Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20.

BACKGROUND: The repurposing of FDA-approved drugs for anti-cancer therapies is appealing due to their established safety profiles and pharmacokinetic properties and can be quickly moved into clinical trials. Cancer progression and resistance to conventional chemotherapy remain the key hurdles in improving the clinical management of colon cancer patients and associated mortality. METHODS: High-throughput screening (HTS) was performed using an annotated library of 1,600 FDA-approved drugs to identify drugs with strong anti-CRC properties. The candidate drug exhibiting most promising inhibitory effects in in-vitro studies was tested for its efficacy using in-vivo models of CRC progression and chemoresistance and patient derived organoids (PTDOs). RESULTS: Albendazole, an anti-helminth drug, demonstrated the strongest inhibitory effects on the tumorigenic potentials of CRC cells, xenograft tumor growth and organoids from mice. Also, albendazole sensitized the chemoresistant CRC cells to 5-fluorouracil (5-FU) and oxaliplatin suggesting potential to treat chemoresistant CRC. Mechanistically, Albendazole treatment modulated the expression of RNF20, to promote apoptosis in CRC cells by delaying the G2/M phase and suppressing anti-apoptotic-Bcl2 family transcription. CONCLUSIONS: Albendazole, an FDA approved drug, carries strong therapeutic potential to treat colon cancers which are aggressive and potentially resistant to conventional chemotherapeutic agents. Our findings also lay the groundwork for further clinical testing.

Motion-robust free-running volumetric cardiovascular MRI.

PURPOSE: To present and assess an outlier mitigation method that makes free-running volumetric cardiovascular MRI (CMR) more robust to motion. METHODS: The proposed method, called compressive recovery with outlier rejection (CORe), models outliers in the measured data as an additive auxiliary variable. We enforce MR physics-guided group sparsity on the auxiliary variable, and jointly estimate it along with the image using an iterative algorithm. For evaluation, CORe is first compared to traditional compressed sensing (CS), robust regression (RR), and an existing outlier rejection method using two simulation studies. Then, CORe is compared to CS using seven three-dimensional (3D) cine, 12 rest four-dimensional (4D) flow, and eight stress 4D flow imaging datasets. RESULTS: Our simulation studies show that CORe outperforms CS, RR, and the existing outlier rejection method in terms of normalized mean square error and structural similarity index across 55 different realizations. The expert reader evaluation of 3D cine images demonstrates that CORe is more effective in suppressing artifacts while maintaining or improving image sharpness. Finally, 4D flow images show that CORe yields more reliable and consistent flow measurements, especially in the presence of involuntary subject motion or exercise stress. CONCLUSION: An outlier rejection method is presented and tested using simulated and measured data. This method can help suppress motion artifacts in a wide range of free-running CMR applications.

Nano-therapeutics: The upcoming nanomedicine to treat cancer.

Nanotechnology is considered a successful approach for cancer diagnosis and treatment. Preferentially, cancer cell recognition and drug targeting via nano-delivery system include the penetration of anticancer agents into the cell membrane to damage the cancer cell by protein modification, DNA oxidation, or mitochondrial dysfunction. The past research on nano-delivery systems and their target has proven the beneficial achievement in a malignant tumor. Modern perceptions using inventive nanomaterials for cancer management have been offered by a multifunctional platform based on various nano-carriers with the probability of imaging and cancer therapy simultaneously. Emerging nano-delivery systems in cancer therapy still lack knowledge of the biological functions behind the interaction between nanoparticles and cancer cells. Since the potential of engineered nanoparticles addresses the various challenges, limiting the success of cancer therapy subsequently, it is a must to review the molecular targeting of a nano-delivery system to enhance the therapeutic efficacy of cancer. This review focuses on using a nano-delivery system, an imaging system, and encapsulated nanoparticles for cancer therapy.

MRI recovery with self-calibrated denoisers without fully-sampled data.

OBJECTIVE: Acquiring fully sampled training data is challenging for many MRI applications. We present a self-supervised image reconstruction method, termed ReSiDe, capable of recovering images solely from undersampled data. MATERIALS AND METHODS: ReSiDe is inspired by plug-and-play (PnP) methods, but unlike traditional PnP approaches that utilize pre-trained denoisers, ReSiDe iteratively trains the denoiser on the image or images that are being reconstructed. We introduce two variations of our method: ReSiDe-S and ReSiDe-M. ReSiDe-S is scan-specific and works with a single set of undersampled measurements, while ReSiDe-M operates on multiple sets of undersampled measurements and provides faster inference. Studies I, II, and III compare ReSiDe-S and ReSiDe-M against other self-supervised or unsupervised methods using data from T1- and T2-weighted brain MRI, MRXCAT digital perfusion phantom, and first-pass cardiac perfusion, respectively. RESULTS: ReSiDe-S and ReSiDe-M outperform other methods in terms of peak signal-to-noise ratio and structural similarity index measure for Studies I and II, and in terms of expert scoring for Study III. DISCUSSION: We present a self-supervised image reconstruction method and validate it in both static and dynamic MRI applications. These developments can benefit MRI applications where the availability of fully sampled training data is limited.

Muslim pilgrims' knowledge, attitudes, and practices regarding complementary and alternative medicine (CAM); a study conducted during Hajj season.

Complementary and alternative medicine (CAM) has attracted much interest, and its prevalence in both developed and developing countries has increased. During the Hajj season, millions of Muslims from many different countries travel to Makkah for the pilgrimage. In dealing with health issues during the holy season, many pilgrims prefer to self-medicate with traditional remedies instead of visiting medical practitioners, which could affect the efforts of state healthcare organizations to maintain overall public health during this mass gathering. This study aims to gauge the prevalence of CAM use during Hajj, and to assess pilgrims' beliefs and knowledge of CAM therapies, with particular reference to products available in Makkah. A cross-sectional survey was conducted in several camps and hotels occupied by Hajj pilgrims in Makkah, during Hajj 2023. CAM modalities were used by 68.8 % of the study participants during the Hajj season. There were almost equal numbers of men (53.7 %) and women (46.3 %) participants, with 88 % of the CAM users being non-Saudi and only 12 % Saudi. The majority of the CAM users belonged to two age groups, the 31-40 year group (29.9 %) and the 41-50 year group (34.5 %). The most frequent self-practice therapies were religious prayer/rituals (30.2 %), and the most popular practitioner therapies was herbal treatments (12.3 %). The most common source of CAM-related information was family/friends (29.2 %), for improving well-being reason (25.8 %). More than half of the participants (56.8 %) strongly believed that CAM therapies have the potential to cure disease, although they were unaware of possible interactions between CAM and conventional drugs (76.7 %). More than half of the participants (57.8 %) did not disclose their CAM usage to healthcare practitioners. Half of the sample said they used CAMs during Hajj because of the common belief that therapeutic products from the holy city of Makkah, such as Zamzam water, are more effective. In conclusion, CAM therapies are commonly used by Hajj pilgrims as they are presumed to be natural and therefore safe, raising concerns about the potential risks of relying on CAM without adequate consultation with healthcare providers or awareness of potential interactions between prescription drugs and CAM treatments.

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach.

Cancer is the leading cause of mortality and morbidity worldwide, and its cases are rapidly increasing every year. Several factors contribute to the development of tumorigenesis. including radiation, dietary lifestyle, smoking, environmental, and genetic factors. The cell cycle is regulated by a variety of molecular signaling proteins. However, when the proteins involved in the cell cycle regulation are altered, cellular growth and proliferation are significantly affected. Natural products provide an important source of new drug development for a variety of ailments. including cancer. Phytosterols (PSs) are an important class of natural compounds reported for numerous pharmacological activities, including cancer. Various PSs, such as ergosterol, stigmasterol, sitosterol, withaferin A, etc., have been reported for their anti-cancer activities against a variety of cancer by modulating the tumor microenvironment via molecular signaling pathways discussed within the article. These signaling pathways are associated with the production of pro-inflammatory mediators, growth factors, chemokines, and pro-apoptotic and anti-apoptotic genes. These mediators and their upstream signaling are very active within the variety of tumors and by modulating these signalings, thus PS exhibits promising anti-cancer activities. However, further high-quality studies are needed to firmly establish the clinical efficacy as well the safety of the phytosterols.

On Coverage of Critical Nodes in UAV-Assisted Emergency Networks.

Unmanned aerial vehicle (UAV)-assisted networks ensure agile and flexible solutions based on the inherent attributes of mobility and altitude adaptation. These features render them suitable for emergency search and rescue operations. Emergency networks (ENs) differ from conventional networks. They often encounter nodes with vital information, i.e., critical nodes (CNs). The efficacy of search and rescue operations highly depends on the eminent coverage of critical nodes to retrieve crucial data. In a UAV-assisted EN, the information delivery from these critical nodes can be ensured through quality-of-service (QoS) guarantees, such as capacity and age of information (AoI). In this work, optimized UAV placement for critical nodes in emergency networks is studied. Two different optimization problems, namely capacity maximization and age of information minimization, are formulated based on the nature of node criticality. Capacity maximization provides general QoS enhancement for critical nodes, whereas AoI is focused on nodes carrying critical information. Simulations carried out in this paper aim to find the optimal placement for each problem based on a two-step approach. At first, the disaster region is partitioned based on CNs' aggregation. Reinforcement learning (RL) is then applied to observe optimal placement. Finally, network coverage over optimal UAV(s) placement is studied for two scenarios, i.e., network-centric and user-centric. In addition to providing coverage to critical nodes, the proposed scheme also ensures maximum coverage for all on-scene available devices (OSAs).

An Insight into the Machine-Learning-Based Fileless Malware Detection.

In recent years, massive development in the malware industry changed the entire landscape for malware development. Therefore, cybercriminals became more sophisticated by advancing their development techniques from file-based to fileless malware. As file-based malware depends on files to spread itself, on the other hand, fileless malware does not require a traditional file system and uses benign processes to carry out its malicious intent. Therefore, it evades conventional detection techniques and remains stealthy. This paper briefly explains fileless malware, its life cycle, and its infection chain. Moreover, it proposes a detection technique based on feature analysis using machine learning for fileless malware detection. The virtual machine acquired the memory dumps upon executing the malicious and non-malicious samples. Then the necessary features are extracted using the Volatility memory forensics tool, which is then analyzed using machine learning classification algorithms. After that, the best algorithm is selected based on the k-fold cross-validation score. Experimental evaluation has shown that Random Forest outperforms other machine learning classifiers (Decision Tree, Support Vector Machine, Logistic Regression, K-Nearest Neighbor, XGBoost, and Gradient Boosting). It achieved an overall accuracy of 93.33% with a True Positive Rate (TPR) of 87.5% at zeroFalse Positive Rate (FPR) for fileless malware collected from five widely used datasets (VirusShare, AnyRun, PolySwarm, HatchingTriage, and JoESadbox).

Ensuring respiratory phase consistency to improve cardiac function quantification in real-time CMR.

PURPOSE: To develop an automatic method for selecting heartbeats with consistent respiratory phase to improve accuracy of cardiac function quantification in real-time (RT) cardiac MRI. METHODS: The respiratory signal is extracted by a principal component analysis method from RT cine images. Then, a two-step procedure is used to determine the directionality (sign) of the respiratory signal. With the motion in a manually selected region-of-interest as a reference, the quality of the extracted respiratory signal is assessed using multislice RT cine data from 11 volunteers and 10 patients. In addition, the impact of selecting heartbeats with consistent respiratory phase on the cardiac function quantification is evaluated. RESULTS: The extracted respiratory signal using the proposed method exhibits a high, positive correlation with the reference in all cases and is more robust compared to a recently proposed method. Also, for right ventricular function quantification, selecting heartbeats at expiratory position improves agreement between RT cine and breath-held reference. CONCLUSION: The proposed method enables fully automatic extraction and directionality determinations of respiratory signal from RT cardiac cine images, allowing accurate cardiac function quantification.

A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS).

Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6-20% of females in reproductive age. Most symptoms of PCOS arise early during puberty. Since PCOS involves a combination of signs and symptoms, thus it is considered as a heterogeneous disorderliness. The most accepted diagnostic criteria is Rotterdam criteria which involves two of the latter three features: (a) hyperandrogenism, (b) oligo- or an-ovulation, and (c) polycystic ovaries. The persistent hormonal imbalance leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females. Insulin resistance, cardiovascular diseases, abdominal obesity, psychological disorders, infertility, and cancer are also related to PCOS. These pathophysiologies associated with PCOS are interrelated with each other. Hyperandrogenism causes insulin resistance and hyperglycemia, leading to ROS formation, oxidative stress, and abdominal adiposity. In consequence, inflammation, ROS production, insulin resistance, and hyperandrogenemia also increase. Elevation of AGEs in the body either produced endogenously or consumed from diet exaggerates PCOS symptoms and is also related to ovarian dysfunction. This review summarizes how AGE formation, inflammation, and oxidative stress are significantly essential in PCOS progression. Alterations during prenatal development like exposure to excess AMH, androgens, or toxins (bisphenol-A, endocrine disruptors, etc.) may also be the etiologic mechanism behind PCOS. Although the etiology of this disorder is unclear, environmental and genetic factors are primarily involved. Physical inactivity, as well as unhealthy eating habits, has a vital role in the progression of PCOS. This review outlines a collection of specific genes phenotypically linked with PCOS. Furthermore, beneficial effect of metformin in maintaining endocrine abnormalities and ovarian function is also mentioned. Kisspeptin is a protein which helps in onset of puberty and increases GnRH pulsatile release during ovulation as well as role of KNDy neurons in GnRH pulsatile signal required for reproduction are also elaborated. This review also focuses on the immunology related to PCOS involving chronic low-grade inflammation, and how the alterations within the follicular microenvironment are intricated in the development of infertility in PCOS patients. How PCOS develops following antiepileptic and psychiatric medication is also expanded in this review. Initiation of antiandrogen treatment in early age (≤ 25 years) might be helpful in spontaneous conception in PCOS women. The role of BMP (bone morphogenetic proteins) in folliculogenesis and their expression in oocytes and granulosa cells are also explained. GDF8 and SERPINE1 expression in PCOS is given in detail.

Getting Smarter about Smart Cities: Improving Data Security and Privacy through Compliance.

Smart cities assure the masses a higher quality of life through digital interconnectivity, leading to increased efficiency and accessibility in cities. In addition, a huge amount of data is being exchanged through smart devices, networks, cloud infrastructure, big data analysis and Internet of Things (IoT) applications in the various private and public sectors, such as critical infrastructures, financial sectors, healthcare, and Small and Medium Enterprises (SMEs). However, these sectors require maintaining certain security mechanisms to ensure the confidentiality and integrity of personal and critical information. However, unfortunately, organizations fail to maintain their security posture in terms of security mechanisms and controls, which leads to data breach incidents either intentionally or inadvertently due to the vulnerabilities in their information management systems that either malicious insiders or attackers exploit. In this paper, we highlight the importance of data breaches and issues related to information leakage incidents. In particular, the impact of data breaching incidents and the reasons contributing to such incidents affect the citizens' well-being. In addition, this paper also discusses various preventive measures such as security mechanisms, laws, standards, procedures, and best practices, including follow-up mitigation strategies.

Alias-Free Arrays.

Nonuniform array geometries provide freedom for increased aperture and reduced mutual coupling. A necessary and sufficient condition is given for an array of isotropic sensor elements to be unambiguous for any specified set of directions of arrival. The set of unambiguous spatial frequencies is shown to be a parallelepiped, admitting simple geometrical interpretation. Results are used in design of linear, planar, and 3D arrays.

The vital role of animal, marine, and microbial natural products against COVID-19.

CONTEXT: Since the outbreak of SARS-CoV-2, researchers have been working on finding ways to prevent viral entry and pathogenesis. Drug development from naturally-sourced pharmacological constituents may be a fruitful approach to COVID-19 therapy. OBJECTIVE: Most of the published literature has focussed on medicinal plants, while less attention has been given to biodiverse sources such as animal, marine, and microbial products. This review focuses on highlighting natural products and their derivatives that have been evaluated for antiviral, anti-inflammatory, and immunomodulatory properties. METHODS: We searched electronic databases such as PubMed, Scopus, Science Direct and Springer Link to gather raw data from publications up to March 2021, using terms such as 'natural products', marine, micro-organism, and animal, COVID-19. We extracted a number of documented clinical trials of products that were tested in silico, in vitro, and in vivo which paid specific attention to chemical profiles and mechanisms of action. RESULTS: Various classes of flavonoids, 2 polyphenols, peptides and tannins were found, which exhibit inhibitory properties against viral and host proteins, including 3CLpro, PLpro, S, hACE2, and NF-κB, many of which are in different phases of clinical trials. DISCUSSION AND CONCLUSIONS: The synergistic effects of logical combinations with different mechanisms of action emphasizes their value in COVID19 management, such as iota carrageenan nasal spray, ermectin oral drops, omega-3 supplementation, and a quadruple treatment of zinc, quercetin, bromelain, and vitamin C. Though in vivo efficacy of these compounds has yet to be established, these bioproducts are potentially useful in counteracting the effects of SARS-CoV-2.

Investigation on the elemental profiles of lip cosmetic products: Concentrations, distribution and assessment of potential carcinogenic and non-carcinogenic human health risk for consumer safety.

Metal contamination of lip care products can cause potential adverse effects for consumers, hence assessment of human health risks associated with the consumption of these products is inevitable to ensure the consumers' safety. In the presented study, the profiles of 18 elements in 37 of the most popular lip cosmetic products, of various types and brands, sold in the Saudi Arabian markets, were investigated and their associated potential carcinogenic and non-carcinogenic human health risks were assessed. The metal concentrations were determined using inductively coupled plasma mass spectrometry preceded by microwave digestion for sample preparation. In general, the concentrations of the investigated metals were lower than the safe permissible limits with the exception of Cd, Pb and Hg. The results found that Cd was regarded as the primary metal contaminant present in the analyzed lip products contributing to 66.3% of the total determined carcinogenic health risk. Overall, however it was observed that there was no significant non-carcinogenic (hazard index < 1) or carcinogenic (RiskT < 10-4) health risks associated with the use of the investigated lip products. Although all the calculated values in this study were within the acceptable limits, special attention should be taken in order to prioritize minimizing the trace metals in lip products, especially for Cd, Pb, Ti and Hg. This study could provide vital data needed to ascertain the degree to which heavy metal exposure through cosmetics is prevalent.

Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis.

By limiting the nitrogen source to glutamic acid, we isolated cyclic peptides from Euglena gracilis containing asparagine and non-proteinogenic amino acids. Structure elucidation was accomplished through spectroscopic methods, mass spectrometry and chemical degradation. The euglenatides potently inhibit pathogenic fungi and cancer cell lines e.g., euglenatide B exhibiting IC50 values of 4.3 µM in Aspergillus fumigatus and 0.29 µM in MCF-7 breast cancer cells. In an unprecedented convergence of non-ribosomal peptide synthetase and polyketide synthase assembly-line biosynthesis between unicellular species and the metazoan kingdom, euglenatides bear resemblance to nemamides from Caenorhabditis elegans and inhibited both producing organisms E. gracilis and C. elegans. By molecular network analysis, we detected over forty euglenatide-like metabolites in E. gracilis, E. sanguinea and E. mutabilis, suggesting an important biological role for these natural products.

High-dimensional fast convolutional framework (HICU) for calibrationless MRI.

PURPOSE: To present a computational procedure for accelerated, calibrationless magnetic resonance image (Cl-MRI) reconstruction that is fast, memory efficient, and scales to high-dimensional imaging. THEORY AND METHODS: Cl-MRI methods can enable high acceleration rates and flexible sampling patterns, but their clinical application is limited by computational complexity and large memory footprint. The proposed computational procedure, HIgh-dimensional fast convolutional framework (HICU), provides fast, memory-efficient recovery of unsampled k-space points. For demonstration, HICU is applied to 6 2D T2-weighted brain, 7 2D cardiac cine, 5 3D knee, and 1 multi-shot diffusion weighted imaging (MSDWI) datasets. RESULTS: The 2D imaging results show that HICU can offer 1-2 orders of magnitude computation speedup compared to other Cl-MRI methods without sacrificing imaging quality. The 2D cine and 3D imaging results show that the computational acceleration techniques included in HICU yield computing time on par with SENSE-based compressed sensing methods with up to 3 dB improvement in signal-to-error ratio and better perceptual quality. The MSDWI results demonstrate the feasibility of HICU for a challenging multi-shot echo-planar imaging application. CONCLUSIONS: The presented method, HICU, offers efficient computation and scalability as well as extendibility to a wide variety of MRI applications.

Compact electron spin resonance skin oximeter: Properties and initial clinical results.

PURPOSE: Skin oxygen level is of significance for the diagnosis and treatment of many clinical problems, such as chronic wounds and diabetic foot ulcers. Furthermore, skin oxygen levels can be correlated to arterial oxygen partial pressure, thereby revealing potentially dangerous conditions such as hyperoxia (too much oxygen), which may occur in ventilated neonates. Traditionally, skin oxygen levels are measured using electrochemical methods and, more recently, also by fluorescence lifetime techniques. These approaches suffer from several drawbacks, rendering them suboptimal. The purpose of this work is to develop an electron spin resonance (ESR) -based method for monitoring oxygen partial pressure (pO2 ) in skin tissue. METHODS: A compact sensor for pulsed ESR is designed and constructed. Our ESR-based method makes use of a unique exogenous paramagnetic spin probe that is placed on the skin in a special partially sealed sticker, and subsequently measuring its signal with the compact pulsed ESR sensor that includes a miniature magnet and a small S-band (~2.3 GHz) microwave resonator. The inverse of the spin-spin relaxation time (1/T2 ) measured by ESR is shown to be linearly correlated with pO2 levels. RESULTS: The sensor and its matching sticker were tested both in vitro and in vivo (with human subjects). Measured skin pO2 levels reached equilibrium after ~2-3 h and were found to be comparable to those measured by continuous-wave (CW) ESR using a large electromagnet. CONCLUSIONS: A compact pulsed ESR sensor with a matching paramagnetic sticker can be used for pO2 monitoring of the skin tissue, similar to large bulky CW ESR systems.

Prospective correction of patient-specific respiratory motion in myocardial T1 and T2 mapping.

PURPOSE: Respiratory motion in cardiovascular MRI presents a challenging problem with many potential solutions. Current approaches require breath-holds, apply retrospective image registration, or significantly increase scan time by respiratory gating. Myocardial T1 and T2 mapping techniques are particularly sensitive to motion as they require multiple source images to be accurately aligned prior to the estimation of tissue relaxation. We propose a patient-specific prospective motion correction (PROCO) strategy that corrects respiratory motion on the fly with the goal of reducing the spatial variation of myocardial parametric mapping techniques. METHODS: A rapid, patient-specific training scan was performed to characterize respiration-induced motion of the heart relative to a diaphragmatic navigator, and a parametric mapping pulse sequence utilized the resulting motion model to prospectively update the scan plane in real-time. Midventricular short-axis T1 and T2 maps were acquired under breath-hold or free-breathing conditions with and without PROCO in 7 healthy volunteers and 3 patients. T1 and T2 were measured in 6 segments and compared to reference standard breath-hold measurements using Bland-Altman analysis. RESULTS: PROCO significantly reduced the spatial variation of parametric maps acquired during free-breathing, producing limits of agreement of -47.16 to 30.98 ms (T1 ) and -1.35 to 4.02 ms (T2 ), compared to -67.77 to 74.34 ms (T1 ) and -2.21 to 5.62 ms (T2 ) for free-breathing acquisition without PROCO. CONCLUSION: Patient-specific respiratory PROCO method significantly reduced the spatial variation of myocardial T1 and T2 mapping, while allowing for 100% efficient free-breathing acquisitions.

Fully self-gated whole-heart 4D flow imaging from a 5-minute scan.

PURPOSE: To develop and validate an acquisition and processing technique that enables fully self-gated 4D flow imaging with whole-heart coverage in a fixed 5-minute scan. THEORY AND METHODS: The data are acquired continuously using Cartesian sampling and sorted into respiratory and cardiac bins using the self-gating signal. The reconstruction is performed using a recently proposed Bayesian method called ReVEAL4D. ReVEAL4D is validated using data from 8 healthy volunteers and 2 patients and compared with compressed sensing technique, L1-SENSE. RESULTS: Healthy subjects-Compared with 2D phase-contrast MRI (2D-PC), flow quantification from ReVEAL4D shows no significant bias. In contrast, the peak velocity and peak flow rate for L1-SENSE are significantly underestimated. Compared with traditional parallel MRI-based 4D flow imaging, ReVEAL4D demonstrates small but significant biases in net flow and peak flow rate, with no significant bias in peak velocity. All 3 indices are significantly and more markedly underestimated by L1-SENSE. Patients-Flow quantification from ReVEAL4D agrees well with the 2D-PC reference. In contrast, L1-SENSE markedly underestimated peak velocity. CONCLUSIONS: The combination of highly accelerated 5-minute Cartesian acquisition, self-gating, and ReVEAL4D enables whole-heart 4D flow imaging with accurate flow quantification.

Ganoderma lucidum (Reishi) an edible mushroom; a comprehensive and critical review of its nutritional, cosmeceutical, mycochemical, pharmacological, clinical, and toxicological properties.

Reishi owes an exceptional value in nutritional, cosmeceutical, and medical treatments; however, none of the studies has provided its future-driven critical assessment. This study documents an up-to-date review (2015-2020, wherever applicable) and provide valuable insights (preclinical and clinical evidence-based) with comprehensive and critical assessments. Various databases 'Google scholar', 'Web of Science', 'ScienceDirect', 'PubMed', 'Springer Link', books, theses, and library resources were used. The taxonomic chaos of G. lucidum and its related species was discussed in detail with solution-oriented emphasis. Reishi contains polysaccharides (α/ß-D-glucans), alkaloids, triterpenoids (ganoderic acids, ganoderenic acids, ganoderol, ganoderiol, lucidenic acids), sterols/ergosterol, proteins (LZ-8, LZ-9), nucleosides (adenosine, inosine, uridine), and nucleotides (guanine, adenine). Some active drugs are explored at an optimum level to make them potential drug candidates. The pharmacological potential was observed in diabetes, inflammation, epilepsy, neurodegeneration, cancer, anxiety, sedation, cardiac diseases, depression, hepatic diseases, and immune disorders; however, most of the studies are preclinical with a number of drawbacks. In particular, quality clinical data are intensely needed to support pharmacological activities for human use. The presence of numerous micro-, macro, and trace elements imparts an essential nutritional and cosmeceutical value to Reishi, and various marketed products are available already, but the clinical studies regarding safety and efficacy, interactions with foods/drinks, chronic use, teratogenicity, mutagenicity, and genotoxicity are missing for Reishi. Reishi possesses many valuable pharmacological activities, and the number of patents and clinical trials is increasing for Reishi. Yet, a gap in research exists for Reishi, which is discussed in detail in the forthcoming sections.