Miracle-dz/UniFAR-FTUs huggingface dataset:
RETRACTED ARTICLE: Sustained Delivery of Timolol Using Nanostructured Lipid Carriers-Laden Soft Contact Lenses

The contact lens prepared by the conventional soaking method using timolol-soaking solution showed poor drug uptake and high burst release with altered critical lens properties. In this study, timolol-loaded nanostructured lipid carriers (NLCs) were prepared and evaluated for enhanced timolol uptake and sustained release for the effective management of glaucoma. The characterization studies indicated that timolol-loaded NLCs were spherical in shape with an average size of 130–138 nm and a zeta potential of −46.6 to 51.3 mV. Critical lens properties such as swelling, optical transmittance, and protein adherence were improved with NLC-laden lenses compared to the conventional soaked lenses (SM-TB). Moreover, SM-TB lens showed low timolol uptake, high burst release, and short release duration up to 24 h compared to timolol-NLC-laden lens that showed high timolol uptake, and the cumulative release was sustained up to 96 h. The ability to sustain timolol release improved proportionally with an increase in the amount of Capmul MCMC8 (liquid lipid) in NLCs. In addition, NLC-laden lens was found to be safe according to the results of ocular irritation and histopathological studies. In the rabbit tear fluid model, NLC-30%-Cap-CL batch showed high timolol concentration at all time points up to 60 h. Further, pharmacodynamic study showed sustained reduction in IOP by NLC-30%-Cap-CL batch for 96 h compared to 48 h and 6 h with SM-TB lens and eye drop solution, respectively. In conclusion, NLCs enhanced timolol uptake in the contact lens from the soaking solution using soaking method with improved in vitro and in vivo results for better clinical outcomes in the patients with glaucoma.
A review of graphene‐TiO2 and graphene‐ZnO nanocomposite photocatalysts for wastewater treatment

Technologies for wastewater remediation have been growing ever since the environmental and health concern is realized. Development of nanomaterials has enabled mankind to have different methods to treat the various kinds of inorganic and organic pollutants present in wastewater from many resources. Among the many materials, semiconductor materials have found many environmental applications due to their outstanding photocatalytic activities. TiO2 and ZnO are more effectively used as photocatalyst or adsorbents in the withdrawal of inorganic as well as organic wastes from the wastewater. On the other hand, graphene is tremendously being investigated for applications in environmental remediation in view of the superior physical, optical, thermal, and electronic properties of graphene nanocomposites. In this work, graphene‐TiO2 and graphene‐ZnO nanocomposites have been reviewed for photocatalytic wastewater treatment. The various preparation techniques of these nanocomposites have been discussed. Also, different design strategies for graphene‐based photocatalyst have been revealed. These nanocomposites exhibit promising applications in most of the water purification processes which are reviewed in this work. Along with this, the development of these nanocomposites using biomass‐derived graphene has also been introduced.
Merlin functions as a critical regulator in Staphylococcus aureus‐induced osteomyelitis

Merlin is known as a tumor suppressor, while its role in osteomyelitis remains unclear. This study aimed to investigate the role of Merlin in Staphylococcus aureus‐induced osteomyelitis and its underlying mechanisms. S. aureus‐induced osteomyelitis mouse model was established in Merlinfl/flLyz2cre/+ and Merlinfl/flLyz2+/+ mice. Bone marrow–derived macrophages (BMDMs) were isolated and stimulated by lipopolysaccharide (LPS). Bioassays, including quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blot analysis, and enzyme‐linked immunosorbent assays, were conducted to determine the levels of target genes or proteins. Immunoprecipitation was applied to determine the interactions between proteins. DCAF1fl/fl mice were further crossed with Lyz2‐Cre mice to establish myeloid cell conditional knockout mice (DCAF1fl/flLyz2cre/+). It was found that the level of Merlin was elevated in patients with osteomyelitis and S. aureus‐infected BMDMs. Merlin deficiency in macrophages suppressed the production of inflammatory cytokines and ameliorated the symptoms of osteomyelitis induced by S. aureus. Merlin deficiency in macrophages also suppressed the production of proinflammatory cytokines in BMDMs induced by LPS. The inhibitory effects of Merlin deficiency on the inflammatory response were associated with DDB1‐Cul4‐associated factor 1 (DCAF1). In summary, Merlin deficiency ameliorates S. aureus‐induced osteomyelitis through the regulation of DCAF1.
Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer

Background Durable efficacy of immune checkpoint blockade (ICB) occurred in a small number of patients with metastatic gastric cancer (mGC) and the determinant biomarker of response to ICB remains unclear. Methods We developed an open-source TMEscore R package, to quantify the tumor microenvironment (TME) to aid in addressing this dilemma. Two advanced gastric cancer cohorts (RNAseq, N=45 and NanoString, N=48) and other advanced cancer (N=534) treated with ICB were leveraged to investigate the predictive value of TMEscore. Simultaneously, multi-omics data from The Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) were interrogated for underlying mechanisms. Results The predictive capacity of TMEscore was corroborated in patient with mGC cohorts treated with pembrolizumab in a prospective phase 2 clinical trial (NCT02589496, N=45, area under the curve (AUC)=0.891). Notably, TMEscore, which has a larger AUC than programmed death-ligand 1 combined positive score, tumor mutation burden, microsatellite instability, and Epstein-Barr virus, was also validated in the multicenter advanced gastric cancer cohort using NanoString technology (N=48, AUC=0.877). Exploration of the intrinsic mechanisms of TMEscore with TCGA and ACRG multi-omics data identified TME pertinent mechanisms including mutations, metabolism pathways, and epigenetic features. Conclusions Current study highlighted the promising predictive value of TMEscore for patients with mGC. Exploration of TME in multi-omics gastric cancer data may provide the impetus for precision immunotherapy.
Responses of oil degrader enzyme activities, metabolism and degradation kinetics to bean root exudates during rhizoremediation of crude oil contaminated soil

Abstract During rhizoremediation process, plant roots secrete the specific exudates which enhance or stimulate growth and activity of microbial community in the rhizosphere resulting in effective degradation of pollutants. The present study characterized cowpea (CP) and mung bean (MB) root exudates and examined their influences on the degradation of total petroleum hydrocarbons (TPHs) and polycyclic aromatic hydrocarbons (PAHs) by the two oil degraders Micrococcus luteus WN01 and Bacillus cereus W2301. The effects of root exudates on soil microbial population dynamic and their enzymes dehydrogenase (DHA), and catechol 2,3 dioxygenase (C23O) activities were assessed. Both root exudates enhanced the degradation by both oil degraders. Cowpea root exudates maximized the removal of TPHs and PAHs by M. luteus WN01. Both bacterial population and DHA increased significantly in the presence of both root exudates. However, the C23O activities were significantly higher in WN01 treated. No significant influence of root exudates was observed on the C23O activities of W2301 treated. By using gas chromatography -mass spectroscopy, the dominant compounds found in cowpea and mung bean root exudates were 4-methoxy-cinnamic acid and terephthalic acid. Found in lower amount were propionic, malonic acid, and citric acid which were associated with enhanced PAHs desorption from soil and subsequent degradation. Novelty statement This is the first study to characterize the low molecular weight organic acids from root exudates of cowpea and mung bean and their influences on hydrocarbon desorption and hence enhancing the biodegradation process. The findings of the present study will greatly contribute to a better understanding of plant-microbe interaction in total petroleum hydrocarbons contaminated soil.
Orthodontic clinicians’ attitudes and knowledge of dentogingival aesthetics: A cross-sectional survey of BOS members

Objective: To assess orthodontic clinicians’ knowledge and attitudes towards dentogingival aesthetics and to explore characteristics that predict the knowledge of dentogingival aesthetics. Design: Cross-sectional questionnaire Setting: On-line survey of members of the British Orthdontic Society. Materials and Methods: An 11-item online questionnaire was sent to orthodontic practitioners for completion. The questionnaire covered respondent demographics and questions relating to both knowledge and attitudes towards dentogingival aesthetics (six parameters). Descriptive statistics were calculated for study characteristics and summary values for the survey items. Responses to the eight knowledge-based questions were converted to a binary outcome (correct and incorrect answer). The maximum score that could be achieved was eight. Multivariable modelling was used in order to examine associations between the study characteristics and the aggregate score. Results: A total of 252 responses were obtained resulting in a response rate of 17%. Within this cohort, the respondents were primarily women (52.8%) and aged 30–40 years (35.7%). The mean score for the eight knowledge-based questions was 3.8 ± 1.8 (range = 0−8). Knowledge of the ideal gingival margin position of the anterior teeth was high (92.4%). Knowledge of the other five dentogingival aesthetic parameters was variable. In the multivariable analysis, lower knowledge scores were predicated by respondents who did not have a special interest in dental aesthetics (−0.54; 95% confidence interval [CI] = −1.01 to −0.07; P = 0.02), who could not recall attending courses, lectures or seminars on dental aesthetics in the past five years (−0.80; 95% CI = −1.43 to −0.17; P = 0.01) and with increasing age (−0.43; 95% CI = −0.62 to −0.23; P < 0.001). Conclusion: Knowledge of ideal dentogingival parameters is generally suboptimal among orthodontists in the UK. The reported lack of knowledge of the ideal dentogingival parameters may also influence respondents’ attitudes towards the importance of dentogingival aesthetics. Further teaching or courses related to dentogingival aesthetics is desired by orthodontic clinicians.
Does the ICU Requirement Score allow the poisoned patient to be safely managed without admission to the intensive care unit? – a validation cohort study

Abstract Background The Intensive care unit (ICU) Requirement Score (IRS) has been defined as identifying poisoned patients on hospital admission who do not require ICU referral, in an effort to reduce health expenses. However, this score has been poorly validated. We aimed to evaluate the IRS in a large cohort of poisoned patients. Methods We performed a single-center retrospective cohort study. IRS was calculated using clinical parameters obtained on admission including age, systolic blood pressure, heart rate, Glasgow coma score, intoxication type, co-morbidities (i.e., arrhythmia, cirrhosis, and respiratory insufficiency), and the combination of the intoxication with another reason for ICU admission. We evaluated the ability of IRS < 6 determined on admission to predict the lack of need for ICU treatment, defined as the need for mechanical ventilation, vasopressors, and/or renal replacement therapy in the first 24 h post-admission and/or death during the hospital stay. This score was compared to the usual prognostic scores, i.e., SAPS II and III, SOFA score, and PSS. Results During the 10-year study period, 2,514 poisoned patients were admitted, 1,011 excluded as requiring ICU treatment on admission, and 1,503 included. Among these patients, 232 met the endpoint whereas only 23/510 patients with IRS < 6 (4.5%) presented the endpoint and one patient died. The area under the curve of the IRS ROC curve was 0.736 (95% confidence interval (CI), 0.702–0.770). The negative predictive value of IRS < 6 was 95% (95% CI, 93–97), sensitivity 89% (95% CI, 85–93), specificity 38% (95% CI, 36–41), and positive predictive value 21% (95% CI, 18–24). IRS performance was similar to those of the other tested scores, which are however not readily available on admission. Conclusion Our data demonstrate the excellent negative predictive value of the IRS, allowing the exclusion of ICU requirements for poisoned patients with IRS < 6. IRS usefulness should be confirmed based on a prospective multicenter cohort study before extensive routine use.
Diversity of metazoan parasites in fish Triportheus angulatus and Triportheus auritus living in sympatry in the Brazilian Amazon.

The aim of this study was to compare the diversity and community structure of metazoan parasites in sympatric populations of Triportheus angulatus and Triportheus auritus in the Jari River basin, in the eastern Brazilian Amazon. All the specimens of T. angulatus and T. auritus examined were infected by Anacanthorus furculus, Anacanthorus pithophallus, Digenea gen. sp. , Procamallanus (Spirocamallanus) inopinatus, Rhabdochona acuminata, Contracaecum sp. , Ergasilus sp. and Acarina gen. sp. These parasites displayed aggregated or random dispersion. The parasite community in T. angulatus and T. auritus presented a similarity of 78%. The diversity indice and richness of parasite species were greater in T. auritus and there were differences in levels of host parasite infection for some infracommunities. Phyllodistomum spatula occurred only in T. angulatus, while metacercariae of Clinostomum marginatum and Digenea gen. sp.2 occurred only in T. auritus. The species richness of the parasites was influenced by host size, as well as the abundance of some parasite infracommunities. This is the first report of these parasites for T. angulatus and T. auritus, except for P. (S.) inopinatus and Contracaecum sp. for T. angulatus.
Evaluating the Beijing Version of Montreal Cognitive Assessment for Identification of Cognitive Impairment in Monolingual Chinese American Older Adults

Objective: This study aims to evaluate the performance of a Chinese version of the Montreal Cognitive Assessment (MoCA) as a screener to detect mild cognitive impairment (MCI) and dementia from normal cognition in the monolingual Chinese-speaking immigrant population. Method: A cohort of 176 Chinese-speaking older adults from the National Alzheimer’s Coordinating Center Uniform Data Set is used for analysis. We explore the impact of demographic variables on MoCA performance and calculate the optimal cutoffs for the detection of MCI and dementia from normal cognition with appropriate demographic adjustment. Results: MoCA performance is predicted by age and education independent of clinical diagnoses, but not by sex, years of living in the U.S., or primary Chinese dialect spoken (i.e., Mandarin vs. Cantonese). With adjustment and stratification for education and age, we identify optimal cutoff scores to detect MCI and dementia, respectively, in this population. These optimal cutoff scores are different from the established scores for non-Chinese-speaking populations residing in the U.S. Conclusions: Our findings suggest that the Chinese version of MoCA is a valid screener to detect cognitive decline in older Chinese-speaking immigrants in the U.S. They also highlight the need for population-based cutoff scores with appropriate considerations for demographic variables.
A hierarchy of correlates impacting adults’ sensor-based physical activity and sedentary time

ABSTRACT Investigation into correlates across all levels of the socio-ecological model predictive of objectively measured physical activity has rarely been assessed in adults. While considering a diversity of correlates, we determined which correlates best predict sensor-based moderate-to-vigorous physical activity (MVPA) and sedentary-time (ST) in adults. A Chi-squared Automatic Interaction Detection algorithm was used to hierarchize the correlates associated with high ST (≥66.6thpercentile) and sufficient MVPA (≥150 min/week) in 865 adults. The main correlate predictive of being active was currently partaking in sport/exercise. The following relevant correlates were being male for the exercisers and having trees in the neighbourhood for the non-exercisers. The final correlate to boost male exercisers’ MVPA was having lots of shops in the neighbourhood and not having television in the bedroom for women. The primary correlate for high ST was job activity level, with individuals having highly active jobs being less likely to exhibit high levels of ST; being single, male, and a former athlete also increased the chances of being highly sedentary. To increase adults’ MVPA, promotion of sport participation, neighbourhood landscape planning, shop availability, as well as limiting television in the bedroom must be prioritized. For counteracting ST, increasing workplace activity level is warranted.
Polygenic Risk Scores Derived From Varying Definitions of Depression and Risk of Depression.

Importance Genetic studies with broad definitions of depression may not capture genetic risk specific to major depressive disorder (MDD), raising questions about how depression should be operationalized in future genetic studies. Objective To use a large, well-phenotyped single study of MDD to investigate how different definitions of depression used in genetic studies are associated with estimation of MDD and phenotypes of MDD, using polygenic risk scores (PRSs). Design, Setting, and Participants In this case-control polygenic risk score analysis, patients meeting diagnostic criteria for a diagnosis of MDD were drawn from the Australian Genetics of Depression Study, a cross-sectional, population-based study of depression, and controls and patients with self-reported depression were drawn from QSkin, a population-based cohort study. Data analyzed herein were collected before September 2018, and data analysis was conducted from September 10, 2020, to January 27, 2021. Main Outcome and Measures Polygenic risk scores generated from genome-wide association studies using different definitions of depression were evaluated for estimation of MDD in and within individuals with MDD for an association with age at onset, adverse childhood experiences, comorbid psychiatric and somatic disorders, and current physical and mental health. Results Participants included 12 106 (71% female; mean age, 42.3 years; range, 18-88 years) patients meeting criteria for MDD and 12 621 (55% female; mean age, 60.9 years; range, 43-87 years) control participants with no history of psychiatric disorders. The effect size of the PRS was proportional to the discovery sample size, with the largest study having the largest effect size with the odds ratio for MDD (1.75; 95% CI, 1.73-1.77) per SD of PRS and the PRS derived from ICD-10 codes documented in hospitalization records in a population health cohort having the lowest odds ratio (1.14; 95% CI, 1.12-1.16). When accounting for differences in sample size, the PRS from a genome-wide association study of patients meeting diagnostic criteria for MDD and control participants was the best estimator of MDD, but not in those with self-reported depression, and associations with higher odds ratios with childhood adverse experiences and measures of somatic distress. Conclusions and Relevance These findings suggest that increasing sample sizes, regardless of the depth of phenotyping, may be most informative for estimating risk of depression. The next generation of genome-wide association studies should, like the Australian Genetics of Depression Study, have both large sample sizes and extensive phenotyping to capture genetic risk factors for MDD not identified by other definitions of depression.
Association of Silent Cerebrovascular Disease Identified Using Natural Language Processing and Future Ischemic Stroke

Background and Objectives Silent cerebrovascular disease (SCD), comprising silent brain infarction (SBI) and white matter disease (WMD), is commonly found incidentally on neuroimaging scans obtained in routine clinical care. Their prognostic significance is not known. We aimed to estimate the incidence of and risk increase in future stroke in patients with incidentally discovered SCD. Methods Patients in the Kaiser Permanente Southern California (KPSC) health system aged ≥50 years, without prior ischemic stroke, transient ischemic attack (TIA), or dementia/Alzheimer disease receiving a head CT or MRI between 2009 and 2019 were included. SBI and WMD were identified by natural language processing (NLP) from the neuroimage report. Results Among 262,875 individuals receiving neuroimaging, NLP identified 13,154 (5.0%) with SBI and 78,330 (29.8%) with WMD. The incidence of future stroke was 32.5 (95% confidence interval [CI] 31.1, 33.9) per 1,000 patient-years for patients with SBI: 19.3 (95% CI 18.9, 19.8) for patients with WMD and 6.8 (95% CI 6.7, 7.0) for patients without SCD. The crude hazard ratio (HR) associated with SBI was 3.40 (95% CI 3.25 to 3.56) and for WMD 2.63 (95% CI 2.54 to 2.71). With MRI-discovered SBI, the adjusted HR was 2.95 (95% CI 2.53 to 3.44) for those <65 years of age and 2.15 (95% CI 1.91 to 2.41) for those ≥65. With CT scan, the adjusted HR was 2.48 (95% CI 2.19 to 2.81) for those <65 and 1.81 (95% CI 1.71 to 1.91) for those ≥65. The adjusted HR associated with a finding of WMD was 1.76 (95% CI 1.69 to 1.82) and was not modified by age or imaging modality. Discussion Incidentally discovered SBI and WMD are common and associated with increased risk of subsequent symptomatic stroke, representing an important opportunity for stroke prevention.
Globally Adaptive Neural Network Tracking for Uncertain Output-Feedback Systems

This article investigates the problem of global neural network (NN) tracking control for uncertain nonlinear systems in output feedback form under disturbances with unknown bounds. Compared with the existing NN control method, the differences of the proposed scheme are as follows. The designed actual controller consists of an NN controller working in the approximate domain and a robust controller working outside the approximate domain, in addition, a new smooth switching function is designed to achieve the smooth switching between the two controllers, in order to ensure the globally uniformly ultimately bounded of all closed-loop signals. The Lyapunov analysis method is used to strictly prove the global stability under the combined action of unmeasured states and system uncertainties, and the output tracking error is guaranteed to converge to an arbitrarily small neighborhood through a reasonable selection of design parameters. A numerical example and a practical example were put forward to verify the effectiveness of the control strategy.
Treatment patterns and outcomes for patients with newly diagnosed glioblastoma multiforme: a retrospective cohort study

Aim: Investigate real-world outcomes and healthcare utilization of patients with glioblastoma multiforme (GBM) related to O6-methylguanine DNA methyltransferase (MGMT) promoter testing and methylation. Patients & methods: US Oncology Network data were analyzed for patients receiving first-line (1L) treatment for GBM. Results: Most patients received 1L radiation with temozolomide. Unadjusted median overall survival (OS) was higher in tested versus untested (median:18.1 vs 11.8 months) and in methylated versus unmethylated (median: 25.5 vs 12.4 months). Untested status, unmethylated MGMT and older age were associated with reduced OS and longer 1L treatment with increased OS. Similar findings were observed for progression-free survival. Utilization was similar between cohorts. Conclusion: In community oncology practices, MGMT methylation and testing were predictive of better survival in GBM.