bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Bleaching Associated with Er:YAG and Nd:YAG Laser on Enamel Structure and Bacterial Biofilm Formation
Authors: Hou Xiuxiu , Yuan Keyong , Huang Zhengwei , Ma Rui
Published: December 2021

Objective. To compare the effects of bleaching associated with Er:YAG and Nd:YAG laser on enamel structure and mixed biofilm formation on teeth surfaces. Materials and Methods. Sixty-eight enamel samples were randomly divided into four groups (

n
=
17

), control, Opalescence Boost only, Opalescence Boost plus Er: YAG laser, and Opalescence Boost plus Nd:YAG laser. The structure was observed using SEM after bleaching. Subsequently, the treated enamel samples were also cultured in suspensions of Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus, and Fusobacterium nucleatum (Fn) for 24 and 48 h. Biofilm formation was quantified by crystal violet staining, and the structure was visualized by confocal laser scanning microscopy. The data were analyzed using the Kruskal-Wallis method. Results. The enamel structure significantly changed after bleaching. There was no obvious difference in the biofilm formation after 24 h; however, after 48 hours, the amount of biofilm increased significantly. Remarkably, the amount was significantly higher on enamel bleached only, however, there was no significant difference between samples bleached with Er:YAG or Nd:YAG laser compared to the control. Conclusions. Bleaching only appeared to markedly promote biofilm formation after 48 h, and the biofilms on samples bleached with Er:YAG or Nd:YAG laser did not change significantly, showing that bleaching with Er:YAG or Nd:YAG laser can be safely applied in clinical practice.
Design and Study of an mmWave Wearable Textile Based Compact Antenna for Healthcare Applications
Authors: Monirujjaman Khan Mohammad , Hossain Junayed , Islam Kaisarul , Ovi Nazmus Sadat , Shovon Md. Nakib Alalm , Abbasi Muhammad Inam , Bourouis Sami
Published: December 2021

In this study, the design of a compact and novel millimeter wave cotton textile-based wearable antenna for body-centric communications in healthcare applications is presented. The free space and on-body antenna performance parameters for the proposed antenna at 60 GHz are investigated and analyzed. The antenna is based on a 1.5 mm thick cotton substrate and has an overall dimension of 7.0 × 4.5 × 1.5 mm3. In free space, the antenna is resonant at 60 GHz and achieves a wide impedance bandwidth. The maximum gain at this resonant frequency is 6.74 dBi, and the radiation efficiency is 93.30%. Parametric changes were carried out to study the changes in the resonant frequency, gain, and radiation efficiency. For body-centric communications, the antenna was simulated at 5 different distances from a three-layer human torso-equivalent phantom. The radiation efficiency dropped by 24% and gradually increased with the gap distance. The antenna design was also analyzed by using 10 different textile substrates for both free space and on-body scenarios. The major benefits of the antenna are discussed as follows. Compared to a previous work, the antenna is very efficient, compact, and has a wide bandwidth. In BCWCs for e-health applications, the antenna needs to be very compact due to the longer battery life, and it has to have a wide bandwidth for high data rate communication. Since the antenna will be wearable with a sensor system, the shape of the antenna needs to be planar, and it is better to design the antenna on a textile substrate for integration into clothes. The antenna also needs to show high gain and efficiency for power-efficient communication. This proposed antenna meets all these criteria, and hence, it will be a good candidate for BCWCs in e-health applications.
Lightweight Design and Dynamics Analysis of ZYL‐15000D Directional Drill Reducer
Authors: Zhao Xiaohong , Yan Xianguo , Chen Zhi , Su Hang
Published: December 2021

Since the output torque of the rotary reducer of the ZYL‐15000D‐kilometer directional drill is proportional to the gear train transmission ratio, the output torque is large enough when the input speed and output speed meet the design goal. This paper selects the method of reducing the transmission ratio to optimize the size parameters of the reducer. MATLAB genetic algorithm is used in the optimization design, and the minimum volume of the rotary part reducer is taken as the objective of optimization design, while the design variables and constraints are determined. The optimal value of design variables was obtained through optimization, and the parameter values of each gear were determined accordingly. Through analysis, the total volume of the optimized gear reducer was reduced by 49.6%. Then, the 3D model of the optimized gear was created, and the analysis of the transient dynamics of the optimized gear was carried out with ANSYS Workbench software. According to the analysis results, the optimized gear met the strength requirements and provided a reference for the subsequent optimization design of other types of gear reducers.
An Impact‐Echo Experimental Approach for Detecting Concrete Structural Faults
Authors: Yang Ya-xun , Chai Wen-hao , Liu De-chuang , Zhang Wei-de , Lu Jia-cheng , Yang Zhi-kui
Published: December 2021

For the current problem of detection of grouting defects in posttensioned prestressed concrete members, the paper takes a single‐layer arrangement of prestressed pipes as the object of study. The influence law of the main factors such as pipe material, defect size, defect critical surface location, and prestressing reinforcement location on the results of the impact‐echo method for detecting concrete grouting defects was studied. Firstly, the ABAQUS finite element software was used to simulate these factors to obtain the influence law on the detection results, and a modal test was conducted to verify them. The results show that the impact‐echo method can effectively test the location of defects and the degree of burial depth, and the pipe material influences the test results, and the impact of corrugated metal pipe is smaller and more accurate than the PVC pipe. In addition, the greater the plate thickness frequency drift rate, the larger the transverse size of the defect, so the plate thickness frequency drift rate and the measured defect depth are combined to quantitatively determine the depth of the defect.
miR-23b-3p Inhibits the Oncogenicity of Colon Adenocarcinoma by Directly Targeting NFE2L3
Authors: Huang Guohong , Yang Yimei , Lv Mengxin , Huang Tian , Zhan Xiaoyan , Yao Yingjie , Hou Jianghou
Published: December 2021

Background and Aims. MicroR-23b-3p (miR-23b-3p) has been found to be abnormally expressed in a variety of malignant tumors and to play a role in tumor inhibition or promotion. However, the regulatory mechanism of miR-23b-3p in COAD remains unclear. The purpose of this study was to investigate the clinical significance of miR-23b-3p expression in COAD cells and to explore its role and regulatory mechanism in the growth of COAD. Materials and Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure miR-23b-3p expression in COAD tissues and cell lines. After transfecting miR-23b-3p mimics into two human COAD cell lines (SW620 and LoVo), the cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to detect cell proliferation, the Transwell assay was used to measure cell migration and invasion capacity, and flow cytometry was used to evaluate cell apoptosis in vitro. In addition, a luciferase reporter assay was used to determine whether miR-23b-3p targets NFE2L3. The downstream regulatory mechanisms of miR-23b-3p action in COAD cells were also investigated. For in vivo tumorigenesis assay, COAD cells stably overexpressing miR-23b-3p were injected subcutaneously into the flank of nude mice to obtain tumors. Results. Significantly decreased expression of miR-23b-3p was detected in COAD tissues and cell lines. Exogenous miR-23b-3p expression inhibited cell proliferation, migration, and invasion and promoted cell apoptosis of COAD cells in vitro. Nuclear factor erythroid 2 like 3 (NFE2L3) was identified as a direct target gene of miR-23b-3p. In addition, reintroduction of NFE2L3 partially abolished the anticancer effects of miR-23b-3p on COAD cells. Furthermore, miR-23b-3p overexpression hindered the growth of COAD cells in vivo. Conclusion. miR-23b-3p inhibited the oncogenicity of COAD cells in vitro and in vivo by directly targeting NFE2L3, suggesting the importance of the miR-23b-3p/NFE2L3 pathway in the development of COAD.
Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility
Authors: Prisco Sasha Z. , Hartweck Lynn M. , Rose Lauren , Lima Patricia D.A. , Thenappan Thenappan , Archer Stephen L. , Prins Kurt W.
Published: December 2021

Background:

Right ventricular dysfunction (RVD) is the leading cause of death in pulmonary arterial hypertension (PAH), but no RV-specific therapy exists. We showed microtubule-mediated junctophilin-2 dysregulation (MT-JPH2 pathway) causes t-tubule disruption and RVD in rodent PAH, but the druggable regulators of this critical pathway are unknown. GP130 (glycoprotein 130) activation induces cardiomyocyte microtubule remodeling in vitro; however, the effects of GP130 signaling on the MT-JPH2 pathway and RVD resulting from PAH are undefined.

Methods:

Immunoblots quantified protein abundance, quantitative proteomics defined RV microtubule-interacting proteins (MT-interactome), metabolomics evaluated the RV metabolic signature, and transmission electron microscopy assessed RV cardiomyocyte mitochondrial morphology in control, monocrotaline, and monocrotaline-SC-144 (GP130 antagonist) rats. Echocardiography and pressure-volume loops defined the effects of SC-144 on RV-pulmonary artery coupling in monocrotaline rats (8–16 rats per group). In 73 patients with PAH, the relationship between interleukin-6, a GP130 ligand, and RVD was evaluated.

Results:

SC-144 decreased GP130 activation, which normalized MT-JPH2 protein expression and t-tubule structure in the monocrotaline RV. Proteomics analysis revealed SC-144 restored RV MT-interactome regulation. Ingenuity pathway analysis of dysregulated MT-interacting proteins identified a link between microtubules and mitochondrial function. Specifically, SC-144 prevented dysregulation of electron transport chain, Krebs cycle, and the fatty acid oxidation pathway proteins. Metabolomics profiling suggested SC-144 reduced glycolytic dependence, glutaminolysis induction, and enhanced fatty acid metabolism. Transmission electron microscopy and immunoblots indicated increased mitochondrial fission in the monocrotaline RV, which SC-144 mitigated. GP130 antagonism reduced RV hypertrophy and fibrosis and augmented RV-pulmonary artery coupling without altering PAH severity. In patients with PAH, higher interleukin-6 levels were associated with more severe RVD (RV fractional area change 23±12% versus 30±10%,
P
=0.002).

Conclusions:

GP130 antagonism reduces MT-JPH2 dysregulation, corrects metabolic derangements in the RV, and improves RVD in monocrotaline rats.
Verification of Atellica 1500 and comparison with Iris urine analyser and urine culture
Authors: Čičak Helena , Bejuk Danijela , Radišić Biljak Vanja , Šimundić Ana-Maria , Nikler Ana
Published: December 2021

The aims of study were to assess: 1) performance specifications of Atellica 1500, 2) comparability of Atellica 1500 and Iris, 3) the accuracy of both analysers in their ability to detect bacteria.
Carryover, linearity, precision, reproducibility, and limit of blank (LoB) verification were evaluated for erythrocyte and leukocyte counts. ICSH 2014 protocol was used for estimation of carryover, CLSI EP15-A3 for precision, and CLSI EP17 for LoB verification. Comparison for quantitative parameters was evaluated by Bland-Altman plot and Passing-Bablok regression. Qualitative parameters were evaluated by Weighted kappa analysis. Sixty-five urine samples were randomly selected and sent for urine culture which was used as reference method to determine the accuracy of bacteria detection by analysers.
Analytical specifications of Atellica 1500 were successfully verified. Total of 393 samples were used for qualitative comparison, while 269 for sediment urinalysis. Bland-Altman analysis showed statistically significant proportional bias for erythrocytes and leukocytes. Passing-Bablok analysis for leukocytes pointed to significant constant and minor proportional difference, while it was not performed for erythrocytes due to significant data deviation from linearity. Kappa analysis resulted in the strongest agreements for pH, ketones, glucose concentrations and leukocytes, while the poorest agreement for bacteria. The sensitivity and specificity of bacteria detection were: 91 (59-100)% and 76 (66-87)% for Atellica 1500 and 46 (17-77)% and 96 (87-100)% for Iris.
There are large differences between Atellica 1500 and Iris analysers, due to which they are not comparable and can not be used interchangeably. While there was no difference in specificity of bacteria detection, Iris analyser had greater sensitivity.
Evaluation of the clinical chemistry tests analytical performance with Sigma Metric by using different quality specifications - Comparison of analyser actual performance with manufacturer data
Authors: Keleş Murat
Published: December 2021

The interest in quality management tools/methodologies is gradually increasing to ensure quality and accurate results in line with international standards in clinical laboratories. Six Sigma stands apart from other methodologies with its total quality management system approach. However, the lack of standardization in tolerance limits restricts the advantages for the process. Our study aimed both to evaluate the applicability of analytical quality goals with Roche Cobas c 702 analyser and to determine achievable goals specific to the analyser used.
The study examined under two main headings as Sigmalaboratory and Sigmaanalyser. Sigmalaboratory was calculated using internal and external quality control data by using Roche Cobas c 702 analyser for 21 routine biochemistry parameters and, Sigmaanalyser calculation was based on the manufacturer data presented in the package inserts of the reagents used in our laboratory during the study. Sigma values were calculated with the six sigma formula.
Considering the total number of targets achieved, Sigmaanalyser performed best by meeting all CLIA goals, while Sigmalaboratory showed the lowest performance relative to biological variation (BV) desirable goals.
The balance between the applicability and analytical assurance of “goal-setting models” should be well established. Even if the package insert data provided by the manufacturer were used in our study, it was observed that almost a quarter of the evaluated analytes failed to achieve even “acceptable” level performance according to BV-based goals. Therefore, “state-of-the-art” goals for the Six Sigma methodology are considered to be more reasonable, achievable, and compatible with today’s technologies.
Factors Affecting Language Proficiency in Heritage Language: The Case of Young Russian Heritage Speakers in Spain
Authors: Vorobyeva Tamara , Bel Aurora
Published: December 2021

This study focuses on the issue of language proficiency attainment among young heritage speakers of Russian living in Spain and examines factors that have been claimed to promote heritage language proficiency, namely, age, gender, age of onset to L2, quantity of exposure and family language use. A group of 30 Russian-Spanish-Catalan trilingual children aged 7–11 participated in the study. In order to measure heritage language proficiency (L1 Russian), oral narratives were elicited.

The results demonstrated a significant relationship between L1 proficiency and three sociolinguistic variables (age of onset to L2, quantity of exposure and family language use). Additionally, the multiply regression model demonstrated that the only significant variable affecting language proficiency was family language use and it accounted only for 33% of the variation of children’s language proficiency. The study raises the question about what are the other, yet unknown factors, which can affect heritage language proficiency.
Three new species of Scolytoplatypus Schaufuss from China, and notes on the movement and functions of the prosternal processes (Coleoptera: Curculionidae: Scolytinae)
Authors: GEBHARDT HEIKO , BEAVER ROGER A. , ALLGAIER CHRISTOPH
Published: December 2021

Three new species from China (Yunnan), Scolytoplatypus costatus Gebhardt & Beaver, S. geminus Gebhardt & Beaver and S. peniculatus Gebhardt & Beaver, are described and compared with related species of the genus. The male prosternum of Asian Scolytoplatypus species shows species-specific characters, and frequently bears a pair of processes on or close to the anterior margin. We comment here for the first time on the movement of the processes and their likely functions, and survey their occurrence in Asian species of Scolytoplatypus.
Optimization and prediction of engine block vibration using micro-electro-mechanical systems capacitive accelerometer, fueled with diesel-bioethanol (water-hyacinth) blends by response surface methodology and artificial neural network
Authors: Choudhary Akhilesh Kumar , Chelladurai H , Panchal Hitesh
Published: December 2021

The current investigation is focused on the vibration signals analysis for health status diagnosis of the single-cylinder diesel engine fueled with bioethanol diesel mixture. The water hyacinth (WH) plants (Eichhornia crassipes) are used as raw materials for bioethanol production. The bio-ethanol obtained from WH has been mixed with diesel fuel (WBED) to various extent. Systematically designed experiments were conducted with different working parameters like load, fuel injection pressure (FIP), and compression ratio (CR) in a diesel engine. The Micro-Electro-Mechanical Systems (MEMS) capacitive accelerometer was used to get vibration signals from the engine while operating with blended fuels. The obtained experimental vibrations data have been used to predict the engine vibration by using Response Surface Methodology (RSM) technique and Artificial Neural Network (ANN). The experimental results have been compared with RSM and ANN prediction results. From results, it is elicited that the acceleration declines with the increase in load and CR. At all tested blends, FIP produces a significant effect on the engine block vibration. Among all blends, WBED 5 and WBED 10 produce less vibration as compared to other diesel bioethanol blends. At optimized operating condition the engine block vibration for WBED 5; the experimental acceleration is 0.016962 m/s2 and the predicted acceleration by RSM and ANN is 0.016182 m/s2 and 0.0166 m/s2, respectively. For WBED 10, the acceleration is 0.0172604 m/s2 and the predicted acceleration by RSM and ANN 0.016207 m/s2 0.017 m/s2, respectively, has been found.
The age structure of cases as the key of COVID-19 severity: Longitudinal population-based analysis of European countries during 150 days
Authors: Hulíková Tesárková Klára , Dzúrová Dagmar
Published: December 2021

Aims:

Over a million confirmed cases of the coronavirus disease (COVID-19) across 16 European countries were observed during the first wave of the pandemic. Epidemiological measures like the case fatality rate (CFR) are generally used to determine the severity of the illness. The aim is to investigate the impact of the age structure of reported cases on the reported CFR and possibilities of its demographic adjustment for a better cross-country comparison (age-standardized CFRs, time delay between cases detection and death).

Methods:

This longitudinal study uses prospective, population-based data covering 150 days, starting on the day of confirmation of the 100th case in each country. COVerAGE-DB and the Human Mortality Database were used in this regard. The age-standardized CFRs were calculated with and without the time delay of the number of deaths after the confirmation of the cases.

Results:

The observed decline in the CFRs at the end of the first wave is partly given by the changes in the age structure of confirmed cases. Using the adjusted (age-standardized) CFRs with time delay, the risk of death among confirmed cases is much more stable in comparison to crude (observed) CFRs.

Conclusions:

Preventing the spread of COVID-19 among the elderly is an important way to positively influence the overall fatality rate, decrease the number of deaths, and not overload the health systems. The crude CFRs (still often presented) are not sufficient for a proper evaluation of the development across populations nor as a means of identifying the influencing factors.
Inflammatory bowel disease in adults
Authors: Qazi Umang
Published: December 2021

Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of disorders characterised by chronic inflammation of the gastrointestinal tract, of which ulcerative colitis and Crohn’s disease are the most common. It is estimated that 500 000 people in the UK currently live with IBD. There are two peaks of incidence, the first of which is between 15 and 30 years of age, with a second smaller peak between 60 and 80 years of age. Its prevalence is ever increasing, and GPs play an important role in early diagnosis, which is the key in reducing the need for aggressive treatment.
The effects of cellulose nanofibers compounded in water-based undercoat paint on the discoloration and deterioration of painted wood products
Authors: Shimokawa Tomoko , Hishikawa Yukako , Togawa Eiji , Shibuya Hajime , Kobayashi Masahiko , Ishikawa Atsuko , He Xin , Ohki Hironari , Magara Kengo
Published: December 2021

Cellulose nanofibers (CNFs) have many potentials as filler to improve the properties of the other materials. We have developed the novel paints containing CNFs, and which controlled the discoloration of wood products. To clarify the discoloration mechanism of wood panels using an undercoat paint containing CNFs, prepared by an integrated process from Cryptomeria japonica, the composites and films made of CNFs and acryl resin that was a raw material for the paints were prepared. Observation of the surface of the CNFs/acryl resin composite film by atomic force microscopy showed that the fibers and the resin were uniformly mixed. The composite film prevented light transmittance in the ultraviolet (UV) light region, as well as oxygen gas permeation. The permeability coefficient of the oxygen gas decreased to 60% with the addition of 1.5 wt% of CNFs to the acryl resin. The addition of CNFs also increased the breaking stress by approximately 1.5 times compared with the acryl resin film. Electron spin resonance (ESR) analysis after UV irradiation resulted in the lowest radical formation of a piece of wood wrapped in the CNFs/acryl resin composite compared with the acryl-coated specimen and the wood as it was. Therefore, the CNFs composite film shielded the UV rays and oxygen more effectively than the original acryl resin, making it difficult for these factors to reach the wood’s surface, and thus, perhaps suppressing the generation of radicals from the wood. These actions would suppress the production of coloring substances caused by the radicals, resulting in the suppression of discoloration. Furthermore, the increase in the film’s strength by the addition of CNFs would have enhanced the stability of overall the paints with a CNF-containing undercoat. These effects might have contributed not only to the prevention of discoloration but also to the prevention of the occurrence of minute cracks caused by various weather deterioration factors.
Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States
Authors: McAllister Peter , Lamerato Lois , Krasenbaum Lynda J. , Cohen Joshua M. , Tangirala Krishna , Thompson Stephen , Driessen Maurice , Casciano Julian , Dotiwala Zenobia , Mauskop Alexander
Published: December 2021

Background

Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation.

Methods

Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation.

Results

Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P < 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P < 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232).

Conclusions

Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting.
FCLQC: fast and concurrent lossless quality scores compressor
Authors: Cho Minhyeok , No Albert
Published: December 2021

Background

Advances in sequencing technology have drastically reduced sequencing costs. As a result, the amount of sequencing data increases explosively. Since FASTQ files (standard sequencing data formats) are huge, there is a need for efficient compression of FASTQ files, especially quality scores. Several quality scores compression algorithms are recently proposed, mainly focused on lossy compression to boost the compression rate further. However, for clinical applications and archiving purposes, lossy compression cannot replace lossless compression. One of the main challenges for lossless compression is time complexity, where it takes thousands of seconds to compress a 1 GB file. Also, there are desired features for compression algorithms, such as random access. Therefore, there is a need for a fast lossless compressor with a reasonable compression rate and random access functionality.

Results

This paper proposes a Fast and Concurrent Lossless Quality scores Compressor (FCLQC) that supports random access and achieves a lower running time based on concurrent programming. Experimental results reveal that FCLQC is significantly faster than the baseline compressors on compression and decompression at the expense of compression ratio. Compared to LCQS (baseline quality score compression algorithm), FCLQC shows at least 31x compression speed improvement in all settings, where a performance degradation in compression ratio is up to 13.58% (8.26% on average). Compared to general-purpose compressors (such as 7-zip), FCLQC shows 3x faster compression speed while having better compression ratios, at least 2.08% (4.69% on average). Moreover, the speed of random access decompression also outperforms the others. The concurrency of FCLQC is implemented using Rust; the performance gain increases near-linearly with the number of threads.

Conclusion

The superiority of compression and decompression speed makes FCLQC a practical lossless quality score compressor candidate for speed-sensitive applications of DNA sequencing data. FCLQC is available at https://github.com/Minhyeok01/FCLQC and is freely available for non-commercial usage.
Intellectual disability genomics: current state, pitfalls and future challenges
Authors: Maia Nuno , Nabais Sá Maria João , Melo-Pires Manuel , de Brouwer Arjan P. M. , Jorge Paula
Published: December 2021

Intellectual disability (ID) can be caused by non-genetic and genetic factors, the latter being responsible for more than 1700 ID-related disorders. The broad ID phenotypic and genetic heterogeneity, as well as the difficulty in the establishment of the inheritance pattern, often result in a delay in the diagnosis. It has become apparent that massive parallel sequencing can overcome these difficulties. In this review we address: (i) ID genetic aetiology, (ii) clinical/medical settings testing, (iii) massive parallel sequencing, (iv) variant filtering and prioritization, (v) variant classification guidelines and functional studies, and (vi) ID diagnostic yield. Furthermore, the need for a constant update of the methodologies and functional tests, is essential. Thus, international collaborations, to gather expertise, data and resources through multidisciplinary contributions, are fundamental to keep track of the fast progress in ID gene discovery.
The role of matrix metalloproteinases in patients with pulmonary hypertension: data from a prospective study
Authors: Marc Adriana , Pop Calin , Sitar-Taut Adela-Viviana , Budisan Liviuta , Berindan-Neagoe Ioana , Pop Dana
Published: December 2021

Background

Despite several therapies, pulmonary hypertension (PH) is still a severe disease which can lead to right heart failure. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cardiac and vascular remodeling in PH. Therefore, these biomarkers play an important role in PH patients. This study investigated whether TIMP-4, MMP-2, and N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) plasma levels are useful in assessing the severity of PH and other clinical or echocardiographic parameters.

Methods

The concentrations of MMP-2, TIMP-4, and NT-proBNP in 68 PH patients were compared with those of 12 controls without PH. All patients underwent a physical examination, echocardiography, and were checked for the presence of cardiovascular risk factors; also, plasma concentrations of MMP-2, TIMP-4, NT-proBNP, total cholesterol, and triglycerides were determined.

Results

In PH patients, significantly elevated plasma levels of TIMP-4 (PH: 2877.99 ± 1363.78 pg/ml, control: 2028.38 ± 762.67 pg/ml, p = 0.0068) and NT-proBNP ( PH: 2405.00 pg/ml—5423.47 ± 6703.38 pg/ml, control: 411.0000 pg/ml—421.75 ± 315.37 pg/ml, p = 0.01) were detected. We also observed that MMP-2 and NT-proBNP were significantly increased in patients with higher WHO functional class (p = 0.001 for MMP-2, p = 0.008 for NT-proBNP), higher pressure in the pulmonary artery (p = 0.002 for MMP-2, p = 0.001 for NT-proBNP), and more severe tricuspid regurgitation (p = 0.001 for MMP-2, p = 0.009 for NT-proBNP). TIMP-4 was elevated in patients with more severe pressure in the pulmonary artery (p = 0.006).

Conclusions

The plasma levels of TIMP-4 and NT-proBNP are higher in PH patients. MMP-2 and NT-proBNP correlates with different PH parameters severity (WHO functional class, sPAP severity, TV regurgitation severity). Therefore, plasmatic levels of MMP-2 and NT-proBNP at this kind of patients reflect disease severity and may have a prognostic role. MMP-2 can help assess the beneficial effects of PH pharmacotherapy on tissue remodeling. These remodeling biomarkers may not have a diagnostic value but they have the potential to predict survival. Nevertheless, a greater understanding of the involvement of MMPs in PH is mandatory to further explore the prognostic role and the possibilities of therapeutic MMP inhibition in PH.
Early experience with an opt-in research register - Scottish Health Research Register (SHARE): a multi-method evaluation of participant recruitment performance
Authors: Shi Wen , Vasishta Shobna , Dow Louise , Cavellini Daniella , Palmer Colin , McKinstry Brian , Sullivan Frank
Published: December 2021

Background

Recruiting participants to a clinical study is a resource-intensive process with a high failure rate. The Scottish Health Research Register (SHARE) provides recruitment support service which helps researchers recruit participants by searching patients’ Electronic Health Records (EHRs). The current study aims to evaluate the performance of SHARE in participant recruitment.

Methods

Recruitment projects eligible for evaluation were those that were conducted for clinical trials or observational studies and finished before 2020. For analysis of recruitment data, projects with incomplete data were excluded. For each project we calculated, from SHARE records, 1) the fraction of the participants recruited through SHARE as a percentage of the number requested by researchers (percentage fulfilled), 2) the percentage of the potential candidates provided by SHARE to researchers that were actually recruited (percentage provided and recruited), 3) the percentage of the participants recruited through SHARE of all the potentially eligible candidates identified by searching registrants’ EHRs (percentage identified and recruited). Research teams of the eligible projects were invited to participate in an anonymised online survey. Two metrics were derived from research teams’ responses, including a) the fraction of the recruited over the study target number of participants (percentage fulfilled), and b) the percentage of the participants recruited through SHARE among the candidates received from SHARE (percentage provided and recruited).

Results

Forty-four projects were eligible for inclusion. Recruitment data for 24 projects were available (20 excluded because of missingness or incompleteness). Survey invites were sent to all the eligible research teams and received 12 responses. Analysis of recruitment data shows the overall percentage fulfilled was 34.2% (interquartile 13.3–45.1%), the percentage provided and recruited 29.3% (interquartile 20.6–52.4%) and percentage identified and recruited 4.9% (interquartile 2.6–10.2%). Based on the data reported by researchers, percentage fulfilled was 31.7% (interquartile 5.8–59.6%) and percentage provided and recruited was 20.2% (interquartile 8.2–31.0%).

Conclusions

SHARE may be a valuable resource for recruiting participants for some clinical studies. Potential improvements are to expand the registrant base and to incorporate more data generated during patients’ different health care encounters into the candidate-searching step.
Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study
Authors: Suzuki Fumitaka , Suzuki Yoshiyuki , Karino Yoshiyasu , Tanaka Yasuhito , Kurosaki Masayuki , Yatsuhashi Hiroshi , Atarashi Tomofumi , Atsukawa Masanori , Watanabe Tsunamasa , Enomoto Masaru , Kudo Masatoshi , Maeda Naoto , Kohno Hiroshi , Joko Kouji , Michitaka Kojiro , Miki Koichiro , Takahashi Kazuhiro , Ide Tatsuya , Fujiyama Shigetoshi , Kohno Tomoko , Itoh Hiroshi , Tsukamoto Sakiyo , Suzuki Yuko , Kawano Yoshiaki , Sugiura Wataru , Kumada Hiromitsu
Published: December 2021

Background

Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.

Methods

In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks.

Results

At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was −0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]).

Conclusions

In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF.

ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1
Ultrasound contrast agent Sonazoid for the diagnosis of hepatic epithelioid angiomyolipoma: a case report
Authors: Huang Zhe , Xin Jun-yi , Li Kai-yan
Published: December 2021

Background

An angiomyolipoma usually occurs in the kidneys and rarely in the liver. Hepatic epithelioid angiomyolipoma (HEAML), a rare variant of angiomyolipoma, possesses malignant potential and mimics the imaging features of hepatocellular carcinoma. Sonazoid® (perfluorobutane microbubbles), a new contrast agent that facilitates hepatic parenchyma-specific Kupffer phase imaging on contrast-enhanced ultrasonography (CEUS), is useful for the detection and characterization of focal liver lesions.

Case presentation

A 30-year-old man with HEAML underwent CEUS using Sonazoid®, in which new concepts for ultrasonography-based differentiation between HEAML and hepatocellular carcinoma were applied.

Conclusions

This case report provides clinicians and radiologists with a reference for distinguishing HEAML from hepatocellular carcinoma based on CEUS using Sonazoid®.
Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature
Authors: Amanati Ali , Zekavat Omid Reza , Foroutan Hamidreza , Azh Omidreza , Tadayon Ali , Monabati Ahmad , Anbardar Mohammad Hossein , Bozorgi Haleh
Published: December 2021

Background

Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis.

Case presentation

We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention.

Conclusion

Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.
A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report
Authors: Shirai Yoko , Miura Kenichiro , Kaneko Naoto , Ishizuka Kiyonobu , Endo Amane , Hashimoto Taeko , Kanda Shoichiro , Harita Yutaka , Hattori Motoshi
Published: December 2021

Background

Heterozygous truncating variants in the Tripartite motif containing 8 (TRIM8) gene have been reported to cause epileptic encephalopathy, both with and without proteinuria. A recent study showed a lack of TRIM8 protein expression, with suppressor of cytokine signaling 1 (SOCS1) overexpression, in podocytes and tubules from a patient with a TRIM8 variant, who presented with epileptic encephalopathy and focal segmental glomerulosclerosis (FSGS). To date, no patients with TRIM8 variants who presented with nephrotic syndrome but without neurological manifestations have been described.

Case presentation

An 8-year-old girl presented with nephrotic syndrome, without epilepsy or developmental delay. Her kidney biopsy specimens showed FSGS and cystic dilatations of the distal tubules. Whole-exome sequencing identified a novel de novo heterozygous variant in the C-terminal encoding portion of TRIM8 (c.1461C > A), resulting in a premature stop codon (p.Tyr487*). Reverse transcription-polymerase chain reaction using peripheral blood mononuclear cells identified the mRNA sequence of the mutant allele, which confirmed an escape from nonsense-mediated mRNA decay. Immunofluorescence studies showed a lack of TRIM8 expression in glomerular and tubular cells and cystic dilatation of distal tubules. Immunohistochemical studies showed overexpression of SOCS1 in glomerular and tubular cells.

Conclusions

We reported a patient with FSGS, associated with a de novo heterozygous TRIM8 variant, without any neurological manifestations. Our results expanded the clinical phenotypic spectrum of TRIM8 variants.
Renal function in β-thalassemia major patients treated with two different iron-chelation regimes
Authors: Tanous Osama , Azulay Yossi , Halevy Raphael , Dujovny Tal , Swartz Neta , Colodner Raul , Koren Ariel , Levin Carina
Published: December 2021

Background

Renal injury in transfusion dependent β thalassemia patients (TDT) has been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied renal function in TDT patients treated with two different ICT regimes.

Patients and methods

We studied 36 TDT patients: 26 received deferasirox (DFX) and 10 were treated with deferoxamine (DFO) +/− deferiprone (DFP).

Results

Increased uNAG was found in 30% of the DFX group vs. 10% of the DFO+/−DFP group, the mean uNAG level in the DFX group was significantly higher than in the DFO+/−DFP group, (P < 0.05). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (P = 0.03), more pronounced for the DFO+/−DFP group. Twenty nine patients had had their renal function evaluated 10 years earlier; eGFR significantly declined in patients switched to DFX (P = 0.0093) but not in patients who continued DFO+/−DFP.

Conclusions

A high prevalence of renal tubular damage was observed in our TDT patients, particularly those treated with DFX; uNAG was negatively associated with mean 10-year serum ferritin, suggesting ICT’s involvement in tubular injury. A significant decline in eGFR compared to a decade earlier was observed only in patients currently treated with DFX. Strict follow-up of renal function in TDT patients is warranted.
The association of workplace smoke-free policies on individual smoking and quitting-related behaviours
Authors: Lin Haoxiang , Li Min , Chen Meijun , Liu Yihua , Lin Yuting , Liu Zhao , Zheng Zhijie , Chang Chun
Published: December 2021

Background

Our study aims to provide information about workplace smoke-free (SF) policy coverage in mainland China and to assess the relationship between workplace SF policies and secondhand smoke (SHS) exposure, current smoking, smoking harm awareness and quitting intention among smokers.

Method

Data from the 2018 Asia Best Workplace Mainland China programme were used to address these aims. This cross-sectional study included 14,195 employees from the 2018 survey and 14,953 employees from the 2019 survey. Logistic regression with year-fixed effects was applied to these data. The dependent variables were SHS exposure, smoking or smoking harm awareness. The explanatory variable was the SF workplace policy.

Results

A total of 21,275 participants (73.0%) reported working under SF policies. The overall prevalence of smoking and SHS exposure were 20.3% and 52.5%, respectively. The workplace SF policy was significantly associated with lower SHS exposure (OR: 0.48, 95% CI: 0.45–0.51), lower current smoking employees (OR: 0.81, 95% CI: 0.76–0.87) and higher awareness of smoking harm (OR: 1.76, 95% CI: 1.61–1.91). However, workplace SF policy was not significantly associated with quitting intention (OR: 0.99, 95% CI: 0.84–1.16).

Conclusion

Our study identified that although most companies had established workplace SF policies, the overall prevalence of SHS exposure remained very high. Workplace SF policy is associated with lower SHS exposure, lower overall current smoking and higher awareness of smoking harm. These findings provide valuable evidence to promote such policies in all workplaces.
Risk factors of opioid use associated with an enhanced-recovery programme after total knee arthroplasty
Authors: Cao Guorui , Xiang Shiqi , Yang Minglu , Quan Songtao , Yao Junna , Cai Litao , Feng Wei , Yang Xiuli , Xu Hong , Huang Zeyu , Zhang Shaoyun , Yue Chen , Tan Honglue , Pei Fuxing
Published: December 2021

Background

Characterizing the impacts of postoperative opioid use on total knee arthroplasty (TKA) patients may help optimize the pain management after TKA. The aim of the study is to examine the prevalence and risk factors for opioid use with an enhanced-recovery programme after primary TKA.

Methods

We identified 361 patients undergoing TKA, and separated those on the basis of whether to receive opioid use after surgery. Themultivariate logistic regression model was used to identify independent risk factors for opioid use after primary TKA. Length of stay (LOS) and postoperative complications were also recorded and compared.

Results

The prevalence of opioid use after primary TKA was 23.0%. The significant risk factor was the longer operative time (OR [odds ratio] = 1.017, 95% CI [confidence interval] = 1.001 to 1.032, p = 0.034) and the protective factor was the utilization of tranexamic acid(OR= 0.355, 95% CI = 0.161 to 0.780, p = 0.010). In addition, the LOS was longer in opioid group (p < 0.05).

Conclusion

Considering the adverse health effects of opioid use, strategies need to be developed to prevent persistent opioid use after TKA. Reducing operative time and the application of tranexamic acid could lower the risk of opioid use with an enhanced-recovery programme after primary TKA.