Miracle-dz/UniFAR-FTUs huggingface dataset:
Tropism and Pathogenicity of Rickettsiae

Rickettsiae are obligate intracellular parasitic bacteria that cause febrile exanthematous illnesses such as Rocky Mountain spotted fever, Mediterranean spotted fever, epidemic, and murine typhus, etc. Although the vector ranges of each Rickettsia species are rather restricted; i.e., ticks belonging to Arachnida and lice and fleas belonging to Insecta usually act as vectors for spotted fever group (SFG) and typhus group (TG) rickettsiae, respectively, it would be interesting to elucidate the mechanisms controlling the vector tropism of rickettsiae. This review discusses the factors determining the vector tropism of rickettsiae. In brief, the vector tropism of rickettsiae species is basically consistent with their tropism toward cultured tick and insect cells. The mechanisms responsible for rickettsiae pathogenicity are also described. Recently, genomic analyses of rickettsiae have revealed that they possess several genes that are homologous to those affecting the pathogenicity of other bacteria. Analyses comparing the genomes of pathogenic and non-pathogenic strains of rickettsiae have detected many factors that are related to rickettsial pathogenicity. It is also known that a reduction in the rickettsial genome has occurred during the course of its evolution. Interestingly, Rickettsia species with small genomes, such as Rickettsia prowazekii, are more pathogenic to humans than those with larger genomes. This review also examines the growth kinetics of pathogenic and non-pathogenic species of SFG rickettsiae (SFGR) in mammalian cells. The growth of non-pathogenic species is restricted in these cells, which is mediated, at least in part, by autophagy. The superinfection of non-pathogenic rickettsiae-infected cells with pathogenic rickettsiae results in an elevated yield of the non-pathogenic rickettsiae and the growth of the pathogenic rickettsiae. Autophagy is restricted in these cells. These results are discussed in this review.
Nodal signaling regulates specification of ascidian peripheral neurons through control of the BMP signal

The neural crest and neurogenic placodes are thought to be a vertebrate innovation that gives rise to much of the peripheral nervous system (PNS). Despite their importance for understanding chordate evolution and vertebrate origins, little is known about the evolutionary origin of these structures. Here, we investigated the mechanisms underlying the development of ascidian trunk epidermal sensory neurons (ESNs), which are thought to function as mechanosensory neurons in the rostral-dorsal trunk epidermis. We found that trunk ESNs are derived from the anterior and lateral neural plate border, as is the case in the vertebrate PNS. Pharmacological experiments indicated that intermediate levels of bone morphogenetic protein (BMP) signal induce formation of ESNs from anterior ectodermal cells. Gene knockdown experiments demonstrated that HrBMPa (60A-subclass BMP) and HrBMPb (dpp-subclass BMP) act to induce trunk ESNs at the tailbud stage and that anterior trunk ESN specification requires Chordin-mediated antagonism of the BMP signal, but posterior trunk ESN specification does not. We also found that Nodal functions as a neural plate border inducer in ascidians. Nodal signaling regulates expression of HrBMPs and HrChordin in the lateral neural plate, and consequently specifies trunk ESNs. Collectively, these findings show that BMP signaling that is regulated spatiotemporally by Nodal signaling is required for trunk ESN specification, which clearly differs from the BMP gradient model proposed for vertebrate neural induction.
Entropy of Entropy: Measurement of Dynamical Complexity for Biological Systems

Healthy systems exhibit complex dynamics on the changing of information embedded in physiologic signals on multiple time scales that can be quantified by employing multiscale entropy (MSE) analysis. Here, we propose a measure of complexity, called entropy of entropy (EoE) analysis. The analysis combines the features of MSE and an alternate measure of information, called superinformation, useful for DNA sequences. In this work, we apply the hybrid analysis to the cardiac interbeat interval time series. We find that the EoE value is significantly higher for the healthy than the pathologic groups. Particularly, short time series of 70 heart beats is sufficient for EoE analysis with an accuracy of 81% and longer series of 500 beats results in an accuracy of 90%. In addition, the EoE versus Shannon entropy plot of heart rate time series exhibits an inverted U relationship with the maximal EoE value appearing in the middle of extreme order and disorder.
Autosomal Dominant Polycystic Kidney Disease: New Treatment Options and How to Test Their Efficacy

Autosomal dominant polycystic kidney disease (ADPKD) represents a slowly progressing cystic kidney disorder which evolves into end-stage renal disease in the majority of patients. Currently, there are no established treatments to retard the progression of the disease, but several promising therapeutic options are being tested in ongoing clinical trials. An inherent dilemma for the investigation of therapies in ADPKD is the dissociation of the early onset and constant rate of cyst growth from the delayed but accelerated loss of renal function. In order to prevent the latter, one needs to act on the former, i.e. current belief by experts in the field is that (1) retardation of cyst growth will ultimately improve the loss of glomerular filtration rate, and (2) cyst volume is an ideal surrogate parameter for outcome in early ADPKD. The present review will discuss the utility and the techniques for kidney and cyst volume measurements to assess disease progression in ADPKD, and summarizes ongoing clinical trials testing novel therapeutic options.
Fibromuscular dysplasia.

Most often it affects the renal and internal carotid artery (ICA), although any artery can be involved. Internal carotid arteries are affected in 25-30% of patients. When carotid arteries are involved, cervical segments C1-C2 are most often affected. Intracranial aneurysms often occur in patients with fibromuscular dysplasia of the cephalic arterial system, their frequency being as high as 51%. FMD has been associated with intracranial aneurysms in 7-50% cases, but FMD associated with a giant (> 2.5 cm) intracranial aneurysm is rare. Extracranial internal carotid aneurysms are uncommon, with only 3% caused by FMD .
Radiation countermeasure agents: an update (2011 – 2014)

Introduction: Despite significant scientific advances over the past 60 years towards the development of a safe, nontoxic and effective radiation countermeasure for the acute radiation syndrome (ARS), no drug has been approved by the US FDA. A radiation countermeasure to protect the population at large from the effects of lethal radiation exposure remains a significant unmet medical need of the US citizenry and, thus, has been recognized as a high priority area by the government. Area covered: This article reviews relevant publications and patents for recent developments and progress for potential ARS treatments in the area of radiation countermeasures. Emphasis is placed on the advanced development of existing agents since 2011 and new agents identified as radiation countermeasure for ARS during this period. Expert opinion: A number of promising radiation countermeasures are currently under development, seven of which have received US FDA investigational new drug status for clinical investigation. Four of these agents, CBLB502, Ex-RAD, HemaMax and OrbeShield, are progressing with large animal studies and clinical trials. G-CSF has high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the US FDA in the future.
Role of Environmental Conditions in the Habitat Segregation of Two Abundant Vascular Epiphytes in a Warm-Temperate Forest

The relationship between vertical stratification of vascular epiphytes on host trees and epiphyte ecophysiological strategy was examined. We compared the relative growth rate (RGR) of two epiphytic ferns, Lemmaphyllum microphyllum and Lepisorus thunbergianus, which grow at different canopy positions in warm-temperate forests. The experiment was conducted under two different light and water conditions. In L. thunbergianus, the RGR of the leaves and roots were high under high-light conditions, while the mean RGR of the leaves was <0 under low-light conditions. In L. microphyllum, the RGR of the leaves was high under high-light conditions. Differences in the water supply did not have significant effects on epiphyte growth. However, L. microphyllum showed faster growth than that by L. thunbergianus under increased water and light conditions. Different responses of the two epiphyte species to light and water conditions corresponded approximately to their growing position on host trees. The positive influence of high-light conditions and negative influence of low-light conditions on the growth of L. thunbergianus demonstrate the importance of light conditions for the growth and survival of the species, which inhabits a relatively bright zone (upper canopy). On the other hand, high growth rate of L. microphyllum, which is found at regions ranging from the bottom of the stems to the basal part of the canopy, with increased light and water conditions indicates the importance of the two conditions for the growth and survival of the species.
Predicting persistence or withdrawal in female handballers with social exchange theory

Two complementary studies were conducted to explain the dropout phenomenon with French female handball players, utilizing the tenets of social exchange theory (Thibaut & Kelley, 1959; Rusbult, 1980). In the first study, the aim was to more fully explore the sources of enjoyment by emphasizing the key variables in the costs/benefits analysis. We postulate that the costs/benefits analysis consists in each athlete estimating the probability of reaching the most desired consequences for him or her (e.g., learn and improve skill, affiliation with others, be better than the others). The subjects were 488 French women aged from 15-19 years. Structural equation modeling (SEM) revealed that enjoyment in handball was predicted by a latent variable (named perceived benefits) subjacent to perceptions of competence, autonomy, relatedness, progress, coach's support, and time of play. In the second study, we tested a sport commitment model based on the social exchange postulates, using SEM analyses and a prospective des.
Classification Comparison of Prediction of Solvent Accessibility From Protein Sequences

The prediction of residue solvent accessibility from protein sequences has been studied by various methods. The direct comparison of these methods is impossible due to the variety of datasets used and the difference in structure definition. In this paper we choose 5 classification approaches (decision tree (DT), Support Vector Machine (SVM), Bayesian Statistics (BS), Neural Network (NN) and Multiple Linear Regression (MLR)) for predicting solvent accessibility based on the same dataset and using the same structure definition so that we can directly compare different methods. We evaluate these methods in a cross-validation test on 2148 unique proteins using single sequences and multiple sequences approaches with a cutoff of 20% for two-state definition of solvent accessibility. According to the experiment results, SVM and NN are both the best predictors with accuracy 79%, correlation coefficient 0.59, 2~4% superior to other three methods on multiple sequences prediction. A further test result on a blind test set from Critical Assessment of Techniques for Protein Structure Prediction experiment (CASP5) is consistent with this result. On single sequence prediction, DT, BS and MLR perform about the same at 71~72% with correlation coefficient 0.43. The improvement over the baseline model that use only the identity of target residue is small. Local sequence seems embed very little information on accessibility. Separate training according to protein size improves the prediction when there are sufficiently large dataset available. The consensus prediction combining the 5 approaches is not significantly better than the best single method.
Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect

Purpose Autosomal dominant optic atrophy (ADOA, OMIM 165500), an inherited optic neuropathy that leads to retinal ganglion cell degeneration and reduced visual acuity during the early decades of life, is mainly associated with mutations in the OPA1 gene. Here we report a novel ADOA phenotype associated with a new pathogenic OPA1 gene mutation. Methods The patient, a 62-year-old woman, was referred for acute, painless, and severe visual loss in her right eye. Acute visual loss in her left eye occurred a year after initial presentation. MRI confirmed the diagnosis of isolated atrophic bilateral optic neuropathy. We performed DNA sequencing of the entire coding sequence and the exon/intron junctions of the OPA1 gene, and we searched for the mitochondrial DNA mutations responsible for Leber hereditary optic atrophy by sequencing entirely mitochondrial DNA. Mitochondrial respiratory chain complex activity and mitochondrial morphology were investigated in skin fibroblasts from the patient and controls. Results We identified a novel heterozygous missense mutation (c.2794C>T) in exon 27 of the OPA1 gene, resulting in an amino acid change (p.R932C) in the protein. This mutation, which affects a highly conserved amino acids, has not been previously reported, and was absent in 400 control chromosomes. Mitochondrial DNA sequence analysis did not reveal any mutation associated with Leber hereditary optic neuropathy or any pathogenic mutations. The investigation of skin fibroblasts from the patient revealed a coupling defect of oxidative phosphorylation and a larger proportion of short mitochondria than in controls. Conclusions The presence of an OPA1 mutation indicates that this sporadic, late-onset acute case of optic neuropathy is related to ADOA and to a mitochondrial energetic defect. This suggests that the mutational screening of the OPA1 gene would be justified in atypical cases of optic nerve atrophy with no evident cause.
Large and moderate deviations for matching problems and empirical discrepancies

We study the two-sample matching problem and its connections with the Monge-Kantorovich problem of optimal transportation of mass. We exploit this connection to obtain moderate and large deviation principles. For the classical problem on the unit square we present a conjecture which, if true, yields an explicit formula for the rate function.
Shape representation and classification using the Poisson equation

Silhouettes contain rich information about the shape of objects that can be used for recognition and classification. We present a novel approach that allows us to reliably compute many useful properties of a silhouette. Our approach assigns for every internal point of the silhouette a value reflecting the mean time required for a random walk beginning at the point to hit the boundaries. This function can be computed by solving Poisson's equation, with the silhouette contours providing boundary conditions. We show how this function can be used to reliably extract various shape properties including part structure and rough skeleton, local orientation and aspect ratio of different parts, and convex and concave sections of the boundaries. In addition to this we discuss properties of the solution and show how to efficiently compute this solution using multi-grid algorithms. We demonstrate the utility of the extracted properties by using them for shape classification.
Short-term couplings of the cardiovascular system in pregnant women suffering from pre-eclampsia

Pre-eclampsia (PE), a serious pregnancy-specific disorder, causes significant neonatal and maternal morbidity and mortality. Recent studies showed that cardiovascular variability parameters as well as the baroreflex sensitivity remarkably improve its early diagnosis. For a better understanding of the dynamical changes caused by PE, in this study the coupling between respiration, systolic and diastolic blood pressure, and heart rate is investigated. Thirteen datasets of healthy pregnant women and 10 of subjects suffering from PE are included. Nonlinear additive autoregressive models with external input are used for a model-based coupling analysis following the idea of Granger causality. To overcome the problem of misdetections of standard methods in systems with a dominant driver, a heuristic ensemble approach is used here. A coupling is assumed to be real when existent in more than 80 per cent of the ensemble members, and otherwise denoted as artefacts. As the main result, we found that the coupling structure between heart rate, systolic blood pressure, diastolic blood pressure and respiration for healthy subjects and PE patients is the same and reliable. As a pathological mechanism, however, a significant increased respiratory influence on the diastolic blood pressure could be found for PE patients (p=0.003). Moreover, the nonlinear form of the respiratory influence on the heart rate is significantly different between the two groups (p=0.002). Interestingly, the influence of systolic blood pressure on the heart rate is not selected, which indicates that the baroreflex sensitivity estimation strongly demands the consideration of causal relationships between heart rate, blood pressure and respiration. Finally, our results point to a potential role of respiration for understanding the pathogenesis of PE.
Outcome after resection and radiofrequency ablation of liver metastases from small intestinal neuroendocrine tumours

In patients with small intestinal neuroendocrine tumour (SI‐NET), liver resection or radiofrequency ablation (RFA) of liver metastases is performed for palliation of carcinoid syndrome, and in an effort to improve survival. Data are generally reported from case series, and no randomized trials have studied these treatments. The aim was to compare outcome after liver resection and/or RFA with that of non‐surgical treatment in patients with liver metastases from SI‐NET.
Phenoxyl Free Radical Formation during the Oxidation of the Fluorescent Dye 2′,7′-Dichlorofluorescein by Horseradish Peroxidase

The oxidation of the fluorescent dye 2′,7′-dichlorofluorescein (DCF) by horseradish peroxidase was investigated by optical absorption, electron spin resonance (ESR), and oxygen consumption measurements. Spectrophotometric measurements showed that DCF could be oxidized either by horseradish peroxidase-compound I or -compound II with the obligate generation of the DCF phenoxyl radical (DCF⋅). This one-electron oxidation was confirmed by ESR spin-trapping experiments. DCF⋅ oxidizes GSH, generating the glutathione thiyl radical (GS⋅), which was detected by the ESR spin-trapping technique. In this case, oxygen was consumed by a sequence of reactions initiated by the GS⋅ radical. Similarly, DCF⋅ oxidized NADH, generating the NAD⋅ radical that reduced oxygen to superoxide (O⨪2), which was also detected by the ESR spin-trapping technique. Superoxide dismutated to generate H2O2, which reacted with horseradish peroxidase, setting up an enzymatic chain reaction leading to H2O2 production and oxygen consumption. In contrast, when ascorbic acid reduced the DCF phenoxyl radical back to its parent molecule, it formed the unreactive ascorbate anion radical. Clearly, DCF catalytically stimulates the formation of reactive oxygen species in a manner that is dependent on and affected by various biochemical reducing agents. This study, together with our earlier studies, demonstrates that DCFH cannot be used conclusively to measure superoxide or hydrogen peroxide formation in cells undergoing oxidative stress.
Toward a Digital Twin: Combining Sensing, Machine Learning, and Data Visualization for the Effective Management of a Coastal Lagoon Environment

Coastal lagoons serve as highly productive ecosystems, delivering essential ecosystem services contributing to human welfare and well-being. Unfortunately, these intricate systems are particularly vulnerable to climatic and anthropogenic pressures, such as intensive agriculture and extensive urbanization. This paper presents a Digital Twin prototype of the Mar Menor lagoon in Spain, that utilizes environmental data collected from sensors and predicted data generated through machine learning algorithms. It covers the prototype's architecture, the corresponding API layer designed for interoperability with other systems, and its data visualization dashboard aimed at enhancing decision-making processes.
The Inverses of Block Hankel and Block Toeplitz Matrices

A set of new formulae for the inverse of a block Hankel (or block Toeplitz) matrix is given. The formulae are expressed in terms of certain matrix Pade forms, which approximate a matrix power series associated with the block Hankel matrix.By using Frobenius-type identities between certain matrix Pade forms, the inversion formulae are shown to generalize the formulae of Gohberg–Heinig and, in the scalar case, the formulae of Gohberg–Semencul and Gohberg–Krupnik.The new formulae have the significant advantage of requiring only that the block Hankel matrix itself be nonsingular. The other formulae require, in addition, that certain submatrices be nonsingular.Since effective algorithms for computing the required matrix Pade forms are available, the formulae are practical. Indeed, some of the algorithms allow for the efficient calculation of the inverse not only of the given block Hankel matrix, but also of any nonsingular block principal minor.
Improving Quality Measurement for Anticoagulation: Adding International Normalized Ratio Variability to Percent Time in Therapeutic Range

Background—Among patients receiving warfarin, percent time in therapeutic range (TTR) and international normalized ratio (INR) variability predict adverse events individually. Here, we examined what is added to the prediction of adverse events by using both measures together. Methods and Results—We included 40 404 patients anticoagulated for atrial fibrillation, aged 65+, within the Veterans Health Administration. TTR and log-transformed INR variability were calculated for each patient. Our study outcomes were ischemic stroke and major bleeding, defined using International Classification of Diseases-9 codes. We estimated the hazard ratios (HRs) for the study outcomes using 3 nested Cox regression models, including (1) TTR or log INR variability separately; (2) TTR and log INR variability together; and (3) both predictors together plus an interaction term. We divided TTR into 3 categories (high, >70%; moderate, 50% to 70%; low, <50%) and log INR variability into 2 categories (stable and unstable). The reference groups high TTR and stable anticoagulation each denote good control.Higher log INR variability (ie, unstable control) predicted ischemic stroke (HR=1.45, P<0.001) and major bleeding (HR=1.57, P<0.001) independently, regardless of TTR levels. Our model with interaction terms showed that High log INR variability predicted a significantly higher risk for ischemic stroke and major bleeding compared with low log INR variability, at moderate TTR levels (HR= 1.27 and HR=1.29, respectively) and at high TTR levels (HR=1.55 and HR=1.56, respectively), but not at low TTR levels. Conclusions—Unstable anticoagulation predicts warfarin adverse effects independent of TTR. Moreover, knowledge about anticoagulation stability further stratifies the risk for adverse events at given levels of TTR.