achieving balanced contact distribution in simulated weight-bearing standing.
Mitotic Cell Division in Caenorhabditis elegans

Mitotic cell divisions increase cell number while faithfully distributing the replicated genome at each division. The Caenorhabditis elegans embryo is a powerful model for eukaryotic cell division. Nearly all of the genes that regulate cell division in C. elegans are conserved across metazoan species, including humans. The C. elegans pathways tend to be streamlined, facilitating dissection of the more redundant human pathways. Here, we summarize the virtues of C. elegans as a model system and review our current understanding of centriole duplication, the acquisition of pericentriolar material by centrioles to form centrosomes, the assembly of kinetochores and the mitotic spindle, chromosome segregation, and cytokinesis.
Sweet and Umami Taste Perception Differs with Habitual Exercise in Males

Taste is influenced by several factors. However, whether habitual exercise level is associated with differences in taste perception has received little investigation. The aim of this study was to determine if habitual exercise is associated with differences in taste perception in men. Active (n = 16) and inactive (n = 14) males, between ages 18–55, underwent two days of sensory testing, using prototypical taste stimuli of high and low concentrations for sweet, salt, bitter, sour, umami, and carbohydrate (maltodextrin). Mean perceived intensity and hedonic ratings were recorded. Eating behaviour was assessed by the three factor eating questionnaire and food intake by EPIC food frequency questionnaire (FFQ). There were moderate to large differences between the two groups in perceived intensity for sweet taste at the high concentration and umami taste at both high and low concentrations, with active males recording a higher perceived intensity (p < 0.05 for all). The active group also recorded a greater dislike for umami low and carbohydrate low concentration (p < 0.01). Salt, bitter and sour perception did not significantly differ between the two groups. FFQ analysis showed no difference in % energy from macronutrients between the groups. Eating behaviour traits correlated with sweet taste intensity and umami taste liking, independent of activity status. Results indicated that sweet and umami taste perception differ in active compared to inactive males. Habitual exercise level should be considered in taste perception research and in product development. Whether differences in taste perception could be one factor influencing food intake and thus energy balance with habitual exercise warrants further investigation.
Numerical Study and Optimization of a Novel Piezoelectric Transducer for a Round-Window Stimulating Type Middle-Ear Implant

Round window (RW) stimulation is a new application of middle ear implants for treating hearing loss, especially for those with middle ear disease. However, most reports on it are based on the use of the floating mass transducer (FMT), which was not originally designed for round window stimulation. The mismatch of the FMT’s diameter and the round window membrane’s diameter and the uncontrollable preload of the transducer, leads to a high variability in its clinical outcomes. Accordingly, a new piezoelectric transducer for the round-window-stimulating-type middle ear implant is proposed in this paper. The transducer consists of a piezoelectric stack, a flextensional amplifier, a coupling rod, a salver, a plate, a titanium housing and a supporting spring. Based on a constructed coupling finite element model of the human ear and the transducer, the influences of the transducer design parameters on its performance were analyzed. The optimal structure of the supporting spring, which determines the transducer’s resonance frequency, was ascertained. The results demonstrate that our designed transducer generates better output than the FMT, especially at low frequency. Besides this, the power consumption of the transducer was significantly decreased compared with a recently reported RW-stimulating piezoelectric transducer.
Use of Lipid Nanocarriers to Improve Oral Delivery of Vitamins

The chemical environment and enzymes in the gastrointestinal (GI) membrane limit the oral absorption of some vitamins. The GI epithelium also contributes to the poor permeability of numerous antioxidant agents. Thus, lipophilic vitamins do not readily dissolve in the GI tract, and therefore they have low bioavailability. Nanomedicine has the potential to improve the delivery efficiency of oral vitamins. In particular, the use of lipid nanocarriers for certain vitamins that are administered orally can provide improved solubility, chemical stability, epithelium permeability and bioavailability, half-life, nidus targeting, and fewer adverse effects. These lipid nanocarriers include self-emulsifying drug delivery systems (SEDDSs), nanoemulsions, microemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). The use of nontoxic excipients and sophisticated material engineering of lipid nanosystems allows for control of the physicochemical properties of the nanoparticles and improved GI permeation via mucosal or lymphatic transport. In this review, we highlight recent progress in the development of lipid nanocarriers for vitamin delivery. In addition, the same lipid nanocarriers used for vitamins may also be effective as carriers of vitamin derivatives, and therefore enhance their oral bioavailability. One example is the incorporation of d-α-tocopheryl polyethylene glycol succinate (TPGS) as the emulsifier in lipid nanocarriers to increase the solubility and inhibit P-glycoprotein (P-gp) efflux. We also survey the concepts and discuss the mechanisms of nanomedical techniques that are used to develop vitamin-loaded nanocarriers.
Bildgebung in der Kornea mittels optischer Kohärenztomografie – historische Entwicklung und neueste technische Fortschritte

Zusammenfassung Die optische Kohärenztomografie (OCT) hat seit ihrer Einführung für die retinale Bildgebung in den 90er-Jahren eine rasante Entwicklung genommen und die Ophthalmologie revolutioniert. Während sie zu Beginn nur zur Untersuchung der Retina zum Einsatz kam, wurden in der Zwischenzeit auch zahlreiche Systeme zur Beurteilung des vorderen Augenabschnitts entwickelt. Basierend auf der Detektion und Verarbeitung des vom Gewebe zurückreflektierten und gestreuten Lichts, eröffnete sie dem Ophthalmologen völlig neue Möglichkeiten zur Untersuchung der Strukturen des vorderen Augenabschnitts. Je nach technischer Umsetzung erlauben OCT-Systeme für den vorderen Augenabschnitt die präzise Vermessung einzelner Schichten der Kornea und des Kammerwinkels oder – in Form von ultrahoch auflösender OCT – die detailreiche Darstellung der Hornhautmorphologie mit nahezu histologischer Auflösung. Letztere könnte durch weitere technische Entwicklungen vor allem hinsichtlich der Erhöhung der Aufnahmegeschwindigkeit zu einem wesentlichen Werkzeug in der Differenzialdiagnose und Verlaufsbeobachtung verschiedenster Erkrankungen der Hornhaut werden, das auch neue Einsichten in die Pathophysiologie dieser Erkrankungen liefert.
Dynamic adaptive X-ray optics. Part II. High-speed piezoelectric bimorph deformable Kirkpatrick–Baez mirrors for rapid variation of the 2D size and shape of X-ray beams

Demonstrated here is the first simultaneous high-speed beamline operation of a pair of piezoelectric bimorph deformable Kirkpatrick–Baez mirrors for the rapid and repeatable change and stabilization of the vertical and horizontal size of a synchrotron X-ray beam within only a few seconds. This enables continuous adaptive shaping of the X-ray beam in almost real time. Such innovations could lead to a major scientific change in how deformable X-ray mirrors are used at synchrotron and X-ray free-electron laser sources.
Real-time control of reactive ion etching using neural networks

Consistent demands on semiconductor manufacturers to produce circuits with increased-density and complexity have made stringent process control an issue of growing importance in the industry. Recent work has shown that neural networks offer great promise in modeling complex fabrication processes such as reactive ion etching (RIE). Motivated by these results, this paper explores the use of neural networks for real-time, model-based feedback control of RIE. This objective is accomplished in part by constructing a predictive model for the system; which can be inverted (or approximately inverted) to achieve the desired control. The efficacy of this approach can be demonstrated using experimental data from an actual RIE process to examine real-time control of critical process responses such as etch rate, uniformity, selectivity, and anisotropy.
The Function and Regulatory Network of Pax9 Gene in Palate Development

Cleft palate, a common congenital deformity, can arise from disruptions in any stage of palatogenesis, including palatal shelf growth, elevation, adhesion, and fusion. Paired box gene 9 (Pax9) is recognized as a vital regulator of palatogenesis with great relevance to cleft palate in humans and mice. Pax9-deficient murine palatal shelves displayed deficient elongation, postponed elevation, failed contact, and fusion. Pax9 is expressed in epithelium and mesenchyme, exhibiting a dynamic expression pattern that changes according to the proceeding of palatogenesis. Recent studies highlighted the Pax9-related genetic interactions and their critical roles during palatogenesis. During palate growth, PAX9 interacts with numerous molecules and members of pathways (e.g., OSR2, FGF10, SHOS2, MSX1, BARX1, TGFβ3, LDB1, BMP, WNT β-catenin dependent, and EDA) in the mesenchyme and functions as a key mediator in epithelial-mesenchymal communications with FGF8, TBX1, and the SHH pathway. During palate elevation, PAX9 is hypothesized to mediate the time point of the elevation event in the anterior and posterior parts of the palatal shelves. The delayed elevation of Pax9 mutant palatal shelves probably results from abnormal expressions of a series of genes (Osr2 and Bmpr1a) leading to deficient palate growth, abnormal tongue morphology, and altered hyaluronic acid distribution. The interactions between PAX9 and genes encoding the OSR2, TGFβ3, and WNT β-catenin-dependent pathways provide evidence that PAX9 might participate in the regulation of palate fusion. This review summarizes the current understanding of PAX9’s functions and emphasizes the interactions between PAX9 and vital genes during palatogenesis. We hope to provide some clues for further exploration of the function and mechanism of PAX9, especially during palate elevation and fusion events.
DETERMINING THE EFFECT OF DIABETES DURATION ON RETINAL AND CHOROIDAL THICKNESSES IN CHILDREN WITH TYPE 1 DIABETES MELLITUS.

PURPOSE Determining the effect of diabetes mellitus duration on retinal and choroidal thicknesses in children with Type 1 diabetes mellitus (T1DM). METHODS Children (aged 6-18 years) with Type 1 diabetes and no diabetic retinopathy and age-matched controls were examined using Topcon spectral domain optical coherence tomography. Choroidal thickness and retinal thickness in macula area were measured. The study group was divided into 3 subgroups depending on diabetes mellitus duration-Group 1: <5 years (n = 52), Group 2: 5 to 10 years (n = 39), and Group 3: >10 years (n = 30). RESULTS One hundred and twenty-one diabetic children and 32 controls were included. The central choroidal thickness increased from 305.5 μm (SD: 61.7 μm) in the control group to 309.2 μm (SD: 70.1 μm) in Group 1, 315.2 μm (SD: 64.3 μm) in Group 2, and 367.4 μm (SD: 66.0 μm) in Group 3. Group 3 differed significantly from Group 1 (P = 0.0002), Group 2 (P = 0.0014), and the control group (P = 0.0003). The choroid-to-retina thickness ratio was lowest in controls, 1.01 (SD: 0.17), and highest in Group 3, 1.21 (SD: 0.2). Group 3 differed significantly from Group 1, Group 2, and the control group with P = 0.0002, P = 0.0014, and P = 0.0001, respectively. No retina thickening was found. CONCLUSION Changes in the choroid may occur before the development of diabetic retinopathy and seem to progress with increasing diabetes mellitus duration despite the absence of diabetic retinopathy and without associated retina thickening. Choroidal thickness could be valuable for screening in diabetic children.
Bisubstrate inhibitors to target histone acetyltransferase 1

Developing selective enzyme inhibitors allows for the expansion of molecular toolboxes to investigate functions and activities of target enzymes. The histone acetyltransferase 1 (HAT1) is among the first histone acetyltransferase (HAT) enzymes that were discovered in the mid‐1990s; however, it remains one of the poorly studied enzymes in comparison with the other HATs. Although HAT1 has been linked to various disease states, no inhibitors have been reported to target HAT1. Here, we designed a set of peptide‐CoA conjugates as bisubstrate inhibitors of HAT1 with submicromolar potency. In particular, the bisubstrate inhibitor H4K12CoA exhibited a low Ki value of 1.1 nM for HAT1. In addition, H4K12CoA was shown to be a competitive inhibitor with respect to both AcCoA and H4 peptide, suggesting a unique kinetic mechanism of HAT1 catalysis. Creating these submicromolar inhibitors offers mechanistic tools to better understand how HAT1 recognizes substrates and cofactors, as well as provides chemical leads to further develop therapeutic agents to target this important enzyme for disease therapy.
Statistical force-field for structural modeling using chemical cross-linking/mass spectrometry distance constraints

Motivation Chemical cross-linking/Mass Spectrometry (XLMS) is an experimental method to obtain distance constraints between amino acid residues which can be applied to structural modeling of tertiary and quaternary biomolecular structures. These constraints provide, in principle, only upper limits to the distance between amino acid residues along the surface of the biomolecule. In practice, attempts to use of XLMS constraints for tertiary protein structure determination have not been widely successful. This indicates the need of specifically designed strategies for the representation of these constraints within modeling algorithms. Results A force-field designed to represent XLMS-derived constraints is proposed. The potential energy functions are obtained by computing, in the database of known protein structures, the probability of satisfaction of a topological cross-linking distance as a function of the Euclidean distance between amino acid residues. First, the strategy suggests that XL constraints should be set to shorter distances than usually assumed. Second, the complete statistical force-field improves the models obtained and can be easily incorporated into current modeling methods and software. The force-field was implemented and is distributed to be used within the Rosetta ab initio relax protocol. Availability Force-field parameters and usage instructions are freely available at http://m3g.iqm. unicamp.br/topolink/xlff. Supplementary information Supplementary data are available at Bioinformatics online.