Miracle-dz/UniFAR-FTUs huggingface dataset:
Brentuximab vedotin as a bridge to allogeneic stem-cell transplantation for refractory or relapsing patients with CD30 positive anaplastic or T-cell non-Hodgkin lymphomas: a study on behalf of the SFGM-TC

Sylvain Garciaz, Mickael Loschi, Ad ele De Masson, Lucie Biard, M elanie Mercier, C ecile Tomowiak, Jeremy Delage, H el ene Labussiere-Wallet, David Sibon, Oph elie Cassuto, C ecile Borel, J erome Cornillon, Stanislas Nimubona, Amandine Charbonnier, Pauline Brice, G erard Soci e, Reda Bouabdallah, R egis Peffault de Latour and Flore Sicre de Fontbrune Department of Hematology, Institut Paoli-Calmettes, Marseille, France; Hematology service, Centre Hospitalier Universitaire, Nice, France; Dermatology service, INSERM U976, Hôpital Saint Louis APHP, Paris, France; Biostatistics and medical information unit, INSERM U1153 ECSTRA team Hôpital Saint-Louis, Paris, France; Hematology service, CHU Angers, Angers, France; Oncohematology and cellular therapy service, CHU Poitiers, Poitiers, France; Hematology service, CHU Lapeyronie, Montpellier, France; Hematology service, Centre Hospitalier Lyon Sud Hospices Civiles de Lyon, Lyon, France; Hematology service, Hôpital Necker, APHP, Paris, France; Hematology service, CHU Purpan, Toulouse, France; Hematology service, Institut de canc erologie Lucien Neuwirth, Saint-Etienne, France; Hematology service, CHU Rennes, Rennes, France; Hematology service, CHU Amiens Sud, Amiens, France; Hemato-oncology service, Hôpital Saint-Louis, Paris, France; Hematology and stem-cell transplantation unit, Hôpital Saint-Louis, Universit e Paris Diderot, Paris, France
On-Line Monitoring of Pipe Wall Thinning by a High Temperature Ultrasonic Waveguide System at the Flow Accelerated Corrosion Proof Facility

Pipe wall thinning and leakage due to flow accelerated corrosion (FAC) are important safety concerns for nuclear power plants. A shear horizontal ultrasonic pitch/catch technique was developed for the accurate monitoring of the pipe wall-thickness. A solid couplant should be used to ensure high quality ultrasonic signals for a long operation time at an elevated temperature. We developed a high temperature ultrasonic thickness monitoring method using a pair of shear horizontal transducers and waveguide strips. A computer program for on-line monitoring of the pipe thickness at high temperature was also developed. Both a conventional buffer rod pulse-echo type and a developed shear horizontal ultrasonic waveguide type for a high temperature thickness monitoring system were successfully installed to test a section of the FAC proof test facility. The overall measurement error was estimated as ±15 μm during a cycle ranging from room temperature to 150 °C. The developed waveguide system was stable for about 3300 h and sensitive to changes in the internal flow velocity. This system can be used for high temperature thickness monitoring in all industries as well as nuclear power plants.
Predicting responsiveness to a sustained reading and spelling intervention in children with dyslexia

The present study aimed to predict responsiveness to a sustained two‐phase reading and spelling intervention with a focus on declarative and procedural learning respectively in 122 second‐grade Dutch children with dyslexia. We related their responsiveness to intervention to precursor measures (phonological awareness, rapid automatized naming ability, letter knowledge, and verbal working memory) and related word and pseudoword reading and spelling outcomes of the sustained intervention to initial reading and spelling abilities, and first‐phase, initial treatment success. Results showed that children with dyslexia improved in reading accuracy and efficiency and in spelling skills during the two phases of the intervention although the gap with typical readers increased. In reading efficiency, rapid automatized naming, and in reading and spelling accuracy phoneme deletion predicted children's responsiveness to intervention. Additionally, children's initial reading abilities at the start of the intervention directly (and indirectly, via initial treatment success, in reading efficiency) predicted posttest outcomes. Responsiveness to intervention in spelling was predicted by phoneme deletion, and spelling at posttest was indirectly, via initial treatment success, predicted by children's initial spelling abilities. Finally, children's initial treatment success directly predicted reading efficiency and spelling outcomes at posttest.
Pharmacokinetics of salvianolic acid B, rosmarinic acid and Danshensu in rat after pulmonary administration of Salvia miltiorrhiza polyphenolic acid solution.

A sensitive and accurate LC-MS/MS method was established for quantifying salvianolic acid B (Sal B), rosmarinic acid (Ros A) and Danshensu (DA) in rat plasma. Salvia miltiorrhiza polyphenolic acid (SMPA), active water-soluble ingredients isolated and purified from Salvia miltiorrhiza Bge included Sal B, Ros A and DA. The pharmacokinetic analysis of Sal B, Ros A and DA after pulmonary administration of SMPA solution to rat was performed by LC-MS/MS. Results from the pharmacokinetic studies showed that the peak concentration of DA was 21.85 ± 6.43 and 65.39 ± 3.83 ng/mL after pulmonary and intravenous administration, respectively. DA was not detected at 2 h after administration. The absolute bioavailabilities of Sal B and Ros A were respectively 50.37 ± 27.04 and 89.63 ± 12.16% after pulmonary administration of 10 mg/kg SMPA solution in rats. The absolute bioavailability of Sal B increased at least 10-fold after pulmonary administration, compared with oral administration. It was concluded that the newly established LC-MS/MS method was suitable for describing the pharmacokinetic characteristics of Sal B, Ros A and DA in rat after pulmonary administration of SMPA solution. The data from this study will provide a preclinical insight into the feasibility of pulmonary administration of SMPA.
Analysis of Quorum Sensing Activity in Staphylococci by RP- HPLC of Staphylococcal δ-Toxin

Staphylococcus aureus and Staphylococcus epidermidis rank among the most important pathogens involved in nosocomial infections. Most virulence factors of these bacteria are controlled by the agr locus, which encodes a quorum-sensing system required for celldensity-dependent control of protein expression. The activity of the agr system is an important determinant of staphylococcal pathogenicity, and deletion of the agr locus results in diminished virulence. So far, measurement of agr activity has been performed by Northern analyses of RNAIII, the intracellular regulatory molecule of the agr system. RNAIII controls expression of the target pathogenicity factor genes such as α-, β-, γ-toxin, toxic shock syndrome toxin, lipase, protease, several endotoxins and protein A, to name a few (9). Here, we present a new method for qualitative and quantitative measurement of the activity of the agr system by HPLC analysis of δ-toxin. The gene for δ-toxin, which itself represents a virulence factor, is encoded within RNAIII. Determination of δ-toxin expression therefore offers an alternative to the measurement of RNAIII expression to analyze agr activity. δ-toxin is an amphiphilic molecule with surfactant-like properties. It is often used as a model substance for membrane insertion (6,13). Its amino acid sequence and three-dimensional structure have already been reported (4,8,14). Different purification procedures for δ-toxin have been described, all requiring many purification steps (3,4). We combined hydrophobic interaction chromatography using polystyrene/divinylbenzene materials with a water/acetonitrile gradient to purify and analyze δ-toxin in a one-step procedure. The most important advantage of this procedure is that pretreatment of the samples before analytical HPLC is unnecessary. Supernatants are not normally injected directly onto an analytical HPLC column, but require initial purification by precipitation or initial chromatographic steps, for example. δ-toxin was analyzed directly in the supernatants of bacterial cultures grown in a commonly used complex media [tryptic soy broth and basic medium: 1% tryptone (Difco Laboratories, Detroit, MI, USA), 0.5% yeast extract (Life Technologies, Eggenstein, Germany), 0.5% NaCl, 0.1% K2HPO4 and 0.1% glucose]. The media was centrifuged at 19 000× g for 5 min in a normal bench centrifuge. Benchmarks
Investigation of In-Vitro Antioxidant and Electrochemical Activities of Isolated Compounds from Salvia chamelaeagnea P.J.Bergius Extract

We have investigated the in-vitro antioxidant activity and electrochemical redox properties of a number of natural compounds (carnosol, carnosic acid, 7-ethoxyrosmanol, ursolic acid, rosmanol and ladanein) isolated from the methanolic extract of Salvia chamelaeagnea collected from the Cape floristic region, South Africa. The results from trolox equivalent antioxidant capacity (TEAC), ferric-ion reducing antioxidant parameter (FRAP) oxygen radical absorbance capacity (ORAC), as well as the inhibition of Fe2+-induced lipid peroxidation showed strong antioxidant capacities for carnosol and rosmanol. A structural analysis of the compounds suggests that multiple OH substitution, conjugation and lactone ring in carnosol and rosmanol are important determinants of the free radical scavenging activity and electrochemical behavior. Pharmacophore generated demonstrates H-donor/acceptor capabilities of the most active compounds. Rosmanol, when compared to other compounds, exhibits the lowest oxidation potential value with an anodic peak potential (Epa) value of 0.11 V, indicating that rosmanol has the highest antioxidant power, which is in good agreement with ORAC and lipid peroxidation experiments. The lipophilic nature of carnosol, carnosic acid and rosmanol enhanced their absorption and activity against oxidative stress related to the treatment of age-related diseases. These results confirm the first report on the in-vitro antioxidant and electrochemical activities of S. chamelaeagnea constituents and underline the medicinal uses of this plant as natural preservatives for skin ageing or in pharmaceutical applications.
Environmental Risk Factors for Inflammatory Bowel Diseases: an Umbrella Review of Meta-analyses.

BACKGROUND & AIMS Multiple environmental factors have been associated with development of inflammatory bowel diseases (IBD). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis we considered the random-effects estimate, its 95% CI, the estimates of heterogeneity and small-study effects, and graded the evidence according to prespecified criteria. Methodologic quality was assessed using AMSTAR 2. RESULTS We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), Helicobacter pylori infection (CD, UC, and IBD). Epidemiologic evidence for all these associations were of high to moderate strength; we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or results of recall bias. CONCLUSIONS In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD, and their pathogenic mechanisms.
Mining for Oxysterols in Cyp7b1−/− Mouse Brain and Plasma: Relevance to Spastic Paraplegia Type 5

Deficiency in cytochrome P450 (CYP) 7B1, also known as oxysterol 7α-hydroxylase, in humans leads to hereditary spastic paraplegia type 5 (SPG5) and in some cases in infants to liver disease. SPG5 is medically characterized by loss of motor neurons in the corticospinal tract. In an effort to gain a better understanding of the fundamental biochemistry of this disorder, we have extended our previous profiling of the oxysterol content of brain and plasma of Cyp7b1 knockout (-/-) mice to include, amongst other sterols, 25-hydroxylated cholesterol metabolites. Although brain cholesterol levels do not differ between wild-type (wt) and knockout mice, we find, using a charge-tagging methodology in combination with liquid chromatography–mass spectrometry (LC–MS) and multistage fragmentation (MSn), that there is a build-up of the CYP7B1 substrate 25-hydroxycholesterol (25-HC) in Cyp7b1-/- mouse brain and plasma. As reported earlier, levels of (25R)26-hydroxycholesterol (26-HC), 3β-hydroxycholest-5-en-(25R)26-oic acid and 24S,25-epoxycholesterol (24S,25-EC) are similarly elevated in brain and plasma. Side-chain oxysterols including 25-HC, 26-HC and 24S,25-EC are known to bind to INSIG (insulin-induced gene) and inhibit the processing of SREBP-2 (sterol regulatory element-binding protein-2) to its active form as a master regulator of cholesterol biosynthesis. We suggest the concentration of cholesterol in brain of the Cyp7b1-/- mouse is maintained by balancing reduced metabolism, as a consequence of a loss in CYP7B1, with reduced biosynthesis. The Cyp7b1-/- mouse does not show a motor defect; whether the defect in humans is a consequence of less efficient homeostasis of cholesterol in brain has yet to be uncovered.
Probabilistic geometric grammars for object recognition

This thesis presents a generative three-dimensional (3D) representation and recognition framework for classes of objects. The framework uses probabilistic grammars to represent object classes recursively in terms of their parts, thereby exploiting the hierarchical and substitutive structure inherent to many types of objects. The framework models the 3D geometric characteristics of object parts using multivariate conditional Gaussians over dimensions, position, and rotation. I present algorithms for learning geometric models and rule probabilities given parsed 3D examples and a fixed grammar. I also present a parsing algorithm for classifying unlabeled, unparsed 3D examples given a geometric grammar. Finally, I describe the results of a set of experiments designed to investigate the chosen model representation of the framework. Thesis Supervisor: Leslie Pack Kaelbling Title: Professor Thesis Supervisor: Tomás Lozano-Pérez Title: Professor
Extracorporeal membrane oxygenation after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) but can result in respiratory and cardiac complications that may require extracorporeal membrane oxygenation (ECMO). We reviewed our experience with ECMO in patients undergoing PEA.
Effect of site‐directed point mutations on protein misfolding: A simulation study

A Monte Carlo simulation based sequence design method is proposed to investigate the role of site‐directed point mutations in protein misfolding. Site‐directed point mutations are incorporated in the designed sequences of selected proteins. While most mutated sequences correctly fold to their native conformation, some of them stabilize in other nonnative conformations and thus misfold/unfold. The results suggest that a critical number of hydrophobic amino acid residues must be present in the core of the correctly folded proteins, whereas proteins misfold/unfold if this number of hydrophobic residues falls below the critical limit. A protein can accommodate only a particular number of hydrophobic residues at the surface, provided a large number of hydrophilic residues are present at the surface and critical hydrophobicity of the core is preserved. Some surface sites are observed to be equally sensitive toward site‐directed point mutations as the core sites. Point mutations with highly polar and charged amino acids increases the misfold/unfold propensity of proteins. Substitution of natural amino acids at sites with different number of nonbonded contacts suggests that both amino acid identity and its respective site‐specificity determine the stability of a protein. A clash‐match method is developed to calculate the number of matching and clashing interactions in the mutated protein sequences. While misfolded/unfolded sequences have a higher number of clashing and a lower number of matching interactions, the correctly folded sequences have a lower number of clashing and a higher number of matching interactions. These results are valid for different SCOP classes of proteins.
Free Energies and Entropies of Binding Sites Identified by MixMD Cosolvent Simulations

In our recent efforts to map protein surfaces using mixed-solvent molecular dynamics (MixMD) (Ghanakota, P.; Carlson, H. A. Moving Beyond Active-Site Detection: MixMD Applied to Allosteric Systems. J. Phys. Chem. B 2016, 120, 8685-8695), we were able to successfully capture active sites and allosteric sites within the top-four most occupied hotspots. In this study, we describe our approach for estimating the thermodynamic profile of the binding sites identified by MixMD. First, we establish a framework for calculating free energies from MixMD simulations, and we compare our approach to alternative methods. Second, we present a means to obtain a relative ranking of the binding sites by their configurational entropy. The theoretical maximum and minimum free energy and entropy values achievable under such a framework along with the limitations of the techniques are discussed. Using this approach, the free energy and relative entropy ranking of the top-four MixMD binding sites were computed and analyzed across our allosteric protein targets: Abl Kinase, Androgen Receptor, Pdk1 Kinase, Farnesyl Pyrophosphate Synthase, Chk1 Kinase, Glucokinase, and Protein Tyrosine Phosphatase 1B.
Expression Analysis of Auxin Regulated Genes in Populus

Due to its many advantageous characteristics, such as a small sequenced genome, ease of vegetative propagation and availability of genomic tools and databases, Populus is widely becoming accepted as the model species among trees. In addition, DOE has chosen hybrid poplar as the model bioenergy feedstock tree. Due to the growing importance of the Populus species, genetic and genomic resources (EST and BLAST databases, genetic maps, etc.) are becoming increasingly available and are leading to a greater understanding of the functionality of the Populus genome. The goal of this study was to use these resources to further characterize the genetic controls of root growth and development so that these mechanisms may eventually be manipulated to improve carbon sequestration ability in belowground sinks. Because auxin is known to play an important role in lateral root growth as well as many other aspects of plant development, a sequenced subtracted cDNA library from poplar was used to study the expression of genes up and down-regulated in response to exogenous auxin treatments. Results from this study indicate that a daily 9-day exogenous auxin treatment may have induced a stress response as indicated by the high percentage of WRKY transcription factors and stress related proteins that were up-regulated in response to the treatment regimen. A second study was also done using whole-genome oligonucleotide microarray technology to further analyze: auxin regulated gene expression including Populus homologs of AUX/IAA and ARF genes in Arabidopsis. Results from this study did not appear to correlate well with real-time RT-PCR results indicating that, in the future, more reps need to be used to give the experiment the statistical power necessary to accurately find differentially expressed genes. Results from these gene expression studies can then be used to guide the development of poplar transgenics with increased root growth.
Using Surgeon Hand Motions to Predict Surgical Maneuvers

Objective: This study explores how common machine learning techniques can predict surgical maneuvers from a continuous video record of surgical benchtop simulations. Background: Automatic computer vision recognition of surgical maneuvers (suturing, tying, and transition) could expedite video review and objective assessment of surgeries. Method: We recorded hand movements of 37 clinicians performing simple and running subcuticular suturing benchtop simulations, and applied three machine learning techniques (decision trees, random forests, and hidden Markov models) to classify surgical maneuvers every 2 s (60 frames) of video. Results: Random forest predictions of surgical video correctly classified 74% of all video segments into suturing, tying, and transition states for a randomly selected test set. Hidden Markov model adjustments improved the random forest predictions to 79% for simple interrupted suturing on a subset of randomly selected participants. Conclusion: Random forest predictions aided by hidden Markov modeling provided the best prediction of surgical maneuvers. Training of models across all users improved prediction accuracy by 10% compared with a random selection of participants. Application: Marker-less video hand tracking can predict surgical maneuvers from a continuous video record with similar accuracy as robot-assisted surgical platforms, and may enable more efficient video review of surgical procedures for training and coaching.
Characterizing trunk muscle activations during simulated low-speed rear impact collisions

Abstract Objective: The purpose of this study was to evaluate the activation profiles of muscles surrounding the lumbar spine during unanticipated and braced simulated rear-end collisions. Methods: Twenty-two low-speed sled tests were performed on 11 human volunteers (V = 4 km/h). Each volunteer was exposed to one unanticipated impact and one braced impact. Accelerometers were mounted on the test sled and participants’ low back. Six bilateral channels of surface electromyography (EMG) were collected from the trunk during impact trials. Peak lumbar accelerations, peak muscle activation delay, muscle onset time, and peak EMG magnitudes, normalized to maximum voluntary contractions (MVCs), were examined across test conditions. Results: Though not statistically significant, bracing for impact tended to reduce peak lumbar acceleration in the initial rearward impact phase of the occupant’s motion by approximately 15%. The only trunk muscles with peak activations exceeding 10% MVC during the unanticipated impact were the thoracic erector spinae. Time of peak muscle activation was slightly longer for the unanticipated condition (unanticipated = 296 ms; braced = 241 ms). Conclusions: Results from this investigation demonstrate that during an unanticipated low-speed rear-end collision, the peak activation of muscles in the lumbar spine are low in magnitude. As such, muscle activation likely has minimal contribution to the internal joint loads that are experienced in the lumbar intervertebral joints during low-speed rear impact collisions. These findings justify the use of simplified joint models in estimating the joint loads in the lumbar spine during low-speed rear impact collisions and support the application of cadaveric and anthropomorphic test device (ATD) testing in understanding the resultant joint loads in the lumbar spine associated with rear-end collisions.