bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature Measurement Timings and the Fever Detection Rate After Gastrointestinal Surgery: Retrospective Cross-Sectional Study (Preprint)
Authors: Wang Shiqi , Ji Gang , Feng Xiangying , Huang Luguang , Luo Jialin , Yu Pengfei , Zheng Jiyang , Yang Bin , Wang Xiangjie , Zhao Qingchuan
Published: July 2023

BACKGROUND

Postoperative fever frequently indicates surgical complications and is commonly used to evaluate the efficacy of interventions against surgical stress. However, the presence of circadian rhythms in body temperature may compromise the accurate detection of fever.

OBJECTIVE

This study aimed to investigate the detection rate of fever under intermittent measurement.

METHODS

We retrospectively reviewed the clinical records of patients who underwent nonemergency gastrointestinal surgery between November 2020 and April 2021. Patients’ temperature data were continuously collected every 4 seconds using a wireless axillary thermometer, and fever was defined as a temperature exceeding 38 °C within a day. To simulate intermittent measurement in clinical practice, the body temperature at each hour was selected from the continuously collected temperature dataset. Considering that temperatures are measured multiple times per day, all possible measurement plans using intermittent measurement were composed by combining 1-24 time points from the 24-hour daily cycle. Fever was clinically diagnosed based on the temperature readings at the selected time points per day. The fever detection rates for each plan, with varying measurement times, were listed and ranked.

RESULTS

Based on the temperature data continuously collected by the thermometer, fever occurred in 60 (40.8%) of the 147 included patients within 3 days after surgery. Of the measurement plans that included 1-24 measurements daily, the fever detection rates ranged from 3.3% (2/60) to 85% (51/60). The highest detection rates and corresponding timings for measurement plans with 1, 2, 3, and 4 measurements daily were 38.3% (23/60; at 8 PM), 56.7% (34/60; at 3 AM and 7 or 8 PM), 65% (39/60; at 3 AM, 8 PM, and 10 or 11 PM), and 70% (42/60; at 12 AM, 3 AM, 8 PM, and 11 PM), respectively; and the lowest detection rates were 3.3% (2/60), 6.7% (4/60), 6.7% (4/60), and 8.3% (5/60), respectively. Although fever within 3 days after surgery was not correlated with an increased incidence of postoperative complications (5/60, 8.3% vs 6/87, 6.9%; P=.76), it was correlated with a longer hospital stay (median 7, IQR 6-9 days vs median 6, IQR 5-7 days; P<.001).

CONCLUSIONS

The fever detection rate of the intermittent approach is determined by the timing and frequency of measurement. Measuring at randomly selected time points can miss many fever events after gastrointestinal surgery. However, we can improve the fever detection rate by optimizing the timing and frequency of measurement.
"Assessing the Impact of a Mobile Application on Cancer Risk Health Literacy: A Cross-Sectional Study Design" (Preprint)
Authors: Westerlinck Philippe , Maes Nathalie , Coucke Philippe
Published: July 2023

BACKGROUND

The "Cancer Risk Calculator” mobile application aims to inform patients about their personal risks of cancer and their risk factors impacting said risks. The present analysis examines the responses to a questionnaire submitted by oncology patients treated with radiotherapy or their family members.

OBJECTIVE

The primary objective was to determine the utility and impact of the app on the user's awareness and potential habit changes related to cancer risk. Further, the study aimed to discern any relationships between respondent characteristics and their questionnaire responses.

METHODS

A total of 162 patients were included in the analysis. Each patient's data comprised gender, date of birth, entry date, respondent type, type of cancer, and responses to 12 application-related questions. Statistical methods such as multiple regression models were employed to identify any effects of the respondent's characteristics on their responses. Statistical significance was set at p<0.05.

RESULTS

The patients aged between 21 and 87 years old (mean ± SD: 62.6 ± 10.8), with 64.2% being 60 or older. Notably, 96.3% of respondents were the patients themselves. The majority of cancer cases were breast cancers (60.5%). In response to the application questions, 67.1% of respondents found the application useful, and 63.4% reported learning something new. More than half (52.5%) indicated a willingness to change their habits based on the information provided. Factors such as breast cancer diagnosis (p=0.044) and age (p=0.049) influenced specific question responses.

CONCLUSIONS

The "Cancer Risk Calculator” app appears to have a significant utility in educating its users about cancer risk and potentially influencing habit change. However, some respondent characteristics, such as age and type of cancer, were found to impact their response to certain aspects of the application.
The state of cognitive functions and diffusion processes in the white matter of the cerebral hemispheres in healthy middle-aged and elderly people
Authors: Semonova O.V. , Myronyak L.A.
Published: July 2023

Background. The growing number of patients with dementia in aging population of developed countries significantly increases the relevance of differential diagnosis of cognitive impairment and age-associated cognitive disorders. The purpose of the study was to determine the criteria for physiological changes in cognitive status and diffusion processes in brain’s white matter in healthy middle-aged and elderly people. Material and ­methods. Thirty-nine healthy middle-aged (45–59 years, n = 19) and elderly patients (60–75 years, n = 20) were examined. Neuropsychological testing was performed using the following scales: Montreal Cognitive Assessment, Mini-Mental State Examination, Frontal Assessment Battery, Semantic Verbal Fluency (SVF) and Phonemic Verbal Fluency (PVF). Molecular diffusion in brain’s white matter was investigated by diffusion tensor imaging (Ingenia 3.0T, Philips). Results. Moderate positive correlations were found between age and the Frontal Assessment Battery score (rs = –0.443), memory (rs = –0.444) and executive function (rs = –0.542). Cognitive functions in middle-aged and elderly patients didn’t differ in cognitive domains of naming (II), memory (III), language (VIII), delayed reproduction (X), orientation (XI), semantic and phonemic verbal fluency. At the same time, differences in attention (IV, VI, AIS: p = 0.038; 0.043; < 0.001), language (VII, LIS: p < 0.001), abstraction (IX: p = 0.008) and visuospatial function (VIS: p = 0.002) were significant. Physiolo-gical age-related changes of molecular diffusion in the white matter of the cerebral hemispheres are characterized by a decrease of 21.0–37.0 % (p = 0.02 — < 0.001) in anisotropic and an increase of 16.3–29.5 % (p < 0.001) in free diffusion of water molecules in the conductive tracts and beyond them.
Headaches and facial pain syndromes
Authors: Zozulya I.S. , Volosovets A.O. , Volosovets T.M. , Trostyansky Y.V.
Published: July 2023

Headaches (cephalalgia) are one of the most frequent complaints with which patients visit a doctor and are the cause of 10–20 % of all visits. Special epidemiological studies have shown that in Germany headaches occur in 71 % of the population, in the United States headaches occur at least once a year in 99 % of young women, and 91 % of young men. Almost everyone has experienced a headache at least once in their life. Sometimes it is the leading one, and in other cases it is the only symptom. Headache is not a separate disease, but a symptom that can sometimes be significant and impairs quality of life. Headache is one of the 3 most common causes of temporary disability. Headaches are divided into 2 main groups: primary and secondary (symptomatic). Headache and facial pain syndromes are multifactorial. Pain occurs when receptors in the skin, subcutaneous tissue, tendons, blood vessels, periosteum, brain membranes, intracranial vessels, veins and venous sinuses are irritated. Cranial nerves, which include sensory fibers, are also sensitive to pain. Facial pain syndromes occur in case of nerve (trigeminal) damage, pathology of teeth, paranasal sinuses, nerves of the oral cavity. The intracranially located sensory nerves (V, VII, IX, X) and the first three cervical roots of the spinal cord are involved in the conduction of pain impulses from receptors to the brain. The purpose of our lecture is to highlight the pathogenetic mechanisms of headache and facial pain syndromes, their differential diagnosis, clinical picture, emergency care and treatment.
Analysis of the lipid plasma spectrum in patients with long-term consequences after traumatic brain injury
Authors: Lekomtseva Ye.
Published: July 2023

Background. Lipids are an integral part of the general metabolism involved in the processes of adaptation and regulation of many neuron functions, including cell membrane regulation. We have assessed the lipid plasma spectrum and peculiarities of lipid metabolism in patients with long-term consequences after traumatic brain injury (TBI). Materials and methods. Seventy-nine patients with long-term consequences after TBI (mean age ± standard deviation 43.27 ± 16.91 years) and thirty age-matched healthy controls (29.60 ± 4.73 years) were examined for total cholesterol, high-density lipoprotein cholesterol (Ch-HDL), triglycerides, low-density lipoprotein cholesterol (Ch-LDL) and very low-density lipoproteins plasma levels using spectrophotometry. Results. This study showed that in the general patient group, there was a significant increase in total cholesterol by 23 % compared to controls, together with Ch-LDL by 54 % associated with a decrease in Ch-HDL by 16.2 % (p < 0.05). Analysis of lipid plasma spectrum data depending on the injury type has revealed more severe changes in the lipid metabolism in patients with a history of brain contusion compared to the persons from group 1, however, without statistically significant differences between these groups (p > 0.05, t = 0.64). Our study showed that in the patients with long-term consequences after TBI, the most significant changes in lipid metabolism and lipid plasma spectrum were observed in a disease duration of more than 15 years (p < 0.05). Conclusions. The patients with long-term consequences after TBI showed higher levels of total cholesterol and Ch-LDL with a decrease in Ch-HDL indicating lipid metabolism disorders that might play an important role in the pathogenesis of these consequences and/or increasing risks of atherosclerosis in this cohort.
Study of Transverse and Longitudinal Crack Propagation in Human Bone Using the Finite Element Method with MATLAB
Authors: Assi Abdullah Dhayea
Published: July 2023

A finite element is a study that is capable of predicting crack initiation and simulating crack propagation of human bone. The material model is implemented in MATLAB finite element package, which allows extension to any geometry and any load configuration. The fracture mechanics parameters for transverse and longitudinal crack propagation in human bone are analyzed. A fracture toughness as well as stress and strain contour are generated and thoroughly evaluated. Discussion is given on how this knowledge needs to be extended to allow prediction of whole bone fracture from external loading to aid the design of protective systems.
Optimizing the Parameters of Hot-wire CNC Machine to Enhance the Cutting of Plastic Foam
Authors: Mohammed Israa Q. , Kadhum Ali H.
Published: July 2023

Hot-wire cutting is one of the important, non-traditional thermomechanical way to cut polymer, usually expanded foam and extruded foam, in low volume manufacturing. The study and analysis of Hot-Wire cutting parameters play an important role to enhance the quality and accuracy of the process and products. The effects on the surface have been investigated by using experimental tests designed according to the Taguchi orthogonal array (OA). In this study, four parameters with five levels for each parameter have been used: [temperature of wire (A) (100, 120, 130, 150, 160) °C], [diameter of wire (B) (0.3,0.4,0.5,0.7,0.8) mm], [velocity of cutting (C) (200, 300,400,500,600) mm/min], [and density of foam (D) (0.01,0.027,0.029,0.032,0.037) g/cm3]. Statistical software (MINITAB17) used to find the optimum conditions, which they are in Material Removal: 100 ˚C, 0.5 mm, 300mm/min, 0.032 g/cm3.
Adsorption of Heavy Metals from Aqueous Solution onto Sawdust Activated Carbon
Authors: Khalid Marah W. , Salman Sami D.
Published: July 2023

In this study, sawdust as a cheap method and abundant raw material was utilized to produce active carbon (SDAC). Physiochemical activation was utilized where potassium hydroxide   used as a chemical activating agent and carbon dioxide was used as a physical activating agent. Taguchi method of experimental design was used to find the optimum conditions of SDAC production. The produced SDAC was characterized using SEM to investigate surface morphology and BET to estimate the specific surface area. SDAC was used in aqueous lead ions adsorption. Adsorption process was modeled statistically and represented by an empirical model. The highest specific surface area of SDAC was 688.3 m2/gm. Langmuir and Freundlich isotherms were used to fit the adsorption process, where equilibrium data was best represented by Langmuir isotherm model.  Pseudo-first order and pseudo-second order equations were used to study adsorption kinetics, lead adsorption on SDAC fitted pseudo- second order more adequately. Best removal efficiency was found to be 99.63% with highest adsorption capacity of 19.92 mg/g.
Study the Effect of Residence Time Parameters on Thermal Cracking Extract Phase Lubricating Oil
Authors: Obyed Saleem Mohammed
Published: July 2023

This work studies with produce of light fuel fractions of gasoline, kerosene and gas oil from treatment of residual matter that will be obtained from the solvent extraction process as by product from refined lubricate to improve oil viscosity index in any petroleum refinery. The percentage of this byproduct is approximately 10% according to all feed (crude oil) in the petroleum refinery process. The objective of this research is to study the effect of the residence time parameter on the thermal cracking process of the byproduct feed at a constant temperature, (400 °C). The first step of this treatment is the thermal cracking of this byproduct material by a constructed batch reactor occupied with control device at a selective range of residence time (duration of the reaction) 30, 45, 60 and 75 minutes respectively at a constant temperature (400 °C). The conversion of this byproduct by thermal cracking process reaches 90% for all these residence times. The second step for this study is distillation this cracked extract liquid by atmospheric distillation device, for these various residence times according to the ASTM-D86 method, to obtain light fuel fractions of gasoline, kerosene and gas oil,in volume percentages  15, 75 and 0 for residence time 30, 5, 60 and 25, for residence time 45, 5, 10, 75, for residence time 60 and (10, 60 and 20) for residence time 75, which separates according to its boiling point. The major physical and chemical properties for feed (extract phase) and cracking extract liquid with its light fuel fractions were experimentally calculated and the results refer to acceptable properties compared with other standard property.
Electrodepositing of Multi-Layer Ni-Ag Coated by Copper Nanoparticles for Solar Absorber
Authors: Kadhim Mohammed J. , Sukkar Khalid A. , Abbas Ahmed S.
Published: July 2023

In this work, the effect of the addition of bright nickel plating and silver carried out by the electroplating method has been studied, on the coating of copper nanoparticles on the copper base metal via the process of thermal evaporation. The improvement of the solar absorber using CuNP in combination with the bright nickel and silver was obtained to be better than copper nanoparticles individually. A bright nickel enhanced the absorbed thermal stability. Also, other optical properties, absorptions, and emissivity slightly decreased from (93% to 87%), while the existence of silver had a slight impact on absorption of about (86.50%). On the other hand, thermal conductivity was evaluated using hot disk analyzer. The results showed a good improvement obtained by copper nanoparticles of about (89%) deposited on the copper substrate, while it decreased with 18.8% in the presence of bright nickel combined with copper nanoparticles. The other characteristics, like structure and phases of coating layers, were achieved using X-ray diffraction. Topographic maps were obtained using an Atomic Force Microscope and Scanning Electron Microscope.
Fuzzy Analytical Hierarchy Process for Embedded Risk Reduction in Selecting the Right Planning Decision
Authors: Abdul-Razaq Faten F. , Al-Zubaidi Sawsan S. , Kassam AllaEldin H.
Published: July 2023

The aim of this work is to provide an efficient selection technique as a part of planning process to guide the decision makers to decide the preferences of one supplier over another for purchasing lab instruments in education domain. Fuzzy Analytical Hierarchy Process has used as a multi-criteria decision process, as an industrial engineering tool with certain emphasis on the qualitative aspects required to the decision makers. While the concept of degree of possibility for each criterion is used to reach its relative weights, a specific methodology created to reach the final objective decision of supplier selection. A questionnaire form was developed and distributed to five universities located in Baghdad province with a total number of 100 questionnaires. The response was very adequate. Three main criteria are adopted- supplier, instruments and service performance grade. Moreover, there are sixteen sub-criteria for evaluating three potential suppliers. The final decision is reached with almost risk-free as it relates to the qualitative aspects of experts. The conclusion reached is that local supplier has a large priority weight. Microsoft Excel is used to achieve the sequential calculations for Fuzzy AHP.
Wear Behavior Performance of Polymeric Matrix Composites Using Taguchi Experiments
Authors: Mohammed Reem Alaa , Abdul Raheem Ruaa Haitham , Khazaal Shaymaa Hasan
Published: July 2023

This research estimates the effect of independent factors like filler  (3%, 6%, 9%, 11% weight fraction), normal load (5N, 10N, 15N), and time sliding (5,7 , 9 minutes) on wear behavior of unsaturated polyester resin reinforced with jute fiber and waste eggshell and, rice husk powder composites by utilizing a statistical approach. The specimens polymeric composite prepared from resin unsaturated polyester filled with (4% weight fraction) jute fiber, and (3%, 6%, 9%, 11% weight fraction) eggshell, and rice husk by utilizing (hand lay-up) molding. Dry sliding wear experiments were carried utilizing a standard (pin on disc test setup) following a well designed empirical schedule that depends on Taguchi’s experimental design L9 (MINITAB 16) with the determined (S/N) ratio and analysis of different (ANOVA) optimal factors to minimize the wear rate. Results exhibit that the presence the of 11% weight fraction eggshell and rice husk powder with 4% weight fraction jute fiber improves the wear resistance of unsaturated polyester composite materials significantly. The filler content was observed to be the major significant factor influencing the wear rate followed by time sliding and normal load. From the results of the S/N ratio, the optimization of wear parameters is obtained at specimens A3, A6, A7, and A10 as to minimize wear rate.
An Experimental Study on Electrochemical Grinding Parameters on Hardness and Material Removal Rate for Stainless Steel 316
Authors: Ghadban Abdullah J. , Ibrahim Abbas F.
Published: July 2023

Electrochemical Grinding (ECG) process is a mechanically assisted electrochemical process for material processing. The process is able to successfully machine electrically conducting harder materials at faster rate with improved surface finish and dimensional control. This research studies the effect of applied current, electrolyte concentration, spindle speed and the gap between workpiece and tool on hardness and material removal rate during electrochemical grinding for stainless steel 316. The characteristic features of the electrochemical grinding process are explored through Taguchi-design-based experimental studies. The better hardness can be obtained at 10 A of the current, 150 g/l of the electrolyte concentration, 0.3 mm of gap and spindle speed of 180 rpm, and the maximum material removal rate can be obtained at 40 A of the current, 250 g/l of the concentration, 0.2 mm of a gap and 180 rpm of spindle speed.
Optimization the Effect of Electrode Material Change on EDM Process Performance Using Taguchi Method
Authors: Aghdeab Shukry H. , Abdulameer Ahmed Ghazi , Abdulameer Lujain Hussein , Mohammed Atheer Rasim
Published: July 2023

Electrical Discharge Machining (EDM) is a widespread Nontraditional Machining (NTM) processes for manufacturing of a complicated geometry or very hard metals parts that are difficult to machine by traditional machining operations. Electrical discharge machining is a material removal (MR) process characterized by using electrical discharge erosion. This paper discusses the optimal parameters of EDM on high-speed steel (HSS) AISI M2 as a workpiece using copper and brass as an electrode. The input parameters used for experimental work are current (10, 24 and 42 A), pulse on time (100, 150 and 200 µs), and pulse off time (4, 12 and 25 µs) that have effect on the material removal rate (MRR), electrode wear rate (EWR) and wear ratio (WR). A Minitab software environment was used to adopt Taguchi method to analyze the effect of input on output parameters of EDM. The results of the present work showed that the best of MRR in copper and brass electrodes with (current 42 A, pulse on time 100 µs and pulse off time 25 µs) are (84.355×10-3 g/min) and (43.243×10-3 g/min) respectively, and the MRR predicted by Taguchi are (86.1751×10-3 g/min) in copper electrode by using the parameters with (current 10 A, pulse on time 200 µs and pulse off time 25 µs) and (43.2979×10-3 g/min) in brass electrode at current 42 A, pulse on time 100 µs, and pulse off time 25 µs. The lowest EWR occurs with a value of (1.4510×10-3 g/min) with (current 10 A, pulse on time 100 µs, pulse off time 4 µs) variables when using a copper electrode. The highest WR (2.602508) was found for the brass electrode with (current 24 A, pulse on time 200 µs, pulse off time 4 µs) variables.
Selection of OptimumRadiant Barrier System (RBS) Location in Double Skin Ventilated Roofs
Authors: Ghanim Mohannad R. , Ahmed Sabah T.
Published: July 2023

Double skin ventilated roof is one of the important passive cooling techniques that aims to reduce solar heat gain through roofs by reducing both the conduction and convection heat transfer from the roof to the ceiling of buildings. On the other hand, radiant barrier system (RBS) is very powerful in blocking the radiation heat transfer between the two skins. In this research,the effect of placing a thin layer of aluminium foil at different locations on the thermal insulation performance of a double skin ventilated roof model is investigated experimentally and the optimum location that transmits less heat flux from the lower skinis specified.The model is made of two parallel inclined galvanized steel plates. Galvanized steel has been used in the roof construction of industrial buildings and storehouses in Iraq.The radiant barrierisapplied alternately, on the outer surface of the upper skin, on the inner surface of the upper skin, suspended in the airgap between the skins, and on the inner surface of the lower skin.These casesareconsidered as Model A, Model B, Model C, and Model D, respectively. It is found that the radiant barrier can block up to78% of the heat in Model A, 71% in Model B, 94% in Model C, and 91% in Model D as compared with the Basic Model.Since the radiant barrierin both Model C and Model D blocks almost the same amount of heat, the location of the radiant barrierin Model D is chosen as the optimumradiant barrierlocation because this model is more practical.
Inverse Kinematics Analysis and Simulation of a 5 DOF Robotic Arm using MATLAB
Authors: Abaas Tahseen F. , Khleif Ali A. , Abbood Mohanad Q.
Published: July 2023

Kinematics is the mechanics branch which dealswith the movement of the bodies without taking the force into account. In robots, the forward kinematics and inverse kinematics are important in determining the position and orientation of the end-effector to perform multi-tasks. This paper presented the inverse kinematics analysis for a 5 DOF robotic arm using the robotics toolbox of MATLAB and the Denavit-Hartenberg (D-H) parameters were used to represent the links and joints of the robotic arm. A geometric approach was used in the inverse kinematics solution to determine the joints angles of the robotic arm and the path of the robotic arm was divided into successive lines to accomplish the required tasks of the robotic arm.Therefore, this method can be adopted for engineering applications. MATLAB (Graphical User Interface) program was used to simulate the movement of the robotic arm in 3D. Also, MATLAB (GUI) has been used to view the position of each joint.The results showed thatthe maximum error in the x, y, and z coordinates of the end-effector were 0.0251 %, 0.0239 %, and 0.1085 % respectively.
THE EFFECT OF ADDITION 5% PROPOLIS NANOPARTICLES IN EPOXY RESIN AND BIOCERAMIC SEALERS ON THE GROWTH OF ENTEROCOCCUS FAECALIS ATCC 29212 AND THE DENTINAL TUBULAR PENETRATION: IN VITRO
Authors: WAHYUNI NELMI , YANTI NEVI , ABIDIN TRIMURNI , PRASETIA WIDI , SURYANTO DWI
Published: July 2023

Objective: The goal of endodontic treatment is to eliminate bacteria and their products from the root canal. Bacteria are the main etiological factors of pulpal and periapical diseases. Chemomechanical preparation and administration of root canal medicaments cannot completely eliminate bacteria in the root canal system, especially Enterococcus faecalis, which have high resistancy, therefore, an ideal obturation material is required. Adequate root canal filling quality affects the success of endodontic treatment. The aim of this study was to observe the effect of addition 5% propolis nanoparticles to the commercial epoxy resin and the bioceramic sealer on the growth of E. faecalis ATCC 29212 and the dentinal tubular penetration. Methods: Thirty-five tooth samples were randomly divided into 5 groups. Root canal preparation was carried out with the same working length of 14 mm by cutting the tooth at the Cementoenamel Junction (CEJ); sample was inoculated with E. faecalis ATCC 29212 for 48 h. Obturation used four types of sealer, Group I (epoxy resin with 5% propolis nanoparticles), Group II (bioceramic with 5% propolis nanoparticles), Group III (bioceramic) and Group IV (epoxy resin). Data were analyzed using the Kruskal wallis test with a significant level of p<0.05. Results: In the bacterial growth test, there was a significant difference in the number of bacterial colonies between the epoxy resin groups with 5% propolis nanoparticles, bioceramic with 5% of propolis nanoparticles, bioceramic and epoxy resin (p = 0.000<0.05). In the dentinal tubular penetration there was a significant difference between epoxy resin with 5% of propolis nanoparticles, bioceramic sealer with 5% propolis nanoparticles, bioceramic, and epoxy resin (p = 0.001<0.05). Conclusion: The addition of 5% propolis nanoparticles to commercial bioceramic and epoxy resin sealers can eliminate E. faecalis bacteria in the root canals and increase dentinal tubular penetration. Bioceramic sealer has a higher antibacterial effect and dentinal tubular penetration compared to epoxy resin.
NANOTHERANOSTICS IN CARDIOVASCULAR DISEASES: A NOVEL TOOL
Authors: NIZAM IMRANKHAN , AASAITHAMBI KALAISELVI , SRINIVASAN ASHA , CHIDAMBARAM SARVANA BABU , KRISHNAMURTHY PRAVEEN THAGGIKUPPE , MADHUNAPANTULA SUBBA RAO V. , THIMMULAPPA RAJESH , KUPPUSAMY GOWTHAMARAJAN
Published: July 2023

The leading cause of mortality worldwide is cardiovascular disease (CVD). Myocardial infarction, ischemic heart disease, ischemic injury, damaged arteries, thrombosis, and atherosclerosis are among the heart and blood vessel issues referred to as CVD. The most prevalent cause of CVD is atherosclerosis, an inflammatory disease of the arterial blood wall. Because of the complexity of CVD, pathophysiology, diagnosis, and therapy remain vital issues. The inadequacies of current treatment and diagnostic methods have given rise to theranostic nanomaterials. "Theranostic nanomaterials" describes a chemical with dual uses, including therapeutic and diagnostic applications. Theranostic nanoparticle imaging contrast can be advantageous for computed tomography (C. T.), positron emission tomography (P. E. T.), and magnetic resonance imaging (M. R. I.).
Additionally, they can cure CVD by employing medication delivery by nanoparticles or photothermal ablation. This study reviews the prevalence of the most recent developments in theranostic nanomaterials for identifying and treating CVD following the order in which diseases advance. Theranostics techniques for CVD detection include M. R. I., CT, near-infrared spectroscopy (NIR), and fluorescence. There have also been discussions of other theranostic nanoparticle-based CVD therapeutic methods.
DESIGN, OPTIMIZATION, AND CHARACTERIZATION OF A NOVEL AMORPHOUS SOLID DISPERSION FORMULATION FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF TICAGRELOR
Authors: SRIVASTAVA ABHISHEK , KHAN MOHAMMAD AHMAD , BEDI SIMRATA , BHANDARI UMA
Published: July 2023

Objective: The study aims to enhance the solubility and dissolution of ticagrelor by formulating an amorphous solid dispersion using the hot melt extrusion technique.
Methods: Solubility of ticagrelor is very limited in water and buffers of pH 1.2 to 6.8, which is one of the prime reasons for its low oral bioavailability. Amorphous solid dispersions were prepared using the Hot Melt Extrusion technique using different polymers, plasticizers, and surfactants. The formulation is optimized based on the level of polymer in the formulation. The final formulation of Ticagrelor Amorphous Solid Dispersion is made with a drug-polymer ratio of 1:3, keeping the plasticizer level at 10% of the polymer along with a surfactant Sodium Lauryl Sulfate.
Results: The formulation showed an increase in solubility of 193.95-times in water, 50.71-times in 0.1 N HCl, 332.74-times in pH 4.5 acetate buffer, and 85.20-times in pH 6.8 phosphate buffer as compared to the pure drug. The drug release of the final formulation was found to be 70.0±4.4%, 55.4±1.1%, 35.5±2.1%, and 30.0±0.8% at 90 min, while the reference product showed a release of 9.4±1.1%, 20.7±0.5%, 8.4±0.3%, and 7.8±0.2% at 90 min in water, 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 Phosphate Buffer respectively. The drug release of the final formulation was found to be 99.1±3.8% at 60 min in 0.2% w/v Polysorbate-80 in water.
Conclusion: In the present study, the amorphous solid dispersion of the poorly-soluble drug ticagrelor was successfully prepared. The polymer, Plasdone S630, is considered the most suitable with ticagrelor for formulating amorphous solid dispersion using Hot Melt Extrusion technology to increase the solubility and dissolution of the drug.
DRUG IN ADHESIVE TRANSDERMAL SYSTEM OF FUROSEMIDE: IN VITRO IN VIVO EVALUATION
Authors: YALLAMALLI INDIRA MUZIB , MANNAM REVATHI , YELLAMELLI RAMJIAMBEDKAR
Published: July 2023

Objective: The objective of the present work aims to check the effect of penetration enhancers on release kinetics in a novel drug in the adhesive transdermal system of furosemide. Methods: The adhesive systems were evaluated for pharmacotechnical properties and in vitro permeation of the drug through the excised rat epidermis. Among the DURO-TAKs screened for in vitro permeation studies. The results were quantified using RP-HPLC. The optimized drug in the adhesive system was subjected to in vivo kinetic studies using New Zealand male rabbits. The adhesive systems were further evaluated for tack properties and skin irritation studies. Results: DURO-TAK 2510 demonstrated a best permeation profile than DURO-TAK 2852. A combination of penetration enhancers was proved to more be efficient than alone, in the case of F9 (IPM: PG 7.5:2.5) maximum permeation of the drug (314.45±5.97 µg/cm2) was observed by the end of the study with a flux of 9.2052±0.33 μg/cm2/h. The optimized drug in the adhesive system was subjected to in vivo kinetic studies using New Zealand male rabbits. The studies confirmed that controlled release of the drug for a prolonged duration with an extended AUC and MRT decreased Cmax in adhesive systems compared to the oral route, which can provide a promising pharmacological effect the in the DIA system compared to the oral route. Conclusion: The findings in the present study confirmed that drugs in adhesive systems can provide promising results and can enhance both bioavailability and patient compliance with a combination of penetration enhancers in the development of DIA systems.
BOX-BEHNKEN DESIGN-BASED DEVELOPMENT AND CHARACTERIZATION OF POLYMERIC FREEZE-DRIED NANOPARTICLES OF ISRADIPINE FOR IMPROVED ORAL BIOAVAILABILITY
Authors: GHOSE DEBASHISH , PATRA CHINAM NIRANJAN , SWAIN SURYAKANTA , SRUTI JAMMULA
Published: July 2023

Objective: This study aimed to develop and optimize isradipine-loaded polymeric freeze-dried nanoparticles prepared by solvent shifting method with the help of the experiment design for improving oral drug bioavailability and minimizing dosing intervals.
Methods: Isradipine is a potent anti-hypertensive drug that is matrixed in polymeric freeze-dried nanoparticles using solvent shifting. In this work, a 3-factor, 3-level box-Behnken design was used to optimize the process parameters like a drug: PLA concentration (A), poloxamer 407 concentration (B), and stirring speed (C). In addition, responses were measured as dependent variables such as percentage drug release, particle size (nm), Zeta potential (mV), and % entrapment efficiency.
Results: Mathematical equations and response surface plots were used to relate the dependent and independent variables. The optimization model exhibited 97.36 % drug release, 153.14 nm particle size,-25.9 mV Zeta potential, and 78.25% entrapment efficiency, respectively. The observed responses were in close agreement with the predicted values of the optimized process. Fourier transform infrared spectroscopy, morphological studies, and in vitro drug release studies characterized the prepared polymeric nanoparticles.
Conclusion: The improved freeze-dried polymeric nanoparticle samples exhibited an in vitro drug release rate of more than 90% at 24h. Based on in vivo pharmacokinetic parameters, the isradipine-loaded polymeric nanoparticles show better bioavailability than pure drug's suspension form.
BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF MARALIXIBAT IN RAT PLASMA BY LC-MS/MS DETECTION AND ITS APPLICATION TO A PHARMACOKINETIC STUDY
Authors: NIMMAKAYALA MADHUSUDHANA REDDY , KOLLI DEEPTI , DURGA BHAVANI PASUPULETI NAVEENA
Published: July 2023

Objective: To quantify maralixibat in rat plasma utilizing liquid-liquid extraction (LLE) approach, a practical, efficient, and accurate LC-MS/MS approach was devised.
Methods: As an internal standard (IS), Elobixibat was adopted. Utilizing an Agilent eclipse C18, 150 mm x 4.6 mm, 3.5 µm column, the drug separation was accomplished using an isocratic mobile phase entailing acetonitrile (ACN) and buffer (1 ml Tri fluoro acetic acid into 1liter water and stir well. Filtered through 0.22µ membrane filter paper) composition of 70:30 (v/v), dispensed at 1.0 ml/min.
Results: Multiple reaction monitoring (MRM) positive mode allowed for the simultaneous detection of maralixibat and elobixibat exhibiting proton adducts around m/z 676.0278-290.3625 and m/z 696.8541-480.6328, correspondingly. The correlation coefficient (r2) of the approach was ≥0.99977 across a linearity concentration spanning between 5.00–100.00 ng/ml. This technique achieved intra-day accuracy and precision between 99.31-100.93% and 0.22-6.55%, correspondingly. Across 3 freeze-thaw sessions, bench top testings, and postoperative stability investigations, maralixibat was shown to be stable.
Conclusion: Through intravenous injection, this approach was effectively utilized in rats for studying the drug's pharmacokinetics.
QBD APPROACH FOR THE DEVELOPMENT OF CAPSAICIN-LOADED GLYCYRRHETINIC ACID CONJUGATED STEARIC ACID GRAFTED CHITOSAN POLYMERIC MICELLES FOR ACTIVE HEPATIC TARGETING
Authors: K. MAYURI , S. SUNITHA
Published: July 2023

Objective: Capsaicin (CAP) is a naturally occurring alkaloid forecasted in the treatment of Alcoholic Hepatitis (AH), but least studied due to its hydrophobicity, low bioavailability, and less target-specific release. Hence, the present study aimed to synthesize glycyrrhetinic acid conjugated stearic acid grafted chitosan (GA-CS-g-SA) and prepare CAP-loaded GA-CS-g-SA micelles.
Methods: Quality by design (QbD) approach in coordination with "Box-Behnken Designs (BBD)" was used to optimize the process parameters. GA-CS-g-SA was synthesized and characterized for its physic-chemical.
Results: The "Proton Nuclear Magnetic Resonance (1H NMR)" spectrum depicted a strong signal at d=1.0 ppm and endorsed to-CH2 group of SA and d=3.5-3.65 ppm depicting GA, which confirms the formation of GA-CS-g-SA. Critical micellar concentration (CMC) was found to be 13.45±1.72 µg/ml and amino groups substitute degree (SD %) was 10.12%±1.09%, indicating successful linkage of GA and SA on CS. The prominent peaks of CAP (0.9 and 1.31 ppm) in 1H NMR spectra disappeared, indicating drug loading in the micellar core. Micelle's normal particle range was 167.54 nm, and encapsulation efficiency was 67.85%. The CAP-GA-CS-g-SA was found to be biocompatible following the hemolysis test. In vitro release pattern showed 78.68±3.12% in 24h, indicating the slower release of CAP from micelle, whereas 99.48±2.56% was released from non-micellar formulations in 6 h. CAP release from drug-loaded micelles showed a biphasic model with an early burst release in four hours, following a slower and sustained release pattern till 24h.
Conclusion: CAP-GA-CS-g-SA micelle is a hopeful advancement to progress bioavailability and controlled release of highly hydrophobic CAP. Further in vivo studies would be evident for targeting hepatocytes and treating AH using CAP-GA-CS-g-SA.
LIQUID CHROMATOGRAPHY DEPENDENT STABILITY INDICATING METHODOLOGY: DEVELOPMENT AND AUTHENTICATION FOR FORMULATIONS OF CAPSULE TYPE CONTAINING TEGAFUR, GIMERACIL, AND OTERACIL
Authors: HARITHA KUMARI MAILAMURI , KHANDAPU BALA MURALI KRISHNA , RAJU RUDRARAJU RAMESH
Published: July 2023

Objective: This investigation entitles the development and authentication of a rapid, selective and explicit RP-HPLC technique to assay tegafur (TGR), gimeracil (GMR), and oteracil (OTR) simultaneously in bulk and formulations of capsule type.
Methods: The separation, detection and assessment of TGR, GMR and OTR were achieved using a C18 Agilent Zorbax (25 cm; 4.6 mm; 5 µm particle dimension) reverse phase column. The acetonitrile (40% by volume) and 0.1% triethylamine in distilled water (pH 2.5, 60% by volume) was utilized as mobile phase. The validation of the method and degradation study was performed as per the strategy given by ICH.
Results: The retention periods in Agilent Zorbax column for OTR, TGR, and GMR were 2.458 min, 7.236 min and 8.629 min, respectively. Linearity was seen in the concentration series of 5.0-30.0 µg/ml (TGR), 1.45-8.70 µg/ml (GMR), and 3.95-23.70 µg/ml (OTR). The regression coefficient was greater than 0.999. The LOQ values were 0.606 µg/ml (TGR), 0.175 µg/ml (GMR), and 0.478 µg/ml (OTR). The percent comparative standard deviation (exactness) values were bestowed to be 0.243%-0.676%, 0.293%-1.894% and 0.269%-0.615% for TGR, GMR and OTR, respectively. The percent recoveries (accuracy) were in the range of 100.044%-100.493 for TGR, 99.730%-100.335% for GMR and 100.064%-100.543% for OTR.
Conclusion: The research results of the degradation investigation proved the technique's specificity as well as stability indicating feature. The process could be used for routine evaluation of OTR, TGR, and GMR in formulations of capsule type.
MOLECULAR DOCKING AND INVESTIGATION OF BOSWELLIA SERRATA PHYTOCOMPOUNDS AS CANCER THERAPEUTICS TO TARGET GROWTH FACTOR RECEPTORS: AN IN SILICO APPROACH
Authors: B. R. JAYASURYA , J. S. SWATHY , D. SUSHA , SHARMA SAMEER
Published: July 2023

Objective: Boswellia serrata is a plant with a long history of use in traditional medicine, particularly for its anti-inflammatory and anti-cancer properties. Growth factors and their receptors are significant components in the initiation and progression of malignancy, and aberrant functioning of these pathways can result in unrestrained cell division and expansion.
Methods: In this study, an in silico approach was used to explore the potential of Boswellia serrata phytochemicals as cancer therapeutics to target growth factor receptors. The virtual screening involved molecular docking simulations (PyRx) to predict the binding affinity between the phytochemicals and the receptors.
Results: The seventy-four phytocompounds identified from Boswellia serrata were preliminarily screened based on their binding towards growth factor receptors. The ligands demonstrated better binding with the GFR targets, and the binding score less than-7 kcal/mol was considered for further investigation results demonstrated that Alpha-boswellic exhibited strong binding affinity to the receptors, suggesting their potential as targeted cancer therapies. This study provides a foundation for future in vitro and in vivo experiments to validate the efficacy of these phytochemicals as cancer treatments.
Conclusion: The results suggest that Boswellic acid derivatives from Boswellia serrata could be a promising source of new cancer therapies.
ENHANCED SOLUBILITY AND DISSOLUTION BY SURFACE-MODIFIED SOLID DISPERSION OF ALECTINIB HYDROCHLORIDE
Authors: SAHA SUMIT KUMAR , JOSHI AMITA , SINGH ROMI , DUBEY KIRAN
Published: July 2023

Objective: Alectinib hydrochloride (AH), a poorly soluble drug, exhibits low solubility thereby very low bioavailability. The present study aims to develop and optimize surface-modified solid dispersion of AH (AH-SMSD) with enhanced solubility and dissolution using Soluplus® (SOL) and Gelucire 44/14 (GEL) as a polymer and surfactant, respectively.
Methods: Design of Experiments (DoE) was implemented to optimize the weight ratio of SOL (X1), and GEL (X2), keeping the drug weight constant to maximize the solubility (Y1) and dissolution (Y2). The optimized solid dispersion was subjected to solubility and dissolution in bio-relevant media and characterized using differential scanning calorimetry (DSC), Powder X-ray diffraction (pXRD), Fourier-transform infrared (FTIR), and scanning electron microscopy (SEM).
Results: A statistically significant model is obtained for solubility and dissolution through DoE. Formulation (F9) containing AH: SOL: GEL in weight ratios 1:5:5 showed a 547-fold increase in solubility. This solubility enhancement further translated into dissolution improvement with drug release of >80% in 15 min. The optimized formulation also showed improved solubility and dissolution in fasted-state bio-relevant media. DSC and pXRD showed a change in the crystallinity pattern of the drug. FTIR showed the existence of weak intermolecular interactions. Morphological evaluation through SEM demonstrated that the drug particles were dispersed to a hydrophilic carrier matrix, thus, transforming the hydrophobic drug into a hydrophilic form.
Conclusion: AH-SMSD with enhanced solubility and dissolution was successfully developed. The optimized formulation also showed improvement in the bio-relevant media and therefore has the potential to improve in vivo oral bioavailability (however, needs to be experimentally explored).
FORMULATION AND EVALUATION OF DISPERSIBLE TABLETS OF FLAVONOID PGAL ISOLATED FROM SARACA ASOCA LEAVES
Authors: SHRIVASTAV SONIKA , RATHORE KAMAL SINGH , PRASAD NEELKANT
Published: July 2023

Objective: The study aimed to design and evaluate a dispersible tablet of flavonoid PGAL isolated from Saraca asoca leaves for antidepressant activity.
Methods: The phytoconstituent was isolated from a methanolic extract of Saraca asoca leaves using silica gel column (60-120 mesh) chromatography. The dispersible tablets were prepared by direct compression and then evaluated for various tablet evaluation parameters and antidepressant activity, performing Tail Suspension Test (TST), Forced Swim Test (FST), Locomotion activity, Brain glutamate level and brain nitrite level.
Results: Hardness of 2.85±0.13 kg/cm2 to 3.25±0.15 kg/cm2 and friability of 0.35% to 0.48% indicate that the prepared tablets were mechanically sound. Test for weight variation was also within tolerance limits, i.e. 2.04% to 4.25% difference in weight of the tablet from the average weight of 10 tablets. The tablets also passed the test for drug content uniformity, 97.35% to 100.35%, i.e. always within the prescribed limits of 95% to 105%. Disintegration time, 2 min to 2.75 min, and dispersion time, 3.25 min to 3.75 min, were also exemplary. The antidepressant activity was displayed by the optimized formulation as indicated by a significant decrease (p<0.05) in immobility time in TST as well as FST; a significant decrease (p<0.05) in the level of brain tissue glutamate as well as nitrite in PGAL formulation treated mice when compared with negative control, as did by standard drug fluoxetine.
Conclusion: The formulation has been optimized based on dispersion time. The formulation with minimum dispersion time, i.e. F1, has been considered an optimized formulation. The prepared optimized formulation was found to comply with all physical parameters and antidepressant activity.
DEVELOPMENT OF NANO IN SITU GELS OF BEVACIZUMAB FOR THE TREATMENT OF OCULAR ANGIOGENESIS: IN VITRO ASSESSMENT OF ANTI-ANGIOGENESIS ACTIVITY AND MOLECULAR DOCKING ANALYSIS
Authors: NARAYANA SOUMYA , AHMED MOHAMMED GULZAR , NASRINE ARFA
Published: July 2023

Objective: The present investigation aims to develop nano in situ gels of bevacizumab and evaluate their safety and efficacy.
Methods: Nanoparticles were designed using the desolvation and double emulsion solvent evaporation technique. The hen’s egg test: chorioallantoic membrane (HET-CAM) assay was adopted to evaluate the anti-angiogenesis and irritancy potential of prepared nano in situ gel. Computational docking study carried out using glide module of Schrodinger software.
Results: The FT-IR study showed no interaction between the components. The drug-loaded nanoparticle showed particle size in the range of 369±5.3 to 410±3.5, followed by PDI 0.41±0.1 to 0.73±0.1, and ζ–Potential-13±2.3 to-9±3.4. The entrapment efficiency of nanoparticles was found in between the range of 72.35±1.4 to 87.22±1.1, followed by loading efficiency of 8.81±0.3 to 12.78±0.7. The FE-SEM studies resulted in an irregular pattern of aggregated particles. The spherical shape of the particles was confirmed through the HR-TEM study. The nano in situ gel exhibited pH in the range of 7.2±0.2 to 7.3±0.1 followed by a viscosity of 325.2±8.7 to 498.7±5.8 mPa. s. CAM assays revealed the safety and anti-angiogenesis activity of the developed formulation. All different concentrations of in situ gels of bevacizumab showed a significant anti-angiogenic effect. The outcome of the molecular docking study revealed the well-binding capacity of bevacizumab with vascular endothelial growth factor (-7.325) and human serum albumin (-5.620) residues.
Conclusion: The above outcomes improved our perception regarding the anti-angiogenic activity and safety of nano-in situ gels of bevacizumab. Overall, these findings denoted that implementing the current idea in the therapy of ocular angiogenesis might be a promising platform for better treatment.