bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial bioremediation as a tool for the removal of heavy metals
Authors: Abo-Alkasem Mohamed I. , Hassan Ne’mat H. , Abo Elsoud Mostafa Mostafa 
Published: February 2023

Abstract
Background
The demand for designing a new technology that can emphasize the complete removal of heavy metals increased as a result of the industrial revolution. Bioremediation was found to have a potent impact on the degradation of organic and inorganic environmental pollutants.

Main body
Bioremediation is a multidisciplinary technology that possesses safe, efficient, and low-cost characteristics. Also, one of the important features of bioremediation technology is the in-situ treatment which reduces the possibility of transmitting the contaminants to another site. The application of genetic engineering, to engineer a microorganism to acquire the ability to remove different types of heavy metals at a time or to generate a transgenic plant, is considered one of the new promising bioremediation approaches.

Short conclusion
Removal of heavy metal pollution still represents a big challenge for ecologists that’s why this review shed some light on bioremediation technology; its importance, mechanism of action, and prospects.
Robustness optimization for rapid prototyping of functional artifacts based on visualized computing digital twins
Authors: Xu Jinghua , Liu Kunqian , Wang Linxuan , Guo Hongshuai , Zhan Jiangtao , Liu Xiaojian , Zhang Shuyou , Tan Jianrong 
Published: February 2023

AbstractThis study presents a robustness optimization method for rapid prototyping (RP) of functional artifacts based on visualized computing digital twins (VCDT). A generalized multiobjective robustness optimization model for RP of scheme design prototype was first built, where thermal, structural, and multidisciplinary knowledge could be integrated for visualization. To implement visualized computing, the membership function of fuzzy decision-making was optimized using a genetic algorithm. Transient thermodynamic, structural statics, and flow field analyses were conducted, especially for glass fiber composite materials, which have the characteristics of high strength, corrosion resistance, temperature resistance, dimensional stability, and electrical insulation. An electrothermal experiment was performed by measuring the temperature and changes in temperature during RP. Infrared thermographs were obtained using thermal field measurements to determine the temperature distribution. A numerical analysis of a lightweight ribbed ergonomic artifact is presented to illustrate the VCDT. Moreover, manufacturability was verified based on a thermal-solid coupled finite element analysis. The physical experiment and practice proved that the proposed VCDT provided a robust design paradigm for a layered RP between the steady balance of electrothermal regulation and manufacturing efficacy under hybrid uncertainties.
Usefulness of combined diffusion tensor imaging, arterial spin labelling and spectroscopic interictal analysis in refractory epilepsy
Authors: Reda Alaa Mohamed , Elsharkawy Ahmed , Hasby Sara Essam 
Published: February 2023

Abstract
Background
Epilepsy is a common neurological disorder especially in pediatric population. Patients with non-lesional epilepsy have normal conventional MRI findings. In the recent era of advances in neuroimaging studies, diffusion tensor imaging (DTI) and MR spectroscopy (MRS) can assess the tissue microstructure. Also, arterial spin labeling (ASL) is a noninvasive modality that evaluates cerebral blood flow. Multiple recent publications aimed at use of single or two new modalities in lateralization of epileptogenic focus in epilepsy, but the current study aimed to evaluate the added value of combined (DTI, ASL and MRS) in vivo localization of interactable epilepsy with negative conventional MRI findings.

Results
This prospective case control study was carried out in the period from January 1st, 2022 to October 1st, 2022 after approval of local ethical committee in our institution. Written informed consent was obtained from patients and healthy volunteers who were enrolled in this study. The current study included 46 patients with temporal lobe epilepsy and 20 age- and sex-matched healthy volunteers as a control group. The mean age in the patient group was 22.3 ± 12.2 years, and in the control group, it was 23.8 ± 15.1 years. The highest area under the curve (AUC) was for spectroscopy (0.913), the difference in NAA/Cr showed sensitivity of 94.1% and a specificity of 90%, while NAA/Cho + Cr showed a sensitivity of 91.8% and a specificity of 88%, the difference in rCBF showed an AUC of 0.89, with a cutoff value of 3.815 had a sensitivity of 80.4% and a specificity of 85%. As regards DTI, the changes in DTI parameters show sensitivity of 79.6% and a specificity of 80% in lateralization of the epileptic focus. The difference in FA only showed an AUC of 0.86, with a cutoff value of 0.01 had a sensitivity of 77% and a specificity of 75% and the difference in MD only showed an AUC of 0.771, with a cutoff value of 0.545 had a sensitivity of 67.4% and a specificity of 70%. The diagnostic performance of MRS in terms of the AUC was significantly higher than ASL parameters (difference in NAA/Cr, p = 0.033 and difference in NAA/Cho + Cr, p = 0.044), and MD (p = 0.02). No other statistically significant differences were shown between the studied parameters. When the three methods were combined, all patients’ epileptogenic foci were correctly localized and lateralized.

Conclusions
Combining ASL, DTI and H-MRS provided excellent diagnostic performance in localization and lateralization of the epileptogenic focus. If this combination is not applicable in clinical practice, ASL could provide a considerably accurate and feasible method in this context. The present study supported the value of the new noninvasive MRI techniques in the elaboration of hidden brain pathology.
Diagnostic value of diffusion-weighted MRI using apparent diffusion coefficient (ADC) in evaluation of median nerve in carpal tunnel syndrome
Authors: Elkima Samia Elsayed Ahmed Abdelsalam , Abdelaziz Alsiagy Ali , Alsergany Mervat Abdelsattar , Nagy Hanan Ahmad 
Published: February 2023

Abstract
Background
The diagnosis of carpal tunnel syndrome is based on a combination of clinical history, clinical examination and frequent use of electrodiagnostics as nerve conduction study and electromyography which often do not provide the spatial and anatomical localizing information, especially with small nerves of the extremities. Conventional magnetic resonance imaging can reveal morphological changes in carpal tunnel syndrome patients.

Aim
The purpose of our study was to assess the efficacy of diffusion magnetic resonance imaging as a functional imaging in evaluation of median nerve in carpal tunnel syndrome.

Patients and methods
This prospective study included a group of 33 patients with carpal tunnel syndrome diagnosed by both clinical examination and electromyography; 40 writs were examined. A control group of 20 subjects of matched age group were also included. All the participants were subjected to conventional and diffusion magnetic resonance imaging studies.

Results
Median nerve apparent diffusion coefficient values of patients are lower than those of controls. The sensitivity and diagnostic accuracy of diffusion conventional magnetic resonance imaging were 95% and 97.5%, respectively, versus 25% and 62.5% of conventional magnetic resonance imaging. A cut-off apparent diffusion coefficient value ≤ 0.99 obtained at distal radio-ulnar joint level and > 1.07 at pisiform level as well as apparent diffusion coefficient ratio at a cut-off ≤ 0.2 was significantly valid for diagnosing carpal tunnel syndrome.

Conclusions
Diffusion magnetic resonance imaging provides functional evaluation of median nerve in patients with carpal tunnel syndrome.
Biosensing and anti-inflammatory effects of silver, copper and iron nanoparticles from the leaf extract of Catharanthus roseus
Authors: Sultana Mst.Jesmin , Nibir Al Ibne Shahariar , Ahmed Fazle Rabbi Shakil 
Published: February 2023

Abstract
Background
In this study, we present a low-cost, environmentally friendly method for producing silver, copper, and iron nanoparticles using fresh Catharanthus roseus leaf extract. The biomolecules found in the plant extract play a crucial role as stabilizing and reducing agents. The spectral profile of the UV–visible spectrophotometer was measured to confirm and identify the biosynthesized nanoparticles. The synthesized nanoparticles were tested for biosensing activities and anti-inflammatory effects.

Result
UV–visible spectra showed a prominent surface resonance peak of 415 nm, 300 nm, and 400 nm, corresponding to the formation of silver, copper, and iron nanoparticles, respectively. The in vitro anti-inflammatory properties of the synthesized AgNPs, CuNPs, and FeNPs showed the maximum inhibition of protein denaturation at 58%, 54.15%, and 44.26% at a concentration of 400 µg/ml, respectively. Furthermore, at a 400 µg/ml concentration, Diclofenac, utilized as a control, showed a maximal inhibition of 93.37%. According to the biosensing activity, these nanoparticles are also a good source for biosensing hazardous heavy salts. So, this article provides the first description of the silver, copper, and iron nanoparticles from Catharanthus roseus leave biosensing capabilities and anti-inflammatory characteristics.

Conclusion
Overall, this study revealed that due to their biocompatibility, silver, copper, and iron nanoparticles could be appealing and environmentally acceptable options that could be used as innovative therapeutic agents for the prevention and treatment of inflammation. The primary outcome of the research will be the development of potential pharmaceutical uses for the C. roseus medicinal plant in the biomedical and nanotechnology-based industries.
CRISPR-Cas9 mediated phage therapy as an alternative to antibiotics
Authors: Balcha Fikre Birhanu , Neja Sultan Abda 
Published: February 2023

AbstractInappropriate use of antibiotics is globally creating public health hazards associated with antibiotic resistance. Bacteria often acquire antibiotic resistance by altering their genes through mutation or acquisition of plasmid-encoding resistance genes. To treat drug-resistant strains of bacteria, the recently developed CRISPR-Cas9 system might be an alternative molecular tool to conventional antibiotics. It disables antibiotic-resistance genes (plasmids) or deactivates bacterial virulence factors and sensitizes drug-resistant bacteria through site-specific cleavage of crucial domains of their genome. This molecular tool uses phages as vehicles for CRISPR-cas9 delivery into bacteria. Since phages are species-specific and natural predators of bacteria, they are capable of easily injecting their DNA to target bacteria. The CRISPR system is packaged into phagemid vectors, in such a way that the bacteria containing the antibiotic-resistance plasmid sequence or that containing specific DNA sequences were made to be targeted. Upon CRISPR delivery, Cas9 is programmed to recognize target sequences through the guide RNA thereby causing double-strand cleavage of targeted bacterial DNA or loss of drug resistance plasmid, which results in cell death. Remarkably, the safety and efficacy of this newly developed biotechnology tool and the biocontrol product need to be further refined for its usage in clinical translation.
When Less Can Be More: How the 10-Year Updated Results From the Randomized Controlled AMAROS Trial Should Affect Axillary Management in the Setting of a Positive Node
Authors: Esserman Laura J. , Ali Hirra , McKenzie Tesia 
Published: February 2023

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. It is important to reflect on how far we as a medical community have come when treating breast cancer. Ongoing research, clinical trials, and better understanding of biology have transformed our understanding and treatment of breast cancer. There is still much to learn. Although progress was slow for decades, treatments have evolved more quickly in the recent past. The Halsted radical mastectomy, first popularized in 1894, was performed for almost a century, and although it decreased local recurrence, it did not improve survival. This well-intentioned surgery disfigured women and was abandoned as better systemic therapies were introduced and less aggressive surgical procedures were found to be equivalent in clinical trials. The evolution of trials in the modern era has taught us an important lesson. De-escalation of surgical interventions in the setting of improved systemic therapy can lead to better patient outcomes. We present a case of a clinician with an early-stage invasive ductal carcinoma responsive to neoadjuvant endocrine therapy and who subsequently underwent a partial mastectomy with axillary sentinal lymph node biopsy. Although clinically node-negative, she was pathologically node-positive, and concerned about both optimizing her outcomes and minimizing the risk of lymphedema. The release of 10-year follow-up data from the AMAROS trial furthers our knowledge and understanding of the impact of local control measures of the axilla. The concepts illustrated by the findings of AMAROS may be applied in clinical practice and ultimately help us make rational treatment choices and support shared decision making for patients like ours.
Prognostic Significance of Tumor-Infiltrating Lymphocytes Determined Using LinkNet on Colorectal Cancer Pathology Images
Authors: Liu Anran , Li Xingyu , Wu Hongyi , Guo Bangwei , Jonnagaddala Jitendra , Zhang Hong , Xu Steven 
Published: February 2023

PURPOSE Tumor-infiltrating lymphocytes (TILs) have a significant prognostic value in cancers. However, very few automated, deep learning-based TIL scoring algorithms have been developed for colorectal cancer (CRC). MATERIALS AND METHODS We developed an automated, multiscale LinkNet workflow for quantifying TILs at the cellular level in CRC tumors using H&E-stained images from the Lizard data set with annotations of lymphocytes. The predictive performance of the automatic TIL scores ([Formula: see text]) for disease progression and overall survival (OS) was evaluated using two international data sets, including 554 patients with CRC from The Cancer Genome Atlas (TCGA) and 1,130 patients with CRC from Molecular and Cellular Oncology (MCO). RESULTS The LinkNet model provided outstanding precision (0.9508), recall (0.9185), and overall F1 score (0.9347). Clear continuous TIL-hazard relationships were observed between [Formula: see text] and the risk of disease progression or death in both TCGA and MCO cohorts. Both univariate and multivariate Cox regression analyses for the TCGA data demonstrated that patients with high TIL abundance had a significant (approximately 75%) reduction in risk for disease progression. In both the MCO and TCGA cohorts, the TIL-high group was significantly associated with improved OS in univariate analysis (30% and 54% reduction in risk, respectively). The favorable effects of high TIL levels were consistently observed in different subgroups (classified according to known risk factors). CONCLUSION The proposed deep-learning workflow for automatic TIL quantification on the basis of LinkNet can be a useful tool for CRC. [Formula: see text] is likely an independent risk factor for disease progression and carries predictive information of disease progression beyond the current clinical risk factors and biomarkers. The prognostic significance of [Formula: see text] for OS is also evident.
Validation of Predictive Analyses for Interim Decisions in Clinical Trials
Authors: Avalos-Pacheco Alejandra , Ventz Steffen , Arfè Andrea , Alexander Brian M. , Rahman Rifaquat , Wen Patrick Y. , Trippa Lorenzo 
Published: February 2023

PURPOSE Adaptive clinical trials use algorithms to predict, during the study, patient outcomes and final study results. These predictions trigger interim decisions, such as early discontinuation of the trial, and can change the course of the study. Poor selection of the Prediction Analyses and Interim Decisions (PAID) plan in an adaptive clinical trial can have negative consequences, including the risk of exposing patients to ineffective or toxic treatments. METHODS We present an approach that leverages data sets from completed trials to evaluate and compare candidate PAIDs using interpretable validation metrics. The goal is to determine whether and how to incorporate predictions into major interim decisions in a clinical trial. Candidate PAIDs can differ in several aspects, such as the prediction models used, timing of interim analyses, and potential use of external data sets. To illustrate our approach, we considered a randomized clinical trial in glioblastoma. The study design includes interim futility analyses on the basis of the predictive probability that the final analysis, at the completion of the study, will provide significant evidence of treatment effects. We examined various PAIDs with different levels of complexity to investigate if the use of biomarkers, external data, or novel algorithms improved interim decisions in the glioblastoma clinical trial. RESULTS Validation analyses on the basis of completed trials and electronic health records support the selection of algorithms, predictive models, and other aspects of PAIDs for use in adaptive clinical trials. By contrast, PAID evaluations on the basis of arbitrarily defined ad hoc simulation scenarios, which are not tailored to previous clinical data and experience, tend to overvalue complex prediction procedures and produce poor estimates of trial operating characteristics such as power and the number of enrolled patients. CONCLUSION Validation analyses on the basis of completed trials and real world data support the selection of predictive models, interim analysis rules, and other aspects of PAIDs in future clinical trials.
New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape
Authors: Schultz Chad R. , Sheldon Ryan D. , Xie Huirong , Demireva Elena Y. , Uhl Katie L. , Agnew Dalen W. , Geerts Dirk , Bachmann André S. 
Published: February 2023

ABSTRACT
The eukaryotic translation initiation factor 5A1 (eIF5A1) and 5A2 (eIF5A2) are important proteins in a variety of physiological and pathophysiological processes and their function has been linked to neurodevelopmental disorders, cancer, and viral infections. Here, we report two new genome-edited mouse models, generated using a CRISPR-Cas9 approach, in which the amino acid residue lysine 50 is replaced with arginine 50 (K50R) in eIF5A1 or in the closely related eIF5A2 protein. This mutation prevents the spermidine-dependent post-translational formation of hypusine, a unique lysine derivative that is necessary for activation of eIF5A1 and eIF5A2. Mouse brain lysates from homozygous eif5a2-K50R mutant mice (eif5a2K50R/K50R) confirmed the absence of hypusine formation of eIF5A2, and metabolomic analysis of primary mouse dermal fibroblasts revealed significant alterations in the metabolite landscape compared to controls including increased levels of tryptophan, kyrunenine, pyridoxine, nicotinamide adenine dinucleotide, riboflavin, flavin adenine dinucleotide, pantothenate, and coenzyme A. Further supported by new publicly available bioinformatics data, these new mouse models represent excellent in vivo models to study hypusine-dependent biological processes, hypusination-related disorders caused by eIF5A1 and eIF5A2 gene aberrations or mRNA expression dysregulation, as well as several major human cancer types and potential therapies.
New advances in CRISPR/Cas-mediated precise gene-editing techniques
Authors: Richardson Chris , Kelsh Robert N. , J. Richardson Rebecca 
Published: February 2023

ABSTRACTOver the past decade, CRISPR/Cas-based gene editing has become a powerful tool for generating mutations in a variety of model organisms, from Escherichia coli to zebrafish, rodents and large mammals. CRISPR/Cas-based gene editing effectively generates insertions or deletions (indels), which allow for rapid gene disruption. However, a large proportion of human genetic diseases are caused by single-base-pair substitutions, which result in more subtle alterations to protein function, and which require more complex and precise editing to recreate in model systems. Precise genome editing (PGE) methods, however, typically have efficiencies of less than a tenth of those that generate less-specific indels, and so there has been a great deal of effort to improve PGE efficiency. Such optimisations include optimal guide RNA and mutation-bearing donor DNA template design, modulation of DNA repair pathways that underpin how edits result from Cas-induced cuts, and the development of Cas9 fusion proteins that introduce edits via alternative mechanisms. In this Review, we provide an overview of the recent progress in optimising PGE methods and their potential for generating models of human genetic disease.
Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway
Authors: Rickman Matthew , Ghim Mean , Pang Kuin , von Huelsen Rocha Ana Cristina , Drudi Elena M. , Sureda-Vives Macià , Ayoub Nicolas , Tajadura-Ortega Virginia , George Sarah J. , Weinberg Peter D. , Warboys Christina M. 
Published: February 2023

ABSTRACT
Multidirectional or disturbed flow promotes endothelial dysfunction and is associated with early atherogenesis. Here we investigated the role of Wnt signalling in flow-mediated endothelial dysfunction. The expression of Frizzled-4 was higher in cultured human aortic endothelial cells (ECs) exposed to disturbed flow compared to that seen for undisturbed flow, obtained using an orbital shaker. Increased expression was also detected in regions of the porcine aortic arch exposed to disturbed flow. The increased Frizzled-4 expression in cultured ECs was abrogated following knockdown of R-spondin-3. Disturbed flow also increased the nuclear localisation and activation of β-catenin, an effect that was dependent on Frizzled-4 and R-spondin-3. Inhibition of β-catenin using the small-molecule inhibitor iCRT5 or knockdown of Frizzled-4 or R-spondin-3 resulted in reduced expression of pro-inflammatory genes in ECs exposed to disturbed flow, as did inhibition of WNT5A signalling. Inhibition of the canonical Wnt pathway had no effect. Inhibition of β-catenin also reduced endothelial paracellular permeability; this was associated with altered junctional and focal adhesion organisation and cytoskeletal remodelling. These data suggest the presence of an atypical Frizzled-4-β-catenin pathway that promotes endothelial dysfunction in response to disturbed flow.