bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico characterization of fructosyl peptide oxidase properties from Eupenicillium terrenum
Authors: Rahmatabadi Seyyed Soheil , Mobini Keivan , Askari Soudabeh , Najafian Javad , Karami Keyvan , Soleymani Bijan , Mostafaie Ali
Published: June 2022

Fructosyl peptide oxidase (FPOX) enzyme from Eupenicillium terrenum has a high potential to be applied as a diagnostic enzyme. The aim of the present study is the characterization of FPOX from E. terrenum using different bioinformatics tools. The computational prediction of the RNA and protein secondary structures of FPOX, solubility profile in Escherichia coli, stability, domains, and functional properties were performed. In the FPOX protein, six motifs were detected. The d‐amino acid oxidase motif was found as the most important motif that is a FAD‐dependent oxidoreductase. The cysteines including 97, 154, 234, 280, and 360 showed a lower score than −10 that have a low possibility for participitation in the formation of the SS bond. The 56.52% of FPOX amino acids are nonpolar. Random coils are dominant in the FPOX sequence, followed by alpha‐helix and extended strand. The fpox gene is capable of generating a stable RNA secondary structure (−423.90 kcal/mol) in E. coli. FPOX has a large number of hydrophobic amino acids. FPOX showed a low solubility in E. coli which has several aggregation‐prone sites in its 3‐D structure. According to the scores, the best mutation candidate for increasing solubility was the conversion of methionine 302 to arginine. The melting temperature of FPOX based on its amino acid sequence was 55°C to 65°C. The amounts of thermodynamic parameters for the FPOX enzyme were −137.4 kcal/mol, −3.59 kcal/(mol K), and −6.8 kcal/mol for standard folding enthalpy, heat capacity, and folding free energy, respectively. In conclusion, the in silico study of proteins can provide a valuable method for better understanding the protein properties and functions for use in our purposes.
Pretreatment Multiparametric MRI‐Based Radiomics Analysis for the Diagnosis of Breast Phyllodes Tumors
Authors: Ma Xiaowen , Gong Jing , Hu Feixiang , Tang Wei , Gu Yajia , Peng Weijun
Published: June 2022

Background

Preoperative pathological grading assessment is important for patients with breast phyllodes tumors (PTs).

Purpose

To develop and validate a clinical–radiomics model based on multiparametric MRI and clinical information for the pretreatment differential diagnosis of PTs.

Study Type

Retrospective.

Population

A total of 216 patients with PTs, 133 in the training cohort (55 benign PTs [BPTs] and 78 borderline/malignant PTs [BMPTs]) and 83 in the validation cohort (28 BPTs and 55 BMPTs).

Field Strength/Sequence

1.5 T and 3 T; T2‐weighted imaging (T2WI), precontrast T1‐weighted imaging (T1WI) and dynamic contrast‐enhanced T1‐weighted imaging (DCE‐T1WI).

Assessment

A total of 3138 radiomics features were computed to decode the imaging phenotypes of PTs. To build the classification models, the following workflow was followed: minimum–maximum scaling normalization method, recursive feature elimination based on ridge regression (Ridge‐RFE), synthetic minority oversampling technique, and support vector machine classifier. We established several models based on the statistically significant features (Ridge‐RFE selected) of each sequence to distinguish BPTs from BMPTs, including precontrast T1WI model, DCE‐T1WI phase 1 model, T1WI feature fusion model, T2WI model, T1WI + T2WI model, clinical feature model, conventional MRI characteristics model, and combined clinical–radiomics model.

Statistical Tests

Univariate analysis was utilized to compare variables between the BPT and BMPT groups. The receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic performance of these models.

Results

In the training cohort, the clinical–radiomics model had excellent diagnostic efficiency, with an area under ROC (AUC) of 0.91 ± 0.02 (95% CI: 0.87–0.94). In the validation cohort, the AUCs were 0.79 ± 0.05 (95% CI: 0.70–0.87) for the combined model and 0.77 ± 0.05 (95% CI: 0.67–0.85) for the radiomics model.

Data Conclusion

Compared with conventional MRI characteristics, radiomics features extracted from multiparametric MRI are helpful for improving the accuracy of differentiating the pathological grades of PTs preoperatively. The model based on radiomics and clinical information is expected to become a potential noninvasive tool for the assessment of PTs grades.

Evidence Level

4

Technical Efficacy

Stage 2
Transchromosomic bovines‐derived broadly neutralizing antibodies as potent biotherapeutics to counter important emerging viral pathogens with a special focus on SARS‐CoV‐2, MERS‐CoV, Ebola, Zika, HIV‐1, and influenza A virus
Authors: Saied AbdulRahman A. , Nascimento Manuela Sales Lima , do Nascimento Rangel Adriano Henrique , Skowron Krzysztof , Grudlewska‐Buda Katarzyna , Dhama Kuldeep , Shah Jaffer , Abdeen Ahmed , El‐Mayet Fouad S. , Ahmed Hassan , Metwally Asmaa A.
Published: June 2022

Historically, passive immunotherapy is an approved approach for protecting and treating humans against various diseases when other alternative therapeutic options are unavailable. Human polyclonal antibodies (hpAbs) can be made from convalescent human donor serum, although it is considered limited due to pandemics and the urgent requirement. Additionally, polyclonal antibodies (pAbs) could be generated from animals, but they may cause severe immunoreactivity and, once "humanized," may have lower neutralization efficiency. Transchromosomic bovines (TcBs) have been developed to address these concerns by creating robust neutralizing hpAbs, which are useful in preventing and/or curing human infections in response to hyperimmunization with vaccines holding adjuvants and/or immune stimulators over an extensive period. Unlike other animal‐derived pAbs, potent hpAbs could be promptly produced from TcB in large amounts to assist against an outbreak scenario. Some of these highly efficacious TcB‐derived antibodies have already neutralized and blocked diseases in clinical studies. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has numerous variants classified into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring. Although these variants possess different mutations, such as N501Y, E484K, K417N, K417T, L452R, T478K, and P681R, SAB‐185 has shown broad neutralizing activity against VOCs, such as Alpha, Beta, Gamma, Delta, and Omicron variants, and VOIs, such as Epsilon, Iota, Kappa, and Lambda variants. This article highlights recent developments in the field of bovine‐derived biotherapeutics, which are seen as a practical platform for developing safe and effective antivirals with broad activity, particularly considering emerging viral infections such as SARS‐CoV‐2, Ebola, Middle East respiratory syndrome coronavirus, Zika, human immunodeficiency virus type 1, and influenza A virus. Antibodies in the bovine serum or colostrum, which have been proved to be more protective than their human counterparts, are also reviewed.
Development of an efficient iterative genome editing method in Bacillus subtilis using the CRISPR‐AsCpf1 system
Authors: Zhao Xingcong , Chen Xi , Xue Yanbing , Wang Xuedong
Published: June 2022

Bacillus subtilis is a useful chassis in the fields of synthetic biology and metabolic engineering for chemical production. Here, we constructed CRISPR‐AsCpf1‐based expression plasmids with the temperature‐sensitive replicon for iterative genome editing in B. subtilis. This method allowed gene insertion and large genomic deletion with an editing efficiency of up 80%–100% and rapid plasmid curing to facilitate the iterative genome editing in B. subtilis 168. Using the customized CRISPR‐AsCpf1 system, we successfully and efficiently implemented the related gene editing in B. subtilis 168 for hyaluronic acid (HA) biosynthesis, HA synthase gene (hasA) insertion, UDP‐glucose‐dehydrogenase gene (tuaD) insertion, and eps gene cluster (epsA‐O) deletion. The heterologous production of HA was realized by the engineered strain with a yield of 1.39 g/L. These results support the finding that the CRISPR‐AsCpf1 system is highly efficient in bacteria genome editing and provide valuable guidance and essential references for genome engineering in B. subtilis using the CRISPR‐AsCpf1 system.
Efficient searching for NICE public health guidelines: Would using fewer sources still find the evidence?
Authors: Levay Paul , Heath Andrea , Tuvey Daniel
Published: June 2022

Systematic searches are integral to identifying the evidence that is used in National Institute for Health and Care Excellence (NICE) public health guidelines (PHGs). This study analyses the sources, including bibliographic databases and other techniques, required for PHGs. The aims were to analyse the sources used to identify the publications included in NICE PHGs; and to assess whether fewer sources could have been searched to retrieve these publications. Data showing how the included publications had been identified was collated using search summary tables. Three scenarios were created to test various combinations of sources to determine whether fewer sources could have been used. The sample included 29 evidence reviews, compiled using 13 searches, to support 10 PHG topics. Across the PHGs, 23 databases and six other techniques retrieved included publications. A mean reduction in total results of 6.5% could have been made if the minimum set of sources plus Cochrane Library, Embase, and MEDLINE were searched. On average, Cochrane Library, Embase, and MEDLINE contributed 76.8% of the included publications, with other databases adding 11% and other techniques 12.2%. None of the searches had a minimum set that was comprised entirely of databases. There was not a core set of sources for PHGs. A range of databases and techniques, covering a multi‐disciplinary evidence base, was required to identify all included publications. It would be possible to reduce the number of sources searched and make some gains in productivity. It is important to create a tailored set of sources to do an efficient search.
Temporal Sequence of Laryngeal Vestibule Closure and Reopening is Associated With Airway Protection
Authors: Shu Kechen , Perera Subashan , Mahoney Amanda S. , Mao Shitong , Coyle James L. , Sejdić Ervin
Published: June 2022

Background

Upper esophageal sphincter opening (UESO), and laryngeal vestibule closure (LVC) are two essential kinematic events whose timings are crucial for adequate bolus clearance and airway protection during swallowing. Their temporal characteristics can be quantified through time‐consuming analysis of videofluoroscopic swallow studies (VFSS).

Objectives

We sought to establish a model to predict the odds of penetration or aspiration during swallowing based on 15 temporal factors of UES and laryngeal vestibule kinematics.

Methods

Manual temporal measurements and ratings of penetration and aspiration were conducted on a videofluoroscopic dataset of 408 swallows from 99 patients. A generalized estimating equation model was deployed to analyze association between individual factors and the risk of penetration or aspiration.

Results

The results indicated that the latencies of laryngeal vestibular events and the time lapse between UESO onset and LVC were highly related to penetration or aspiration. The predictive model incorporating patient demographics and bolus presentation showed that delayed LVC by 0.1 s or delayed LVO by 1% of the swallow duration (average 0.018 s) was associated with a 17.19% and 2.68% increase in odds of airway invasion, respectively.

Conclusion

This predictive model provides insight into kinematic factors that underscore the interaction between the intricate timing of laryngeal kinematics and airway protection. Recent investigation in automatic noninvasive or videofluoroscopic detection of laryngeal kinematics would provide clinicians access to objective measurements not commonly quantified in VFSS. Consequently, the temporal and sequential understanding of these kinematics may interpret such measurements to an estimation of the risk of aspiration or penetration which would give rise to rapid computer‐assisted dysphagia diagnosis.

Level of Evidence

2 Laryngoscope, 133:521–527, 2023
Understanding the influencing factors and mechanisms (land use changes and check dams) controlling changes in the soil organic carbon of typical loess watersheds in China
Authors: Cao Taohong , She Dongli , Zhang Xiang , Yang Zhen
Published: June 2022

Studying the distribution patterns and controlling mechanisms of soil organic carbon (SOC) based on the comprehensive performance of vegetation restoration and check dams at the watershed scale is important for understanding carbon cycling processes in nature. Two typical watersheds (Xinshui River and Zhujiachuan watershed) of the Loess Plateau were selected to evaluate the factors affecting the change in SOC content, and then the key factors were considered in the genetic algorithm‐support vector regression (GA‐SVR) model to predict SOC content. The results showed that the topography, vegetation, and soil characteristics had significant effects on the SOC content in the upland hillslopes, while the SOC content in the check dams was significantly affected by depth and soil characteristics. The soil organic carbon storage (TSOC) in the check dams could be evaluated and predicted by the vegetation index (NGRDI) and area of the subwatershed. The GA‐SVR model had good prediction accuracy and stable performance in predicting SOC content. According to the model simulation results, bulk density (BD), mean weight diameter (MWD), elevation, NGRDI, clay ratio (CR), and slope could be used to predict the surface SOC content of the Loess Plateau. Furthermore, depth, CR, MWD, BD, and median particle size (D50) could be applied in the model to predict the SOC content at different depths in the check dams. This study explored the potential control factors of SOC content and predicted SOC content from multiple angles, which can provide basic support for the study of the carbon sequestration on the Loess Plateau.
Impact of ineffective measures on the increasing land degradation in a monsoon‐dominated region of India: Issues and policy implications
Authors: Roy Paramita , Pal Subodh Chandra , Chakrabortty Rabin , Islam Abu Reza Md. Towfiqul , Chowdhuri Indrajit , Saha Asish
Published: June 2022

Land degradation is a phenomenon that affects many environment, including drylands, resulting in a long‐term decline in ecosystems and productivity loss in agriculture. Asia has the highest ranked position in land degradation, followed by Africa and Europe, respectively. In more than 100 countries, 2.6 billion people are suffering from land degradation, and more than 33% of the Earth's land surface is under desertification. Various natural causes are drought, tsunami, earthquake, fire, flood, etc., while anthropogenic causes are land degradation through land clearance, overgrazing, planting of unsuitable species, wrong agricultural practices, inappropriate irrigation schemes, urban sprawl, and pollution from industries. The implications and effects of land degradation have reduced the productivity of agricultural land, damaged basic resources and ecosystem functions, and caused biodiversity losses. The main aim of this study is to identify the impact of ineffective measures on land degradation in a monsoon dominated region of India. In our this study, we have applied the Indian soil erosion model to predict soil erosion due to the implementation of structural and non‐structural measures. Our study finally found non‐structural measures effective for the health of the soil. Implementation of sustainable agriculture practices can reduce environmental effects without affecting productivity. This research we hope will be beneficial to local and global policymakers and those developing regulations to manage the land degradation process.
Pricing strategy and coordination of small‐ to medium‐sized enterprises based on bank‐insurance cooperative financing
Authors: Ma Junhai , Gong Lijiao , Fan Jie
Published: June 2022

With the increasingly serious environmental problems, the concept of environmental protection has been deeply rooted in people's minds. The development of small‐ to medium‐sized enterprises (SMEs) is also highly concerned, but such technology‐led enterprises are still subject to more constraints in financing. This paper introduces the loan guarantee insurance, establishes the income model of each participant under the two financing modes of traditional accounts receivable financing and accounts receivable financing under the cooperation of bank and insurer, and explores the role of loan guarantee insurance in financing of SMEs based on the Stackelberg game model. If the manufacturer's default risk premium is high, at the same time, when the loan interest rate announced by the bank under bank‐insurance cooperation is lower than the traditional model, the manufacturer under the loan guarantee insurance model produces and sells more products. However, while guaranteeing their own profits, the bank and insurer can lower the loan interest rate and insurance premium rate as far as possible, which can stimulate the market. By analyzing the complexity of the system, it is found that the decision‐maker's choice of adjusting speed and initial value affects the development state of the system.
Molecular autopsy and clinical family screening in a case of sudden cardiac death reveals ACTN2 mutation related to hypertrophic/dilated cardiomyopathy and a novel LZTR1 variant associated with Noonan syndrome
Authors: Kraoua Lilia , Jaouadi Hager , Allouche Mohamed , Achour Ahlem , Kaouther Hakim , Ahmed Habib Ben , Chaker Lilia , Maazoul Faouzi , Ouarda Fatma , Zaffran Stéphane , M'rad Ridha
Published: June 2022

Background

Genetic cardiac diseases are the main trigger of sudden cardiac death (SCD) in young adults. Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy and accounts for 0.5 to 1% of SCD cases per year.

Methods

Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM.

Results

For the deceased young adult, postmortem whole‐exome sequencing (WES) revealed a missense variant in the ACTN2 gene: c.355G > A; p.(Ala119Thr) confirming the mixed hypertrophic/dilated cardiomyopathy phenotype detected in the autopsy. For the pediatric case, WES allowed us the identification of a novel frameshift variant in the LZTR1 gene: c.1745delT; p.(Val582Glyfs*10) which confirms a clinical suspicion of HCM related to Noonan syndrome.

Conclusion

The present study adds further evidence on the pathogenicity of ACTN2: p. Ala119Thr variant in SCD and expands the mutational spectrum of the LZTR1 gene related to Noonan syndrome.
Survey: Nearly half of US adults needing MH, SUD care, did not receive it
Authors: Canady Valerie A.
Published: June 2022

A staggering 43% of adults who need mental health care or substance use care are not receiving it, compared with 21% of adults who seek primary care and don't receive it, according to a national poll released May 31 by the National Council for Mental Wellbeing (National Council) and conducted online by The Harris Poll.
Minnesota lawmakers approve investments in MH at close of session
Authors: Enos Gary
Published: June 2022

With mere minutes to spare before the required close of their state legislative session, Minnesota lawmakers last month approved a comprehensive set of mental health initiatives that include enhancements targeting crisis care and the behavioral health workforce.
New campaign partnership supports MH in LGBTQ+ community
Authors: Canady Valerie A.
Published: June 2022

Being seen, being heard, and the realization that one is not alone, are key messages behind a new campaign aimed at normalizing conversations about depression in the LGBTQ+ community. Launched last month by Janssen Pharmaceutical companies, the campaign has also partnered with such groups as Mental Health America, the National Alliance on Mental Illness, and the National Coalition for LGBTQ Health.
Research finds guns in the home pose suicide risk for teens
Authors: Canady Valerie A.
Published: June 2022

New research has found that having firearm access poses suicide risk for teenagers. Researchers compared suicidal ideation, prior suicide attempt and associated self‐reported risk factors in adolescents with and without access to firearms.
Stability analysis of within‐host SARS‐CoV‐2/HIV coinfection model
Authors: Al Agha Afnan D. , Elaiw Ahmed M. , Azoz Shaimaa A. , Ramadan Esraa
Published: June 2022

The world has been suffering from the coronavirus disease 2019 (COVID‐19) since late 2019. COVID‐19 is caused by a virus called the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The human immunodeficiency virus (HIV) coinfection with SARS‐CoV‐2 has been reported in many patients around the world. This has raised the alarm for the importance of understanding the dynamics of coinfection and its impact on the lives of patients. As in other pandemics, mathematical modeling is one of the important tools that can help medical and experimental studies of COVID‐19. In this paper, we develop a within‐host SARS‐CoV‐2/HIV coinfection model. The model consists of six ordinary differential equations. It depicts the interactions between uninfected epithelial cells, infected epithelial cells, free SARS‐CoV‐2 particles, uninfected CD4+ T cells, infected CD4+ T cells, and free HIV particles. We confirm that the solutions of the developed model are biologically acceptable by proving their nonnegativity and boundedness. We compute all possible steady states and derive their positivity conditions. We choose suitable Lyapunov functions to prove the global asymptotic stability of all steady states. We run some numerical simulations to enhance the global stability results. Based on our model, weak CD4+ T cell immune response or low CD4+ T cell counts in SARS‐CoV‐2/HIV coinfected patient increase the concentrations of infected epithelial cells and SARS‐CoV‐2 viral load. This causes the coinfected patient to suffer from severe SARS‐CoV‐2 infection. This result agrees with many studies which showed that HIV patients are at greater risk of suffering from severe COVID‐19 when infected. More studies are needed to understand the nature of SARS‐CoV‐2/HIV coinfection and the role of different immune responses during infection.
AAPM task group report 303 endorsed by the ABS: MRI implementation in HDR brachytherapy—Considerations from simulation to treatment
Authors: Prisciandaro Joann , Zoberi Jacqueline (Esthappan) , Cohen Gil'ad , Kim Yusung , Johnson Perry , Paulson Eric , Song William , Hwang Ken‐Pin , Erickson Beth , Beriwal Sushil , Kirisits Christian , Mourtada Firas
Published: June 2022

The task group (TG) on magnetic resonance imaging (MRI) implementation in high‐dose‐rate (HDR) brachytherapy (BT)—Considerations from simulation to treatment, TG 303, was constituted by the American Association of Physicists in Medicine's (AAPM's) Science Council under the direction of the Therapy Physics Committee, the Brachytherapy Subcommittee, and the Working Group on Brachytherapy Clinical Applications. The TG was charged with developing recommendations for commissioning, clinical implementation, and on‐going quality assurance (QA). Additionally, the TG was charged with describing HDR BT workflows and evaluating practical consideration that arise when implementing MR imaging. For brevity, the report is focused on the treatment of gynecologic and prostate cancer. The TG report provides an introduction and rationale for MRI implementation in BT, a review of previous publications on topics including available applicators, clinical trials, previously published BT‐related TG reports, and new image‐guided recommendations beyond CT‐based practices. The report describes MRI protocols and methodologies, including recommendations for the clinical implementation and logical considerations for MR imaging for HDR BT. Given the evolution from prescriptive to risk‐based QA, an example of a risk‐based analysis using MRI‐based, prostate HDR BT is presented. In summary, the TG report is intended to provide clear and comprehensive guidelines and recommendations for commissioning, clinical implementation, and QA for MRI‐based HDR BT that may be utilized by the medical physics community to streamline this process. This report is endorsed by the American Brachytherapy Society.
Multi‐echo balanced SSFP with a sequential phase‐encoding order for functional MR imaging at 7T
Authors: Liang Huilou , Pan Ziyi , Qian Chencan , Liu Chengwen , Sun Kaibao , Weng Dehe , An Jing , Zhuo Yan , Wang Danny J. J. , Guo Hua , Xue Rong
Published: June 2022

Purpose

To develop a 2D multi‐echo passband balanced SSFP (bSSFP) sequence using an echo‐train readout with a sequential phase‐encoding order (sequential multi‐echo bSSFP), and evaluate its performance in fast functional brain imaging at 7 T.

Methods

As images of sequential multi‐echo bSSFP exhibit multiple ghosts due to periodic k‐space modulations, a GRAPPA‐based reconstruction method was proposed to eliminate ghosting artifacts. MRI experiments were performed to compare the image quality of multi‐echo bSSFP and conventional single‐echo bSSFP. Submillimeter‐resolution fMRI using a checkerboard visual stimulus was conducted to compare the activation characteristics of multi‐echo bSSFP, conventional single‐echo bSSFP and standard gradient‐echo EPI (GE‐EPI).

Results

A higher mean structural similarity index was found between images of single‐echo bSSFP and multi‐echo bSSFP with a shorter echo train length (ETL). Multi‐echo bSSFP (ETL = 3) showed higher temporal SNR (tSNR) values than GRAPPA‐accelerated single‐echo bSSFP (R = 2). In submillimeter‐resolution fMRI experiments, multi‐echo bSSFP (ETL = 3) approached the imaging speed of GRAPPA‐accelerated single‐echo bSSFP (R = 2), but without tSNR penalty and reduced activation due to acceleration. The median t‐value and the number of significantly activated voxels were comparable between GE‐EPI and multi‐echo bSSFP (ETL = 3) that provides virtually distortion‐free functional images and inherits the activation patterns of conventional bSSFP.

Conclusion

Sequential multi‐echo bSSFP (ETL = 3) is suitable for fast fMRI with submillimeter in‐plane resolution, and offers an option to accelerate bSSFP imaging without tSNR penalty like parallel imaging.
Highly rigid & transparent supramolecular fibrils of tyrosine
Authors: Adhikari Ramesh Y. , Pujols Jeiko J.
Published: June 2022

Various peptides and amino acids can self‐assemble into fibrils in a solution environment both in vivo and in vitro. These fibrils can aggregate as amyloids in the organs of individuals with certain genetic mutations, and can also be assembled in‐vitro for their potential application as bioinspired and biocompatible material. Here, we present our study of the mechanical properties of self‐assembled fibrils of enantiomers of tyrosine, one of the essential amino acids found in living systems. We have observed that Young's modulus of fibrils of L‐tyrosine, the biologically relevant enantiomer, can be as high as 43 GPa with a point stiffness of about 454 N m–1 making these fibrils to be one of the highly rigid bioinspired structures. We have also observed that films of highly rigid L‐tyrosine fibrils also have high optical transmittance of 65% while films of enantiomer D‐tyrosine fibrils and fibrils of an equimolar mixture of D‐ and L‐tyrosine are opaque. This suggests that individual amino acids can self‐assemble into highly rigid fibrils and opens up avenues for using amino acids for constructing mechanically robust structures with varying optical properties.
Physicomechanical and cellular behavior of 3D printed polycaprolactone/poly(lactic‐co‐glycolic acid) scaffold containing polyhedral oligomeric silsesquioxane and extracellular matrix nanoparticles for cartilage tissue engineering
Authors: Alidadi Shamsabadi Zahra , Mahdavi Hamid , Shojaei Shahrokh , Salehi Hossien , Valiani Ali
Published: June 2022

The common disease of articular cartilage is osteoarthritis, which can be diagnosed with the degradation of the articular cartilage a well as formation of osteophytes, subchondral sclerosis, synovial inflammation and ultimate loss of joint function. Due to the lack of articular cartilage regeneration as well as shortage of appropriate treatment, tissue engineering has been widely used to fabricate hybrid scaffolds for supporting cartilage tissue regeneration using 3D fabrication and design techniques. In this study a 3D scaffold was designed using polycaprolactone (PCL)/poly(lactic‐co‐glycolic acid) (PLGA) biomaterial inks. Moreover, in order to achieve mechanical consistency and optimize the printing process, different concentrations of polyhedral oligomeric silsesquioxane (POSS) nanoparticles including 0, 3 and 5 (% w/v) were added. The cartilage derived extracellular matrix (ECM) particles were used as the filler to improve hydrophilicity, optimal porosity formation, optimal mechanical properties and print resolution. The samples were evaluated in terms of morphology, thermal properties, physicochemical structure, hydrophilicity, mechanical properties, biodegradation as well as thermal and cell culture study. Results showed that the compressive modulus of the PCL/PLGA/20%ECM/3%POSS 3D printed scaffolds was higher than other scaffolds. By adding 20% (w/w) ECM to the basic biomaterial ink viscosity of the biomaterial ink, porosity and water uptake were increased significantly. The 3D printed scaffold containing PCL/PLGA/5%POSS/20%ECM components demonstrated high biocompatibility as well as cell viability. Therefore, it was concluded that 3% POSS accompanying 20% ECM addition was the most suitable bioink composition for fabricating the most biocompatible and applicable scaffold for cartilage tissue engineering applications.
Low‐rank fusion convolutional neural network for prediction of remission after stereotactic radiosurgery in patients with acromegaly: a proof‐of‐concept study
Authors: Qiao Nidan , Yu Damin , Wu Guoqing , Zhang Qilin , Yao Boyuan , He Min , Ye Hongying , Zhang Zhaoyun , Wang Yongfei , Wu Hanfeng , Zhao Yao , Yu Jinhua
Published: June 2022

Artificial intelligence approaches to analyze pathological images (pathomic) for outcome prediction have not been sufficiently considered in the field of pituitary research. A total of 5,504 hematoxylin & eosin‐stained pathology image tiles from 58 acromegalic patients with a good or poor outcome were integrated with other clinical and genetic information to train a low‐rank fusion convolutional neural network (LFCNN). The model was externally validated in 1,536 patches from an external cohort. The primary outcome was the time to the first endocrine remission after stereotactic radiosurgery (SRS). The median time of initial endocrine remission was 43 months (interquartile range [IQR]: 13–60 months) after SRS, and the 24‐month initial cumulative remission rate was 57.9% (IQR: 46.4–72.3%). The patient‐wise accuracy of the LFCNN model in predicting the primary outcome was 92.9% in the internal test dataset, and the sensitivity and specificity were 87.5 and 100.0%, respectively. The LFCNN model was a strong predictor of initial cumulative remission in the training cohort (hazard ratio [HR] 9.58, 95% confidence interval [CI] 3.89–23.59; p < 0.001) and was higher than that of established prognostic markers. The predictive value of the LFCNN model was further validated in an external cohort (HR 9.06, 95% CI 1.14–72.25; p = 0.012). In this proof‐of‐concept study, clinically and genetically useful prognostic markers were integrated with digital images to predict endocrine outcomes after SRS in patients with active acromegaly. The model considerably outperformed established prognostic markers and can potentially be used by clinicians to improve decision‐making regarding adjuvant treatment choices. © 2022 The Pathological Society of Great Britain and Ireland.
Brentuximab vedotin in the treatment of paediatric patients with relapsed or refractory Hodgkin's lymphoma: Results of a real‐life study
Authors: Massano Davide , Carraro Elisa , Mussolin Lara , Buffardi Salvatore , Barat Veronica , Zama Daniele , Muggeo Paola , Vendemini Francesca , Sau Antonella , Moleti Maria Luisa , Verzegnassi Federico , D'Amico Salvatore , Casini Tommaso , Garaventa Alberto , Schiavello Elisabetta , Cellini Monica , Vinti Luciana , Farruggia Piero , Perruccio Katia , Cesaro Simone , De Santis Raffaela , Marinoni Maddalena , D'Alba Irene , Mura Rosa Maria , Burnelli Roberta , Mascarin Maurizio , Pillon Marta
Published: June 2022

Background

Brentuximab vedotin (BV) is an antibody drug‐conjugated anti‐CD30 approved for the treatment of adult classical Hodgkin's lymphoma (HL), whereas it is considered as off‐label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed HL.

Materials and methods

In this multicentre, retrospective study, 68 paediatric patients who received at least one dose of BV between November 2011 and August 2020 were enrolled. A median of nine doses of BV were administered as monotherapy (n = 31) or combined with other therapies (n = 37). BV was administrated alone as consolidation therapy after stem cell transplantation (SCT) in 12 patients, before SCT in 18 patients, whereas in 15 patients it was used before and after SCT as consolidation therapy. Median follow‐up was 2.8 years (range: 0.6–8.9 years).

Results

The best response was observed in the 86% of patients; the overall response rate was 66%. The 3‐year progression‐free survival was 58%, whereas the overall survival was 75%. No statistically significant differences between patients treated with BV monotherapy or combination were highlighted. In multivariate analysis, patients with non‐nodular sclerosis HL and not transplanted had an increased risk of failure. Overall, 46% of patients had grade 3–4 adverse events that led to BV discontinuation in five of them.

Conclusion

In conclusion, our study confirms that BV was a safe and effective drug, able to induce complete remission, either as monotherapy or in association with standard therapy.
Functionalization of poly(methyl acrylate) with formate esters and polyester through ester‐ester exchange reaction
Authors: Katoh Takayoshi , Ohta Yoshihiro , Yokozawa Tsutomu
Published: June 2022

Alkoxide‐catalyzed ester‐ester exchange reaction of poly(methyl acrylate) (PMA) with alkyl formate or polyester was investigated. In the transesterification of PMA with benzyl formate (1a), we found that the reaction of PMA with 2 equivalents of 1a in the presence of 5 mol% of potassium tert‐butoxide (tBuOK) in diglyme under reduced pressure (90 Torr) at 120°C resulted in quantitative conversion of the methyl ester moiety of PMA to the benzyl ester. Under similar conditions, hexyloxy, 2‐methylpentyloxy, and 2‐pyrenemethoyl groups were introduced into PMA with high efficiency by means of the transesterification of PMA with the corresponding formate. Furthermore, the transesterification of PMA with 23 mol% of poly(dodecamethylene isophthalate) (PEs) proceeded in the presence of 7 mol% of tBuOK in diglyme at 120°C for 1 day to afford PMA grafted with PEs (composition molar ratio PEs/PMA = 19/81). As another approach to the graft copolymer, we attempted the polycondensation of 1,12‐dodecanediol formate (2) and methyl isophthalate (3) in the presence of 20 mol% of PMA and 5 mol% of tBuOK in toluene under reduced pressure at 60°C, but this reaction afforded a gel. However, the polycondensation of 2 and 3 followed by the reaction with PMA at 60°C gave a soluble graft copolymer with PEs/PMA = 87/13 in good yield.
A ready‐to‐use fast gelation/liquefying hydrogel towards enzyme free three‐dimensional cell culture
Authors: Dong Xiaofei , Jiang Zhiqi , Hu Qiaoling
Published: June 2022

Trypsin treatment employed in traditional cell desorption method cause the damage of extracellular matrix protein and cell membrane integrity. Two‐dimensional thermo‐sensitive cell culture dish has the limitation of insufficient area. This report describes an ingenious design and synthesis of a thermoresponsive chitosan‐based hydrogel, N‐succinyl chitosan (NSCS) grafted poly(N‐isopropylacrylamide) (PNIPAM), named NSCS‐g‐PNIPAM. We then demonstrate the ultrafast gelation and liquefying of NSCS‐g‐PNIPAM by reversibly tuning the temperature of hydrogel solution above (gelation) or below (liquefying) 32°C. These unique features render the NSCS‐g‐PNIPAM hydrogel an ideal matrix for enzyme‐free three‐dimensional cell culture. As an exemplar, the skeleton muscle cell is chosen for in vitro cellular studies. The data suggests that after seven passages and harvesting, the amount of total protein, laminin and fibronectin of cell collected from the thermoreponsive hydrogel group shows unsignificant decrease after seven passages. The proteins on the cell surface are well protected compared to the conventional trypsin‐treated method. In addition, by labeling the NSCS‐g‐PNIPAM hydrogels with tetraphenylethylene (TPE)‐based aggregation‐induced‐emission (AIE) luminogenes, NSCS‐g‐PNIPAM were observed by confocal microscopy and they remain outside during entire cell culturing period.
Germline genetics of prostate cancer
Authors: Khan Hiba M. , Cheng Heather H.
Published: June 2022

Background

An important fraction (>/~10%) of men with high‐risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.

Aims

Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications.

Results

The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings.

Discussion

The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer.
Model‐informed bridging of rivaroxaban doses for thromboprophylaxis in pediatric patients aged 9 years and older with congenital heart disease
Authors: Willmann Stefan , Ince Ibrahim , Ahsman Maurice , Coboeken Katrin , Zhang Yang , Thelen Kirstin , Kubitza Dagmar , Zannikos Peter , Zhou Wangda , Pina Liza Miriam , Post Teun , Lippert Jörg
Published: June 2022

Rivaroxaban is approved in various regions for the treatment of acute venous thromboembolism (VTE) in children aged between 0 and 18 years and was recently investigated for thromboprophylaxis in children aged between 2 and 8 years (with body weights <30 kg) with congenital heart disease who had undergone the Fontan procedure. In the absence of clinical data, rivaroxaban doses for thromboprophylaxis in post‐Fontan children aged 9 years and older or ≥30 kg were derived by a bridging approach that used physiologically‐based pharmacokinetic (PBPK) and population pharmacokinetic (popPK) models based on pharmacokinetic (PK) data from 588 pediatric patients and from adult patients who received 10 mg once daily for thromboprophylaxis after major orthopedic surgeries as a reference. Both models showed a tendency toward underestimating rivaroxaban exposure in post‐Fontan patients aged between 2 and 5 years but accurately described rivaroxaban PK in post‐Fontan patients aged between 5 and 8 years. Under the assumption that hepatic function is not impaired in post‐Fontan patients, PBPK and popPK simulations indicated that half of the rivaroxaban doses for the same body weight given to pediatric patients treated for acute VTE would yield in pediatric post‐Fontan patients exposures similar to the exposure observed in adult patients receiving 10 mg rivaroxaban once daily for thromboprophylaxis. Simulation‐derived doses (7.5 mg rivaroxaban once daily for body weights 30–<50 kg and 10 mg once daily for body weights ≥50 kg) were therefore included in the recent US label of rivaroxaban for thromboprophylaxis in children aged 2 years and older with congenital heart disease who have undergone the Fontan procedure.
Life prediction of lithium thionyl chloride batteries based on the pulse load test and accelerated degradation test
Authors: Ye Xuerong , Sun Qisen , Li Wenwen , Zhai Guofu
Published: June 2022

The lithium thionyl chloride (Li/SOCl2) battery is widely used as an important long‐life backup power source. Accurate battery life prediction is essential to ensure the reliability of equipment and systems. In this paper, a novel method was proposed for the life prediction of Li/SOCl2 batteries based on the pulse load test and accelerated degradation test (ADT). The proposed pulse load test method can estimate the primary battery capacity accurately and nondestructively, which solves the challenge of quantifying degradation due to unknown initial values. Furthermore, we noticed a new phenomenon that capacity loss was affected by electrolyte fluidity, and unexpected capacity loss was observed for batteries at different discharge angles. By analyzing the mechanism of this phenomenon, we avoided serious capacity measurement errors in the 24‐week ADT. A life prediction model with a satisfactory ability to approximate the measured data was established depending on the exponential influence of time and temperature on capacity degradation.
Three‐Pronged Attack by Hybrid Nanoplatform Involving MXenes, Upconversion Nanoparticle and Aggregation‐Induced Emission Photosensitizer for Potent Cancer Theranostics
Authors: Wang Yuanwei , Niu Niu , Huang Yang , Song Shanliang , Tan Hui , Wang Lei , Wang Dong , Tang Ben Zhong
Published: June 2022

Inspired by the excellent photothermal conversion ability and inherent nanomedicine platform property of MXenes, efficient reactive oxygen species production and prominent fluorescence emission feature of aggregation‐induced emission (AIE)‐active photosensitizers (PSs), as well as the extending excitation wavelength capability of upconversion nanoparticles (UCNPs), a versatile nanoplatform comprised of Ti3C2 nanosheets (NSs), AIE‐active PSs and UCNPs is intelligently fabricated. This three‐pronged strategy takes advantages of each component simultaneously, and realizes fluorescence imaging/photoacoustic imaging/photothermal imaging triple‐modal imaging‐guided photothermal/photodynamic synergetic therapy under 808 nm laser irradiation. The introduction of UCNPs actualizes the long wavelength‐activation of AIE‐active PSs, which significantly increases the tissue penetration depth. Spatially isolation of AIE‐active PSs and Ti3C2 NSs is beneficial for suppressing the fluorescence quenching effect of Ti3C2 NSs, bringing about ultimately brilliant fluorescence. The covalently bonded polymer surface endows the nanoplatform with excellent physiological stability and efficient tumor accumulation. These outputs reveal a win‐win cooperation of multiple inorganic/organic nanocomposites for phototheranostics, and present great potential for future clinical translations.
Many reptiles under threat of extinction
Authors: Mills Georgina
Published: June 2022

Georgina Mills reports on new research that assessed the risk of extinction for more than 10,000 reptile species
Something for everyone at BVA Live
Authors: Innes Harriet
Published: June 2022

Tickets are still available for BVA Live, our brand‐new, in‐person event, taking place at the Birmingham NEC on 23–24 June. Harriet Innes, BVA events and marketing officer, encourages you to join us.
Expression of tumour transcription factor GLI1 in canine mammary tumours tissue
Authors: Liu Penggang , Lu Yurong , Yang Yang , Chen Xueli , Xiong Wenbing , Sun Jing
Published: June 2022

Background

Mammary tumor is one of the most common diseases of canine in pet clinics.

Objectives

This study investigates the distribution and expression of the tumor transcription factor GLI1 and the downstream proteins, Bmi1 and Sox2, in canine mammary tumors and paracancerous tissues.

Methods

Cancerous and paracancerous normal mammary tissues were detected using western blotting (WB), and immunohistochemistry.

Results

The results showed that the histopathology of different types in mammary tumors by microscopic observation. GLI1/Bmi1/Sox2 expression was significantly higher in canine mammary invasive carcinoma than in ductal carcinoma and adjacent normal mammary tissues (p < 0.01). The expression of GLI1 in invasive carcinoma tissues was significantly higher than Bmi1 and Sox2, while Sox2 expression in ductal carcinoma tissues was significantly higher than GLI1 and Bmi1 (p < 0.01). GLI1/Bmi1/Sox2 all showed positive reactions in both mammary tumor and adjacent normal mammary tissues with immunohistochemistry. GLI1 and Sox2 showed strong positive staining in the cytoplasm of invasive mammary carcinoma and ductal carcinoma cells, and weak positive staining in the nuclei. The positive Bmi1 reaction was mainly concentrated in the cytoplasm of invasive carcinoma and ductal carcinoma cells, while the positive reaction on the cell membrane was weak.

Conclusions

We speculate that GLI1 and related proteins play an important role in regulating the proliferation and differentiation of tumors. Therefore, it provides important reference for the pathogenesis and pathogenicity of canine mammary tumor.
The Contested Concept of ‘Integration’
Authors: Spencer Sarah
Published: June 2022

A fundamental problem in the study of ‘integration’ has been a failure to separate the empirical is from the normative ought: that is, to study what is happening in society separately from implicit assumptions on a desired end-goal. A crucial question, Castles et al. (2014, p. 264) write, concerns how immigrants and their descendants “can become part of receiving societies and nations”. This process, they note, is most commonly referred to as integration, “but this can imply a specific idea of where the process should lead, so we prefer the more neutral term ‘incorporation’”.
Migration Governance
Authors: Geddes Andrew
Published: June 2022

There are perhaps few terms that are used so frequently in the study of migration yet have as little definitional clarity as ‘governance’. This is perhaps not surprising, for, as the political scientist Claus Offe (2009) has observed, governance might best be understood as an ‘empty signifier’. What he meant by this was that governance acquires meaning through the ideas, processes, and practices that become associated with it rather than through a prior independent meaning that it possesses. For example, if migration governance is described as ‘multilevel’, as it often is, then this tells us that it occurs in lots of different places across ‘levels’ (local, national, international), whilst the actual meaning of governance remains unclear. This is a useful observation to take forward for the analysis that follows.