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Innovative art selection through neutrosophic hesitant fuzzy partitioned Maclaurin symmetric mean aggregation operator
Nickel-Catalyzed Asymmetric Homobenzylic Hydroamidation of Aryl Alkenes to Access Chiral β-Arylamides
Combatting antibiotic resistance in Gardnerella vaginalis: A comparative in silico investigation for drug target identification
Gardnerella vaginalis is the most frequently identified bacterium in approximately 95% of bacterial vaginosis (BV) cases. This species often exhibits resistance to multiple antibiotics, posing challenges for treatment. Therefore, there is an urgent need to develop and explore alternative therapeutic strategies for managing bacterial vaginosis. The objective of this study was to identify virulence factors and potential drug targets against Gardnerella vaginalis by utilizing in silico methods, including subtractive and comparative genomics. These methods enabled the systematic comparison of genetic sequences to pinpoint specific features unique to G. vaginalis and crucial for its pathogenicity, which could then inform the development of targeted therapeutic strategies. The analysis of the pathogen's proteomic data aimed to identify proteins that fulfilled specific criteria. These included being non-homologous to human proteins, essential for bacterial survival, amenable to drug targeting, involved in virulence, and contributing to antibiotic resistance. Following these analyses and an extensive literature review, the phospho-2-dehydro-3-deoxyheptonate aldolase enzyme emerged as a promising drug target. To deepen our understanding of the biological function of the identified protein, comprehensive protein structural modeling, validation studies, and network topology analyses were conducted. The subsequent structural analysis, encompassing modeling, validation, and network topology assessment, is aimed at further characterizing the protein. Using a library of around 9,000 FDA-approved compounds from the DrugBank database, a virtual screening was conducted to identify potential compounds that could effectively target the proposed drug target. This approach facilitated the evaluation of existing drugs for their ability to inhibit the target, potentially offering an efficient pathway for developing new treatments against the pathogen. Leveraging the established efficacy, safety, pharmacokinetics, and pharmacodynamics of these compounds, the study suggests repurposing them for Gardnerella vaginalis infections. Among the screened compounds, five specific agents—DB03332, DB07452, DB01262, DB02076, and DB00727—were identified as cost-effective therapeutic options for treating infections related to Gardnerella vaginalis. These compounds were selected based on their efficacy in targeting the pathogen while maintaining economic feasibility. While the results indicate potential efficacy in treating infections caused by the pathogen, further experimental studies are essential to validate these findings.
Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner
Abstract Advanced colorectal cancer (CRC) continues to present with poor survival and treatment options remain limited. We have shown that increased activin A (activin) expression in the tumor microenvironment (TME) is associated with poor outcome in a cohort of stage III and IV CRC patients. Here, we hypothesized that activin promotes stage specific outcomes in CRC, enhancing metastasis and tolerance in late-stage CRC exclusively. We employed Digital Spatial Profiling (DSP) technology on a cohort of stage II and III CRC patient tissue samples obtained at the time of curative surgery to show that activin co-localization was associated with increased mitogenic signaling, proliferation, and immunosuppression in stage III, but not stage II, CRCs. Furthermore, we found strong linear correlations between markers of immunosuppression and signaling proteins in activin (+) areas, an effect that was not observed in activin (-) areas of tissue. Taken together these data suggest activin exerts pro-metastatic and immunosuppressive effects in stage III, but not stage II, CRC providing an attractive therapeutic target for advanced CRC.
An Operationally Unsaturated Iridium-Pincer Complex That C–H Activates Methane and Ethane in the Crystalline Solid-State
The efficacy of the corpus-based error correction method on revision in writing classrooms
Despite the growing interests in investigating the application of data-driven learning (DDL), much existing research remains outcome-oriented. Limited attention has been paid to learners’ interactions with corpora, especially the experiences of consulting corpora and decision-making processes during revision in second language (L2) writing. In this regard, this study investigates how corpora assist language learning during the revision process in a classroom-based foreign language learning context. We recruited 123 non-English major undergraduates from a university in China, learners’ revision behaviours and outcomes were analysed in each draft. To gather the learners’ experiences and perceptions of using the BAWE corpus for error correction, a stimulated recall interview was conducted using the revised drafts as stimuli. Quantitative results indicated that corpus consultation was highly effective for revising word form errors (93.6%), and participants were more likely to use the BAWE corpus to correct collocation and phrase errors (62.7%). Interview results demonstrated that the corpus-based error correction method was effective in enhancing correctness and facilitating language learning. Learners were able to utilise corpora to identify patterns, shape writing habits, and test linguistic hypothesis. The findings and the implications of this study also provide valuable insights for teachers into the potential role and implementation of corpora in designing classroom writing tasks.
Development of hybrid robust model based on computational modeling and machine learning for analysis of drug sorption onto porous adsorbents
Enantiopurity by Directed Evolution of Crystal Stabilities and Nonequilibrium Crystallization
Comparison between Go-GutDx, a novel diagnostic stool test kit with potential impact in low-income countries, and BioFire test
Introduction Infectious diarrheal diseases are one of the leading causes of worldwide morbidity and mortality. The incidence of diarrhea is higher in Low-Middle-Income Countries (LMIC), where more than 90% of deaths from diarrheal diseases occur. Diagnostic tests for infectious diarrhea are not readily available in Low-Middle-Income Countries. Our study evaluates a novel, cost-effective, easy-to-use DNA stool testing kit for infectious diarrhea that can easily be rolled out in low-resource settings and has comparable performance to current testing modalities in the USA in terms of diagnostic utility. Methods 435 stool samples were tested using the novel stool testing Kit (Go-GutDx®). The stool samples were in groups of 8 and were tested using floating microspheres DNA extraction followed by Recombinase Polymerase Amplification (RPA) and lateral flow assay detection. Pathogens tested include Clostridium difficile, Campylobacter jejuni, Salmonella enterica Typhimurium, Shigella spp., STEC (stx1, stx2), Vibrio spp., and Yersinia enterocolitica. The same samples were tested using BioFire GI Panel (gold standard), and the results were compared. Descriptive analysis was summarized as raw counts and frequencies and compared using Fisher’s exact test. We conducted specificity and sensitivity analysis of the two diagnostic tests using the diagnostic testing package in STATA. Graphical illustrations were conducted using two-way line graphs with custom margins and axis. All analyses with p-values ≤ 0.05 were significant. All analyses were conducted using STATA version 17. Results Results showed a sensitivity of 56.1% for C. difficile, and 58.6% for Campylobacter jejuni. 46.1% for STEC (stx1, stx2), 83.3% for Salmonella, 0% for Yersinia enterocolitica, 66.7% for Vibrio spp and 65.0% for Shigella spp. Specificities were > 97% for all pathogens. The positive predictive value was highest for Campylobacter jejuni 94.4%, followed by C. difficile 93.5%, Salmonella 86.2%, Shigella 76.5%, STEC (stx1, stx2) 50%, Vibrio spp 40%, and Yersinia 0%. The negative predictive value was 75.8% for C. difficile, with all other pathogens being above 98.3%. Table 3. The concordance between BioFire and Go-GutDx® for C. difficile testing was 80%. All other organisms showed a concordance of greater than 97% Table 2. Discussion Our study confirms that Go-GutDx® is a novel diagnostic tool for diarrheal pathogens with statistically comparable sensitivity, specificity, positive and negative predictive values with the current gold standard testing kit, BioFire. In addition, the simplicity of the technology and lower price both to healthcare systems and to patients makes Go-GutDx® an ideal diagnostic test to be implemented in low- and middle-income countries.
Publisher Correction: Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages
Coping with chronic periprosthetic joint infection after failed revision of total knee and hip arthroplasty: a qualitative study on patient’s experiences in treatment and healing
Periprosthetic joint infections (PJI), along with the extensive medical and surgical interventions required for treatment, impose a substantial psychological burden on patients. Given the need for patients to adapt to long-term physical limitations and ongoing medical challenges, this qualitative study aims to explore the nature of psychological coping amongst patients with chronic cases of PJI. A total of 18 patients (8 men and 10 women, aged 55 to 92) who underwent a total knee or hip arthroplasty revision due to chronic PJI were recruited at a single academic institution between August 2022 and July 2023. Semi-structured interviews were conducted at two timepoints and analyzed using thematic analysis. We identified the nature of coping with PJI as patients’ process-orientation towards healing. This encapsulates constant adaptation to challenges and losses in day-to-day life, managing expectations and proactively developing a sense of self-efficacy during treatment and healing. Patients expressed uncertainty and unpredictability to treatment trajectories and getting a feeling of being stuck, where health and well-being oscillates between progression and regression. These experiences contributed to unstable relationships with healthcare practitioners which were influenced by loss of trust and perceived treatment failures. A holistic view on patients, taking them seriously in their concerns and providing clear information were identified as crucial factors in shaping a positive patient-physician relationship. Acknowledging the fluctuating nature of chronic PJI treatment, physicians should adopt a process-oriented approach that promotes step-by-step healing while maintaining a positive patient-physician relationship. Recognizing the profound psychological impact, we propose the establishment of a new subdiscipline, namely ‘Psycho-Endoprosthetics’, to facilitate interdisciplinary collaborations for research and practice in septic surgery.
A hybrid framework for curve estimation based low light image enhancement
Non-targeted metabolomic study in plasma in rats with post-traumatic osteoarthritis model
Purpose This study aimed to examine the differential expression profiles of plasma metabolites in rat models of post-traumatic osteoarthritis (PTOA) and elucidate the roles of metabolites and their pathways in the progression of PTOA using bioinformatics analysis. Method Plasma samples were collected from 24 SD female rats to model PTOA, and metabolomic assays were conducted. The samples were divided into three groups: the surgically induced mild PTOA group (Group A: 3 weeks postoperative using the modified Hulth model; age 2 months), the surgically induced severe PTOA group (Group B: 5 weeks postoperative using the modified Hulth model; age 2 months), and the normal control group (Group C: healthy rats aged 2 months). Metabolites were structurally identified by comparing the retention times, molecular masses, secondary fragmentation spectra, collision energies, and other metabolite data with a database (provided by Shanghai Applied Protein Technology Co., Ltd.). Target prediction and pathway analysis were subsequently performed using bioinformatics analysis. Results The experiment revealed that in the mild PTOA group, levels of Alpha-ketoglutarate, Isocitric acid, Dichloroacetate, and other metabolites increased significantly compared with the normal group, whereas Linolenic acid, Lactose, and others decreased significantly. These findings suggest that these metabolites can serve as biomarkers for the diagnosis of early PTOA. In the severe PTOA group, Diosgenin, Indoleacrylic acid, Alpha-ketoglutarate, Isocitric acid, and others were elevated and may also be used as biomarkers for PTOA diagnosis. Adrenosterone, (+)-chlorpheniramine, and Phenanthridine levels were higher in the severe PTOA group compared to the mild PTOA group, while Menadione, Adenosine 5’-monophosphate, and Arg-Gly-Asp levels were lower. Conclusions Taurocholate, indoleacrylic acid, alpha-ketoglutarate, and isocitric acid may serve as biomarkers for PTOA joint injury in rats. Menadione, adenosine 5’-monophosphate, and Arg-Gly-Asp exhibited differential expression between severe and mild PTOA groups in rats, potentially reflecting the injury’s severity. Further investigation into these molecules in human tissues is warranted to ascertain their utility as biomarkers for PTOA in humans.
Phytotoxic effects of petroleum hydrocarbons on germination and growth of the native halophyte Salicornia sinus persica in oil contaminated soil
Transition-State-Dependent Spontaneous Generation of Reactive Oxygen Species by Aβ Assemblies Encodes a Self-Regulated Positive Feedback Loop for Aggregate Formation
Broadcasting American red squirrel vocalizations influences detection probability
Territorial responses by North American red squirrels (Tamiasciurus hudsonicus) to conspecifics vary seasonally with peaks during mating and dispersal periods. Broadcast of squirrel vocalizations during surveys may elicit territorial defense behaviors such as calling and movement that make individuals more available for detection, with implications for subsequent occupancy and abundance analyses. We examined the effect of vocalization broadcasts on detection probability during point counts throughout a 14-month period at two locations (year-round study) and during two summers at a third location (summer-only study) on Newfoundland, Canada. Overall detection probability based on sight and sound varied seasonally but the use of vocalization broadcast consistently enhanced detection probability. Squirrels were also more likely to be seen during vocalization broadcast survey periods than during silent point counts. Response to vocalization broadcast was highest when local population density was lowest. Higher detection probability during the initial silent periods of our surveys, when population density was high, likely reflects the greater chance of spontaneous vocalizations in response to the behavior of neighbors.
Disparities in overall survival of gastric cancer patients after radical gastrectomy: an age and rural-urban residence-based cohort study with propensity score matching analysis
Circular Workflow for Thermosets: Activatable Repeat Unit Design for Regenerative Frontal Polymerization
Analysis and prediction of addiction among virtual reality users
Objective To understand the addiction situation and influencing factors of virtual reality users, and provide reference basis for timely and effective prevention and intervention of user addiction. Methods Based on a questionnaire survey, univariate analysis, multivariate analysis, and model prediction were conducted on the data of 1164 participants in VR related Facebook groups and Reddit subedits. Results The single factor analysis results show that the user’s own attributes, usage duration, perception level, and application types of virtual reality devices can significantly affect the degree of addiction; The results of multivariate analysis showed that the age of users, the number of days used per week, the number of hours used per day, and the perceived level of the device can significantly affect the probability of addiction. In addition, this study used decision tree algorithm to predict adolescent virtual reality device addiction, with a prediction accuracy of 0.957. Conclusion The addiction of virtual reality users is related to multiple factors such as gender, age, usage time, application type, and perception level. When developing VR applications and content, consideration should be given to balancing user immersion and healthy use, and reasonable control of usage time is also an effective means to prevent VR addiction.