Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicenter Results With an Active Transcutaneous Bone Conduction Implant in Patients With Single-sided Deafness

Supplemental Digital Content is available in the text Objective: To evaluate the audiological and subjective benefit from hearing rehabilitation with an active bone conduction implant in subjects with single-sided sensorineural deafness (SSD). Study Design: Prospective, multicenter, single-subject repeated measures. Setting: Tertiary referral center, five clinics in Germany and Switzerland. Patients: Seventeen subjects aged 18 years and older with severe to profound unilateral sensorineural hearing loss and contralateral normal hearing were followed up for 24 months. Intervention: Active bone conduction implant. Main Outcome Measures: Speech understanding in noise was assessed in three situations: with signal from front, deaf, or normal hearing side (with noise from front in all set-ups). Subjective benefit was evaluated using the Speech, Spatial, and Qualities of Hearing (SSQ-B) and Bern Benefit in Single-Sided Deafness (BBSS) questionnaire. Results: When the signal was coming from the deaf side the mean improvement of the speech reception threshold in noise ranged from 1.5 up to 2.2 dB with the device and was statistically and clinically significant at all tested timepoints. No significant difference between the aided and unaided situation was found when signal and noise were coming from the front. With the signal from the normal hearing side no clinically significant difference, that is, greater than 1 dB between the aided and unaided situation was found. The SSQ-B and BBSS questionnaire showed an overall improvement with no significant difference between time points. Conclusions: The study demonstrates long-term efficacy and benefit of the device in adults with SSD. Patients reported substantial and persistent subjective benefit from the active bone conduction implant.
Self‐Healing Hydrogel Embodied with Macrophage‐Regulation and Responsive‐Gene‐Silencing Properties for Synergistic Prevention of Peritendinous Adhesion

Antiadhesion barriers such as films and hydrogels used to wrap repaired tendons are important for preventing the formation of adhesion tissue after tendon surgery. However, sliding of the tendon can compress the adjacent hydrogel barrier and cause it to rupture, which may then lead to unexpected inflammation. Here, a self‐healing and deformable hyaluronic acid (HA) hydrogel is constructed as a peritendinous antiadhesion barrier. Matrix metalloproteinase‐2 (MMP‐2)‐degradable gelatin‐methacryloyl (GelMA) microspheres (MSs) encapsulated with Smad3‐siRNA nanoparticles are entrapped within the HA hydrogel to inhibit fibroblast proliferation and prevent peritendinous adhesion. GelMA MSs are responsively degraded by upregulation of MMP‐2, achieving on‐demand release of siRNA nanoparticles. Silencing effect of Smad3‐siRNA nanoparticles is around 75% toward targeted gene. Furthermore, the self‐healing hydrogel shows relatively attenuated inflammation compared to non‐healing hydrogel. The mean adhesion scores of composite barrier group are 1.67 ± 0.51 and 2.17 ± 0.75 by macroscopic and histological evaluation, respectively. The proposed self‐healing hydrogel antiadhesion barrier with MMP‐2‐responsive drug release behavior is highly effective for decreasing inflammation and inhibiting tendon adhesion. Therefore, this research provides a new strategy for the development of safe and effective antiadhesion barriers.
Mechanical characterisation of metal material properties in additive layer processes

This paper presents experimental work to demonstrate the effects of machine parameters on mechanical properties, dimensional accuracy, roughness and build time in SLS, DMLS and LC technologies. The research was carried out using a design of experiments methodology, which involved using three parameters with two levels each, and measuring the different results. The experiments conducted showed that build direction had the most effect on mechanical properties and accuracy. However, a thickness effect on Young’s modulus when the LC process was used was also observed. It is assumed that the process parameters for that material developed by the machine vendor would give optimum results, but it was demonstrated that results can vary depending on the process parameters used. Two major applications have been made from this research: the results help industrial companies estimate mechanical properties before part production and it provides a useful comparison of technologies with different build process parameters.
A reliability‐based investigation into ductility measures of RC beams designed according to fib Model Code 2010

A reliability‐based investigation into the ductility measures for reinforced concrete (RC) beams designed according to the current fib Model Code for Concrete Structures 2010 is presented in this paper. Based on the ductility ratio (= ratio of strain in tensile rebar to yield stress of steel), a limit state to ensure adequate ductility in RC beams is proposed. Results show that the ductility ratio generally follows a right‐skewed distribution, and due to variability in the material properties and model error, there is high variability in the strain ductility. This high variability in the ductility ratio leads to a high probability of non‐ductile behaviour for RC beam designs based on the code. This is more pronounced for normal‐strength concrete and grade S500 steel. Based on a target probability taken from the literature, a modification to the allowable neutral axis depth advised by the code is proposed. The results presented in this paper indicate that more reliability‐based studies of the safety factors provided by fib Model Code 2010 are needed in order to ensure adequate ductility in RC beams.
Assessing the Effectiveness of Scrubber Installation on Air Pollution Emissions Reductions Among Coal-Fired Power Plants: Application of Statistical Methods for Causal Inference

The 1990 amendment to the Clean Air Act implemented a cap-and-trade system that required electricity-generating power plants to dramatically reduce Sulfur Dioxide (SO2) and Nitrogen Oxide (NOx) emissions. Plants impacted by this legislation had a variety of compliance options, including decreasing factory operation, purchasing carbon credits, installing scrubbers, and changing fuel inputs. Using data from 1997-2012 of 995 coal-burning power plants, we examine the effectiveness of scrubber installation in reducing SO2 and NOx emissions. Specifically, we employ two methods—a propensity score algorithm and a matching algorithm—to estimate: 1) the causal effect of scrubber installation prior 1997 on the emissions during 1997; and 2) the causal effect of scrubber installation at any time during the period 1997-2012 on emissions two months following scrubber installation. Using a propensity score method, we found that pre1997 SO2 scrubbers reduced 1997 SO2 emissions by 68% (95% CI 58% to 76%), and pre-1997 NOx scrubbers reduced 1997 NOx emissions by 28% (16%, 38%). Additionally, installing SO2 and NOx scrubbers at any time during the period 1997-2012 reduces SO2 and NOx emissions by 89% (88%, 90%) and 21% (19%, 24%) two months following installation, respectively. These final two results are corroborated by a matching algorithm, which finds scrubbers cause SO2 and NOx emissions decline by 88% (87%, 89%) and by 20%. (17%, 22%) two months following installation, respectively.
Evaluation of flexibility in FMS by VIKOR methodology

The evaluation of the most appropriate flexibility in the manufacturing sector is one of the strategic issues that may affect the flexible manufacturing system (FMS). In this paper, a multiple attribute decision making method methodology is structured to resolve this problem. The two decision making methods, which are analytic hierarchy process (AHP) and compromise solution method, also known as the VIekriterijumsko KOmpromisno Rangiranje (VIKOR) method, are integrated in order to make the best use of information available. The purpose of using AHP is to turn over the weights of the variable and the VIKOR method is allowed to rank flexibility in FMS. Furthermore, the method uses fuzzy logic to alter the qualitative attributes into the quantitative attributes. Fifteen factors are taken for the evaluation of 15 flexibilities. In this paper, we concluded that production flexibility has the most impact in 15 flexibilities and programme flexibility has the least impact in these 15 flexibilities by this methodology.
4DCT and VMAT for lung patients with irregular breathing

Abstract Purpose Irregular breathing in lung cancer patients is a common contra‐indication to 4D computerized tomography (4DCT), which may then limit radiotherapy treatment options. For irregular breathers, we investigated whether 3DCT or 4DCT (1) better represents tumor motion, (2) better represents average tumor densities, and (3) better allows for volumetric modulated arc threarpy (VMAT) plans delivered with acceptable dosimetric accuracy. Methods Ten clinical breathing traces were identified with irregularities in phase and amplitude, and fed to a programmable moving platform incorporating an anthropomorphic lung tumor phantom. 3DCT and 4DCT data resorted by phase (4DCT‐P) and amplitude (4DCT‐A) were acquired for each trace. Tumors were delineated by Hounsfield unit (HU) thresholding and apparent motion range assessed. HU profiles were extracted from each image and agreement with calculated expected profiles quantified using area‐under‐curve (AUC) scoring. Clinically representative VMAT plans were created for each image, delivered to the irregularly moving phantom, and measured with a small‐volume ion chamber at the tumor center. Results Median difference from expected tumor motion range for 3DCT, 4DCT‐P, and 4DCT‐A was 2.5 [1.6–3.6] cm, 1.1 [0.1–1.9] cm, and 1.3 [0.4–1.9] cm, respectively (p = 0.005, 4DCT‐P vs. 3DCT). Median AUC scores (ideal = 0) for 3DCT, 4DCT‐P, and 4DCT‐A were 0.25 [0.14–0.49], 0.12 [0.05–0.42], and 0.13 [0.09–0.44], respectively (p = 0.005, 4DCT‐P vs. 3DCT). Nine of ten 4DCT‐P plans and all 4DCT‐A plans measured within 2.5% of expected dose in the treatment planning system (TPS), compared with seven 3DCT plans. Conclusion For the cases studied tumor motion range and average density was better represented with 4DCT compared with 3DCT, even in the presence of irregular breathing. 4DCT images allowed for delivery of VMAT plans with acceptable dosimetric accuracy. No significant differences were detected between phase and amplitude resorting. In combination with 4D cone beam imaging at treatment, our findings have given us confidence to introduce 4DCT and VMAT for lung radiotherapy patients with irregular breathing.
An overview of regulations for bioequivalence assessment of locally acting orally inhaled drug products for the United States, Europe, Canada, and India

ABSTRACT Introduction Bioequivalence is established by comparing the bioequivalence study results of generic drugs with the reference listed drug. Several global regulatory agencies have published the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. Areas covered The prime intent of the present article is to compare the regulatory guidance for bioequivalence assessment of locally acting OIDPs published by global regulatory authorities. Regulatory recommendations on bioequivalence were based on assessment for different parameters such as inhaler device, formulation, reference product selection, in-vitro, and in-vivo studies. The United States Food and Drug Administration and Health Canada suggest an aggregated weight of evidence approach and the European Medicines Agency promotes a stepwise approach, whereas though the Indian authorities have not published guidance specifically on OIDPs but provided guidelines for bioavailability and bioequivalence studies. Expert opinion For OIDPs, currently, there is no universally adopted methodology, and regulatory guidance has not been globally harmonized. By understanding and comparing bioequivalence recommendations for different regions, we can create more sensitive, and economic evaluation methods for OIDPs. This could open more alternatives of safe, effective generic OIDPs to the public.
Combustion Characteristics of a Helmholtz-Type Valveless Self-Excited Pulse Combustor

Combustion characteristics of a Helmholtz-type valveless self-excited pulse combustor with continuous supply of gas and air were studied. The physical and mathematical models are established based on the actual pulse combustor, and the combustion characteristics are simulated with CFD. The results show that the possible re-ignition sources for the pulse combustion may be three. The first source may be the hot remnant gas near gas/air mixture. The second re-ignition source may be the high-temperature combustion chamber wall. The third ignition source is the unburned mixture. The pressure, temperature and mass fraction of propane in the combustion chamber have the phase relations and the combustion process stimulates the acoustic oscillation.
The Prognostic Value of Circulating Tumor DNA in Ovarian Cancer: A Meta-Analysis

Background: Studies have shown that circulating tumor DNA (ctDNA) indicates a poor prognosis in ovarian cancer. In this study, meta-analysis was used to assess the relationship between ctDNA and the prognosis of patients with epithelial ovarian cancer. Methods: The clinical trials included in this study were obtained via a search of PubMed, the Cochrane Library, the Web of Science and Embase between the period of establishment and March 2020. We selected clinical studies using qualitative or quantitative ctDNA methods to analyse the prognosis of ovarian epithelial cancer, screened the studies according to the determined inclusion and exclusion criteria, and used the modified JADAD score scale and NOS scale for evaluation, with OS (overall survival) and PFS (progression-free survival) as end events. The Cochrane Evaluation Tool was used to evaluate the quality of the randomized controlled trials. Stata 15.0 software was used to combine the effect ratio (hazard ratio, HR) and its 95% confidence interval (CI). In addition, a source analysis of ctDNA specimens, an analysis of ctDNA detection methods and a subgroup and sensitivity analysis of FIGO staging were performed. Results: A total of 8 studies were included in this meta-analysis, and ctDNA was found to be an independent risk factor for patients with epithelial ovarian cancer (OS: HR = 2.36, 95% CI [1.76,3.17], P < .001; PFS: HR = 2.51, 95% CI [1.83,3.45]). Conclusions: The results of our analysis suggested that ctDNA is a potential biomarker that can be used to evaluate the prognosis of patients with ovarian cancer.
Quantitative correlative microscopy reveals the ultrastructural distribution of endogenous endosomal proteins

Van der Beek et al. introduce a quantitative CLEM method using fluorescence to label electron microscopy images by overlay. By comparing the ultrastructural distributions of the endosomal regulators Rab5, Rab7, EEA1, APPL1, and PI(3)P, they reveal distinct endosomal subpopulations and an unexpected localization of EEA1 to late endosomes.
Low levels of minimal residual disease after induction chemotherapy for BCR‐ABL1‐negative acute lymphoblastic leukaemia in adults are clinically relevant

The aim of the present study was to evaluate the significance of low‐level minimal/measurable residual disease (MRD) during early consolidation treatment in adult BCR‐ABL1–negative acute lymphoblastic leukaemia. The MRD load was monitored by immunoglobulin/T‐cell receptor rearrangements and assessed as negative [complete MRD response (CMR)], positive non‐quantifiable (MRDnq) and positive quantifiable (MRDq). MRDnq before the first and second consolidation blocks had a comparable negative effect on survival as MRDq. The 5‐year overall survival for CMR, MRDnq and MRDq at week 11 was 74·0%, 42·3% and 35·0% respectively. No central nervous system infiltration and MRD at week 11 were independent prognostic factors for survival on multivariate analysis (hazard ratios 0·32 and 2·25).
Blowin’ in the wind: Dispersal, structure, and metacommunity dynamics of aeolian diatoms in the McMurdo Sound region, Antarctica

Diatom metacommunities are structured by environmental, historical, and spatial factors that are often attributed to organism dispersal. In the McMurdo Sound region (MSR) of Antarctica, wind connects aquatic habitats through delivery of inorganic and organic matter. We evaluated the dispersal of diatoms in aeolian material and its relation to the regional diatom metacommunity using light microscopy and 18S rRNA high‐throughput sequencing. The concentration of diatoms ranged from 0 to 8.76 * 106 valves · g−1 dry aeolian material. Up to 15% of whole cells contained visible protoplasm, indicating that up to 3.43 * 104 potentially viable individuals could be dispersed in a year to a single 2 ‐cm2 site. Diatom DNA and RNA was detected at each site, reinforcing the likelihood that we observed dispersal of viable diatoms. Of the 50 known morphospecies in the MSR, 72% were identified from aeolian material using microscopy. Aeolian community composition varied primarily by site. Meanwhile, each aeolian community was comprised of morphospecies found in aquatic communities from the same lake basin. These results suggest that aeolian diatom dispersal in the MSR is spatially structured, is predominantly local, and connects local aquatic habitats via a shared species pool. Nonetheless, aeolian community structure was distinct from that of aquatic communities, indicating that intrahabitat dispersal and environmental filtering also underlie diatom metacommunity dynamics. The present study confirms that a large number of diatoms are passively dispersed by wind across a landscape characterized by aeolian processes, integrating the regional flora and contributing to metacommunity structure and landscape connectivity.
Psychometric properties of the psychosocial impact of assistive devices scale (PIADS): A systematic review

ABSTRACT The Psychosocial Impact of Assistive Devices Scale (PIADS) is commonly used to assess the psychosocial effects of an assistive device. Given its growing use, an appraisal of the evidence regarding its psychometric properties is required. We conduct a systematic review using validated critical appraisal scales to analyze both the quality and content of the evidence on the psychometric properties of the PIADS. PubMed/Medline, Embase, and CINAHL were systematically searched for identification of studies. Two independent reviewers appraised the retrieved studies using MacDermid and COSMIN-RoB checklists, and extracted data regarding the psychometric measurements reported. MacDermid scores showed that 8 out of 11 studies were, at least, of good methodological quality. COSMIN-RoB scores ranged from inadequate to very good. Except criterion and construct validity, which have presented a moderate level of evidence, the other psychometric properties assessed have demonstrated a high level of evidence. Cross‐cultural validity, measurement error, and responsiveness have not been studied. Few studies have yet evaluated the psychometric properties of the PIADS. However, the quality of the evidence that they provide is mostly adequate. Therefore, this review supports the use of the PIADS, which has overall good psychometric properties.
Variation and Evolution of Human Centromeres: A Field Guide and Perspective

We are entering a new era in genomics where entire centromeric regions are accurately represented in human reference assemblies. Access to these high-resolution maps will enable new surveys of sequence and epigenetic variation in the population and offer new insight into satellite array genomics and centromere function. Here, we focus on the sequence organization and evolution of alpha satellites, which are credited as the genetic and genomic definition of human centromeres due to their interaction with inner kinetochore proteins and their importance in the development of human artificial chromosome assays. We provide an overview of alpha satellite repeat structure and array organization in the context of these high-quality reference data sets; discuss the emergence of variation-based surveys; and provide perspective on the role of this new source of genetic and epigenetic variation in the context of chromosome biology, genome instability, and human disease.
Diverse thermophilic Bacillus species with multiple biotechnological activities are associated within the Egyptian soil and compost samples

Thermophilic strains of Bacillus can express enzymes of higher thermal stability, which allows carrying out industrial fermentations under higher temperatures. This lowers the contamination potential, accelerates mixing rates and facilitates the recovery of fermentation end products. The present study was thus designed to isolate and characterize thermophilic Bacillus cultures from soil and compost samples. Forty-two thermophilic Bacillus isolates could be identified employing morphological, physiological and the 16S rRNA gene sequencing analyses. The isolates showed a high degree of biological diversity involving 13 Bacillus species and 1 subspecies but were dominated by Bacillus licheniformis. Phylogenetic analysis of B. licheniformis isolates based on the DNA sequencing of gyrA and rpoB genes presented them in two main genetic groups. Isolates of five thermophilic species including B. licheniformis, Bacillus altitudinis, Bacillus paralicheniformis, Bacillus subtilis and Bacillus thermoamylovorans showed multiple activities to degrade all of cellulose, hemicellulose and lignin. Those multifunctional thermophilic Bacillus isolates can be harnessed in the degradation of plant wastes for the production of biofuels and compost.
Assay technologies facilitating drug discovery for ADP‐ribosyl writers, readers and erasers

ADP‐ribosylation is a post‐translational modification catalyzed by writer enzymes – ADP‐ribosyltransferases. The modification is part of many signaling events, can modulate the function and stability of target proteins, and often results in the recruitment of reader proteins that bind to the ADP‐ribosyl groups. Erasers are integral actors in these signaling events and reverse the modification. ADP‐ribosylation can be targeted with therapeutics and many inhibitors against writers exist, with some being in clinical use. Inhibitors against readers and erasers are sparser and development of these has gained momentum only in recent years. Drug discovery has been hampered by the lack of specific tools, however many significant advances in the methods have recently been reported. We discuss assays used in the field with a focus on methods allowing efficient identification of small molecule inhibitors and profiling against enzyme families. While human proteins are focused, the methods can be also applied to bacterial toxins and virus encoded erasers that can be targeted to treat infectious diseases in the future.
Towards a Design Process Ontology

ABSTRACT In the absence of any single coherent all-encompassing theoretical model of designing, this study seeks to review and rationalize theories of design process as the foundational framework for exploring where value is added through design. This leads to an interim design process ontology, or more simply; a terminological framework which can accommodate the significant developments in design process modelling of the last 50 years alongside identification of other significant factors which affect design outcomes. Within the resulting ontology class hierarchy, design process is placed within the wider context of design domain and an Input-Process-Output classification. Within the Process class, Motivation, Scale, Path and Design Process Structures are identified as significant subclasses. Research challenges resulting from the interim design ontology are identified.