Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer.

OBJECTIVE Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. METHODS The study population consisted of 42 consecutive patients with resectable stage III-IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). RESULTS Grade 3-4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P < 0.001 and = 0.003), overall survival (OS) (P < 0.001 and = 0.004) and laryngeal preservation survival (LPS) (P = 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. CONCLUSIONS Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.
Feasibility of nonhyperbolic moveout inversion in transversely isotropic media

Inversion of reflection traveltimes in anisotropic media can provide estimates of anisotropic coefficients required for seismic processing and lithology discrimination. Nonhyperbolic P-wave moveout for transverse isotropy with a vertical symmetry axis (VTI media) is controlled by the parameter η (or, alternatively, by the horizontal velocity Vhor), which is also responsible for the influence of anisotropy on all time‐processing steps, including dip‐moveout (DMO) correction and time migration. Here, we recast the nonhyperbolic moveout equation, originally developed by Tsvankin and Thomsen, as a function of Vhor and normal‐moveout (NMO) velocity Vnmo and introduce a correction factor in the denominator that increases the accuracy at intermediate offsets. Then we apply this equation to obtain Vhor and η from nonhyperbolic semblance analysis on long common midpoint (CMP) spreads and study the accuracy and stability of the inversion procedure. Our error analysis shows that the horizontal velocity becomes relat.
Spontaneous and Evoked Laryngeal Electromyography of the Thyroarytenoid Muscles: A Canine Model for Intraoperative Recurrent Laryngeal Nerve Monitoring

Objectives: We sought to determine the feasibility of performing spontaneous and evoked intraoperative laryngeal electromyography (L-EMG) using nerve monitoring equipment and to compare recording electrode configurations and methods of recurrent laryngeal nerve (RLN) stimulation in dogs. Methods: Four beagles underwent crush injury of the left RLN, and 2 beagles underwent left RLN transection. Serial spontaneous and evoked L-EMG was recorded with the NIM-Response nerve monitoring system under sedation. Transesophageal, percutaneous, and direct open RLN stimulation was performed. Recordings of spontaneous and evoked responses were made with endotracheal tube surface electrodes and bipolar vocal fold needle electrodes. The L-EMG procedures were repeated every 1 to 2 weeks after injury, and intersubject and intertrial differences were evaluated. Results: Low-amplitude motor unit action potentials, polyphasic potentials, fasciculations, and fibrillations were detected in injured animals with bipolar needle recording electrodes with this system of spontaneous L-EMG. The surface recording electrodes did not detect pathologic waveforms. Percutaneous needle stimulation of the RLN is possible at currents slightly higher than those used for direct stimulation. Consistent, discrete, transesophageal stimulation of the RLN could not be reliably performed. Recording evoked responses with needle electrodes generated sharper waveforms, facilitating calculation of latency and wave duration. Evoked L-EMG utilizing surface recording electrodes limited the intertrial and intersubject variability of evoked amplitude. Conclusions: Typical patterns of nerve injury can be detected with this system of intraoperative L-EMG in a canine model. Quantitative measures of amplitude, latency, and wave duration in healthy and injured canine RLNs may be determined with this system.
A novel expression system of domain I of human beta 2 glycoprotein I in Escherichia coli

Background: The antiphospholipid syndrome (APS), characterised by recurrent miscarriage and thrombosis, is a significant cause of morbidity and mortality. Domain I (DI) of human beta 2 glycoprotein I (β2GPI) is thought to contain crucial antibody binding epitopes for antiphospholipid antibodies (aPL), which are critical to the pathogenesis of APS. Expressing this protein in bacteria could facilitate studies investigating how this molecule interacts with aPL. Methods: Using a computer programme called Juniper, sequentially overlapping primers were designed to be used in a recursive polymerase chain reaction (PCR) to produce a synthetic DI gene. Specifically Juniper incorporates 'major' codons preferred by bacteria altering 41 codons out of 61. This was cloned into the expression plasmid pET(26b) and expressed in BL21(DE3) Escherichia coli (E. coli). By virtue of a pelB leader sequence, periplasmic localisation of DI aided disulphide bond formation and toxicity was addressed by tightly regulating expression through the high stringency T7lac promoter. Results: Purified, soluble his-tagged DI in yields of 750 μg/L bacterial culture was obtained and confirmed on Western blot. Expression using the native human cDNA sequence of DI in the same construct under identical conditions yielded significantly less DI compared to the recombinant optimised sequence. This constitutes the first description of prokaryotic expression of soluble DI of β2GPI. Binding to murine monoclonal antibodies that recognise conformationally restricted epitopes on the surface of DI and pathogenic human monoclonal IgG aPL was confirmed by direct and indirect immunoassay. Recombinant DI also bound a series of 21 polyclonal IgG samples derived from patients with APS. Conclusion: By producing a synthetic gene globally optimised for expression in E. coli, tightly regulating expression and utilising periplasmic product translocation, efficient, soluble E. coli expression of the eukaryotic protein DI of β2GPI is possible. This novel platform of expression utilising pan-gene prokaryote codon optimisation for DI production will aid future antigenic studies. Furthermore if DI or peptide derivatives of DI are eventually used in the therapeutic setting either as toleragen or as a competitive inhibitor of pathogenic aPL, then an E. coli production system may aid cost-effective production. Published: 10 February 2006 BMC Biotechnology 2006, 6:8 doi:10.1186/1472-6750-6-8 Received: 22 July 2005 Accepted: 10 February 2006 This article is available from: http://www.biomedcentral. com/1472-6750/6/8 © 2006 Ioannou et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nanostructure and molecular mechanics of spider dragline silk protein assemblies

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis. The structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly beta-sheet crystal domains, while disorderly regions are formed by glycine-rich repeats that consist of 31-helix type structures and beta-turns. Our structural predictions are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content. Mechanical shearing simulations on selected structures illustrate that the nanoscale behaviour of silk protein assemblies is controlled by the distinctly different secondary structure content and hydrogen bonding in the crystalline and semi-amorphous regions. Both structural and mechanical characterization results show excellent agreement with available experimental evidence. Our findings set the stage for extensive atomistic investigations of silk, which may contribute towards an improved understanding of the source of the strength and toughness of this biological superfibre.
Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23-q25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans . Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.
Modelling the mating system of polar bears: a mechanistic approach to the Allee effect

Allee effects may render exploited animal populations extinction prone, but empirical data are often lacking to describe the circumstances leading to an Allee effect. Arbitrary assumptions regarding Allee effects could lead to erroneous management decisions so that predictive modelling approaches are needed that identify the circumstances leading to an Allee effect before such a scenario occurs. We present a predictive approach of Allee effects for polar bears where low population densities, an unpredictable habitat and harvest-depleted male populations result in infrequent mating encounters. We develop a mechanistic model for the polar bear mating system that predicts the proportion of fertilized females at the end of the mating season given population density and operational sex ratio. The model is parametrized using pairing data from Lancaster Sound, Canada, and describes the observed pairing dynamics well. Female mating success is shown to be a nonlinear function of the operational sex ratio, so that a sudden and rapid reproductive collapse could occur if males are severely depleted. The operational sex ratio where an Allee effect is expected is dependent on population density. We focus on the prediction of Allee effects in polar bears but our approach is also applicable to other species.
Mixing times for the interchange process

Consider the interchange process on a connected graph G = (V,E) on n vertices . I.e. shuffle a deck of cards by first placing one card at each vertex of G in a fixed order and then at each tick of the clock, picking an edge uniformly at random and switching the two cards at the end vertices of the edge with probability 1/2. Well known special cases are the random transpositions shuffle, where G is the completegraph, and the transposing neighbors shuffle, where G is the n-path. Other cases that have been studied are thed-dimensional grid, the hypercube, lollipop graphs and Erdos-Renyi random graphs above the threshold for connectedness. In this paper the problem is studied for general G. Special attention is focused on trees, random trees and the giant component of critical and supercritical G(N, p) randomgraphs. Upper and lower bounds on the mixing time are given. In many of the cases, we establish the exact order of the mixing time. We also mention the cases when G is the hypercube and when G is a bounded-degree expander, giving upper and lower bounds on the mixing time.
Loss of Neurofilaments Alters Axonal Growth Dynamics

The highly regulated expression of neurofilament (NF) proteins during axon outgrowth suggests that NFs are important for axon development, but their contribution to axon growth is unclear. Previous experiments in Xenopuslaevis embryos demonstrated that antibody-induced disruption of NFs stunts axonal growth but left unresolved how the loss of NFs affects the dynamics of axon growth. In the current study, dissociated cultures were made from the spinal cords of embryos injected at the two-cell stage with an antibody to the middle molecular mass NF protein (NF-M), and time-lapse videomicroscopy was used to study early neurite outgrowth in descendants of both the injected and uninjected blastomeres. The injected antibody altered the growth dynamics primarily in long neurites (>85 μm). These neurites were initiated just as early and terminated growth no sooner than did normal ones. Rather, they spent relatively smaller fractions of time actively extending than normal. When growth occurred, it did so at the same velocity. In very young neurites, which have NFs made exclusively of peripherin, NFs were unaffected, but in the shaft of older neurites, which have NFs that contain NF-M, NFs were disrupted. Thus growth was affected only after NFs were disrupted. In contrast, the distributions of α-tubulin and mitochondria were unaffected; thus organelles were still transported into neurites. However, mitochondrial staining was brighter in descendants of injected blastomeres, suggesting a greater demand for energy. Together, these results suggest a model in which intra-axonal NFs facilitate elongation of long axons by making it more efficient.
Endovascular treatment of a grade IV transverse sinus dural arteriovenous fistula by sinus recanalization, angioplasty, and stent placement: technical case report.

OBJECTIVE AND IMPORTANCE The frequent association of dural arteriovenous fistulae (DAVFs) and dural sinus thrombosis may render the treatment of these complex lesions difficult. We report a case of DAVF eradicated by recanalization of the chronically thrombosed transverse sinus (TS) and sigmoid sinus followed by balloon angioplasty and stent deployment at the site of the fistula. CLINICAL PRESENTATION A 52-year-old man presented with a Type IV DAVF of the left TS with widespread white matter changes secondary to venous hypertension. Arterial feeders arose from the left internal carotid, external carotid, and vertebral arteries. The distal segment of the left TS, the left sigmoid sinus, and the proximal segment of the right TS were occluded. Reverse flow was observed in the deep venous system and in the superior sagittal sinus. INTERVENTION Endovascular access was gained through the left internal jugular vein. Mechanical recanalization of the thrombosed left TS and sigmoid sinus was followed by balloon angioplasty and placement of six overlapping stents extending from the TS to the proximal internal jugular vein. Angiograms performed after surgery showed resaturation of antegrade venous drainage as well as complete eradication of the fistulous connections. The patient was discharged with an improving clinical CONCLUSION Recanalization of a chronically occluded dural venous sinus through a jugular approach is feasible. In addition to eradicating cerebral venous hypertension by reestablishing antegrade venous drainage, balloon angioplasty and stent deployment at the DAVF site produced complete closure of the fistula. This may prove to be a new therapeutic strategy for management of DAVF.
Automatic accent detection: effect of base units and boundary information

Automatic prominence or pitch accent detection is important as it can perform automatic prosodic annotation of speech corpora, as well as provide additional features in other tasks such as keyword detection. In this paper, we evaluate how accent detection performance changes according to different base units and what kind of boundary information is available. We compare word, syllable, and vowel-based units when their boundaries are provided. We also automatically estimate syllable boundaries using energy contours when phone-level alignment is available. In addition, we utilize a sliding window with fixed length under the condition of unknown boundaries. Our experiments show that when boundary information is available, using longer base unit achieves better performance. In the case of no boundary information, using a moving window with a fixed size achieves similar performance to using syllable information on word-level evaluation, suggesting that accent detection can be performed without relying on a speech recognizer to generate boundaries.
New Episodic Learning Interferes with the Reconsolidation of Autobiographical Memories

It is commonly assumed that, with time, an initially labile memory is transformed into a permanent one via a process of consolidation. Yet, recent evidence indicates that memories can return to a fragile state again when reactivated, requiring a period of reconsolidation. In the study described here, we found that participants who memorized a story immediately after they had recalled neutral and emotional experiences from their past were impaired in their memory for the neutral (but not for the emotional) experiences one week later. The effect of learning the story depended critically on the preceding reactivation of the autobiographical memories since learning without reactivation had no effect. These results suggest that new learning impedes the reconsolidation of neutral autobiographical memories.
The Impact of the Degree of Aquifer Confinement and Anisotropy on Tidal Pulse Propagation

Oceanic tidal fluctuations which propagate long distances up coastal rivers can be exploited to constrain hydraulic properties of riverbank aquifers. These estimates, however, may be sensitive to degree of aquifer confinement and aquifer anisotropy. We analyzed the hydraulic properties of a tidally influenced aquifer along the Meghna River in Bangladesh using: (1) slug tests combined with drilling logs and surface resistivity to estimate Transmissivity (T); (2) a pumping test to estimate T and Storativity (S) and thus Aquifer Diffusivity (DPT); and (3) the observed reduction in the amplitude and velocity of a tidal pulse to calculate D using the Jacob‐Ferris analytical solution. Average Hydraulic Conductivity (K) and T estimated with slug tests and borehole lithology were 27.3 m/d and 564 m2/d, respectively. Values of T and S determined from the pumping test ranged from 400 to 500 m2/d and 1 to 5 × 10−4, respectively with DPT ranging from 9 to 40 × 105 m2/d. In contrast, D estimated from the Jacob‐Ferris model ranged from 0.5 to 9 × 104 m2/d. We hypothesized this error resulted from deviations of the real aquifer conditions from those assumed by the Jacob‐Ferris model. Using a 2D numerical model tidal pulses were simulated across a range of conditions and D was calculated with the Jacob‐Ferris model. Moderately confined (Ktop/Kaquifer < 0.01) or anisotropic aquifers (Kx/Kz > 10) yield D within a factor of 2 of the actual value. The order of magnitude difference in D between pumping test and Jacob‐Ferris model at our site argues for little confinement or anisotropy.
Allergic asthma: a tale of many T cells

Asthma is a common immune‐mediated disorder characterized by reversible airway inflammation, mucus production, and variable airflow obstruction with airways hyperresponsiveness (AHR). In most cases the airway inflammation characteristic of asthma is thought to result from an allergic‐type reaction to an inhaled substance from the environment (so‐called allergic asthma). In allergic asthma, allergen exposure stimulates eosinophilic inflammation of the airways associated with infiltration of T cells. Although the recruitment of eosinophils into the airways is an important component in the pathogenesis of asthma, the trafficking of T lymphocytes into the airways is now believed to establish and orchestrate the asthmatic inflammatory response. This review explores the roles of various T cell subsets in the pathogenesis of allergic airway inflammation and highlights the contributions of these cells in regulating asthma.
The association between follicular size at the time of spontaneous rupture and pregnancy rates in clomiphene citrate treated PCOS patients in coit cycles

Abstract Objective: To investigate the follicular size at spontaneous rupture on pregnancy rate in patients with polycystic ovary syndrome (PCOS) undergoing clomiphene citrate (CC) ovulation. Design: Cross-sectional study. Patients and methods: One hundred and four women with ovulatory cycles after use of CC followed by ultrasound to determine the follicle size at the time of rupture, which was subsequently correlated with the occurrence of pregnancy or not in coit cycles. Results: In the group of follicular rupture at a mean diameter ≤25 mm (n = 54), pregnancy rate was 35.1% and when follicular rupture occurred at a mean diameter >25 mm (n = 50), it was 34% (p > 0.05). When different diameters at follicular rupture were randomly correlated with the pregnancy rate, there was no significant difference. Conclusion: Our data suggest that the occurrence of pregnancy after ovulation induction with CC in women with PCOS is not associated with follicle size at the time of rupture.