bluuebunny/crossref_metadata_2025 huggingface dataset:
Calyx Yield and Nitrogen Use Efficiency of Roselle (Hibiscus sabdariffa L.) as Affected by Variety and Levels of Nitrogen Fertilizer
Authors: Wachamo Hailu Lire , Nebiyu Amsalu , Gessese Tesfaye Shimbir
Published: June 2022

Roselle (Hibiscus sabdariffa L.) is an important beverage and leafy vegetable plant. Its growth and yield attributes are affected by constraints like poor soil fertility and lack of improved varieties. A field trial was conducted to assess the Calyx yield response and nitrogen use efficiency of roselle. The experiment consisted of two roselle varieties (WG-Hibiscus-Jamaica and WG-Hibiscus-Sudan) and six levels of nitrogen fertilizer (Kg ha− 1 (0, 23, 46, 69, 92, 105) laid out in factorial combination arrangement in randomized complete block design with three replications. Data on calyx yield, growth variables and nitrogen use efficiency parameters were recorded and analyzed by using SAS version 9.4. Results showed that the variety WG-Hibiscus-Jamaica exhibited higher plant height (196.2cm) and branch number plant− 1 (34.9) from the application of 115kg ha− 1 N; while lower values of these attributes were recorded on an unfertilized plot of both varieties. Variety WG-Hibiscus-Sudan exhibited the highest number of calyx plant− 1 (50.3), fresh calyx yield ha− 1 (5934 kg), and dry calyx yield ha− 1 (1866 kg) from the application of 92 kg ha− 1 N while lower values were recorded from the unfertilized plot of WG-Hibiscus-Jamaica variety. Higher NER (42.5 kg kg− 1) were recorded from WG-Hibiscus-Sudan while lower was recorded from WG-Hibiscus-Jamaica. Higher (12.5kg) and lower (0.7kg) AE were recorded from 92 and 115 kg ha − 1 N application respectively. WG-Hibiscus-Sudan was effective but not reactive, while WG-Hibiscus-Jamaica was not effective but reactive. In conclusion, for maximum commercial produce, calyx yield and profitability, applying 69 kg ha− 1 N on WG-Hibiscus-Sudan and 92 kg ha− 1 on WG-Hibiscus-Jamaica was found best. Nevertheless, further investigation of the response and efficiency of roselle varieties to nitrogen fertilization, including other nutrients at different locations should be undertaken to get ample data for a conclusive recommendation.
Radial-Tangential Mode of Single-Wall Carbon Nanotubes Manifested by Landau Regulation: Reinterpretation of Low- and Intermediate-Frequency Raman Signals
Authors: Lee Jae-Kap , Hembram K. P. S. S. , Kim Jin-Gyu , Lee Sang-Gil , Park Jeongwon
Published: June 2022

The low-frequency Raman signals of single-wall carbon nanotubes (SWNTs), appearing in the range of 100-300 cm-1, have been interpreted as radial-breathing mode (RBM) comprising pure radial Eigenvectors. Here, we report that the majority of the low-frequency, as well as the intermediate-frequency signals of SWNTs are radial-tangential modes (RTMs) coexisting radial and tangential Eigenvectors, while only the first peak at the low-frequency side is the RBM. Density functional theory simulation for a SWNT of ~2 nm in diameter shows that dozens of RTMs exhibit following the RBM (~150 cm-1) up to G-mode (~1592 cm-1) in order with Landau regulation. We specify the RBM and the RTM on Raman spectra obtained from SWNTs, where both appear as a prominent peak between 149 cm-1 and 170 cm-1 and as ripple-like peaks between 166 cm-1 and 1440 cm-1, respectively. We report that the RTMs have been regarded as RBM (~300 cm-1) and ambiguously named as intermediate-frequency mode (300-1300 cm-1) without assignment. The RTMs gradually interlink the RBM and the G-mode resulting in the symmetric Raman spectra in intensity. We reveal high-resolution transmission microscope evidence for a helical structure of SWNTs informing the typical diameter of commercial SWNTs to be 1.4-2 nm.
Arterial stiffness indices, pulse wave velocity and central pulse pressure, are able to discriminate between obese and non-obese children
Authors: Bittencourt Juliana Cabral , Scheinbein Giovanna Hermont Abbes , Junior Walmer Cardoso de Oliveira , Bassi Roberta Leão , Moura Luiza Bretas , Correa Ana Luisa Drumond , Bernardes Raquel Gil de Lima , Freitas Leticia Silveira , Lemos Julia Correa , Gonçalves Gleisy Kelly Neves , Rodrigues-Machado Maria da Glória
Published: June 2022

Purpose: The objectives of this study were to verify, first, if arterial stiffness indices can discriminate between obese and healthy children. Second, to evaluate arterial stiffness index predictors and hemodynamic parameters in obese children. Arterial stiffness indices evaluated were pulse wave velocity (PWV), central systolic blood pressure (SBPc), and central pulse pressure (PPc). Methods and Results: A cross-sectional, descriptive, comparative study design was used. The sample consisted of 78 normal-weight children (8.1±1.96 years) and 58 obese children (9.0±1.87 years). PWV, PPc, and SBPc were significantly higher in the group of obese children than in the control group. The ROC curve analysis showed that maximum PWV and SBPc sensitivity and specificity in differentiating obese from non-obese children occurred at 4.09 m/s and 86.17 mmHg, respectively. PPc did not exhibit a discriminatory capacity between the two groups. Peripheral systolic blood pressure (SBPp), peripheral pulse pressure (PPp), and PPc (R2 = 98%) were predictors of increased PWV. Augmentation pressure, PPp, and reflection coefficient (R2 = 87.3%) were predictors of PPc. Age, augmentation index, total vascular resistance, cardiac index, and mean fat percentage (R2 = 0.801) were predictors of SBPc. Conclusion: This study shows for the first time that PWV > 4.09 m/s and SBP > 86.17 mmHg are cut-off points associated with a higher risk of obesity. These results indicate that the simple, rapid, and noninvasive measurement of arterial stiffness adds prognostic information regarding cardiovascular risk, in addition to increased body mass index.
Lnc-TMEM132D-AS1 Confers Acquired Resistance to Osimertinib in Non-Small-Cell Lung Cancer
Authors: Wang Nan , Zhao Qilin , Huang Yutang , Wen Chunjie , Li Yaji , Wu Lanxiang
Published: June 2022

Objective: Acquired resistance is a major obstacle to the therapeutic efficacy of osimertinib in non-small-cell lung cancer (NSCLC). Current knowledge about the role of long non-coding RNAs (lncRNAs) in this phenomenon is insufficient. Here, we aim to identify candidate lncRNAs associated with acqured resistance to osimertinib in NSCLC, and explore the role and underlying mechanism of one of these lncRNAs, lnc-TMEM132D-AS1. Methods and Results: RNA Sequencing (RNA-Seq) and quantitative real-time PCR (qPCR) were used to screen and validate the differentially expressed lncRNAs between osimertinib-sensitive and -resistant NSCLC cell lines. Lnc-TMEM132D-AS1 was screened out, and was found to be upregulated in the osimertinib-resistant NSCLC cell lines as well as the plasma of NSCLC patients. Results from CCK-8, colony formation, flow cytometry assays showed that lnc-TMEM132D-AS1 knockdown significantly increased the sensitivity of osimertinib-resistant NSCLC cells to osimertinib. After identifying the cytoplasmic localization of lnc-TMEM132D-AS1, a functional lnc-TMEM132D-AS1-miRNA-mRNA interaction network and protein-protein interaction (PPI) network were constructed to analyze its putative target genes and biological functions. Using qPCR and TISIDB database analysis, ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1) was confirmed to be a target mRNA of lnc-TMEM132D-AS1, and was associated with tumor infiltration of immunosuppressive cells and poor prognosis in patients with NSCLC.Conclusion: In summary, lnc-TMEM132D-AS1 plays a crucial role in osimertinib resistance. It may serve as a prognostic biomarker and a potential therapeutic target for acquired resistance to osimertinib in NSCLC.
Proposing an indigenous sustainable methodology for evaluating the effectiveness of industrial parks: A real-life application in Iran
Authors: Moghimi Farshad , Baradaran Vahid , Hosseinian Amirhossein
Published: June 2022

The goal of this research is to develop a hybrid methodology consisting of qualitative and quantitative approaches to find the factors that significantly affect the effectiveness of industrial parks of Iran. Through using this methodology, the impacts of the detected factors are analyzed. The methodology seeks to direct Iran’s industrial parks to sustainable development; hence, the factors include sustainability-related elements as well. For the qualitative approach, the literature has been scrutinized and with the help of practitioners in focus groups, some of the most important factors influencing the effectiveness of industrial parks have been discovered. Three of the discovered factors investigate the impact of sustainability on the effectiveness of industrial parks. For the quantitative approach, a reliable questionnaire has been designed which asked the importance of the identified factors from a community of experts. Having acquired the viewpoints of the experts, the Structural Equation Modeling (SEM), with the help of the Confirmatory Factor Analysis (CFA), has been applied to investigate the relations between the factors and the effectiveness of parks. Reliability of the designed questionnaire has been tested by the Cronbach’s alpha coefficient. Results of the developed model have been thoroughly analyzed by means of diverse performance measures. According to the outputs, the factors “accessibility to infrastructural facilities”, “economic elements”, and “existence of supporting services” had the highest impact on the effectiveness of Iran’s parks. On the opposite, the “environmental elements” had the least influence on the parks of Iran. This fact implies that the environmental degradations should be considered more seriously for Iran’s industries on the path of sustainable development. The convergent and discriminant validity of the proposed model have been demonstrated and approved via several performance evaluation metrics. The proposed model has been applied to provinces of Iran. An overall effectiveness score has been computed for each province. The provinces have been sorted based on their effectiveness scores.
Pathobiont-mediated spatial structuring enhances biofilm virulence in childhood oral disease
Authors: Cho Hunyong , Ren Zhi , Divaris Kimon , Roach Jeff , Lin Bridget , Lin Chuwen , Azcarate-Peril Andrea , Simancas-Pallares Miguel , Shrestha Poojan , Orlenko Alena , Ginnis Jeannie , North Kari , Zandona Andrea Ferreira , Ribeiro Apoena , Wu Di , Koo Hyun
Published: June 2022

Microbiome studies are revealing complex microbiota in biofilm-mediated human diseases commonly linked with specific bacterial pathogens. Streptococcus mutans has been implicated as the primary pathogen in childhood dental caries (tooth decay). While the role of polymicrobial communities is appreciated, it remains unclear whether other microorganisms are active contributors, inactive cohabitants, or interact with known pathogens such as S. mutans. Here, we integrate multi-omics of human dental plaque (biofilm) from two community-based samples of preschool-age children in a discovery-validation pipeline involving bioinformatics, laboratory, and in vivo experimental approaches to identify disease-relevant inter-species interactions. In metagenomics and metatranscriptomics analyses among 416 preschool-age children, we identify 16 taxa strongly associated with childhood caries. Using multiscale imaging, virulence assays, microcalorimetry, and computational analyses, we investigate biofilm formation dynamics, microscale spatial arrangement, and metabolic activity by Selenomonas sputigena, Prevotella salivae and Leptotrichia wadei either individually or with S. mutans. Notably, we discover that the flagellated S. sputigena, a subgingival anaerobe with previously unknown role in supragingival biofilm virulence, becomes trapped in foreign streptococcal exoglucans, loses its motility but actively proliferates to build a honeycomb-like multicellular superstructure encapsulating S. mutans and enhances acidogenesis. Rodent model experiments reveal a previously unrecognized ability of S. sputigena to colonize supragingival tooth surfaces. While incapable of causing caries on its own, S. sputigena exacerbates the disease severity in vivo when co-infected with S. mutans, causing extensive lesions on tooth enamel. Our data reveal a pathobiont from a disparate habitat in a prevalent disease that cooperates with a known pathogen to build a unique 3D spatial structure and heighten biofilm virulence—which may be relevant to other polymicrobial diseases.
Age-dependent Aedes mosquito resistance profiling and mortality rate to repeated insecticides exposure in Western region, Saudi Arabia
Authors: AlNazawi Ashwaq , Weetman David
Published: June 2022

Background: Little is documented on Aedes aegypti age-dependent role on different resistance mechanisms to repeated insecticides exposures. The study examined the age-dependence of mortality rate and genetic resistance in two mechanistically pyrethroid resistant mosquito strains exposed once or repeatedly at different ages.Methods: WHO bioassays and real time polymerase chain reaction (qPCR) were performed to ascertain their association between age-dependent exposures related mortality rate and single/repeated resistance in the Jeddah and Makkah. Candidate genes of interest (CYP9J7, CYP9J27, CYP9J26, AAEL006953, CYP9P450, AAEL006013) were assessment.Results: Age dependent and exposure duration had a significant effect on the survival of the Jeddah and resistant Cayman. Our results showed that in a single exposure assays, age had no significant effect on mortality in the Cayman strain (χ2=2.76, df=1, P=0.097), but there was significantly increased mortality in the Jeddah strain younger age (χ2=5.46, df=1, P=0.02) , but not statistically significant at older age. In the multiple exposure assay, GLiM analysis showed a significant strain, day and strain*day interaction indicating mortality rate is influenced by the strain or day (which also corresponds to age).The Jeddah strain showed generally lower survival, , there was a highly significant association of survival with repeated exposures in the Jeddah strain (χ2=43.6, df=1, P=4.1X10E-11) and the Cayman strain (χ2=12.5, df=1, P=0.0004).Mortality rate correlated statistically and significantly with the number of days of exposure in the Cayman strain (Spearman rank correlation ρ=-0.77, P=0.01), but in the Jeddah strain it was not statistically significant (ρ= -0.42, P=0.23). After repeated insecticide exposure, the AAEL006013 was statistically and significantly over-expressed compared to the control (P=0.03).Conclusion: To the best of our knowledge, this is one of the first research on age and exposure linked genomic and bioassay on field Ae. aegypti in Jeddah, KSA. The study showed that repeated exposure to pyrethroids reduced the Aedes mosquito population mortality rate. This suggests that there is indeed increasing age-dependent resistance or survival with multiple exposure high-doses of same or repeated insecticide, thus indicating the need to rethink on integrated vector control policy and interventions and technical assistance in the Kingdom.
Effects of the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine on immune-related adverse events and disease outcomes in cancer patients receiving immune checkpoint inhibitors
Authors: Nelli Fabrizio , Giannarelli Diana , Fabbri Agnese , Virtuoso Antonella , Berrios Julio Rodrigo Giron , Marrucci Eleonora , Mazzotta Marco , Schirripa Marta , Signorelli Carlo , Chilelli Mario Giovanni , Primi Francesca , Panichi Valentina , Topini Giuseppe , Silvestri Maria Assunta , Ruggeri Enzo Maria
Published: June 2022

Background
The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors (ICIs) are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes.
Methods
Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of ICI treatment before vaccination for an advanced solid malignancy were eligible.
Results
The current analysis included 56 patients with metastatic disease (median age: 66 years; 71% male), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 3424 AU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 3424 AU/mL) or high-responders (High-R, ≥ 3424 AU/mL). After a median follow-up time of 131 days, 20% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but a significant increase in the cumulative incidence of immuno-related thyroiditis was observed within High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality.
Conclusions
Our findings would strengthen the recommendation not to change immunotherapy plans based on current or future immunization schedules, implying that all these patients should be closely monitored.
Focusing on the metabolic changes caused by the COVID-19 disease. A Metabolomic approach using urine
Authors: Marhuenda-Egea F. C. , Narro-Serrano J. , Shalabi-Benavent M. J. , Álamo-Marzo J. M. , Amador-Prous C. , Algado-Rabasa J. T. , Garijo-Saiz A. M. , Marco-Escoto M.
Published: June 2022

Analysis of urine samples from COVID-19 patients by 1H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. To detect these alterations, we have compared urine samples from COVID-19 patients with healthy people. We have used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods. The generated mathematical models allow us to evaluate the differences between the two groups, COVID-19 and healthy people. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The evidence in these metabolites would be indicating that the SARS-CoV-2 virus would be causing a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance.
Liquid assisted Grindstone Chemistry: An eco-friendly scalable approach for diverse organocatalytic mechanochemical domino multicomponent reactions by employing the reactivity of cyclic 1,3-diketones at ambient conditions
Authors: Borah Biplob , Swain Sidhartha , Patat Mihir , Kumar Bhupender , Prajapat Ketan Kumar , Biswas Rathindranath , Chowhan L. Raju
Published: June 2022

Here, we have demonstrated a metal-free energy-efficient mechanochemical approach for expedient access to a diverse set of 2-amino-3-cyano-aryl/heteroaryl-4H-chromenes, tetrahydrospiro[chromene-3,4´-indoline], 2,2'-aryl/heteroarylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) as well as tetrahydro-1H-xanthen-1-one by employing the reactivity of 5,5-dimethylcyclohexane-1,3-dione/cyclohexane-1,3-dione with TsOH.H2O as a mild organocatalyst under water-assisted grinding conditions at ambient temperature. The ability to accomplish multiple C-C, C = C, C-O, and C-N bonds from readily available starting materials via a domino multicomponent strategy in the absence of metal-catalyst as well as volatile organic solvents with an immediate reduction in the cost of the transformation without necessitates complex operational procedures, features the significant highlights of this approach. The excellent yield of the products, broad functional group tolerances, easy set-up, column-free, scalable synthesis with ultralow catalyst loading, short reaction time, waste-free, ligand-free, and toxic-free, are other notable advantages of this approach. The greenness and sustainability of the protocol were also established by demonstrating several green metrics parameters.
Extended Pelvic Lymph Node Dissection during Robotic Prostate Surgery Reduces Biochemical Recurrence: A Propensity Score- matched Analysis for High-risk Prostate Cancer
Authors: Yashi Masahiro , Yokoyama Megumi , Nakamura Gaku , Uematsu Toshitaka , Suzuki Issei , Sakamoto Kazumasa , Nishihara Daisaku , Kijima Toshiki , Ishida Kazuyuki , Kaji Yasushi , Kamai Takao
Published: June 2022

Objectives
To avoid misunderstandings based on the failure to demonstrate oncological benefit from extended pelvic lymph node dissection (PLND) during radical prostatectomy in a recent randomized controlled trial. We evaluated early survival outcome in contemporary patients with limited to high-risk prostate cancer (PCa) using propensity score (PS)-matched analysis.
Materials and Methods
Three-hundred and forty-seven patients with high-risk PCa were enrolled. They were determined to have a lymph node (LN) involvement probability of greater than 5%. Biochemical recurrence (BCR)-free survival was compared between two groups divided by adherence with extended template and timeframe related to improving PLND procedure.
Results
The mean LN yield was 23.4 and 2.7, and the positive LN rate was 19.3 and 2.0% in the extended PLND and other groups, respectively. In the entire unmatched cohort, the estimated curve was 13.1% superior in 3-year BCR-free survival for the extended PLND group. The PS-matched cohort was converged in each LN yield group to 99 patients, and the difference in the 3-year BCR-free survival widened to 22.2% (hazard ratio 0.46, 95% confidence interval 0.27–0.80; p = 0.005). The statistical difference was consistent in standard high-risk PCa, and was a significant trend in very high-risk PCa. In the analysis of two groups divided by timeframe, the difference in the BCR-free survival was a significant trend.
Conclusion
The results possibly demonstrate the therapeutic role of extended PLND in high-risk PCa. Statistical demonstration of benefits depends on the quality of extended PLND and whether the study cohort is the optimal composition of cancer risk.
Human Urine as an Alternative Source of nutrient for Biomass Production of Scenedesmus dimorphus
Authors: M Vennila , D Manikandavelu , S Aruna , C Rajeshweri
Published: June 2022

Microalgae are known to produce an array of value-added components like pigments. The nutrient medium used to cultivate microalgae is generally more expensive. The prominence of this work is on the practicality of human urine as a low-cost source of nutrients for microalgae culture, as it includes major nutrients and minor minerals and is cost-effective. Of course, it is a digressive approach from the aesthetic point of view. Nevertheless, the ultimate products can be purified, obviating pathogenicity. Human urine was collected, sterilized and different dilutions were prepared (5%,10%,15%,25%,50%,75%,100%). Cultures of Scenedesmus dimorphus were inoculated into a diluted human urine medium and incubated for 15 days at room temperature (around 29ºC) under window spread sunlight. The concentrations of 5%, 10%, and 15% have supported the production of microalgae. The maximum biomass was observed in 5% human urine concentration with a cell density of 1.74×106 cells/mL with 3.2 g/L biomass production. The biomass productivity was 0.257 g/L /day. Growth cessation could be perceived at more than 25% of human urine concentration. This study offers scope for considering human urine for algal production, targeting value-added products, aside from obnoxious liquid waste utilization.
Neural invasion is an independent prognostic factor in young and lymph node negative gastric cancer patients underwent curative gastrectomy
Authors: Wang Linjun , Xia Yiwen , Jiang Tianlu , Li Ying , Li Fengyuan , Wang Weizhi , Zhang Diancai , Xu Hao , Yang Li , Xu Zekuan
Published: June 2022

Background: The prognostic significance of neural invasion (NI) in gastric cancer (GC) has not been established. This study is to investigate the characteristic and prognostic value of NI in GC.Methods: 592 patients who had undergone gastrectomy for GC were retrospectively analyzed. NI was defined when cancer cells infiltrated into the perineurium or neural fascicles by hematoxylin and eosin staining of surgical specimens. NI and the other clinical factors were analyzed.Results: NI was detected in 270 of the 592 patients. NI was associated with tumor size, site, depth of invasion, lymph node metastasis, TNM stage, tumor differentiation, Lauren classification, and blood vessel invasion. NI was associated with the overall survival. Multivariate analysis indicated that NI was not an independent prognostic factor for total patients, while NI independently predicted prognosis for age<60 and lymph node metastasis negative patients by subgroup analysis. Concomitant existence of NI with tumor size ≥3cm, TNM stage III, or diffused Lauren classification independently predicted prognosis.Conclusions: The frequency of NI is high in GC patients and increases with disease progression. NI is related to poor survival in GC patients who underwent curative gastrectomy and provides independent prognostic value for young and lymph node metastasis negative patients.
Smart-Plexer: a breakthrough workflow for hybrid development of multiplex PCR assays
Authors: Miglietta Luca , Chen Yuwen , Luo Zhi , Xu Ke , Ding Ning , Peng Tianyi , Moniri Ahmad , Kreitmann Louis , Cacho-Soblechero Miguel , Holmes Alison , Georgiou Pantelis , Rodriguez-Manzano Jesus
Published: June 2022

Developing multiplex PCR assays requires an extensive amount of experimental testing, the number of which exponentially increases by the number of multiplexed targets. Dedicated efforts must be devoted to the design of optimal multiplex assays for specific and sensitive identification of multiple analytes in a single well reaction. Inspired by data-driven approaches, we reinvent the way of designing and developing multiplex assays by proposing a hybrid, easy-to-use workflow, named Smart-Plexer, which couples empirical testing of singleplex assays and computer simulation of multiplexing. The Smart-Plexer leverages kinetic inter-target distances among amplification curves to generate optimal multiplex PCR primer sets for accurate multi-pathogen identification. The optimal single-channel assays, together with a novel data-driven approach, Amplification Curve Analysis (ACA), were demonstrated to be capable of classifying the presence of desired targets in a single test for seven common respiratory infection pathogens.
Delayed Antibiotic Prescriptions in a Primary Care Clinic
Authors: Alsamah Wasim , Acker Kristi , Fritch Rober
Published: June 2022

Purpose
Unnecessary Antibiotic Prescription remains an ongoing problem for countries around the world, including United States. One of the most successful methods was implementing delayed prescription (DAP). DAP is providing the patient with a prescription and a recommendation to fill out only if the initial symptoms worsen. However, many primary care providers are either unaware of DAP or reluctant to implement it. The purpose of this study is to increase providers’ knowledge of antibiotic resistance in the community and to determine the barriers of primary care providers to starting patients on DAP.
Methods
This quality improvement study was conducted with a pretest-intervention-posttest strategy. A questionnaire was administered to participants to determine participants’ knowledge of and barriers to initiating DAP. Following the pretest, a 30-minute educational intervention was presented on DAP, then providers were given one month to integrate the DAP program when applicable, followed by administration of the questionnaire as a posttest. The results of both questionnaires were compared with descriptive statistics and a paired-sample t test.
Results
Paired t tests demonstrate that 6 items indicated significant improvements from pretest: providers’ view of DAP in reducing scheduled visits, inappropriate use of antibiotics, emergency visits, optimizing resources in clinic, providers’ knowledge about DAP, and changing patients’ perceptions to antibiotics. Further analysis revealed insignificant differences in 2 items; providers’ willingness to discuss DAP with their patients, and their readiness to initiate it.
Transcriptomic profiling of Early-onset sporadic Alzheimer’s disease patients
Authors: Caldwell Andrew B , Anantharaman Balaji G , Ramachandran Srinivasan , Nguyen Phuong , Liu Qing , Trinh Ivy , Galasko Douglas R , Desplats Paula A , Wagner Steven L , Subramaniam Shankar
Published: June 2022

Alzheimer’s disease (AD) manifested before 65 years of age is commonly referred to as early-onset AD (EOAD) [1]. Significant research on EOAD has focused on autosomal-dominant familial mutations in PSEN1, PSEN2, and APP; however, these mutations only represent 5–10% of EOAD cases. Although EOAD has a higher heritability (92–100%) than sporadic late-onset AD (LOAD, 70%), which is polygenic, EOAD may be due to autosomal recessive inheritance or combinatorial polygenic risk [2, 3]. Even though the endpoint clinicopathological changes, i.e., Aβ plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous [4]. The heterogeneity, leading to temporally distinct age of onset (AOO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes [5–7]. Further, analyses of large cohorts of postmortem brains demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling [4]. Areas of the brain less affected by AD pathology at early disease stages—such as the primary visual cortex—exhibit similar transcriptomic dysregulation as those regions traditionally affected, and therefore may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology [8]. To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD), using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AOO may not directly correlate with the identity and severity of AD endotypes.
Bayesian inference of physicochemical quality elements of tropical lagoon Nokoué (Benin)
Authors: HOUNYEME Romuald , LOGEZ Maxime , MAMA Daouda , ARGILLIER Christine
Published: June 2022

In view of the very strong degradation of aquatic ecosystems, it is urgent to set up monitoring systems that are best able to report on the effects of the stresses they undergo. This is particularly true in developing countries, where specific and relevant quality standards and funding for monitoring programs are lacking. The objective of this study was to make a relevant and objective choice of physico-chemical parameters informative of the main stressors occurring on African lakes and to identify their alteration thresholds. Based on statistical analyses of the relationship between several driving forces and the physico-chemical parameters of the Nokoué lagoon, relevant physico-chemical parameters were selected for its monitoring. An innovative method based on Bayesian statistical modeling was used. Eleven physico-chemical parameters were selected for their response to at least one stressor and their threshold quality standards also established: Total Phosphorus (<4.5mg/L) , Orthophosphates (<0.2mg/L), Nitrates (<0.5 mg/L), TKN (<1.85 mg/L), Dry Organic Matter (<5 mg/L) , Dissolved Oxygen (>4 mg/L), BOD (<11.6 mg/L) , Salinity (7.6 ‰) , Water Temperature (<28.7 °C) , pH (>6.2) , and Transparency (>0.9 m) . According to the System for the Evaluation of Coastal Water Quality, these thresholds correspond to "good to medium" suitability classes, except for total phosphorus. One of the original features of this study is the use of the bounds of the credibility interval of the fixed-effect coefficients as local weathering standards for the characterization of the physico-chemical status of this anthropized African ecosystem.
Rapprochement of the Roman Catholic Church and the World Council of Churches in the 1960s: Orthodox attitude to this problem
Authors:   Moscow Theological Academy, Trinity Lavra of St. Sergius, Pismeniuk Priest Ilia
Published: June 2022

In the article, the author talks about the stage of rapprochement between the Roman Catholic Church and the largest ecumenical organization, the World Council of Churches (WCC), at the turn of the 1950s–1960s, as well as about the continuation of interaction between the Vatican and the WCC within the framework of the Joint Working Group. At the initial stage of the World Council of Churches’ history the Roman Catholic Church refused any ecumenical contacts and n reacted negatively to the ecumenical movement. The article explains the reasons that served to change the position of the Roman Catholic Church in relation to the WCC as major ecumenical organization and to the whole ecumenical movement. The author paid special attention to the attitude to this process of the Orthodox Churches that were WCC members. The latter was an important factor, since The WCC was limited in its actions in case of disagreement on any matter between it member churches and the relationship between Catholicism and Orthodoxy was highly complicated during the second millennium. The article provides Orthodoxy representatives’ statements at meetings of the WCC governing bodies permitting the understanding of the origins of the Orthodox position on the issue of interaction between the Vatican and the WCC, as well as general historical assessments on the matter.
Additive Manufacturing and Printing Approaches for the Development of Pharmaceutical
Dosage Forms with Improved Biopharmaceutical Attributes
Authors: Kawish Syed M. , Sharma Shwetakshi , Almalki Waleed H. , Alghamdi Saad , Afzal Obaid , Kazmi Imran , Altamimi Abdulmalik S.A. , Al-Abbasi Fahad A. , Beg Sarwar , Ahmad Farhan J.
Published: June 2022

Pharmaceutical industry is moving ahead with the future experiencing an innovation in drug development through the introduction of personalized medicine technologies. Instead of adapting the dose which a patient actually needs, they were adapted to the manufacturer’s dose. Now patient specific or customized method of dosing and dose combinations has superior insistence rather than the standard mass medicines. Printing technology has gained interest during the last years for manufacturing of personalized dosage forms. For manufacturing of personalized drug products three dimensional printing (3DP) has expanded to the pharmaceutical industry. With the approval of first 3DP product an unprecedented opportunity for the discovery of new compounds and technologies has arisen. In this article, we have re-evaluated various printing technology and its utilization in personalized medicines. Further, we also discussed its history, advantages, challenges and various types of printing technologies with advantages and limitations particularly in the area of pharmaceutical research.
Human Colon Cancer HT29 Cell Line Treatment with High-Dose LAscorbic
Acid Results to Reduced Angiogenic Proteins Expression
and Elevated Pro-apoptotic Proteins Expression
Authors: Samie Kosar Abbasi , Dayer Dian , Eshkiki Zahra Shokati
Published: June 2022

Background:

Some studies have shown anticarcinogenic effects of high dose L-Ascorbic Acid. However, there are controversies around the therapeutic administration of Ascorbic acid as an anticancer medicine.

Objective:

we conducted a case-control study to investigate the role of pharmacologic concentration of Ascorbic acid on viability and angiogenesis of human colon cancer (HT29) cell line.

Methods:

The HT29 cells were cultured in DMEM-HG and treated with 10 mM ascorbic acid for 3h. The culture medium was exchanged, and after incubation at 37 ˚C for 24 h, the cells were collected and utilized to evaluate viability, ROS production, gene expression and protein expression levels. The control group consisted of untreated HT29 cells. The viability of the cells was determined using the MTT method. Moreover, Nitro Blue Tetrazolium (NBT) was used to detect the ROS production capacity. The mRNA transcript’s level and protein expression were evaluated by Real-time PCR and Western blotting, respectively.

Results:

The ascorbic acid-treated group showed a significant increase in ROS production and an obvious reduction in viability compared to the control group. The treated group showed significant increased levels of both early apoptotic markers (Bax, Cyt C, Caspase3, and Caspase 9) and late apoptotic marker (Caspase 8). Bcl2 expression showed significantly decreased levels relative to the control group. Ascorbic acid therapy substantially reduced the expression of bFGF, bFGFR, PDGF, PDGFR and PLC- γ compared to the control group.

Conclusion:

The results confirm that high- dose L-ascorbic acid reduces HT29 cell line viability in vitro.
Facile Synthesis of Three Types of Mesoporous Silica Microspheres as
Drug Delivery Carriers and their Sustained-Release Properties
Authors: Zhu Yameng , Wang Boyao , Chen Jian , He Jun , Qiu Xilong
Published: June 2022

Background:

Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers for drug delivery. MSNs have been widely used in pharmaceutical research as drug carriers because
of their large pore volume, high surface area, excellent biocompatibility, nontoxicity, ease to functionalize, and sustained release effects. MSNs have attracted much attention during drug delivery because of
their special structure.

Objective:

The present study aimed to synthesize mesoporous silica nanoparticles (MSNs), dendritic
mesoporous silica nanoparticles (DMSN), and hollow mesoporous silica nanoparticles (HMSN) through
facile methods, and to compare the drug release properties of nano-porous silica with different pore
structures as a stroma for PUE drug.

Methods:

MSN, DMSN, and HMSN were characterized by SEM, TEM, FT-IR, nitrogen adsorptiondesorption isotherms, XRD, and zeta potential methods. Subsequently, puerarin (PUE) was used as the
active ingredient and loaded into the three mesoporous materials, respectively. And, the drug delivery
behavior was measured in PBS solution with different pH values. The sustained-release properties of
MSN, DMSN, and HMSN loaded with PUE were investigated. Finally, the biocompatibility and stability of MSN, DMSN, and HMSN were studied by MTT assay and hemolysis assay.

Results:

Our results showed that MSN, DMSN, and HMSN were successfully synthesized and the three
types of mesoporous silica nanoparticles had higher drug loading and encapsulation efficiency. According to the first-order release equation curve and Higuchi equation parameters, the results showed that the
PUE-loaded MSN, DMSN, and HMSN exhibited sustained-release properties. Finally, MTT and hemolysis methods displayed that MSN, DMSN, and HMSN had good biocompatibility and stability.

Conclusion:

In this study, MSN, DMSN, and HMSN were successfully synthesized, and to compare the
drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug, we
provided a theoretical and practical basis for the application of PUE.
Quinic and Digallic acids from Pistacia atlantica Desf. Leaves Extracts as
Potent Dual Effect Inhibitors against main Protease and RNA-dependent
RNA Polymerase of SARS-CoV-2
Authors: Benguechoua Mebarka Imane , Benarous Khedidja , Benahmed Ziyad , Boukhalkhal Sarah , Silva Artur M. S. , Yousfi Mohamed
Published: June 2022

Background:

Through this study, the Chemical composition realized by UHPLC-DAD-ESI-MSn allowed the detection of different phenolic compounds groups from Pistacia atlantica Desf. leaves extracts. We studied the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 by the identified molecules through molecular docking.

Objective:

The objective of this study is to identify compounds from Pistacia atlantica Desf. leaves extracts, which might have anti-viral effects.

Methods:

Chemical composition realized by UHPLC-DAD-ESI-MSn, the inhibition of main protease (CL3 Mpro) and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 is studied using molecular docking with Autodock Vina software. ADMET analysis was carried out.

Results:

The identified compounds are quinic acid, digallic acid, galloylquinic acid, gallic acid, trigallic acid, digalloylquinic acids, trigalloylquinic acids and methyl gallate; digallic and quinic acids are the best inhibitors. Digallic acid had binding affinity energy (BAE) of -8.2 kcal/mol, and Ki of 1µM for the CL3 Mpro, Ki of 0.62 mM for the RdRp. Quinic acid showed Ki of 4.6 mM, recorded for both enzymes. Through ADMET analysis, we have found that the two molecules are good drugs candidate.

Conclusion:

This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves is studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.
Modeling the Influence of Extraction Parameters on the Recovery of
Antioxidant Compounds of Microwave Extracted Citrus (Citrus reticulata)
Peel by Response Surface Methodology
Authors: Martati Erryana , Utari Dwiyani P. , Wulan Siti N.
Published: June 2022

Background:

Microwave-assisted extraction (MAE) is a green extraction technology that
saves both in energy and time and that bioactive compounds can be extracted without loss as much as in
traditional extraction methods.

Objectives:

This study aims to optimize the MAE process for maximizing the recovery of antioxidant
compounds of flavonoids and the activity of radical scavenging of DPPH (2,2-diphenyl-1-picrylhydrazyl)
from citrus peels (CP).

Methods:

The modeling used Box-Behnken Design (BBD) experimental design for optimizing three extraction
parameters of time (5, 15, and 25 min), ethanol concentration (50%, 70%, and 90%), and extraction
temperature (55, 65, and 75 °C). UHPLC-MS analysis was performed to identify the qualitative flavonoid
content in the extract.

Results:

Our results showed that the optimum MAE conditions that maximize the total flavonoid content
and antioxidant activity of the CP extract were extraction time of 16.87 min, 50% ethanol, and temperature
at 75°C. The obtained CP extract had a TFC of 14.10 mg QE/g and antioxidant activity of 51.52%,
which was in line with the predicted values. Flavonoids of neohesperidin, naringin, hesperidin, narirutin,
and nobiletin were identified in the extract of CP.

Conclusion:

The ethanolic extract of CP was confirmed to have high flavonoids content with potent antioxidant
activity.
A Highly Sensitive Room-Temperature NO2 Gas Sensor based on Porous
MnO2/rGO Hybrid Composites
Authors: Sun Youyi , Zhang Hui , Ou Kangtai , Guan Ruihua , Cao Yang , Li Xiao
Published: June 2022

Background:

The NOX (e.g. NO2) is harmful to human health and environmental
quality. It is of great interest to monitor the hazardous NOx with a simple, reliable, and sensitive
sensor. Currently, the commonly used detection methods have disadvantages of complex operation,
unstable cycling performance and low sensitivity.

Objective:

In this paper, rGO coated Ni foam supported MnO2 is synthesized to develop a more
advanced detection method for the rapid analysis of NO2.

Methods:

A three-dimensional nickel foam supported MnO2 and rGO (MnO2/rGO@NF) was
prepared by a hydrothermal method for application in binder-free electrode of NO2 sensor.

Results:

The MnO2/rGO@NF composite displayed significantly better NO2 sensing performance
compared to single MnO2@NF or rGO@NF. The excellent sensing response (5.9%) as well as
high cycling stability were observed in the presence of 50.0 ppm NO2 at room temperature. Furthermore,
the mechanism of the great gas-sensing performance was also investigated by the density
functional theory (DFT).

Conclusion:

These results were very important to further design and prepare new sensitive materials
applied in binder-free electrode of gas NO2 sensors.
Novel Molecular Targets and Mechanisms for Neuroprotective Modulation
in Neurodegenerative Disorders
Authors: Irannejad Hamid , Azari Aala , Goodarzi Amin , Jafarkhani Behrouz , Eghbali Mohammad , Karimi Zohreh , Hosseini Balef Seyed Sajad
Published: June 2022

Background:

Neuronal death underlies the symptoms of several human neurological
disorders, including Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral
sclerosis and their precise pathophysiology have not yet been elucidated. According to various
studies, the prohibition is the best therapy with neuroprotective approaches, which are advanced
and safe methods.

Methods:

This review summarizes some of the already-known and newly emerged neuroprotective
targets and strategies and their experimental effects have also been reported. Accordingly, literature
was studied from 2000 to 2021, and appropriate articles were searched in Google Scholar and
Scopus with the keywords given in the keywords section of the current review.

Results:

Lewy bodies are the histopathologic characteristics of neurodegenerative disorders and
are protein-rich intracellular deposits in which Alpha-Synuclein is its major protein. Alpha-
Synuclein’s toxic potential provides a compelling rationale for therapeutic strategies aimed at decreasing
its burden in neuronal cells through numerous pathways, including ubiquitin-proteasome
system and autophagy-lysosome pathway, proteolytic breakdown via cathepsin D, kallikrein-6
(neurosin), calpain-1 or MMP9, heat shock proteins, and proteolysis targeting chimera which consists
of a target protein-ligand and an E3 ubiquitin ligase (E3) followed by target protein ubiquitination
(PROTACs). Other targets that have been noticed recently are the mutant huntingtin, tau
proteins and glycogen synthase kinase 3β; their accumulation proceeds extensive neuronal damage
and up to the minute approach such as Proteolysis Targeting Chimera promotes its degradation in
cells. Various studies demonstrated that Mendelian gene mutations can result in neurodegenerative
diseases. An additional target that has gained much interest is epigenetics, such as mutation, phosphodiesterase,
RNA binding proteins and Nuclear respiratory factor 1.

Conclusion:

The novel molecular targets and new strategies compiled and introduced here can be
used by scientists to design and discover more efficient small molecule drugs against neurodegenerative
diseases. And also, the genes in which their mutations can lead to the α-synuclein aggregation
or accumulation have been discussed and considered a valuable information on epigenetics in
dementia.