bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.