bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism
Authors: Lou Bowen , Wu Haoyu , Ott Hannes , Bennewitz Katrin , Wang Chen , Poschet Gernot , Liu Hui , Yuan Zuyi , Kroll Jens , She Jianqing
Published: January 2023

Background
Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction.
Methods and Results
Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation.
Conclusions
Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.
The impact of MPOWER tobacco control policies on tobacco use in African countries
Authors: Ogbodo Stephen Chukwuma
Published: January 2023

Aim
This study aims to evaluate the impact of MPOWER tobacco control policies on smoking and smokeless tobacco (SLT) use prevalence in Africa, between 2007 and 2018.
Subject and Methods:
This is a longitudinal ecological study using panel data from 40 African countries at 6 time-points between 2007 and 2018. MPOWER scores and tobacco use prevalence data were obtained from the WHO global health repository. Two-way fixed effects regression models were used to assess the impact of the MPOWER policies on smoking and SLT use prevalence among African adults. The analysis was stratified by sex and UN African sub-region.
Results
In the primary analysis of all included countries, only the fiscal tobacco control measure (represented by the price of cigarettes) was significantly associated with a decrease in tobacco use among African adults – each $10 increase in the price of a 20-cigarette pack was associated with a 2.90 (95% CI: 0.30, 5.50) percentage point decrease in smoking prevalence, and a 1.10 (95% CI: 0.02, 2.00) percentage point decrease in SLT use prevalence, among men. In the stratified analysis by UN African sub-regions, the greatest impact was observed in Western and Northern Africa, and MPOWER policies appeared to be more effective in reducing smoking prevalence than SLT use prevalence.
Conclusion
The MPOWER package (especially its fiscal component) has had an impact on tobacco use in African countries. However, more attention needs to be paid to SLT use in Africa, which appears to have been impacted to a much lesser extent than smoking.
Risk factors for patients with acute hospital-acquired symptomatic pulmonary thromboembolism
Authors: Ye Lujuan , Xie Hailiang , Lai Minggui , Zheng Guofu , Xie Yuancai , Liu Xiaochun
Published: January 2023

This study aimed to identify independent risk factors for acute hospital-acquired symptomatic pulmonary embolism (HA-SPE) by comparing the clinical data of HA-SPE and acute nonhospital-acquired symptomatic pulmonary embolism (NHA-SPE). A total of 292 patients were included in the analysis and divided into two groups: 191 patients had acute NHA-SPE, and 101 patients had acute HA-SPE. The average age of these 292 patients was 63.2 years, and the sample included 145 males. The K-M curve showed that the hazard ratio (HR) of the HA group to the NHA group in all-cause mortality was 3.807 (95% CI, [1.987,7.295], P = 0.0061). Multivariate analysis showed that malignant tumour (OR, 3.811; 95% CI [1.914-7.586], P=.000), recent surgery (OR, 7.310; 95% CI 3.392-15.755], P=.000), previous VTE (OR, 5.973; 95% CI 2.194 16.262], P =. 000), and the length of stay (LOS) (OR, 1.075; 95% CI [1.040-1.111], P=.000) were independent risk factors for acute HA-AEP (Table 2). The c-statistic for this model was 0.758 (95% CI, [0.698-0.800], P<.0001). Strengthening the prevention and control of patients with these risk factors may reduce the incidence of acute HA-SPE.
Optimized simplified constitutive models with an atlas-based finite element analysis can be utilized to predict personalized progression of knee osteoarthritis: Data from the Osteoarthritis Initiative
Authors: Mononen Mika E. , Carvajal Alexander Paz , Liukkonen Mimmi K. , Turunen Mikael J.
Published: January 2023

New technologies are required to support a radical shift towards preventive healthcare. Here we focus on evaluating the possibility of finite element (FE) analysis-aided prevention of knee osteoarthritis (OA), a disease that affects 100 million citizens in the US and EU and this number is estimated to increase drastically. Current clinical methods to diagnose or predict joint health status relies on symptoms and tissue failures obtained from clinical imaging. In a joint with no detectable injuries, the diagnosis of the future health of the knee can be assumed to be very subjective. Quantitative approaches are therefore needed to assess the personalized risk for the onset and development of knee OA. FE analysis utilizing an atlas-based modeling approach has shown a preliminary capability for simulating subject-specific cartilage mechanical responses. However, it has been verified with a very limited subject number. Thus, the aim of this study is to verify the real capability of the atlas-based approach to simulate cartilage degeneration utilizing different material descriptions for cartilage. A fibril reinforced poroviscoelastic (FRPVE) material formulation was considered as state-of-the-art material behavior and simulated mechanical tissue responses and predicted cartilage degenerations within knee joint were compared against to simpler constitutive models for cartilage. The capability of the atlas-based modeling to offer a feasible approach with quantitative evaluation for the risk for the OA development (healthy vs osteoarthritic knee, p < 0.01, AUC ~ 0.7) was verified with 214 knees. Furthermore, the results suggest that accuracy for simulation of cartilage degeneration with simpler material models is similar to models using FPRVE materials if the material parameters are chosen properly.
Identification and validation of the first EST-SSR markers based on transcriptome of Anopheles darlingi, the primary transmitter of malaria in Brazil
Authors: de Souza Alex Tomaz , Batista Jacqueline da Silva , Guimarães-Marques Giselle Moura , Rafael Míriam Silva
Published: January 2023

Background Anopheles darlingi is a monotypic species in terms of its morphological, genetic, and behavioral aspects and is the primary transmitter of human malaria (99%) in Brazil, especially in the Brazilian Amazon. In this pioneering study, 15 expressed sequence tag (EST)-simple sequence repeat (SSR) markers were obtained and characterized in samples from the municipality of São Gabriel da Cachoeira, Amazonas state, Brazil, with polymorphisms that can be used for further genetic research.
Methods and Results The specimens (from egg to larval stage) collected were bred in the insectary at INPA (National Institute for Amazonian Research). The SSR repeats within the contigs of the A. darlingi EST banks were confirmed on the Vector Base site. DNA was extracted and amplified using polymerase chain reaction and then genotyped. Fifteen polymorphic SSR loci were identified and characterized. The number of alleles totaled 76, and ranged from 2 to 9. The observed heterozygosity varied between 0.026 and 0.769, the expected heterozygosity between 0.025 and 0.776, and the mean polymorphism information content was 0.468. Eight loci showed Hardy-Weinberg equilibrium (HWE) after Bonferroni correction (P: (5%) ≤ 0.0005). No linkage disequilibrium was found among the loci.
Conclusions The polymorphic SSRs of the loci have been shown to be efficient for investigation of the variability and genetic population structure of A. darlingi.
Keyless Cryptosystem Based on Latin Square for Blockchain and Covert Communications
Authors: Desoky Abdelrahman
Published: January 2023

The authors have requested that this preprint be removed from Research Square.
Emergence of teicoplanin-non-susceptible Staphylococcus epidermidis strains: a 6-year retrospective study
Authors: Kim Subin , Choi Jae-Phil , Oh Dong Hyun , Ahn Mi Young , Yang Eunmi
Published: January 2023

The use of glycopeptide antibiotics for the treatment of Staphylococcus epidermidis infections has recently increased owing to increased oxacillin resistance. This study aimed to characterize and evaluate the clinical significance of teicoplanin-resistant S. epidermidis isolated at our hospital over a 6-year period.
During the study period, 328 strains of S. epidermidis were isolated, of which 17 (5.2%) were teicoplanin-non-susceptible. All strains were vancomycin-susceptible, and 292 (89%) were oxacillin resistant. Analysis of vancomycin and teicoplanin prescriptions revealed an increase in annual teicoplanin prescription in 2020. Although there was a decrease in glycopeptide antibiotic usage in 2020 and 2021 owing to the COVID-19 pandemic, there was a rapid increase in the number of of teicoplanin-non-susceptible S.epidermidis strains isolated in 2021 (13; 32.5%). These data suggest that extensive teicoplanin use may have induced S.epidermidis antibiotic resistance in the hospital setting through selective pressure.
The incidence of S.epidermidis teicoplanin resistance has rapidly increased at our hospital due to increased teicoplanin use. The emergence of teicoplanin-non-susceptible S.epidermidisreduces available antibiotic options and increases the risk of treatment failure. The cause of the emergence of teicoplanin-non-susceptible S.epidermidis strains needs to be further analyzed and countermeasures need to be developed against this resistance.
Thrips composition in cotton agroecosystem: a single species or a species complex?
Authors: Rao Naveen , Gaur Ram Karan , Singh Satnam , Rachana R.R. , Kumar Rishi , Pandher Suneet , Kaur Ramandeep , Yadav Sunita , Udikeri Shashikant S , Srini A J
Published: January 2023

Thrips have emerged as a major sucking pest of cotton, limiting crop productivity through direct feeding and virus transmission. Cotton thrips have been long presumed to be a single species, with all the studies from northern India reporting it as Thrips tabaci. Even the majority of work from southern and central India reports it as the sole species, T. tabaci in their studies conducted on pesticide efficacy, population dynamics, host plant resistance, and others. The present study has attempted to decode the thrips species composition in cotton collected from 22 locations representing the north-western, central, and southern zones of India using both morphological and molecular tools. The studies report the prevalence of a thrips species complex in cotton, which is dominated by Thrips palmi with the coexistence of other thrips species, viz., T. tabaci, Scirtothrips sp., and Frankliniella schultzei. Our studies also suggest the maiden report of Chaetanaphothrips orchidii and Asprothrips bimaculatus thrips species in cotton from India. The T. palmi genetic diversity analysis revealed the presence of cryptic species, and haplotyping showed the existence of 53 haplotypes globally, out of which two new haplotypes have been reported in the present study. The possible reasons for the change in cotton thrips composition from a single species to a complex over the years have also been analyzed using historical population dynamics data from the past 15 years, which indicates that the invasion of new species over the previous years might be responsible for the change in the population structure of thrips in cotton.
A CpG-based prediction model for the diagnosis of hepatocellular carcinoma patients
Authors: Luo Biyuan , Zhou Ning , Chen Zui , Liu Xianling
Published: January 2023

Objective: Hepatocellular carcinoma(HCC),the most prevalent form of liver cancer, owns high morbidity and mortality. Early diagnosis for HCC is critical for the treatment and prognosis. Early diagnosis plays an important role in the improvement of HCC prognosis.
Methods: All clinical characteristics of 233 participants from multicenter were collected, including 115 HCC patients, 103 patients with cirrhosis, and 15 samples from healthy individuals. We identified several indicators significantly associated with HCC morbidity through logistic analysis to develop the prediction model. Further analysis revealed the independent predictive capacity of the predictive model. A nomogram comprising the predictive model was established, and data on 133 patients was utilized for the development of the model and on 100 patients was utilized for the validation. Furthermore, dozens of patients with tumors smaller than 2cm were collected for additional validation. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the predictive model.
Results: As a result, we identified five indicators that were significantly associated with HCC morbidity through univariate analysis and multivariate analysis. The predictive model was consist of age, drinking status and blood indicators, including AFP(alpha-fetoprotein),HBV(hepatitis B virus)infection status and a differential methylation CpG site. All the factors above were incorporated into the nomogramand the application of the nomogram gave good discrimination and good calibration. Calibration curves showed a favorable consistency between the predicted probabilities. ROC curve analysis showed that the nomogram had good discrimination, with AUC of 0.852 and 0.857 in the training group and validation group, respectively. Moreover, decision curve analysis has been implemented to evaluate and compare prediction nomogram.
Conclusion: The study provides a novel model for early diagnosis HCC, better than traditional screening and diagnostic indicators.
Suppressing infiltration and coffee-ring effects of colorimetric reagents on paper for trace-level detection of Ni (II)
Authors: Chen Yiyu , Nilghazd Azadeh , Liu Ruitong , Liu Shan , Li Lizi , Kong Yuling , Wan Xiaofang , Tian Junfei
Published: January 2023

PVA matrix was induced to suppress infiltration and coffee-ring effects during the colorimetric analysis on a paper substrate and was applied to improve the trace-level detection of nickel ions (Ni2+) in environmental samples. To improve the color response, cross-linked PVA matrix was used to anchor the indicator reagent of Ni2+ on the surface of the porous paper substrate as well as reduce evaporation flow with increasing hydrogen bonding in the sample droplet. These phenomena mitigated the loss of color signal by suppression of the infiltration and coffee-ring effects. Under an optimized condition — in terms of crosslinker's concentration and addition order, type of commercial filter paper, and loading volume of the PVA/indicator mixture — the sensor obtained a limit of detection (LOD) as low as 0.92 ppm and a notable linear behavior of R2>0.97 at a linear range of 0.5-50 ppm which is sufficient for the detection of legal maximum residue limit (MRL) of Ni2+ in wastewaters in China. The PVA-assisted sensor showed good selectivity to most metal ions and could normally work at different pH levels ranging from 3 to 9. The sensor also possessed highly sensitive and stable performance at a normalized level in repetitive measurements and a shelf-life of more than 3 months. These results suggest that our work can provide a facile approach to boost the sensitivity and reliability of paper-based sensor to monitor Ni2+ concentration at trace level in aqueous samples with good selectivity and prolonged shelf-life.
A practical two-step procedure for taking into account all available information (prior and current) about influence quantities in measurement uncertainty analysis
Authors: Huang Hening
Published: January 2023

This paper considers the problem of computing the combined standard uncertainty of an indirect measurement, in which the measurand is related to multiple influence quantities through a measurement model. In practice, there may be prior information or current information, or both, about the influence quantities. We propose a practical two-step procedure for taking into account all available information (prior and current) about influence quantities in measurement uncertainty analysis. The first step is to combine prior and current information to form the merged information for each influence quantity based on the weighted average method or the law of combination of distributions. The second step deals with the propagation of the merged information to calculate the combined standard uncertainty using the law of propagation of uncertainty (LPU) or the principle of propagation of distributions. The proposed two-step procedure is based entirely on frequentist statistics. A case study on the calibration of a test weight (mass calibration) is presented to demonstrate the effectiveness of the proposed two-step procedure and compare it with a subjective Bayesian approach.
Hazards are the key drivers of uncertainties surrounding riverine flood risks
Authors: Hosseini-Shakib Iman , Alipour Atieh , Lee Benjamin Seiyon , Srikrish Vivek , Nicholas Robert , Keller Klaus , Sharma Sanjib
Published: January 2023

Flooding drives considerable risks. Designing strategies to manage these risks is complicated by the often-large uncertainty surrounding flood risk projections. Uncertainty surrounding riverine flood risks can stem, for example, from choices regarding boundary conditions, model structures, and parameters as well as interactions among hazards, exposures, and vulnerabilities. A quantitative understanding of which factors drive uncertainties surrounding flood hazards and risks can inform the design of mission-oriented research. Here we analyze a case study to (i) characterize key uncertainties impacting flood risk projections and (ii) characterize the most important drivers of the uncertainties surrounding riverine flood hazards and risks. We find that the projected flood risk is most sensitive to factors associated with flood hazards: upstream discharge, riverbed elevation, channel roughness, and the digital elevation model resolution. Our framework and results can help to improve flood-hazard and risk projections.
Geodiversity and Biodiversity to Delimit Natural Protected Areas. Examples From the Jaén Province (Southern Spain)
Authors: Nieto LUIS M. , Fernández TOMÁS , Leiva-Lozano Juan-Enrique
Published: January 2023

Geodiversity and biodiversity have been assessed in an area of the Jaén province (Southern Spain). The first one from the consideration of partial indexes based on lithology, geomorphology, pedology, hydrology, paleontology, mineralogy and geosites. Biodiversity, considering a biodiversity index and endangered species index. This area shows the contact between the Guadalquivir Basin and the Betic External Zones. In addition, several natural protected areas have been defined, among which the Cazorla, Segura and Las Villas Natural Park (where mainly Prebetic materials outcrop) and the Sierra Mágina Natural Park (made up of Subbetic materials) stand out. The high and very high values of geodiversity have been located in an area where mainly Subbetic materials outcrop, including the Sierra Mágina Natural Park, and which coincides to a large extent with the front of the Betic External Zones and its contact with the Guadalquivir Basin. However, the Cazorla, Segura and Las Villas Natural Park is outside this area of high or very high geodiversity. Both natural parks fit well in areas where biodiversity and threatened species are important. These differences between the geodiversity values and the boundaries of these natural areas allows suggesting that, for delimitation of any natural protected area, its boundaries should be defined based on knowledge of the geodiversity and biodiversity of the region where the natural area is located.
Characteristics of nutrients accumulation in the bottom sediment of the surface-flow constructed wetlands of Mata lake during its operational maturity，China
Authors: Duan Zhenhao , Xing Liqi , Niu Xiaoyin , Li Menghong , Ma Yanfei , Gao Peiling , Teng Haowei
Published: January 2023

As a nutrients reservoir of surface-flow constructed wetlands (SFCWs), the substrate plays an important role in water purification, and it is significant to investigate the accumulation and release characteristics of nutrients to maximize the efficiency of constructed wetlands (CWs) for wastewater purification. In this study, we analyzed the total nitrogen (TN), total phosphorus (TP) and organic matter (OM) in the bottom sediment and conducted static release experiments on column core samples in order to evaluate the accumulation characteristics of nutrients and the current status of the ecological water environment in the SFCWs of Mata Lake, which has been in operation for 6 years. Results showed that: (1) The average contents of TN, TP and OM were 2.30 ± 0.006 g/kg, 0.26 ± 0.0006 g/kg and 10.49 ± 0.04 g/kg, respectively. There were differences in the spatial distribution of nutrients based on ArcGIS spatial interpolation simulation analysis. (2) The organic index (Org-index) in the sediment was evaluated as lightly polluted and the TP was evaluated as clean, but the organic nitrogen (Org-N) index was evaluated as heavily polluted. (3) The release amount of nutrients in the static release experiment showed a general trend of ascending and then descending, and the maximum release rate was observed between 9 and 12 days.
The Role of Heuristics and Biases in Complex Choices
Authors: Gurney Nikolos , Miller John , Pynadath David
Published: January 2023

Many choices are complex. These choices entail consideration of multiple variables characterized by non-linear interactions. Prior research into the complex choice process of people neglects two categories of major choice determinants: heuristics and biases. This research takes on the challenge of integrating such behavior determinants into the study of complex choices. We do so using a new experimental paradigm in which participants tune on-screen dials that represent choice variables. Through their tuning efforts, participants can discover information about the choice space. Specifically, this new paradigm allows us to document how anchoring and framing effects impact the complex choice process. We find that loss framing incites participants to expend more effort examining choice variables before selecting an option. An aspirational anchor, on the other hand, was correlated with decreased search effort by participants. Interestingly, the two did not share an interaction. Additionally, when participants did not have an aspirational anchor, the data suggest they relied on prior experience for an anchor value.
Etiological Diagnosis of Infectious Coxitis Depending on the Patient's HIV Status
Authors: Gerasimov I. A. , Peretsmanas E. O. , Tyulkova T. E. , Panova A. E. , Zubikov V. S. , Beresnev O. V.
Published: January 2023

The objective: to develop the procedure for etiological diagnosis of infectious coxitis (IC) depending on the patient's HIV status.

Subjects and Methods. The data of medical records of 97 patients with signs of IC were analyzed. Patients were divided into group depending on their HIV status.

Results. The time required to diagnose IC was identified, and it made 7.35 ± 1.30 months for HIV-positive patients, and 6.25 ± 0.90 months for HIV negative patients (p > 0.05). The procedure was developed to be implemented when a patient complained of pain in the hip joint. Patients with HIV infection and suspected IC should undergo computed tomography (CT) of the hip joints, and HIV-negative patients should have CT done if the hip joint X-ray is not informative. The use of CT in the HIV+ Group reduced the diagnostic time from 9.4 ± 1.3 to 5.3 ± 1.3 months (p = 0.680), in the HIV- Group – from 8.7 ± 1.2 to 3.8 ± 0.6 months (p = 0.02). The reason why diagnosis took that long was the rare use of invasive methods at the outpatient stage. Thus, puncture of the hip joint was performed in the HIV+ Group in 2.7% of cases, in the HIV- Group – in 10%. Trepanobiopsy performed in a hospital made it possible to establish the etiology of IC in all patients. The diagnostic efficacy of microbiological tests in case of tuberculous coxitis made 48.64% in the HIV+ Group and 30.0% in the HIV- Group, in case of nonspecific coxitis it was 32.43% and 30.0%, respectively.
Modeling Automatic Room Temperature and Humidity Monitoring System with Fan Control on the Internet of Things
Authors: Hendajani Fivtatianti , Mughni Arif , Wardhani Ire Puspa , Hakim Abdul
Published: January 2023

The Internet of Things (IoT) aims to expand the benefits of being connected to the Internet network continuously. It functions as a control system that has been widely applied in various fields because in certain case people are not allowed in certain rooms for security reasons. The research aimed to create a temperature and humidity monitoring system using as many fan controls as expected by utilizing IoT. The model used input in the form of temperature and humidity sensors. The output was a motor driver that drove a fan and used a microcontroller as the main processor. IoT-based systems consisted of hardware and software. Hardware included NodeMCU ESP8266 V3, DHT22 sensor, L298N motor driver module, fan, and computer. Meanwhile, the microcontroller software was made using Arduino IDE. From the test results, the system model works well. Fan control is set manually based on desired room temperature and humidity monitoring based on IoT. A mobile phone can also monitor temperature and humidity and control fans. The DHT22 sensor can read temperature and humidity every two seconds so that the resulting data is stable to display. Then, the L298N motor driver can adjust the fan speed with Pulse Width Modulation (PWM) using analog data ranging from 1 to 1.024.
Spatio-temporal variability of glacier surface area, ELA, and AAR in the Mago river basin of Arunachal Pradesh
Authors: Nunchhani V. , Mekro V. , Bandyopadhyay A. , Bhadra A.
Published: January 2023

The spatial and temporal variations of glacier surface area, annual equilibrium line altitude (ELA), and accumulation area ratio (AAR) in Mago basin, Eastern Himalaya, are studied over 1988–2019 using Landsat data. The glacier surface area was mapped using automatic glacier extraction index (AGEI) and 49 glaciers named as G1–G49 were found in 2019. Fifteen glaciers with area greater than 1 km2 in 2019 were selected for analysis. An automatic GIS tool comprising area altitude balance ratio (AABR), AAR, and mean glacier elevation (MGE), and combination of NIR band and Otsu threshold, were used for determining ELA. All glaciers experienced area shrinkage with a total loss of 15.22 km2 (28.48%) at 0.49 km2 (0.92%) per annum. G1, G9, G15, G35, G41, and G42 showed significant decreasing trend in area. Glaciers facing South-West showed highest deglaciation. For the annual ELA, all glaciers showed increasing trend and significant increasing trend was observed in G2, G15, and G40. Overall, there was an increase in ELA by 137.3 m at 4.43 m/year. The average AAR varied from 0.44 to 0.97. Average AAR of about 0.8 was observed in South, South-East, and North facing, about 0.6 in South-West and West facing, and about 0.7 in East facing glaciers.
Detection of Acanthamoeba spp. in groundwater sources in a rural area in the Philippines
Authors: Padua Mark F F E. , Masangkay Frederick Ramirez , Alejandro Grecebio Jonathan D. , Milanez Giovanni De Jesus
Published: January 2023

Research on free-living amoebae (FLA) and its public health implication as an etiologic agent of parasitic infection in humans has recently gained traction in the Philippines. This study aimed to identify potential FLAs in collected groundwater samples from Masinloc, Zambales, Philippines. Fifty-four (54) water samples were collected in 250-mL sterile polyethylene containers by purposive sampling from selected groundwater sources in six (6) barangays of Masinloc. The samples were vacuum filtered through a 1.2-μm pore glass microfiber filter, cultured onto non-nutrient agar (NNA) lawned with Escherichia coli, and observed microscopically for amoebic growth for 14 days using light microscopy. Amoebic growth was observed in 11.1% (6/54) of water samples. DNAs from positive samples were extracted and were made to react with polymerase chain reaction using Acanthamoeba-specific JDP1 (5′-GGCCCAGATCGTTTACCGTGAA-3′) and JDP2 (5′-TCTCACAAGCTGCTAGGGAGTCA-3′) primers, and universal primer Euk A (5′-AACCTGGTTGATCCTGCCAGT-3′) and Euk B (5′-TGATCCTTCTGCAGGTTCACCTAC-3′). The presence of Acanthamoeba genotypes T4, T7, and T11 was confirmed using molecular and phylogenetic analysis. Our results confirmed that groundwater sources from two of six sampling sites (33.3%) in Masinloc, Zambales, were contaminated with potentially pathogenic FLAs. Proper identification of risk factors that may cause contamination consequently leads to the implementation of programs that will prevent future infections.
The Analysis of Cyclophosphamide and its Metabolites
Authors: Malet-Martino Myriam , Gilard Veronique , Martino Robert
Published: January 2023

Cyclophosphamide (CP) has been in clinical use for the treatment of malignant disease for over 40 years. CP is inactive until it undergoes complex metabolic pathways leading to the ultimate alkylating agent, phosphoramide mustard, but also to inactive and toxic metabolites. Sensitive and specific methods are now available for the measurement of CP and its enantiomers, its metabolites and their stereoisomers, in biological matrices. An overview is given of the methods of
analysis of CP and its metabolites described in literature since 1993 as well as the current knowkJge about its metabolism. Five classes of methods are described: (1) thin-layer chromatography-photographic densitometry, (2) high performance liquid chromatography, (3) gas chromatography and gas chromatography coupled to mass spectrometry, (4) phosphorus-31 nuclear magnetic resonance and (5) enantiomeric separation. In each case, sample clean up and preparation are described. Precision and limits of quantification of the assays are indicated. A table summarizes all the analytical methods for assaying each metabolite.
Advances in Non-Peptide Glucagon Receptor Antagonists
Authors: Madsen P. , Brand C. L. , Holste J. J. , Knudsen L.B.
Published: January 2023

This review deals with glucagon receptor antagonism as a possible treatment of Type 2 diabetes. The role of glucagon in animal models has been studied by glucagon antibodies as model antagonists. Depending upon the animal model studied, selective glucagon deficiency produced by immunoneutralisation suggests that glucagon plays a modest (rats) to substantial (rabbits) role in the maintenance of euglycaemia and is an important diabetogenic factor. These data strongly suggest that glucagon antagonism may be a beneficial and safe therapeutic approach for the treatment of Type 2 diabetes. Further, the progress on non-peptide glucagon receptor antagonists is reviewed with special focus on the different classes of glucagon receptor antagonists published, namely quinoxalines / pyrrolo[l ,2-a]quinoxalines, mercaptobenzimidazoles, 2-pyridyl-3,5-diarylpyrroles, quinoline hydrazones,
·4.-phenylpyridines, and alkylidene hydrazides.
Treating Asthma with Anti-IgE or Anti-IL5
Authors: Lotvall Jan , Pullerits Teet
Published: January 2023

In the last decades, several key mechanisms driving asthma pathophysiooogy have been discovered. These include the role of IgE in allergic disease, and the role of IL-5 in eosinophilic inflammation. In the last few years, tools to block each of these have been developed. At this time, early clinical studies with neutralizing antibodies against both IgE and IL-5 have been performed in asthma patients, with promising results, and larger studies are underway. The mechanisms of, and possible role of, both anti-IgE and anti-IL-5 treatment in asthma are discussed in this review article.
Structural and Mechanistic Aspects of Evolution of β-Lactamases and Penicillin-Binding Proteins
Authors: Massova Irina , Mobashery Shahriar
Published: January 2023

Penicillin-binding proteins (PBPs) and β-lactamases are related enzymes, the former are the targets for β-lactam antibiotics and the latter are resistance enzyme to these antibiotics. The two families of enzymes share structural topologies and certain mechanistic features. However, these classes of enzymes have diversified substantially and have broadened the reaction repertoire for their catalytic properties. This report addresses the issues of the evolution of function of these proteins.
The Immune System and the Effects of Non-volatile Anesthetics on Neutrophil Transmigration Through Endothelial Cell Monolayers
Authors: Hofbauer Roland , Kaye Alan D. , Kapiotis Stylianos , Wagner Oswald , Frass Michael
Published: January 2023

Inflammation represents the consequence of capillary dilation with accumulation of fluid and transmigration of leukocytes into the surrounding tissue. Leukocytes play a major role in the defense system of the body against invading microorganisms. This defense system has a non-specific branch consisting of granulocytes and macrophages and a specific branch of lymphocytes. Granulocytes release cytotoxic compounds from their intracellular granules into their local environment when encountering microorganisms. This random destruction happens rapidly, but it may also harm healthy tissue of the body. Leukocytes patrol the body by circulating through the blood and lymphatic system ensuring a continuous surveillance which is a prerequisite for an efficient defense. Upon tissue damage and inflammation, leukocytes are recruited from the blood to sites of injury, and this trafficking displays exquisite specificity.

In the late 1890's, Metchnikoff noted the power of certain blood cells to move towards microorganisms and ingest them. In fact, leukocytes adhere to the endothelium of the blood vessels, and subsequently leave the circulation by transmigration through the intercellular junctions of the endothelial cell monolayer. Transmigration is driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to the endothelium, basement membranes, and other surfaces is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation may become chronic in many pathophysiologic processes and disease states.

In long-term mechanically ventilated critically ill patients, non-volatile anesthetics are needed over a prolonged time period. Perioperative infections are a major cause of morbidity and mortality in critically ill patients. Therefore, the influence of non-volatile anesthetics and opioid agents on the immune system is of high interest.

After presentation of the different effectors of the immune system and their fluxes through the body, the aim of this review is to propose a general model of leukocyte transmigration through endothelial cell monolayers. It emphasizes in which way different non-volatile anesthetic drugs may affect the non-specific branch of the immune system, i.e. the leukocyte transmigration through endothelial cell monolayers.
Computational Repurposing of Potential Dimerization Inhibitors against SARS-CoV-2 Main Protease
Authors: Borkotoky Subhomoi , Prakash Archisha , Modi Gyan Prakash , Dubey Vikash Kumar
Published: January 2023

Background:

The screening, design, and synthesis of various dimerization inhibitors have been
an active area of interest for structure-based drug design efforts. Functionally important dimers, such as
human immunodeficiency virus (HIV) protease and surviving, are being targeted for such studies over
time. Computational repurposing of potential drug candidates provides a cost and time-efficient way in
the drug discovery life cycle.

Objective:

Concerning the current coronavirus disease (COVID-19) scenario, the functionally active dimer
of SARS-CoV-2 (severe acute respiratory syndrome) main protease (Mpro) is used as a target to
screen possible dimerization inhibitors.

Methods:

A database of small molecule protein-protein interaction inhibitors was screened for the study.
This study used molecular docking, followed by molecular dynamics (MD) simulation and postsimulation
binding energy predictions.

Results:

From the selected 183 compounds, a diazene-based compound and a salicylic-type compound
were identified as possible dimerization inhibitors in this study. These two compounds formed stable
complexes with the Mpro during the MD simulations. The complexes formed by these two compounds
were also unable to form important salt bridge interactions required for the dimerization of the protomers.

Conclusion:

Experimental studies on both compounds were previously conducted as dimerization inhibitors
in HIV. The data led to the possibility of exploring the identified compounds as dimerization inhibitors,
which could be important for SARS-CoV-2 therapeutics.
Hemodynamic Changes after Continuing or Omitting Regular Angiotensin
Converting Enzyme Inhibitors before Cataract Surgery: A Comparative
Study
Authors: Khademi Saeed , Jouybar Reza , Ahmadi Sedigheh , Asmarian Naeimehossadat , Ghadimi Maryam , Salari Mehrdad , Emami Soodabeh
Published: January 2023

Aims:

In this study, we aimed to appraise the effects of interrupting (discontinuing) vs. continuing
Angiotensin receptor blockers (ARBs) and Angiotensin-Converting Enzyme Inhibitors
(ACEIs) on the hemodynamic changes of patients during and after cataract surgery.

Methods and Materials:

Patients aged 40-70 years, American society of anesthesiologist (ASA) class
II, taking ACEI/ARB medications, who were admitted to Khalili hospital (Shiraz, south of Iran) for
cataract surgery, were enrolled in the study. Patients were randomly divided into two groups for continuing
or withdrawing the use of ACEI/ARBs. Group 1 included the patients who continued
ACEI/ARB administration, and group 2 included those who discontinued them before surgery. In the
operating room, relevant demographic information was collected in addition to the data on patients’
basic clinical status, including heart rate and blood pressure, before induction of anesthesia, during,
and after that. The collected data were analyzed using SPSS 21, and p-values < 0.05 were considered
statistically significant.

Results:

Any significant differences were not revealed in demographic variables (age, sex, diabetes,
hypertension, Myocardial infarction, Smoking, and duration of drug therapy) between the two groups.
Time effect was significant (p<0.001) for systolic blood pressure, diastolic blood pressure, and heart
rate, and interaction between time*group was not significant (p=0.431, p=0.566, and 0.355) for systolic
blood pressure, diastolic blood pressure, and heart rate. However, the group effect wasn’t significant
(p=0.701, p=0.663, and p=0.669) for systolic blood pressure, diastolic blood pressure, and heart rate.

Conclusion:

It seems that in some minor surgeries, such as cataract surgery, withdrawal or continuation of
ACEIs/ARBs have no significant effect on the hypotension and heart rate of patients during orafter an operation.

Clinical Trial Registration Number:

The study has been registered in the Iranian registry for clinical trials
(IRCT20141009019470N78).
Discovery of Novel Tetramethylpyrazine Containing Chalcone Derivatives as Anti-Inflammatory Agents
Authors: Bukhari Syed Nasir Abbas , Abdelgawad Mohamed Abdelwahab , Amjad Muhammad Wahab , Munir Muhammad Usman , Sheikh Fatima Akbar
Published: January 2023

Background:

Chalcones are precursors of flavonoids and exhibit a broad spectrum of pharmacological activity.

Objective:

As anti-inflammatory agents, two series of chalcone derivatives and chalcone-based oximes were synthesized and characterized. To integrate the tetramethylpyrazine moiety into these novel molecules, the multifunctional natural chemical ligustrazine was employed.

Methods:

A variety of newly synthesized ligustrazine-based chalcones were utilized as precursors for the synthesis of new oximes and their inhibitory activity against COX-1, COX-2, and LOX-5 enzymes were compared.

Results:

The conversion of ketones to their oxime derivatives increased the effectiveness of COX-1 and COX-2 inhibition. Due to the substituted ether groups, oxime derivative 5d had the lowest IC50 values of 0.027 ± 0.004 μM and 0.150 ± 0.027 μM for COX-1 and COX-2 isoenzymes, respectively. Notably, the oxime derivative's highest effectiveness is conferred by the presence of methoxymethoxy or hydroxy groups at the C-3 and C-4 positions on the phenyl ring. The 6b derivative with a long alkyl chain ether group was shown to be the most powerful 5-LOX inhibitor. All compounds were also assessed for their ability to inhibit nitric oxide generation and LPS-induced IL-6, IL-1β, and TNF-α production in RAW 264.7 macrophages. Finally, in order to determine the structural effects responsible for the binding mechanism of compounds, they were docked into the binding sites of COX-1, COX-2, and 5-LOX, which revealed an inhibitory mechanism of action and demonstrated the relevance of various types of interactions.

Conclusion:

The findings showed that these novel compounds had a significant impact on antiinflammatory actions.
Network Pharmacological Study of Compound Kushen Injection in
Esophageal Cancer
Authors: Guo Dongli , Jin Jing , Liu Jianghui , Ren Meng , He Yutong
Published: January 2023

Aim:

To provide new methods and ideas for the clinical application of integrated traditional
Chinese and Western medicine in the treatment of esophageal cancer.

Background:

Traditional Chinese medicine compound Kushen injection (CKI) has been widely
used in the clinic with adjuvant radiotherapy and chemotherapy. However, the mechanism of action
of CKI as adjuvant therapy for esophageal cancer has not yet been described.

Method:

This study is based on network pharmacology, data mining, and molecular docking
technology to explore the mechanism of action of CKI in the treatment of esophageal cancer. We
obtained the effective ingredients and targets of CKI from the traditional Chinese medicine system
pharmacology database and analysis platform (TCMSP) and esophageal cancer-related genes from
the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases.

Result:

CKI mainly contains 58 active components. Among them, the top 5 active ingredients are
quercetin, luteolin, naringenin, formononetin, and beta-sitostero. The target protein of the active
ingredient was matched with the genes associated with esophageal cancer. The active ingredients
targeted 187 esophageal cancer target proteins, including AKT1, MAPK1, MAPK3, TP53,
HSP90AA1, and other proteins. Then, we enriched and analyzed the Gene Ontology (GO) and
Kyoto Encyclopedia of Genes and Genomes (KEGG) and used AutoDockVina to dock the core
targets and compounds. Finally, PyMOL and Ligplot were used for data visualization.

Conclusion:

This study provides a new method and ideas for the clinical application of integrated
traditional Chinese and Western medicine in the treatment of esophageal cancer.
Fatal Clostridium sporogenes Soft Tissue Polymicrobial Infections in Two
Immunocompetent Cases: Case Report
Authors: Gulati Neelam , Chaudhary Preeti , Gupta Varsha , Dhanda Gazal , Kumar Mani Bhushan , Sharma Swati , Goel Anku , Kumar Attri Ashok
Published: January 2023

Background:

Clostridium sporogenes is reported rarely in literature. Reports from the skin
and soft tissue infections are even less, more so in immunocompetent patients.

Case Presentation:

Two skin and soft tissue infections with C. sporogenes in immunocompetent patients
have been presented in this study. One of the cases was following an electrical burn wound, and
the other was following a bedsore. Both patients expired despite antibacterial treatment and debridement.

Discussion and Conclusion:

C. sporogenes had usually been reported after trauma particularly after
penetrating and deep wound infection. More attention should be given to these patients so that the infection
can be treated and diagnosed early in suspected anaerobic infections like Clostridium species.
Guggulsterone Promotes Nasopharyngeal Carcinoma Cells Exosomal
Circfip1L1 to Mediate miR-125a-5p/VEGFA Affecting Tumor Angiogenesis
Authors: Zhou Ting , Zhao Shunli , Tang Sanyuan , Wang Yongli , Wu Ruoxia , Zeng Xiaoyan , Yang Ping , Zhang Xi , Tian Xuefei
Published: January 2023

Background:

Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone
(GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on
NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1
from NPC cells and its regulatory mechanism.

Methods:

NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal
epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments.
HNE1 cells were treated with GS (20, 40, 60 μmol/L). The expressions of miR-125a-5p and circFIP1L1
were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and
flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and
VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs
angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to
evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs.

Results:

miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of
exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression
of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a-
5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting
the VEGFA pathway to repress HUVECs angiogenesis.

Conclusions:

GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis
affecting tumor angiogenesis.
Introductory Notes on Mechanisms in Oxygen Atom Transfer Reactions of Transition Metal Complexes
Authors: Bakhtchadjian Robert
Published: January 2023

Investigations of the mechanisms of oxygen atom transfer reactions of transition metal organometallic complexes are mainly related to their abundance in chemical syntheses and biological oxidation processes. They are important stages in the catalytic and enzymatic oxidation cycles of substrates, as well as in the catalytic oxidation of water. These brief notes on the mechanisms of oxygen atom transfer reactions involve certain fundamentals (geometric and electronic structures, spin states and reactivity of oxocomplexes), as well as some specific peculiarities of the oxo-atom transfer reactions of transition metal complexes (hydrogen atom abstraction and oxygen rebound mechanisms, intra- and intermolecular types of oxo-atom transfer, multistate reactivity). This chapter introduces readers to the categorization and place of oxo-atom transfer reactions in the classification of catalytic oxidation processes in the context of general problems of the mechanisms in this area. The chapter also provides readers with certain data on the activation of dioxygen and the functionalization of C-H bonds in oxidation processes via the oxo-atom transfer reactions of transition metal complexes. The role of the two and multiple spin states reactivity in the mechanisms of these reactions has also been discussed. This chapter is written mainly for non-specialist readers in this area and serves as a general introduction to the next chapters of this collection of works.