Search results for: clinical trial optimization

Authors: Sam Derakhshan Deilami, Iain N. Kings, Lynne E. Macaskie, Brajendra K. Sharma, Anthony V. Bridgwater, Joseph Wood

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This paper reports the application of a bacteria-supported palladium catalyst to the hydrodeoxygenation (HDO) of pyrolysis bio-oil, towards producing an upgraded transport fuel. Biofuels are key to the timely replacement of fossil fuels in order to mitigate the emissions of greenhouse gases and depletion of non-renewable resources. The process is an essential step in the upgrading of bio-oils derived from industrial by-products such as agricultural and forestry wastes, the crude oil from pyrolysis containing a large amount of oxygen that requires to be removed in order to create a fuel resembling fossil-derived hydrocarbons. The bacteria supported catalyst manufacture is a means of utilizing recycled metals and second life bacteria, and the metal can also be easily recovered from the spent catalysts after use. Comparisons are made between bio-Pd, and a conventional activated carbon supported Pd/C catalyst. Bio-oil was produced by fast pyrolysis of beechwood at 500 C at a residence time below 2 seconds, provided by Aston University. 5 wt % BioPd/C was prepared under reducing conditions, exposing cells of E. coli MC4100 to a solution of sodium tetrachloropalladate (Na2PdCl4), followed by rinsing, drying and grinding to form a powder. Pd/C was procured from Sigma-Aldrich. The HDO experiments were carried out in a 100 mL Parr batch autoclave using ~20g bio-crude oil and 0.6 g bio-Pd/C catalyst. Experimental variables investigated for optimization included temperature (160-350C) and reaction times (up to 5 h) at a hydrogen pressure of 100 bar. Most of the experiments resulted in an aqueous phase (~40%) and an organic phase (~50-60%) as well as gas phase (<5%) and coke (<2%). Study of the temperature and time upon the process showed that the degree of deoxygenation increased (from ~20 % up to 60 %) at higher temperatures in the region of 350 C and longer residence times up to 5 h. However minimum viscosity (~0.035 Pa.s) occurred at 250 C and 3 h residence time, indicating that some polymerization of the oil product occurs at the higher temperatures. Bio-Pd showed a similar degree of deoxygenation (~20 %) to Pd/C at lower temperatures of 160 C, but did not rise as steeply with temperature. More coke was formed over bio-Pd/C than Pd/C at temperatures above 250 C, suggesting that bio-Pd/C may be more susceptible to coke formation than Pd/C. Reactions occurring during bio-oil upgrading include catalytic cracking, decarbonylation, decarboxylation, hydrocracking, hydrodeoxygenation and hydrogenation. In conclusion, it was shown that bio-Pd/C displays an acceptable rate of HDO, which increases with residence time and temperature. However some undesirable reactions also occur, leading to a deleterious increase in viscosity at higher temperatures. Comparisons are also drawn with earlier work on the HDO of Chlorella derived bio-oil manufactured from micro-algae via hydrothermal liquefaction. Future work will analyze the kinetics of the reaction and investigate the effect of bi-metallic catalysts.

Keywords: bio-oil, catalyst, palladium, upgrading

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Authors: Keda Li, Hong Hu

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Auxetic materials, as an emerging artificial designed metamaterial has attracted growing attention due to their promising negative Poisson’s ratio behaviors and tunable properties. The conventional auxetic lattice structures for which the deformation process is governed by a bending-dominated mechanism have faced the limitation of poor mechanical performance for many potential engineering applications. Recently, both load-bearing and energy absorption capabilities have become a crucial consideration in auxetic structure design. This study reports the finite element analysis of a class of hexagonal double-arrowhead auxetic structures with enhanced stiffness and energy absorption performance. The structure design was developed by extending the traditional double-arrowhead honeycomb to a hexagon frame, the stretching-dominated deformation mechanism was determined according to Maxwell’s stability criterion. The finite element (FE) models of 2D lattice structures established with stainless steel material were analyzed in ABAQUS/Standard for predicting in-plane structural deformation mechanism, failure process, and compressive elastic properties. Based on the computational simulation, the parametric analysis was studied to investigate the effect of the structural parameters on Poisson’s ratio and mechanical properties. The geometrical optimization was then implemented to achieve the optimal Poisson’s ratio for the maximum specific energy absorption. In addition, the optimized 2D lattice structure was correspondingly converted into a 3D geometry configuration by using the orthogonally splicing method. The numerical results of 2D and 3D structures under compressive quasi-static loading conditions were compared separately with the traditional double-arrowhead re-entrant honeycomb in terms of specific Young's moduli, Poisson's ratios, and specified energy absorption. As a result, the energy absorption capability and stiffness are significantly reinforced with a wide range of Poisson’s ratio compared to traditional double-arrowhead re-entrant honeycomb. The auxetic behaviors, energy absorption capability, and yield strength of the proposed structure are adjustable with different combinations of joint angle, struts thickness, and the length-width ratio of the representative unit cell. The numerical prediction in this study suggests the proposed concept of hexagonal double-arrowhead structure could be a suitable candidate for the energy absorption applications with a constant request of load-bearing capacity. For future research, experimental analysis is required for the validation of the numerical simulation.

Keywords: auxetic, energy absorption capacity, finite element analysis, negative Poisson's ratio, re-entrant hexagonal honeycomb

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Authors: Sergey Nikitenko, Vladimir Klishin, Yury Malakhov, Elena Goosen

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Transition to renewable energy sources (solar, wind, bioenergy, etc.) and launching of alternative energy generation has weakened the role of coal as a source of energy. The Paris Agreement and assumption of obligations by many nations to orderly reduce CO₂ emissions by means of technological modernization and climate change adaptation has abridged coal demand yet more. This paper aims to assess current resilience of the coal industry to stress and to define prospects for coal production optimization using high technologies pursuant to global challenges and requirements of energy transition. Our research is based on the resilience concept adapted to the coal industry. It is proposed to divide the coal sector into segments depending on the prevailing value chains (VC). Four representative models of VC are identified in the coal sector. The most promising lines of upgrading VC in the coal industry include: •Elongation of VC owing to introduction of clean technologies of coal conversion and utilization; •Creation of parallel VC by means of waste management; •Branching of VC (conversion of a company’s VC into a production network). The upgrade effectiveness is governed in many ways by applicability of advanced coal processing technologies, usability of waste, expandability of production, entrance to non-rival markets and localization of new segments of VC in receiving regions. It is also important that upgrade of VC by means of formation of agile high-tech inter-industry production networks within the framework of operating surface and underground mines can reduce social, economic and ecological risks associated with closure of coal mines. Such promising route of VC upgrade is application of methanotrophic bacteria to produce protein to be used as feed-stuff in fish, poultry and cattle breeding, or in production of ferments, lipoids, sterols, antioxidants, pigments and polysaccharides. Closed mines can use recovered methane as a clean energy source. There exist methods of methane utilization from uncontrollable sources, including preliminary treatment and recovery of methane from air-and-methane mixture, or decomposition of methane to hydrogen and acetylene. Separated hydrogen is used in hydrogen fuel cells to generate power to feed the process of methane utilization and to supply external consumers. Despite the recent paradigm of carbon-free energy generation, it is possible to preserve the coal mining industry using the differentiated approach to upgrade of value chains based on flexible technologies with regard to specificity of mining companies.

Keywords: resilience, resilience concept, resilience indicator, resilience in the Russian coal industry, value chains

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Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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Authors: Tatjana Stefanovic Stanojevic, Milica Tosic Radev, Aleksandra Bogdanovic

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Depression is considered to be a leading cause of death and disability in the female population, and that is the reason why understanding the dynamics of the onset of depressive symptomatology is important. A review of the literature indicates the relationship between depressive symptoms and insecure attachment patterns, but very few studies have examined the mechanism underlying this relation. The aim of the study was to examine the pathway from the preoccupied attachment pattern to depressive symptomatology, as well as to test the mediation effect of mentalization, social anxiety and rumination in this relationship using a serial mediation model. The research was carried out on a geographical cluster sample from the general population of Serbia included within the project ‘Indicators and models of family and work roles harmonization’ funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia. This research was carried out on a subsample of 791 working-age female adults from 37 urban and rural locations distributed through 20 administrative districts of Serbia. The respondents filled in a battery of instruments, including Relationship Questionnaire - Clinical Version (RQ - CV), The Mentalization Scale (MentS), Scale of Social Anxiety (SA), Patient Ruminative Thought Style Questionnaire (RTSQ), Health Questionnaire (PHQ-9). The results confirm our assumption that the total indirect effect of the preoccupied attachment pattern to depressive symptoms is significant across all mediators separately. More importantly, this effect is still present in a model with a sequential mediator relationship, where social anxiety, rumination, and mentalization were perceived as serial mediators of a relationship between preoccupied attachment and depressive symptoms (estimated indirect effect=0.004, boot-strapped 95% CI=0.002 to 0.007). Our findings suggest that there is a significant specific indirect effect of the preoccupied attachment pattern to depressive symptoms, occurring through mentalization, social anxiety and rumination, indicating that preoccupied attachment cause decrease of a self related mentalization, which in turn causes increasing of social anxiety and rumination, concluding in depressive symptoms as a final consequence. The finding that the path from the preoccupied attachment pattern to depressive symptoms is typical in women is understandable from the perspective of both evolutionary and culturally conditioned gender differences. The practical implications of the study are reflected in the recommendations for the prevention and forehand psychotherapy response among preoccupied women with depressive symptomatology. Treatment of this specific group of depressed patients should be focused on strengthening mentalization, learning to accept and to understand herself better, reducing anxiety in situations where mistakes are visible to others, and replacing the rumination strategy with more constructive coping strategies.

Keywords: preoccupied attachment, depression, serial mediation model, mentalization, rumination

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Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

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Authors: Debjit Ray

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Horizontal gene transfer (HGT) and recombination leads to the emergence of bacterial antibiotic resistance and pathogenic traits. HGT events can be identified by comparing a large number of fully sequenced genomes across a species or genus, define the phylogenetic range of HGT, and find potential sources of new resistance genes. In-depth comparative phylogenomics can also identify subtle genome or plasmid structural changes or mutations associated with phenotypic changes. Comparative phylogenomics requires that accurately sequenced, complete and properly annotated genomes of the organism. Assembling closed genomes requires additional mate-pair reads or “long read” sequencing data to accompany short-read paired-end data. To bring down the cost and time required of producing assembled genomes and annotating genome features that inform drug resistance and pathogenicity, we are analyzing the performance for genome assembly of data from the Illumina NextSeq, which has faster throughput than the Illumina HiSeq (~1-2 days versus ~1 week), and shorter reads (150bp paired-end versus 300bp paired end) but higher capacity (150-400M reads per run versus ~5-15M) compared to the Illumina MiSeq. Bioinformatics improvements are also needed to make rapid, routine production of complete genomes a reality. Modern assemblers such as SPAdes 3.6.0 running on a standard Linux blade are capable in a few hours of converting mixes of reads from different library preps into high-quality assemblies with only a few gaps. Remaining breaks in scaffolds are generally due to repeats (e.g., rRNA genes) are addressed by our software for gap closure techniques, that avoid custom PCR or targeted sequencing. Our goal is to improve the understanding of emergence of pathogenesis using sequencing, comparative genomics, and machine learning analysis of ~1000 pathogen genomes. Machine learning algorithms will be used to digest the diverse features (change in virulence genes, recombination, horizontal gene transfer, patient diagnostics). Temporal data and evolutionary models can thus determine whether the origin of a particular isolate is likely to have been from the environment (could it have evolved from previous isolates). It can be useful for comparing differences in virulence along or across the tree. More intriguing, it can test whether there is a direction to virulence strength. This would open new avenues in the prediction of uncharacterized clinical bugs and multidrug resistance evolution and pathogen emergence.

Keywords: genomics, pathogens, genome assembly, superbugs

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Authors: Chu-Tzu Chen, Angela S. Huang, Yu-Min Chou, Chin-Hui Yang

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Dengue is a major public health concern throughout tropical and sub-tropical regions. Taiwan is located in the Pacific Ocean and overlying the tropical and subtropical zones. The island remains humid throughout the year and receives abundant rainfall, and the temperature is very hot in summer at southern Taiwan. It is ideal for the growth of dengue vectors and would be increasing the risk on dengue outbreaks. During the first half of the 20th century, there were three island-wide dengue outbreaks (1915, 1931, and 1942). After almost forty years of dormancy, a DEN-2 outbreak occurred in Liuchiu Township, Pingtung County in 1981. Thereafter, more dengue outbreaks occurred with different scales in southern Taiwan. However, there were more than ten thousands of dengue cases in 2014 and in 2015. It did not only affect human health, but also caused widespread social disruption and economic losses. The study would like to reveal the epidemiology of dengue on Taiwan, especially the severe outbreak in 2015, and try to find the effective interventions in dengue control including dengue vaccine development for the elderly. Methods: The study applied the Notifiable Diseases Surveillance System database of the Taiwan Centers for Disease Control as data source. All cases were reported with the uniform case definition and confirmed by NS1 rapid diagnosis/laboratory diagnosis. Results: In 2014, Taiwan experienced a serious DEN-1 outbreak with 15,492 locally-acquired cases, including 136 cases of dengue hemorrhagic fever (DHF) which caused 21 deaths. However, a more serious DEN-2 outbreak occurred with 43,419 locally-acquired cases in 2015. The epidemic occurred mainly at Tainan City (22,760 cases) and Kaohsiung City (19,723 cases) in southern Taiwan. The age distribution for the cases were mainly adults. There were 228 deaths due to dengue infection, and the case fatality rate was 5.25 ‰. The average age of them was 73.66 years (range 29-96) and 86.84% of them were older than 60 years. Most of them were comorbidities. To review the clinical manifestations of the 228 death cases, 38.16% (N=87) of them were reported with warning signs, while 51.75% (N=118) were reported without warning signs. Among the 87 death cases reported to dengue with warning signs, 89.53% were diagnosed sever dengue and 84% needed the intensive care. Conclusion: The year 2015 was characterized by large dengue outbreaks worldwide. The risk of serious dengue outbreak may increase significantly in the future, and the elderly is the vulnerable group in Taiwan. However, a dengue vaccine has been licensed for use in people 9-45 years of age living in endemic settings at the end of 2015. In addition to carry out the research to find out new interventions in dengue control, developing the dengue vaccine for the elderly is very important to prevent severe dengue and deaths.

Keywords: case fatality rate, dengue, dengue vaccine, the elderly

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Authors: Abhijit Trailokya

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Background: Cardiovascular diseases (CVD’s) are the major cause of morbidity and mortality in both developed and developing countries. Many clinical trials have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, reduces the incidence of coronary and cerebrovascular events across a broad spectrum of patients at risk. Guidelines for the management of patients at risk have been established in Europe and North America. The guidelines have advocated progressively lower LDL-C targets and more aggressive use of statin therapy. In Indian patients, comprehensive data on dyslipidemia management and its treatment outcomes are inadequate. There is lack of information on existing treatment patterns, the patient’s profile being treated, and factors that determine treatment success or failure in achieving desired goals. Purpose: The present study was planned to determine the lipid control status in high-risk dyslipidemic patients treated with lipid-lowering therapy in India. Methods: This cross-sectional, non-interventional, single visit program was conducted across 483 sites in India where male and female patients with high-risk dyslipidemia aged 18 to 65 years who had visited for a routine health check-up to their respective physician at hospital or a healthcare center. Percentage of high-risk dyslipidemic patients achieving adequate LDL-C level (< 70 mg/dL) on lipid-lowering therapy and the association of lipid parameters with patient characteristics, comorbid conditions, and lipid lowering drugs were analysed. Results: 3089 patients were enrolled in the study; of which 64% were males. LDL-C data was available for 95.2% of the patients; only 7.7% of these patients achieved LDL-C levels < 70 mg/dL on lipid-lowering therapy, which may be due to inability to follow therapeutic plans, poor compliance, or inadequate counselling by physician. The physician’s lack of awareness about recent treatment guidelines also might contribute to patients’ poor adherence, not explaining adequately the benefit and risks of a medication, not giving consideration to the patient’s life style and the cost of medication. Statin was the most commonly used anti-dyslipidemic drug across population. The higher proportion of patients had the comorbid condition of CVD and diabetes mellitus across all dyslipidemic patients. Conclusion: As per the European Society of Cardiology guidelines the ideal LDL-C levels in high risk dyslipidemic patients should be less than 70%. In the present study, 7.7% of the patients achieved LDL-C levels < 70 mg/dL on lipid lowering therapy which is very less. Most of high risk dyslipidemic patients in India are on suboptimal dosage of statin. So more aggressive and high dosage statin therapy may be required to achieve target LDLC levels in high risk Indian dyslipidemic patients.

Keywords: cardiovascular disease, diabetes mellitus, dyslipidemia, LDL-C, lipid lowering drug, statins

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Authors: Mustafa M. Donma, Orkide Donma

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Metabolic syndrome (MetS) is a severe health problem which is common among obese individuals. The components of MetS are rather stable in adults compared to the components discussed for children. Due to the ambiguity in this group of the population, how to diagnose MetS in morbid obese (MO) children still constitutes a matter of discussion. For this purpose, a formula, which facilitates the diagnosis of MetS in MO children, was investigated. The aim of this study was to develop a formula which was capable of discriminating MO children with and without MetS findings. Study population comprised MO children. Age and sex-dependent body mass index (BMI) percentiles of the children were above 99. Metabolic syndrome components were also determined. Elevated systolic and diastolic blood pressures (SBP and DBP), elevated fasting blood glucose (FBG), elevated triglycerides (TRG), and/or depressed high density lipoprotein cholesterol (HDL-C) in addition to central obesity were listed as MetS components for each child. Presence of at least two of these components confirmed that the case was MetS. Two groups were constituted. In the first group, there were forty-two MO children without MetS components. Second group was composed of forty-four MO children with at least two MetS components. Anthropometric measurements, including weight, height, waist, and hip circumferences, were performed following physical examination. Body mass index and homeostatic model assessment of insulin resistance values were calculated. Informed consent forms were obtained from the parents of the children. Institutional Non-Interventional Ethics Committee approved the study design. Blood pressure values were recorded. Routine biochemical analysis, including FBG, insulin (INS), TRG, HDL-C were performed. The performance and the clinical utility of the Diagnostic Obesity Notation Model Assessment Metabolic Syndrome Index (DONMA MetS index) [(INS/FBG)/(HDL-C/TRG)*100] was tested. Appropriate statistical tests were applied to the study data. p value smaller than 0.05 was defined as significant. Metabolic syndrome index values were 41.6±5.1 in MO group and 104.4±12.8 in MetS group. Corresponding values for HDL-C values were 54.5±13.2 mg/dl and 44.2±11.5 mg/dl. There were statistically significant differences between the groups (p<0.001). Upon evaluation of the correlations between MetS index and HDL-C values, a much stronger negative correlation was found in MetS group (r=-0.515; p=0.001) in comparison with the correlation detected in MO group (r=-0.371; p=0.016). From these findings, it was concluded that the statistical significance degree of the difference between MO and MetS groups was highly acceptable for this recently introduced MetS index as expected. This was due to the involvement of all of the biochemically defined MetS components into the index. This is particularly important because each of these four parameters used in the formula is cardiac risk factor. Aside from discriminating MO children with and without MetS findings, MetS index introduced in this study is important from the cardiovascular risk point of view in MetS group of children.

Keywords: children, fasting blood glucose, high density lipoprotein cholesterol, index, insulin, metabolic syndrome, morbid obesity, triglycerides.

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Authors: Dian Mayasari, Yosi Bayu Murti, Sylvia Utami Tunjung Pratiwi, Sudarsono

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Melastoma malabathricum L. is an Indo-Pacific herb that has been traditionally used to treat several ailments such as wounds, dysentery, diarrhea, toothache, and diabetes. This plant is common across tropical Indo-Pacific archipelagos and is tolerant of a range of soils, from low-lying areas subject to saltwater inundation to the salt-free conditions of mountain slopes. How the soil and environmental variation influences secondary metabolite production in the herb, and an understanding of the plant’s utility as traditional medicine, remain largely unknown and unexplored. The objective of this study is to evaluate the variability of the metabolic profiles of M. malabathricum L. across its geographic distribution. By employing high-performance liquid chromatography-diode array detector (HPLC-DAD), a highly established, simple, sensitive, and reliable method was employed for establishing the chemical fingerprints of 72 samples of M. malabathricum L. leaves from various geographical locations in Indonesia. Specimens collected from six terrestrial and archipelago regions of Indonesia were analyzed by HPLC to generate chromatogram peak profiles that could be compared across each region. Data corresponding to the common peak areas of HPLC chromatographic fingerprint were analyzed by hierarchical component analysis (HCA) and principal component analysis (PCA) to extract information on the most significant variables contributing to characterization and classification of analyzed samples data. Principal component values were identified as PC1 and PC2 with 41.14% and 19.32%, respectively. Based on variety and origin, the high-performance liquid chromatography method validated the chemical fingerprint results used to screen the in vitro antioxidant activity of M. malabathricum L. The result shows that the developed method has potential values for the quality of similar M. malabathrium L. samples. These findings provide a pathway for the development and utilization of references for the identification of M. malabathricum L. Our results indicate the importance of considering geographic distribution during field-collection efforts as they demonstrate regional metabolic variation in secondary metabolites of M. malabathricum L., as illustrated by HPLC chromatogram peaks and their antioxidant activities. The results also confirm the utility of this simple approach to a rapid evaluation of metabolic variation between plants and their potential ethnobotanical properties, potentially due to the environments from whence they were collected. This information will facilitate the optimization of growth conditions to suit particular medicinal qualities.

Keywords: fingerprint, high performance liquid chromatography, Melastoma malabathricum l., metabolic profiles, principal component analysis

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Authors: Seyed Hamed Mousavi, Juha M. Hijmans, Reza Rajabi, Ron Diercks, Johannes Zwerver, Henk van der Worp

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Introduction: Running is one of the most popular sports activity among people. Improper sagittal plane ankle, knee and hip kinematics are considered to be associated with the increase of injury risk in runners. Motion assessing smart-phone applications are increasingly used to measure kinematics both in the field and laboratory setting, as they are cheaper, more portable, accessible, and easier to use relative to 3D motion analysis system. The aims of this study are 1) to compare the results of 3D gait analysis system and CE; 2) to evaluate the test-retest and intra-rater reliability of coach’s eye (CE) app for the sagittal plane hip, knee, and ankle angles in the touchdown and toe-off while running. Method: Twenty subjects participated in this study. Sixteen reflective markers and cluster markers were attached to the subject’s body. Subjects were asked to run at a self-selected speed on a treadmill. Twenty-five seconds of running were collected for analyzing kinematics of interest. To measure sagittal plane hip, knee and ankle joint angles at touchdown (TD) and toe off (TO), the mean of first ten acceptable consecutive strides was calculated for each angle. A smartphone (Samsung Note5, android) was placed on the right side of the subject so that whole body was simultaneously filmed with 3D gait system during running. All subjects repeated the task with the same running speed after a short interval of 5 minutes in between. The CE app, installed on the smartphone, was used to measure the sagittal plane hip, knee and ankle joint angles at touchdown and toe off the stance phase. Results: Intraclass correlation coefficient (ICC) was used to assess test-retest and intra-rater reliability. To analyze the agreement between 3D and 2D outcomes, the Bland and Altman plot was used. The values of ICC were for Ankle at TD (TRR=0.8,IRR=0.94), ankle at TO (TRR=0.9,IRR=0.97), knee at TD (TRR=0.78,IRR=0.98), knee at TO (TRR=0.9,IRR=0.96), hip at TD (TRR=0.75,IRR=0.97), hip at TO (TRR=0.87,IRR=0.98). The Bland and Altman plots displaying a mean difference (MD) and ±2 standard deviation of MD (2SDMD) of 3D and 2D outcomes were for Ankle at TD (MD=3.71,+2SDMD=8.19, -2SDMD=-0.77), ankle at TO (MD=-1.27, +2SDMD=6.22, -2SDMD=-8.76), knee at TD (MD=1.48, +2SDMD=8.21, -2SDMD=-5.25), knee at TO (MD=-6.63, +2SDMD=3.94, -2SDMD=-17.19), hip at TD (MD=1.51, +2SDMD=9.05, -2SDMD=-6.03), hip at TO (MD=-0.18, +2SDMD=12.22, -2SDMD=-12.59). Discussion: The ability that the measurements are accurately reproduced is valuable in the performance and clinical assessment of outcomes of joint angles. The results of this study showed that the intra-rater and test-retest reliability of CE app for all kinematics measured are excellent (ICC ≥ 0.75). The Bland and Altman plots display that there are high differences of values for ankle at TD and knee at TO. Measuring ankle at TD by 2D gait analysis depends on the plane of movement. Since ankle at TD mostly occurs in the none-sagittal plane, the measurements can be different as foot progression angle at TD increases during running. The difference in values of the knee at TD can depend on how 3D and the rater detect the TO during the stance phase of running.

Keywords: reliability, running, sagittal plane, two dimensional

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Authors: Aaron Samuels, Ahmad Badeghiesh, Haitham Baghlaf, Michael H. Dahan

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Importance: Cervical cancer is the fourth most common cancer among women globally and a significant cause of cancer-related deaths. Understanding the impact of cervical cancer diagnosed during pregnancy on maternal, delivery, and neonatal outcomes is crucial for improving clinical management and outcomes for affected women and their children. Objective: The goal is to determine the effects of cervical cancer diagnosed during pregnancy on maternal, delivery, and neonatal outcomes using a population-based American database. Design: This study is a retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database. The study period spans between 2004-2014, and the analysis was conducted in 2023. Setting: The study used the HCUP-NIS database, which includes data from hospital stays across the United States, covering 48 states and the District of Columbia. Participants: The study included all women who delivered a child or had a maternal death from 2004-2014, with pregnancies at 24 weeks or above. The population was comprised of 9,096,788 pregnant women, including 222 diagnosed with cervical cancer prior to delivery. Exposures: The exposure was a diagnosis of cervical cancer during pregnancy, identified using International Classification of Diseases 9th Revision codes 180.0, 180.1, 180.8, and 180.9. Main Outcomes and Measures: Primary outcomes included maternal, delivery, and neonatal complications including preterm delivery, cesarean section, hysterectomy, blood transfusion, deep venous thrombosis, pulmonary embolism, congenital anomalies, intrauterine fetal demise, and small-for-gestational-age neonates. Logistic regression analyses were conducted to evaluate the association between cervical cancer diagnosis and these outcomes, adjusting for potential confounding factors. Results: Women with cervical cancer were older (25.2% ≥35 years vs. 14.7%, p=0.001, respectively); more likely to have Medicare insurance (1.4% vs. 0.6%, p=0.005, respectively); use illicit drugs (4.1% vs. 1.4%, p=0.001, respectively); smoke tobacco during pregnancy (14.9% vs. 4.9%, p=0.001, respectively); and have chronic hypertension (3.6% vs. 1.8%, p=0.046, respectively). These women also had higher rates of preterm delivery (OR = 4.73, 95% CI (3.53-6.36), p=0.001); cesarean section (OR = 5.40, 95% CI (4.00-7.30), p=0.001); hysterectomy (OR = 390.23, 95% CI (286.43-531.65), p=0.001); blood transfusions (OR = 19.23, 95% CI (13.57-27.25), p=0.001); deep venous thrombosis (OR = 9.42, 95% CI (1.32-67.20), p=0.025); and pulmonary embolism (OR = 20.22, 95% CI (2.83-144.48), p=0.003). Neonatal outcomes, including congenital anomalies, intrauterine fetal demise, and small-for-gestational-age neonates, were comparable between groups. Conclusions and Relevance: Cervical cancer during pregnancy is associated with significant maternal and delivery risks; however, neonatal outcomes are largely unaffected. These findings highlight the need for a multidisciplinary approach to managing pregnant cervical cancer patients involving oncological, obstetrical, and neonatal care specialists.

Keywords: cervical cancer, maternal outcomes, neonatal outcomes, delivery outcomes

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Authors: Vanessa Bennemann, Gabriela Laste, Márcia Inês Goettert

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The gestational period is a phase in which the pregnant woman undergoes constant physiological and hormonal changes, which are part of the woman’s biological cycle, the development of the fetus, childbirth, and lactation. These are factors of response to the immunological adaptation of the human reproductive process that is directly related to the pregnancy’s well-being and development. Although most pregnancies occur without complications, about 15% of pregnant women will develop potentially fatal complications, implying maternal and fetal risk. Therefore, requiring specialized care for high-risk pregnant women (HRPW) with obstetric interventions for the survival of the mother and/or fetus. Among the risk factors that characterize HRPW are the women's age, gestational diabetes mellitus (GDM), autoimmune diseases, infectious diseases such as syphilis and HIV, hypertension (SAH), preeclampsia, eclampsia, HELLP syndrome, uterine contraction abnormalities, and premature placental detachment (PPD), thyroid disorders, among others. Thus, pregnancy has an impact on the thyroid gland causing changes in the functioning of the mother's thyroid gland, altering the thyroid hormone (TH) profiles and production as pregnancy progresses. Considering, throughout the gestational period, the interpretation of the results of the tests to evaluate the thyroid functioning depends on the stage in which the pregnancy is. Thyroid disorders are directly related to adverse obstetric outcomes and in child development. Therefore, the adequate release of TH is important for a pregnancy without complications and optimal fetal growth and development. Objective: Investigate the physiological effects caused by thyroid disorders in the gestational period. Methods: A search for articles indexed in PubMed, Scielo, and MDPI databases, was performed using the term “AND”, with the descriptors: Pregnancy, Thyroid. With several combinations that included: Melatonin, Thyroidopathy, Inflammatory processes, Cytokines, Anti-inflammatory, Antioxidant, High-risk pregnancy. Subsequently, the screening was performed through the analysis of titles and/or abstracts. The criteria were: including clinical studies in general, randomized or not, in the period of 10 years prior to the research, in the English literature; excluded: experimental studies, case reports, research in the development phase. Results: In the preliminary results, a total of studies (n=183) were found, (n=57) excluded, such as studies of cancer, diabetes, obesity, and skin diseases. Conclusion: To date, it has been identified that thyroid diseases can impair the fetus’s brain development. Further research is suggested on this matter to identify new substances that may have a potential therapeutic effect to aid the gestational period with thyroid diseases.

Keywords: pregnancy, thyroid, melatonin, high-risk pregnancy

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Authors: Wei-Chih Huang, Pei-Lung Chung, Ching-Heng Lin, Hsuan-Chia Yang, Der-Ming Liou

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Background: In-Hospital Cardiac Arrest (IHCA) threaten life of the inpatients, cause serious effect to patient safety, quality of inpatients care and hospital service. Health providers must identify the signs of IHCA early to avoid the occurrence of IHCA. This study will consider the potential association between early signs of IHCA and the essence of patient care provided by nurses and other professionals before an IHCA occurs. The aim of this study is to identify significant associations between nursing interventions and abnormal early evaluation results of IHCA that can assist health care providers in monitoring inpatients at risk of IHCA to increase opportunities of IHCA early detection and prevention. Materials and Methods: This study used one of the data mining techniques called association rules mining to compute associations between nursing interventions and abnormal early evaluation results of IHCA. The nursing interventions and abnormal early evaluation results of IHCA were considered to be co-occurring if nursing interventions were provided within 24 hours of last being observed in abnormal early evaluation results of IHCA. The rule based methods were utilized 23.6 million electronic medical records (EMR) from a medical center in Taipei, Taiwan. This dataset includes 733 concepts of nursing interventions that coded by clinical care classification (CCC) codes and 13 early evaluation results of IHCA with binary codes. The values of interestingness and lift were computed as Q values to measure the co-occurrence and associations’ strength between all in-hospital patient care measures and abnormal early evaluation results of IHCA. The associations were evaluated by comparing the results of Q values and verified by medical experts. Results and Conclusions: The results show that there are 4195 pairs of associations between nursing interventions and abnormal early evaluation results of IHCA with their Q values. The indication of positive association is 203 pairs with Q values greater than 5. Inpatients with high blood sugar level (hyperglycemia) have positive association with having heart rate lower than 50 beats per minute or higher than 120 beats per minute, Q value is 6.636. Inpatients with temporary pacemaker (TPM) have significant association with high risk of IHCA, Q value is 47.403. There is significant positive correlation between inpatients with hypovolemia and happened abnormal heart rhythms (arrhythmias), Q value is 127.49. The results of this study can help to prevent IHCA from occurring by making health care providers early recognition of inpatients at risk of IHCA, assist with monitoring patients for providing quality of care to patients, improve IHCA surveillance and quality of in-hospital care.

Keywords: in-hospital cardiac arrest, patient safety, nursing intervention, association rule mining

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Authors: E. Nakamachi, S. Tanaka, K. Yamamoto, Y. Morita

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In this study, we developed a three-dimensional (3D) direct current electric field (DCEF) stimulation bio-reactor for axonal outgrowth enhancement to generate the neural network of the central nervous system (CNS). By using our newly developed 3D DCEF stimulation bio-reactor, we cultured the rat pheochromocytoma cells (PC12) and investigated the effects on the axonal extension enhancement and network generation. Firstly, we designed and fabricated a 3D bio-reactor, which can load DCEF stimulation on PC12 cells embedded in the collagen gel as extracellular environment. The connection between the electrolyte and the medium using salt bridges for DCEF stimulation was introduced to avoid the cell death by the toxicity of metal ion. The distance between the salt bridges was adopted as the design variable to optimize a structure for uniform DCEF stimulation, where the finite element (FE) analyses results were used. Uniform DCEF strength and electric flux vector direction in the PC12 cells embedded in collagen gel were examined through measurements of the fabricated 3D bio-reactor chamber. Measurement results of DCEF strength in the bio-reactor showed a good agreement with FE results. In addition, the perfusion system was attached to maintain pH 7.2 ~ 7.6 of the medium because pH change was caused by DCEF stimulation loading. Secondly, we disseminated PC12 cells in collagen gel and carried out 3D culture. Finally, we measured the morphology of PC12 cell bodies and neurites by the multiphoton excitation fluorescence microscope (MPM). The effectiveness of DCEF stimulation to enhance the axonal outgrowth and the neural network generation was investigated. We confirmed that both an increase of mean axonal length and axogenesis rate of PC12, which have been exposed 5 mV/mm for 6 hours a day for 4 days in the bioreactor. We found following conclusions in our study. 1) Design and fabrication of DCEF stimulation bio-reactor capable of 3D culture nerve cell were completed. A uniform electric field strength of average value of 17 mV/mm within the 1.2% error range was confirmed by using FE analyses, after the structure determination through the optimization process. In addition, we attached a perfusion system capable of suppressing the pH change of the culture solution due to DCEF stimulation loading. 2) Evaluation of DCEF stimulation effects on PC12 cell activity was executed. The 3D culture of PC 12 was carried out adopting the embedding culture method using collagen gel as a scaffold for four days under the condition of 5.0 mV/mm and 10mV/mm. There was a significant effect on the enhancement of axonal extension, as 11.3% increase in an average length, and the increase of axogenesis rate. On the other hand, no effects on the orientation of axon against the DCEF flux direction was observed. Further, the network generation was enhanced to connect longer distance between the target neighbor cells by DCEF stimulation.

Keywords: PC12, DCEF stimulation, 3D bio-reactor, axonal extension, neural network generation

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Authors: Suman Som, Abhijit Maity, Sunil B. Daschakraborty, Sujit Chaudhuri, Manik Pradhan

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Background: Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. Currently H. pylori infection is detected by both invasive and non-invasive way but the diagnostic accuracy is not up to the mark. Aim: To set up an optimal diagnostic cut-off value of 13C-Urea Breath Test to detect H. pylori infection and evaluate a novel c-PDR methodology to overcome of inconclusive grey zone. Materials and Methods: All 83 subjects first underwent upper-gastrointestinal endoscopy followed by rapid urease test and histopathology and depending on these results; we classified 49 subjects as H. pylori positive and 34 negative. After an overnight, fast patients are taken 4 gm of citric acid in 200 ml water solution and 10 minute after ingestion of the test meal, a baseline exhaled breath sample was collected. Thereafter an oral dose of 75 mg 13C-Urea dissolved in 50 ml water was given and breath samples were collected upto 90 minute for 15 minute intervals and analysed by laser based high precisional cavity enhanced spectroscopy. Results: We studied the excretion kinetics of 13C isotope enrichment (expressed as δDOB13C ‰) of exhaled breath samples and found maximum enrichment around 30 minute of H. pylori positive patients, it is due to the acid mediated stimulated urease enzyme activity and maximum acidification happened within 30 minute but no such significant isotopic enrichment observed for H. pylori negative individuals. Using Receiver Operating Characteristic (ROC) curve an optimal diagnostic cut-off value, δDOB13C ‰ = 3.14 was determined at 30 minute exhibiting 89.16% accuracy. Now to overcome grey zone problem we explore percentage dose of 13C recovered per hour, i.e. 13C-PDR (%/hr) and cumulative percentage dose of 13C recovered, i.e. c-PDR (%) in exhaled breath samples for the present 13C-UBT. We further explored the diagnostic accuracy of 13C-UBT by constructing ROC curve using c-PDR (%) values and an optimal cut-off value was estimated to be c-PDR = 1.47 (%) at 60 minute, exhibiting 100 % diagnostic sensitivity , 100 % specificity and 100 % accuracy of 13C-UBT for detection of H. pylori infection. We also elucidate the gastric emptying process of present 13C-UBT for H. pylori positive patients. The maximal emptying rate found at 36 minute and half empting time of present 13C-UBT was found at 45 minute. Conclusions: The present study exhibiting the importance of c-PDR methodology to overcome of grey zone problem in 13C-UBT for accurate determination of infection without any risk of diagnostic errors and making it sufficiently robust and novel method for an accurate and fast non-invasive diagnosis of H. pylori infection for large scale screening purposes.

Keywords: 13C-Urea breath test, c-PDR methodology, grey zone, Helicobacter pylori

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Authors: M. Karzhauov, А. Mukhambetova, M. Sarsenova, E. Raimagambetov, V. Ogay

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Regeneration of injured articular cartilage remains one of the most difficult and unsolved problems in traumatology and orthopedics. Currently, for the treatment of cartilage defects surgical techniques for stimulation of the regeneration of cartilage in damaged joints such as multiple microperforation, mosaic chondroplasty, abrasion and microfractures is used. However, as shown by clinical practice, they can not provide a full and sustainable recovery of articular hyaline cartilage. In this regard, the current high hopes in the regeneration of cartilage defects reasonably are associated with the use of tissue engineering approaches to restore the structural and functional characteristics of damaged joints using stem cells, growth factors and biopolymers or scaffolds. The purpose of the present study was to investigate the effects of chondroinductive growth factors and synovium-derived mesenchymal stem cells (SD-MSCs) on the regeneration of cartilage defects in rabbits. SD-MSCs were isolated from the synovium membrane of Flemish giant rabbits, and expanded in complete culture medium α-MEM. Rabbit SD-MSCs were characterized by CFU-assay and by their ability to differentiate into osteoblasts, chondrocytes and adipocytes. The effects of growth factors (TGF-β1, BMP-2, BMP-4 and IGF-I) on MSC chondrogenesis were examined in micromass pellet cultures using histological and biochemical analysis. Articular cartilage defect (4mm in diameter) in the intercondylar groove of the patellofemoral joint was performed with a kit for the mosaic chondroplasty. The defect was made until subchondral bone plate. Delivery of SD-MSCs and growth factors was conducted in combination with hyaloronic acid (HA). SD-MSCs, growth factors and control groups were compared macroscopically and histologically at 10, 30, 60 and 90 days aftrer intra-articular injection. Our in vitro comparative study revealed that TGF-β1 and BMP-4 are key chondroinductive factors for both the growth and chondrogenesis of SD-MSCs. The highest effect on MSC chondrogenesis was observed with the synergistic interaction of TGF-β1 and BMP-4. In addition, biochemical analysis of the chondrogenic micromass pellets also revealed that the levels of glycosaminoglycans and DNA after combined treatment with TGF-β1 and BMP-4 was significantly higher in comparison to individual application of these factors. In vivo study showed that for complete regeneration of cartilage defects with intra-articular injection of SD-MSCs with HA takes time 90 days. However, single injection of SD-MSCs in combiantion with TGF-β1, BMP-4 and HA significantly promoted regeneration rate of the cartilage defects in rabbits. In this case, complete regeneration of cartilage defects was observed in 30 days after intra-articular injection. Thus, our in vitro and in vivo study demonstrated that combined application of rabbit SD-MSC with chondroinductive growth factors and HA results in strong synergistic effect on the chondrogenesis significantly enhancing regeneration of the damaged cartilage.

Keywords: Mesenchymal stem cells, synovium, chondroinductive factors, TGF-β1, BMP-2, BMP-4, IGF-I

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Authors: Chin-Chia Jane

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In a transportation network, travel time refers to the transmission time from source node to destination node, whereas reliability refers to the probability of a successful connection from source node to destination node. With an increasing emphasis on quality of service (QoS), both performance indexes are significant in the design and analysis of transportation systems. In this work, we extend the well-known flow network model for transportation networks so that travel time and reliability are integrated into the QoS measurement simultaneously. In the extended model, in addition to the general arc capacities, each intermediate node has a time weight which is the travel time for per unit of commodity going through the node. Meanwhile, arcs and nodes are treated as binary random variables that switch between operation and failure with associated probabilities. For pre-specified travel time limitation and demand requirement, the QoS of a transportation network is the probability that source can successfully transport the demand requirement to destination while the total transmission time is under the travel time limitation. This work is pioneering, since existing literatures that evaluate travel time reliability via a single optimization path, the proposed QoS focuses the performance of the whole network system. To compute the QoS of transportation networks, we first transfer the extended network model into an equivalent min-cost max-flow network model. In the transferred network, each arc has a new travel time weight which takes value 0. Each intermediate node is replaced by two nodes u and v, and an arc directed from u to v. The newly generated nodes u and v are perfect nodes. The new direct arc has three weights: travel time, capacity, and operation probability. Then the universal set of state vectors is recursively decomposed into disjoint subsets of reliable, unreliable, and stochastic vectors until no stochastic vector is left. The decomposition is made possible by applying existing efficient min-cost max-flow algorithm. Because the reliable subsets are disjoint, QoS can be obtained directly by summing the probabilities of these reliable subsets. Computational experiments are conducted on a benchmark network which has 11 nodes and 21 arcs. Five travel time limitations and five demand requirements are set to compute the QoS value. To make a comparison, we test the exhaustive complete enumeration method. Computational results reveal the proposed algorithm is much more efficient than the complete enumeration method. In this work, a transportation network is analyzed by an extended flow network model where each arc has a fixed capacity, each intermediate node has a time weight, and both arcs and nodes are independent binary random variables. The quality of service of the transportation network is an integration of customer demands, travel time, and the probability of connection. We present a decomposition algorithm to compute the QoS efficiently. Computational experiments conducted on a prototype network show that the proposed algorithm is superior to existing complete enumeration methods.

Keywords: quality of service, reliability, transportation network, travel time

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Halimat M. Ajose-Adeogun, Zaynab A. Bello

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Artificial Intelligence (AI) and Natural Language Processing (NLP) have transformed computer language comprehension, allowing computers to comprehend spoken and written language with human-like cognition. NLP, a multidisciplinary area that combines rule-based linguistics, machine learning, and deep learning, enables computers to analyze and comprehend human language. NLP applications in medicine range from tackling issues in electronic health records (EHR) and psychiatry to improving diagnostic precision in orthopedic surgery and optimizing clinical procedures with novel technologies like chatbots. The technology shows promise in a variety of medical sectors, including quicker access to medical records, faster decision-making for healthcare personnel, diagnosing dysplasia in Barrett's esophagus, boosting radiology report quality, and so on. However, successful adoption requires training for healthcare workers, fostering a deep understanding of NLP components, and highlighting the significance of validation before actual application. Despite prevailing challenges, continuous multidisciplinary research and collaboration are critical for overcoming restrictions and paving the way for the revolutionary integration of NLP into medical practice. This integration has the potential to improve patient care, research outcomes, and administrative efficiency. The research methodology includes using NLP techniques for Sentiment Analysis and Emotion Recognition, such as evaluating text or audio data to determine the sentiment and emotional nuances communicated by users, which is essential for designing a responsive and sympathetic chatbot. Furthermore, the project includes the adoption of a Personalized Intervention strategy, in which chatbots are designed to personalize responses by merging NLP algorithms with specific user profiles, treatment history, and emotional states. The synergy between NLP and personalized medicine principles is critical for tailoring chatbot interactions to each user's demands and conditions, hence increasing the efficacy of mental health care. A detailed survey corroborated this synergy, revealing a remarkable 20% increase in patient satisfaction levels and a 30% reduction in workloads for healthcare practitioners. The poll, which focused on health outcomes and was administered to both patients and healthcare professionals, highlights the improved efficiency and favorable influence on the broader healthcare ecosystem.

Keywords: natural language processing, artificial intelligence, healthcare communication, electronic health records, patient care

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Authors: Wenhsuan Lee, Yachi Chang, Yingyih Shih

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In clinical practices, it is common that while facing the unknown progress of their disease, palliative care patients may easily feel anxious and depressed. These types of reactions are a cause of psychosomatic diseases and may also influence treatment results. However, the purpose of palliative care is to provide relief from all kinds of pains. Therefore, how to make patients more comfortable is an issue worth studying. This study adopted the “bio-psycho-social model” proposed by Engel and applied spontaneous breathing training, in the hope of seeing patients’ psychological state changes caused by their physiological state changes, improvements in their anxious conditions, corresponding adjustments of their cognitive functions, and further enhancement of their social functions and the social support system. This study will be a one-year study. Palliative care outpatients will be recruited and assigned to the experimental group or the control group for six outpatient visits (once a month), with 80 patients in each group. The patients of both groups agreed that this study can collect their physiological quantitative data using an HRV device before the first outpatient visit. They also agreed to answer the “Beck Anxiety Inventory (BAI)”, the “Taiwanese version of the WHOQOL-BREF questionnaire” before the first outpatient visit, to fill a self-report questionnaire after each outpatient visit, and to answer the “Beck Anxiety Inventory (BAI)”, the “Taiwanese version of the WHOQOL-BREF questionnaire” after the last outpatient visit. The patients of the experimental group agreed to receive the breathing training under HRV monitoring during the first outpatient visit of this study. Before each of the following three outpatient visits, they were required to fill a self-report questionnaire regarding their breathing practices after going home. After the outpatient visits, they were taught how to practice breathing through an HRV device and asked to practice it after going home. Later, based on the results from the HRV data analyses and the pre-tests and post-tests of the “Beck Anxiety Inventory (BAI)”, the “Taiwanese version of the WHOQOL-BREF questionnaire”, the influence of the breathing training in the bio, psycho, and social aspects were evaluated. The data collected through the self-report questionnaires of the patients of both groups were used to explore the possible interfering factors among the bio, psycho, and social changes. It is expected that this study will support the “bio-psycho-social model” proposed by Engel, meaning that bio, psycho, and social supports are closely related, and that breathing training helps to transform palliative care patients’ psychological feelings of anxiety and depression, to facilitate their positive interactions with others, and to improve the quality medical care for them.

Keywords: palliative care, breathing training, bio-psycho-social model, heart rate variability

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Authors: Magdalena B. Kaziuk, Waldemar Kosiba, Marek J. Kuzniewski

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Introduction: Adipose tissue is a typical place for storage water-insoluble toxins in the body. It's connective tissue, where the intercellular substance consist of fat, which level in people with low physical activity should be 18-25% for women and 13-18% for men. Due to the fat distribution in the body we distinquish two types of obesity: android (visceral, abdominal) and gynoidal (gluteal-femoral, peripheral). Abdominal obesity increases the risk of complications of the cardiovascular system diseases, and impaired renal and liver function. Through the influence on disorders of metabolism, lipid metabolism, diabetes and hypertension, leading to emergence of the metabolic syndrome. So thus, obesity will especially overload kidney function in patients after transplantation. Aim: An attempt was made to estimate the impact of amount fat tissue on transplanted kidney function and excretory function of the liver in patients after Ktx. Material and Methods: The study included 108 patients (50 females, 58 male, age 46.5 +/- 12.9 years) with active kidney transplant after more than 3 months from the transplantation. An analysis of body composition was done by using electrical bioimpedance (BIA) and anthropometric measurements. Estimated basal metabolic rate (BMR), muscle mass, total body water content and the amount of body fat. Information about physical activity were obtained during clinical examination. Nutritional status, and type of obesity were determined by using indicators: Waist to Height Ratio (WHR) and Waist to Hip Ratio (WHR). Excretory functions of the transplanted kidney was rated by calculating the estimated renal glomerular filtration rate (eGFR) using the MDRD formula. Liver function was rated by total bilirubin and alanine aminotransferase levels ALT concentration in serum. In our patients haemolitic uremic syndrome (HUS) was excluded. Results: In 19.44% of patients had underweight, 22.37% of the respondents were with normal weight, 11.11% had overweight, and the rest were with obese (49.08%). People with android stature have a lower eGFR compared with those with the gynoidal stature (p = 0.004). All patients with obesity had higher amount of body fat from a few to several percent. The higher amount of body fat percentage, the lower eGFR had patients (p <0.001). Elevated ALT levels significantly correlated with a high fat content (p <0.02). Conclusion: Increased amount of body fat, particularly in the case of android obesity can be a predictor of kidney and liver damage. Due to that obese patients should have more frequent control of diagnostic functions of these organs and the intensive dietary proceedings, pharmacological and regular physical activity adapted to the current physical condition of patients after transplantation.

Keywords: obesity, body fat, kidney transplantation, glomerular filtration rate, liver function

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Authors: Anuj Pathare, Aleksandra Birn-Jeffery

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Background: The Anterior Cruciate Ligament(ACL) helps stabilize the knee joint minimizing tibial anterior translation. Anterior Cruciate Ligament (ACL) injury is common in racquet sports and often occurs due to sudden acceleration, deceleration or changes of direction. This mechanism in badminton most commonly occurs during landing after an overhead stroke. Knee biomechanics during dynamic movements such as walking, running and stair negotiation, do not return to normal for more than a year after an ACL reconstruction. This change in the biomechanics may lead to re-injury whilst performing non-steady movements during sports, where these injuries are most prevalent. Aims: To compare if the knee kinetics and kinematics in ACL injury recovered athletes return to the same level as those from an uninjured cohort during standard movements used for clinical assessment and badminton shots. Objectives: The objectives of the study were to determine: Knee valgus during the single leg squat, vertical drop jump, net shot and drop shot; Degree of internal or external rotation during the single leg squat, vertical drop jump, net shot and drop shot; Maximum knee flexion during the single leg squat, vertical drop jump and net shot. Methods: This case-control study included 14 participants with three ACL injury recovered athletes and 11 uninjured participants. The participants performed various functional tasks including vertical drop jump, single leg squat; the forehand net shot and the forehand drop shot. The data was analysed using the two-way ANOVA test, and the reliability of the data was evaluated using the Intra Class Coefficient. Results: The data showed a significant decrease in the range of knee rotation in ACL injured participants as compared to the uninjured cohort (F₇,₅₅₆=2.37; p=0.021). There was also a decrease in the maximum knee flexion angles and an increase in knee valgus angles in ACL injured participants although they were not statistically significant. Conclusion: There was a significant decrease in the knee rotation angles in the ACL injured participants which could be a potential cause for re-injury in these athletes in the future. Although the results for decrease in maximum knee flexion angles and increase in knee valgus angles were not significant, this may be due to a limited sample of ACL injured participants; there is potential for it to be identified as a variable of interest in the rehabilitation of ACL injuries. These changes in the knee biomechanics could be vital in the rehabilitation of ACL injured athletes in the future, and an inclusion of sports based tasks, e.g., Net shot along with standard protocol movements for ACL assessment would provide a better measure of the rehabilitation of the athlete.

Keywords: ACL, biomechanics, knee injury, racquet sport

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Authors: Alessandra Turini Bolsoni Silva, Nilson Rogério Da Silva

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The hospitalization process for long periods and the experience of invasive and painful clinical procedures can trigger a set of stressors in children, family members and professionals, leading to stress. Mothers are, in general, the main caregivers and, therefore, have a high degree of sadness and stress with an impact on mental health. However, the father, in the face of the mother's absence, needs to assume other responsibilities such as domestic activities and healthy children in addition to work activities. In addition, he has to deal with changes in family and work relationships during the child's hospitalization, with disagreements and changes in the relationship with the partner, changes in the relationship with the children, and finding it difficult to reconcile the new tasks as a caregiver and work. A consequence of the hospitalization process is the interruption of the routine activities of both the child and the family members responsible for the care, who can go through stressful moments due to the consequences of family breakdown, attention focused only on the child and sleepless nights. In this sense, both the mother and the father can have their health affected by their child's hospitalization. The present study aims to compare the prevalence of stress and overload in mothers and fathers of hospitalized children, as well as possible associations with activities related to care. The participants were 10 fathers and 10 mothers of children hospitalized in a hospital located in a medium-sized city in the interior of São Paulo. Three instruments were used for data collection: 1) Script to characterize the participants; 2) The Lipp Stress Symptom Inventory (ISSL, 2000) 3) Zarit Burden Interview Protocol – ZBT. Contact was made with the management of the hospital in order to present the objectives of the project, then authorization was requested for the participation of the parents; after an agreement, the time and place were convenient for the participant to carry out the interview. Thus, they signed the Free and Informed Consent Term. Data were analyzed according to the instrument application manuals and organized in Figures and Tables. The results revealed that fathers and mothers have their family and professional routine affected by the hospitalization of their children, with the consequent presence of stress and overload indicators. However, the study points to a greater presence of stress and overload in mothers due to their role as the main caregiver, often interrupting their professional life to exercise care. In the case of the father, the routine is changed due to taking on household chores and taking care of the other children, with the professional life being less affected. It is hoped that the data can guide future interventions that promote and develop strategies that favor care and, at the same time, preserve the health of caregivers and that include mothers and fathers, considering that both are affected, albeit in a different way.

Keywords: stress, overload, caregivers, parents

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Authors: E. Tugba Topcu

Abstract:

The emergency services are usually the first places to encounter forensic cases. Hence, it is important to consider forensics from the perspective of the emergency services staff and the physiological and psychological consequences that may arise as a result of behaviour by itself or another person. Accurate and detailed documentation of the situation in which the patient first arrives at the emergency service and preservation of the forensic findings is pivotal for the subsequent forensic investigation. The first step in determining whether or not a forensic case exists is to perform a medical examination of the patient. For each individual suspected to be part of a forensic case, police officers should be informed at the same time as the medical examination is being conducted. Violent events are increasing every year and with an increase in the number of forensic cases, emergency service workers have increasing responsibility and consequently play a key role in protecting, collecting and arranging the forensic evidence. In addition, because the emergency service workers involved in forensic events typically have information about the accused and/or victim, as well as evidence related to the events and the cause of injuries, police officers often require their testimony. However, both nurses and other health care personnel do not typically have adequate expertise in forensic medicine. Emergency nurses should take an active role for determining that whether any patient admitted to the emergency services is a clinical forensic patient the emergency service with injury and requiring possible punishment and knowing of their roles and responsibilities in this area provides legal protection as well as the protection of the judicial affair. Particularly, in emergency services, where rapid patient turnover and high workload exists, patient registration and case reporting may not exist. In such instances, the witnesses, typically the nurses, are often consulted for information. Knowledge of forensic medical matters plays a vital role in achieving justice. According to the Criminal Procedure Law, Article 75, Paragraph 3, ‘an internal body examination or the taking of blood or other biological samples from the body can be performed only by a doctor or other health professional member’. In favour of this item, the clinic nurse and doctor are mainly responsible for evaluating forensic cases in emergency departments, performing the examination, collecting evidence, and storing and reporting data. The courts place considerable importance on determining whether a suspect is the victim or accused and, thus, in terms of illuminating events, it is crucial that any evidence is gathered carefully and appropriately. All the evidence related to the forensic case including the forensic report should be handed over to the police officers. In instances where forensic evidence cannot be collected and the only way to obtain the evidence is the hospital environment, health care personnel in emergency services need to have knowledge about the diagnosis of forensic evidence, the collection of evidence, hiding evidence and provision of the evidence delivery chain.

Keywords: emergency department, emergency nursing, forensic cases, forensic nursing

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Authors: Souradip Paul, Arijit Paramanick, M. Suheshkumar Singh

Abstract:

Traumatic injury is the leading worldwide health problem. Annually, millions of surgical wounds are created for the sake of routine medical care. The healing of these unintended injuries is always monitored based on visual inspection. The maximal restoration of tissue functionality remains a significant concern of clinical care. Although minor injuries heal well with proper care and medical treatment, large injuries negatively influence various factors (vasculature insufficiency, tissue coagulation) and cause poor healing. Demographically, the number of people suffering from severe wounds and impaired healing conditions is burdensome for both human health and the economy. An incomplete understanding of the functional and molecular mechanism of tissue healing often leads to a lack of proper therapies and treatment. Hence, strong and promising medical guidance is necessary for monitoring the tissue regeneration processes. Photoacoustic imaging (PAI), is a non-invasive, hybrid imaging modality that can provide a suitable solution in this regard. Light combined with sound offers structural, functional and molecular information from the higher penetration depth. Therefore, molecular and structural mechanisms of tissue repair will be readily observable in PAI from the superficial layer and in the deep tissue region. Blood vessel formation and its growth is an essential tissue-repairing components. These vessels supply nutrition and oxygen to the cell in the wound region. Angiogenesis (formation of new capillaries from existing blood vessels) contributes to new blood vessel formation during tissue repair. The betterment of tissue healing directly depends on angiogenesis. Other optical microscopy techniques can visualize angiogenesis in micron-scale penetration depth but are unable to provide deep tissue information. PAI overcomes this barrier due to its unique capability. It is ideally suited for deep tissue imaging and provides the rich optical contrast generated by hemoglobin in blood vessels. Hence, an early angiogenesis detection method provided by PAI leads to monitoring the medical treatment of the wound. Along with functional property, mechanical property also plays a key role in tissue regeneration. The wound heals through a dynamic series of physiological events like coagulation, granulation tissue formation, and extracellular matrix (ECM) remodeling. Therefore tissue elasticity changes, can be identified using non-contact photoacoustic elastography (PAE). In a nutshell, angiogenesis and biomechanical properties are both critical parameters for tissue healing and these can be characterized in a single imaging modality (PAI).

Keywords: PAT, wound healing, tissue coagulation, angiogenesis

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Authors: Parvesh Singh, Vipan Kumar, Vishu Mehra

Abstract:

Quinoline-4-ones represent an important class of heterocyclic scaffolds that have attracted significant interest due to their various biological and pharmacological activities. This heterocyclic unit also constitutes an integral component in drugs used for the treatment of neurodegenerative diseases, sleep disorders and in antibiotics viz. norfloxacin and ciprofloxacin. The synthetic accessibility and possibility of fictionalization at varied positions in quinoline-4-ones exemplifies an elegant platform for the designing of combinatorial libraries of functionally enriched scaffolds with a range of pharmacological profles. They are also considered to be attractive precursors for the synthesis of medicinally imperative molecules such as non-steroidal androgen receptor antagonists, antimalarial drug Chloroquine and martinellines with antibacterial activity. 2-Aryl-2,3-dihydroquinolin-4(1H)-ones are present in many natural and non-natural compounds and are considered to be the aza-analogs of favanones. The β-lactam class of antibiotics is generally recognized to be a cornerstone of human health care due to the unparalleled clinical efficacy and safety of this type of antibacterial compound. In addition to their biological relevance as potential antibiotics, β-lactams have also acquired a prominent place in organic chemistry as synthons and provide highly efficient routes to a variety of non-protein amino acids, such as oligopeptides, peptidomimetics, nitrogen-heterocycles, as well as biologically active natural and unnatural products of medicinal interest such as indolizidine alkaloids, paclitaxel, docetaxel, taxoids, cyptophycins, lankacidins, etc. A straight forward route toward the synthesis of quinoline-4-ones via the triflic acid assisted Fries rearrangement of N-aryl-βlactams has been reported by Tepe and co-workers. The ring expansion observed in this case was solely attributed to the inherent ring strain in β-lactam ring because -lactam failed to undergo rearrangement under reaction conditions. Theabovementioned protocol has been recently extended by our group for the synthesis of benzo[b]-azocinon-6-ones via a tandem Michael addition–Fries rearrangement of sorbyl anilides as well as for the single-pot synthesis of 2-aryl-quinolin-4(3H)-ones through the Fries rearrangement of 3-dienyl-βlactams. In continuation with our synthetic endeavours with the β-lactam ring and in view of the lack of convenient approaches for the synthesis of C-3 functionalized quinolin-4(1H)-ones, the present work describes the single-pot synthesis of C-3 functionalized quinolin-4(1H)-ones via the trific acid promoted Fries rearrangement of C-3 vinyl/isopropenyl substituted β-lactams. In addition, DFT calculations and MD simulations were performed to investigate the stability profles of synthetic compounds.

Keywords: dihydroquinoline, fries rearrangement, azetidin-2-ones, quinoline-4-ones

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Authors: K. Verma, v. S. Moholkar

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In developed countries, water pollution caused by industrial discharge has emerged as a significant environmental concern over the past decades. However, despite ongoing efforts, a fully effective and sustainable remediation strategy has yet to be identified. This paper describes how enzymatic and sonochemical treatments have demonstrated great promise in degrading bio-refractory pollutants. Mainly, a compelling area of interest lies in the combined technique of sono-enzymatic treatment, which has exhibited a synergistic enhancement effect surpassing that of the individual techniques. This study employed the covalent attachment method to immobilize Laccase from Trametes versicolor onto amino-functionalized magnetic Fe₃O₄ nanoparticles. To comprehensively characterize the synthesized free nanoparticles and the laccase-immobilized nanoparticles, various techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and surface area through Brunauer-Emmett-Teller (BET) were employed. The size of immobilized Fe₃O₄@Laccase was found to be 60 nm, and the maximum loading of laccase was found to be 24 mg/g of nanoparticle. An investigation was conducted to study the effect of various process parameters, such as immobilized Fe₃O₄ Laccase dose, temperature, and pH, on the % Chemical oxygen demand (COD) removal as a response. The statistical design pinpointed the optimum conditions (immobilized Fe₃O₄ Laccase dose = 1.46 g/L, pH = 4.5, and temperature = 66 oC), resulting in a remarkable 65.58% COD removal within 60 minutes. An even more significant improvement (90.31% COD removal) was achieved with ultrasound-assisted enzymatic reaction utilizing a 10% duty cycle. The investigation of various kinetic models for free and immobilized laccase, such as the Haldane, Yano, and Koga, and Michaelis-Menten, showed that ultrasound application impacted the kinetic parameters Vmax and Km. Specifically, Vmax values for free and immobilized laccase were found to be 0.021 mg/L min and 0.045 mg/L min, respectively, while Km values were 147.2 mg/L for free laccase and 136.46 mg/L for immobilized laccase. The lower Km and higher Vmax for immobilized laccase indicate its enhanced affinity towards the substrate, likely due to ultrasound-induced alterations in the enzyme's confirmation and increased exposure of active sites, leading to more efficient degradation. Furthermore, the toxicity and Liquid chromatography-mass spectrometry (LC-MS) analysis revealed that after the treatment process, the wastewater exhibited 70% less toxicity than before treatment, with over 25 compounds degrading by more than 75%. At last, the prepared immobilized laccase had excellent recyclability retaining 70% activity up to 6 consecutive cycles. A straightforward manufacturing strategy and outstanding performance make the recyclable magnetic immobilized Laccase (Fe₃O₄ Laccase) an up-and-coming option for various environmental applications, particularly in water pollution control and treatment.

Keywords: kinetic, laccase enzyme, sonoenzymatic, ultrasound irradiation

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Authors: Aleksander Ejsmont, Stefan Wuttke, Joanna Goscianska

Abstract:

Gaining control over particle shape, size and crystallinity is an ongoing challenge for many materials. Especially metalorganic frameworks (MOFs) are recently widely studied. Besides their remarkable porosity and interesting topologies, morphology has proven to be a significant feature. It can affect the further material application. Thus seeking new approaches that enable MOF morphology modulation is important. MOFs are reticular structures, where building blocks are made up of organic linkers and metallic nodes. The most common strategy of ensuring metal source is using salts, which usually exhibit high solubility and hinder morphology control. However, there has been a growing interest in using metal oxides as structure-directing agents towards MOFs due to their very low solubility and shape preservation. Metal oxides can be treated as a metal reservoir during MOF synthesis. Up to now, reports in which receiving MOFs from metal oxides mostly present ZnO conversion to ZIF-8. However, there are other oxides, for instance, Co₃O₄, which often is overlooked due to their structural stability and insolubility in aqueous solutions. Cobalt-based materials are famed for catalytic activity. Therefore the development of their efficient synthesis is worth attention. In the presented work, an optimized Co₃O₄transition to Co-MOFviaa solvothermal approach was proposed. The starting point of the research was the synthesis of Co₃O₄ flower petals and needles under hydrothermal conditions using different cobalt salts (e.g., cobalt(II) chloride and cobalt(II) nitrate), in the presence of urea, and hexadecyltrimethylammonium bromide (CTAB) surfactant as a capping agent. After receiving cobalt hydroxide, the calcination process was performed at various temperatures (300–500 °C). Then cobalt oxides as a source of cobalt cations were subjected to reaction with trimesic acid in solvothermal environment and temperature of 120 °C leading to Co-MOF fabrication. The solution maintained in the system was a mixture of water, dimethylformamide, and ethanol, with the addition of strong acids (HF and HNO₃). To establish how solvents affect metal oxide conversion, several different solvent ratios were also applied. The materials received were characterized with analytical techniques, including X-ray powder diffraction, energy dispersive spectroscopy,low-temperature nitrogen adsorption/desorption, scanning, and transmission electron microscopy. It was confirmed that the synthetic routes have led to the formation of Co₃O₄ and Co-based MOF varied in shape and size of particles. The diffractograms showed receiving crystalline phase for Co₃O₄, and also for Co-MOF. The Co₃O₄ obtained from nitrates and with using low-temperature calcination resulted in smaller particles. The study indicated that cobalt oxide particles of different size influence the efficiency of conversion and morphology of Co-MOF. The highest conversion was achieved using metal oxides with small crystallites.

Keywords: Co-MOF, solvothermal synthesis, morphology control, core-shell

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