gebhart/patrepeval huggingface dataset:
Automated Surgical Approach Planning for Complex Skull Base Targets: Development and Validation of a Cost Function and Semantic At-las (2018)

Successful multidisciplinary treatment of skull base pathology requires precise preoperative planning. Current surgical approach (pathway) selection for these complex procedures depends on an individual surgeon's experiences and background training. Because of anatomical variation in both normal tissue and pathology (eg, tumor), a successful surgical pathway used on one patient is not necessarily the best approach on another patient. The question is how to define and obtain optimized patient-specific surgical approach pathways? In this article, we demonstrate that the surgeon's knowledge and decision making in preoperative planning can be modeled by a multiobjective cost function in a retrospective analysis of actual complex skull base cases. Two different approaches- weighted-sum approach and Pareto optimality-were used with a defined cost function to derive optimized surgical pathways based on preoperative computed tomography (CT) scans and manually designated pathology. With the first method, surgeon's preferences were input as a set of weights for each objective before the search. In the second approach, the surgeon's preferences were used to select a surgical pathway from the computed Pareto optimal set. Using preoperative CT and magnetic resonance imaging, the patient-specific surgical pathways derived by these methods were similar (85% agreement) to the actual approaches performed on patients. In one case where the actual surgical approach was different, revision surgery was required and was performed utilizing the computationally derived approach pathway.
Formation of galacto‐oligosaccharides during lactose hydrolysis by a novel β‐galactosidase from the moderately thermophilic fungus Talaromyces thermophilus (2006)

Discontinuous and continuous processes of lactose hydrolysis and concomitant galacto-oligosaccharide (GalOS) formation were studied. To this end a wide experimental range of the main variables was evaluated, including the initial lactose concentration, the degree of lactose conversion, the pH value and the temperature for discontinuous transformations, while the initial lactose concentration and the feed rate were varied for the continuous process. For both processes a high-initial lactose concentration proved to be advantageous for the formation of GalOS. The maximum amount of GalOS (100 g/L, corresponding to a yield of approximately 50% based on the initially employed lactose) was obtained after 8 h of incubation when using 200 g/L lactose as substrate and 90% lactose hydrolysis was observed. GalOS productivity in the continuous process (g/L.h) was enhanced by an increase of the flow rate. The maximum GalOS productivity of 70 g/L.h was obtained at a flow rate of 24 mL/h when using a reactor with a total working volume of 21 mL. As was evident from these experiments, this beta-galactosidase from a moderately thermophilic fungus showed a strong transgalactosylation activity and can be used for the formation of GalOS, sugars that are of considerable interest for functional food applications because of their presumed healthpromoting effects.
Identification of Novel Bisbenzimidazole Derivatives as Anticancer Vacuolar (H+)-ATPase Inhibitors (2017)

The vacuolar (H⁺)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached human clinical trials to date. Thus, V-ATPases are emerging as important targets for the identification of potential novel therapeutic agents. We identified a bisbenzimidazole derivative (<b>V</b>) as an initial hit from a similarity search using four known V-ATPase inhibitors (<b>I</b>-<b>IV</b>). Based on the initial hit (<b>V</b>), we designed and synthesized a focused set of novel bisbenzimidazole analogs (<b>2a</b>-<b>e</b>). All newly prepared compounds have been screened for selected human breast cancer (MDA-MB-468, MDA-MB-231, and MCF7) and ovarian cancer (A2780, Cis-A2780, and PA-1) cell lines, along with the normal breast epithelial cell line, MCF10A. The bisbenzimidazole derivative (<b>2e</b>) is active against all cell lines tested. Remarkably, it demonstrated high cytotoxicity against the triple-negative breast cancer (TNBC) cell line, MDA-MB-468 (IC<sub>50</sub> = 0.04 ± 0.02 μM). Additionally, it has been shown to inhibit the V-ATPase pump that is mainly responsible for acidification. To the best of our knowledge the bisbenzimidazole pharmacophore has been identified as the first V-ATPase inhibitor in its class. These results strongly suggest that the compound <b>2e</b> could be further developed as a potential anticancer V-ATPase inhibitor for breast cancer treatment.
Data from Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future (2023)

&lt;div&gt;Abstract&lt;p&gt;Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. &lt;i&gt;Cancer Res; 77(6); 1261–70. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Nuclear Transplantation as a Method for Cloning Embryos (1990)

The concept of transferring nuclei from multicell stage embryos to enucleated oocytes was first proposed by Spemann in 1938 (1). Spemann was a developmental biologist whose concern at the time was that of nuclear equivalence. The idea of the basic composition of the nuclei changing during early embryo development gave rise to the theory that nuclei from different tissues were not equal. To answer this question, Spemann proposed an experiment to transfer nuclei from progressively more advanced embryos to enucleated, activated oocytes. The conclusion of the experiment would be determined when inequivalence was achieved and the transferred nucleus would not support development to a mature adult. Results from Spemann's experiment were first reported in 1952 by Briggs and King (2) in the amphibian Rana pipiens. They (2) showed that nuclei from preblastula stage embryos could promote development to the blastula stage. In addition, they alluded to the observation that nuclei from beyond the blastula stage had a lesser probability of promoting development after nuclear transfer. The spin-off of such a project is the possibility of cloning. Since all of the nuclei of the early embryo are presumed to be identical (all containing the same complement of genetic material), subsequent transfer to enucleated, activated oocytes with development to term should result in genetically identical individuals (the reality of identical individuals will be discussed later). This procedure, in combination with serial nuclear transfer (i.e., growing the first nuclear transfer embryos to the donor cell stage and then repeating the procedures) could, theoretically, result in an unlimited number of identical individuals. The possibility of this in mammals became much more likely after the successes of such procedures were reported in 1986 by Willadsen (3) and Prather et al. (4) in sheep and cattle, respectively.
Electrical and structural properties of polycrystalline silicon (2000)

This work links the structural and electrical properties of thin polycrystalline silicon films at the level of individual grains. A four point “transparent probe” technique was developed which allowed a small number of grains to be isolated and measured electrically in test structures which can be nondestructively prepared for direct imaging in a transmission electron microscope (TEM). By measuring the temperature dependence of electrical resistance in many test structures, the distribution of individual grain boundary activation energies for resistance was determined. After electrical measurements, grains in the test regions were imaged by TEM. Grain size, shape and crystallographic grain boundary character were measured and the distribution of relative grain misorientations was found. Measured boundaries were compared to coincident-site lattice-related boundaries whose character has been the subject of single boundary studies. Single grain boundaries were characterized both electrically and structurally. Electrical results from the transparent probe structures were compared with standard energy band theory developed for blanket film properties and with results from a Monte Carlo model of a network of thermally activated resistors. These results demonstrate how a distribution of grain structures and orientations fundamentally determines the electrical properties of the blanket film.
Bottlenecks to clinical translation of direct brain-computer interfaces (2014)

Despite several decades of research into novel brain-implantable devices to treat a range of diseases, only two-cochlear implants for sensorineural hearing loss and deep brain stimulation for movement disorders-have yielded any appreciable clinical benefit. Obstacles to translation include technical factors (e.g., signal loss due to gliosis or micromotion), lack of awareness of current clinical options for patients that the new therapy must outperform, traversing between federal and corporate funding needed to support clinical trials, and insufficient management expertise. This commentary reviews these obstacles preventing the translation of promising new neurotechnologies into clinical application and suggests some principles that interdisciplinary teams in academia and industry could adopt to enhance their chances of success.
CONTRALATERAL ELBOW RADIOGRAPHS CAN RELIABLY DIAGNOSE RADIAL HEAD IMPLANT OVER-LENGTHENING (2012)

Purpose Radial head implant over-lengthening, a common cause of capitellar wear and clinical failure, is difficult to diagnose using radiographs of the injured elbow. The purpose of this study was to determine if a novel measurement technique based on contralateral elbow radiographs, termed the RACER method, could be used to accurately estimate the magnitude of radial head implant over-lengthening. Part I of this study examined the side-to-side consistency of radiographic landmarks used in the measurement technique. Part II of this study validated the technique using simulated radial head implant over-lengthening in a cadaveric model. Method Part I: A side-to-side comparison of elbow joint dimensions was performed in 50 patients (100 radiographs). Part II: Radial head prostheses of varying lengths (0,+2mm,+4mm,+6mm,+8mm) were implanted in 4 paired cadaveric specimens (8 elbows). Radiographs were obtained and measurements were performed by 2 examiners blinded to implant size to determine if contralateral radiographs could diagnose and provide a valid estimate of the magnitude of implant over-lengthening. Intra and inter-rater reliability was determined. Results No significant side-to-side differences (p>0.2) in radiographic measurements were identified between paired elbows. The RACER measurement technique using contralateral radiographs was successful in predicting the implant size (1mm) in 104 of 120 (87%) of scenarios tested. The sensitivity of the technique, the ability of the test to correctly identify over-lengthening when it was present within 1mm, was 98%. The intra-rater agreement for a single orthopaedic surgeon measuring on 2 separate occasions was excellent (ICC>0.90). The inter-rater agreement between two separate surgeons was also excellent, with the 95% lower confidence interval exceeding 0.90 in all cases. Conclusion A novel measurement technique based on contralateral elbow radiographs can be used to diagnose and calculate the magnitude of radial head implant over-lengthening. Clinical Significance: Implantation of an incorrectly sized radial head prosthesis is not uncommon. The described technique can be used to effectively diagnose and determine the magnitude of over-lengthening.
(Invited) Crystal Chemistry of NaxMM'(PO4)3 Nasicon Electrodes (M,M' = V, Fe, Mn, Ti, Cr) (2021)

International audience
Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shock (2007)

Liposome-encapsulated Hb (LEH) is being developed as an artificially assembled, low-toxicity, and spatially isolated Hb-based oxygen carrier (HBOC). Standard methods of evaluating oxygen carriers are based on surrogate indicators of physiology in animal models of shock. Assessment of actual delivery of oxygen by HBOCs and resultant improvement in oxygen metabolism at the tissue level has been a technical challenge. In this work, we report our findings from 15O-positron emission tomographic (15O-PET) evaluation of LEH in a rat model of 40% hypovolemic shock. In vitro studies showed that PEGylated LEH formulation containing approximately 7.5% Hb and consisting of neutral lipids (distearoylphosphatidylcholine:cholesterol:alpha-tocopherol, 51.4:46.4:2.2) efficiently picks up 15O-labeled oxygen gas. The final preparation of LEH contained 5% human serum albumin to provide oncotic pressure. Cerebral PET images of anesthetized rats inhaling 15O-labeled O2 gas showed efficient oxygen-carrying and delivery capacity of LEH formulation. From the PET images, we determined cerebral metabolic rate of oxygen (CMR(O2)) as a direct indicator of oxygen-carrying capacity of LEH as well as oxygen delivery and metabolism in rat brain. Compared with control fluids [saline and 5% human serum albumin (HSA)], LEH significantly improved CMR(O2) to approximately 80% of baseline level. Saline and HSA resuscitation could not improve hypovolemia-induced decrease in CMR(O2). On the other hand, resuscitation of shed blood was the most efficient in restoring oxygen metabolism. The results suggest that 15O-PET technology can be successfully employed to evaluate potential oxygen carriers and blood substitutes and that LEH resuscitation in hemorrhage enhances oxygen delivery to the cerebral tissue and improves oxygen metabolism in brain.
Recognition of Human Grasp by Fuzzy Modeling (2010)

This chapter contains sections titled: Introduction An Experimental Platform for PBD Modeling of Grasp Primitives Recognition of Grasps??????-??????Three Methods Experiments and Simulations Conclusion References
A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma (2017)

A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pretreatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multipeptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix-assisted laser desorption/ionization time of flight mass spectrometry. These data combined with clinical data identified patients with better or worse outcomes. The test was applied to five independent patient cohorts treated with checkpoint inhibitors and its biology investigated using enrichment analyses. A signature consisting of 209 proteins or peptides was associated with progression-free and overall survival in a multivariate analysis. The test performance across validation cohorts was consistent with the development set results. A pooled analysis, stratified by set, demonstrated a significantly better overall survival for "sensitive" relative to "resistant" patients, HR = 0.15 (95% confidence interval: 0.06-0.40, <i>P</i> < 0.001). The test was also associated with survival in a cohort of ipilimumab-treated patients. Test classification was found to be associated with acute phase reactant, complement, and wound healing pathways. We conclude that a pretreatment signature of proteins, defined by mass spectrometry analysis and machine learning, predicted survival in patients receiving PD-1 blocking antibodies. This signature of proteins was associated with acute phase reactants and elements of wound healing and the complement cascade. This signature merits further study to determine if it identifies patients who would benefit from PD-1 blockade. <i>Cancer Immunol Res; 6(1); 79-86. ©2017 AACR</i>.
Intra‐nucleus mosaic pattern ( InMop ) and whole‐cell Haralick combined‐descriptor for identifying and characterizing acute leukemia blasts on single cell peripheral blood images (2023)

Acute leukemia is usually diagnosed when a test of peripheral blood shows at least 20% of abnormal immature cells (blasts), a figure even lower in case of recurrent cytogenetic abnormalities. Blast identification is crucial for white blood cell (WBC) counting, which depends on both identifying the cell type and characterizing the cellular morphology, processes susceptible of inter- and intraobserver variability. The present work introduces an image combined-descriptor to detect blasts and determine their probable lineage. This strategy uses an intra-nucleus mosaic pattern (InMop) descriptor that captures subtle nuclei differences within WBCs, and Haralick's statistics which quantify the local structure of both nucleus and cytoplasm. The InMop captures WBC inner-nucleus structure by applying a multiscale Shearlet decomposition over a repetitive pattern (mosaic) of automatically-segmented nuclei. As a complement, Haralick's statistics characterize the local structure of the whole cell from an intensity co-occurrence matrix representation. Both InMoP and Haralick-based descriptors are calculated using the b-channel from Lab color-space. The combined-descriptor is assessed by differentiating blasts from nonleukemic cells with support vector machine (SVM) classifiers and different transformation kernels, in two public and independent databases. The first database-D1 (n = 260) is composed of healthy and acute lymphoid leukemia (ALL) single cell images, and second database-D2 contains acute myeloid leukemia (AML) blasts (n = 3294) and nonblast (n = 15,071) cell images. In a first experiment, blasts versus nonblast differentiation is performed by training with a subset of D2 (n = 6588) and testing in D1 (n = 260), obtaining a training AUC of 0.991 ± 0.002 and AUC = 0.782 for the independent validation. A second experiment automatically differentiates AML blasts (260 images from D2) from ALL blasts (260 images from D1), with an AUC of 0.93. In a third experiment, state-of-the-art strategies, VGG16 and RESNEXT convolutional neural networks (CNN), separate blast from nonblast cells in both databases. The VGG16 showed an AUC of 0.673 and the RESNEXT of 0.75. Reported metrics for all the experiments are area under the ROC curve (AUC), accuracy and F1-score.
Multi-task ensembles with teacher-student training (2017)

Ensemble methods often yield significant gains for automatic speech recognition. One method to obtain a diverse ensemble is to separately train models with a range of context dependent targets, often implemented as state clusters. However, decoding the complete ensemble can be computationally expensive. To reduce this cost, the ensemble can be generated using a multi-task architecture. Here, the hidden layers are merged across all members of the ensemble, leaving only separate output layers for each set of targets. Previous investigations of this form of ensemble have used cross-entropy training, which is shown in this paper to produce only limited diversity between members of the ensemble. This paper extends the multi-task framework in several ways. First, the multi-task ensemble can be trained in a teacher-student fashion toward the ensemble of separate models, with the aim of increasing diversity. Second, the multi-task ensemble can be trained with a sequence discriminative criterion. Finally, a student model, with a single output layer, can be trained to emulate the combined ensemble, to further reduce the computational cost of decoding. These methods are evaluated on the Babel conversational telephone speech, AMI meeting transcription, and HUB4 English broadcast news tasks.
Data from Phase I and Preliminary Phase II Study of TRC105 in Combination with Sorafenib in Hepatocellular Carcinoma (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Endoglin (CD105) is an endothelial cell membrane receptor highly expressed on proliferating tumor vasculature, including that of hepatocellular carcinoma (HCC), and is associated with poor prognosis. Endoglin is essential for angiogenesis, and its expression is induced by hypoxia and VEGF pathway inhibition. TRC105 is a chimeric IgG1 CD105 mAb that inhibits angiogenesis and causes antibody-dependent cellular cytotoxicity and apoptosis of proliferating endothelium.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Patients with HCC (Child–Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, and 15 mg/kg every 2 weeks given with sorafenib 400 mg twice daily. Correlative biomarkers included DCE-MRI and plasma levels of angiogenic factors, including soluble endoglin. Pharmacokinetics were assessed in serum.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Twenty-six patients were enrolled, of whom 25 received treatment, 15 with cirrhosis. Hep B/C: 3/15; M:F 19:6; mean age of 60 (range, 18–76); 1 DLT (grade 3 AST) occurred at 10 mg/kg. The most frequent toxicity was low-grade epistaxis, a known toxicity of TRC105. One patient experienced an infusion reaction and was replaced. One patient with coronary stenosis developed a fatal myocardial infarction, and one patient developed G3 cerebral tumor hemorrhage. MTD was not established and DL4 (15 mg/kg) was expanded. The overall response rate in 24 evaluable patients at all 4 dose levels was 21% [95% confidence interval (CI), 7.1–42.2], and 25% (95% CI, 8.7–49.1) in patients with measureable disease. Four patients had confirmed stable disease, one of whom was treated for 22 months. Median progression-free survival (PFS) for 24 patients evaluable for PFS was 3.8 months (95% CI, 3.2–5.6 months); median overall survival was 15.5 months (95% CI, 8.5–26.3 months).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; TRC105 combined with sorafenib was well tolerated at the recommended single agent doses of both drugs. Encouraging evidence of activity to date (PR rate 25%) was observed, and the study is now continuing to recruit in the phase II stage as a multicenter study to confirm activity of the combination. &lt;i&gt;Clin Cancer Res; 23(16); 4633–41. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;