Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of computer-based and conventional audiometers

In most developing countries, routine hearing screening programmes are often not available due to unaffordable resources. There is an urgent need to develop a cost-effective but reliable audiometer for use in such regions. The purpose of this study was to investigate the screening accuracy of a low cost, computer-based audiometer compared with a conventional audiometer. An additional purpose was to find out whether there were frequency effects in the accuracy of the computer-based audiometer. A total of 80 children were screened using both conventional and computer-based audiometers. There was no significant difference between the two different audiometers for screening referral rates in the mid and high frequencies at the passing criterion of 40 dBHL (p>0.05). This suggested that computer-based audiometers may be a promising, low-cost alternative for developing country use.
Time Series Forecasting Using Wavelet-Least Squares Support Vector Machines and Wavelet Regression Models for Monthly Stream Flow Data

This study explores the least square support vector and wavelet technique (WLSSVM) in the monthly stream flow forecasting. This is a new hybrid technique. The 30 days periodic predicting statistics used in this study are derived from the subjection of this model to the river flow data of the Jhelum and Chenab rivers. The root mean square error (RMSE), mean absolute error (RME) and correlation (R) statistics are used for evaluating the accuracy of the WLSSVM and WR models. The accuracy of the WLSSVM model is compared with LSSVM, WR and LR models. The two rivers surveyed are in the Republic of Pakistan and cover an area encompassing 39,200 km2 for the Jhelum River and 67,515 km2 for the Chenab River. Using discrete wavelets, the observed data has been decomposed into sub-series. These have then appropriately been used as inputs in the least square support vector machines for forecasting the hydrological variables. The resultant observation from this comparison indicates the WLSSVM is more accurate than the LSSVM, WR and LR models in river flow forecasting.
Contributions of aromatic pairs to the folding and stability of long‐lived human γD‐crystallin

Human γD‐crystallin (HγD‐Crys) is a highly stable protein that remains folded in the eye lens for the majority of an individual's lifetime. HγD‐Crys exhibits two homologous crystallin domains, each containing two Greek key motifs with eight β‐strands. Six aromatic pairs (four Tyr/Tyr, one Tyr/Phe and one Phe/Phe) are present in the β‐hairpin sequences of the Greek keys. Ultraviolet damage to the aromatic residues in lens crystallins may contribute to the genesis of cataract. Mutant proteins with these aromatic residues substituted with alanines were constructed and expressed in E. coli. All mutant proteins except F115A and F117A had lower thermal stability than the WT protein. In equilibrium experiments in guanidine hydrochloride (GuHCl), all mutant proteins had lower thermodynamic stability than the WT protein. N‐terminal domain (N‐td) substitutions shifted the N‐td transition to lower GuHCl concentration, but the C‐terminal domain (C‐td) transition remained unaffected. C‐td substitutions led to a more cooperative unfolding/refolding process, with both the N‐td and C‐td transitions shifted to lower GuHCl concentration. The aromatic pairs conserved for each Greek key motif (Greek key pairs) had larger contributions to both thermal stability and thermodynamic stability than the other pairs. Aromatic‐aromatic interaction was estimated as 1.5–2.0 kcal/mol. In kinetic experiments, N‐td substitutions accelerated the early phase of unfolding, while C‐td substitutions accelerated the late phase, suggesting independent domain unfolding. Only substitutions of the second Greek key pair of each crystallin domain slowed refolding. The second Greek keys may provide nucleation sites during the folding of the double‐Greek‐key crystallin domains.
Electrothermal frequency tuning of folded and coupled vibrating micromechanical resonators

The use of constrained thermal expansion to tune the resonant frequency of vibrating micromechanical resonators is explored. A simple model is developed to predict the power sensitivity obtained with folded and unfolded geometries, including the effects of electrothermal heating, and conduction and convection cooling. It is shown that the sensitivity of folded structures can change sign as the ambient gas pressure is lowered in contrast to the behavior of unfolded structures. Tuning is then by tensile axial stress rather than compressive stress. Using folded laterally resonant bulk-micromachined comb-drive electrostatic actuators, tuning ranges of -25% and +50% are obtained (at atmospheric pressure and at 10 mTorr, respectively, with powers of 10 and 1.5 mW, respectively). A nested coupled resonator is then presented in which the frequency of one resonator may be tuned without effecting that of the other, thus allowing frequency matching to be obtained.
Understanding Thermal Behavior in Lens Processing of Structural Materials

In direct laser metal deposition technologies, such as the Laser (LENS) process, it is important to understand and control the Engineered Net Shaping thermal behavior during fabrication. With this control, components can be reliably fabricated with desired structural material properties. This talk will describe the use of contact and imaging techniques to monitor the thermal signature during LENS processing. Recent results show a direct correlation between thermal history and material properties, where the residual stress magnitude decreases as the laser power, and therefore thermal signature, increases. Development of an understanding of solidification behavior, residual stress, and microstructural evolution with respect to thermal behavior will be discussed.
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.

PURPOSE Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC. METHODS KEYNOTE-012 (ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1-positive (expression in stroma or ≥ 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort. RESULTS Among 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1-positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade ≥ 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to ≥ 47.3 weeks). CONCLUSION This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing.
Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering.

Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol® ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 658-667, 2017.
Quantitative detection method for Roundup Ready soybean in food using duplex real-time PCR MGB chemistry.

BACKGROUND Methodologies that enable the detection of genetically modified organisms (GMOs) (authorized and non-authorized) in food and feed strongly influence the potential for adequate updating and implementation of legislation together with labeling requirements. Quantitative polymerase chain reaction (qPCR) systems were designed to boost the sensitivity and specificity on the identification of GMOs in highly degraded DNA samples; however, such testing will become economically difficult to cope with due to increasing numbers of approved genetically modified (GM) lines. Multiplexing approaches are therefore in development to provide cost-efficient solution. RESULTS Construct-specific primers and probe were developed for quantitative analysis of Roundup Ready soybean (RRS) event glyphosate-tolerant soybean (GTS) 40-3-2. The lectin gene (Le1) was used as a reference gene, and its specificity was verified. RRS- and Le1-specific quantitative real-time PCR (qRTPCR) were optimized in a duplex platform that has been validated with respect to limit of detection (LOD) and limit of quantification (LOQ), as well as accuracy. The analysis of model processed food samples showed that the degradation of DNA has no adverse or little effects on the performance of quantification assay. CONCLUSION In this study, a duplex qRTPCR using TaqMan minor groove binder-non-fluorescent quencher (MGB-NFQ) chemistry was developed for specific detection and quantification of RRS event GTS 40-3-2 that can be used for practical monitoring in processed food products.
Postoperative Thyroglobulin and Neck Ultrasound in the Risk Restratification and Decision to Perform 131I Ablation.

Context There is much debate surrounding the choice of which patient should be submitted to postsurgical remnant radioiodine remnant ablation (RRA), particularly in low-risk (LR) and intermediate-risk (IR) differentiated thyroid cancer (DTC). Objective The aim of this study was to evaluate the role of postoperative high-sensitive thyroglobulin (Tg) on L-thyroxine (LT4-HSTg) and postoperative neck ultrasound (US) in risk restratification and decision to perform RRA. Patients We evaluated 505 patients with LR or IR DTC 3 to 4 months after total thyroidectomy (TTx). All patients underwent RRA and a posttherapeutic whole body scan (ptWBS). Results After TTx, 29.7% DTC patients had LT4-HSTg <0.1 ng/mL (Group A) and could be restratified as cured: 1 of 150 had lymph node metastases (LN mets) detected by neck US but negative at ptWBS. 56.8% DTC patients had LT4-HSTg between 0.1 and ≤1 ng/mL (Group B) and could be restratified either as cured or not cured. In this group, 15 of 287 (5.2%) had metastases but only 7 were detected by ptWBS; 13.5% DTC patients had LT4-HSTg >1 ng/mL (Group C) and could not be considered as cured by definition. LN mets were present in 11 of 68(16.2%) cases, all detected by neck US. No correlation was found with the presence of metastases and serum LT4-HSTg values or with the level of risk. Conclusions LT4-HSTg measured 3 to 4 months after TTx is important in the risk restratification of DTC patients but is less relevant than neck US in the decision to perform RRA.
Microwear Mechanisms of Silicon Sliding Against Diamond in Water Vapor

Microwear mechanisms of single-crystal silicon (111) in water vapor have been investigated. A diamond pin with a radius of 10 μm was used as a pin specimen. All tests were carried out in the chamber of environmental scanning electron microscopy (ESEM), with which contact point could be observed simultaneously during the sliding test. The water vapor pressure was changed from 40 Pa (0.3 Torr) to 2667 Pa (20 Torr). Three different wear modes were observed in the tests and consolidated as wear mode diagram according to initial maximum Hertzian contact pressure and friction coefficient. These wear modes are A No removal of material B Microcutting of feather-like wear particles C Fracture Corresponding to these wear modes, the friction coefficients are 0.07 ∼ 0.13 in Wear Mode A, 0.19 ∼ 0.23 in Wear Mode B and 0.16 ∼ 0.18 in Wear Mode C. Transitions of wear mode are not influenced by water vapor in the range of 40 ∼ 2667 Pa. Friction coefficient changes by the change of water vapor pressure in Range A but does.
Does the Relation between Rapid Automatized Naming and Reading Depend on Age or on Reading Level? A Behavioral and ERP Study

Reading predictors evolve through age: phonological awareness is the best predictor of reading abilities at the beginning of reading acquisition while Rapid Automatized Naming (RAN) becomes the best reading predictor in more experienced readers (around 9–10 years old). Those developmental changes in the relationship between RAN and reading have so far been explained in term of participants' age. However, it should be noted that in the previous experiments age always co-vary with participants reading level. It is thus not clear whether RAN-reading relationship is developmental in nature or related to the reading system itself. This study investigates whether the behavioral changes in the relationship between RAN and reading and their electrophysiological correlates are related to the chronological age or to the reading level of the participants. Thirty two French-speaking children aged 7–10 years took part to the experiment: they were divided into groups contrasted on age but with similar reading levels and the other way round. Participants performed two reading tasks and four RAN tasks. EEG/ERP was recorded during discrete letter and picture RAN. Behavioral results revealed that alphanumeric RAN is more sensitive to age variations than reading level differences. The inverse profile was revealed for picture RAN, which discriminate poor and good readers among typically developed children within the same age-group. ERPs of both letter and picture RAN differed across age groups whereas only for the picture RAN ERPs differed across reading levels. Taken together, these results suggest that picture RAN is a particularly good indicator of reading level variance independently of age.
Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Normal epithelial and endothelial renewal and healing after bacterial and viral challenges are essential for homeostasis along the intestine and the blood and lymphatic vessels. We thus investigated whether and how virus affects migration of human epithelial cells and specifically how the nucleocapsid protein (N) modulates the cellular proteome and interactome using human Caco-2 cells in a wound-healing assay with Hazara virus as a model. Here, Hazara virus blocked cell migration in a dose- and time-dependent manner, disrupted the actin cytoskeleton and specifically reduced the expression of the IQ-motif-containing GTPase-activating protein 1 (IQGAP1) and water channel aquaporin 6 (AQP6) that regulate cytoskeletal organization, water homeostasis and vesicle communication. Moreover, in the Caco-2 cell proteome, we identified several distinct groups of molecules associating with N upon Hazara virus infection, being involved in the ensemble of important cellular processes, e.g., chaperone activity, metabolism, cellular defense against infections, cell morphology, and migration. These events do not only facilitate the virus life cycle, but they are also crucial for membrane and cytoskeleton dynamics, cellular self-renewal and wound healing, being so essential for body integrity and homeostasis.
Dynamical Bifurcation in Gas-Phase XH- + CH3 Y SN 2 Reactions: The Role of Energy Flow and Redistribution in Avoiding the Minimum Energy Path.

The gas-phase reactions of XH- (X=O, S) + CH3 Y (Y=F, Cl, Br) span nearly the whole range of SN 2 pathways, and show an intrinsic reaction coordinate (IRC) (minimum energy path) with a deep well owing to the CH3 XH⋅⋅⋅Y- (or CH3 S- ⋅⋅⋅HF) hydrogen-bonded postreaction complex. MP2 quasiclassical-type direct dynamics starting at the [HX⋅⋅⋅CH3 ⋅⋅⋅Y]- transition-state (TS) structure reveal distinct mechanistic behaviors. Trajectories that yield the separated CH3 XH+Y- (or CH3 S- +HF) products directly are non-IRC, whereas those that sample the CH3 XH⋅⋅⋅Y- (or CH3 S- ⋅⋅⋅HF) complex are IRC. The IRCIRC/non-IRC ratios of 90:10, 40:60, 25:75, 2:98, 0:100, and 0:100 are obtained for (X, Y)=(S, F), (O, F), (S, Cl), (S, Br), (O, Cl), and (O, Br), respectively. The properties of the energy profiles after the TS cannot provide a rationalization of these results. Analysis of the energy flow in dynamics shows that the trajectories cross a dynamical bifurcation, and that the inability to follow the minimum energy path arises from long vibration periods of the X-C⋅⋅⋅Y bending mode. The partition of the available energy to the products into vibrational, rotational, and translational energies reveals that if the vibrational contribution is more than 80 %, non-IRC behavior dominates, unless the relative fraction of the rotational and translational components is similar, in which case a richer dynamical mechanism is shown, with an IRC/non-IRC ratio that correlates to this relative fraction.
The effect of three-component total ankle replacement malalignment on clinical outcome: pain relief and functional outcome in 317 consecutive patients.

BACKGROUND Total ankle replacement has become an increasingly popular treatment for patients with end-stage ankle osteoarthritis. The surgery is technically demanding and generally performed by only experienced foot and ankle surgeons. An important complication of total ankle replacement is malposition of the talar component. The biomechanical effect of malposition has been reported; however, the functional outcomes of patients with varying degrees of talar component malposition have not. The purpose of this study was to assess the influence of talar component malposition on postoperative pain relief and functional outcome. METHODS This retrospective cohort study included 317 total ankle replacements in 317 patients. The anteroposterior offset ratio was measured with use of lateral ankle radiographs made with the patient in a standing, weight-bearing position. Patients were classified into one of three groups: those with an anteroposterior offset ratio of 0 (127 ankles), those with a ratio of >0 (103 ankles), and those with a ratio of <0 (eighty-seven ankles). Postoperative pain relief was assessed with use of a visual analogue scale. Functional outcome was assessed with the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and measurement of ankle range of motion. The mean duration of follow-up (and standard deviation) was 53.2 ± 18.4 months (range, twenty-four to ninety-eight months). RESULTS The postoperative pain level in the group with an anteroposterior offset ratio of 0 was significantly lower than that for both the group with a ratio of >0 (p < 0.001) and the group with a ratio of <0 (p = 0.017). Also, the functional outcome, measured with use of the AOFAS hindfoot score, was significantly higher, and ankle motion was significantly greater, in the group with an anteroposterior offset ratio of 0 than in the group with a ratio of >0 (p = 0.003 and p < 0.001, respectively) and the group with a ratio of <0 (p = 0.007 and p = 0.080). CONCLUSIONS The anteroposterior offset ratio may be a useful predictor of outcome in patients with total ankle replacement with regard to both pain and function. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Structural flexibility and protein adaptation to temperature: Molecular dynamics analysis of malate dehydrogenases of marine molluscs

Significance Analysis of structural and functional properties of cytosolic malate dehydrogenase (cMDH) orthologs of five genera of marine molluscs adapted to an ∼60 °C range of temperatures reveals the role of protein flexibility in adaptation to temperature. Molecular dynamics simulation (MDS) analysis reveals protein-wide as well as local adaptation in flexibility. Sequence regions involved in binding and catalysis show significant interspecific, temperature-related differences in flexibility. MDS analysis is shown to provide a powerful means of examining adaptive change in protein evolution at different temperatures. Orthologous proteins of species adapted to different temperatures exhibit differences in stability and function that are interpreted to reflect adaptive variation in structural “flexibility. ” However, quantifying flexibility and comparing flexibility across proteins has remained a challenge. To address this issue, we examined temperature effects on cytosolic malate dehydrogenase (cMDH) orthologs from differently thermally adapted congeners of five genera of marine molluscs whose field body temperatures span a range of ∼60 °C. We describe consistent patterns of convergent evolution in adaptation of function [temperature effects on KM of cofactor (NADH)] and structural stability (rate of heat denaturation of activity). To determine how these differences depend on flexibilities of overall structure and of regions known to be important in binding and catalysis, we performed molecular dynamics simulation (MDS) analyses. MDS analyses revealed a significant negative correlation between adaptation temperature and heat-induced increase of backbone atom movements [root mean square deviation (rmsd) of main-chain atoms]. Root mean square fluctuations (RMSFs) of movement by individual amino acid residues varied across the sequence in a qualitatively similar pattern among orthologs. Regions of sequence involved in ligand binding and catalysis—termed mobile regions 1 and 2 (MR1 and MR2), respectively—showed the largest values for RMSF. Heat-induced changes in RMSF values across the sequence and, importantly, in MR1 and MR2 were greatest in cold-adapted species. MDS methods are shown to provide powerful tools for examining adaptation of enzymes by providing a quantitative index of protein flexibility and identifying sequence regions where adaptive change in flexibility occurs.