bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release
Authors: Ijäs Heini , Shen Boxuan , Heuer-Jungemann Amelie , Keller Adrian , Kostiainen Mauri A , Liedl Tim , Ihalainen Janne A , Linko Veikko
Published: February 2021

Doxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.
Promotion effect of nitrogen-doped functional carbon nanodots on the early growth stage of plants
Authors: Chen Qiong , Ren Xiaohua , Li Yuqian , Liu Beibei , Wang Xiuli , Tu Jiangping , Guo Zhijiang , Jin Gong , Min Guanghui , Ci Lijie
Published: February 2021

The objective of this paper is to study the effects of nitrogen-doped functional carbon nanodots (N-FCNs) on the early growth stage of plants. Hydrosoluble and biocompatible N-FCNs with high content of available N (ammonium and amino groups) and carboxyl groups are synthesized by a super green electrochemical method. N-FCNs universally express good eurytopic influence on different species of plants by inducing seeds germination, promoting root development, biomass accumulation, root cell length, chlorophyll level and transpiration of young seedlings. When functional carbon nanodots without N doping (FCNs) promote tomato and corn seeds germination rate by 92.4% and 76.2% maximally, N-FCNs could further improve the germination rate by about 17.0% and 25.5%. N-FCNs can even significantly raise the green vegetable (pakchoi) yield to 2.1 and 1.4 times on the 18th and 30th day. Leaf chlorophyll content is also increased to 1.36 and 1.55 times compared with FCNs treated group and the control group, respectively. The promotion effect of the nanodots is apparently depended on their composition, nanostructure, as well as plant species and age. Nanoscale structure and abundant hydrophilic functional groups can enable N-FCNs regulating the seed germination and plant growth by promoting the uptake and transportation of water and nutrients. The accumulation and transport of N-FCNs are investigated, which reveals N-FCNs are friendly to cells because they are absorbed and transported through nonprotoplast pathway in plant. As a result, N-FCNs have great potential for horticulture application as a biocompatible nano-medium to regulate both metabolism and early development of plants.
TCP transcription factors suppress cotyledon trichomes by impeding a cell differentiation-regulating complex
Authors: Lan Jingqiu , Zhang Jinzhe , Yuan Rongrong , Yu Hao , An Fengying , Sun Linhua , Chen Haodong , Zhou Yue , Qian Weiqiang , He Hang , Qin Genji
Published: February 2021

Trichomes are specialized epidermal cells that act as barriers against biotic and abiotic stresses. Although the formation of trichomes on hairy organs is well studied, the molecular mechanisms of trichome inhibition on smooth organs are still largely unknown. Here, we demonstrate that the CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors inhibit the formation of trichomes on cotyledons in Arabidopsis (Arabidopsis thaliana). The tcp2/3/4/5/10/13/17 septuple mutant produces cotyledons with ectopic trichomes on the adaxial sides. The expression patterns of TCP genes are developmentally regulated during cotyledon development. TCP proteins directly interact with GLABRA3 (GL3), a key component of the MYB transcription factor/basic helix–loop–helix domain protein/WD40-repeat proteins (MYB–bHLH–WD40, MBW) complex essential for trichome formation, to interfere with the transactivation activity of the MBW complex in cotyledons. TCPs also disrupt the MBW complex–R3 MYB negative feedback loop by directly promoting the expression of R3 MYB genes, which enhance the repression of the MBW complex. Our findings reveal a molecular framework in which TCPs suppress trichome formation on adaxial sides of cotyledons by repressing the activity of the MBW complex at the protein level and the transcripts of R3 MYB genes at the transcriptional level.
Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus
Authors: Wallace Daniel J , Isenberg David A , Morand Eric F , Vazquez–Mateo Cristina , Kao Amy H , Aydemir Aida , Pudota Kishore , Ona Victor , Aranow Cynthia , Merrill Joan T
Published: February 2021

Objectives

Atacicept reduced SLE disease activity in the phase 2b ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II.

Methods

In the 24-week, randomized, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo. Atacicept was continued at the same dose in atacicept-treated patients in the LTE; placebo-treated patients switched to atacicept 150 mg. Long-term safety was the primary endpoint. Secondary endpoints included SLE responder index (SRI)-4 and SRI-6 response rates and flares.

Results

In total, 253 patients entered the ADDRESS II LTE; 88 received atacicept 150 mg, 82 atacicept 75 mg and 83 placebo/atacicept 150 mg. Median active treatment duration in the LTE was 83.8 weeks. Frequencies of treatment-emergent adverse events (TEAEs) were similar across groups (90.4–93.2%), and 12.5%, 14.6% and 21.7% of patients in the atacicept 150 mg, atacicept 75 mg and placebo/atacicept 150 mg groups reported serious TEAEs during the treatment period. The proportions of patients with TEAEs leading to discontinuation were 5.7%, 4.9% and 10.8%, respectively. SRI-4 and SRI-6 response rates were maintained with atacicept in the modified intent-to-treat and HDA populations and those on continuous 150 mg had a reduced risk of first severe flare and longer time to first severe flare vs those who initially received placebo.

Conclusion

Long-term treatment with atacicept 150 mg in SLE patients had an acceptable safety profile, with durable efficacy.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT02070978.
Is the intima-media thickness of temporal and axillary arteries influenced by cardiovascular risk?
Authors: Martire María Victoria , Cipolletta Edoardo , Di Matteo Andrea , Di Carlo Marco , Jesus Diogo , Grassi Walter , Filippucci Emilio
Published: February 2021

Objectives

To measure with US the intima-media thickness (IMT) of temporal (superficial, parietal and frontal branches) and axillary arteries in subjects without a diagnosis of GCA and/or PMR with different cardiovascular (CV) risk; and to assess the performance of previously proposed cut-off values for normal IMT.

Methods

Subjects ≥ 50 years without a diagnosis of GCA or PMR were included. Bilateral US of the temporal arteries, including the frontal and parietal branches, and axillary arteries was performed by two sonographers using a 10–22 MHz and 6–18 MHz probe. The following previously proposed cut-offs were considered: superficial temporal artery: 0.42 mm; frontal branch: 0.34 mm; parietal branch: 0.29 mm; axillary artery: 1.0 mm.

Results

A total of 808 arteries in 101 subjects were evaluated; of these, 31 (30.7%) were classified as very high CV risk, seven (6.9%) as high, 34 (33.7%) as moderate and 29 (28.7%) as low risk. Subjects with very high or high risk showed higher IMT than those with moderate or low risk in the superficial temporal arteries [0.23 (s.d. 0.07) vs 0.20 (s.d. 0.04), P < 0.01] and in the axillary arteries [0.54 (s.d. 0.17) vs 0.48 (s.d. 0.10), P = 0.002] . The IMT was higher than the reference cut-off in 13/808 (1.6%) arteries, in ≥1 artery in 10/101 subjects (10.1%). Of these 10 subjects, 8 (80%) were classified as having very high or high risk.

Conclusion

Our results suggest that CV risk might influence the US-determined IMT of the temporal and axillary arteries in subjects without GCA. Therefore, in patients with suspected GCA, particular attention should be paid when measuring the IMT in those patients with very high/high CV risk.
Factors associated with incident severe pulmonary arterial hypertension in systemic autoimmune rheumatic diseases: a nationwide study
Authors: Chen Hsin-Hua , Lin Ching-Heng , Hsieh Tsu-Yi , Chen Der-Yuan , Ying Jia-Ching , Chao Wen-Cheng
Published: February 2021

Objective

To assess the association of severe pulmonary arterial hypertension (PAH) with particulate matter <2.5 μm (p.m.2.5) and clinical data in patients with systemic autoimmune rheumatic diseases (SARDs).

Methods

We used the 2003–2017 nationwide data in Taiwan to identify patients with SARDs, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis/polymyositis and primary Sjögren’s syndrome. We identified 479 cases with severe PAH and selected controls matched (1:4) for age, sex, and index year. We used conditional logistic regression analysis to determine factors associated with risks for severe PAH shown as odds ratios (ORs) with 95% confidence intervals (CIs).

Results

We found that severe PAH was highly associated with interstitial lung disease (OR, 8.57; 95% CI: 5.52, 13.32), congestive heart failure (OR, 7.62; 95% CI: 5.02, 11.55), valvular heart disease (OR, 3.34; 95% CI: 2.03, 5.50) and slightly associated with thyroid diseases (OR, 1.88; 95% CI: 1.18, 3.00), but not the level of exposure to p.m.2.5. Increased risk for PAH was found in patients receiving corticosteroid (prednisolone equivalent dosage, mg/day, OR, 1.03; 95% CI: 1.01, 1.05), biologics (OR, 2.18; 95% CI: 1.15, 4.12) as well as immunosuppressants, including ciclosporin (OR, 2.17; 95% CI: 1.31, 3.59), azathioprine (OR, 1.96; 95% CI: 1.48, 2.61), cyclophosphamide (OR, 2.01; 95% CI: 1.30, 3.11) and mycophenolate mofetil/mycophenolic acid (OR, 2.42; 95% CI: 1.37, 4.27), and those with the highest level of insured amount (reference, lowest level; OR, 0.53; 95% CI: 0.34, 0.83).

Conclusion

The population-based study identified risks for severe PAH in patients with SARDs, and these findings provide evidence for PAH risk stratification in patients with SARDs.
Cell type classification and discovery across diseases, technologies and tissues reveals conserved gene signatures and enables standardized single-cell readouts
Authors: Chamberlain Mathew , Hanamsagar Richa , Nestle Frank O. , de Rinaldis Emanuele , Savova Virginia
Published: February 2021

Autoimmune diseases are a major cause of mortality1,2. Current treatments often yield severe insult to host tissue. It is hypothesized that improved “precision medicine” therapies will target pathogenic cells selectively and thus reduce or eliminate severe side effects, and potentially induce robust immune tolerance3. However, it remains challenging to systematically identify which cellular phenotypes are present in cellular ensembles. Here, we present a novel machine learning approach, Signac, which uses neural networks trained with flow-sorted gene expression data to classify cellular phenotypes in single cell RNA-sequencing data. We demonstrate that Signac accurately classified single cell RNA-sequencing data across diseases, technologies, species and tissues. Then we applied Signac to identify known and novel immune-relevant precision medicine candidate drug targets (n = 12) in rheumatoid arthritis. A full release of this workflow can be found at our GitHub repository (https://github.com/mathewchamberlain/Signac).
Bufotenidinium iodide
Authors: Pham Duyen N. K. , Chadeayne Andrew R. , Golen James A. , Manke David R.
Published: February 2021

The title compound, 5-hydroxy-N,N,N-trimethyltryptammonium (5-HTQ) iodide {systematic name: [2-(5-hydroxy-1H-indol-3-yl)ethyl]trimethylazanium iodide}, C13H19N2O+·I−, has a single tryptammonium cation and one iodide anion in the asymmetric unit. The ions are held together by N—H...I and O—H...I hydrogen bonds in infinite chains along [100].
Decision making under interval uncertainty: toward (somewhat) more convincing justifications for Hurwicz optimism-pessimism approach
Authors: Chinnakum Warattaya , Berrout Ramos Laura , Iyiola Olugbenga , Kreinovich Vladik
Published: February 2021

Purpose

In real life, we only know the consequences of each possible action with some uncertainty. A typical example is interval uncertainty, when we only know the lower and upper bounds on the expected gain. A usual way to compare such interval-valued alternatives is to use the optimism–pessimism criterion developed by Nobelist Leo Hurwicz. In this approach, a weighted combination of the worst-case and the best-case gains is maximized. There exist several justifications for this criterion; however, some of the assumptions behind these justifications are not 100% convincing. The purpose of this paper is to find a more convincing explanation.

Design/methodology/approach

The authors used utility approach to decision-making.

Findings

The authors proposed new, hopefully more convincing, justifications for Hurwicz’s approach.

Originality/value

This is a new, more intuitive explanation of Hurwicz’s approach to decision-making under interval uncertainty.
Remote deepwater subsea pipeline maintenance system
Authors: Luo Yu , Jiao Xiangdong , Fang Zewei , Zhang Shuxin , Wu Xuan , Wang Dongyao , Chu Qin
Published: February 2021

Purpose

This paper aims to propose a diverless weld bead maintenance welding technology to prevent the leakage of subsea oil and gas pipeline and solve the key problems in the maintenance of subsea pipeline.

Design/methodology/approach

Based on the analysis of the cross-section of the fillet weld, the multi-layer and multi-pass welding path planning of the submarine pipeline sleeve fillet weld is studied, and thus a multi-layer and multi-pass welding path planning strategy is proposed. A welding seam filling method is designed, and the end position of the welding gun is planned, which provides a theoretical basis for the motion control of the maintenance system.

Findings

The trajectory planning and adjustment of multi-layer and multi-pass fillet welding and the motion stability control of the rotating mechanism are realized.

Research limitations/implications

It provides the basis for the prototype design of the submarine pipeline maintenance and welding robot system, and also lays the foundation for the in-depth research on the intelligent maintenance system of submarine pipeline.

Originality/value

The maintenance of diverless subsea pipeline is a new type of maintenance method, which can solve the problem of large amount of subsea maintenance work with high efficiency.
The work–family balance of British working women during the COVID-19 pandemic
Authors: Adisa Toyin Ajibade , Aiyenitaju Opeoluwa , Adekoya Olatunji David
Published: February 2021

Purpose

The COVID-19 pandemic has affected women in unique gender-specific ways, particularly their traditional status as home managers. This study aims to draw on the role theory to examine the impact of the COVID-19 pandemic on women's work–family balance during the lockdown.

Design/methodology/approach

The current COVID-19 pandemic, which has altered the ways in which we live and work, requires specific methodological tools to be understood. The authors, therefore, opted for an interpretive–constructivist and constructivist–phenomenologist approach. The dataset, thus, comprises of semi-structured interviews with 26 working women in the UK.

Findings

The findings illustrate how the COVID-19 lockdown has intensified British women's domestic workload and has, thus, caused unbridled role conflict, which has further been exacerbated by structural and interactional roles undertaken by women, especially during the lockdown. Remote working has contributed to women's role congestion and role conflict and poses severe challenges to role differentiation. Furthermore, we found that the lockdown has facilitated the rediscovery of family values and closeness, which is connected to the decline in juvenile delinquency and low crime rate that has resulted from the lockdown.

Originality/value

Through the lens of the role theory, this study concludes that the cohabitation of work and family duties within the domestic space undermines the ability to achieve work–family balance and role differentiation due to the occurrence of inter-role conflicts. This study enriches our understanding of the effect of remote working on female employees' work–family balance during the unprecedented COVID-19 pandemic lockdown.
Development of novel pH-sensitive azo dyes from Cardanol as a bioresource
Authors: Mestry Siddhesh Umesh , Mahajan Umesh Ratan , M. Aswathy , Mhaske Shashank T.
Published: February 2021

Purpose

The purpose of this paper is to use the bio-based resource as the starting material for the synthesis of azo dye. Cardanol is one of the most used bio-based resources for carrying out the synthesis of various compounds having numerous end applications. The study presents an attempt to develop an azo dye from Cardanol having end applications in pH-responsive dyes.

Design/methodology/approach

The cardanol was sulfonated to block the para position by which ortho positioned hydroxyl group after diazotization and coupling will provide necessary pH-sensitivity. The diazotization of two naphthalene derivatives, i.e. 1-naphthol-8-amino-3,6-disulfonic acid (H-acid) and 7-amino-4-hydroxy-2-naphthalene sulfonic acid (J-acid) was carried out using the standard practice, and the diazotized compounds were coupled with the sulfonated cardanol. The obtained dyes were characterized by Fourier transform infrared, nuclear magnetic resonance, carbon-hydrogen-nitrogen-sulfur analysis and hydroxyl value. The colour properties were checked using UV-vis spectrophotometry and density functional theory, while thermogravimetric analysis was used for the thermal degradation studies of both the dyes.

Findings

Water-soluble cardanol-based azo dyes were prepared successfully having good thermal stability, and the obtained results are being presented in this paper.

Originality/value

The originality lies between the use of cardanol as a bio-based resource for the synthesis of azo-dye and the obtained azo-dye has the pH-sensitivity.
Investigation on the performance of fiber reinforced concrete subjected to standard fire exposure
Authors: Varghese Alwyn , N. Anand , Andrushia Diana , Arulraj Prince
Published: February 2021

Purpose

Aim of this research work is to examine the stress–strain behavior and modulus of elasticity of fiber-reinforced concrete (FRC) exposed to elevated temperature. The purpose of this paper is to study the effect of standard fire exposure on the mechanical and microstructure characteristics of concrete specimens with different strength grade.

Design/methodology/approach

An electrical bogie hearth furnace was developed to simulate the ISO 834 standard fire curve. Specimens were exposed to high temperatures of 821°C, 925°C and 986°C for the duration of 30, 60 and 90 min, respectively, as per standard fire curve. Peak stress, peak strain, modulus of elasticity and damage level of heated concrete specimens were evaluated by experimental investigation. SEM-based microstructure investigation has been carried out to analyze the microstructure characteristics of heated concrete specimens.

Findings

The results revealed that carbon fiber reinforced concrete was found to be better than the FRC made with other fibers on improving the modulus of elasticity of concrete. An empirical relationship has been established to predict the modulus of elasticity of temperature exposed specimens with different type of fiber and grade of concrete. In comparison with low melting point fibers, high melting point fibers exhibited higher modulus of elasticity under all tested conditions. Surface damage and porosity level of concrete with carbon and basalt fibers were found to be lower than other FRC.

Originality/value

Empirical relationship was developed to determine the modulus of elasticity of concrete exposed to elevate temperature, and this will be useful for concrete design applications. This research work may be useful for finding the residual compressive strength of concrete exposed to elevate temperature. So that it will be helpful to identify the suitable repair/retrofitting technique for reinforced concrete elements.
Benchmarking the performance of Pool‐seq SNP callers using simulated and real sequencing data
Authors: Guirao‐Rico Sara , González Josefa
Published: February 2021

Population genomics is a fast‐developing discipline with promising applications in a growing number of life sciences fields. Advances in sequencing technologies and bioinformatics tools allow population genomics to exploit genome‐wide information to identify the molecular variants underlying traits of interest and the evolutionary forces that modulate these variants through space and time. However, the cost of genomic analyses of multiple populations is still too high to address them through individual genome sequencing. Pooling individuals for sequencing can be a more effective strategy in Single Nucleotide Polymorphism (SNP) detection and allele frequency estimation because of a higher total coverage. However, compared to individual sequencing, SNP calling from pools has the additional difficulty of distinguishing rare variants from sequencing errors, which is often avoided by establishing a minimum threshold allele frequency for the analysis. Finding an optimal balance between minimizing information loss and reducing sequencing costs is essential to ensure the success of population genomics studies. Here, we have benchmarked the performance of SNP callers for Pool‐seq data, based on different approaches, under different conditions, and using computer simulations and real data. We found that SNP callers performance varied for allele frequencies up to 0.35. We also found that SNP callers based on Bayesian (SNAPE‐pooled) or maximum likelihood (MAPGD) approaches outperform the two heuristic callers tested (VarScan and PoolSNP), in terms of the balance between sensitivity and FDR both in simulated and sequencing data. Our results will help inform the selection of the most appropriate SNP caller not only for large‐scale population studies but also in cases where the Pool‐seq strategy is the only option, such as in metagenomic or polyploid studies.
Cone beam computed tomography in dentistry: practitioner awareness and attitudes. A scoping review
Authors: Stokes Kelsie , Thieme Raine , Jennings Ernest , Sholapurkar Amar
Published: February 2021

Familiarity with cone beam computed tomography is a requisite for all dental practitioners involved in its use or referral. This scoping review examines the knowledge, attitudes, competence and confidence of dental practitioners and students towards cone beam computed tomography in the dental setting. A search of Medline, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature was conducted to identify and chart existing evidence. Relevant studies written in English and published after 1998 and up to July 2020 were included. Of 679 papers, 39 studies were included for analysis. Key findings include deficient knowledge despite a widespread recognition of its importance and willingness to increase proficiency in its use, as well as a largely positive and optimistic view of the technology. Future studies on practitioners’ knowledge and attitudes towards cone beam computed tomography are suggested to consider the contexts of an Australian setting.
A new approach to individualize dialysis fluid sodium concentration using a four‐stream, bicarbonate‐based fluid delivery system
Authors: Lew Susie Q. , Cheng Yuk‐Lun , Tzamaloukas Antonios H. , Ing Todd S.
Published: February 2021

We propose a new 45X, four‐stream, triple‐concentrate, bicarbonate‐based dialysis fluid delivery system, allowing a wide range of dialysis fluid sodium concentrations\\ (DFNa) without affecting the concentrations of other crucial solutes. The four streams consist of product water (W), and concentrates with sodium chloride (S), acid (A), and sodium bicarbonate (B). An adjustment in the DFNa in this new system requires changes only in the W and S concentrate streams. The ingredients in A and B concentrates do not change.
Defining inclusion criteria and endpoints for clinical trials: a prospective cross‐sectional study in CRB1‐associated retinal dystrophies
Authors: Talib Mays , van Schooneveld Mary J. , Wijnholds Jan , van Genderen Maria M. , Schalij‐Delfos Nicoline E. , Talsma Herman E. , Florijn Ralph J. , ten Brink Jacoline B. , Cremers Frans P.M. , Thiadens Alberta A.H.J. , van den Born L. Ingeborgh , Hoyng Carel B. , Meester‐Smoor Magda A. , Bergen Arthur A. , Boon Camiel J.F.
Published: February 2021

Purpose

To investigate the retinal structure and function in patients with CRB1‐associated retinal dystrophies (RD) and to explore potential clinical endpoints.

Methods

In this prospective cross‐sectional study, 22 patients with genetically confirmed CRB1‐RD (aged 6–74 years), and who had a decimal best‐corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral‐domain optical coherence tomography (SD‐OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full‐field electroretinography (ERG) and full‐field stimulus testing (FST). Ten patients were from a genetic isolate (GI).

Results

Patients had retinitis pigmentosa (n = 19; GI and non‐GI), cone‐rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non‐GI). Median age at first symptom onset was 3 years (range 0.8–49). Median decimal BCVA in the better and worse‐seeing eye was 0.18 (range 0.05–0.83) and 0.08 (range light perception‐0.72), respectively. Spectral‐domain optical coherence tomography (SD‐OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well‐preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full‐field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes.

Conclusions

Despite the generally severe course of CRB1‐RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.
Adolescent vocational interests predict early career success: Two 12‐year longitudinal studies
Authors: Hoff Kevin A. , Chu Chu , Einarsdóttir Sif , Briley Daniel A. , Hanna Alexis , Rounds James
Published: February 2021

Vocational interests are relatively stable individual differences that can change across the lifespan. However, little is known about the importance of interest changes, relative to stable interest levels, for predicting career outcomes. This study assessed the long‐term predictive power of adolescent interest levels and interest growth for five career outcomes: degree attainment, occupational prestige, income, and career‐ and job‐satisfaction. The study used two 12‐year longitudinal samples (N1 = 485; N2 = 1290) with vocational interests measured across multiple waves from late adolescence to young adulthood. Results from both samples converged on three key findings. First, adolescents who showed better interest fit with their eventual vocation were more satisfied with their jobs over a decade later. Second, adolescent interests predicted objective career outcomes (i.e. degree attainment, occupational prestige, and income), revealing that early interests shaped educational and career choices. Third, interest changes were typically not associated with career outcomes, indicating that adolescent interest levels played a larger role. Together, these findings highlight the critical importance of childhood and adolescent interest development for guiding career trajectories and outcomes. We discuss implications for interest development theories, educational policies, and applied interventions.
Prospective association of parental and child internalizing symptoms: Mediation of parenting practices and irritability
Authors: Valencia Fátima , Penelo Eva , de la Osa Núria , Navarro J. Blas , Ezpeleta Lourdes
Published: February 2021

Maternal internalizing symptoms have been linked with child internalizing symptoms, but paternal internalizing difficulties have received little attention. Our aims were to prospectively analyse the simultaneous effect of maternal and paternal internalizing symptoms on child internalizing difficulties, examining gender differences, and to verify the mediating effect of parenting practices and child irritability. The sample included 470 families assessed at child ages 3, 6, 8, and 11. Multi‐group structural equation modelling was performed with Mplus8.2. Complete equivalence was found between boys and girls for all paths. Maternal internalizing symptoms at age 3 had an indirect effect on child internalizing symptoms at age 11, via irritability at age 8. Paternal internalizing symptoms at age 3 were not associated with any of the variables under study. Maternal internalizing symptoms and child irritability are targets for intervention in order to prevent child internalizing difficulties.
Altered cytokine responses in children with cerebral palsy: pathogenesis and novel therapies
Authors: Schleiss Mark R
Published: February 2021

This commentary is on the original article by Zareen et al. on pages 407–412 of this issue.
Adsorption of Cr(VI) onto a low‐cost ceramsite: Preparation, kinetics, and thermodynamics
Authors: Li Bin , Zhao Mingxing , Qi Yanxia , Wang Qidong , Jiang Nan , Luo Wenqin
Published: February 2021

A novel composite ceramsite derived from bamboo powders and bentonite was developed as adsorbents for waste water treatment. The microstructure, morphology, and thermal properties of ceramsite were characterized by X‐ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, energy dispersive X‐ray fluorescence, and differential thermal analysis. The effect of compositions, sintering temperatures, sintering time, pH, and adsorption time on the adsorption performance of the ceramsites were studied. The results revealed that the maximum Cr(VI) removal rate of 99% can be obtained in the ceramsite with weight ratio bamboo to bentonite of 6:4, the annealing temperature of 1000°C, the solution pH 1 and contact time of 12 h. The adsorption kinetics and adsorption isotherm analysis revealed that the adsorption process best followed pseudo‐second‐order reaction kinetics and the Freundlich adsorption isotherm. The adsorption mechanism was discussed and both chemisorption and physiosorption were proposed as adsorption mechanism of Cr(VI). Moreover, the thermodynamic parameters, including changes in Gibbs free energy, entropy, and enthalpy, were studied in detail. The bamboo powder/bentonite composite ceramsite developed in this work is a promising candidate as an effective and economical adsorbent for Cr(VI) ions removal.
Effects of alpha lipoic acid on iron overload, lipid profile and oxidative stress indices in β‐thalassemia major patients: A cross‐over randomised controlled clinical trial
Authors: Sharifi‐Zahabi Elham , Abdollahzad Hadi , Mostafa Nachvak Seyed , Moloudi Jalal , Golpayegani Mohammad Reza , Asiaei Sahar , Rezavand Laya , Iraji Zeynab , Jamshidi Khadijeh
Published: February 2021

Aims

β‐Thalassemia major (β‐TM) is associated with iron overload, abnormal lipid levels and oxidative stress. Alpha lipoic acid (ALA) showed anti‐oxidant and iron chelating properties, but its effect in β‐TM patients is unclear. We investigated the effects of ALA on iron levels, lipid profile and oxidative stress.

Methods

In this cross‐over randomised clinical trial, 26 β‐TM patients were assigned to receive 600 mg/d ALA or placebo (corn starch), for 8 weeks with a 21‐days washout period. Serum ferritin, total cholesterol, triglycerides, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), LDL‐C/HDL‐C, total antioxidant capacity, malondialdehyde (MDA) and MDA/LDL‐C were assessed at baseline and the end of each intervention phase.

Results

Twenty‐two patients completed the study. Serum ferritin (P = .004), MDA (P = .025) and MDA/LDL‐C ratio (P =.002) were decreased and HDL‐C (P =.035) increased significantly during ALA consumption. In comparison with placebo, ALA decreased the serum ferritin significantly (P = .02). Also, the changes in serum ferritin between ALA and placebo (−123.1 ± 40.0 vs −34.3 ± 21.0, P =.03) was significant in women subgroup. ALA had no significant effects on the other biomarkers.

Conclusion

The results of this study indicated that supplementation with 600 mg/d ALA may decrease serum ferritin in β‐TM. Further studies are needed to confirm the findings.
Using cone beam CT scans to reveal headfirst ingestion and possible prey manipulation tactics in sawsharks
Authors: Burke Patrick J. , Williamson Jane E.
Published: February 2021

Prey manipulation through headfirst ingestion is a common foraging tactic in predatory taxa. Sawsharks possess a toothed rostrum that is thought to assist in prey capture, but the process from prey contact to ingestion is unknown. This study provides evidence of headfirst ingestion and possible prey orientation in situ through the use of cone beam CT scans in the common sawshark (Pristiophorus cirratus). CT scans provide an efficient method for assessing ingestion and proposing plausible behavioural tactics for food manipulation in a species difficult to observe in the wild or maintain in captivity.
Deletion of adipocytes induced by a novel device simultaneously delivering synchronized radiofrequency and hifem: Human histological study
Authors: Goldberg David J.
Published: February 2021

Background

Radiofrequency (RF) is commonly recognized treatment option for fat reduction, utilizing heat‐induced adipocyte deletion. HIFEM treatment has been proven to be an effective tool for body shaping.

Objectives

To document the structural changes in human subcutaneous tissue induced by the combination of RF treatment with the HIFEM procedure.

Methods

Four subjects (51.50 ± 6.35 years, 22.59 ± 3.21 kg/m2) received three 30‐minute abdominal treatments consisting of RF therapy and HIFEM. One subject (57 years, 23.60 kg/m2) served as a control. Punch biopsies were collected at baseline, 1‐week, and 1‐month post‐treatment. Samples were sliced and stained with H&E. Waist circumference, digital photographs, satisfaction, and therapy comfort were assessed. Subjects were monitored for any adverse event, and fat temperatures were measured.

Results

Baseline samples showed a healthy appearance of adipocytes, composed of round‐shaped unilocular cells of uniform size. At follow‐up, treated adipocytes demonstrated nuclear and shape changes with consequent fat reduction. Adipocytes were found to be flattened/shrunken and of smaller size (−33.5% at 1 week; −31.7% at 1‐month) along with occasional ruptures of the cytoplasmic membrane. In contrast to baseline, pyknotic nuclei with condensed nuclear chromatin were seen at 1‐week and 1‐month post‐treatment. The control samples showed no treatment‐related changes. Waist circumference decreased by an average of 2.20 cm in the treated patients. No adverse events were observed. The fat temperature reached 42‐45°C, during treatment; the therapy was comfortable with high patient satisfaction.

Conclusions

Results suggest the efficacy and safety of the therapy combining RF and HIFEM. The adipocyte deletion and shrinkage resulted in overall reduction of fat tissue.
Use of allograft dermal matrix for repairing large oral epithelial defects: Outcomes of patients with lingual and buccal leukoplakia
Authors: Zhou Bin , Yuan Kai‐fang , Chen Wei‐liang
Published: February 2021

Background

The best treatment approach for wide oral leukoplakia (OL) remains to be determined.

Aims

To evaluate the outcomes of using an allograft dermal matrix (ADM) for reconstructing large oral epithelial defects following resection of OLs.

Patients and Methods

A total of 27 OLs in 26 patients were excised, and residual large lingual and buccal epithelial defects were reconstructed using an ADM, which ranged in size from 3.0 × 5.0 to 6.0 × 6.0 cm. The patients were classified into mild (n = 1), moderate (n = 13), and severe dysplasia (n = 12) groups; 57.7% of the patients were tobacco smokers, 46.2% were alcoholics, 47.2% were both smokers and alcoholics, and 11.5% were both smoking and betel quid chewers. Patients who underwent surgery were advised to quit smoking, drink alcohol in moderation, or quit betel quid chewing.

Results

Two patients developed slight hematomas that resolved spontaneously within 2 weeks. A total of 76.9% of the smokers followed the advice to quit smoking, 83.3% of the alcoholics followed the advice to drink in moderation, and all three betel quid chewers followed the advice to quit chewing betel quid. The mean follow‐up was 26.7 months. No MT occurred and recurrence was seen in two patients.

Conclusions

Large epithelial defect reconstruction using an ADM following resection of wide lingual and buccal OLs was safe and reliable for preventing MT of OL. The recurrence of OL may be related to patient habits such as tobacco smoking or/and drinking alcohol.
The relationship between patient obesity and nursing workload: An integrative review
Authors: Huang Sizhao L. , Cheng Heilok , Duffield Christine , Denney‐Wilson Elizabeth
Published: February 2021

Aims and objectives

To explore the relationship between patient obesity and nursing workload, and discuss the nursing activities most affected by patient obesity.

Background

The increasing number of patients with obesity, and the severity of obesity, impacts the healthcare workforce, particularly to nurses who provide most direct care to patients. There is growing evidence to suggest that patient obesity may increase nursing workload and time taken for clinical care.

Design

Integrative review.

Methods

A comprehensive search of academic databases for primary research related to patient obesity and nursing workload, published since 2000, was conducted. References of relevant articles were hand‐searched.

Results

27 articles were analysed. Analysis was undertaken at the levels of patient characteristics, nursing work and the healthcare system. The increasing number of patients with obesity, and the severity of patient obesity, increases nursing workload by affecting nursing time needed to deliver care. An increased number of nurses, particularly with increased clinical skill, are needed to deliver care meeting these increased needs. Organisational change is required to provide infrastructure and bariatric equipment that enables effective nursing care of patients with obesity. Organisations must consider additional time and staff needs when delivering care for patients with obesity.

Conclusions

The current health system is not established to address the challenge of providing nursing care to the increasing numbers of patients with obesity. Further research on accurately and objectively quantifying the impact and severity of patient obesity on nursing clinical activities is required.

Relevance to clinical practice

When determining staffing, healthcare organisations must consider the increased nursing staff, time and clinical skill required to provide care for patients with obesity. Healthcare organisations should implement policies that ensure sufficient staffing in areas where care of patients with obesity is prevalent, and provide training for and workplace availability of bariatric equipment.
Performance evaluation of fungal DNA PCR amplification from formalin‐fixed paraffin‐embedded tissue for diagnosis: Experience of a tertiary reference laboratory
Authors: Lysen Colleen , Silva‐Flannery Luciana , Zaki Sherif R. , Gary Joy M. , Lockhart Shawn R.
Published: February 2021

Background

Diagnosis of invasive fungal infections from formalin‐fixed paraffin‐embedded (FFPE) tissues by PCR amplification is a developing technology. One of the difficulties of establishing a validated protocol for this testing is that the gold standard, culture, is much less sensitive than the test being validated.

Objectives

To validate FFPE PCR as a refence laboratory identification methodology in the absence of abundant gold standard specimens.

Methods

In this validation, PCR from FFPE tissue was compared to other diagnostic methods for genus/species identification. Four different groups of correlative data from FFPE tissues were used to validate this procedure. Thirteen specimens had culture or serology results and FFPE PCR results, 49 specimens had both immunohistochemistry (IHC) identification and FFPE PCR results, 118 specimens had histological evidence of fungal elements, 64 of which also had FFPE PCR results, and 36 fungal mock tissues or fungal negative tissues were used.

Results

The sensitivity determined from the tissues with positive fungal histopathology was 54%. The specificity of the cases for which there were both culture and FFPE PCR results was 100%. For the correlation with IHC, the specificity was 98%. For the mock tissues and fungal negative tissues, the calculated analytical sensitivity was 94%, specificity was 95%, and accuracy was 94%.

Conclusions

By uniquely combining various data sources, this study provides a comprehensive framework for how validation can be achieved in the absence of a gold standard and outlines the excellent performance of PCR from FFPE tissue, despite relatively the low sensitivity when compared to histopathology.
Cerebral autoregulation in infants during sevoflurane anesthesia for craniofacial surgery
Authors: Jildenstål Pether , Widarsson Norbeck Daniel , Snygg Johan , Ricksten Sven‐Erik , Lannemyr Lukas
Published: February 2021

Background

Data on cerebral pressure‐flow autoregulation in the youngest children are scarce. We studied the correlation between mean arterial pressure and cerebral tissue oxygen saturation (rSO2) by near‐infrared spectroscopy (NIRS) in patients undergoing nose, lip, and palate surgery.

Aim

We tested the hypothesis that cerebral pressure‐flow autoregulation is impaired in children less than 1 year undergoing surgery and general anesthesia with sevoflurane under controlled mechanical ventilation.

Method

After approval from the Ethical board, 15 children aged <1 year were included. Before anesthesia induction, a NIRS sensor (INVOSTM, Medtronic, Minneapolis, USA) was placed over the cerebral frontal lobe. Frontal rSO2, a surrogate for cerebral perfusion, mean arterial pressure, end‐tidal CO2‐ and sevoflurane concentration, and arterial oxygen saturation were sampled every minute after the induction. A repeated measures correlation analysis was performed to study correlation between mean arterial pressure and cerebral rSO2, and the repeated measures correlation coefficient (rrm) was calculated.

Results

Fifteen patients, aged 7.7 ± 1.9 months, were studied. rSO2 showed a positive correlation with mean arterial pressure ([95% CI: 9.0‐12.1], P < 0.001) with a moderate to large effect size (rrm = 0.462), indicating an impaired cerebral pressure‐flow autoregulation. The slopes of the rSO2‐mean arterial pressure correlations were steeper in patients who were hypotensive (mean arterial pressure <50 mm Hg) compared to patients having a mean arterial pressure ≥50 mm Hg, indicating that at lower mean arterial pressure, the cerebral pressure dependence of cerebral oxygenation is even more pronounced.

Conclusion

During sevoflurane anesthesia in the youngest pediatric patients, cerebral perfusion is pressure‐dependent, suggesting that the efficiency of the cerebral blood flow autoregulation is limited.
B6‐Dct‐H2BGFP bitransgenic mice: A standardized mouse model for in vivo characterization of melanocyte development and stem cell differentiation
Authors: Tandukar Bishal , Kalapurakal Emmanual , Hornyak Thomas J.
Published: February 2021

Melanocyte stem cells (McSCs) are key components of the hair follicle (HF) stem cell system that regenerate differentiated melanocytes during successive HF cycles. To facilitate continued research on melanocyte development and differentiation and McSCs, we backcrossed inducible Dct‐H2BGFP mice into the C57BL/6J background (B6‐Dct‐H2BGFP). We compared the expression pattern of B6‐Dct‐H2BGFP to that of Dct‐H2BGFP mice on a mixed genetic background reported previously. To characterize B6‐Dct‐H2BGFP mice, we confirmed not only the expression of GFP in all melanocyte lineage cells, but also doxycycline regulation of GFP expression. Furthermore, ex vivo culture of the McSC subsets isolated by fluorescence‐activated cell sorting (FACS) showed the propensity of bulge/CD34+ McSCs to differentiate with expression of non‐melanocytic, neural crest lineage markers including glia (Gfap and CNPase, 73 ± 1% and 77 ± 2%, respectively), neurons (Tuj1 26 ± 5%), and smooth muscle (α‐Sma, 31 ± 9%). In contrast, CD34−/secondary hair germ (SHG) McSCs differentiated into pigmented melanocytes, with higher expression of melanogenic markers Tyr (71 ± 1%), Tyrp1 (68 ± 4%), and Mitf (75 ± 7%). These results establish the utility of B6‐Dct‐H2BGFP bitransgenic mice for future in vivo studies of melanocytes requiring a defined genetic background.