bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-Step Reinforcement Learning for Multistage Strategy Card Game
Authors: Godlewski Konrad , Sawicki Bartosz
Published: July 2024

This study introduces a two-step reinforcement learning (RL) strategy tailored for "The Lord of the Rings: The Card Game", a complex multistage strategy card game. The research diverges from conventional RL methods by adopting a phased learning approach, beginning with a foundational learning step in a simplified version of the game and subsequently progressing to the complete, intricate game environment. This methodology notably enhances the AI agent’s adaptability and performance in the face of the unpredictable and challenging nature of the game. The paper also explores a multi-phase system where distinct RL agents are employed for various decision-making phases of the game. This approach has demonstrated remarkable improvement, with the RL agents achieving a winrate of 78.5 % at the highest difficulty level.
Configuration design methodof hybrid electric agricultural machinery system based on layered two-dimensional matrix
Authors: Li Baogang , Pan Jinbo , Sun Rui , Li Yuhuan , Liu Zunmin , Huang Wanyou , Jiang Hanjun , Liu Fuhao
Published: July 2024

The working environment and objects of agricultural machinery are different from those of automobiles, andagricultural machinery is greatly affected by the working environment and working conditions, and the power output systemismore complex. Agricultural machinery not only has drive output, but also PTO output and hydraulic output, whichtogetherconstitute the output system of agricultural machinery. Agricultural machinery conditions can be dividedintoroadtransportation working conditions and field operation working conditions. The working conditions of agricultural machinerycan be divided into different load conditions according to the different traction tools and whether the hydraulic andPTOwork,such as ploughing, rotary tillage, fertilization, and transportation. Therefore, developing hybrid electric agricultural machinerysystems that are suitable for various complex working conditions holds great theoretical significance and practical value. Giventhe complex working conditions of agricultural machinery systems in agricultural work and the intricate challengesindesigning hybrid agricultural machinery systems. In this paper, the two-dimensional matrix is used to represent thephysicalstructure and dynamics of the multi-channel power output agricultural mechanism. A hierarchical two-dimensional matrixmethod for the generation and screening of hybrid electric agricultural machinery systems with multi-power output powerisproposed. The components of agricultural machinery are divided into an input layer and an output layer, and these componentsare coded and defined, and then transformed into a matrix. The hierarchical two-dimensional matrix method is usedtogenerateand screen the hybrid electric agricultural mechanism type. Through the stratification of the matrix, the complexityoftheconfiguration generation is reduced, and the constraints are applied to the basic screening of the generated configurations. Therationality of the configurations obtained after generation and screening is verified by Simulink simulation. The resultsshowthat the configuration screened by this method can meet the performance requirements of agricultural machinery.
An Improved Thermal Management of Lithium Based Batteries Employing Genetic Algorithm Optimization
Authors: Yüksek Gökhan , Lale Timur
Published: July 2024

Lithium-based battery systems (LBS) are used in various applications, from the smallest electronic devices to power generation plants. LBS energy storage technology, which can offer high power and high energy density simultaneously, can respond to continuous energy needs and meet sudden power demands. The lifetime of LBSs, which are seen as a high-cost storage technology, depends on many parameters such as usage habits, temperature and charge rate. Since LBSs store energy electrochemically, they are seriously affected by temperature. High-temperature environments increase the thermal stress on the LBS and cause its chemical structure to deteriorate much faster. In addition, the fast charging feature of LBSs, which is presented as an advantage, increases the internal temperature of the cell and negatively affects the battery life. The proposed energy management approach ensures that the ambient temperature affects the charging speed of the battery and that the charging speed is adaptively updated continuously. So, the two parameters that harm battery health absorb each other, and the battery has a longer life. A new differential approach has been created for the proposed energy management system. The total amount of energy that can be withdrawn from the LBS is increased by 14.18% compared to the LBS controlled with the standard energy management system using the genetic algorithm optimized parameters. In this way, the LBS replacement period is extended, providing both cost benefits and environmentally friendly management by LBSs turning into chemical waste later.
Differential vibrating-wire strain gauge for concrete deformation measurements
Authors: Kanciruk Adam , Matus Elżbieta
Published: July 2024

The basic measuring element of vibrating-wire strain gauges is a steel piano wire, functioning in the elastic range. This element is constantly under tension. Therefore, its material gradually deforms permanently. This deformation causes its stress to relax. This relaxation results in a measurement errors of the strain gauges. This error, as demonstrated by both in situ and laboratory tests, can reach values of even several percent of the strain gauge measuring range (FSR) over periods of 10 years. Therefore, a concept of a differential strain gauge was proposed, for the construction of which two measuring wires would be used. Changing the input value of the strain gauge, i.e. a displacement of one of its anchors in relation to the other one would cause one wire to lengthen while the other wire shortened identically. The measured displacement would be calculated on the basis of the difference in the frequency of the wires vibrations. In this way, the influence of the simultaneous relaxation of the wires on the measurement result would be greatly reduced. Based on this concept, a prototype differential strain gauge for measuring concrete deformation was realized. In addition to two wires, it also contains two electromagnets, placed together with the wires in a common body-housing. After the strain gauge was assembled, its first tests were carried out under laboratory conditions.
Review of surface metrology artifacts for additive manufacturing
Authors: Mietliński Patryk , Gapiński Bartosz , Królczyk Jolanta B. , Niesłony Piotr , Bogdan-Chudy Marta , Trych-Wildner Anna , Wojciechowska Natalia , Królczyk Grzegorz M. , Wieczorowski Michał , Bartkowiak Tomasz
Published: July 2024

Test artifacts, resembling real machine parts, allow quantitative evaluation of system performance and insight into individual errors, aiding in improvement and standardization in additive manufacturing. The article provides a comprehensive overview of existing test artifacts, categorized based on geometric features and material used. Various measurement techniques such as stylus profilometry and computed tomography are employed to assess these artifacts. It was shown that Selective Laser Melting (SLM) technology and titanium alloys are prevalent in artifact creation. Specific artifact categories include slits, angular aspects, length parameters, variable surfaces, and others, each accompanied by examples from research literature, highlighting diverse artifact designs and their intended applications. The paper critically discusses the main problems with existing geometries. It paper underscores the importance of user-friendly and unambiguous artifacts for dimensional control, particularly in surface metrology. It anticipates the continued growth of metrological verification in future manufacturing environments, emphasizing the need for precise and reliable measurement results to support decision-making in production conditions
Optimized Design of Downhole Heater Seal for Oil Shale In-Situ Heat Injection
Authors: Li Qiang , Bu Qingfeng , Li Xiaole , Zeng Hao
Published: July 2024

Sealing is an important prerequisite for downhole heater work. This paper proposes a combination of soft and hard and welding sealing programs, which were analyzed using theoretical calculations, numerical simulation, and in-situ testing. The results show that 316 stainless steel can meet the stuffing seal requirements; The first stuffing compresses and gradually reduces, while the second stuffing essentially does not deform. Stuffing deformation to fill the gap in the sealing hole, resulting in a sealing layer. The compression rate is 0.43%, 8.45%, and 12.64%, indicating that the locking stress should be more than 2000 N; The temperature at the weld is heated by heat conduction and distributed in a concentric circle. Thermal stress will influence the 50mm barrier, but the 100mm boundary will be mostly unaffected. Actually, the thermal stress that destroys the weld seal may be reduced by adjusting the heater's output or raising the gas injection rate. During the beginning of the in-situ heat injection, the temperature of the heating rods rises simultaneously with the outlet temperature. As consequently, the two show opposite tendencies. The heat generated by the heating rods will cause the injected gas to be preheated in advance.
Eco-chic or trendy-chic? Decoding consumer preferences in sustainable and fast fashion across the EU
Authors: Apetrei Andreea , Constantin Marius , Deaconu Elena-Mădălina , Dinu Mihai , Pătărlăgeanu Simona Roxana , Petrescu Irina-Elena
Published: July 2024

The ongoing transformation of the fashion industry is driven by an increasing focus on sustainability, ethical practices, and responsible consumer behavior. Simultaneously, social media platforms have emerged as influential forces in this field, shaping fashion trends and consumer preferences. Despite a substantial body of literature investigating consumer preferences between fast and sustainable fashion, a gap in understanding the intricate relationship between fashion preferences, socio-economic profiling, and social media engagement is evident. Thus, this research was aimed at comparatively decoding EU consumers’ preferences for fast fashion against sustainable fashion by exploring the interplay of demographic factors ‒ age, gender, and geographical location ‒ on fashion preferences, as expressed through the digital engagement with fashion-related content on the Meta social platforms. The research methodology implied resorting to logistic regression analysis, aiming to uncover the underlying patterns that fundamentally characterize consumers’ preferences for fashion in the EU. The results provide novel insights into how digital engagement with fashion-related content can act as a barometer for regional fashion identities and preferences, useful for the identification of both convergence and inflection points. Moreover, findings offer a robust foundation for crafting strategies that promote sustainable fashion practices, tailored to specific EU age, gender, and location demographics, by leveraging the insights gained about EU consumer preferences.
Assessing the influence of inspirational value on experience quality and electronic word-of-mouth in non-formal music education settings in Indonesia
Authors: Purnama Teddy , Antonio Ferdi , Berlianto Margaretha Pink
Published: July 2024

Non-formal music courses are currently experiencing rapid development in emerging countries, many young people are voluntarily taking music courses in addition to their formal education. With the increasing number of music courses, the level of competition is getting tougher putting marketing issues upfront. Unfortunately, research on consumer experience in the setting of marketing music courses owned by private parties is still limited. This study focuses on the examination of positive electronic word-of-mouth (EWOM) behavior which supports the business performance from experience quality in music education institutions. To that end, this study applied the theory of perceived value and added a new proposed variable “inspirational value” to the combination of epistemic, emotional, sensorial, and social values. This quantitative survey study aimed to analyze the influences of perceived value on the experience and further the positive EWOM among music school students. Over two months, data was collected from 176 students of two music courses, to then be analyzed using the PLS-SEM method. As a new concept, inspirational value was determined as distinct from emotional value, where it more on appeals and driving factors arising from future orientation. The findings of the study emphasize the significance of sensory value in improving experience quality, followed by inspirational, epistemic, and emotional values. Furthermore, this study suggests that music courses should focus on creating inspiring, emotionally resonant experiences to foster positive EWOM that can support the marketing activity.
Navigating waiting situations at retail checkouts: associated emotional discomfort and its impact on shopping satisfaction
Authors: Pallikkara Vinish , Pinto Prakash , Thonse Hawaldar Iqbal
Published: July 2024

Waiting is a ubiquitous constituent of many purchase situations. This research investigates the emotional discomfort experienced by customers visiting retail stores in India throughout the checkout process, focusing on three distinct phases: before joining the queue, while waiting, and during billing. The study examines the circumstances and underlying factors that lead to emotional discomfort among customers while they wait at the checkout counter. A cross-sectional survey involving 385 participants was undertaken to evaluate perceptions related to the waiting experience. Structural Equation Modeling (SEM) was utilized to validate the conceptual model. The study uncovers diverse contributors to emotional discomfort during queueing, such as extended wait times, physical constraints, and perceived time prolongation, highlighting the multifaceted nature of this experience. Notably, the absence of a significant link between emotional discomfort and overall satisfaction implies that, while emotional discomfort is a factor, other elements such as pricing, promotions, and product offerings may exert a more significant influence on customers’ comprehensive satisfaction assessments. The research makes a significant contribution by shedding light on the challenges associated with prolonged waiting times at checkout counters in multi-brand food and grocery retailers. The results provide valuable insights into the emotional experiences of customers during waits and their impact on overall shopping satisfaction.
Digital economy: towards a conceptual research framework based on bibliometric and in-depth analyses
Authors: Savastano Marco , Spremić Mario , Stojcic Nebojsa , Gobbi Laura
Published: July 2024

The improvements in connectivity, artificial intelligence, and automation and their increasing penetration into all aspects of society and economy require informed decisions based on rigorous research on the determinants and outcomes of the digital economy. This context has promoted policy incentives dedicated to the digital transformation of business models and societal settings with a potential to disrupt existing markets and form a backbone of future development. The interest in digital economy and the research domains strongly connected to it has generated a wide array of terms that created confusion over its theoretical foundations. Several bibliometric analyses in recent years have attempted to map scientific findings and provide guidelines for future research in this area. However, such analyses draw their conclusions from algorithms that focus on attributes common to all studies without looking at their content. Our study combines bibliometric and in-depth content analyses to shed light on the definition, theoretical underpinnings, and state of the art of research on the digital economy. Our findings show that research in this domain is still in its infancy and the stated focus of studies on digital economy is often not reflected in their content. The study design allows us to make an original contribution by more precisely identifying gaps in the existing knowledge, outlining a detailed research agenda, and providing guidelines for future studies as well as informed policy decisions based on rigorous research on the determinants and outcomes of the digital economy.
Organizational strategies and tools of employee well-being as perceived by employees
Authors: Molnár Csilla , Csehné Papp Imola , Juhász Tímea
Published: July 2024

The purpose of the study was to examine the organizational strategy and tools of employee well-being, as perceived by employees. Although improving physical, mental, and social conditions of employees have positive impact on economic performance and competitiveness of organizations, little is known about how employee wellbeing appears in human resource management strategy and practices of organizations. Few research is available examining the adaptability of well-being strategy and tools from the perspective of employees as stakeholders. Therefore, the methodology of the current study was an exploratory sequential mixed method, with an embedded case study. Qualitative exploratory phase consisted of 27 semi-structured interviews with human resource management experts of Hungarian and international for-profit organizations. The results supported the definition for selection criteria of case study sampling and the design of a research tool for the quantitative phase. In the case study, interviews and quantitative research were conducted at the selected organization. The self-developed questionnaire included the Workplace PERMA Profile, reflecting the five pillars of well-being: Positive emotions, Engagement, Relationships, Meaning, and Accomplishment. The questionnaire has been filled out by 222 employees. The data integration results explored that the well-being is less characterized by a strategic approach, despite its importance defined by respondents. Employee perception analysis has led to the creation of employee well-being profiles, mapping organizational tools supporting employee satisfaction, and highlighting the inconsistences of organizational strategy and employee perceptions. The results could contribute to further studies and development of human resource management practices to improve employee well-being by directing the focus on its growing importance in economic and labor competitiveness.
Financial Performance Among Top10 Automotive Leaders in the EU: Essential Techniques to Investigate the Structure of Moments While Using the GMM with Dynamic Panel Data
Authors: Heryán Tomáš , Růčková Petra , Cerulli Giovanni
Published: July 2024

The automotive industry is widely considered to be crucial for the economy, as it reflects economic development in general. Despite interest in financial performance, few studies have considered paying attention to the ownership structure among stockholders. Hence, the study aims to find out how the degree of ownership concentration, measured through the independence indicator of the Bureau van Dijk, is reflected in the financial management of companies in the automotive industry among selected European countries. The generalized method of moments (GMM) technique is widely used while investigating panel data with a short estimating period, i.e. nine years annually in this case. However, this study reveals that, without deploying techniques, subsequently introduced a modified version of GMM estimators with panel data by providing an implementation using Stata statistical software. Otherwise, these particular econometric tools to analyze a dynamic panel can often give false significant estimates. Overall, liquidity seems to be significant in the case of firms with less concentrated ownership, whereas companies with a major owner are affected more by selected macroeconomic variables.
Transformational Leadership in Indonesian Diversified-Cultural SME Sector: An Investigation of the Settlement Criteria of Job Performance
Authors: Islam Shainima , Hari Pramono , Suliyanto Suliyanto , Setyanto Refius , Suroso Agus , Bahauddin Khalid Md. , Iftakhar Nayma
Published: July 2024

The main goals of the study were to examine how transformational leadership affected organizational citizenship behavior, worker productivity, and employee job satisfaction in Indonesian Small- and Medium-Sized Enterprise (SME) settings. The study used a quantitative technique and included 295 people as samples. Since Indonesia is a multi-cultural nation, responses were gathered from employees in multiple cities. Data was gathered via online and print surveys and was then analyzed using SPSS 23 and Smart PLS Software. The findings of this study point to a clear, positive, and substantial relationship between transformational leadership and worker job satisfaction, organizational citizenship behavior, and work performance. Additionally, to job satisfaction and organizational citizenship, it has been shown that employee job performance is somewhat mediated by employee behavior. This is the first paper in the setting of Indonesian SMEs that looks at the impact of transformational leadership on employee job performance after job satisfaction and organizational citizenship behavior.
Bio-Objectification and Biobanks
Authors: Karastergiou Anestis
Published: July 2024

Bio-objectification is presented in this paper along with a discussion about the boundaries of life in the biomedicalization paradigm, including the biobanking processes that are crucial to the emergence of bio-objects. Regarding methods and materials, STS methodology is implemented and the actor networks that play a significant role to bio-objectification are investigated. The discussion follows through these lens on how bio-objects are co-produced through a multitude of sociotechnical factors, reflecting on how the emergence of bio-objects and the concept of life that stems from them are socially constructed. The standardization of biobanks, population construction through a co-production of technosocial factors, the momentariness of bio-objectification, and the concept of bio-identification are presented and critically reflected upon. The main purpose is to combine a philosophical perspective with an STS one regarding the issue of shifting the boundaries of life through the concept of bio-objectification.
EFFECT OF VITEX TRIFOLIA ON ALLOXAN INDUCED DIABETIC RAT
Authors: Naikwad Harsha M. , Jeedi Neelakanth M.
Published: July 2024

The leaves of plant Vitex trifolia by tradition used to treat of diabetes and correlated complications. Plants V. trifolia and Vitex negundo belongs to the Verbenaceae family, have some similar phytoconstituents. Leaf extract of Vitex negundo proven for its anti-diabetic property. Diterpenoids present in fruits of V. trifolia, they have anti-diabetic property. Vitexilactone a phytoconstituents in V. trifolia has insulin sensitizing property. The present study aimed to investigate in vivo anti-diabetic activity of aqueous leaf extract of V. trifolia in alloxanized diabetic albino wistar rats. Diabetes induced in rats by injecting alloxan hydrate at dose 150 mg/kg body weight. Diabetic rats were treated with 100 and 200 mg/kg of aqueous extract of V. trifolia for 21 days. Anti-diabetic activity of extract assessed by measuring blood glucose by Trinder's method, insulin by enzyme-linked immunosorbent assay, lipid profile by colorimetric methods, total proteins by Biuret method and calcium measured by using ligand Arsenazo III in an aqueous alkaline medium. Aqueous extract of V. trifolia did not show significant changes of blood sugar level in normal rats. But extract significantly reduces blood sugar, total serum cholesterol, triglycerides levels but increases insulin, HDL-cholesterol, total proteins, and calcium in diabetic rats. Aqueous extract of V. trifolia showed significant anti-diabetic activity in alloxan-induced diabetic rats.
Efficacy of cow urine against chlorpyrifos induced toxicity in male wistar rats
Authors: Sharma Shelly , Mehra Sukanya , Chadha Pooja
Published: July 2024

The present study's objective was to study the mitigating potential of cow urine against the detrimental effects of chlorpyrifos (CPF) on different organs of rat. For this purpose antioxidant potential of cow urine was measured using FRAP (Ferric (Fe3+) reducing antioxidant power) assay. Further after LD50 determination, 1/25th i.e., 6.08 mg/kg b.wt, was selected and orally administered along with cow urine for 30 days to Wistar rats. After 30 days, blood, brain, liver and kidney tissues were collected and analysed for genotoxic (comet assay and chromosomal aberrations) and oxidative stress malondialdehyde(MDA), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) induced by CPF and ameliorative potential of cow urine. Noteworthy reduction in MDA and DNA damage and significant elevation GST, SOD, CAT and AChE activities reveals cow urine's alleviating effect.
Physico-Chemical Characterization of Diclofenac and Rasagiline Salts and its Relationship for Development of Sublingual Drug Delivery Systems
Authors: Malathi K , Ramana Murthy KV , Bhikshapathi D V R N , Kusum B
Published: July 2024

The current investigation’s objective was to study the physicochemical characterization of Diclofenac and Rasagiline salts and its relationship to the development of sublingual drug delivery systems. The selected salts of Diclofenac and Rasagiline were evaluated for crystallinity (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), solubility, in vitro dissolution and taste evaluation using e-tongue. The physicochemical characterization of Diclofenac salts demonstrated that potassium, epolamine and sodium salts of diclofenac showed similar results. Diclofenac free acid is not suitable for this route of administration as solubility was very less in sacrospinous fixation (SSF) media. Rasagiline mesylate was found more soluble and stable compared to hemitartrate salt. But being a low dose molecule, the impact of dose on the solubility or dissolution was considered negligible. Hence hemitartrate salt was selected as an alternate salt form for development of new sublingual administration.
Effectiveness Report of T-AYU-HM Premium and Onion Vaporisation on Corona Positive Sickle Cell Anemia Patients: A Case Study
Authors: Desai Atul , Desai Kavita , Desai Hemshree , Desai Chirag , Desai Rutvij
Published: July 2024

Corona virus increases mortality in patients with comorbidities like diabetes, hypertension, cancer, haemoglobin disorders. The entry of corona virus in sickle cell anemia patients demands a personalised medical management strategy because till date standard cure is not available for both the illnesses. Coronavirus infection causes damage to alveoli leading to an impaired oxygen exchange which might result in sickling of red blood corpuscles inducing various complications in patients of sickle cell anemia. Management of sickle cell patients infected with coronavirus has presented with a challenge in the current situation. A case report discuss here is of 2 sickle cell anemia patients with positive Covid-19 test who came to the clinic seeking treatment. With prior consent, we advised T-AYU-HM Premium and Onion vaporisation treatment for 21 days. We observed remarkable clinical improvement in patients’ haemoglobin, RBC, ESR and CRP profiles during followed up visit. The formulation’s impact on red blood corpuscles helps in preventing vaso-occlusive crisis and thereby the requirement of hospitalisation. The patients’ clinical recovery observed without any use of supportive medications commonly required in patients of sickle cell and coronavirus infection. This case report study provides information on the role of an alternative system of medicine in comorbidities in patients infected with coronavirus across the country. This therapeutic approach might open a door for an economical, safe and effective management options for sickle cell anemia patients infected with coronavirus in future.
Treatment of T-AYU-HM Premium and Onion steam vaporisation on possible re-infection or reactivation Covid-19 patient: A case study
Authors: Desai Atul , Desai Kavita , Desai Hemshree , Desai Chirag , Desai Rutvij
Published: July 2024

During the coronavirus pandemic, we are at stage where now observations are being recorded for possibilities of reinfection or reactivation in patients suffered from coronavirus. The heterogeneous natures of coronavirus infection producing complications in patients require a lot of critical care and monitoring. Post-discharge from hospitals, proper self-care and immune booster supplements have become a must. Patient's self-immunity, post-discharge medication non-adherence, casual approaches in self-care might become reasons for reinfection or reactivation of the virus in patients. Reporting case studies on reinfection or reactivation of coronavirus help enhance post-discharge management and safety guidelines. A 50-year-old male infected with coronavirus was admitted to the hospital, receiving treatment and discharge after 10 days. A 2 months later due to difficulty breathing, coughing, and fever he presented to our clinic. On examination and laboratory investigation, it was considered possible reinfection or reactivation of coronavirus in a patient. With proper discussion and prior consent we initiate treatment with T-AYU-HM premium and onion steam vaporization. During follow-up visit the observations like clinical and laboratory markers suggest remarkable improvement and alleviation of symptoms. During 2 months of treatment adherence, we also observed a marked decrease in lung opacities and no honeycombing in HRCT than in previous reports. This case report recommends the importance of an alternative medicine system restricted to the prophylactic purpose and has a role to play in post covid19 infected patients.
Studies on Nephroprotective effect of Methanolic and Aqueous Extract of Bark of Pithecellobium Dulce Roxb. in Rats.
Authors: Patil Ravindra , Yamgar Surekha
Published: July 2024

Kidney failure is a major problem of worldwide proportions. Kidney injury is a sudden loss of kidney function resulting in the accretion of waste materials such as creatinine and urea in the body. There are various agents that exert nephrotoxic effects through distinctive morbific defence mechanisms. Gentamicin, cisplatin and paracetamol are among common nephrotoxicity agents. In recent years, natural compounds are being expanded used in the treatment of kidney diseases. With this backdrop the study has been designed with the aim to studies on nephroprotective effect of methanolic and aqueous extract of bark of Pithecellobium Dulce Roxb. in rats. The methanolic and aqueous extracts of bark of P. Dulce was studied for nephroprotective effect in female Wistar rats against cisplatin, gentamicin and paracetamol induced nephrotoxicity, by estimating serum creatinine, blood urea and serum albumin levels. The dried bark of P. Dulce, Roxb (Leguminosae), contains tannins, flavonoids, triterpenoids, beta-sitosterol and saponin glycoside. Treatments with the methanolic and aqueous extracts could significantly (P < 0.001) reduce the elevated serum levels of creatinine, blood urea and serum albumin. P. Dulce bark extracts significantly prevented the physical, biochemical, histological and structural changes induced by cisplatin, gentamicin and paracetamol in the kidney. The present study reports with the exploration of P. Dulce bark extracts possessed implicit nephroprotective activity. This activity may be attributed due to the abundant phytoconstituents of the plant extracts.
ANALYTICAL STUDY AND IMPURITY PROFILING OF FIXED DOSES COMBINATION OF AMLODIPINE, HYDROCHLOROTHIAZIDE AND OLMESARTAN BY RP-HPLC AND UPLC
Authors: Desai Rajesh , Dhalani Jayesh , Koradia Suresh , Nariya Pankaj
Published: July 2024

A specific and sensitive reverse phase high pressure liquide chromatography (RP-HPLC) and ultra-performance liquide chromatography (UPLC) method for the determination of related substances for fixed-dose combination formulation of Amlodipine Besylate, Hydrochlorothiazide and Olmesartan Medoxomil was developed and validated. By using the gradient RP-HPLC method, a total of 25 known and unknown impurities related to Amlodipine Besylate, Hydrochlorothiazide and Olmesartan Medoxomil in combination formulation were separated and quantified in the linearity range of (0.2 to 3.0 μg/mL) for Amlodipine Besylate, (0.5 to 7.5 μg/mL) for Hydrochlorothiazide and (0.8 to 12.0 μg/mL) for Olmesartan Medoxomil with good squared correlation (>0.99). The recovery study was established from LOQ (0.05%) to 150% of the specification limit. A precision study was performed by spiking each known impurities at the specification level. In this study, two separate analytical methods RP-HPLC and UPLC have been developed, validated, and compare for the simultaneous quantification of Amlodipine Besylate, Hydrochlorothiazide, and Olmesartan Medoxomil tablets with their impurities. In these methods total of 28 peaks were separated in 70 minutes run time by HPLC method while in 45 minutes by UPLC method. Both the methods are developed with high selectivity, sensitivity, and robustness to separate 28 peaks in a single method. The proposed methods have a high degree of sensitivity and will provide fast and cost-effective quantitative control of Pharmaceutical formulations.
Formulation and Characterization of Edaravone Loaded Chitosan Nanoparticles for Treatment of Amyotrophic Lateral Sclerosis
Authors: PATIL GANESH B. , PATIL PRASHANT B. , SONAR AKSHAY P. , MAHAJAN MAHENDRA R. , PATIL JITENDRA H. , Patil Dilip A.
Published: July 2024

Owing to extensive hepatic first pass metabolism, Edaravone (EDV) shows low bioavailability (60 %) when administered orally, this leads to frequent administration of drug which may show toxicity. To overcome the above demerits of oral drug delivery of EDV, the present study is intended to prepare and evaluate EDV-loaded chitosan (CS) nanoparticles (EDV@CS-NPs) for the nose to brain delivery of EDV by ionic gelation technique. Chitosan, a biodegradable and mucoadhesive polymer, was selected for entrapment of EDV. The formulated, EDV@CS-NPs were characterized by UV-Visible spectroscopy, FT-IR spectroscopy, particle size analyser, zeta sizer, DSC, XRD, SEM, EDX, In vitro-Ex-vivo drug diffusion across goat nasal mucosa and Ex-vivo mucoadhesive study on goat nasal mucosa. The developed EDV@CS-NPs showed particle size of 200 ± 0.273 nm, polydispersity index (PDI) of 0.386, zeta potential -29 mV, an entrapment efficiency (EF) 97.52 ± 0.742%, and drug loading (DL) 22.72 ± 0.754%. The in vitro drug diffusion study displayed 91.80% of the drug release within 3 hours. The optimized batch (F2) showed the highest Ex-vivo drug diffusion up to 37.09 ± 0.24 % at the end of 3 hours. Further, DSC studies reveal absence of any incompatible interaction between EDV, and CS. SEM demonstrated a smooth morphology with an uneven shape. Elemental analysis reveals successful formulation of EDV@CS-NPs. Most importantly, better mucoadhesive strength of formulated nanoparticles was observed in Ex-vivo mucoadhesive study on goat nasal mucosa. Formulated EDV@CS-NPs may present a promising drug delivery system to treat many neurodegenerative illnesses like amyotrophic lateral sclerosis (ALS).
Physiology monitoring as a tool of effective venom research
Authors: Deshpande Adwait M. , Sastry K. Venkata , Bhise Satish B.
Published: July 2024

The commercial availability of the snake venom antiserum (SVA) significantly improved the chances of survival of snakebite victims and eventually, the research on phytotherapeutics for snake envenomation declined. India is the capital of snakebite deaths and needs safer molecules for treatment. Systematic investigations on phytotherapeutics are carried out on many animals, and most of them are sacrificed. The study evaluates the possibility of reducing the number of animals sacrificed in venom research by monitoring physiological parameters. Respiratory and electrocardiographic (ECG) monitoring was done in anaesthetized rats after administration of Naja naja (neurotoxic) and Daboia russelii (cytotoxic) venoms separately. Anti-venom action of Woodfordia fruticosa (Lythraceae) extract was evaluated against these venoms and SVA was used as the positive control. Physiological parameters were recorded with the LabChart® program and PowerLab® system coupled with 3 electrode ECG bioamplifier and a respiratory flow-head with a custom-designed mask. Sinus bradycardia was a major cardiac effect imparted by both venoms. The absence or inverted appearance of P-waves, PR prolongation, changes in QRS configuration and QT prolongation were induced by venoms. Significant respiratory depression was observed with N. naja venom and significant ECG changes were observed with D. russelii venom. W. fruticosa extract significantly prevented envenomed animals from developing sinus bradycardia (P < 0.001) for both venoms comparable to the action of SVA. W. fruticosa extract reversed severe respiratory depression induced by N. naja venom up to 70% and D. russelii venom up to 91%. Prolongation of PR and QT intervals induced by both the venoms was significantly reversed by W. fruticosa extract (p < 0.001). Development of RSR’ configuration in ECG and changes to cardiac axis induced by D. russelii venom were reversed by W. fruticosa. Possible mechanisms of venom toxicity and their reversal can be studied with such well-designed methods, and using sub-lethal venom doses would reduce animal sacrifices. Correlating prospective clinical case studies of snakebite victims with these controlled animal studies can generate base data for future venom research.
An Explorative Study of Oral Microemulsion-based Formulation for the Delivery of Cabazitaxel and Piperine
Authors: Rehan Uddin  , Jitendra Singh Rajawat
Published: July 2024

Cabazitaxel is the newest version of taxanes and is a promising drug for managing various cancers. Like other taxanes, this drug also poses a challenge of solubility and permeability, resulting in a poor oral bioavailability. The present study explores a scalable and economic nanoformulation in the microemulsion form for the oral delivery of cabazitaxel. The developed system substantially improved the drug’s anticancer activity on the breast cancer cell lines and in vivo cancer models. Piperine was also loaded in the microemulsion and it was observed that the incorporation of piperine resulted in an oral formulation with substantially higher oral bioavailability of CBZ vis-à-vis plain drug as well as the microemulsion. The findings infer that biocompatible microemulsions can enhance the oral bioavailability and anticancer activity of CBZ, which was further improved after incorporating piperine.
A Comparative Analysis of Cell Yield and Viability of Stromal Vascular Fraction from Lipoaspirates Harvested by Ultrasound and Suction Assisted Liposuction
Authors: Sharma Anuka , Sharma Vijay , Ginwalla Rustom , Ghorpade Parag R , Sakhalkar Ulka , Nadkarni Pratiksha , Vichare Kirti , Tripathi Sandeep
Published: July 2024

This study aims to compare two methodologies routinely used for lipoaspiration- a standard Suction Assisted Liposuction (SAL) and Ultra-sound Assisted Lipoaspiration (UAL) on yield, viability, surface markers and trilineage differentiation potential of isolated SVF from both these samples. Subcutaneous fat tissue was collected by UAL and SAL from the same patient (n=8). Stromal Vascular fraction was isolated by enzymatic digestion and the cell yield and viability were compared. Further, the surface markers from both UAL and SAL isolated SVF was assessed. The isolated SVF was used to isolate adipose-derived stem cells (ADSC's) and the surface markers and trilineage differentiation potential were compared. Statistical analysis: All statistical analysis and graph generation were performed using GraphPad Prism version 9.1.1. Results: The results indicate no significant difference in cell, viability and surface markers of SVF isolated from UAL and SAL. Further, we demonstrate that ADSC's isolated from the SVF of both UAL and SAL are capable of trilineage differentiation. There is no statistically significant difference in the yield and viability of SVF isolated from both UAL and SAL techniques. Since UAL can be used for larger volumes of lipoaspiration, we suggest that UAL would be a suitable method for large volume aspirations that do not affect cell yield and viability. Further expansion of these cells demonstrates that they are capable of trilineage differentiation, indicating their possible use in regenerative therapies.
Evaluation of Hepatoprotective Activity of Sonchus oleraceus L. Extract Against CCl4-induced Hepatic Damage In Wistar Rats
Authors: Akki Kusum S. , H C Rashmi , Akki Pratiksha
Published: July 2024

Sonchus oleraceus L. (Asteraceae) has a widespread world distribution and is also common in Brazil. It is a dietary and traditional medicinal plant in Chinese folk culture that can be cooked and eaten to treat inflammatory disease. The aim of the present study was to offer a novel perspective on the medicinal product originating from this species and to test its hepatoprotective activity. Petroleum ether, Ethyl actate and Methanol successive extracts obtained from the aerial parts were used for hepatoprotective study. Compounds that are evaluated for this activity were Flavonoids and Sesquiterpene glycosides, that are identified and quantified by Column chromatography and H1- NMR & Mass Spectra, respectively. Hepatoprotective activity was assessed in vitro, using various biochemical parameters i.e., SGPT, SGOT, SALP, bilirubin (total & direct) and isolated liver. Hepatoprotective activity was tested in rats with experimentally-induced hepatotoxicity by CCl4. The tested extract proved significant hepatoprotective capacity under in-vitro condition. Results of the in-vivo experiment showed that prominent hepatoprotective activity was shown by successive ethyl acetate and petroleum ether extracts. In this way, the present study offered a novel perspective on the medicinal uses of the species, proving significant amounts of Flavonoids and Sesquiterpene glycosides in the composition of the aerial parts, that has proved hepatoprotective activity.
Design and synthesis of new series 6, 7-disubstituted-7H-purine analogues induce G2/M cell cycle arrest and apoptosis in human breast cancer SKBR3 cells via selective EGFR/HER2 dual kinase inhibition
Authors: BAYYA CHANDRAPRAKASH , MANDA SARANGAPANI
Published: July 2024

A unique series of 6, 7-disubstituted 7H-purine analogues were designed with the goal of developing potential EGFR/HER2 dual tyrosine kinase inhibitors to treat human breast cancers. The compounds were rationally developed by replacing the central quinazoline core of lapatinib, an established drug that suppresses both EGFR and HER2, another essential member of this receptor family. Twelve compounds were synthesized by substituting hydrophilic '6-(3-chloro-4-[(substituted pyridin-3-yl) oxy]) anilino' group at 6th position and '(3E)-5-(dimethylamino) pent-3-en-2-ol' side chain at 7th position of purine scaffold which was thought to be considered critical for dual EGFR/HER2 inhibition. The chemical structures of the synthesized compounds were confirmed by 1H, 13C NMR, and HRMS analysis. All these compounds were evaluated for EGFR family tyrosine kinase (EGFR, HER2, HER3, and HER4) in-vitro inhibition. The results showed compound 8e as a potent dual EGFR/HER2 inhibitor with IC50 values of 0.021 ± 0.007 µM (EGFR) and 0.019 ± 0.009 µM (HER2), respectively, which were comparable to lapatinib (EGFR: 0.019 ± 0.007; HER2: 0.016 ± 0.003 µM), a positive control. EGFR/HER2 phosphorylation inhibition studies proved potential for 8e in dual kinase inhibition. In support of the dual inhibitory activity against both EGFR and HER2, compound 8e exhibited potent cytotoxic activity against BT-474 and SKBR3 cells, with IC50 values of 2.26 ± 0.37 µM (BT-474) and 2.17 ± 0.45 µM (SKBR3), which was comparable to the standard Lapatinib (EGFR: 2.63 ± 0.45 µM; HER2: 1.84 ± 0.39 µM). Additionally, compound 8e caused significant G2/M phase cell cycle arrest, resulting in a fivefold increase in cell number compared to control SKBR3 cells, and potentially induced apoptosis in 79% of these cells, which was comparable to that of lapatinib (83%). These new findings could provide an important basis for further developing compound 8e as a potent EGFR/HER2 dual kinase inhibitor.
Retrospective analysis of suspected adverse drug reactions reported in tertiary care hospital
Authors: JAIN SAURABH KUMAR , MISHRA AMUL , Goyal Vandana , Mathur SUNIL KUMAR
Published: July 2024

In the past pharmacovigilance happened 174 years back. In 1848, a little girl (Hannah Greener) died due to chloroform anesthetic before the elimination of an infected toenail. The reason for death was investigated, probably girl died of a lethal arrhythmia or pulmonary aspiration. There were 107 deaths occurred in the USA in 1937, for the reason that of the use of sulfanilamide elixir formulation prepared with the solvent used as a diethyl glycol. In 1938, In 1961, happened the thalidomide disaster. Dr. McBride investigated this disaster; he investigated that the 1.5% incidence of congenital malformations in babies had greater than before up to 20% in women who had taken thalidomide medicine for medical treatment during pregnancy. The WHO Programme for International Drug Monitoring (PIDM) was launched by WHO in 1968, after the thalidomide disaster major changed the system of pharmacovigilance globally, necessary to establish national systems for spontaneous ADR monitoring and reporting after consumer use. To conduct a retrospective observational study of adverse drug reactions for inpatient and outpatient in the different clinical departments in a tertiary care hospital. In the present study, a total of 749 adverse drug reaction reporting forms were reported out of which 990 ADRs occurred in 749 patients (inpatients n=502,67.02% and outpatients n=247,32.97%). The overall incidence of ADR was found0.0194%. At least one ADR was recorded in 0.25% of the admitted patients (IPD) and in 0.0067% of the outdoor patients (OPD). In this study male to female ratio was (60.0%) & (40.0%). A total of (82.62%) of ADRs were found nonserious as compared to serious (17.37%). The majority of the ADRs were reported as gastrointestinal system disorders, type-A (60.40%), probable (86.0%), mild (52.72%), preventable (definitely 67.87% and probably 24.24%). Predisposing factors were associated with age (24.14%), polypharmacy (68.38%), and multiple and intercurrent diseases (15.75%). The studies concluded that most adverse drug reactions involved gastrointestinal system disorders and are mild, preventable, and have a probable causality relationship with the suspected drug. ADR monitoring systems monitor unlisted ADRs and other drug-associated problems that have not been recorded during a clinical trial and prior to regulatory authorities to identify signals of new and suspected unexpected unknown ADRs.