Tag: nevin manimala

J Chem Inf Model. 2022 Jul 22. doi: 10.1021/acs.jcim.2c00258. Online ahead of print.

ABSTRACT

Selecting the most appropriate compounds to synthesize and test is a vital aspect of drug discovery. Methods like clustering and diversity present weaknesses in selecting the optimal sets for information gain. Active learning techniques often rely on an initial model and computationally expensive semi-supervised batch selection. Herein, we describe a new subset-based selection method, Coverage Score, that combines Bayesian statistics and information entropy to balance representation and diversity to select a maximally informative subset. Coverage Score can be influenced by prior selections and desirable properties. In this paper, subsets selected through Coverage Score are compared against subsets selected through model-independent and model-dependent techniques for several datasets. In drug-like chemical space, Coverage Score consistently selects subsets that lead to more accurate predictions compared to other selection methods. Subsets selected through Coverage Score produced Random Forest models that have a root-mean-square-error up to 12.8% lower than subsets selected at random and can retain up to 99% of the structural dissimilarity of a diversity selection.

PMID:35867814 | DOI:10.1021/acs.jcim.2c00258

Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2204761119. doi: 10.1073/pnas.2204761119. Epub 2022 Jul 7.

ABSTRACT

It is established that changes in sea level influence melt production at midocean ridges, but whether changes in melt production influence the pattern of bathymetry flanking midocean ridges has been debated on both theoretical and empirical grounds. To explore the dynamics that may give rise to a sea-level influence on bathymetry, we simulate abyssal hills using a faulting model with periodic variations in melt supply. For 100-ky melt-supply cycles, model results show that faults initiate during periods of amagmatic spreading at half-rates >2.3 cm/y and for 41-ky melt-supply cycles at half-rates >3.8 cm/y. Analysis of bathymetry across 17 midocean ridge regions shows characteristic wavelengths that closely align with the predictions from the faulting model. At intermediate-spreading ridges (half-rates >2.3 cm/y and [Formula: see text]3.8 cm/y) abyssal hill spacing increases with spreading rate at 0.99 km/(cm/y) or 99 ky (n [Formula: see text] 12; 95% CI, 87 to 110 ky), and at fast-spreading ridges (half-rates >3.8 cm/y) spacing increases at 38 ky (n [Formula: see text] 5; 95% CI, 29 to 47 ky). Including previously published analyses of abyssal-hill spacing gives a more precise alignment with the primary periods of Pleistocene sea-level variability. Furthermore, analysis of bathymetry from fast-spreading ridges shows a highly statistically significant spectral peak (P < 0.01) at the 1/(41-ky) period of Earth’s variations in axial tilt. Faulting models and observations both support a linkage between glacially induced sea-level change and the fabric of the sea floor over the late Pleistocene.

PMID:35867751 | DOI:10.1073/pnas.2204761119

Cytopathology. 2022 Jul 22. doi: 10.1111/cyt.13170. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the prevalence of cellular debris (CD) on benign cervicovaginal liquid-based cytology (LBC) smears and which factors predict the presence and larger amount of CD.

METHODS: Cervicovaginal smears evaluated as negative for intraepithelial lesion or malignancy (NILM) between January 1st and March 31st, 2020, were retrospectively reviewed to record the presence and amount of CD. All smears were prepared with the SurePath platform. Patients’ age and past medical and surgical histories were also retrieved. Multivariate regression analyses were performed to find positive predictors of a larger amount of CD.

RESULTS: 349 NILM smears were included in this study. The cohort consisted of 222 cervical smears (CS) and 127 vaginal smears (VS), which were taken from patients who had undergone hysterectomy. Overall, CD was observed in 111 (31.8%) cases. The positive predictors of CD were increasing age, specimen type (VS compared to CS), history of chemotherapy or radiation therapy (CRT), and more than mild background inflmmation. Among VS group, CD was present in 64 cases (50.4%) regardless of the time between the specimen collection and hysterectomy. Positive predictors in the VS group were age and more than mild inflammation. Contrary, in the CS group, the prevalence of CD was 21.2%, and age was the only positive predictor. Histories of CRT, conization and inflammation were not statistically significant positive predictors for CD among CS.

CONCLUSIONS: CD can be seen in as much as 50% of NILM smears taken after hysterectomy, regardless of the time since hysterectomy. Increasing age is a positive predictor of the presence and a larger quantity of CD. These findings are helpful when evaluating smears with moderate to abundant debris in the background with questionable cellular atypia.

PMID:35867812 | DOI:10.1111/cyt.13170

Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2204074119. doi: 10.1073/pnas.2204074119. Epub 2022 Jul 7.

ABSTRACT

Massive scientific productivity accompanied the COVID-19 pandemic. We evaluated the citation impact of COVID-19 publications relative to all scientific work published in 2020 to 2021 and assessed the impact on scientist citation profiles. Using Scopus data until August 1, 2021, COVID-19 items accounted for 4% of papers published, 20% of citations received to papers published in 2020 to 2021, and >30% of citations received in 36 of the 174 disciplines of science (up to 79.3% in general and internal medicine). Across science, 98 of the 100 most-cited papers published in 2020 to 2021 were related to COVID-19; 110 scientists received ≥10,000 citations for COVID-19 work, but none received ≥10,000 citations for non-COVID-19 work published in 2020 to 2021. For many scientists, citations to their COVID-19 work already accounted for more than half of their total career citation count. Overall, these data show a strong covidization of research citations across science, with major impact on shaping the citation elite.

PMID:35867747 | DOI:10.1073/pnas.2204074119

Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2201250119. doi: 10.1073/pnas.2201250119. Epub 2022 Jul 6.

ABSTRACT

Phase separation has emerged as an essential concept for the spatial organization inside biological cells. However, despite the clear relevance to virtually all physiological functions, we understand surprisingly little about what phases form in a system of many interacting components, like in cells. Here we introduce a numerical method based on physical relaxation dynamics to study the coexisting phases in such systems. We use our approach to optimize interactions between components, similar to how evolution might have optimized the interactions of proteins. These evolved interactions robustly lead to a defined number of phases, despite substantial uncertainties in the initial composition, while random or designed interactions perform much worse. Moreover, the optimized interactions are robust to perturbations, and they allow fast adaption to new target phase counts. We thus show that genetically encoded interactions of proteins provide versatile control of phase behavior. The phases forming in our system are also a concrete example of a robust emergent property that does not rely on fine-tuning the parameters of individual constituents.

PMID:35867744 | DOI:10.1073/pnas.2201250119

PLoS One. 2022 Jul 22;17(7):e0271539. doi: 10.1371/journal.pone.0271539. eCollection 2022.

ABSTRACT

Considering the vast biological diversity and high mortality rate in high-grade ovarian cancers, identification of novel biomarkers, enabling precise diagnosis and effective, less aggravating treatment, is of paramount importance. Based on scientific literature data, we selected 80 cancer-related genes and evaluated their mRNA expression in 70 high-grade serous ovarian cancer (HGSOC) samples by Real-Time qPCR. The results were validated in an independent Northern American cohort of 85 HGSOC patients with publicly available NGS RNA-seq data. Detailed statistical analyses of our cohort with multivariate Cox and logistic regression models considering clinico-pathological data and different TP53 mutation statuses, revealed an altered expression of 49 genes to affect the prognosis and/or treatment response. Next, these genes were investigated in the validation cohort, to confirm the clinical significance of their expression alterations, and to identify genetic variants with an expected high or moderate impact on their products. The expression changes of five genes, PROM1, CXCL8, RUNX1, NAV1, TP73, were found to predict prognosis or response to treatment in both cohorts, depending on the TP53 mutation status. In addition, we revealed novel and confirmed known SNPs in these genes, and showed that SNPs in the PROM1 gene correlated with its elevated expression.

PMID:35867729 | DOI:10.1371/journal.pone.0271539

PLoS One. 2022 Jul 22;17(7):e0271677. doi: 10.1371/journal.pone.0271677. eCollection 2022.

ABSTRACT

Soil disinfestation with steam was evaluated as an alternative to fumigation. Following soil disinfestation, plant health has traditionally been measured using plant size and yield. Plant health can be measured in a timely manner more efficiently, more easily and non-destructively using image analysis. We hypothesized that plant health could be quantified and treatments can be differentiated using an RGB (Red, Green, Blue) image analysis program, particularly by observing the greenness of plant leaves. However, plant size or the proportion of green area could be unreliable due to plant loss and camera’s position and angle. To this end, we decided to evaluate plant health by analyzing the RGB codes associated with the green color only, which detects the chlorophyll reflectance and nutrient status, noting that the degree of greenness within the green-leaf-area was not affected by the plant size. We identified five RGB codes that are commonly observed in the plant leaves and ordered them from dark green to light green. Among the five RGB codes, the relative percentage covered by the darkest green to the lightest green was significantly different between the steam and chloropicrin treatments and the control, and it was not significantly different between the steam and chloropicrin treatments. Furthermore, the result was correlated with the total yield, and the trend observed in the first year was replicated in the second year of this experiment. In this study, we demonstrate that the RGB image analysis can be used as an early marker of the treatment effect on the plant health and productivity.

PMID:35867725 | DOI:10.1371/journal.pone.0271677

PLoS One. 2022 Jul 22;17(7):e0272007. doi: 10.1371/journal.pone.0272007. eCollection 2022.

ABSTRACT

Interval estimation with accurate coverage for risk difference (RD) in a correlated 2 × 2 table with structural zero is a fundamental and important problem in biostatistics. The score test-based and Bayesian tail-based confidence intervals (CIs) have good coverage performance among the existing methods. However, as approximation approaches, they have coverage probabilities lower than the nominal confidence level for finite and moderate sample sizes. In this paper, we propose three new CIs for RD based on the fiducial, inferential model (IM) and modified IM (MIM) methods. The IM interval is proven to be valid. Moreover, simulation studies show that the CIs of fiducial and MIM methods can guarantee the preset coverage rate even for small sample sizes. More importantly, in terms of coverage probability and expected length, the MIM interval outperforms other intervals. Finally, a real example illustrates the application of the proposed methods.

PMID:35867721 | DOI:10.1371/journal.pone.0272007

Clin Infect Dis. 2022 Jul 22:ciac577. doi: 10.1093/cid/ciac577. Online ahead of print.

ABSTRACT

BACKGROUND: Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited.

METHODS: We conducted a prospective, test-negative study of children 6 months-17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression.

RESULTS: Of 8,430 children, 4,653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were vaccinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs. 57%, p < 0.001); overall VE against hospitalization was 53% (95% CI: 46%-60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%-12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4,000, p = 0.275). Odds of hospitalization increased 2.9% (95% CI: -5.4%-11.8%) and 9.6% (95% CI: -7.0%-29.1%) per month in children ≤8 years (n = 3,084) and 9-17 years (n = 916), respectively. These findings were not statistically significant.

CONCLUSIONS: We observed minimal, not statistically significant within-season declines in VE. Vaccination following current ACIP guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.

PMID:35867698 | DOI:10.1093/cid/ciac577

JMIR Res Protoc. 2022 Jul 22;11(7):e35565. doi: 10.2196/35565.

ABSTRACT

BACKGROUND: Following radioiodine (¹³¹I) therapy of differentiated thyroid cancer, the salivary glands may become inflamed, leading to dysfunctions and decreases in patients’ nutritional status and quality of life. The incidence of these dysfunctions after ¹³¹I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define at-risk patients, which would allow the delivered activity to be adapted to the expected risk of salivary dysfunctions.

OBJECTIVE: The aims of this study are to estimate the incidence of salivary dysfunctions, and consequences on the quality of life and nutritional status for patients after ¹³¹I-therapy; to characterize at-risk patients of developing posttreatment dysfunctions using clinical, biomolecular, and biochemical factors; and to validate a dosimetric method to calculate the dose received at the salivary gland level for analyzing the dose-response relationship between absorbed doses to salivary glands and salivary dysfunctions.

METHODS: This prospective study aims to include patients for whom ¹³¹I-therapy is indicated as part of the treatment for differentiated thyroid cancer in a Paris hospital (40 and 80 patients in the 1.1 GBq and 3.7 GBq groups, respectively). The follow-up is based on three scheduled visits: at inclusion (T0, immediately before ¹³¹I-therapy), and at 6 months (T6) and 18 months (T18) posttreatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (Hospital Anxiety and Depression scale, Medical Outcomes Study 36-Item Short Form Survey), and nutritional status (visual analog scale) are administered by a trained clinical research associate. At T0 and T6, saliva samples and individual measurements of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before ¹³¹I administration and removed after 5 days. From the doses recorded by the dosimeters, an estimation of the dose received at the salivary glands will be carried out using physical and computational phantoms. Genetic and epigenetic analyses will be performed to search for potential biomarkers of the predisposition to develop salivary dysfunctions after ¹³¹I-therapy.

RESULTS: A total of 139 patients (99 women, 71.2%; mean age 47.4, SD 14.3 years) were enrolled in the study between September 2020 and April 2021 (45 and 94 patients in the 1.1 GBq and 3.7G Bq groups, respectively). T6 follow-up is complete and T18 follow-up is currently underway. Statistical analyses will assess the links between salivary dysfunctions and absorbed doses to the salivary glands, accounting for associated factors. Moreover, impacts on the patients’ quality of life will be analyzed.

CONCLUSIONS: To our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions and will permit clinicians to propose a more adapted follow-up and/or countermeasures to adverse effects.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04876287; https://clinicaltrials.gov/ct2/show/NCT04876287.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35565.

PMID:35867385 | DOI:10.2196/35565