bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of NSAIDs as potential inhibitors of the fatty acid amide hydrolase I (FAAH-1) using three different primary fatty acid amide substrates in vitro
Authors: Dongdem Julius T. , Helegbe Gideon K. , Opare-Asamoah Kwame , Wezena Cletus A. , Ocloo Augustine 
Published: January 2022

Abstract
Background
Pain relief remains a major subject of inadequately met need of patients. Therapeutic agents designed to treat pain and inflammation so far have low to moderate efficiencies with significant untoward side effects. FAAH-1 has been proposed as a promising target for the discovery of drugs to treat pain and inflammation without significant adverse effects. FAAH-1 is the primary enzyme accountable for the degradation of AEA and related fatty acid amides. Studies have revealed that the simultaneous inhibition of COX and FAAH-1 activities produce greater pharmacological efficiency with significantly lowered toxicity and ulcerogenic activity. Recently, the metabolism of endocannabinoids by COX-2 was suggested to be differentially regulated by NSAIDs.

Methods
We analysed the affinity of oleamide, arachidonamide and stearoylamide at the FAAH-1 in vitro and investigated the potency of selected NSAIDs on the hydrolysis of endocannabinoid-like molecules (oleamide, arachidonamide and stearoylamide) by FAAH-1 from rat liver. NSAIDs were initially screened at 500 μM after which those that exhibited greater potency were further analysed over a range of inhibitor concentrations.

Results
The substrate affinity of FAAH-1 obtained, increased in a rank order of oleamide < arachidonamide < stearoylamide with resultant Vmax values in a rank order of arachidonamide > oleamide > stearoylamide. The selected NSAIDs caused a concentration-dependent inhibition of FAAH-1 activity with sulindac, carprofen and meclofenamate exhibiting the greatest potency. Michaelis-Menten analysis suggested the mode of inhibition of FAAH-1 hydrolysis of both oleamide and arachidonamide by meclofenamate and indomethacin to be non-competitive in nature.

Conclusion
Our data therefore suggest potential for study of these compounds as combined FAAH-1-COX inhibitors.
Long-term outcome of percutaneous radiofrequency ablation for periportal hepatocellular carcinoma: tumor recurrence or progression, survival and clinical significance
Authors: Cao Shoujin , Lyu Tianshi , Fan Zeyang , Guan Haitao , Song Li , Tong Xiaoqiang , Wang Jian , Zou Yinghua 
Published: January 2022

Abstract
Background/aim
Recent studies have suggested that periportal location of percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered as one of the independent risk factors for local tumor progression (LTP). However, the long-term therapeutic outcomes of percutaneous RFA as the first-line therapy for single periportal HCCand corresponding impacts on tumor recurrence or progression are still unclear.

Materials and methods
From February 2011 to October 2020, a total of 233 patients with single nodular HCC ≤ 5 cm who underwent RFA ± transarterial chemoembolization (TACE) as first-line therapy was enrolled and analyzed, including 56 patients in the periportal group and 177 patients in the nonperiportal group. The long-term therapeutic outcomes between the two groups were compared, risk factors of tumor recurrence or progression were evaluated.

Results
The LTP rates at 1, 3, and 5 years were significantly higher in the periportal group than those in the nonperiportal group (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year overall survival (OS) rates in the periportal group were significantly worse than those in the nonperiportal group (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P<0.0001). In the subgroup of single HCC ≤ 3 cm, patients with periportal HCC showed significantly worse LTP P = 0.0006) and OS (P<0.0001) after RFA than patients with single nonperiportal HCC; The univariate and multivariate analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. Furthermore, patients with single periportal HCC had significantly higher risk for IDR(P = 0.0012), PVTT(P<0.0001) and extrahepatic recurrence(P = 0.0010) after RFA than those patients with single nonperiportal HCC. .

Conclusion
The long-term therapeutic outcomes of RFA as the first-line therapy for single periportal HCC were worse than those for single nonperiportal HCC, an increased higher risk of tumor recurrence or progression after RFA was significantly associated with periportal HCC.
Autologous omentum transposition for regeneration of a renal injury model in rats
Authors: Bilgiç Tayfun , İnce Ümit , Narter Fehmi 
Published: January 2022

Abstract
Background
After renal trauma, surgical treatment is vital, but sometimes there may be loss of function due to fibrosis. This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model.

Methods
A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups. Iatrogenic renal injuries were repaired using a surgical technique (primary repair 1 group and primary repair 2 group) or transposition of the autologous omentum (omentum repair 1 group and omentum repair 2 group). Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups. All rats were sacrificed on the 7th or 18th day postoperatively, and their right kidneys were taken for histopathological evaluation.

Results
The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group (P = 0.005 and P = 0.004, respectively). There were no other significant changes in urea or creatinine levels within the intervention groups (P > 0.05). There was no significant correlation between the urea and creatinine levels and the histological scores (P > 0.05). The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree (r = 0.824, P < 0.001) and foreign body reaction in the kidney specimen (r = 0.872, P < 0.001) and a strong and negative correlation with the healing process completion score in the kidney (r = − 0.627, P = 0.001). Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen (r = 0.731, P = 0.001) and strongly and negatively correlated with the healing process completion score in the kidney specimen (r = − 0.608, P = 0.002).

Conclusion
Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation. Additionally, the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss.
Intermittent administration of peracetic acid is a mild environmental stressor that elicits mucosal and systemic adaptive responses from Atlantic salmon post-smolts
Authors: Osório João , Stiller Kevin T. , Reiten Britt-Kristin , Kolarevic Jelena , Johansen Lill-Heidi , Afonso Fernando , Lazado Carlo C. 
Published: January 2022

Abstract
Background
Fish encounter oxidative stress several times during their lifetime, and it has a pervasive influence on their health and welfare. One of the triggers of oxidative stress in fish farming is the use of oxidative disinfectants to improve rearing conditions, especially in production systems employing recirculation technology. Here we report the physiological and morphological adaptive responses of Atlantic salmon (Salmo salar L.) post-smolts to intermittent exposure to a potent oxidative agent peracetic acid (PAA). Fish reared in semi-commercial scale brackish water recirculating aquaculture system (RAS) were exposed to 1 ppm PAA every 3 days over 6 weeks. Mucosal and systemic responses were profiled before exposure, 22 and 45 days during the intermittent PAA administration.

Results
Oxidative stress was likely triggered as plasma antioxidant capacity increased significantly during the exposure period. Adaptive stress response to the periodic oxidant challenge was likewise demonstrated in the changes in plasma glucose and lactate levels. PAA-induced alterations in the transcription of antioxidants, cytokines, heat shock proteins and mucin genes showed a tissue-specific pattern: downregulation was observed in the gills and olfactory rosette, upregulation occurred in the skin, and no substantial changes in the liver. Further, PAA exposure resulted in histological changes in key mucosal organs (i.e. olfactory rosette, skin and gills); pathological alterations were predominant in the gills where cases of epithelial lifting, hypertrophy and clubbing were prevalent. In addition, intermittent PAA administration resulted in an apparent overproduction of mucus in the nasal mucosa. Lastly, PAA did not dramatically alter the ability of salmon to mount a physiological stress response in the presence of a secondary stressor, though some subtle interference was documented in the kinetics and magnitude of plasma cortisol and glucose response post-stress.

Conclusions
The present study collectively demonstrated that intermittent oxidant exposure was a mild environmental stressor that salmon could mount strong adaptive responses at systemic and mucosal levels. The results will be valuable in optimising the rearing conditions of post-smolts in RAS, especially in adopting water treatment strategies that do not considerably interfere with fish health and welfare.
Detection of hepatocarcinogens by combination of liver micronucleus assay and histopathological examination in 2-week or 4-week repeated dose studies
Authors: Hamada Shuichi , Shigano Miyuki , Wako Yumi , Kawasako Kazufumi , Satomoto Kensuke , Mitsumoto Tatsuya , Fukuda Takayuki , Ohyama Wakako , Morita Takeshi , Hayashi Makoto 
Published: January 2022

Abstract
Background
Currently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals. In the revised draft, findings such as cellular hypertrophy, diffuse and/or focal cellular hyperplasia, persistent tissue injury and/or chronic inflammation, preneoplastic changes, and tumors are listed as histopathology findings of particular interest for identifying carcinogenic potential. In order to predict hepatocarcinogenicity of test chemicals based on the results from 2- or 4-week repeated dose studies, we retrospectively reanalyzed the results of a previous collaborative study on the liver micronucleus assay. We focused on liver micronucleus induction in combination with histopathological changes including hypertrophy, proliferation of oval cells or bile duct epithelial cells, tissue injuries, regenerative changes, and inflammatory changes as the early responses of hepatocarcinogenesis. For these early responses, A total of 20 carcinogens, including 14 genotoxic hepatocarcinogens (Group A) and 6 non-liver-targeted genotoxic carcinogens (Group B) were evaluated.

Results
In the Group A chemicals, 5 chemicals (NPYR, MDA, NDPA, 2,6-DNT, and NMOR) showed all of the 6 early responses in hepatocarcinogenesis. Five chemicals (DMN, 2,4-DNT, QUN, 2-AAF, and TAA) showed 4 responses, and 4 chemicals (DAB, 2-NP, MCT, and Sudan I) showed 3 responses. All chemicals exhibited at least 3 early responses.
Contrarily, in the Group B chemicals (6 chemicals), 3 of the 6 early responses were observed in 1 chemical (MNNG). No more than two responses were observed in 3 chemicals (MMC, MMS, and KA), and no responses were observed in 2 chemicals (CP and KBrO3).

Conclusion
Evaluation of liver micronucleus induction in combination with histopathological examination is useful for detecting hepatocarcinogens. This assay takes much less time than routine long-term carcinogenicity studies.
Evaluation of risk due to chronic low dose ionizing radiation exposure on the birth prevalence of congenital heart diseases (CHD) among the newborns from high-level natural radiation areas of Kerala coast, India
Authors: Sudheer K. R. , Mohammad Koya P. K. , Prakash Anu J. , Prakash Ambily M. , Manoj Kumar R. , Shyni S. , Jagadeesan C. K. , Jaikrishan G. , Das Birajalaxmi 
Published: January 2022

AbstractBackgroundThe human population residing in monazite bearing Kerala coast are exposed to chronic low dose and low dose rate external gamma radiation due to Th232 deposits in its beach sand. The radiation level in this area varies from < 1.0 to 45.0 mGy/year. This area serves as an ideal source for conducting large-scale epidemiological studies for assessing risk of low dose and low dose rate radiation exposure on human population. The areas with a dose level of ≤1.50 mGy/year are considered as normal level natural radiation areas (NLNRAs) and areas with > 1.50 mGy/year, as high level natural radiation areas (HLNRAs). HLNRAs were further stratified into three dose groups of 1.51-3.0 mGy/year, 3.01-6.00 mGy/year and > 6.0 mGy/year. The present study evaluates the effects of chronic low dose radiation (LDR) exposure on the birth prevalence of Congenital Heart Diseases (CHD) among the live newborns monitored in hospital based prospective study from NLNRAs and HLNRAs of Kerala coast, India.MethodologyConsecutive newborns were monitored from two hospital units located in the study area for congenital malformations. Referred CHD cases among the newborns screened were confirmed by conducting investigations such as pulse oximetry, chest X-ray, electrocardiogram and echocardiogram etc.ResultsAmong the newborns screened, 289 CHDs were identified with a frequency of 1.49‰ among 193,634 livebirths, which constituted 6.03% of overall malformations and 16.29% of major malformations. Multiple logistic regression analysis suggested that the risk of CHD among the newborns of mothers from HLNRAs with a dose group of 1.51-3.0 mGy/year was significantly lower as compared to NLNRA (OR = 0.72, 95% CI: 0.57-0.92), whereas it was similar in HLNRA dose groups of 3.01-6.00 mGy/year (OR = 0.55, 95% CI: 0.31-1.00) and ≥ 6.0 mGy/year (OR = 0.96, 95% CI: 0.50-1.85). The frequency of CHDs did not show any radiation dose related increasing trend. However, a significant (P = 0.005) reduction was observed in the birth prevalence of CHDs among the newborns from HLNRA (1.28‰) as compared to NLNRA (1.79‰).ConclusionChronic LDR exposure did not show any increased risk on the birth prevalence of CHDs from high-level natural radiation areas of Kerala coast, India. No linear increasing trend was observed with respect to different background dose groups. The frequency of CHD was observed to be 1.49 per 1000 livebirths, which was similar to the frequency of severe CHD rate reported elsewhere in India and was much less than the reported frequency of 9 per thousand.
VAL-U: Psychometric properties of a Values and Civic Attitudes Scale for University Students’ Service-Learning
Authors: Ruiz-Ordóñez Yolanda , Salcedo-Mateu Amparo , Turbi Ángel , Novella Carlos , Moret-Tatay Carmen 
Published: January 2022

AbstractThe service-learning disciplines can offer a unique opportunity for civic development in university students, as there is a large body of research that links it to values and civic attitudes including a vast number of ecological issues and citizen variables. Moreover, one should bear in mind that these students are future generations that will face many pressing social and environmental issues. Given the need to develop instruments to measure the impact of a service-learning methodology in university students’ values as well as civic attitudes, VAL-U is proposed. As the university can be considered a learning step prior to the professional field, the main objective of this study was to analyse the internal consistency and factor structure of the proposed VAL-U scale in the Spanish population. The scale confirmed acceptable psychometric properties. Furthermore, the results have shown high reliability and optimal goodness of fit. Promising results are offered to employ VAL-U as a valuable tool for assessing Values and Civic Attitudes Scale for Spanish-speaking University Students’ Service-Learning.
Design, inverted vat photopolymerization 3D printing, and initial characterization of a miniature force sensor for localized in vivo tissue measurements
Authors: Kumat Shashank S. , Shiakolas Panos S. 
Published: January 2022

Abstract
Background
Tissue healthiness could be assessed by evaluating its viscoelastic properties through localized contact reaction force measurements to obtain quantitative time history information. To evaluate these properties for hard to reach and confined areas of the human body, miniature force sensors with size constraints and appropriate load capabilities are needed. This research article reports on the design, fabrication, integration, characterization, and in vivo experimentation of a uniaxial miniature force sensor on a human forearm.

Methods
The strain gauge based sensor components were designed to meet dimensional constraints (diameter ≤3.5mm), safety factor (≥3) and performance specifications (maximum applied load, resolution, sensitivity, and accuracy). The sensing element was fabricated using traditional machining. Inverted vat photopolymerization technology was used to prototype complex components on a Form3 printer; micro-component orientation for fabrication challenges were overcome through experimentation. The sensor performance was characterized using dead weights and a LabVIEW based custom developed data acquisition system. The operational performance was evaluated by in vivo measurements on a human forearm; the relaxation data were used to calculate the Voigt model viscoelastic coefficient.

Results
The three dimensional (3D) printed components exhibited good dimensional accuracy (maximum deviation of 183μm). The assembled sensor exhibited linear behavior (regression coefficient of R2=0.999) and met desired performance specifications of 3.4 safety factor, 1.2N load capacity, 18mN resolution, and 3.13% accuracy. The in vivo experimentally obtained relaxation data were analyzed using the Voigt model yielding a viscoelastic coefficient τ=12.38sec and a curve-fit regression coefficient of R2=0.992.

Conclusions
This research presented the successful design, use of 3D printing for component fabrication, integration, characterization, and analysis of initial in vivo collected measurements with excellent performance for a miniature force sensor for the assessment of tissue viscoelastic properties. Through this research certain limitations were identified, however the initial sensor performance was promising and encouraging to continue the work to improve the sensor. This micro-force sensor could be used to obtain tissue quantitative data to assess tissue healthiness for medical care over extended time periods.
Global health education for the post-pandemic years: parity, people, planet, priorities, and practices
Authors: Jacobsen Kathryn H. , Waggett Caryl E. 
Published: January 2022

AbstractGlobal health degree programs are now offered by institutions of higher education in most world regions. Based on our review of the curricula for many of these programs, we identified five domains that are central to current global health education. “Parity” emphasizes health equity as the ultimate goal of global health. “People” comprises the social, economic, cultural, and political contributors to health and access to medical care for individuals and communities. “Planet” encompasses various aspects of globalization and environmental health that affect population health. “Priorities” and “practices” include the values, data, and tools used to design, implement, and evaluate partnerships, policies, programs, and other global health interventions in countries of all income levels. The pandemic is likely to increase student demand for global health education from the undergraduate through the graduate and professional levels. Our “5 Ps model of global health education” provides a comprehensive framework for the core student learning objectives for global health today. Knowledge of each of these domains is essential for preparing students for meaningful experiential learning and skilled professional practice in global health.
In-silico activity prediction, structure-based drug design, molecular docking and pharmacokinetic studies of selected quinazoline derivatives for their antiproliferative activity against triple negative breast cancer (MDA-MB231) cell line
Authors: Abdullahi Sagiru Hamza , Uzairu Adamu , Shallangwa Gideon Adamu , Uba Sani , Umar Abdullahi Bello 
Published: January 2022

Abstract
Background
Cancer is a major health threat especially in unindustrialized nations. It surpasses coronary diseases and takes the number one killer position as a result of different global wide influences. Among many breast cancer substrates, triple-negative breast cancer (TNBC) is particularly devastating because it rapidly metastasize to other parts of the body, with a high risk of earlier recession and mortality.

Result
In this research work, four (4) quantitative structure activity relationship (QSAR) models were developed using a series of quinazoline derivatives with activities against triple negative breast cancer cell line (MDA-MB231), model 1 was selected due to its statistical fitness with the following validation parameters: R2 = 0.875, Q2 = 0.837, R2 − Q2 = 0.038, Next test set = 5, and R2ext = 0.655. Molecular docking studies was performed for the quinazoline series as well as the reference drug (Gefitinib) and the active site of the epidermal growth factor receptor (EGFR) (pdb id = 3ug2). Eight compounds (6, 10, 13, 16, 17, 18, 19 and 20) were observed to have better docking score docking scores relative to Gefitinib. Compound number nineteen from the training set (pred pIC50 = 5.67, Residual = − 0.04 and MolDock score = − 123.238) was identified as the best compound since it has the best Moldock score and was excellently predicted by the selected model with least residual value, Hence was adopted as template for the design of Ten (10) new novel compounds with better activities and better docking scores. The inhibitive activities of the designed compounds were predicted by the selected model and most of them possess an improved activity relative to the template compound (19). The designed compounds were also redocked on to active pocket of the EGFR receptor and it was observed that they displayed better docking scores compared to the Template and the reference drug (Gefitinib) utilized in the design. Furthermore, the designed compounds were subjected to ADMET and drug-likeness studies using SWISSADME and pkCSM online web tools and they were observed to be pharmacologically active, easily synthesized and do not violate the Lipinski’s rule of five.

Conclusion
Hence, the designed compounds can be employed as inhibitors of MDA-MB231 cell line after passing through in vivo and in vitro evaluation.