Pharmaceutical Industry Research Articles

Unlocking the full potential of digital endpoints for decision making: a novel modular evidence concept enabling re-use and advancing collaboration.

Over the last decade increasing examples indicate opportunities to measure patient functioning and its relevance for clinical and regulatory decision making via endpoints collected through digital health technologies. More recently, we have seen such measures support primary study endpoints and enable smaller trials. The field is advancing fast: validation requirements have been proposed in the literature and regulators are releasing new guidances to review these endpoints. Pharmaceutical companies are embracing collaborations to develop them and working with academia and patient organizations in their development. However, the road to validation and regulatory acceptance is lengthy. The full value of digital endpoints cannot be unlocked until better collaboration and modular evidence frameworks are developed enabling re-use of evidence and repurposing of digital endpoints. This paper proposes a solution by presenting a novel modular evidence framework -the Digital Evidence Ecosystem and Protocols (DEEP)- enabling repurposing of measurement solutions, re-use of evidence, application of standards and also facilitates collaboration with health technology assessment bodies. The integration of digital endpoints in healthcare, essential for personalized and remote care, requires harmonization and transparency. The proposed novel stack model offers a modular approach, fostering collaboration and expediting the adoption in patient care.

Application of microphysiological systems for nonclinical evaluation of cell therapies.

Microphysiological systems (MPS) are gaining broader application in the pharmaceutical industry but have primarily been leveraged in early discovery toxicology and pharmacology studies with small molecules. The adoption of MPS offers a promising avenue to reduce animal use, improve in-vitro-to-in-vivo translation of pharmacokinetics/pharmacodynamics and toxicity correlation, and provide mechanistic understanding of model species suitability. While MPS have demonstrated utility in these areas with small molecules and biologics, cell therapeutic MPS models in drug development have not been fully explored, let alone validated. Distinguishing features of MPS, including long-term viability and physiologically relevant expression of functional enzymes, receptors, and pharmacological targets make them attractive tools for nonclinical characterization. However, there is currently limited published evidence of MPS being utilized to study the disposition, metabolism, pharmacology, and toxicity profiles of cell therapies. This review provides an industry perspective on the nonclinical application of MPS on cell therapies, first with a focus on oncology applications followed by examples in regenerative medicine.

Enhancing Phycocyanobilin Production Efficiency in Engineered Corynebacterium glutamicum: Strategies and Potential Application.

Phycocyanobilin, an algae-originated light-harvesting pigment known for its antioxidant properties, has gained attention as it plays important roles in the food and medication industries and has surged in demand owing to its low-yield extraction from natural resources. In this study, engineered Corynebacterium glutamicum was developed to achieve high PCB production, and three strategies were proposed: reinforcement of the heme biosynthesis pathway with the introduction of two PCB-related enzymes, strengthening of the pentose phosphate pathway to generate an efficient cycle of NADPH, and fed-batch fermentation to maximize PCB production. Each approach increased PCB synthesis, and the final engineered strain successfully produced 78.19 mg/L in a flask and 259.63 mg/L in a 5 L bioreactor, representing the highest bacterial production of PCB reported to date, to our knowledge. The strategies applied in this study will be useful for the synthesis of PCB derivatives and can be applied in the food and pharmaceutical industries.

Isolation and characterization of thymoquinone from Nigella sativa essential oil: antioxidant and antibacterial activities, molecular modeling studies, and cytotoxic effects on lung cancer A549 cells

Thymoquinone (TQ), a bioactive compound found in Nigella sativa seeds, has gained considerable attention due to its potential therapeutic properties. This study aimed to isolate and characterize TQ from Nigella sativa essential oil and evaluate its antioxidant capacity, antibacterial activity, and cytotoxic effects on lung cancer A549 cells. Moreover, The binding potential of TQ to Keap1 (Kelch-like ECH associated protein 1) was investigated through molecular docking. The stability of the resulting complex was evaluated through molecular dynamics (MD) simulation. The CUPRAC assay revealed significant antioxidant capacity of TQ, as indicated by its high molar absorptivity coefficient. TQ also demonstrated notable free radical scavenging activity, with efficacy increasing with concentration. In terms of antiquorum sensing activity, TQ displayed effectiveness against all tested virulence factors in P. aeruginosa PAO1 and Chromobacterium violaceum in different range. Additionally, TQ induced cytotoxicity in non-small lung cancer cells, inhibiting cell viability. In conclusion, this study successfully isolated and characterized TQ from Nigella sativa seeds and demonstrated its remarkable antioxidant capacity, antibacterial activity, and cytotoxic effects on lung cancer cells. These findings suggest the potential of TQ for various applications in the food and pharmaceutical industries. The wet-lab study demonstrated that TQ had an antioxidant effect. The TQ was found to have high binding potential to Keap1 as it formed four conventional hydrogen bonds with the protein. The resulting Keap1-TQ complex was also found to be stable. Further research is warranted to explore the therapeutic potential of TQ and develop novel treatments based on its properties.

Applications of multi-parameter sensing in pharmaceutical, agriculture and mineral industries using THz spectroscopy and Low-Wavenumber Raman spectroscopy

Multi-parameter sensing using non-destructive optical spectroscopic techniques, specifically Terahertz spectroscopy and low-wavenumber Raman spectroscopy (also known as THz-Raman spectroscopy), has significantly reshaped the landscape of analytical methodologies in various industries. This comprehensive review article elucidates the transformative impact of these advanced spectroscopic methods within the fields of pharmaceutical, agriculture, and mineral industry. As technology continues to evolve, the ability to concurrently analyse multiple parameters at the molecular level has become a cornerstone for precision and efficiency in these critical sectors. In the pharmaceutical industry, THz spectroscopy has emerged as a key tool in ensuring the quality and stability of drug formulations, while low-wavenumber Raman spectroscopy complements by offering insights into chemical structure as well as composition. The agricultural sector benefits from the capabilities of these spectroscopic techniques in optimizing crop management, soil analysis, and resource utilization. Simultaneously, the mineral industry leverages THz and low-wavenumber Raman spectroscopy for accurate mineral identification, aiding in exploration, extraction, and processing. Through this review, we aim to provide a nuanced understanding of how multi-parameter sensing through THz and low-wavenumber Raman spectroscopy is driving innovation, enhancing quality control, and fostering sustainable practices across diverse industrial landscapes.

New insight into protective effect against oxidative stress and biosynthesis of exopolysaccharides produced by Lacticaseibacillus paracasei NC4 from fermented eggplant.

Fermented eggplant is a traditional fermented food, however lactic acid bacteria capable of producing exopolysaccharide (EPS) have not yet been exploited. The present study focused on the production and protective effects against oxidative stress of an EPS produced by Lacticaseibacillus paracasei NC4 (NC4-EPS), in addition to deciphering its genomic features and EPS biosynthesis pathway. Among 54 isolates tested, strain NC4 showed the highest EPS yield and antioxidant activity. The maximum EPS production (2.04 ± 0.11g/L) was achieved by culturing in MRS medium containing 60g/L sucrose at 37°C for 48h. Under 2mM H2O2 stress, the survival of a yeast model Saccharomyces cerevisiae treated with 0.4mg/mL NC4-EPS was 2.4-fold better than non-treated cells, which was in agreement with the catalase and superoxide dismutase activities measured from cell lysates. The complete genome of NC4 composed of a circular chromosome of 2,888,896bp and 3 circular plasmids. The NC4 genome comprises more genes with annotated function in nitrogen metabolism, phosphorus metabolism, cell division and cell cycle, and iron acquisition and metabolism as compared to other reported L. paracasei. Of note, the eps gene cluster is not conserved across L. paracasei. Pathways of sugar metabolism for EPS biosynthesis were proposed for the first time, in which gdp pathway only present in few plant-derived bacteria was identified. These findings shed new light on the cell-protective activity and biosynthesis of EPS produced by L. paracasei, paving the way for future efforts to enhance yield and tailor-made EPS production for food and pharmaceutical industries.

Hydrophobic Surfactant-DNA Complex (Surf-DNA) Enables DNA-Encoded-Library-Compatible Decarboxylative Arylation under Anhydrous Conditions.

DNA-encoded libraries (DELs) are a key technology for identifying small-molecule hits in both the pharmaceutical industry and academia, but their chemical diversity is largely limited to water-compatible reactions to aid in the solubility and integrity of encoding DNA tags. To broaden the DEL chemical space, we present a workflow utilizing DNA-cationic surfactant complexation that enables dissolution and reactions on-DNA in anhydrous organic solvents. We demonstrate its utility by developing DEL-compatible photoredox decarboxylative C(sp2)-C(sp3) coupling under water-free conditions. The workflow is optimized for the 96-well format necessary for large-scale DEL productions, and it enables screening and optimization of DEL-compatible reactions in organic solvents.

Network pharmacology combined with an experimental validation study to reveal the effect and mechanism of Lonicera japonica Thunb. extracts against immunomodulation.

Lonicera japonica Thunb. (LJT) is known for its valuable medicinal properties that highlight its potential application in the pharmaceutical and health food industry. We predict that LJT polyphenols by network pharmacology may be involved in immunomodulation, and the study of LJT polyphenols regulating immunity is still insufficient; therefore, we experimentally found that LJT enhances immunity by promoting the proliferation and phagocytic activity of RAW246.7 cells. A model of an immunosuppressed mouse was constructed using cyclophosphamide-induced, and LJT was extracted for the intervention. We found that LJT restored immune homeostasis in immune deficiency mice by inhibiting the abnormal apoptosis in lymphocytes, enhancing natural killer cell cytotoxicity, promoting T lymphocyte proliferation, and increasing the CD4+ and CD8+ T lymphocytes in quantity. Moreover, LJT treatment modulates immunity by significantly downregulating lipopolysaccharide-induced inflammation and oxidative stress levels. We verified the immunomodulatory function of LJT through both cell and animal experiments. The combination of potential-protein interactions and molecular docking later revealed that LJT polyphenols were associated with immunomodulatory effects on MAPK1; together, LJT intervention significantly modulates the immune, with the activation of MAPK1 as the underlying mechanism of action, which provided evidence for the utilization of LJT as a nutraceutical in immune function.

Quality of Essential Medicines from Different Sources in Enugu and Anambra, Nigeria.

This study investigated the quality of 13 essential medicines in the states of Enugu and Anambra, Nigeria. A total of 260 samples were purchased from licensed pharmaceutical manufacturers and wholesalers and from vendors in pharmaceutical markets with unclear licensing status. Samples were analyzed for identity, content, and dissolution according to the United States Pharmacopeia (USP) 42 monographs. Forty-five samples of this study could be examined for authenticity with the Mobile Authentication Service scheme of the Nigerian National Agency for Food and Drug Administration and Control. Out of all samples, 25.4% did not comply with the USP 42 specifications. Strikingly, 21 out of 22 dexamethasone tablet samples (95%) were out of specification (OOS). Nine out of 19 glibenclamide samples (47%) failed dissolution testing, and 7 out of 17 cotrimoxazole samples (41%) failed assay testing. Medicines against noncommunicable diseases showed a slightly higher percentage of OOS samples than anti-infectives (21.2% versus 17.6%). The rates of OOS samples were similar in medicines stated to be produced in Nigeria, India, and China but were very different between individual manufacturers from each of these countries of origin. Therefore, prequalification of products, manufacturers, and suppliers are very important for quality assurance in medicine procurement. Unexpectedly, the total proportions of OOS samples were similar from licensed vendors (25.2%) and from markets (25.5%). Four samples (1.5%), all collected in markets, were clearly falsified and did not contain the declared active pharmaceutical ingredients. The proportion of falsified medicines was found to be lower than frequently reported in the media for Nigeria.

Introducing the glycyrrhizic acid and glabridin rich genotypes from the cultivated Iranian licorice (Glycyrrhiza glabra L.) populations to exploit in production systems

Currently, the stable, uniform, and highly efficient production of raw materials for pharmaceutical companies has received special attention. To meet these criteria and reduce harvesting pressure on the natural habitats of licorice (Glycyrrhiza glabra L.), cultivation of this valuable plant is inevitable. In the present study, to introduce the glycyrrhizic acid (GA)- and glabridin-rich genotypes from cultivated Iranian licorice, forty genotypes from eight high-potential wild populations were cultivated and evaluated under the same environmental conditions. The GA content varied from 5.00 ± 0.04 mg/g DW (TF2 genotype) to 23.13 ± 0.02 mg/g DW (I5 genotype). The highest and lowest glabridin content were found in the K2 (0.72 ± 0.021 mg/g DW) and M5 (0.02 ± 0.002 mg/g DW) genotypes, respectively. The rutin content in the leaves of the studied genotypes varied from 1.27 ± 0.02 mg/g DW in E4 to 3.24 ± 0.02 mg/g DW in BO5 genotypes. The genotypes from the Ilam population were characterized by higher vegetative growth and yield traits in the aerial parts and roots. The average root dry yield was 2.44 tons per hectare (t/ha) among the studied genotypes and a genotype from Ilam (I5) yielded the maximum value (3.08 ± 0.034 t/ha). The highest coefficient of variation among the genotypes was observed for leaf width (CV = 34.9%). The GA and glabridin-rich genotypes introduced in this study can be used in the future breeding programs to release new bred licorice cultivars.

Solvency and Liquidity Analysis of Selected Pharmaceutical Companies in Indian: A Comparative Study

Solvency and Liquidity Analysis of Selected Pharmaceutical Companies in Indian: A Comparative Study

Assessment of the Effect of Surface Modification of Metal Oxides on Silver Nanoparticles: Optical Properties and Potential Toxicity.

Silver nanoparticles (AgNPs) have garnered significant interest due to their distinctive properties and potential applications. Traditional fabrication methods for nanoparticles often involve high-energy physical conditions and the use of toxic solvents. Various green synthesis approaches have been developed to circumvent these issues and produce environmentally benign nanoparticles. Our study focuses on the green synthesis of AgNPs using L-ascorbic acid and explores the modification of their properties to enhance antibacterial and anticancer effects. This is achieved by coating the nanoparticles with Zinc oxide (ZnO) and Silica oxide (SiO2), which alters their optical properties in the visible spectrum. The synthesized formulations-AgNPs, zinc oxide-silver nanoparticles (Ag@ZnO), and silica oxide-silver nanoparticles (Ag@SiO2) core/shell nanoparticles-were characterized using a suite of physicochemical techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta potential measurement, UV-Vis spectroscopy, Refractive Index Measurements, and Optical Anisotropy Assessment. TEM imaging revealed particle sizes of 11 nm for AgNPs, 8 nm for Ag@ZnO, and 400 nm for Ag@SiO2. The Zeta potential values for Ag@ZnO and Ag@SiO2 were measured at -17.0 ± 5 mV and -65.0 ± 8 mV, respectively. UV-Vis absorption spectra were recorded for all formulations in the 320 nm to 600 nm wavelength range. The refractive index of AgNPs at 404.7 nm was 1.34572, with slight shifts observed for Ag@ZnO and Ag@SiO2 to 1.34326 and 1.37378, respectively. The cytotoxicity of the nanocomposites against breast cancer cell lines (MCF-7) was assessed using the MTT assay. The results indicated that AgNPs and Ag@ZnO exhibited potent therapeutic effects, with IC50 values of 494.00 µg/mL and 430.00 µg/mL, respectively, compared to 4247.20 µg/mL for Ag@SiO2. Additionally, the antibacterial efficacy of AgNPs was significantly enhanced under visible light irradiation. Ag@ZnO demonstrated substantial antibacterial activity both with and without light exposure, while the Ag@SiO2 nanocomposites significantly reduced the inherent antibacterial activity of silver. Conversely, the Ag@ZnO nanocomposites displayed pronounced antibacterial and anticancer activities. The findings suggest that silver-based nanocomposites, particularly Ag@ZnO, could be practical tools in water treatment and the pharmaceutical industry due to their enhanced therapeutic properties.

Structural and mechanistic insights into Quinolone Synthase to address its functional promiscuity

Quinolone synthase from Aegle marmelos (AmQNS) is a type III polyketide synthase that yields therapeutically effective quinolone and acridone compounds. Addressing the structural and molecular underpinnings of AmQNS and its substrate interaction in terms of its high selectivity and specificity can aid in the development of numerous novel compounds. This paper presents a high-resolution AmQNS crystal structure and explains its mechanistic role in synthetic selectivity. Additionally, we provide a model framework to comprehend structural constraints on ketide insertion and postulate that AmQNS’s steric and electrostatic selectivity plays a role in its ability to bind to various core substrates, resulting in its synthetic diversity. AmQNS prefers quinolone synthesis and can accommodate large substrates because of its wide active site entrance. However, our research suggests that acridone is exclusively synthesized in the presence of high malonyl-CoA concentrations. Potential implications of functionally relevant residue mutations were also investigated, which will assist in harnessing the benefits of mutations for targeted polyketide production. The pharmaceutical industry stands to gain from these findings as they expand the pool of potential drug candidates, and these methodologies can also be applied to additional promising enzymes.

Social Perceptions of Masculinity and Sexual Esteem Are Impacted by Viagra Use, Testosterone, and Sexual Performance.

Sexual behaviors play a role in the social construction of masculinity. Moreover, this stereotype has been capitalized upon by pharmaceutical companies, as well as those that sell products not approved by the U.S. Food and Drug Administration, for purposes of marketing sexual medicines. Stereotypical notions of masculinity, however, also emphasize the importance of self-reliance, which may cause some to look unfavorably upon the use of sexual medicine. Consistent with this notion, a male target was viewed as more masculine when his female partner consistently reached orgasm, unless he had no history of erectile dysfunction (ED), but was taking Viagra anyway (Experiment 1; N = 522). In addition, when his partner consistently reached orgasm, ratings of his sexual esteem were also lower if he used Viagra than if he did not, but only if he had no history of ED. In Experiment 2 (N = 711), although there was no effect of a male target's use of testosterone, social perception of his masculinity and sexual esteem increased as his "natural" levels of testosterone increased. In addition, exploratory analysis revealed that if the male target had low (but not normal or high) "natural" levels of testosterone, ratings of his masculinity were higher if his female partner consistently had an orgasm, which suggests that female orgasm served to "rescue" masculinity. Because expectations about drugs drive their use, it is important to address preconceived notions about the use of sexual medicines for purposes of enhancing masculinity and sexual esteem, as the social perception of their use is much more complex.

Vaccine hesitancy and trust in sub-Saharan Africa

Lack of trust is a primary reason behind the global rise in vaccine hesitancy. Existing research on the trust—vaccine hesitancy nexus has almost exclusively focused on COVID-19 with the vast majority of studies examining industrialized countries. In this study, we investigated the influence of trust in different policy-relevant actors (government, science, media, pharmaceutical companies, society) on vaccine hesitancy for recently available vaccines related to polio and HPV which we benchmark against a COVID-19 vaccine. Leveraging unique primary data on 5203 individuals from six countries (Ghana, Kenya, Nigeria, South Africa, Tanzania, and Uganda), we showed that individuals’ trust in the government and society are key predictors of vaccine hesitancy. Furthermore, we demonstrated that these relationships are remarkably stable across vaccine, disease, and country contexts.

Trajectory tracking control of parallel manipulator actuated with shape memory wire

This study describes the design of a parallel spatial manipulator with four degrees of freedom actuated with shape memory alloy (SMA) wire to validate the use of SMA in complicated mechatronics systems. The manipulator has a closed kinematic structure, which includes a fixed base and a moving square platform (end effector). The four arms of the manipulator are SMA wires fastened between the fixed base and the end effector. SMA wire-based actuators replace bulky conventional revolute actuators. This work spotlights the development of an actuator model, dimensional analysis, and design of cascade control strategies of various PID and sliding mode controller in their integral and fractional order configurations. Experimental evaluation of the actuator is performed through trajectory tracking to quantify the different controller configurations. The experimental results indicate that the parallel manipulator associated with SMA wire actuators is the best alternative to conventional motion stages for highly precise micro-positioning and tracking applications in the fields of 3D printing, intricate surgical operations, the medical and pharmaceutical industries, and flight and gaming simulators.

Synthesis, modifications, and applications of iron-based nanoparticles.

Magnetic nanoparticles (MNPs) are appealing materials as assistant to resolve environmental pollution issues and as recyclable catalysts for the oxidative degradation of resistant contaminants. Moreover, they can significantly influence the advancement of medical applications for imaging, diagnostics, medication administration, and biosensing. On the other hand, due to unique features, excellent biocompatibility, high curie temperatures and low cytotoxicity of the Iron-based nanoparticles, they have received increasing attention in recent years. Using an external magnetic field, in which the ferrite magnetic nanoparticles (FMNPs) in the reaction mixtures can be easily removed, make them more efficient approach than the conventional method for separating the catalyst particles by centrifugation or filtration. Ferrite magnetic nanoparticles (FMNPs) provide various advantages in food processing, environmental issues, pharmaceutical industry, sample preparation, wastewater management, water purification, illness therapy, identification of disease, tissue engineering, and biosensor creation for healthcare monitoring. Modification of FMNPs with the proper functional groups and surface modification techniques play a significant role in boosting their capability. Due to flexibility of FMNPs in functionalization and synthesis, it is possible to make customized FMNPs that can be utilized in variety of applications. This review focuses on synthesis, modifications, and applications of Iron-based nanoparticles.

Oncology drug pricing: potential medicare savings on cancer-directed and supportive care medications through the Mark Cuban cost plus drug model.

Prescription drug costs within oncology remain a challenge for many patients with cancer. The Mark Cuban Cost Plus Drug Company (MCCPDC) launched in 2022, aiming to provide transparently priced medications at reduced costs. In this study, we sought to describe the potential impact of MCCPDC on Medicare Part-D oncology spending related to cancer-directed (n = 7) and supportive care (n = 26) drugs. We extracted data for drug-specific Part-D claims and spending for 2021. Using 90-count purchases from MCCPDC, we found potential Part-D savings of $857.8 million (91% savings) across the 7 cancer-directed drugs and $28.7 million (67% savings) across 21/26 (5/26 did not demonstrate savings) supportive care drugs. Collectively, our findings support that alternative purchasing models like MCCPDC may promote substantial health care savings.

Based on CiteSpace Insights into Illicium verum Hook. f. Current Hotspots and Emerging Trends and China Resources Distribution

Illicium verum Hook. f. is a globally significant spice, which is recognized in China as a food-medicine homolog and extensively utilized across the pharmaceutical, food, and spice industries. China boasts the world’s leading resources of I. verum, yet its comprehensive utilization remains relatively underexplored. Through a resource survey of I. verum and the application of bibliometric visualization using CiteSpace, this study analyzed 324 papers published in the Web of Science Core Collection (WOSCC) from 1962 to 2023 and 353 core documents from China’s three major databases (CNKI, Wanfang Database, and VIP Database). I. verum from Guangxi province towards various southern provinces in China, with autumn fruits exhibited superior quality and market value over their spring fruits. Literature in WOSCC emerged earlier, with a research emphasis on food science technology and pharmacology pharmacy domains. WOSCC research on I. verum could be divided into two phases: an embryonic period (1962–2001) and a growth period (2002–2023), showing an overall upward trend in publication. The three major Chinese databases contain a larger number of publications, with a focus on the food sector, which could be categorized into three stages: an embryonic period (1990–1999), a growth period (2000–2010), and a stable period (2011–2023), with an overall downward trend in publication. Both Chinese and international research hotspots converge on the medical applications of I. verum, with antioxidant bioactivity research emerging as a prevailing trend. This study delineated the resource distribution of I. verum across China and identified the research hotspots and trends both in China and internationally. The findings are beneficial for guiding researchers in swiftly establishing their research focus and furnishing decision-makers with a comprehensive reference for industry information.

Chromatographic methods and approaches for bioequivalence study, drug screening and enantioseparation of indapamide

AbstractIndapamide (Indp) and certain other diuretics have been abused in sports, therefore, having sensitive methods for its detection and assay in biological fluids (whole blood, plasma, serum, and urine) is of significant importance. The racemic mixture of Indp is being used as an active pharmaceutical ingredient among other commonly prescribed diuretics. The regulatory authorities and pharmaceutical industries demand analytical methods for successful enantioseparation of such molecules. The paper presents a critical overview of the scientific issues of the application of contemporary techniques involving various chromatographic approaches (with liquid or supercritical fluid as mobile phases) and capillary electrophoresis and method development, for drug screening, assay, bioequivalence studies and enantioseparation of indapamide with their results. It also covers the historical developments that led to significant breakthroughs in research and concise evaluations of research in the area.Different types of chromatographic methods (HPLC, CEC, SFC etc) discussed herein provide an insight and a choice to select a method to (i) screen Indp for drug abuse, (ii) separate, isolate and quantify the enantiomers of Indp and (iii) investigate their pharmacokinetics as markedly different species and not as a total drug. The article evaluates the field's status with a broad base and practical oriented approach so that the underlying principles are easily understood to help chemists and non-specialists gain useful insights into the field outside their specialization and provide experts with summaries of key developments. To the best of authors' knowledge there has been no attempt to review such methods for analysis of Indp and this is the first report of its kind.