Tag: nevin manimala

Chem Res Toxicol. 2023 May 19. doi: 10.1021/acs.chemrestox.2c00368. Online ahead of print.

ABSTRACT

Structural alerts are molecular substructures assumed to be associated with molecular initiating events in various toxic effects and an integral part of in silico toxicology. However, alerts derived using the knowledge of human experts often suffer from a lack of predictivity, specificity, and satisfactory coverage. In this work, we present a method to build hybrid QSAR models by combining expert knowledge-based alerts and statistically mined molecular fragments. Our objective was to find out if the combination is better than the individual systems. Lasso regularization-based variable selection was applied on combined sets of knowledge-based alerts and molecular fragments, but the variable elimination was only allowed to happen on the molecular fragments. We tested the concept on three toxicity end points, i.e., skin sensitization, acute Daphnia toxicity, and Ames mutagenicity, which covered both classification and regression problems. Results showed the predictive performance of such hybrid models is, indeed, better than the models based solely on expert alerts or statistically mined fragments alone. The method also enables the discovery of activating and mitigating/deactivating features for toxicity alerts and the identification of new alerts, thereby reducing false positive and false negative outcomes commonly associated with generic alerts and alerts with poor coverage, respectively.

PMID:37207298 | DOI:10.1021/acs.chemrestox.2c00368

Environ Sci Technol. 2023 May 19. doi: 10.1021/acs.est.3c00253. Online ahead of print.

ABSTRACT

Plankton are widely distributed in the aquatic environment and serve as an indicator of water quality. Monitoring the spatiotemporal variation in plankton is an efficient approach to forewarning environmental risks. However, conventional microscopy counting is time-consuming and laborious, hindering the application of plankton statistics for environmental monitoring. In this work, an automated video-oriented plankton tracking workflow (AVPTW) based on deep learning is proposed for continuous monitoring of living plankton abundance in aquatic environments. With automatic video acquisition, background calibration, detection, tracking, correction, and statistics, various types of moving zooplankton and phytoplankton were counted at a time scale. The accuracy of AVPTW was validated with conventional counting via microscopy. Since AVPTW is only sensitive to mobile plankton, the temperature- and wastewater-discharge-induced plankton population variations were monitored online, demonstrating the sensitivity of AVPTW to environmental changes. The robustness of AVPTW was also confirmed with natural water samples from a contaminated river and an uncontaminated lake. Notably, automated workflows are essential for generating large amounts of data, which are a prerequisite for available data set construction and subsequent data mining. Furthermore, data-driven approaches based on deep learning pave a novel way for long-term online environmental monitoring and elucidating the correlation underlying environmental indicators. This work provides a replicable paradigm to combine imaging devices with deep-learning algorithms for environmental monitoring.

PMID:37207295 | DOI:10.1021/acs.est.3c00253

J Phys Chem A. 2023 May 19. doi: 10.1021/acs.jpca.2c08662. Online ahead of print.

ABSTRACT

The reaction between the ground-state hydroxyl radical, OH(²Π), and ethylene, C₂H₄, has been investigated under single-collision conditions by the crossed molecular beam scattering technique with mass-spectrometric detection and time-of-flight analysis at the collision energy of 50.4 kJ/mol. Electronic structure calculations of the underlying potential energy surface (PES) and statistical Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of product branching fractions on the derived PES for the addition pathway have been performed. The theoretical results indicate a temperature-dependent competition between the anti-/syn-CH₂CHOH (vinyl alcohol) + H, CH₃CHO (acetaldehyde) + H, and H₂CO (formaldehyde) + CH₃ product channels. The yield of the H-abstraction channel could not be quantified with the employed methods. The RRKM results predict that under our experimental conditions, the anti– and syn-CH₂CHOH + H product channels account for 38% (in similar amounts) of the addition mechanism yield, the H₂CO + CH₃ channel for ∼58%, while the CH₃CHO + H channel is formed in negligible amount (<4%). The implications for combustion and astrochemical environments are discussed.

PMID:37207281 | DOI:10.1021/acs.jpca.2c08662

Am J Med Open. 2023 Jun;9:100040. doi: 10.1016/j.ajmo.2023.100040. Epub 2023 Mar 22.

ABSTRACT

BACKGROUND: The use of statins, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), and anticoagulants may be associated with fewer adverse outcomes in COVID-19 patients.

METHODS: Nested within a cohort of 800,913 patients diagnosed with COVID-19 between April 1, 2020 and June 24, 2021 from the Optum COVID-19 database, three case-control studies were conducted. Cases-defined as persons who: (1) were hospitalized within 30 days of COVID-19 diagnosis (n = 88,405); (2) were admitted to the intensive care unit (ICU)/received mechanical ventilation during COVID-19 hospitalization (n = 22,147); and (3) died during COVID-19 hospitalization (n = 2300)-were matched 1:1 using demographic/clinical factors with controls randomly selected from a pool of patients who did not experience the case definition/event. Medication use was based on prescription ≤90 days before COVID-19 diagnosis.

RESULTS: Statin use was associated with decreased risk of hospitalization (adjusted odds ratio [aOR], 0.72; 95% confidence interval [95% CI], 0.69, 0.75) and ICU admission/mechanical ventilation (aOR, 0.90; 95% CI, 0.84, 0.97). ACEI/ARB use was associated with decreased risk of hospitalization (aOR, 0.67; 95% CI, 0.65, 0.70), ICU admission/mechanical ventilation (aOR, 0.92; 95% CI, 0.86, 0.99), and death (aOR, 0.60; 95% CI, 0.47, 0.78). Anticoagulant use was associated with decreased risk of hospitalization (aOR, 0.94; 95% CI, 0.89, 0.99) and death (aOR, 0.56; 95% CI, 0.41, 0.77). Interaction effects-in the model predicting hospitalization-were statistically significant for statins and ACEI/ARBs (P < .0001), statins and anticoagulants (P = .003), ACEI/ARBs and anticoagulants (P < .0001). An interaction effect-in the model predicting ventilator use/ICU-was statistically significant for statins and ACEI/ARBs (P = .002).

CONCLUSIONS: Statins, ACEI/ARBs, and anticoagulants were associated with decreased risks of the adverse outcomes under study. These findings may provide clinically relevant information regarding potential treatment for patients with COVID-19.

PMID:37207280 | PMC:PMC10032048 | DOI:10.1016/j.ajmo.2023.100040

Osteoarthr Cartil Open. 2023 Apr 28;5(3):100365. doi: 10.1016/j.ocarto.2023.100365. eCollection 2023 Sep.

ABSTRACT

OBJECTIVE: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees “at risk” of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations.

DESIGN: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were “at risk”, whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n ​= ​59/52). Subregion values were used to compute location-independent change scores.

RESULTS: In KLG0 knees “at risk”, the femorotibial cartilage thinning score (-634 ​± ​516 ​μm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p ​< ​0.01; Cohen D -0.27) than the thinning score in “non-exposed” knees (-501 ​± ​319 ​μm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p ​≥ ​0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden’s nodes, repetitive knee bending were not significantly associated with cartilage thinning (r²<1%), with only knee pain reaching statistical significance.

CONCLUSIONS: Knees “at risk” of incident knee OA displayed greater cartilage thinning scores than those “non-exposed”. Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.

PMID:37207279 | PMC:PMC10188628 | DOI:10.1016/j.ocarto.2023.100365

Continence (Amst). 2022 Mar;1:100014. doi: 10.1016/j.cont.2022.100014. Epub 2022 Mar 18.

ABSTRACT

PURPOSE OR THE RESEARCH: Nearly 300,000 people are affected by spinal cord injury (SCI) with approximately 18,000 new cases annually, according to the National SCI Statistics Center. SCI affects physical mobility and impairs the function of multiple internal organs to cause lower urinary tract (LUT) dysfunctions manifesting as detrusor sphincter dyssynergia (DSD) and neurogenic detrusor overactivity (NDO) with detrimental consequences to the quality of life and increased morbidity. Multiple lines of evidence now support time dependent evolution of the complex SCI pathology which requires a multipronged treatment approach of immediate, specialized care after spinal cord trauma bookended by physical rehabilitation to improve the clinical outcomes. Instead of one size fits all treatment approach, we propose adaptive drug treatment to counter the time dependent evolution of SCI pathology, with three small molecule drugs with distinctive sites of action for the recovery of multiple functions.

PRINCIPAL RESULTS: Our findings demonstrate the improvement in the recovery of hindlimb mobility and bladder function of spinal cord contused mice following administration of small molecules targeting neurotrophin receptors, LM11A-31 and LM22B-10. While LM11A-31 reduced the cell death in the spinal cord, LM22B-10 promoted cell survival and axonal growth. Moreover, the soluble guanylate cyclase (sGC) activator, cinaciguat, enhanced the revascularization of the SCI injury site to promote vessel formation, dilation, and increased perfusion.

MAJOR CONCLUSIONS: Our adaptive three drug cocktail targets different stages of SCI and LUTD pathology: neuroprotective effect of LM11A-31 retards the cell death that occurs in the early stages of SCI; and LM22B-10 and cinaciguat promote neural remodeling and reperfusion at later stages to repair spinal cord scarring, DSD and NDO. LM11A-31 and cinaciguat have passed phase I and IIa clinical trials and possess significant potential for accelerated clinical testing in SCI/LUTD patients.

PMID:37207253 | PMC:PMC10194419 | DOI:10.1016/j.cont.2022.100014

J Ophthalmol. 2023 May 10;2023:5625990. doi: 10.1155/2023/5625990. eCollection 2023.

ABSTRACT

PURPOSE: To investigate the clinical effectiveness of canaloplasty performed with an ab interno technique using the iTrack microcatheter (Nova Eye Medical) in patients with mild-moderate glaucoma as compared to severe glaucoma.

METHODS: This is a retrospective single-center case series. Patients were preoperatively categorized as mild/moderate vs. severe glaucoma assessed using the mean deviation (MD) score and controlled group (baseline intraocular pressure (IOP) ≤18 mmHg) vs. uncontrolled group (>18 mmHg). All patients with glaucoma were eligible for recruitment except those who had undergone previous glaucoma surgery (with the exception of selective laser trabeculoplasty or SLT). Patients underwent canaloplasty via an ab interno surgical technique with or without phacoemulsification and were monitored for IOP, glaucoma medication usage, and surgical complications.

RESULTS: In total, 72 eyes were followed for 3.4 ± 0.5 years. Mean pre-op IOP (mmHg) was 19.3 ± 7.7 in the standalone group (n = 9) and 18.5 ± 5.6 in the combined group (n = 63) (p=0.38). At the last follow-up, mean IOP reduced by 36% to 12.4 ± 4.4 (p=0.02) in the standalone group and by 26% to 13.7 ± 4.8 in the combined group (p < 0.001). Mean pre-op IOP (mmHg) was 18.6 ± 5.2 in the severe group (n = 24) and 18.6 ± 6.2 in the mild-moderate group (n = 48) (p=0.48). Mean IOP was 14.1 ± 6.3 (-24%; p < 0.001) and 13.3 ± 3.7 (-29%; p < 0.001), respectively, at the last follow-up. Mean glaucoma medication usage decreased from 2.5 ± 0.9 to 2.1 ± 0.9 (-15%; p=0.083) in the severe group and 2.3 ± 1.0 to 1.4 ± 1.3 (-40%; p < 0.001) in the mild/moderate group. There was one localized Descemet’s membrane detachment in the moderate group.

CONCLUSION: iTrack canaloplasty achieved a statistically significant IOP reduction in mild-moderate and severe eyes and was found to be an effective option for reducing IOP and medications in patients with mild-moderate primary open-angle glaucoma (POAG). In severe eyes, it has reduced IOP while the medications remained stable.

PMID:37207241 | PMC:PMC10191748 | DOI:10.1155/2023/5625990

Eur Union Polit. 2023 Jun;24(2):327-347. doi: 10.1177/14651165221142504. Epub 2022 Dec 4.

ABSTRACT

The rotating EU presidency’s relevance for EU politics has decreased since the introduction of a permanent council president. However, news salience and framing of the own government acting as the EU presidency can amplify publicity for EU affairs. We, therefore, evaluate the visibility and framing of the EU presidency in 12 Austrian newspapers for 2009-2019. We conduct an automated text analysis of 22 presidencies over 11 years, testing several hypotheses statistically, and qualify results via manually coded frames of the Austrian EU presidency in 2018. The results confirm the crucial importance of the domestication of EU politics, underscoring the potential of the presidency to serve as a window of opportunity for public debate. We discuss our findings with reference to the EU’s democratic deficit.

PMID:37207239 | PMC:PMC10189837 | DOI:10.1177/14651165221142504

Front Immunol. 2023 May 3;14:1160048. doi: 10.3389/fimmu.2023.1160048. eCollection 2023.

ABSTRACT

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. Recently, the pathophysiology and novel drugs of ITP have been the focus of researchers with plenty of publications emerging. Bibliometrics is the process of extracting measurable data through statistical analysis of published research studies to provide an insight into the trends and hotspots.

OBJECTIVE: This study aimed to provide an insight into developing trends and hotspots in the field of ITP by bibliometric analysis.

METHODS: By using three bibliometric mapping tools (bibliometrix R package, VOSviewer, CiteSpace), we summarized the overview information of retrieved publications, as well as the analysis of keyword co-occurrence and reference co-citation.

RESULTS: A total of 3299 publications with 78066 citations on ITP research were included in the analysis. The keyword co-occurrence network identified 4 clusters relating to the diagnosis, pathophysiology, and treatment of ITP respectively. Then the reference co-citation analysis produced 12 clusters with a well-structured and highly credible clustering model, and they can be divided into 5 trends: second-line treatment, chronic ITP, novel therapy and pathogenesis, COVID-19 vaccine. Treg cells, spleen tyrosine kinase, and mesenchymal stem cells were the latest hotspots with strong burstness.

CONCLUSION: This bibliometric analysis provided a comprehensive insight into research hotspots and trends on ITP, which would enrich the review of the ITP research.

PMID:37207211 | PMC:PMC10189105 | DOI:10.3389/fimmu.2023.1160048

Front Immunol. 2023 May 3;14:1162669. doi: 10.3389/fimmu.2023.1162669. eCollection 2023.

ABSTRACT

BACKGROUND: Recent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.

METHODS: Normal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled ‘Naproxen Study’ were obtained and subjected to a tissue microarray for image mass cytometry (IMC) analysis. IMC data was processed using tissue segmentation and functional markers to ascertain cell type abundance. Computational outputs were then used to quantitatively compare immune cell abundance in pre- and post-naproxen specimens.

RESULTS: Using data-driven exploration, unsupervised clustering identified four populations of immune cell types with statistically significant changes between treatment and control groups. These four populations collectively describe a unique cell population of proliferating lymphocytes within mucosal samples from LS patients exposed to naproxen.

CONCLUSIONS: Our findings show that daily exposure of naproxen promotes T-cell proliferation in the colonic mucosa, which paves way for developing combination of immunoprevention strategies including naproxen for LS patients.

PMID:37207208 | PMC:PMC10189148 | DOI:10.3389/fimmu.2023.1162669