bluuebunny/crossref_metadata_2025 huggingface dataset:
Proof-of-concept study for a long-acting formulation of ivermectin injected to cattle as a complementary malaria vector control tool
Authors: Pooda Sié Hermann , Moiroux Nicolas , Porciani Angélique , Courjaud Anne-Laure , Roberge Christophe , Gaudriault Georges , Sidibé Issa , Belem Adrien Marie Gaston , Rayaissé Jean-Baptiste , Dabiré Roch K. , Mouline Karine
Published: August 2022

Background: Peridomestic animals play a role in maintaining residual transmission of Plasmodium, being alternative blood meal sources for malaria vectors. The blood of animals treated with veterinary formulations of ivermectin show a mosquitocidal effect on malaria vectors, but for a too short period of time to impact Plasmodium transmission. This study proposes to treat cattle with innovative long-acting (six months) injectable formulations of ivermectin as a complementary vector control measure.Methods: The local breeds of cattle were used in two treatment arms (Four cattle injected with two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg, and two control arms (Four cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3-5 days old Anopheles coluzzii mosquitoes through direct-skin feeding assays, from one to 210 days after treatments. Formulations’ efficacy was evaluated and compared using Cox proportional hazards survival models, Kaplan-Meier estimates and 4 parameters log-logistic regression on cumulative mortalities. These results were extrapolated to field scenarii using entomological and transmission models, considering different mosquito feeding preferences, hosts abundances, and bed nets uses ratios. Results: Both formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (Hazard ratios > 1). The treatments significantly reduced mosquito survival, with the average median survival times of 4-5 days post-feeding. The Lethal Concentrations to kill 50% of the Anopheles (LC50) before they become infectious (10 days after infectious blood meal) were reached until 210 days post injection for both formulations. Modeling showed that administering long-acting ivermectin formulations to calves would significantly decrease Anopheles populations in the fields. The population of infectious vectors may decrease from 35% to 75% depending mostly on the mosquito feeding preference and on the hosts species relative availability.Conclusions: This study shows that, in complement to bed nets, a long-lasting BEPO® formulation of ivermectin injected to cattle could help to decrease field populations of malaria mosquitoes and residual transmission, the impact of this approach being dependant on the field epidemiological context.
Blockchain-assisted authentication and key agreement scheme for IoT based Healthcare System
Authors: RANI DIVYA , Tripathi Sachin , Tomar Ashish
Published: August 2022

Nowadays, the research work on integration of Blockchain in IoT based Healthcare System is highly focused in order to make the system decentralised, transparent and immutable. However, there are very few works that have integrated Blockchain for authentication and key establishment in IoT based Healthcare System. The patient’s medical data collected through IoT devices are vulnerable to attack by unauthorised user. Therefore, this paper consists of blockchain based authentication and key establishment scheme. Unlike the existing work, this paper uses Consortium Blockchain in order to remove public access and reduce third-party dependency. In addition, a secret key is established between Hospital Server and Smart Device for secure communication between them. A detailed Informal security analysis shows that the proposed protocol is secure and satisfy the predefined security goals. The Blockchain concept is implemented using Hyperledger Fabric platform. This provide multi-channel support where the transactions are executed privately by creating separate channel making the proposed system more confidential. Finally, the performance analysis and comparative study shows that the proposed protocol is computationally effective and have some additional features that makes it different from the existing work.
Long non-coding RNA SLC25A21-AS1 inhibits the development of epithelial ovarian cancer by specifically inducing PTBP3 degradation
Authors: Li Sihui , Shen Shizhen , Ge Wanzhong , Cen Yixuan , Zhang Songfa , Cheng Xiaodong , Wang Xinyu , Xie Xing , Lu Weiguo
Published: August 2022

Background
Epithelial ovarian cancer (EOC) is a highly prevalent disease that rapidly metastasizes and has poor prognosis. Most women are in the middle or late stages when diagnosed and have low survival rates. Recently, long non-coding RNAs (lncRNAs) were recognized to play pivotal roles in the development of EOC.
Methods
The expression of SLC25A21-AS1 and PTBP3 in EOC cells was assessed via qPCR. The proliferation activity of these cells was detected by EdU and CCK8 assays, while the death rate of apoptotic cells and the cell cycle were detected by flow cytometry. Detection of cell transfer rate by Transwell assay. Protein expression was measured through Western immunoblotting. Interactions between SLC25A21-AS1 and PTBP3 were detected through RNA immunoprecipitation (RIP), IF-FISH co-localization experiments and Electrophoretic mobility shift assay (EMSA).The in vivo importance of SLC25A21-AS1 as a tumor suppressor modulator was assessed using murine xenograft models.
Results
The lncRNA SLC25A21-AS1 has negligible expression in ovarian cancer tissues compared with that in normal ovarian tissues. A series of functional tests revealed that the upregulation of SLC25A21-AS1 markedly blocked the proliferation and metastasis of EOC cells in vitro, while its downregulation had the opposite effect. Overexpression of SLC25A21-AS1 in a nude mouse model of EOC in vivo resulted in slower tumor growth and weakened metastatic potential. Moreover, SLC25A21-AS1 reduced the protein stability of PTBP3 and promoted its degradation. Subsequent ubiquitination experiments confirmed that SLC25A21-AS1 acts on PTBP3 through the ubiquitin–proteasome pathway and binds to PTBP3 to exert its proteolytic effect, thereby inhibiting EOC cell proliferation and metastasis.
Conclusions
Our research reveals the effect of SLC25A21-AS1 in EOC development and suggests it can serve as a prognostic target by promoting the degradation of PTBP3 to improve patient survival.
MLACNN: an attention mechanism based CNN architecture for predicting genome-wide DNA methylation
Authors: Bai JianGuo , Yang Hai , Wu ChangDe
Published: August 2022

Methylation, as an important epigenetic regulation of methylation genes, plays an important role in the regulation of some biological processes. Although the traditional methods of detecting methylation in biological experiments are constantly improving, with the development of artificial intelligence, using deep learning and machine learning methods to detect methylation has gradually become a new trend. Traditional machine learning based methods rely too much on manual feature extraction. Although there are some deep learning methods to study methylation, most network architectures extract fewer features due to the simple network structure. We propose a bottleneck network based on attention mechanism, and use some new methods to ensure that the deep network can learn more effective features and minimize overfitting to get more significant prediction results. The model uses three coding methods to encode the original DNA sequence, and then uses the feature fusion based on the attention mechanism to get the best fusion method. The results show that MLACNN is superior to the previous methods and can obtain more satisfactory performance.
Exploring young people’s experiences of equity in relation to everyday challenges: a focus group study
Authors: Gard Helena , Enskär Karin , Ingvarsdotter Karin , Isma Gabriella E. , Mangrio Elisabeth
Published: August 2022

Background
Reports indicate a decrease in youth mental health in Sweden but at the same time research suggests that what is interpreted as mental ill-health could be considered everyday challenges by young people themselves. The distribution of mental health and illness among young people is also uneven, due to structural inequities related to factors such as race, gender, and socioeconomics. Sweden in particular is a country with large socioeconomic inequities in youth mental health and in school results, compared to other European countries. The aim of the study was to explore young people’s experiences of equity in relation to everyday challenges, with a focus on race, gender, and socioeconomics.
Methods
Sixty-five young people aged 13–15 years old were recruited by student health services and participated in focus group discussions at schools in the southernmost part of Sweden. Data was analyzed by secondary analysis with deductive qualitative content analysis, using the ecosocial theory of disease distribution as theoretical framework.
Results
The analysis resulted in one main theme: Navigating equity factors to gain and keep status, with three underlying themes: Guided by social norms, Negative impact in everyday life, and Importance of family influence. Participants were aware and critical of norms and expectations related to race, gender, and socioeconomics. Experiences of prejudice and unfairness were both the participants’ own lived experiences and based on observations of friends and school mates.
Conclusions
Young people identify equity issues related to race, gender, and socioeconomics in their everyday life. Passing norms and expectations related to these issues is a way to lose and gain status in a school setting. Many of the inequities discussed are related to socioeconomics and the direct consequences of having or not having money. Young people’s everyday experiences of equity issues are important to consider in youth mental health promotion aiming to tackle health inequities. Further research is needed on those experiences and how they affect mental health.
Effects of gestational diseases on the distribution of trace elements in the maternal-fetal system
Authors: Ding Ailing , Wan Huimin , Peng Juan , Wang Huizi , Zhu Shaodan , Dong Xudong
Published: August 2022

Purpose
To evaluate the levels and differences of trace elements (Zn, Cu, Fe, Mn, Ni, Cr) in maternal-fetal systems (maternal blood, placenta, umbilical cord blood) of different healthy states. To analyze the influence of pregnancy disease on the distribution of trace elements between the mother and fetus.
Methods
Maternal, placental and umbilical blood samples were collected from 140 parturients (60 in the normal group, 40 in the HDCP group and 40 in the GDM group). The contents of trace elements in paired samples were determined by inductively coupled plasma–mass spectrometry (ICP–MS). SPSS software was used to analyze the differences in trace element levels in matched samples of each group.
Results
The distribution of Fe content in the normal group was as follows: umbilical cord blood > maternal blood > placenta (p < 0.001). Although the distribution characteristics of Fe in the HDCP group and GDM group were the same as those in the normal group, there was no significant difference in Fe content between maternal and umbilical cord blood (p > 0.05). In addition, the levels of Fe in maternal blood, placental blood and umbilical cord blood in the HDCP group were higher than those in the normal control group (p < 0.05). The distribution characteristics of Mn content in the HDCP group and GDM group were placenta > umbilical cord blood > maternal blood. There were significant differences in Mn content between the placenta and maternal and umbilical cord blood (p < 0.001). The distribution characteristics of Mn content in the HDCP group and GDM group were placenta > umbilical cord blood > maternal blood. There were significant differences in the Mn content between the placenta, maternal blood and umbilical blood in the HDCP group (p < 0.05). Only the Mn content between the placenta and maternal blood was significantly different in the GDM group (p < 0.001). In addition, the content of Cr in the placenta and umbilical blood of the HDCP group was higher than that of the normal group (p < 0.05). The content of Ni in the cord blood of the HDCP group and GDM group was higher than that of the normal group (p < 0.05).
Conclusion
HDCP and GDM affect the transport of Fe, Ni and Cr from the placenta to the fetus. In addition, the occurrence of GDM also changes the distribution of Fe and Mn in the maternal-fetal system (maternal blood, placenta and umbilical cord blood).
Generating flavors using Scientific Machine Learning
Authors: Queiroz Luana P. , Rebello Carine M. , Costa Erbet A. , Santana Vinícius V. , Rodrigues Bruno C. L. , Rodrigues Alírio E. , Ribeiro Ana M. , Nogueira Idelfonso B. R.
Published: August 2022

The flavor is an essential component in developing numerous products in the market. The increasing consumption of processed and fast food and healthy packages has upraised the investment in new flavoring agents and, consequently, molecules with flavoring properties. In this context, this work brings a Scientific Machine Learning approach to address this product engineering need. Scientific Machine Learning in computational chemistry has opened paths in predicting a compound's properties without requiring synthesis. This work proposes a novel framework of deep generative models within this context to design new flavor molecules.
Enhanced Gaussian noise model based probabilistic constellation shaping to mitigate non-linearity at increased SNR
Authors: Khaki Zahid G , Qazi Gausia
Published: August 2022

In long-haul unrepeated optical transmission systems, the different input distributions employing constellation shaping, have led to increased achievable information rate (AIR) at the expense of reduced signal-to-noise ratio (SNR). In this paper, at optimal launch power, enhanced Gaussian noise (EGN) model based probabilistic shaping (PS) is implemented to inhibit the fiber non-linearities. The method exploits the inherent system and input conditions to result into maximum mutual information (MI) without using digital signal processors. Using sequential quadratic programming (SQP), a robust 16-QAM coherent optical system is implemented in back-to-back configuration employing probabilistic shaping. The shaping is optimized for minimum values of the objective function, second and fourth order moments of input. The higher order noise coefficients are thereby reduced, resulting in minimal non-linear interference noise (NLIN) at increased values of SNR. The optimized EGN model returns values of 1.41 and 2.24 for μ^4 and μ^6 respectively, having highest SNR value of 14.52 dBm and the least SNR penalty of 0.15 dBm towards the uniform probability distribution.
Porcine Model for Open Robotic Thyroidectomy
Authors: Funk Emily , Park Won Seo , Richter Florian , Ostrander Benjamin T. , Yip Michael , Weissbrod Philip A. , Orosco Ryan K.
Published: August 2022

Background
Well-defined, simple surgical models are useful in translational research in that they provide real world scenarios to evaluate novel technologies. Open porcine thyroidectomy has been used for several decades as a model to study nerve injury in thyroid surgery, but published anatomic descriptions are many decades old. In recent years, experience in robotic thyroidectomy surgery has led to refinements in approach and technique in humans. We present a contemporary review of porcine thyroidectomy with a novel description of an open robotic surgical approach.
Methods
Porcine cadaveric anatomy study.
Results
The porcine infrahyoid musculature is comparable to humans. The primary arterial supply to the thyroid gland comes from the thyroid artery, a branch of the omocervical artery. Thyroid veins can also be identified bilaterally. There is a single thyroid lobe located anterior to the trachea with two parathyroid glands. Open robotic thyroidectomy is described using two instruments (grasping forceps and monopolar cautery) and standardized surgical steps are defined. Dissection around the thyroid parenchyma requires mobilization of prominent thymus tissue. The recurrent laryngeal nerve in the tracheoesophageal groove is separate from the thyroid parenchyma.
Conclusion
Porcine thyroid anatomy is similar to humans. A key difference is the separation between the thyroid parenchyma and the recurrent laryngeal nerves. The ease of setup, access, and simplicity of instrument manipulation makes open robotic porcine thyroidectomy advantageous for translational research purposes. Characterizing the anatomy and defining the surgical steps may help standardize future research efforts toward open, robotic, and minimal-access thyroid surgery.
Evaluation of Oocyte Maturation in Experimental PCOS Model
Authors: Onal Tuna , Uyar Yildiz , Vatansever H. Seda
Published: August 2022

Aim
Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disease and is the most common cause of infertility in women due to ovulation disorder. Although the distinctive morphological features of the polycystic ovary were clearly evaluated, the specific oocyte maturation molecules that are affect oocyte maturation and oocyte quality are currently not understood. In addition, the effect of drugs used to induce ovulation in PCOS on oocyte maturation is unknown. In this study it is aimed to investigate the changes of oocyte maturation proteins (Nobox, Foxl2, Cep55, Cx37, Cx43) post ovulation induction treatment.
Materials and Methods
Four-week-old, female Balb/c mice were subcutaneously injected 6mg/100g dehydroepiandrosterone (DHEA) for 21 consecutive days for experimental PCOS models and divided four groups. In control group, no injections performed. PCOS group, after DHEA administration was not applied any treatment. Treatment groups were given clomiphene citrate (1,5 mg/kg) alone or clomiphene citrate (1,5 mg/kg), metformin (12 mg/kg) and pioglitazone (0,20 mg/kg) as a combine for consecutive 5 days. The distributions of molecules were evaluated by indirect immunoperoxidase staining method in ovarian tissues and immunofluorescence staining method for oocytes. Intensity of immunofluorescence evaluated by ImageJ.
Results
The formation of the PCOS model was demonstrated by the glucose tolerance test, histological and morphological evidence. It was determined that the expression of all investigated molecules significantly decreased in the ovarian tissues of PCOS group but increased in the treated groups. In oocytes, intensities of Nobox, Foxl2, Cep55 and Cx43 were significantly increased in clomiphene citrate administered group compared to the PCOS group.
Conclusion
This study is the first to investigate the effect of drugs used for providing ovulation induction and reducing insulin resistance as single or combined treatments in PCOS mice model through maturation molecules. Both in vivo and in vitro oocyte maturation may trigger with target-specific treatment in PCOS patients. In addition, new molecules could be used in control of the in vitro oocyte maturation during treatment.
Evaluations of imputation methods for missing data with random forest modeling: an application with unbalanced data with a three categories outcome, the linkage to HIV care Uganda study
Authors: Mendoza Nadia B. , Bailey Barbara A. , Kiene Susan M. , Menzies Nicolas A. , Wanyenze Rhoda K. , Schmarje Katherine A. , Ediau Michael , Kalichman Seth C. , Naigino Rose , Lin Chii-Dean
Published: August 2022

Background: Incomplete observation units may contain important information about the population being studied, analysis conducted with the complete portion of the dataset, done in most standard statistical software, may produce biased or low statistical power results. In this paper we investigate the behavior of imputation methods for a linkage to HIV care study dataset with more than 60% incomplete cases.Methods: Missing data imputation algorithms amelia, missForest, mice and hmisc were considered. Two sets of simulations were conducted: first with the subset of data containing only complete observations and second with the whole dataset. Imputation accuracy and general behavior for each imputation algorithm were accessed in the first set. Random forest models were fit to evaluate overall prediction accuracy and sensitivity in both sets of simulations. Results: The imputed values by missForest, a single imputation method, were more accurate for all incomplete variables and scenarios. Median overall prediction accuracy of HIV status, a three levels outcome, was slightly higher after imputations with missForest and amelia (approximately 52%, 61% and 65% for samples of 350, 700 and 1050 units respectively). In general, different missing percentages (20%, 40% and 60%) did not result in large changes in prediction or imputation accuracy and larger sample sizes performance improved for imputation and overall prediction accuracy but mixed results were observed with sensitivity. For the second set of simulations, missForest and amelia produced better overall prediction accuracy with larger samples (1200 versus 350 units). For new HIV positive HIV class, hmisc and mice presented better sensitivity, with median sensitivity 65% versus 50% and approximately 90% versus 20% for samples with 350 and 1200 units respectively, compared to incomplete samples. Conclusions: Imputation with mice and hmisc may be used for imputation when the main interest is to increase sensitivity in predicting new HIV positive. Furthermore, it is interesting to investigate which method gives more advantage for other performance measures of interest. Trial registration: NCT02545673
Full factorial optimization of α-aminophosphonates synthesis using diphenylphosphinic acid as efficient Organocatalyst
Authors: FARREH Meriem , GUEZANE-LAKOUD Samia , BENDJEFFAL Hacene , AISSA Rym , MERABET-KHELASSI Mounia , TOFFANO Martial , ARIBI-ZOUIOUECHE Louisa
Published: August 2022

Diphenylphosphinic acid is used as an efficient and simple catalyst for the synthesis of the α-aminophosphonates by multicomponent Kabachnik-Fields reaction in one pot of aromatic aldehyde, aniline and diethylphosphite. Three physicochemical factors including catalyst amount, reaction time and medium temperature were optimized using a full factorial experiment design (FFD). Additionally, a quadratic polynomial regression model was applied for the analysis of the experimental data at a confidence level of 95% with p-values < 0.05. The high signification effect of the reaction time and the medium temperature on the α-aminophosphonates synthesis were confirmed by the statistical analysis. Besides, the diphenylphosphinic acid amount shows an effect on the reaction yield. ANOVA exhibit that the coefficient determination of this model up to 99.25%. This eco-friendly procedure was extended for the preparation of series of the α-aminophosphonates in ethanol as green solvent, giving the desired products with high chemical yields up to 90%.
Long-term impact of renin-angiotensin system inhibitors for secondary prevention in patients with chronic kidney disease who underwent percutaneous coronary intervention
Authors: Fukase Tatsuya , Dohi Tomotaka , Nishio Ryota , Takeuchi Mitsuhiro , Takahashi Norihito , Chikata Yuichi , Endo Hirohisa , Doi Shinichiro , Nishiyama Hiroki , Okai Iwao , Iwata Hiroshi , Okazaki Shinya , Miyauchi Katsumi , Daida Hiroyuki , Minamino Tohru
Published: August 2022

The impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with coronary artery disease and coexisting chronic kidney disease (CKD) in the long-term remains unclear. Therefore, we investigated how RAS inhibitor use affects long-term clinical outcomes in patients with CKD who underwent percutaneous coronary intervention (PCI). A total of 1190 patients with CKD who underwent their first PCI between 2000 and 2018 were included in this study, and were divided into two groups based on the presence or absence of RAS inhibitor use. In total, 293 patients (24.6%) developed 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke, and 136 patients (11.4%) developed heart failure (HF). The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 40.2%, log-rank test, p = 0.034). However, the cumulative incidence rate of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.2% vs. 13.8%, log-rank test, p < 0.001). In conclusion, the long-term RAS inhibitor use in patients with CKD after PCI could contribute to prevention of cardiovascular events but may increase the risk of HF.
An Ecological Study on Regional Disparity in the Provision of Rehabilitation Services Using Open NDB Data Japan
Authors: Morii Yasuhiro , Abiko Kagari , Ishikawa Tomoki , Fujiwara Kensuke , Konomura Keiko , Ogasawara Katsuhiko
Published: August 2022

Background
Although medical resources related to rehabilitation services should be optimally allocated and utilized uniformly and efficiently, there is few reports on regional differences in the supply/demand balance and the provision of these services. This study analyzed the regional differences to help policymakers provide more uniform and efficient rehabilitation services and optimal allocation of related resources.
Methods
The subjects were 47 prefectures and nine regions in Japan in 2017. Primary indicators were “supply/utilization ratio”, which was calculated by dividing rehabilitation supply converted to service units, by rehabilitation utilized (utilization) and “utilization/needs ratio”, which was calculated by dividing utilization by needs. The needs were defined as utilization expected from the demographic in each area. The utilization/needs ratios were calculated for overall and individual rehabilitation services. Data required to calculate these indicators were collected from open sources such as NDB Open Data Japan.
Results
The supply/utilization ratios were higher in Shikoku, Kyusyu, Tohoku, and Hokuriku regions, and lower in Kanto and Tokai regions. The number of rehabilitation-related providers per population was larger mostly in the western parts of Japan and lower mostly in the eastern parts. The utilization/needs ratios were higher mostly in the western parts such as Shikoku and Kyusyu regions, and lower mostly in the eastern parts such as Tohoku, and Hokuriku regions. The same trend was seen for utilization/needs ratio of cerebrovascular disease and musculoskeletal disorders rehabilitation, which accounted for approximately 84% of rehabilitation services. For disuse syndrome rehabilitation, such a trend did not exist, and the utilization/needs ratio differed by prefectures.
Conclusions
The surplus in rehabilitation supply was attributed to the larger number of providers in the western parts and less amount of utilization in the eastern parts, indicating regional differences in the provision of rehabilitation services. Since cerebrovascular disease and musculoskeletal disorder rehabilitation accounted for a large part of services, priority should be given to them when considering an increase in uniform and efficient rehabilitation services.
Changes in the sediment load in the Red River system (Vietnam) from 1958- 2021 because of dam-reservoirs
Authors: Quang Nguyen Hao , Ngoc Pham Khanh , Phong Nguyen Tan , Banno Masayuki , Nakagawa Yasuyuki , Cuong Pham Manh , Luan Nguyen Thanh
Published: August 2022

The sediment regime of the Red River system has changed since dams and reservoirs were implemented, with implications for river processes downstream. We analyzed data for the daily discharge (Q) and suspended particulate matter (SPM) concentrations collected from 1958–2021 at the Son Tay hydrological gauging station, the outlet of the Red River system and entry to the delta. The results showed that the annual sediment load transported by the Red River system decreased significantly, by about 90.4%, over the 64-year study period. From 1958 to 1971, when there were no dams or reservoirs in place, the annual water discharges and sediment loads in the river system were about 115,592×106 m3/yr and 115×106 ton/yr, respectively. From 1971 to 2016, a series of dam-reservoir systems were gradually implemented (Thac Ba (1971), Hoa Binh (1988), Tuyen Quang (2008), Son La (2010), Ban Chat (2013), Huoi Quang (2015), and Lai Chau (2016)). By 2016, the annual sediment load and water discharges in the Red River system had decreased significantly, and were 9×106 ton/yr and 88,709×106 m3/yr, respectively. The data show that the discharge and sediment loads increased slightly from 2016–2021, perhaps reflecting the combined effects of human activities, such as land-use change, deforestation, and population increases. Climate may also have played a role in these increases, with changes in air temperature and increases in rainfall triggering severe soil erosion and large discharges of sediment into the Red River system.
Residents’ Willingness to Pay for Domestic Nature-Based Tourism in Botswana
Authors: Mogomotsi Patricia Kefilwe , Mogomotsi Goemeone E.J. , Stone Lesego Senyana , Stone Moren Tibabo
Published: August 2022

The COVID-19 pandemic has halted tourism worldwide. This shock has led to job losses, loss of livelihoods and overall revenue losses at national and international levels. The pandemic has reinforced the need to develop strong domestic tourism bases. In Botswana, the domestic tourism market has remained largely unexplored and undeveloped. This study aims to estimate domestic tourists’ willingness to embark on domestic tourism during and post the COVID-19 pandemic. Using primary data derived from questionnaires administered online, this study seeks to estimate the residents’ willingness to pay (WTP) for a standard two-day domestic nature-based tourism package and analyse factors influencing residents’ WTP for domestic nature-based tourism. On average, the respondents were willing to pay for a standard two-day domestic nature-based tourism experience package valued at BWP3 340.66 per person sharing. However, some camps charge as high as BWP72 097.62 for a similar package. There is a need to develop plans that promote pricing and product offerings that accommodate domestic tourists without having an impact on the sustainability of natural resources and the integrity of the natural environment
Giant Omphalocele: A novel technique for primary repair in the neonatal period using Botulinum Toxin
Authors: Rombaldi Marcelo Costamilan , Barreto Caroline Gargioni , Feldens Letícia , Holanda Felipe Colombo , Takamatu Eliziane Emy , Schopf Luciano , Peterson Carlos Alberto Hoff , Costa Eduardo Correa , Cavazzola Leandro Totti , Santis-Isolan Paola Maria Brolin , Fraga Jose Carlos
Published: August 2022

Giant omphalocele (GO) is a complex condition to which many surgical treatments have been developed and yet, no consensus has been reached. The goal of this study is to describe the technique for primary repair of GO during the neonatal period using the BTA.
Towards Predicting the Grade of Peritonitis with a Mamdani-type Fuzzy Decision System: Application of Artificial Intelligence in Surgical Emergency Referrals
Authors: Chattopadhyay Subhagata
Published: August 2022

Diagnostic healthcare has ambiguities due to the literal expression of symptoms, e.g., more, less, moderate, severe, and so on. Acute abdomen, associated with pain, vomiting, and fever of various grades, are commonly encountered in the surgical emergency department. Peritonitis is one of the commonest acute abdomens. It needs immediate medical attention as it can be life-threatening. Developing nations lack experienced clinicians and high-end investigation facilities, especially in the rural setup. Thus, referral of such cases to higher facilities is the mainstay procedure. A timely referral is a challenge. This paper has explained an intelligent referral system (IRS) by developing a fuzzy decision system (FDS) of Mamdani-type. Three symptoms - pain, vomiting, and fever, each having three grades, e.g., poor, average, and good are the inputs to the FDS, while the grade of peritonitis is the output as a low, medium, and high grade based on the fuzzy rule base obtained from an expert clinician. The efficacy of the FDS is tested and validated in three arbitrary cases.
Efficacious hybrid and analytical and numerical methods; phase shift of the ultra-short pulses in optical fibers
Authors: Khater Mostafa M.
Published: August 2022

This paper examines the soliton phase shift using a simplified third-order generalized nonlinear Schrodinger equation (3-order GNLSE). In this investigation, we employ a new direct algebraic (NDA) technique to solve these models. All evaluated solutions are put to the test using two modern numerical (trigonometric quantic and cubic B-spline) schemes. The necessary criteria for implementing numerical systems are derived from the computational solutions. As the model captures the dynamical behavior of ultra-short pulses in optical fiber and quantum fields, this research is crucial. As a wave model, the 3-order GNLSE equation may be used to illustrate the wave nature of matter. It is regarded as a quantum-mechanical state function since it may represent the dynamical and physical behavior of atoms and transistors. The exactness of the answers is shown through two-dimensional, three-dimensional, and contour charts (matching between analytical and numerical solutions). The answers presented in the research are innovative in comparison to earlier findings.AMS classification: 35C08; 37K40; 35C07; 37K40.
Discovery of plasma inflows in laser-produced Sn plasmas contributing to increment of extreme-ultraviolet light output
Authors: TOMITA Kentaro , Pan Yiming , Sunahara Atsushi , Kouge Kouichiro , Mizoguchi Hakaru , Nishihara Katsunobu
Published: August 2022

Plasma dynamics are governed not only by temperature and density but also by macroscopic flows. However, velocity fields (vflow) inside laser-produced plasmas (LPPs) have rarely been measured, owing to their small size (< 1 mm) and short lifetime (< 100 ns). Here, we report, for the first time, two-dimensional vflow measurements of Sn-LPP for extreme-ultraviolet (EUV) light sources for semiconductor lithography using the collective Thomson scattering technique, which is conventionally used to measure electron temperature and density. We discovered plasma inflows exceeding 104 m/s toward a plasma central axis, which plays an important role in improving the total EUV light emission, i.e., plasma inflows maintain the EUV source at a temperature suitable for EUV light emission for a relatively long time and at a high density. These results indicate that controlling the plasma flow can improve EUV light output and that there is sufficient potential to increase the EUV output further.
Protocol: MosTI single-copy transgene insertion in C. elegans using constitutive Cas9 expression.
Authors: Mouridi Sonia El , Frøkjær-Jensen Christian
Published: August 2022

Transgene expression in C. elegans is an important tool for understanding regulatory elements (e.g., promoters and enhancers), for controlling cells using optogenetic effector proteins, and for editing the (epi)genome. Insertion of single-copy transgenes into well-defined safe-harbor locations can be used when consistent expression is required (e.g., to compare expression from different transgenes) or when expression is required in germ cells. Here, we describe a detailed protocol for inserting single-copy transgenes using Modular Safe-harbor Transgene Insertion (MosTI) and constitutive Cas9 expression from a co-injected plasmid.
Arbuscular mycorrhizal colonization of a Cd hyperaccumulator Viola baoshanensis at Baoshan Pb/Zn Mine
Authors: Weiliang Zhong
Published: August 2022

Despite great potential for arbuscular mycorrhizal (AM) fungi associated with heavy metals (HMs) hyperaccumulators in the phytoremediation of contaminated sites, rather limited information is available in literature about the community structure of AM fungi (AMF) in the rhizosphere of hyperaccumulators in nature. A field survey was conducted to investigate the colonization status and community structure of AMF of Viola baoshanensis, a Cd hyperaccumulator, growing at Baoshan Pb/Zn Mine. Shoot/root ratios of 1.78 for Cd, and 2.57 for Zn in V. baoshanensis indicate that these two metals were preferentially transported from roots to shoots, whereas Pb was mainly stored in roots. The roots of V. basshanensis were extensively colonized by AMF with M% of 69.1%, and A% of 46.9%, whereas mycorrhizal colonization was not affected by concentrations of Cd, Zn and Pb in the soil. 15 AMF species ( 5 Glomus, 3Rhizophagus,2 Claroideoglomus, 2 Septoglomus, and each one of Ambispora, Funneliformis, and Sclerocystis ) were identified by a morphological method. The dominant AMF genus was Glomus, showing high tolerance to excess Cd, Zn and Pb, while Glomus ambisporum and Claroideoglomus etunicatum were the most abundant species in the rhizosphere of V. baoshanensis.
E-procurement adoption in Indonesian government: A study of TOE model
Authors: Ardy Susantya Stefanus , Aswar Khoirul , Sumardjo Mahendro , Panjaitan Ingrid , Andreas Andreas
Published: August 2022

Due to innovations, the Industrial Revolution 4.0 has become a popular trend among the public. The Indonesian government is eager to implement e-procurement in accordance with Presidential Regulation No. 16 of 2018 on government procurement. The purpose of this study is to assess the impact of each TOE model factor on Indonesian e-procurement adopters, as well as to investigate how the diffusion of innovation theory categorizes them. This study employed a quantitative method and SmartPLS version 3.0 to examine the model, based on Teo et al. (2009), which set the major structure. In this study, state-owned firms and their subsidiaries, as well as other private enterprises that operate in the infrastructure and construction sectors and participate in Indonesia’s e-procurement system, were used as samples. The result show that top management support (β = 0.279; p < 0.05) and information sharing culture (β = 0.783; p < 0.05) have positive and significant effects on e-procurement adoption. On the other hand, perceived cost (β = 0.097; p > 0.05), firm size (β = –0.080; p > 0.05), and business partner influence (β = –0.057; p > 0.05) did not contribute any effect significantly. This study expects that the organizing committee for government goods and services procurement, as well as participants in government goods and services procurement, would pay attention to and consider significant components in the implementation of e-procurement outside of the applicable legislation.
Comprehensive gain sharing maximizing satisfaction in supply chain collaborations
Authors:   Laboratory of Network Organizational Forms, Higher School of Economics Graduate School of Business, Kovalenok Anastasia Yu.
Published: August 2022

A major challenge in supply chain collaborations is the fair allocation of the coalition gain. In this paper, a comprehensive, yet simple gain sharing system with a special focus on the maximization of the parties’ satisfaction using a minimax regret approach is developed. The gain sharing system is applied to a vertical SCC including one manufacturer, one logistics service provide and one retailer in the Dutch fast moving consumer goods industry. Results identify a fair and robust gain share allocation, which maximizes the parties’ satisfaction and thus increases the probability of sustainable SCCs. We provide theoretical framework, which can be adapted, if necessary, to a particular SCC by using more practical satisfaction functions.
GLP-1 Targeted Novel 3-phenyl-7-hydroxy Substituted Coumarins
Mitigate STZ-induced Pancreatic Damage and Improve Glucose
Homeostasis in OGTT Method
Authors: Gupta Mandeep Kumar , Srivastava Rajnish , Kumar Sushil , Varshney Krishna Kumar , Singh Hariram
Published: August 2022

Background:

Worldwide, type 2 diabetes mellitus accounts for a considerable burden of
disease, with an estimated global cost of >800 billion USD annually. For this reason, the search for
more effective and efficient therapeutic anti-diabetic agents is continuing. Recent studies support the
search for coumarins or related compounds with potential blood glucose-lowering properties.

Aim:

The study aims to design, synthesize and evaluate the hypoglycemic activity of a new class of
7-hydroxy coumarin derivatives.

Objective:

To explore and establish the in-silico-driven pharmacological role of a new class of 7-
hydroxy coumarin derivatives as the therapeutic strategies against type 2 diabetes mellitus.

Methods:

A new class of 7-hydroxy coumarin derivatives was designed by assessment of their
physicochemical properties and molecular docking against the Glucagon-like peptide-1 (GLP-1)
receptor. Two novel series of 30 compounds were synthesized. The chemical structures of all the
synthesized analogues have been elucidated by spectral studies of IR, 1H-NMR, and mass
spectroscopy. After considering the molecular docking score and their physicochemical properties,
the compounds were screened out for the evaluation of their hypoglycemic potential. The compounds
were investigated for their hypoglycemic activity using a streptozotocin (STZ) induced diabetic
model and an oral glucose tolerance test (OGTT) method at different dose levels.

Result:

The molecular docking studies of synthesized derivatives reveal significant molecular
interaction with the various amino acid residues of the GLP-1 receptor. IR spectral analysis revealed a
strong band of -NH stretching in the range of 3406.7-3201.61 cm-1 and one strong band for the
lactone carbonyl group of the coumarin ring in the range of 1722.0-1703.5 cm-1, confirming the
chemical structure of all produced compounds. The synthesized coumarin analogues with the best
docking score exhibited remarkable hypoglycemic potential as assessed by the STZ model and the
OGTT method.

Conclusion:

Coumarin derivatives explored a good structure-activity relationship (SAR) and
produced significant hypoglycemic potential.
Cannabinoids Receptors in COVID-19: Perpetrators and Victims
Authors: Al-Kuraishy Hayder M. , Al-Gareeb Ali I. , Alexiou Athanasios , Batiha Gaber El-Saber
Published: August 2022

COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the present narrative review aimed to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects, suppressing pro-inflammatory cytokines and inhibiting inflammatory signaling pathways.
The Role of MicroRNA-126 in Atherosclerotic Cardiovascular
Diseases
Authors: Theofilis Panagiotis , Oikonomou Evangelos , Vogiatzi Georgia , Sagris Marios , Antonopoulos Alexios S. , Siasos Gerasimos , Iliopoulos Dimitrios C. , Perrea Despoina , Vavouranakis Manolis , Tsioufis Konstantinos , Tousoulis Dimitris
Published: August 2022

Atherosclerotic cardiovascular diseases remain the leading cause of morbidity
and mortality worldwide despite all efforts made towards their management. Other than
targeting the traditional risk factors for their development, scientific interest has been
shifted towards epigenetic regulation, with microRNAs (miRs) being at the forefront.
MiR-126, in particular, has been extensively studied in the context of cardiovascular diseases.
Downregulated expression of this miR has been associated with highly prevalent
cardiovascular risk factors such as arterial hypertension and diabetes mellitus. At the
same time, its diagnostic and prognostic capability concerning coronary artery disease is
still under investigation, with up-to-date data pointing towards a dysregulated expression
in a stable disease state and acute myocardial infarction. Moreover, a lower expression of
miR-126 may indicate a higher disease complexity, as well as an increased risk for future
major adverse cardiac and cerebrovascular events. Ultimately, overexpression of
miR-126 may emerge as a novel therapeutic target in atherosclerotic cardiovascular diseases
due to its potential in promoting therapeutic angiogenesis and anti-inflammatory effects.
However, the existing challenges in miR therapeutics need to be resolved before
translation to clinical practice.
An Insight to Heat Shock Protein 90: A Remedy for Multiple Problems
Authors: Yadav Megha , Singh Ankit Kumar , Kumar Adarsh , Thareja Suresh , Kumar Pradeep
Published: August 2022

Heat shock protein 90 (Hsp90) is a chaperone protein that prevents many other proteins from aggregating by folding them in a certain way. Hsp90 consists of three structural domains: N-terminal, middle and C-terminal domains. Hsp90 has many activities in numerous proteins and signaling pathways like chimeric fusion proteins, steroid hormone receptors, tumor suppressor genes, and cell cycle regulatory proteins. The role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases. This review is a compilation of the pharmacological profile of Hsp90 inhibitors, problems associated with them, and suggested remedies for the same.
Small-molecule High-throughput Screening Identifies an MEK Inhibitor
PD198306 that Enhances Sorafenib Efficacy via MCL-1 and BIM in
Hepatocellular Carcinoma Cells
Authors: Hong Junjie , Zheng Wei , Cai Xiujun
Published: August 2022

Background:

Sorafenib is the most widely used systematic therapy drug for treating unresectable
Hepatocellular Carcinoma (HCC) but showed dissatisfactory efficacy in clinical applications.

Objective:

We conducted a combinational quantitative small-molecule high-throughput screening
(qHTS) to identify potential candidates to enhance the treatment effectiveness of sorafenib.

Methods:

First, using a Hep3B human HCC cell line, 7051 approved drugs and bioactive compounds
were screened, then the primary hits were tested with/without 0.5 μM sorafenib respectively,
the compound has the half maximal Inhibitory Concentration (IC50) shift value greater than 1.5 was
thought to have the synergistic effect with sorafenib. Furthermore, the MEK inhibitor PD198306
was selected for the further mechanistic study.

Results:

12 effective compounds were identified, including kinase inhibitors targeting MEK,
AURKB, CAMK, ROCK2, BRAF, PI3K, AKT and EGFR, and a μ-opioid receptor agonist and a Ltype
calcium channel blocker. The mechanistic research of the combination of sorafenib plus
PD198306 showed that the two compounds synergistically inhibited MEK-ERK and mTORC1-
4EBP1 and induced apoptosis in HCC cells, which can be attributed to the transcriptional and posttranslational
regulation of MCL-1 and BIM.

Conclusion:

Small-molecule qHTS identifies MEK inhibitor PD1938306 as a potent sorafenib enhancer,
together with several novel combination strategies that are valuable for further studies.