Category: Nevin Manimala

AAPS PharmSciTech. 2023 Nov 30;24(8):250. doi: 10.1208/s12249-023-02695-5.

ABSTRACT

Kinetic modeling of accelerated stability data serves an important purpose in the development of pharmaceutical products, providing support for shelf life claims and expediting the path to clinical implementation. In this context, a Bayesian kinetic modeling framework is considered, accommodating different types of nonlinear kinetics with temperature and humidity dependent rates of degradation and accounting for the humidity conditions within the packaging to predict the shelf life. In comparison to kinetic modeling based on nonlinear least-squares regression, the Bayesian approach allows for interpretable posterior inference, flexible error modeling and the opportunity to include prior information based on historical data or expert knowledge. While both frameworks perform comparably for high-quality data from well-designed studies, the Bayesian approach provides additional robustness when the data are sparse or of limited quality. This is illustrated by modeling accelerated stability data from two solid dosage forms and is further examined by means of artificial data subsets and simulated data.

PMID:38036798 | DOI:10.1208/s12249-023-02695-5

Nat Genet. 2023 Nov 30. doi: 10.1038/s41588-023-01597-3. Online ahead of print.

ABSTRACT

Fine-mapping aims to identify causal genetic variants for phenotypes. Bayesian fine-mapping algorithms (for example, SuSiE, FINEMAP, ABF and COJO-ABF) are widely used, but assessing posterior probability calibration remains challenging in real data, where model misspecification probably exists, and true causal variants are unknown. We introduce replication failure rate (RFR), a metric to assess fine-mapping consistency by downsampling. SuSiE, FINEMAP and COJO-ABF show high RFR, indicating potential overconfidence in their output. Simulations reveal that nonsparse genetic architecture can lead to miscalibration, while imputation noise, nonuniform distribution of causal variants and quality control filters have minimal impact. Here we present SuSiE-inf and FINEMAP-inf, fine-mapping methods modeling infinitesimal effects alongside fewer larger causal effects. Our methods show improved calibration, RFR and functional enrichment, competitive recall and computational efficiency. Notably, using our methods’ posterior effect sizes substantially increases polygenic risk score accuracy over SuSiE and FINEMAP. Our work improves causal variant identification for complex traits, a fundamental goal of human genetics.

PMID:38036779 | DOI:10.1038/s41588-023-01597-3

Environ Monit Assess. 2023 Dec 1;195(12):1555. doi: 10.1007/s10661-023-12165-x.

ABSTRACT

This research quantitatively evaluated the diversity of plants to protect vulnerable species. To measure vegetation information, the appropriate sampling plot size was determined based on the canopy cover of the dominant species of the study area (1 m²). Then, in each unit, sampling was done along 3 transects of 100 m. Along each transect, 10 plots with dimensions of one square meter were placed at a distance of 10 m from each other. In each plot, the type, life forms, frequency of plant species, and species density were recorded. Species diversity indices were calculated using Ecological Methodology software. The values obtained from these indicators were analyzed in SPSS 24 statistical software and using the F test. The results of the Analysis of variance (ANOVA) showed that the highest values of the species diversity indices are in the middle altitudes (ecotone) class. ANOVA of the richness, evenness, and heterogeneity indices in different altitude classes showed that the values of the richness indices were not significant, but among the indices related to the heterogeneity, the Hill index and all the evenness indices were significant. Comparing the numerical indices of our communities enables us to determine the impact of environmental stress in a single community to choose the best habitat among a similar group for conservation. A community that has high diversity and richness is important for conservation. Therefore, the authorities must prevent the destruction of the vegetation of the study area in connection with the implementation of principled and correct management by the potential of the region, but also to reduce the pressure of livestock grazing and carry out corrective and restoration operations, to turn these rangelands towards rich diversity.

PMID:38036716 | DOI:10.1007/s10661-023-12165-x

Sci Rep. 2023 Nov 30;13(1):21101. doi: 10.1038/s41598-023-48474-x.

ABSTRACT

Malnutrition might play a key role in the prognosis of patients with Crohn’s disease (CD). The aim of this study was to explore the impact of weight loss from diagnosis of CD to one-year post-diagnosis on disease prognosis in terms of surgery. Patients who were diagnosed with CD at Samsung Medical Center between 1995 to 2020 were included in this study. The study defined the “group with weight loss” as patients with weight loss in one year after diagnosis and the “group without body weight loss” as patients without weight loss in one year after diagnosis. Their data such as demographics, laboratory findings, and medical interventions were collected retrospectively. The primary outcome was confirmation of the difference in the incidence of surgery associated with CD between the group with weight loss and the group without body weight loss. We further analyzed factors associated with surgery outcomes. A total of 165 patients were analyzed in this study. Forty-one patients (24.8%) had body weight loss whereas 124 patients (75.2%) had no body weight loss. Body change at one year showed no significant association with direct surgical incidence. However, the patients with weight loss tended to undergo surgery earlier than patients without body weight loss. Among factors associated with outcomes of Crohn’s surgery, the albumin was the only significant factor. Patients with weight loss had no statistically significant increase in the risk of surgery than patients without weight loss, although they tended to undergo surgery earlier than patients without body weight loss. A prospective study is needed to determine serial body weight changes during follow-up for patients with CD.

PMID:38036713 | DOI:10.1038/s41598-023-48474-x

Nanotechnology. 2023 Nov 30. doi: 10.1088/1361-6528/ad115b. Online ahead of print.

ABSTRACT

Mixed convection flow of two layers nanofluid in a vertical enclosure is studied. The channel consists of two regions. Region I is electrically conducting while Region II is electrically non-conducting. Region I is filled with base fluid water with copper oxides nanoparticles and Region II is filled with base fluid kerosene oil with iron oxides. The simultaneous effects of electro-magnetohydrodynamics and Grashof number are also taken into account. The governing flow problem consists of nonlinear coupled differential equations which is tackled using analytical technique. Analytical results have been obtained by the homotopy analysis method (HAM). The results for the leading parameters, such as the Hartmann numbers, Grashof numbers, ratio of viscosities, width ratio, volume fraction of nanoparticles, and the ratio of thermal conductivities for three different electric field scenarios under heat generation/absorption were examined. It is found that the effect of the negative electric load parameter assists the flow while the effect of the positive electric load parameter opposes the flow as compared to the case when the electric load parameter is zero. All outcomes for significant parameters on velocity and temperature are discussed graphically.

PMID:38035401 | DOI:10.1088/1361-6528/ad115b

J Radiol Prot. 2023 Nov 30. doi: 10.1088/1361-6498/ad1159. Online ahead of print.

ABSTRACT

Justification of medical radiation exposure is one of the main elements of radiation protection for patients. For a medical exposure to proceed, the benefit from the procedure must have been determined to be greater than the detriment. It is rare, however, that justification can be stated quantitatively as a ratio of benefit to detriment, or as a net benefit, and this is particularly true for medical diagnostic exposures associated with non-fatal diseases where survival statistics do not apply. The concept of the disability-adjusted life year (DALY) is well established as a measure of disease severity in public health, and there have been calls to revise the international system of radiation protection dosimetry to employ the DALY as a measure of radiation detriment. This paper looks at possible routes to quantify the benefit and detriment aspects of justification based on initial published results for the use of the DALY as a measure of radiation detriment, together with established values of DALY for a range of diseases. Although spreadsheet-style solutions for the calculation of a justification factor based on statistical life tables can be devised, these will be shown to have some limitations. A justification factor based on the rate of change of benefit divided by the rate of change of detriment following medical exposure is proposed. This factor is simple to calculate, is age independent, can apply to non-fatal diseases and is argued to have logical and ethical advantages for the explanation of the relative benefits and detriments of radiological procedures to patients.&#xD.

PMID:38035392 | DOI:10.1088/1361-6498/ad1159

J Phys Chem Lett. 2023 Nov 30:10935-10942. doi: 10.1021/acs.jpclett.3c02643. Online ahead of print.

ABSTRACT

Break junction experiments allow investigating electronic and spintronic properties at the atomic and molecular scale. These experiments generate by their very nature broad and asymmetric distributions of the observables of interest, and thus, a full statistical interpretation is warranted. We show here that understanding the complete lifetime distribution is essential for obtaining reliable estimates. We demonstrate this for Au atomic point contacts by adopting Bayesian reasoning to make maximal use of all measured data to reliably estimate the distance to the transition state, x^‡, the associated free energy barrier, ΔG^‡, and the curvature, v, of the free energy surface. Obtaining robust estimates requires less experimental effort than with previous methods and fewer assumptions and thus leads to a significant reassessment of the kinetic parameters in this paradigmatic atomic-scale structure. Our proposed Bayesian reasoning offers a powerful and general approach when interpreting inherently stochastic data that yield broad, asymmetric distributions for which analytical models of the distribution may be developed.

PMID:38035375 | DOI:10.1021/acs.jpclett.3c02643

Front Nutr. 2023 Nov 16;10:1295241. doi: 10.3389/fnut.2023.1295241. eCollection 2023.

ABSTRACT

Promoting sustainability in food and nutrition systems is essential to address the various challenges and trade-offs within the current food system. This imperative is guided by key principles and actionable steps, including enhancing productivity and efficiency, reducing waste, adopting sustainable agricultural practices, improving economic growth and livelihoods, and enhancing resilience at various levels. However, in order to change the current food consumption patterns of the world and move toward sustainable diets, as well as increase productivity in the food production chain, it is necessary to employ the findings and achievements of other sciences. These include the use of artificial intelligence-based technologies. Presented here is a narrative review of possible applications of artificial intelligence in the food production chain that could increase productivity and sustainability. In this study, the most significant roles that artificial intelligence can play in enhancing the productivity and sustainability of the food and nutrition system have been examined in terms of production, processing, distribution, and food consumption. The research revealed that artificial intelligence, a branch of computer science that uses intelligent machines to perform tasks that require human intelligence, can significantly contribute to sustainable food security. Patterns of production, transportation, supply chain, marketing, and food-related applications can all benefit from artificial intelligence. As this review of successful experiences indicates, artificial intelligence, machine learning, and big data are a boon to the goal of sustainable food security as they enable us to achieve our goals more efficiently.

PMID:38035357 | PMC:PMC10687214 | DOI:10.3389/fnut.2023.1295241

Front Cell Infect Microbiol. 2023 Nov 16;13:1265777. doi: 10.3389/fcimb.2023.1265777. eCollection 2023.

ABSTRACT

INTRODUCTION: The colonization of the oral cavity by potentially pathogenic antimicrobial-resistant bacteria in adolescents and its consequences is very poorly understood. The present study focused on the occurrence of oral colonization by Gram-negative bacilli (GNB) and their multidrug resistance, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, among healthy adolescents and risk factors associated with GNB colonization.

MATERIALS AND METHODS: This study was conducted as part of “A program for the early detection of risk factors for lifestyle diseases SOPKARD-Junior” (SOPKARD-Junior). Oral samples were collected from 182 adolescents from four public elementary schools in Sopot, Poland, aged 13-14 years. Bacterial strains were identified by the MALDI-TOF MS method. Screening of antimicrobial resistance was performed using a disk diffusion method. The NG-Test^® CARBA-5 was used to detect and differentiate the five most widely distributed carbapenemases. Demographic and clinical data were collected and statistical analysis of risk factors was performed.

RESULTS: A total of 68 out of 182 (37.4%) healthy adolescents was documented oral colonization with Gram-negative bacilli, including 50/182 (27.5%) multidrug resistant (MDR-GNB) strains. Over 60% of oral carriage concerned three main genera Enterobacter spp., Pseudomonas spp., and Serratia spp., which were detected in 22.1%, 19.1%, and 19.1% of participants, respectively. Citrobacter spp., Escherichia coli, Klebsiella spp., Hafnia spp., Aeromonas spp., Acinetobacter spp., and Stenotrophomonas spp. were also isolated. The antimicrobial resistance to ampicillin (100%), ceftazidime (69.1%), meropenem (60.3%), gentamycin (60.3%), piperacillin/tazobactam (52.9%), and piperacillin (45.6%) were the most common. Among 73.5% GNB strains multidrug resistance was observed, including all Pseudomonas spp. strains. Among MDR-GNB, 30.4% were resistant to four groups of antibiotics, half of the MDR Pseudomonas spp. strains were resistant to 10 groups of antibiotics. Extended-spectrum β-lactamases were produced by Enterobacter cloacae, Klebsiella spp., and Serratia spp. (7.4%). Colonization by ESBLs-positive GNB strains was significantly associated with recurrent respiratory infections, nasal congestion, and bronchitis (p<0.05).

CONCLUSION: Our study revealed high oral carriage of multi-drug resistant Gram-negative bacilli in healthy adolescents and the association of ESBL-producing strains with respiratory infections. Further studies on oral colonization with GNB are necessary due to the possibility of distinct infections and the acquisition of antibiotic resistance by resident microbiota.

PMID:38035342 | PMC:PMC10687414 | DOI:10.3389/fcimb.2023.1265777

Innov Pharm. 2023 Oct 10;14(1). doi: 10.24926/iip.v14i1.5174. eCollection 2023.

ABSTRACT

Background: Evidence suggests that goal anti-Xa levels are achieved in only 33% of critically ill patients receiving standard prophylactic enoxaparin dosing. There has been limited focus on the potential suboptimal anticoagulation effect on medical intensive care unit (MICU) patients receiving therapeutic enoxaparin dosing for venous thromboembolism (VTE). Methods: MICU patients receiving enoxaparin 1 mg/kg twice daily or 1.5 mg/kg daily for VTE treatment in a 350-bed community teaching hospital between 2013 and 2019 with at least one peak anti-Xa level measured were included. The primary outcome was the proportion who achieved therapeutic anti-Xa levels with standard dosing. Secondary outcomes included types of dose-adjustments required and the proportion requiring subsequent dose-adjustments. Descriptive statistics were presented for all outcomes. Results: Fifty-three patients were evaluated, including those receiving either twice-daily or once-daily standard therapeutic dosing. Optimal anti-Xa levels at first measurement were recorded after the initiation of enoxaparin in 26.4% (n=14) patients. Dose adjustments were required in 70.7% (n=29) of patients receiving twice-daily dosing and in 83.3% (n=10) receiving once-daily dosing (P=0.97) to appropriately increase or decrease the enoxaparin dose. By the third anti-Xa level measurement, 3 patients remained outside of the therapeutic range. Conclusions: Standard therapeutic enoxaparin dosing did not result in optimal anti-Xa levels for a majority of MICU patients regardless of dosing regimen used or patient specific factors. Future studies should identify patient factors associated with the requirement for higher or lower enoxaparin dosing.

PMID:38035321 | PMC:PMC10686670 | DOI:10.24926/iip.v14i1.5174