bluuebunny/crossref_metadata_2025 huggingface dataset:
High spectral and spatial resolution MRI of prostate cancer: a pilot study
Authors: Medved Milica , Chatterjee Aritrick , Devaraj Ajit , Harmath Carla , Lee Grace , Yousuf Ambereen , Antic Tatjana , Oto Aytekin , Karczmar Gregory S.
Published: May 2021

Purpose

High spectral and spatial resolution (HiSS) MRI is a spectroscopic imaging method focusing on water and fat resonances that has good diagnostic utility in breast imaging. The purpose of this work was to assess the feasibility and potential utility of HiSS MRI for the diagnosis of prostate cancer.

Methods

HiSS MRI was acquired at 3 T from six patients who underwent prostatectomy, yielding a train of 127 phase‐coherent gradient echo (GRE) images. In the temporal domain, changes in voxel intensity were analyzed and linear (R) and quadratic (R1, R2) quantifiers of signal logarithm decay were calculated. In the spectral domain, three signal scaling‐independent parameters were calculated: water resonance peak width (PW), relative peak asymmetry (PRA), and relative peak distortion from ideal Lorentzian shape (PRD). Seven cancer and five normal tissue regions of interest were identified in correlation with pathology and compared.

Results

HiSS‐derived quantifiers, except R2, showed high reproducibility (coefficients of variation, 5%‐14%). Spectral domain quantifiers performed better than temporal domain quantifiers, with receiver operator characteristic areas under the curve ranging from of 0.83 to 0.91. For temporal domain parameters, the range was 0.74 to 0.91. Low absolute values of the coefficients of correlation between monoexponential decay markers (R, PW) and resonance shape markers (PRA, PRD) were observed (range, 0.23‐0.38).

Conclusion

The feasibility and potential diagnostic utility of HiSS MRI in the prostate at 3 T without an endorectal coil was confirmed. Weak correlation between well‐performing markers indicates that complementary information could be leveraged to further improve diagnostic accuracy.
Automatic determination of the regularization weighting for wavelet‐based compressed sensing MRI reconstructions
Authors: Varela‐Mattatall Gabriel , Baron Corey A. , Menon Ravi S.
Published: May 2021

Purpose

To present a method that automatically, rapidly, and in a noniterative manner determines the regularization weighting for wavelet‐based compressed sensing reconstructions. This method determines level‐specific regularization weighting factors from the wavelet transform of the image obtained from zero‐filling in k‐space.

Methods

We compare reconstruction results obtained by our method,, to the ones obtained by the L‐curve,, and the minimum NMSE,. The comparisons are done using in vivo data; then, simulations are used to analyze the impact of undersampling and noise. We use NMSE, Pearson’s correlation coefficient, high‐frequency error norm, and structural similarity as reconstruction quality indices.

Results

Our method,, provides improved reconstructed image quality to that obtained byregardless of undersampling or SNR and comparable quality toat high SNR. The method determines the regularization weighting prospectively with negligible computational time.

Conclusion

Our main finding is an automatic, fast, noniterative, and robust procedure to determine the regularization weighting. The impact of this method is to enable prospective and tuning‐free wavelet‐based compressed sensing reconstructions.
A phase Ib/IIa, open‐label, multiple ascending‐dose trial of domagrozumab in fukutin‐related protein limb‐girdle muscular dystrophy
Authors: Leung Doris G. , Bocchieri Alex E. , Ahlawat Shivani , Jacobs Michael A. , Parekh Vishwa S. , Braverman Vladimir , Summerton Katherine , Mansour Jennifer , Stinson Nikia , Bibat Genila , Morris Carl , Marraffino Shannon , Wagner Kathryn R.
Published: May 2021

Introduction/Aims

In this study we report the results of a phase Ib/IIa, open‐label, multiple ascending‐dose trial of domagrozumab, a myostatin inhibitor, in patients with fukutin‐related protein (FKRP)‐associated limb‐girdle muscular dystrophy.

Methods

Nineteen patients were enrolled and assigned to one of three dosing arms (5, 20, or 40 mg/kg every 4 weeks). After 32 weeks of treatment, participants receiving the lowest dose were switched to the highest dose (40 mg/kg) for an additional 32 weeks. An extension study was also conducted. The primary endpoints were safety and tolerability. Secondary endpoints included muscle strength, timed function testing, pulmonary function, lean body mass, pharmacokinetics, and pharmacodynamics. As an exploratory outcome, muscle fat fractions were derived from whole‐body magnetic resonance images.

Results

Serum concentrations of domagrozumab increased in a dose‐dependent manner and modest levels of myostatin inhibition were observed in both serum and muscle tissue. The most frequently occurring adverse events were injuries secondary to falls. There were no significant between‐group differences in the strength, functional, or imaging outcomes studied.

Discussion

We conclude that, although domagrozumab was safe in patients in limb‐girdle muscular dystrophy type 2I/R9, there was no clear evidence supporting its efficacy in improving muscle strength or function.
Vocal fold injection material does not preclude interpretation of laryngeal electromyography
Authors: Belsky Michael A. , Lin R. Jun , Rosen Clark A. , Munin Michael C. , Smith Libby J.
Published: May 2021

Introduction/Aims

Temporary vocal fold injection (VFI) is a common treatment for acute and subacute vocal fold paralysis (VFP). Laryngeal electromyography (LEMG) is useful for diagnosing neurogenic causes of VFP. This study evaluated whether the presence of VFI material prevents interpretation of LEMG in patients with acute and subacute VFP.

Methods

Patients with acute and subacute unilateral VFP (onset ≤6 mo) who underwent temporary VFI within 3 mo preceding LEMG were evaluated. A matched control group that did not undergo VFI was also studied. The LEMG team (laryngologist and electromyographer) performed and interpreted LEMG using a pre‐specified protocol, including qualitative and quantitative motor unit analysis.

Results

Eighteen patients with VFI underwent LEMG successfully with interpretation of spontaneous activity and motor unit recruitment. Fourteen patients were seen in follow‐up to determine accuracy of established LEMG prognosis. Seven of seven subjects with poor LEMG prognosis did not recover vocal fold motion. Five of seven subjects with fair LEMG prognosis recovered vocal fold motion. Findings were similar for the control group.

Discussion

VFI augmentation material did not prevent interpretation of meaningful LEMG data in patients with acute and subacute VFP, and accurate prognoses of vocal fold motion recovery were established.
Honeycomb scaffolds capable of ectopic osteogenesis: Histological evaluation of osteoinduction mechanism
Authors: Hayashi Koichiro , Ishikawa Kunio
Published: May 2021

Scaffolds capable of inducing ectopic osteogenesis (i.e., osteoinduction) have the potential to treat congenital and massive bone defects. However, the mechanisms underlying osteoinduction remain elusive, largely because of rapid tissue changes occurring early in the process. A model with decelerated osteoinduction is, therefore, needed. Here, we developed carbonate apatite honeycomb scaffolds capable of osteoinduction in rabbit muscle, which inherently exhibits minimal osteoinduction. The key events observed were: (1) fibrin accumulation in scaffolds at week 1; (2) appearance of tartrate‐resistant acid phosphatase (TRAP)‐ and RAM11‐positive cells and formation of collagen fibers and blood vessels between weeks 2 and 3; (3) appearance of osteocalcin‐positive cells and decrease in the number of TRAP‐positive cells between weeks 3 and 4; (4) continuous proliferation of osteocalcin‐positive cells at postoperative week 4 and formation of osteoid and mineralized tissues at weeks 8 and 12, respectively. These findings suggest that the appearance of TRAP‐positive cells that are considered foreign body giant cells is essential for collagen formation, angiogenesis, and osteogenesis. These insights may aid in the development of scaffolds for bone tissue engineering.
Bio‐mediated synthesis – A sustainable strategy for nanomaterials preparation: A comprehensive bibliometric review
Authors: Shen Yun , Zhang Li , Wang Ke , Li Xu , Li Jie , Zhang Shan , Zhao Hanghang , Jiang Xiaoxue , Guan Weisheng , Yang Li
Published: May 2021

Nanomaterials have been widely used in multi‐aspect because of their particular physicochemical properties. However, traditional physical and chemical synthetic methods of nanomaterials are costly, they are easy to produce toxic by‐products which are harmful to environment and human health. In recent years, the synthesis of nanomaterials via biological mediated method has shown great potential with the advantage of environmentally friendly, cost‐effective and high‐efficiency. Plants, microorganisms, and biological extracts are all excellent candidates for biosynthesis. Furthermore, these kinds of bio‐genic materials have been applied in many fields such as environment remediation, catalytic reaction, anti‐microbsis and anti‐tumor. Thus, in order to grasp the research progress and development trend of nanomaterials synthesized by bio‐mediated methods, a comprehensive overview is presented based on Web of Science database and bibliometric analysis. The results proved that the number of publications increased year by year from 2010 to 2020, India and China were the main two contributors. Some research institutions and researchers have formed their stable cooperative groups. Keywords analysis showed that the co‐occurrence network could be divided into four clusters, “green synthesis,” “AgNPs,” “AuNPs,” “nanoparticles,” and “leaf extract” were the most popular words. Moreover, publishing journals, highly cited articles and major disciplines were also studied. The review will provide valuable references for future research.
Influence of TiC nano‐particulates on the physical and mechanical properties of AA7150‐TiC MMC: Fabricated by advanced novel process
Authors: Madhukar Pagidi , Selvaraj N. , Kumar G.B. Veeresh , Rao C. S. P. , Mohammad Faruq , Seetharam R. , Chavali Murthy
Published: May 2021

TiCnp reinforced AA7150 nanocomposites were prepared through a novel fabrication process (a combination of Vortex/Two‐step Stir Casting/Ultrasonication). The effect of TiCnp (0.5, 1.0, 1.5, and 2.0 wt.%) and ultrasonication on both microstructure behavior as well as mechanical properties were investigated at room temperature. Microstructural studies were analyzed through optical and scanning electron microscopy for grain size refinement, nanoparticle distribution and failure analysis. Grain refinement and homogeneous distribution of nanoparticles were achieved due to the ultrasonication effect. The mechanical properties increase with the increase of TiCnp wt.%. The optimal peak value at 175 MPa in tensile strength, 177.05 HV in microhardness, and 41.07 µm in grain size reduction were achieved at 1.5 wt.% of TiCnp content, which was around 48.31% and 17.4% enhanced in strength, in microhardness and 52.37% in grain size reduction. These peculiar achievements resulted from the homogeneous dispersion of TiC nano‐particulates in the nanocomposite material through a novel fabrication process.
Nanocomposites obtained by incorporation of silanized silver nanowires to improve mechanical properties and prevent fungal adhesion
Authors: de Menezes Beatriz Rossi Canuto , Sampaio Aline da Graça , da Silva Diego Morais , Montagna Larissa Stieven , Montanheiro Thaís Larissa do Amaral , Koga Ito Cristiane Yumi , Thim Gilmar Patrocínio
Published: May 2021

In this work, the surfaces of silver nanowires (AgNWs) were modified by silanization process to improve the mechanical and antibiofilm properties of polymethylmethacrylate (PMMA) dental resins. A two‐route methodology was used to silanize the AgNWs: first, a surface treatment using tetraethyl orthosilicate (TEOS) was performed to act as interface agent; and then, γ‐methacryloxypropyltrimethoxysilane (MPS) was used to insert functional groups compatible to the acrylic resin. PMMA/AgNWs composites were obtained using pristine (AgNWP) and modified AgNWs (AgNWM) at concentrations of 0.5 and 1.0 wt%. The mechanical (flexural and impact strength) and antibiofilm properties against Candida albicans was investigated. AgNWM showed an enhancement in the dispersion and adhesion within the PMMA matrix, which were responsible for improvements in the mechanical properties. Results of flexural strength showed significant improvements for the sample with incorporation of 0.5 wt% of AgNWM and no significative changes for the sample with AgNWP. In addition, a reduction of about 50% in the biofilm formation by C. albicans was observed for the samples with 0.5 and 1.0 wt% of AgNWM. The incorporation of silanized‐AgNWs into PMMA dental resins can combine improvements in antimicrobial activity and in the flexural strength, being a potential antimicrobial biomaterial for dental applications.
Fluorescence properties of yellow light emitting carbon quantum dots and their application for effective recognition of heavy metal ions in aqueous medium
Authors: Raj Savan K. , Rathod Nehal H. , Tripathi Balram , Patidar Rajesh , Kulshrestha Vaibhav
Published: May 2021

Water‐dispersible and fluorescence‐stable carbon quantum dots (CQDs) have been synthesized at gram scale using pyrene as carbon precursor by employing the bottom‐up approach. X‐ray diffraction, FTIR, Raman spectroscopy and UV visible spectroscopy confirm the formation of CQDs. TEM images shows that size of the CQDs ranges from 2 to 5 nm. A detailed study of their optical and fluorescence characteristics was performed. Their aqueous dispersion radiates bright yellow light under UV lamp (365 nm). The research work includes derivation of their excitation wavelength, observation of influence of dilution on fluorescence and monitoring of emission intensity for about 4 months. The CQDs can effectively recognize the presence of heavy metal ions in aqueous medium at neutral pH via fluorescence quenching.
Cardiac metabolic imaging using hyperpolarized [1‐13C]lactate as a substrate
Authors: Lau Angus Z. , Chen Albert P. , Cunningham Charles H.
Published: May 2021

Hyperpolarized (HP) [1‐13C]lactate is an attractive alternative to [1‐13C]pyruvate as a substrate to investigate cardiac metabolism in vivo: it can be administered safely at a higher dose and can be polarized to a degree similar to pyruvate via dynamic nuclear polarization. While 13C cardiac experiments using HP lactate have been performed in small animal models, they have not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods as the first human HP 13C cardiac study, 13C metabolic images were acquired following injections of HP [1‐13C]lactate in porcine hearts. Data were also acquired using HP [1‐13C]pyruvate for comparison. The 13C bicarbonate signal was localized to the myocardium and had a similar appearance with both substrates for all animals. No 13C pyruvate signal was detected in the experiments following injection of HP 13C lactate. The signal‐to‐noise ratio (SNR) of injected lactate was 88 ± 4% of the SNR of injected pyruvate, and the SNR of bicarbonate in the experiments using lactate as the substrate was 52 ± 19% of the SNR in the experiments using pyruvate as the substrate. The lower SNR was likely due to the shorter T1 of [1‐13C]lactate as compared with [1‐13C]pyruvate and the additional enzyme‐catalyzed metabolic conversion step before the 13C nuclei from [1‐13C]lactate were detected as 13C bicarbonate. While challenges remain, the potential of HP lactate as a substrate for clinical metabolic imaging of human heart has been demonstrated.
Characterization of anisotropic T2W signals from human knee femoral cartilage: The magic angle effect on a spherical surface
Authors: Pang Yuxi
Published: May 2021

The aim of the current study was to propose a generalized magic angle effect (gMAE) function for characterizing anisotropic T2W signals of human knee femoral cartilage with a spherical surface in clinical studies. A gMAE model function f(α, ε) was formulated for an orientation‐dependent (ε) transverse T2 (i.e., 1/R2) relaxation in cartilage assuming an axially symmetric distribution (α) of collagen fibers. T2W sagittal images were acquired on an adult volunteer's healthy knee at 3 T, and ROI‐based average signals S(ε) were extracted from angularly and radially segmented femoral cartilage. Compared with the standard MAE (sMAE) functions in the deep (DZ, α = 0°) and in the superficial (SZ, α = 90°) zones, a general form of R2 orientation‐dependent function f(α, ε) was fitted to S(ε), including an isotropic R2 contribution (internal reference [REF]). Goodness of fit was evaluated by root‐mean‐square deviations (RMSDs). An F‐test and a paired t‐test were respectively used to assess significant differences between the observed variances and means, with statistical significance set to p less than .05. As a symmetric orientation‐dependence function with a varying dynamic range, the proposed gMAE model outperformed the previous sMAE functions manifested by significantly reduced RMSDs in the DZ (0.239 ± 0.122 vs. 0.267 ± 0.097, p = .014) and in the SZ (0.183 ± 0.081 vs. 0.254 ± 0.085, p < .001). The fitted average angle α (38.5 ± 34.6° vs. 45.1 ± 30.1°, p < .43) and REF (5.092 ± 0.369 vs. 5.305 ± 0.440, p < .001) were smaller in the DZ than those in SZ, in good agreement with the reported collagen fibril microstructural configurations and the nonbound water contribution to R2 in articular cartilage. In conclusion, a general form of the magic angle effect function was proposed and demonstrated for better characterizing anisotropic T2W signals from human knee femoral cartilage at 3 T in clinical studies.
Association Between Nutrition Delivery, Modified Nutrition Risk In Critically III Score, and 28‐Day Mortality
Authors: Chada Radha Reddy , Chidrawar Sachin , Goud Bhagyasri A. , Maska Anita , Medanki Rajiv , Nagalla Balakrishna
Published: May 2021

Background

Nutrition delivery, is a key component in the management of critical illness. Traditional scoring systems are inadequate in the intensive care unit (ICU), as patients are sedated. Our study examines the associations between calorie and protein adequacy, 28‐day mortality, and modified Nutrition Risk in Critically Ill (mNUTRIC) score and identify at‐risk ICU patients who may benefit more from nutrition intervention.

Methods

Prospective observational study of adults admitted for >24h to the ICU of a tertiary care hospital during a period of 7 months. Data were collected on nutrition delivery, mNUTRIC score, use of mechanical ventilation, and ICU/hospital length of stay (LOS). Multivariate logistic regression analysis was done with 28‐day mortality as the primary outcome.

Results

Two hundred forty‐eight patients were recruited for the study with 60% male, 40% female, mean age 60.8 ± 14.7, and body mass index of 24.2 ± 4.8. Patients with inadequate calorie and protein delivery had significantly higher 28‐day mortality than those with adequate provision (P=.032 and P =. 017). In bivariate logistic regression analysis, mNUTRIC score (odds ratio [OR], 1.802; 95% CI, 1.042–3.117; P = .035) and adequacy of energy (OR, 1.92) and protein (OR, 2.49) correlate with 28‐day mortality. The Kaplan‐Meier survival curve showed a survival benefit in the ≥80% energy and protein group among the total patients and was also significantly associated with lower hospital and ICU LOS, even after matching (log‐rank test, P < 0.001).

Conclusion

Adequacy of energy and protein to ≥80% may shorten ICU/hospital LOS and reduce 28‐day mortality among both high and low nutrition risk patients.
Partitioned formulation of contact‐impact problems with stabilized contact constraints and reciprocal mass matrices
Authors: González José A. , Kopačka Ján , Kolman Radek , Park Kwang‐Chun
Published: May 2021

This work presents an efficient and accuracy‐improved time explicit solution methodology for the simulation of contact‐impact problems with finite elements. The proposed solution process combines four different existent techniques. First, the contact constraints are modeled by a bipenalty contact‐impact formulation that incorporates stiffness and mass penalties preserving the stability limit of contact‐free problems for efficient explicit time integration. Second, a method of localized Lagrange multipliers is employed, which facilitates the partitioned governing equations for each substructure along with the completely localized contact penalty forces pertaining to each free substructure. Third, a method for the direct construction of sparse inverse mass matrices of the free bodies in contact is combined with the localized Lagrange multipliers approach. Finally, an element‐by‐element mass matrix scaling technique that allows the extension of the time integration step is adopted to improve the overall performance of the algorithm. A judicious synthesis of the four numerical techniques has resulted in an increased stable explicit step‐size that boosts the performance of the bipenalty method for contact problems. Classical contact‐impact numerical examples are used to demonstrate the effectiveness of the proposed methodology.
Finite temperature atomistic‐informed crystal plasticity finite element modeling of single crystal tantalum (α‐Ta) at micron scale
Authors: Xie Yuxi , Li Shaofan
Published: May 2021

In this work, we have developed a temperature‐dependent higher‐order Cauchy–Born (THCB) rule for multiscale crystal defect dynamics (MCDD) of crystalline solids based on the harmonic approximation. As a template, we employed the THCB rule to develop an atomistic‐informed constitutive model for the body‐centered cubic (BCC) single crystal tantalum (‐Ta). Considering the effect of strain gradients in different process zone elements, the corresponding higher order stress are used to model crystal plasticity of single crystal ‐Ta. Different from face‐centered cubic crystals, BCC crystals are strongly influenced by temperature. It is shown in this article that the developed finite temperature atomistic‐informed crystal plasticity finite element method is able to capture the temperature‐dependent dislocation substructure and hence crystal plastic deformation. The main contributions and novelties of the present work are highlighted by following findings: (1) A THCB rule and an atomistic‐informed strain gradient theory have been developed, and the corresponding temperature‐related higher‐order stress and elastic tensor formulations are derived; (2) The finite temperature MCDD provides an atomistic‐informed crystal plasticity finite element method that can simulate anisotropic crystal plasticity in any orientation within stereographic triangle at micron scale and above; (3) The developed MCDD is able to capture the non‐Schmid effects of BCC single crystal tantalum (‐Ta); (4) The developed MCDD is able to capture the size effect of single crystal plasticity; and (5) The finite temperature MCDD can simulate the temperature dependent dislocation substructure, and it captures cross‐slip in single crystal tantalum at low temperature (∼20 K) and captures dislocation cell structure at high temperature (∼500 K).
Factors associated with the level of prolactin in patients under remission from Alcohol Use Disorder: A gender perspective
Authors: Pandey Susmita , Bolstad Ingeborg , Lien Lars , Bramness Jørgen G.
Published: May 2021

Background

Prolactin mirrors the dopaminergic activity in the brain which is key to understanding alcohol use disorders (AUD). Still, patients with AUD are a heterogenous group and there seem to be gender differences in the relationship between alcohol use and the level of prolactin. In this study, we examined gender‐wise relationship of alcohol use trait‐ and state‐related factors with the level of prolactin among AUD inpatients in remission.

Methods

This cross‐sectional study examined the level of prolactin along with general patient characteristics and alcohol use trait‐ and state‐related factors that could influence the level of prolactin in 112 AUD inpatients at three rehabilitation clinics in Norway. Logistic regression was performed to identify the gender‐specific predictors of level of prolactin.

Results

Male and female AUD patients had similar level of prolactin. Among females, younger age, early alcohol debut, and absence of parental drinking problem predicted higher level of prolactin. In males, presence of other substance dependence predicted a lower level of prolactin.

Conclusions

There were gender differences in the factors associated with the level of prolactin among the AUD patients. Especially in the female AUD patients under remission, alcohol use trait‐related factors were better predictors of the level of prolactin than the alcohol use state‐related factors, indicating that individuals might characteristically have varying degree of dopamine reactivity.
BMI and pneumonia outcomes in critically ill COVID‐19 patients: An international multicenter study
Authors: Chetboun Mikael , Raverdy Violeta , Labreuche Julien , Simonnet Arthur , Wallet Florent , Caussy Cyrielle , Antonelli Massimo , Artigas Antonio , Goma Gemma , Meziani Ferhat , Helms Julie , Mylonakis Eleftherios , Levy Mitchell M. , Kalligeros Markos , Latronico Nicola , Piva Simone , Cerf Charles , Neuville Mathilde , Klouche Kada , Larcher Romaric , Tamion Fabienne , Occhiali Emilie , Snacken Morgane , Preiser Jean‐Charles , Kontar Loay , Riviere Antoine , Silva Stein , Sarton Benjamine , Krouchi Raphael , Dubar Victoria , Palaiodimos Leonidas , Karamanis Dimitrios , Perche Juliette , L'Her Erwan , Busetto Luca , Dicker Dror , Lev Shaul , Duhamel Alain , Jourdain Mercè , Pattou François
Published: May 2021

Objective

Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID‐19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID‐19.

Methods

Patients admitted to intensive care units for COVID‐19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28‐day mortality, respectively.

Results

A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9‐72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4‐32.3); a total of 1,080 patients (73.9%) required IMV; and the 28‐day mortality estimate was 36.1% (95% CI: 33.0‐39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12‐1.45) per 5 kg/m2. An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06‐2.64]).

Conclusions

In critically ill COVID‐19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.
Evaluation of dosing strategies and trough concentrations of vancomycin in patients undergoing continuous venovenous hemofiltration
Authors: Wahby Krista A. , Cunmuljaj Lejla , Mouabbi Karim , Almadrahi Zinah , Wilpula Liz
Published: May 2021

Study Objective

Recommendations regarding vancomycin dosing in critically ill patients on continuous venovenous hemofiltration (CVVH) are limited. The purpose of this study was to evaluate current dosing practices of pharmacists for patients treated with CVVH, develop guidelines for optimal dosing and monitoring of vancomycin to improve target trough attainment, and reduce pharmacist workload.

Design

A retrospective cohort study. was performed of critically ill adult patients from January 2015 to December 2018. Patients were included if they received vancomycin during CVVH for at least 48 h. Patients with significant residual kidney function, defined as daily urine output >400 ml or significant fluctuations (≥1000 ml/h in a 24‐h period) in their hemofiltration rates, were excluded. Interruptions in CVVH up to 6 h/day were permitted. Dosing strategies with two dosing categories were defined: (1) dosing based on random serum levels (dosing by level, DBL) or (2) scheduled vancomycin dosing (SD).

Setting

Academic medical center in Detroit, Michigan.

Patients

Critically ill adult patients.

Measurements and Main Results

During the study period, 942 patients were evaluated and 200 met inclusion criteria, for a total of 586 serum vancomycin levels. There were 141 patients with 443 random vancomycin serum levels in the DBL group and 59 patients with143 vancomycin trough levels in the SD group. Mean vancomycin trough levels were similar between groups (17.1 ± 6 vs. 16.5 ± 4 mcg/ml) for the DBL and SD groups, respectively. For the primary end point of overall target trough achievement of 15–20 mcg/ml, significantly more trough levels in the SD group were in the 15–20 mcg/ml range compared with the DBL group, 50% vs. 38%; p < 0.001, respectively. When target trough range was extended to 10–20 mcg/ml, success rates were similar between groups (74% DBL vs. 82% SD, p = 0.021). The number of interventions required by the pharmacist, including notes per day and orders per day, were reduced by approximately 50% when the SD strategy was utilized. Scheduled vancomycin dosing regimens of 15–22 mg/kg every 12–24 h were required to yield trough levels in the 15–20 mcg/ml range.

Conclusions

Target vancomycin trough achievement of 15–20 mcg/ml occurred more frequently when vancomycin was scheduled at a dose of 15–22 mg/kg every 12–24 h based on ultrafiltration rate and may alleviate the time and cost associated with frequent vancomycin serum monitoring.
School belonging, self‐efficacy, and meaning in life as mediators of bullying victimization and subjective well‐being in adolescents
Authors: Seon Youngwoon , Smith‐Adcock Sondra
Published: May 2021

With an aim to inform school‐based antibullying interventions, this study examined mediating roles of school belonging, self‐efficacy, and meaning in life between bullying victimization and subjective well‐being. Using US student data from the 2018 round of the Program for International Student Assessment, results of structural equation modeling indicated a model that fit the data adequately and each path was statistically significant. School belonging, self‐efficacy, and meaning in life significantly mediated bullying victimization and subjective well‐being, respectively. These findings suggest that interventions focused on school belonging, meaning in life, and self‐efficacy may improve the subjective well‐being of adolescents who experience bullying in school. Limitations of this study and future research directions are discussed.
Exploring gender‐based difference towards academic enablers scales among secondary school students of Pakistan
Authors: Abid Nisar , Ali Rizwan , Akhter Mumtaz
Published: May 2021

The study purposes were to explore the level of students' academic enablers and gender‐based difference towards academic enablers scales (AES) among 3200 students that were selected randomly from 80 high schools of Punjab province of Pakistan. The descriptive design of the positivism research paradigm was used to accomplish the study. Academic enablers scale for students (AES‐students) was adapted to collect data about four academic enabling behaviors (motivation, engagement, interpersonal skills, and study skills). Hence, the psychometric properties of adapted AES‐students exhibited that it is a valid and reliable instrument to measure academic enablers. Results indicated that the majority of students had a competent level in all academic enabling behaviors while they are more motivated as compared to their study skills, interpersonal skills, and engagement. However, engagement is the least contributive enabler. Moreover, results also demonstrated a significant difference in girls' and boys' student perceptions towards AES. It is also determined that gender had a small effect size on students' academic enablers as Cohen's d values among 0.1 to 0.4. Academic enabling behaviors may be enhanced among boy students through the use of different teaching strategies in the classroom, such as enthusiastic demonstration style, group activities, and classroom symposiums.
Achieving oncology mental health providers' usage of an empirically supported treatment: Lessons learned
Authors: Andersen Barbara L. , Dorfman Caroline S. , Conley Claire C.
Published: May 2021

Objective

There is a need for oncology mental health providers to receive training to use empirically supported psychological treatments (ESTs) with their patients. The purpose of this editorial is to describe “lessons learned” from disseminating–conducting EST trainings–and supporting providers' capacity and confidence to use the EST.

Method

Processes and outcomes from conducting six, 3‐days (18 h) EST training institutes from 2012‐2016 are discussed. Institutes trained 166 full time oncology mental health providers from more than 100 different settings. The dissemination was intentionally designed to achieve EST implementation, i.e., therapists' sustained usage of the EST for at least 12 months post training.

Results

Previously published discussion and findings show the effort was successful in achieving positive EST dissemination outcomes and sustained EST implementation by providers. Thus, “lessons learned” include discussions of (1) orientation to design education/training to achieve EST usage using theory based aims and outcomes of training efficacy; (2) multimodal, educational strategies used to achieve therapists' positive attitudes toward and self‐efficacy to implement the EST; (3) guidance to therapists for adapting the EST to their practice settings while maintaining fidelity; (4) assistance to therapists to identify and problem solve implementation challenges; and (5) using patient reported outcome measures to determine clinical change.

Conclusion

Our discussion of the plan, methods, and goals of EST training contributes to the science of dissemination/implementation by providing support for (1) theory‐informed EST dissemination, and (2) mechanisms of EST implementation. For researchers, our experience may guide future EST dissemination/implementation efforts in psycho‐oncology. For therapists, lessons learned provide criteria for evaluating future continuing education options.
Surfactant nebulization therapy during NIPPV ventilation in surfactant‐deficient newborn piglets
Authors: Rey‐Santano Carmen , Mielgo Victoria , Gastiasoro Elena , Bianco Federico , Salomone Fabrizio , Gomez‐Solaetxe Miguel Angel
Published: May 2021

Background

In recent years, nasal intermittent positive pressure ventilation (NIPPV) has been growing in popularity as a form of noninvasive ventilation for respiratory support in the initial treatment of neonates with surfactant (SF) deficiency. The combination of this type of ventilation with noninvasive SF administration (by nebulization) is an attractive treatment option for respiratory distress syndrome (RDS)‐associated pathophysiology of the neonatal lungs. In this study, we aimed to test the tolerability and efficacy of SF nebulization during NIPPV for the treatment of neonatal RDS.

Methods

Spontaneously‐breathing newborn piglets (n = 6/group) with bronchoalveolar lavage (BAL)‐induced RDS were assigned to receive during NIPPV (180 min): poractant alfa (400 mg/kg) via an investigational customized vibrating‐membrane nebulizer (eFlow‐Neos) or poractant alfa (200 mg/kg) as a bolus using the Insure method or no surfactant (controls).

Measurement and results

We assessed pulmonary, hemodynamic and cerebral effects and performed histological analysis of lung and brain tissue. After repeated BAL, newborn piglets developed severe RDS (FiO2: 1, pH < 7.2, PaCO2 > 70 mmHg, PaO2< 70 mmHg, Cdyn < 0.5 ml/cmH2O/kg). In both SF‐treated groups, we observed rapid improvement in pulmonary status and also similar hemodynamic, cerebral behavior, and lung and brain injury scores.

Conclusion

Our results in newborn piglets with severe BAL‐induced RDS show the administration of nebulized poractant alfa using the eFlow‐Neos nebulizer during NIPPV to be well tolerated and efficacious, suggesting that this noninvasive SF administration option should be explored further.
Impact of COVID‐19 outbreak in acute bronchiolitis: Lesson from a tertiary Italian Emergency Department
Authors: Curatola Antonietta , Lazzareschi Ilaria , Bersani Giulia , Covino Marcello , Gatto Antonio , Chiaretti Antonio
Published: May 2021

Aim

To assess the impact of the coronavirus disease 2019 (COVID‐19) outbreak on pediatric emergency department (ED) visits for acute bronchiolitis during the epidemic season.

Methods

A retrospective analytical cross‐sectional study was performed in our hospital, analyzing medical charts of all children under 2 years of age with a diagnosis of acute bronchiolitis admitted to our ED in the last years. Demographics and clinical data of patients affected with acute bronchiolitis during the 2020–2021 season—COVID‐19 outbreak—were compared to those of the 5 previous years.

Results

We observed an average drop of 84% of the rate of acute bronchiolitis managed by pediatricians in ED in 2020–2021 compared with bronchiolitis seasons of 5 previous years. We also reported, during the COVID‐19 outbreak, a higher number of children affected by acute bronchiolitis referred to ED as Emergency Consultations who required hospitalization. Regarding etiological agents, no differences in respiratory virus circulation, especially RSV, were observed in the two groups.

The multivariate analysis showed no correlation between the diagnosis of RSV bronchiolitis and COVID‐19 period or prematurity; lower age was associated with an increased likelihood of exhibiting RSV bronchiolitis (odds ratio 0.9; 95% confidence interval 0.86–0.95p < .01).

Conclusion

Our data emphasize the reduction in the rate of admission to pediatric ED for acute bronchiolitis during the COVID‐19 outbreak, regardless of changes in circulating respiratory viruses. Therefore we want to highlight the importance of nonpharmacological preventive hygiene measures that should be maintained even at the end of the COVID‐19 outbreak.
Application of high‐frequency oscillation ventilation combined with volume guarantee in infants with acute hypoxic respiratory failure after congenital heart surgery
Authors: Zheng Yi‐Rong , Xie Wen‐Peng , Liu Jian‐Feng , Wu Hong‐Lin , Xu Ning , Huang Shu‐Ting , Cao Hua , Chen Qiang
Published: May 2021

Objective

This study aimed to evaluate the efficacy and safety of high‐frequency oscillation ventilation combined with volume guarantee (HFOV‐VG) compared with the safety and efficacy of HFOV alone in infants with acute hypoxemic respiratory failure (AHRF) after congenital heart surgery.

Methods

We retrospectively analyzed the clinical data of 44 infants who were ventilated for AHRF after congenital heart surgery between January 2020 and January 2021. HFOV alone was used in 23 of the 44 infants, whereas HFOV‐VG was used in the other 21 infants.

Results

The average frequency tidal volume (VThf) of the HFOV‐VG group was lower than that of the HFOV group, and the proportion of VThf exceeding the target range of infants in the HFOV‐VG group was also lower (p < .01). In addition, the incidence of hypocapnia and hypercapnia in infants supported with HFOV‐VG was significantly lower (p < .01). Furthermore, the duration of invasive ventilation and the median ventilator adjustment per hour in the HFOV‐VG group was also lower than that in the HFOV group (p < .01).

Conclusions

Compared with HFOV alone, HFOV‐VG decreases the fluctuation of VThf and the incidence of hypercapnia and hypocapnia. Moreover, it reduces the workload of bedside medical staff. Further studies are needed to confirm the efficacy and safety of HFOV‐VG as a routine respiratory support strategy for congenital heart disease during the perioperative period.
Chest MRI as an emerging modality in the evaluation of empyema in children with specific indications: Pilot study
Authors: Sodhi Kushaljit S. , Bhatia Anmol , Nichat Vaibhav , Mathew Joseph L. , Saxena Akshay K. , Samujh Ram , Singh Meenu
Published: May 2021

Objectives

To assess the diagnostic role of chest magnetic resonance imaging (MRI) for evaluating empyema in children with specific indications.

Methods

Nineteen children (5–16 years) with a diagnosis of empyema were enrolled in this prospective study from January 2018 to February 2020. MRI and multidetector computed tomography (MDCT) of the chest was performed within 48 h of each other. Two pediatric radiologists independently evaluated the MRI and CT images for the presence of fluid and air in the pleural cavity, septations within the fluid, pleural thickening, pleural enhancement, drainage tube tip localization, consolidation, and lymphadenopathy. Kappa test of agreement was used to determine the agreement between the MRI and MDCT findings. Chance‐corrected kappa statistics were used for calculating the interobserver variation.

Results

The kappa test showed almost perfect agreement (κ = 1) between MRI and MDCT for detecting fluid, pleural thickening, pleural enhancement, drainage tube tip localization, consolidation, and lymphadenopathy. Septations within the fluid were detected in 16 (84.2%) patients on MRI, and in 14 (73.7%) patients on MDCT. Almost perfect agreement (κ = 0.81–1.00) was seen for all the findings on CT and MRI between the two radiologists, except for pleural thickening for which a strong agreement (κ = 0.642) was observed.

Conclusion

MRI is comparable to MDCT for the detection of various findings in children with empyema. MRI may be considered in lieu of CT, as a problem‐solving tool and as a radiation‐reducing endeavor in children with empyema, specifically, only where CT is required for preoperative planning and evaluation of complications.
An apparent core/shell architecture of polyQ aggregates in the aging Caenorhabditis elegans neuron
Authors: Fisher Rachel S. , Jimenez Rosa Meyo , Soto Elizabeth , Kalev Darin , Elbaum‐Garfinkle Shana
Published: May 2021

Huntington's disease is caused by a polyglutamine (polyQ) expansion in the huntingtin protein which results in its abnormal aggregation in the nervous system. Huntingtin aggregates are linked to toxicity and neuronal dysfunction, but a comprehensive understanding of the aggregation mechanism in vivo remains elusive. Here, we examine the morphology of polyQ aggregates in Caenorhabditis elegans mechanosensory neurons as a function of age using confocal and fluorescence lifetime imaging microscopy. We find that aggregates in young worms are mostly spherical with homogenous intensity, but as the worm ages aggregates become substantially more heterogeneous. Most prominently, in older worms we observe an apparent core/shell morphology of polyQ assemblies with decreased intensity in the center. The fluorescence lifetime of polyQ is uniform across the aggregate indicating that the dimmed intensity in the assembly center is most likely not due to quenching or changes in local environment, but rather to displacement of fluorescent polyQ from the central region. This apparent core/shell architecture of polyQ aggregates in aging C. elegans neurons contributes to the diverse landscape of polyQ aggregation states implicated in Huntington's disease.
Biocontrol of the root‐knot nematodeMeloidogyne incognitaby a nematicidal bacteriumPseudomonas simiaeMB751with cyclic dipeptide
Authors: Sun Xiaowen , Zhang Run , Ding Meijuan , Liu Yongxuan , Li Lin
Published: May 2021

BACKGROUND

Root‐knot nematodes (RKNs) are harmful plant‐parasitic nematodes that cause serious damage to plant hosts. In the long‐term practice of RKN management, bacterial nematicides have attracted increasing attention as an effective biocontrol means. Here we determined the active substances againstMeloidogyne incognitafrom a nematicidal bacterium, developed a biocontrol agent (BCA) based on optimized culture processes. The effects of the BCA on RKN control and plant growth‐promotion were evaluated in tomato pot trials.

RESULTS

Pseudomonas simiaestrain MB751 exhibiting significant nematicidal activity againstM. incognitasecond‐stage juveniles (J2) with approximately 80% mortality (with culture supernatant, 96% volume percentage) was isolated from a vineyard. A set of purification and identification experiments was performed to determine the main nematicidal component in MB751. A cyclic dipeptide Cyclo(L‐Pro‐L‐Leu) was identified with a lethal concentration necessary to kill 50% of the population (LC50) of 65.3 μg mL−1againstM. incognitaJ2. Following optimization trials on culture medium/fermentation conditions, such as the single factor test, Plackett–Burman test, steepest ascent, and response surface methodology experiments, the MB751 fermentation broth was then prepared as a BCA via a cold‐air drying process. The BCA and was evaluated in tomato pot experiments for effectiveness in suppressingM. incognita. Significant effects onM. incognitasuppression and plant‐growth promotion as well as induced systemic resistance toM. incognitaof tomato, were observed.

CONCLUSION

The cyclic dipeptide‐producing bacteriumP. simiaeMB751 exhibited high nematicidal activity and performance. Further development of this BCA should be pursued for the management ofM. incognitain agriculture. © 2021 Society of Chemical Industry.
Personalise vitamin D3 using physiologically based pharmacokinetic modelling
Authors: Huang Zhonghui , You Tao
Published: May 2021

Plasma concentration of vitamin D3 metabolite 25‐hydroxyvitamin D3 (25(OH)D3) is variable among individuals. The objective of this study is to establish an accurate model for 25(OH)D3 pharmacokinetics (PKs) to support selection of a suitable dose regimen for an individual. We collated vitamin D3 and 25(OH)D3 plasma PK data from reported clinical trials and developed a physiologically‐based pharmacokinetic (PBPK) model to appropriately recapitulate training data. Model predictions were then qualified with 25(OH)D3 plasma PKs under vitamin D3 and 25(OH)D3 dose regimens distinct from training data. From data exploration, we observed the increase in plasma 25(OH)D3 after repeated dosing was negatively correlated with 25(OH)D3 baseline levels. Our final model included a first‐order vitamin D3 absorption, a first‐order vitamin D3 metabolism, and a nonlinear 25(OH)D3 elimination function. This structure explained the apparent paradox. Remarkably, the model accurately predicted plasma 25(OH)D3 following repeated dosing up to 1250 μg/d in the test set. It also made sensible predictions for large single vitamin D3 doses up to 50,000 μg in the test set. Model predicts 10 μg/d regimen may be ineffective for achieving sufficiency (plasma 25(OH)D3 ≥ 75 nmol/L) for a severely deficient individual (baseline 25(OH)D3 = 10 nmol/L), and it might take the same person over 200 days to reach sufficiency at 20 μg/d dose. We propose to personalize vitamin D3 supplementation protocol with this PBPK model. It would require measuring 25(OH)D3 baseline levels, which is not routinely performed under the current UK public health advice.

Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Vitamin D PK exhibits substantial inter‐individual variability. Different officially recommended daily doses are confusing.

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WHAT QUESTION DID THIS STUDY ADDRESS?

Is the UK’s recommended 10 µg daily dose sufficient? Should everyone be given same dose?

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WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Our model accurately predicts plasma 25(OH)D under daily oral administration of vitamin D3. The 10 µg daily vitamin D3 dose is insufficient for prophylaxis (plasma 25(OH)D at 75 nmol/L).

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HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?

Combining blood test to measure 25(OH)D baseline with this PBPK model will help inform dosage selection and select follow‐up date to improve effectiveness of Hypovitaminosis D treatment.