Unlocking Diversity in Cardiovascular Clinical Research: Lessons from the Screening for Cardiac Amyloidosis With Nuclear Imaging in a Minority Populations Study.

BACKGROUND: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations study seeks to determine the prevalence of transthyretin cardiac amyloidosis (ATTR-CA) among older Black or Caribbean Hispanic individuals with heart failure and an increased wall thickness. We noticed varied recruitment percentages across the recruiting sites and sought to determine the factors associated with greater percentage enrollment of eligible participants. METHODS: The percentage of enrolled to eligible participants was calculated across study sites. Baseline demographic and clinical characteristics, health literacy, trust in providers, perceived discrimination, area deprivation index (ADI) and English proficiency were compared by site using Kruskal-Wallis's test or one-way ANOVA for continuous variables and the Chi-Square test or Fisher's exact test for categorical variables. Wilcoxon rank sum and Chi-Square tests, with multiple comparisons correction using the false discovery rate (FDR) method, were used as post-hoc analysis when results were statistically significant. RESULTS: Among the four recruiting sites, Boston Medical Center, Columbia University Irving Medical Center, Harlem Hospital and Yale University, which employed different recruitment approaches, the percentage of participants enrolled among eligible participants differed, with the highest rate at Harlem Hospital (n=149 of 310, 48%), followed by Yale University (n=27 of 67, 40%), Boston University (n=247 of 655, 38%), and Columbia University (n=137of 442, 32%), p <0.01. Direct recruitment by the primary cardiovascular care team providing clinical care was associated with higher percent enrolled across sites as were higher education levels and English proficiency. Enrollment differences across sites were not associated with the number of chronic diseases, physician trust, perceived discrimination, or health literacy. CONCLUSIONS: Recruitment of eligible under-represented minorities (URMs) in SCAN-MP was associated with approaches employed in recruitment, including direct initial contact by the primary cardiovascular care team providing the potential participant's clinical care. Such data may help improve approaches to more successful recruitment of URMs in clinical research.

Interlayer Potassium Single-Atom-Coordinated g-C3N4 for Significantly Boosted Visible Light Photocatalytic H2 Production.

In recent years, graphitic carbon nitride (g-C3N4) has attracted considerable attention because it includes earth-abundant carbon and nitrogen elements and exhibits good chemical and thermal stability owing to the strong covalent interaction in its conjugated layer structure. However, bulk g-C3N4 has some disadvantages of low specific surface area, poor light absorption, rapid recombination of photogenerated charge carriers, and insufficient active sites, which hinder its practical applications. In this study, we design and synthesize potassium single-atom (K SAs)-doped g-C3N4 porous nanosheets (CM-KX, where X represents the mass of KHP added) via supramolecular self-assembling and chemical cross-linking copolymerization strategies. The results show that the utilization of supramolecules as precursors can produce g-C3N4 nanosheets with reduced thickness, increased surface area, and abundant mesopores. In addition, the intercalation of K atoms within the g-C3N4 nitrogen pots through the formation of K-N bonds results in the reduction of the band gap and expansion of the visible-light absorption range. The optimized K-doped CM-K12 nanosheets achieve a specific surface area of 127 m2 g-1, which is 11.4 times larger than that of the pristine g-C3N4 nanosheets. Furthermore, the optimal CM-K12 sample exhibits the maximum H2 production rate of 127.78 µmol h-1 under visible light (λ ≥ 420 nm), which is nearly 23 times higher than that of bare g-C3N4. This significant improvement of photocatalytic activity is attributed to the synergistic effects of the mesoporous structure and K SAs doping, which effectively increase the specific surface area, improve the visible-light absorption capacity, and facilitate the separation and transfer of photogenerated electron-hole pairs. Besides, the optimal sample shows good chemical stability for 20 h in the recycling experiments. Density functional theory calculations confirm that the introduction of K SAs significantly boosts the adsorption energy for water and decreases the activation energy barrier for the reduction of water to hydrogen.

SGO: Semantic Group Obfuscation for Location-Based Services in VANETS.

Location privacy is an important parameter to be addressed in the case of vehicular ad hoc networks. Each vehicle frequently communicates with location-based services to find the nearest location of interest. The location messages communicated with the location server may contain sensitive information like vehicle identity, location, direction, and other headings. A Location-Based Services (LBS) server is not a trusted entity; it can interact with an adversary, compromising the location information of vehicles on the road and providing a way for an adversary to extract the future location tracks of a target vehicle. The existing works consider two or three neighboring vehicles as a virtual shadow to conceal location information. However, they did not fully utilize the semantic location information and pseudonym-changing process, which reduces the privacy protection level. Moreover, a lot of dummy location messages are generated that increase overheads in the network. To address these issues, we propose a Semantic Group Obfuscation (SGO) technique that utilizes both location semantics as well as an efficient pseudonym-changing scheme. SGO creates groups of similar status vehicles on the road and selects random position coordinates for communication with the LBS server. It hides the actual location of a target vehicle in a vicinity. The simulation results verify that the proposed scheme SGO improves the anonymization and entropy of vehicles, and it reduces the location traceability and overheads in the network in terms of computation cost and communication cost. The cost of overhead is reduced by 55% to 65% compared with existing schemes. We also formally model and specify SGO using High-Level Petri Nets (HLPNs), which show the correctness and appropriateness of the scheme.

Genome-wide identification and molecular characterization of CRK gene family in cucumber (Cucumis sativus L.) under cold stress and sclerotium rolfsii infection.

BACKGROUND: The plant cysteine-rich receptor-like kinases (CRKs) are a large family having multiple roles, including defense responses under both biotic and abiotic stress. However, the CRK family in cucumbers (Cucumis sativus L.) has been explored to a limited extent. In this study, a genome-wide characterization of the CRK family has been performed to investigate the structural and functional attributes of the cucumber CRKs under cold and fungal pathogen stress. RESULTS: A total of 15 C. sativus CRKs (CsCRKs) have been characterized in the cucumber genome. Chromosome mapping of the CsCRKs revealed that 15 genes are distributed in cucumber chromosomes. Additionally, the gene duplication analysis of the CsCRKs yielded information on their divergence and expansion in cucumbers. Phylogenetic analysis divided the CsCRKs into two clades along with other plant CRKs. Functional predictions of the CsCRKs suggested their role in signaling and defense response in cucumbers. The expression analysis of the CsCRKs by using transcriptome data and via qRT-PCR indicated their involvement in both biotic and abiotic stress responses. Under the cucumber neck rot pathogen, Sclerotium rolfsii infection, multiple CsCRKs exhibited induced expressions at early, late, and both stages. Finally, the protein interaction network prediction results identified some key possible interacting partners of the CsCRKs in regulating cucumber physiological processes. CONCLUSIONS: The results of this study identified and characterized the CRK gene family in cucumbers. Functional predictions and validation via expression analysis confirmed the involvement of the CsCRKs in cucumber defense response, especially against S. rolfsii. Moreover, current findings provide better insights into the cucumber CRKs and their involvement in defense responses.

Governance of a Blockchain-Enabled IoT Ecosystem: A Variable Geometry Approach.

The proliferation of Internet of Things (IoT) applications is rapidly expanding, generating increased interest in the incorporation of blockchain technology within the IoT ecosystem. IoT applications enhance the efficiency of our daily lives, and when blockchain is integrated into the IoT ecosystem (commonly referred to as a blockchain-IoT system), it introduces crucial elements, like security, transparency, trust, and privacy, into IoT applications. Notably, potential domains where blockchain can empower IoT applications include smart logistics, smart health, and smart cities. However, a significant obstacle hindering the widespread adoption of blockchain-IoT systems in mainstream applications is the absence of a dedicated governance framework. In the absence of proper regulations and due to the inherently cryptic nature of blockchain technology, it can be exploited for nefarious purposes, such as ransomware, money laundering, fraud, and more. Furthermore, both blockchain and the IoT are relatively new technologies, and the absence of well-defined governance structures can erode confidence in their use. Consequently, to fully harness the potential of integrating blockchain-IoT systems and ensure responsible utilization, governance plays a pivotal role. The implementation of appropriate regulations and standardization is imperative to leverage the innovative features of blockchain-IoT systems and prevent misuse for malicious activities. This research focuses on elucidating the significance of blockchain within governance mechanisms, explores governance tailored to blockchain, and proposes a robust governance framework for the blockchain-enabled IoT ecosystem. Additionally, the practical application of our governance framework is showcased through a case study in the realm of smart logistics. We anticipate that our proposed governance framework will not only facilitate but also promote the integration of blockchain and the IoT in various application domains, fostering a more secure and trustworthy IoT landscape.

Therapeutic potential of natural products and antibiotics against bovine mastitis pathogen of cows and buffaloes.

The present study aims to evaluate the prevalence and antimicrobial sensitivity of Staphylococcus aureus associated with bovine mastitis to selected antibiotics and plant extracts. In the current study, 140 milk samples were collected from cows and buffaloes. Among the 140 samples, 93 samples were positive for sub-clinical mastitis based on the California Mastitis Test (CMT). Out of the total positive samples, 45 were confirmed for S. aureus on a Mannitol salt agar media. The antimicrobial susceptibility test revealed that 44.82% of the isolates were resistant to cefoxitin (oxacillin) confirming methicillin-resistant S. aureus (MRSA) with a higher percentage (51.61%) in the buffalo than in the cow samples. Furthermore, the PCR assay confirmed the presence of the mecA gene in all the MRSA isolates. Among the seven tested antibiotics, sulfamethoxazole + trimethoprim showed high efficacy (71.1%) against methicillin-susceptible S. aureus isolates (MSSA). Oxytetracycline and sulfamethoxazole + trimethoprim showed 20% efficacy against MRSA followed by enrofloxacin (10%). On the other hand, the tested samples from Pistacia chinensis revealed that the ethyl acetate extract of bark showed a maximum zone of inhibition of 21.3 mm against MSSA and MRSA isolates at 3 000 µg/disc. Moreover, the methanol extract of Cotoneaster microphyllus formed a 12.3 mm and 9.1 mm zone of inhibition against the MSSA and MRSA isolates, respectively.

Whole exome sequencing identifies a novel compound heterozygous GFM1 variant underlying developmental delay, dystonia, polymicrogyria, and severe intellectual disability in a Pakhtun family.

Mitochondrial protein synthesis requires three elongation factors including EF-Tu (TUFM; OMIM 602389), EF-Ts (TSFM; OMIM 604723), and EF-G1 (GFM1; OMIM 606639). Pathogenic variants in any of these three members result in defective mitochondrial translation which can impart an oxidative phosphorylation (OXPHOS) deficiency. In this study, we investigated a consanguineous Pakhtun Pakistani family. There were four affected siblings at the time of this study and one affected girl had died in infancy. The index patient had severe intellectual disability, global developmental delay, dystonia, no speech development, feeding difficulties, and nystagmus. MRI brain presented thinning of corpus callosum and polymicrogyria. Whole exome sequencing revealed a novel compound heterozygous variant in GFM1 located on chromosome 3q25.32. Sanger sequencing confirmed recessive segregation of the maternal (NM_001308164.1:c.409G > A; p.Val137Met) and paternal (NM_001308164.1:c.1880G > A; p.Arg627Gln) variants in all the four affected siblings. These variants are classified as "likely-pathogenic" according to the recommendation of ACMG/AMP guideline. GFM1 alterations mostly lead to severe phenotypes and the patients may die in early neonatal life; however, four of the affected siblings had survived till the ages of 10-17 years, without developing any life-threatening conditions. Mostly, in cousin marriages, the pathogenic variants are identical-by-descent, and affected siblings born to such parents are homozygous. Three homozygous variants were shortlisted in the analysis of the WES data, but Sanger sequencing did not confirm their segregation with the disease phenotype. This is the first report from Pakistan expanding pathogenicity of GFM1 gene.

Magnesium and Zinc Oxide Nanoparticles from Datura alba Improve Cognitive Impairment and Blood Brain Barrier Leakage.

Epilepsy is a neurological disorder involving persistent spontaneous seizures and uncontrolled neuronal excitability that leads to cognitive impairments and blood-brain barrier (BBB) disruption. Currently available antiepileptic drugs present side effects and researchers are trying to discover new agents with properties to overcome these drawbacks. The aim was to synthesize magnesium oxide (MgO) and zinc oxide (ZnO) nanoparticles from Datura alba fresh leaf extracts and evaluate their anti-epileptic potential in mice kindling or a repetitive seizures model. The phytoassisted synthesized nanoparticles were characterized using spectroscopy; FT-IR, XRD, SEM, and EDX. Analysis of the NPs confirmed the crystalline pleomorphic shape using the salts of both zinc and magnesium possibly stabilized, functionalized and reduced by bioactive molecules present in plant extract. By using several characterization techniques, NPs were confirmed. UV-Vis spectroscopy of biologically produced ZnO and MgO revealed distinctive peaks at 380 nm and 242 nm, respectively. Our findings categorically demonstrated the reductive role of biomolecules in the formation of ZnO and MgO NPs. The mice kindling model was induced using seven injections of Pentylenetetrazole (PTZ, 40 mg/kg, i.p) for 15 days alternatively. The results showed that mice post-treated with either ZnO or MgO nanoparticles (10 mg/kg, i.p) significantly improved in respect of behavior and memory as confirmed in the Morris water maze (MWM), open field (OF), novel object recognition (NOR) test compared with PTZ treated mice. Furthermore, the ZnO and MgO nanoparticle treatment also maintained the integrity of the BBB, reducing the leakage, as confirmed by Evans blue dye (EBD) compared with PTZ treated mice only. In summary, the current finding demonstrates that green synthesized ZnO and MgO nanoparticles have neuroprotective, ant-epileptic potential, molecular mechanisms, and clinical implications need to be further explored.

A Novel Image Encryption Scheme Based on Elliptic Curves over Finite Rings.

Image encryption based on elliptic curves (ECs) is emerging as a new trend in cryptography because it provides high security with a relatively smaller key size when compared with well-known cryptosystems. Recently, it has been shown that the cryptosystems based on ECs over finite rings may provide better security because they require the computational cost for solving the factorization problem and the discrete logarithm problem. Motivated by this fact, we proposed a novel image encryption scheme based on ECs over finite rings. There are three main steps in our scheme, where, in the first step, we mask the plain image using points of an EC over a finite ring. In step two, we create diffusion in the masked image with a mapping from the EC over the finite ring to the EC over the finite field. To create high confusion in the plain text, we generated a substitution box (S-box) based on the ordered EC, which is then used to permute the pixels of the diffused image to obtain a cipher image. With computational experiments, we showed that the proposed cryptosystem has higher security against linear, differential, and statistical attacks than the existing cryptosystems. Furthermore, the average encryption time for color images is lower than other existing schemes.

Investigation of Echinococcus multilocularis in foxes and dogs in Pakistan by detection of copro-DNA.

Alveolar echinococcosis (AE) is a zoonosis caused by Echinococcus multilocularis, a heteroxenous parasite belonging to Cestoda class. AE is currently considered an important public health issue, but epidemiological and notably molecular data from several endemic countries, including Pakistan, are sparse. Here we report the first detection of Echinococcus multilocularis in wildlife from Pakistan after real-time PCR and sequencing confirmation in the faecal samples of three foxes from northern Kaghan and Siran regions. The occurrence is estimated at 4.4% (95% CI 0.9-12.4). In order to go further in the epidemiological investigations on E. multilocularis and due to the potential presence of other Echinococcus species, we suggest the need for further epidemiological surveys targeting E. multilocularis and E. granulosus sensu lato isolates from humans and intermediate hosts as well as definitive hosts from wildlife in Pakistan.

Threat Modeling-How to Visualize Attacks on IOTA?

Internet of Things (IoT) has been deployed in a vast number of smart applications with the aim to bring ease and comfort into our lives. However, with the expansion of IoT applications, the number of security and privacy breaches has also increased, which brings into question the resilience of existing security and trust mechanisms. Furthermore, the contemporaneous centralized technology is posing significant challenges viz scalability, transparency and efficiency to wide range of IoT applications such as smart logistics, where millions of IoT devices need to be connected simultaneously. Alternatively, IOTA is a distributed ledger technology that offers resilient security and trust mechanisms and a decentralized architecture to overcome IoT impediments. IOTA has already been implemented in many applications and has clearly demonstrated its significance in real-world applications. Like any other technology, IOTA unfortunately also encounters security vulnerabilities. The purpose of this study is to explore and highlight security vulnerabilities of IOTA and simultaneously demonstrate the value of threat modeling in evaluating security vulnerabilities of distributed ledger technology. IOTA vulnerabilities are scrutinized in terms of feasibility and impact and we have also presented prevention techniques where applicable. To identify IOTA vulnerabilities, we have examined existing literature and online blogs. Literature available on this topic is very limited so far. As far as we know IOTA has barely been addressed in the traditional journals, conferences and books. In total we have identified six vulnerabilities. We used Common Vulnerability Scoring System (CVSS v3.0) to further categorize these vulnerabilities on the basis of their feasibility and impact.

Hybrid Task Coordination Using Multi-Hop Communication in Volunteer Computing-Based VANETs.

Computation offloading is a process that provides computing services to vehicles with computation sensitive jobs. Volunteer Computing-Based Vehicular Ad-hoc Networking (VCBV) is envisioned as a promising solution to perform task executions in vehicular networks using an emerging concept known as vehicle-as-a-resource (VaaR). In VCBV systems, offloading is the primary technique used for the execution of delay-sensitive applications which rely on surplus resource utilization. To leverage the surplus resources arising in periods of traffic congestion, we propose a hybrid VCBV task coordination model which performs the resource utilization for task execution in a multi-hop fashion. We propose an algorithm for the determination of boundary relay vehicles to minimize the requirement of placement for multiple road-side units (RSUs). We propose algorithms for primary and secondary task coordination using hybrid VCBV. Extensive simulations show that the hybrid technique for task coordination can increase the system utility, while the latency constraints are addressed.

Virtual Pseudonym-Changing and Dynamic Grouping Policy for Privacy Preservation in VANETs.

Location privacy is a critical problem in the vehicular communication networks. Vehicles broadcast their road status information to other entities in the network through beacon messages to inform other entities in the network. The beacon message content consists of the vehicle ID, speed, direction, position, and other information. An adversary could use vehicle identity and positioning information to determine vehicle driver behavior and identity at different visited location spots. A pseudonym can be used instead of the vehicle ID to help in the vehicle location privacy. These pseudonyms should be changed in appropriate way to produce uncertainty for any adversary attempting to identify a vehicle at different locations. In the existing research literature, pseudonyms are changed during silent mode between neighbors. However, the use of a short silent period and the visibility of pseudonyms of direct neighbors provides a mechanism for an adversary to determine the identity of a target vehicle at specific locations. Moreover, privacy is provided to the driver, only within the RSU range; outside it, there is no privacy protection. In this research, we address the problem of location privacy in a highway scenario, where vehicles are traveling at high speeds with diverse traffic density. We propose a Dynamic Grouping and Virtual Pseudonym-Changing (DGVP) scheme for vehicle location privacy. Dynamic groups are formed based on similar status vehicles and cooperatively change pseudonyms. In the case of low traffic density, we use a virtual pseudonym update process. We formally present the model and specify the scheme through High-Level Petri Nets (HLPN). The simulation results indicate that the proposed method improves the anonymity set size and entropy, provides lower traceability, reduces impact on vehicular network applications, and has lower computation cost compared to existing research work.

Complete genome sequence of begonia flower breaking virus, a novel member of the genus Potyvirus.

We determined the complete genomic sequence of begonia flower breaking virus (BFBV), a novel putative member of the genus Potyvirus isolated from Begonia bowerae cv. 'Tiger' plants grown in Kunming. The genomic RNA comprises 9540 nucleotides (nt), excluding the 3'-terminal poly(A) tail, and contains a typical open reading frame (ORF) of potyviruses. The ORF consists of 9219 nucleotides and encodes a 3073-amino-acid polyprotein that is predicted to be proteolytically cleaved into 10 mature peptides. Sequence comparison indicated that BFBV shares 43.9-55.12% amino acid sequence identity with known potyviruses and that BFBV shares the highest amino acid sequence identity (55.12%) with beet mosaic virus. The results from the complete genomic sequence analysis further suggest that BFBV is a member of a novel species in the genus Potyvirus.

Image Encryption Using Elliptic Curves and Rossby/Drift Wave Triads.

We propose an image encryption scheme based on quasi-resonant Rossby/drift wave triads (related to elliptic surfaces) and Mordell elliptic curves (MECs). By defining a total order on quasi-resonant triads, at a first stage we construct quasi-resonant triads using auxiliary parameters of elliptic surfaces in order to generate pseudo-random numbers. At a second stage, we employ an MEC to construct a dynamic substitution box (S-box) for the plain image. The generated pseudo-random numbers and S-box are used to provide diffusion and confusion, respectively, in the tested image. We test the proposed scheme against well-known attacks by encrypting all gray images taken from the USC-SIPI image database. Our experimental results indicate the high security of the newly developed scheme. Finally, via extensive comparisons we show that the new scheme outperforms other popular schemes.

Motor relearning program along with electrical stimulation for improving upper limb function in stroke patients: A quasi experimental study.

OBJECTIVE: To determine the effectiveness of motor relearning program along with electrical stimulation for improving upper limb function in patients with sub-acute stroke. METHODS: A quasi experimental study was conducted at Physiotherapy Department of SAIDU Group of Teaching Hospitals Swat Khyber Pakhtunkhwa from January to June 2019. Forty four subjects with post stroke duration of 3-9 months (sub-acute) participated in the study. Subjects received electrical stimulations for the effected arm for 15 minutes along with motor relearning programme for an hour five days a week for six weeks. The upper limb sub scales of motor assessment scale were used to collect pre and post treatment data. SPSS version 20 was used to analyze the data. RESULTS: The mean age of the participants was 54.95±13.2 years. Out of 44 participants 31(70.5%) were male and 13 (29.5%) were female. Pretreatment upper arm function, hand movement and advance hand activities scores were 1.36 ± 0.49, 1.18 ± 0.39 and 1.04 ± 0.21 respectively while their post treatment scores were 5.18 ± 0.96, 4.77 ± 1.02 and 3.95 ± 1.21 respectively. There was significant differences (P<0.05) between pre and post treatment scores of upper arm function, hand movement and advance hand activities. CONCLUSION: Motor relearning program along with electrical stimulation significantly improves upper limb function in patients with sub-acute stroke.

Rescue of neural crest-derived phenotypes in a zebrafish CHARGE model by Sox10 downregulation.

CHD7 mutations are implicated in a majority of cases of the congenital disorder, CHARGE syndrome. CHARGE, an autosomal dominant syndrome, is known to affect multiple tissues including eye, heart, ear, craniofacial nerves and skeleton and genital organs. Using a morpholino-antisense-oligonucleotide-based zebrafish model for CHARGE syndrome, we uncover a complex spectrum of abnormalities in the neural crest and the crest-derived cell types. We report for the first time, defects in myelinating Schwann cells, enteric neurons and pigment cells in a CHARGE model. We also observe defects in the specification of peripheral neurons and the craniofacial skeleton as previously reported. Chd7 morphants have impaired migration of neural crest cells and deregulation of sox10 expression from the early stages. Knocking down Sox10 in the zebrafish CHARGE model rescued the defects in Schwann cells and craniofacial cartilage. Our zebrafish CHARGE model thus reveals important regulatory roles for Chd7 at multiple points of neural crest development viz., migration, fate choice and differentiation and we suggest that sox10 deregulation is an important driver of the neural crest-derived aspects of Chd7 dependent CHARGE syndrome.

Exome sequencing of primary breast cancers with paired metastatic lesions reveals metastasis-enriched mutations in the A-kinase anchoring protein family (AKAPs).

BACKGROUND: Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression. Characterization of paired primary- and metastatic tissues should therefore be fundamental in order to understand mechanisms of tumor progression, clonal relationship to tumor evolution as well as the therapeutic aspects of systemic disease. METHODS: We performed full exome sequencing of primary breast cancers and their metastases in a cohort of ten patients and further confirmed our findings in an additional cohort of 20 patients with paired primary and metastatic tumors. Furthermore, we used gene expression from the metastatic lesions and a primary breast cancer data set to study the gene expression of the AKAP gene family. RESULTS: We report that somatic mutations in A-kinase anchoring proteins are enriched in metastatic lesions. The frequency of mutation in the AKAP gene family was 10% in the primary tumors and 40% in metastatic lesions. Several copy number variations, including deletions in regions containing AKAP genes were detected and showed consistent patterns in both investigated cohorts. In a second cohort containing 20 patients with paired primary and metastatic lesions, AKAP mutations showed an increasing variant allele frequency after multiple relapses. Furthermore, gene expression profiles from the metastatic lesions (n = 120) revealed differential expression patterns of AKAPs relative to the tumor PAM50 intrinsic subtype, which were most apparent in the basal-like subtype. This pattern was confirmed in primary tumors from TCGA (n = 522) and in a third independent cohort (n = 182). CONCLUSION: Several studies from primary cancers have reported individual AKAP genes to be associated with cancer risk and metastatic relapses as well as direct involvement in cellular invasion and migration processes. Our findings reveal an enrichment of mutations in AKAP genes in metastatic breast cancers and suggest the involvement of AKAPs in the metastatic process. In addition, we report an AKAP gene expression pattern that consistently follows the tumor intrinsic subtype, further suggesting AKAP family members as relevant players in breast cancer biology.

Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions.

Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol-induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta-1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.