Miracle-dz/UniFAR-FTUs huggingface dataset:
Particle therapy for clinically diagnosed stage I lung cancer: Comparison with pathologically proven non-small cell lung cancer

Abstract Background. The purpose of the present study was to present the treatment outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed as stage I non-small cell lung cancer, including a comparative analysis involving pathologically proven lung cancer (PPLC). Material and methods. A total of 54 patients (57 lesions) who underwent particle therapy for IPNs were enrolled in this study. Median patient age was 76 (range 52–87) years. T-classification was: T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was delivered at total doses of 52.8–80 Gy equivalent in 4–26 fractions. The PPLC cohort included 111 patients. Results. The median follow-up time was 41 (range 7–90) months. For all IPN patients, the three-year overall survival, progression-free survival, local control and distant progression-free survival rates were 90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and neuropathy (2%). No ≥ grade 3 toxicities were observed. In univariate analysis, the IPN group showed significantly better survival relative to the PPLC group. However, after adjustment for baseline imbalances between these two groups in multivariate analysis, pathological confirmation did not correlate with survival. Conclusions. Particle therapy for IPNs provided favorable outcomes with minimal toxicities, which may be comparable to those for PPLC patients. Further studies are needed to clarify the optimal management of IPN patients.
Molecular interaction of cyanidin-3-O-glucoside with ovalbumin: insights from spectroscopic, molecular docking and in vitro digestive studies

Abstract Anthocyanins bound with proteins have influence on the digestibility of proteins. In this study, the interaction between cyanidin-3-O-glucoside (C3G) and ovalbumin (OVA) was investigated through multi-spectroscopy and molecular docking. The interactive effect of C3G on OVA digestibility was estimated by an in vitro digestion model. Fluorescence studies indicated that C3G quenched the fluorescence of OVA in a static mode, where the binding constants (Ka) at 298, 308 and 318 K were above 105 M–1, indicating a strong binding affinity of C3G with OVA. The negative values of thermodynamic parameters (ΔG, ΔH and ΔS) revealed a spontaneous binding process, where hydrogen and van der Waals forces were involved in stabilizing the OVA-C3G complex. The secondary structure of OVA was modified by C3G binding, with augmented β-sheet (21.5%–25.1%) and diminished α-helix (23.3%–21.6%). Besides, C3G substantially inhibited the digestion of OVA in pancreatin solution whereas it had negligible effect on pepsin. Furthermore, molecular docking and cleavage site prediction studies showed that the hydrogen binding sites of C3G are not near to the cleavage sites of pepsin but partially overlap trypsin cleavages sites in OVA, which might lead to an inhibited effect on pancreatic digestion. These results provide a better understanding of the anthocyanin-protein interactions and their effect on the protein digestibility. Communicated by Ramaswamy H. Sarma
Selenoprotein T as a new positive inotrope in the goldfish, Carassius auratus

ABSTRACT Selenoprotein T (SELENOT) is a thioredoxin-like protein, which mediates oxidoreductase functions via its redox active motif Cys-X-X-Sec. In mammals, SELENOT is expressed during ontogenesis and progressively decreases in adult tissues. In the heart, it is re-expressed after ischemia and induces cardioprotection against ischemia–reperfusion (IR) injury. SELENOT is present in teleost fish, including the goldfish Carassius auratus. This study aimed to evaluate the cardiac expression of SELENOT, and the effects of exogenous PSELT (a 43–52 SELENOT-derived peptide) on the heart function of C. auratus, a hypoxia tolerance fish model. We found that SELENOT was expressed in cardiac extracts of juvenile and adult fish, located in the sarcoplasmic reticulum (SR) together with calsequestrin-2. Expression increased under acute hypoxia. On ex vivo isolated and perfused goldfish heart preparations, under normoxia, PSELT dose dependently increased stroke volume (VS), cardiac output and stroke work (SW), involving cAMP, PKA, L-type calcium channels, SERCA2a pumps and pAkt. Under hypoxia, PSELT did not affect myocardial contractility. Only at higher concentrations (10−8 to 10−7 mol l−1) was an increase of VS and observed. It also reduced the cardiac expression of 3-NT, a tissue marker of nitrosative stress, which increases under low oxygen availability. These data are the first to propose SELENOT 43–52 (PSELT) as a cardiac modulator in fish, with a potential protective role under hypoxia. Summary: SELENOT, a thioredoxin-like protein, is proposed as a cardiac modulator in the goldfish Carassius auratus, with a potential role in hypoxia tolerance.
Computer-assisted pedicle screw trajectory planning using CT-inferred bone density: A demonstration against surgical outcomes.

PURPOSE Image-guided spine surgery and preoperative computer-assisted planning provide spine surgeons with tools to improve the safety, accuracy, and reliability of pedicle screw placement. The purpose of this study is to demonstrate a computer-assisted pedicle screw placement planning tool in comparison to screws as delivered by a spine surgeon. METHODS We describe a novel computer-assisted tool for preoperative pedicle screw placement planning in computed tomography (CT) images, designed with respect to the vertebral shape and structure, and augmented with respect to the considerations of surgical practice. The approach is based on three-dimensional (3D) modeling of the vertebral body and pedicles, and planning of the pedicle screw size and insertion trajectory by maximizing the screw fastening strength, evaluated through CT-inferred bone density maps. The approach is augmented by yielding screw plans consistent with the straight-forward surgical technique of aligning screws parallel to vertebral endplates, and the screw entry points following the spinal curvature to facilitate rod attachment. For a cohort of 25 patients, placement plans were retrospectively obtained for 204 pedicle screws with the computer-assisted tool from preoperative CT images, while reference trajectories of inserted pedicle screws were reconstructed in 3D from postoperative biplanar radiographs. RESULTS The best performing version of the computer-assisted tool achieved clinically acceptable preoperative pedicle screw placement plans in 96.6% of the cases, while the comparison to the postoperative reconstructions resulted in 3.4 ± 2.5 mm for the screw entry point location, 2.7 ± 1.6 mm for the screw crossing point location, and 7.4 ± 5.3∘ for the screw sagittal inclination (mean absolute difference ± standard deviation). CONCLUSION Quantitative comparison revealed that the preoperative placement plans are consistent with the postoperative results, and that the computer-assisted tool integrating bone density and surgical constraints can successfully incorporate important aspects of pedicle screw placement. The results therefore confirm the accuracy of the tool prior to being integrated in an image-guidance system.
Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma.

PURPOSE To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL). METHODS Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [(123)I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A. RESULTS The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4). CONCLUSION Although serious toxicity may occur, the survival and response rates achieved with high-dose [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
Are Current Protein Recommendations for the Critically Ill Adequate for Patients on VV ECMO: Experience From a High-Volume Center.

BACKGROUND The nutrition needs of patients requiring extracorporeal membrane oxygenation (ECMO) have not been established in the literature. The purpose of this study is to investigate if current protein recommendations are adequate to achieve nitrogen equilibrium in patients on venovenous ECMO (VV ECMO). METHODS Patients aged ≥18 years on VV ECMO admitted November 2016 through January 2018 with a documented nitrogen balance (NB) study were included. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m2 ) and nonobese (BMI < 30 kg/m2 ) categories for analysis. RESULTS After exclusions, 55 NB studies in 29 patients were analyzed. Twelve nonobese patients received a median of 2.1 g protein/kg actual body weight (ABW) (interquartile range [IQR]: 1.7-2.5), and median NB was -2.2 g/d (IQR: -7.4 to 2.8). In 17 obese patients, median protein delivery of 2 g protein/kg ideal body weight (IBW) (IQR: 1.7-2.5) achieved a median NB of -7.3 g/d (IQR: -12.6 to -2.8). Obese patients exhibited greater urinary urea nitrogen excretion than nonobese patients did (24.6 vs 17.6 g/d, P < 0.0001). CONCLUSIONS Obese and nonobese patients undergoing VV ECMO may require more protein than is currently recommended for critical illness. Monitoring nutrition delivery and serial NB to assess prescription adequacy should be incorporated into routine patient care. Further research is needed to confirm these findings and create specific guidelines for patients on VV ECMO.
Overexpression of tensin homolog deleted on chromosome ten (PTEN) by ciglitazone sensitizes doxorubicin‐resistance leukemia cancer cells to treatment

Overcoming multidrug resistance (MDR) is a final goal of various recent studies, in which combination of different compounds and conventional chemotherapeutics results in circumventing MDR and hence cancer progression. Therefore, we aimed to investigate the effects of peroxisome proliferator‐activated receptors (PPARs)‐γ on MDR in doxorubicin‐resistant human myelogenous leukemia cells. The effect of doxorubicin on cell viability following treatment with ciglitazone was measured using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. The activity of P‐glycoprotein (P‐gp), as one of the membrane transporters, was determined by the rhodamine 123 (Rho 123) assay. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blot were used for the measurement of P‐gp, and tensin homolog deleted on chromosome ten (PTEN) expression at mRNA and protein, respectively. For evaluation of doxorubicin (DOX)‐induced apoptosis by annexin V/PI staining was used. Ciglitazone significantly increases the cytotoxic effects of DOX. In addition, ciglitazone considerably decreased the expression levels and activity of P‐gp in DOX‐resistant K562 cells. Furthermore, upon the ciglitazone treatment, PTEN expression could be increased in K562/DOX cells in a PPARγ–dependent manner. Moreover, ciglitazone significantly enhanced DOX‐induced apoptosis in K562/DOX cells. The combination treatment of K562/DOX leukemia cancer cells with doxorubicin and ciglitazone might be an effective strategy in inducing apoptosis and reversing developed MDR, and more importantly decreasing the adverse side effects of these agents.
A Measurement of the Cosmic Microwave Background Lensing Potential and Power Spectrum from 500 deg2 of SPTpol Temperature and Polarization Data

We present a measurement of the cosmic microwave background lensing potential using 500 deg2 of 150 GHz data from the SPTpol receiver on the South Pole Telescope. The lensing potential is reconstructed with signal-to-noise per mode greater than unity at lensing multipoles L ≲ 250, using a quadratic estimator on a combination of cosmic microwave background temperature and polarization maps. We report measurements of the lensing potential power spectrum in the multipole range of 100 < L < 2000 from sets of temperature-only (T), polarization-only (POL), and minimum-variance (MV) estimators. We measure the lensing amplitude by taking the ratio of the measured spectrum to the expected spectrum from the best-fit Λ cold dark matter model to the Planck 2015 TT + low P + lensing data set. For the minimum-variance estimator, we find A MV = 0.944 ± 0.058 ( Stat . ) ± 0.025 ( Sys . ) ; restricting to only polarization data, we find A POL = 0.906 ± 0.090 ( Stat . ) ± 0.040 ( Sys . ) . Considering statistical uncertainties alone, this is the most precise polarization-only lensing amplitude constraint to date (10.1σ) and is more precise than our temperature-only constraint. We perform null tests and consistency checks and find no evidence for significant contamination.
Myelination key factor krox‐20 is downregulated in Schwann cells and murine sciatic nerves infected by Mycobacterium leprae

Schwann cells (SCs) critically maintain the plasticity of the peripheral nervous system. Peripheral nerve injuries and infections stimulate SCs in order to retrieve homeostasis in neural tissues. Previous studies indicate that Mycobacterium leprae (ML) regulates the expression of key factors related to SC identity, suggesting that alterations in cell phenotype may be involved in the pathogenesis of neural damage in leprosy. To better understand whether ML restricts the plasticity of peripheral nerves, the present study sought to determine the expression of Krox‐20, Sox‐10, c‐Jun and p75NTR in SC culture and mice sciatic nerves, both infected by ML Thai‐53 strain. Primary SC cultures were stimulated with two different multiplicities of infection (MOI 100:1; MOI 50:1) and assessed after 7 and 14 days. Sciatic nerves of nude mice (NU‐Foxn1nu) infected with ML were evaluated after 6 and 9 months. In vitro results demonstrate downregulation of Krox‐20 and Sox‐10 along with the increase in p75NTR‐immunolabelled cells. Concurrently, sciatic nerves of infected mice showed a significant decrease in Krox‐20 and increase in p75NTR. Our results corroborate previous findings on the interference of ML in the expression of factors involved in cell maturation, favouring the maintenance of a non‐myelinating phenotype in SCs, with possible implications for the repair of adult peripheral nerves.
Spectral Clustering of Signed Graphs via Matrix Power Means

Signed graphs encode positive (attractive) and negative (repulsive) relations between nodes. We extend spectral clustering to signed graphs via the one-parameter family of Signed Power Mean Laplacians, defined as the matrix power mean of normalized standard and signless Laplacians of positive and negative edges. We provide a thorough analysis of the proposed approach in the setting of a general Stochastic Block Model that includes models such as the Labeled Stochastic Block Model and the Censored Block Model. We show that in expectation the signed power mean Laplacian captures the ground truth clusters under reasonable settings where state-of-the-art approaches fail. Moreover, we prove that the eigenvalues and eigenvector of the signed power mean Laplacian concentrate around their expectation under reasonable conditions in the general Stochastic Block Model. Extensive experiments on random graphs and real world datasets confirm the theoretically predicted behaviour of the signed power mean Laplacian and show that it compares favourably with state-of-the-art methods.
Game Theoretic Optimization via Gradient-based Nikaido-Isoda Function

Computing Nash equilibrium (NE) of multi-player games has witnessed renewed interest due to recent advances in generative adversarial networks. However, computing equilibrium efficiently is challenging. To this end, we introduce the Gradient-based Nikaido-Isoda (GNI) function which serves: (i) as a merit function, vanishing only at the first-order stationary points of each player's optimization problem, and (ii) provides error bounds to a stationary Nash point. Gradient descent is shown to converge sublinearly to a first-order stationary point of the GNI function. For the particular case of bilinear min-max games and multi-player quadratic games, the GNI function is convex. Hence, the application of gradient descent in this case yields linear convergence to an NE (when one exists). In our numerical experiments, we observe that the GNI formulation always converges to the first-order stationary point of each player's optimization problem.
Cardiovascular autonomic modulation and baroreflex control in the second trimester of pregnancy: A cross sectional study

Purpose The aim is to evaluate and characterize cardiovascular autonomic control and baroreflex function and their response to an orthostatic stressor in the second trimester of pregnancy via time, frequency, information and symbolic analyses. Methods We evaluated 22 women at 18 weeks of pregnancy, labeled as pregnant group (PG) (30.8±4.4 years), and 22 non-pregnant women (29.8±5.4 years), labeled as control group (CG). Electrocardiogram, non-invasive photoplethysmographic arterial pressure (AP) and respiratory signals were recorded at rest at left lateral decubitus (REST) and during active standing (STAND) for 10 minutes. The heart period (HP) variability and systolic AP (SAP) variability were assessed in the frequency domain. High frequency (HF) and low frequency (LF) spectral indexes were computed. Nonlinear indexes such as symbolic markers (0V%, 1V%, 2LV% and 2UV% indexes), Shannon entropy (SE) and normalized complexity index (NCI) were calculated as well. Baroreflex control was assessed by cross-spectral HP-SAP analysis. We computed baroreflex sensitivity (BRS), HP-SAP squared coherence (K2) and phase in LF and HF bands. Results At REST, the PG had lower mean, variance and HF power of HP series and lower K2(LF), BRS(LF) and BRS(HF) than the CG. During STAND, CG and PG decreased the mean, CI, NCI and 2UV% and increased 0V% of the HP series and augmented the SAP variance. LFabs of SAP series increased during STAND solely in CG. BRS(HF) was reduced during in both PG and CG, while HFabs of HP series did not diminish during STAND either in PG or CG. Complexity of the autonomic control was similar in PG and CG regardless of the experimental condition. Conclusion We conclude that the second trimester of pregnancy was characterized by a lower parasympathetic modulation and reduced BRS at REST, preserved complexity of cardiac and vascular controls, limited sympathetic response to STAND and general conservation of the baroreflex responses to posture changes. Trial registration Begistro Brasileiro de Ensaios clínicos, Number: RBR-9s8t88.
On the isometric conjecture of Banach

Let $V$ be a Banach space where for fixed $n$, $1<n<\dim(V)$, all of its $n$-dimensional subspaces are isometric. In 1932, Banach asked if under this hypothesis $V$ is necessarily a Hilbert space. Gromov, in 1967, answered it positively for even $n$ and all $V$. In this paper we give a positive answer for real $V$ and odd $n$ of the form $n=4k+1$, with the possible exception of $n=133. $ Our proof relies on a new characterization of ellipsoids in ${\mathbb{R}}^n$, $n\geq 5$, as the only symmetric convex bodies all of whose linear hyperplane sections are linearly equivalent affine bodies of revolution.
Tunability of the Dual Feedback Genetic Oscillator Modeled by the Asymmetry in Transcription and Translation

Oscillatory gene circuits are ubiquitous to biology and are involved in fundamental processes of cell cycle, circadian rhythms and developmental systems. The synthesis of small, non-natural oscillatory genetic circuits have been increasingly used to test fundamental principles of genetic network dynamics. A recently developed fast, tunable genetic oscillator by Stricker et al. [23] has demonstrated robustness and tunability of oscillatory behavior by combining positive and negative feedback loops. This oscillator combining lacI (negative) and araC (positive) feedback loops, was however modeled using multiple layers of differential equations to capture the molecular complexity of regulation, in order to explain the experimentally measured oscillations. We have developed a reduced model based on delay differential equations (DDEs) of this dual feedback loop oscillator, that reproduces the tunability of oscillator period and amplitude based on the concentration of the two inducers isopropyl β-D-1-thiogalactopyranoside (IPTG) and arabinose. Previous work had predicted a need for an asymmetry in copy numbers of activator (araC) and repressor (lacI) genes encoded on plasmids. We use our reduced model to redesign the network by comparing the effect of asymmetry in gene expression at the level of (a) DNA copy numbers and the rates of (b) mRNA translation and (c) degradation. We find the minimal period of the oscillator 1 ar X iv :1 90 5. 06 30 1v 1 [ qbi o. M N ] 1 5 M ay 2 01 9 is sensitive to DNA copy number asymmetry, but translation rate asymmetry has an identical effect as plasmid copy numbers, while modulating the asymmetry in mRNA degradation can improve the tunability of period of the oscillator, together with increased robustness to replication ‘noise’ and influence of the host cell cycle. Thus, our model predicts experimentally testable principles to redesign a potentially more robust oscillatory genetic network.