Tag: nevin manimala

PLoS Comput Biol. 2022 Jun 3;18(6):e1010177. doi: 10.1371/journal.pcbi.1010177. Online ahead of print.

ABSTRACT

Engineered microbial cells present a sustainable alternative to fossil-based synthesis of chemicals and fuels. Cellular synthesis routes are readily assembled and introduced into microbial strains using state-of-the-art synthetic biology tools. However, the optimization of the strains required to reach industrially feasible production levels is far less efficient. It typically relies on trial-and-error leading into high uncertainty in total duration and cost. New techniques that can cope with the complexity and limited mechanistic knowledge of the cellular regulation are called for guiding the strain optimization. In this paper, we put forward a multi-agent reinforcement learning (MARL) approach that learns from experiments to tune the metabolic enzyme levels so that the production is improved. Our method is model-free and does not assume prior knowledge of the microbe’s metabolic network or its regulation. The multi-agent approach is well-suited to make use of parallel experiments such as multi-well plates commonly used for screening microbial strains. We demonstrate the method’s capabilities using the genome-scale kinetic model of Escherichia coli, k-ecoli457, as a surrogate for an in vivo cell behaviour in cultivation experiments. We investigate the method’s performance relevant for practical applicability in strain engineering i.e. the speed of convergence towards the optimum response, noise tolerance, and the statistical stability of the solutions found. We further evaluate the proposed MARL approach in improving L-tryptophan production by yeast Saccharomyces cerevisiae, using publicly available experimental data on the performance of a combinatorial strain library. Overall, our results show that multi-agent reinforcement learning is a promising approach for guiding the strain optimization beyond mechanistic knowledge, with the goal of faster and more reliably obtaining industrially attractive production levels.

PMID:35658018 | DOI:10.1371/journal.pcbi.1010177

PLoS One. 2022 Jun 3;17(6):e0269556. doi: 10.1371/journal.pone.0269556. eCollection 2022.

ABSTRACT

Due to greater environmental awareness, domestic laundry habits are changing, and antimicrobial control by chemical methods has become an essential factor to compensate for the use of lower temperatures during washing machine cycles. Disinfectants added to laundry detergents are a preventive strategy to reduce the transmission of bacteria, fungi, and viruses in the home, correct aesthetic damage (e.g., spotting, discolouration, and staining), and control the microbial contamination that leads to malodour. In Europe, disinfectants are regulated by the EU Biocidal Products Regulation (No. 528/2012), which stipulates that antimicrobial efficacy must be evaluated according to standardized methods. Current European standards for laundry sanitization only apply to clinical settings (EN 16616: 2015) and are restricted to the main wash cycle. Therefore, there is a gap in the EU standards regarding the testing of product efficacy in household laundering. With the aim of addressing this gap, an international ring trial was organized to evaluate the robustness of a new method (prEN 17658) designed to test the efficacy of antimicrobial laundry products in a domestic setting. The seven participating laboratories were equipped with 5 different laboratory-scale devices to simulate the washing process, and they evaluated 7 microbial parameters for 2 experimental conditions and 3 levels of active substance. The analysis of data according to ISO 5725-2 and ISO 13528 demonstrated that the method was robust. All reproducibility standard deviation values were between 0.00 and 1.40 and the relative standard deviation indicates satisfactory reproducibility. Values of logarithmic reduction ranged from less than 2 log10 for tests with water to more than 5 log10 when disinfectants were added. The evidence generated by the ring trial was presented in a proposal for a standardized method under CEN/TC 216, in which the SOP used in the ring trial is referred to as the prEN 17658 phase 2 step 2 test method covering chemothermal textile disinfection in domestic settings.

PMID:35658049 | DOI:10.1371/journal.pone.0269556

PLoS Biol. 2022 Jun 3;20(6):e3001626. doi: 10.1371/journal.pbio.3001626. eCollection 2022 Jun.

ABSTRACT

The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.

PMID:35658016 | DOI:10.1371/journal.pbio.3001626

J Clin Oncol. 2022 Jun 3:JCO2200912. doi: 10.1200/JCO.22.00912. Online ahead of print.

ABSTRACT

PURPOSE: Resistance to immune checkpoint inhibition (ICI) in advanced non-small-cell lung cancer (NSCLC) represents a major unmet need. Combining ICI with vascular endothelial growth factor (VEGF)/VEGF receptor inhibition has yielded promising results in multiple tumor types.

METHODS: In this randomized phase II Lung-MAP nonmatch substudy (S1800A), patients ineligible for a biomarker-matched substudy with NSCLC previously treated with ICI and platinum-based chemotherapy and progressive disease at least 84 days after initiation of ICI were randomly assigned to receive ramucirumab plus pembrolizumab (RP) or investigator’s choice standard of care (SOC: docetaxel/ramucirumab, docetaxel, gemcitabine, and pemetrexed). With a goal of 130 eligible patients, the primary objective was to compare overall survival (OS) using a one-sided 10% level using the better of a standard log-rank (SLR) and weighted log-rank (WLR; G[rho = 0, gamma = 1]) test. Secondary end points included objective response, duration of response, investigator-assessed progression-free survival, and toxicity.

RESULTS: Of 166 patients enrolled, 136 were eligible (69 RP; 67 SOC). OS was significantly improved with RP (hazard ratio [80% CI]: 0.69 [0.51 to 0.92]; SLR one-sided P = .05; WLR one-sided P = .15). The median (80% CI) OS was 14.5 (13.9 to 16.1) months for RP and 11.6 (9.9 to 13.0) months for SOC. OS benefit for RP was seen in most subgroups. Investigator-assessed progression-free survival (hazard ratio [80% CI]: 0.86 [0.66 to 1.14]; one-sided SLR, P = .25 and .14 for WLR) and response rates (22% RP v 28% SOC, one-sided P = .19) were similar between arms. Grade ≥ 3 treatment-related adverse events occurred in 42% of patients in the RP group and 60% on SOC.

CONCLUSION: This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously treated with ICI and chemotherapy. The safety was consistent with known toxicities of both drugs. These data warrant further evaluation.

PMID:35658002 | DOI:10.1200/JCO.22.00912

PLoS One. 2022 Jun 3;17(6):e0269393. doi: 10.1371/journal.pone.0269393. eCollection 2022.

ABSTRACT

To investigate impression formation, researchers tend to rely on statements that describe a person’s behavior (e.g., “Alex ridicules people behind their backs”). These statements are presented to participants who then rate their impressions of the person. However, a corpus of behavior statements is costly to generate, and pre-existing corpora may be outdated and might not measure the dimension(s) of interest. The present study makes available a normed corpus of 160 contemporary behavior statements that were rated on 4 dimensions relevant to impression formation: morality, competence, informativeness, and believability. In addition, we show that the different dimensions are non-independent, exhibiting a range of linear and non-linear relationships, which may present a problem for past research. However, researchers interested in impression formation can control for these relationships (e.g., statistically) using the present corpus of behavior statements.

PMID:35657992 | DOI:10.1371/journal.pone.0269393

PLoS One. 2022 Jun 3;17(6):e0269450. doi: 10.1371/journal.pone.0269450. eCollection 2022.

ABSTRACT

This study suggested a new four-parameter Exponentiated Odd Lomax Exponential (EOLE) distribution by compounding an exponentiated odd function with Lomax distribution as a generator. The proposed model is unimodal and positively skewed whereas the hazard rate function is monotonically increasing and inverted bathtubs. Some important properties of the new distribution are derived such as quintile function and median; asymptotic properties and mode; moments; mean residual life, mean path time; mean deviation; order statistics; and Bonferroni & Lorenz curve. The value of the parameters is obtained from the maximum likelihood estimation, least-square estimation, and Cramér-Von-Mises methods. Here, a simulation study and two real data sets, “the number of deaths per day due to COVID-19 of the first wave in Nepal” and ”failure stresses (In Gpa) of single carbon fibers of lengths 50 mm”, have been applied to validate the different theoretical findings. The finding of an order of COVID-19 deaths in 153 days in Nepal obey the proposed distribution, it has a significantly positive relationship between the predictive test positive rate and the predictive number of deaths per day. Therefore, the intended model is an alternative model for survival data and lifetime data analysis.

PMID:35657989 | DOI:10.1371/journal.pone.0269450

PLoS One. 2022 Jun 3;17(6):e0269473. doi: 10.1371/journal.pone.0269473. eCollection 2022.

ABSTRACT

OBJECTIVE OF THE STUDY: The objective of this study was to identify determinants of syphilis infection among pregnant women attending antenatal care in hospitals in the Wolaita zone, Southern Ethiopia,2020.

METHODS: An unmatched facility-based case-control study was conducted among pregnant women who received antenatal care at four randomly selected hospitals from September 1 to October 30, 2020. A two-stage sampling technique was used in the selection of hospitals and study participants. The data were collected from the participants using a pre-tested structured questionnaire and analyzed using STATA Release 15. Bivariate and multivariate logistic regression analyses were used to determine syphilis infection determinants. Crude and adjusted odds ratios were used for each explanatory variable with a 95% confidence level. A statistically significant association was declared when a p-value was less than 0.05.

RESULTS: A total of 296 (74 cases and 222 controls) pregnant women participated, with a recruitment rate of 97.4%. In multivariate logistic regression, the likelihood of developing a maternal syphilis infection was higher in pregnant women who had more than one-lifetime sexual partner [AOR = 3.59, 95% CI (1.09-11.71)]; a history of sexually transmitted infections [AOR = 3.46, 95%CI (1.32-9.08)] and used a substance [AOR = 3.39, 95%CI (1.31-8.77)].

CONCLUSION: Sexual-related factors continued to be a major determinant of syphilis in pregnant women. The results suggest that there is a need to promote safe sexual behavior, raise awareness about the risk of STIs, and early diagnosis and treatment of STIs to control syphilis infection, and necessary to make the antenatal care service comprehensive for pregnant women.

PMID:35657978 | DOI:10.1371/journal.pone.0269473

Lab Med. 2022 Jun 3:lmac053. doi: 10.1093/labmed/lmac053. Online ahead of print.

ABSTRACT

OBJECTIVE: Several biomarkers have been reported to exhibit a seasonal variation, which might also be associated with the seasonality observed for certain disorders, such as cardiovascular disease. Ferritin is a marker of iron stores but may be influenced by other factors including inflammation. The aim of this study was to determine whether there is a seasonal variation for plasma ferritin.

METHODS: The study included all ferritin tests performed on blood donors between November 2009 and November 2016 in the county of Uppsala, Sweden.

RESULTS: Median ferritin values were found to be highest in August to October (autumn) and lowest in April to May and December. The differences between the highest and lowest median values were 6 µg/L for males and 5 µg/L for females. This corresponds to approximately 12% difference for males and 15% difference for females.

CONCLUSION: A modest but statistically significant seasonal periodicity for ferritin was shown for blood donors.

PMID:35657988 | DOI:10.1093/labmed/lmac053

PLoS One. 2022 Jun 3;17(6):e0268690. doi: 10.1371/journal.pone.0268690. eCollection 2022.

ABSTRACT

BACKGROUND: Closure of a patent foramen ovale reduces the risk of recurrent stroke compared with medical therapy alone in young patients with cryptogenic strokes revealed by randomized control trials. Some cost-effectiveness analyses outside Japan have shown that patent foramen ovale closure is cost-effective, but no studies have examined cost-effectiveness in Japan. The objective of this study is to assess cost-effectiveness, from the perspective of a Japanese healthcare payer, of patent foramen ovale closure versus medical therapy alone for patients with patent foramen ovale related to cryptogenic strokes.

METHODS: A cost-effectiveness study was conducted by developing a decision tree and a Markov model. Probabilities and a 5.9-year time horizon followed the RESPECT study. Utilities and costs were based upon published studies and assumptions. All assumptions were assessed by experts, including a cardiologist and a statistical expert. The target population comprised patients with cryptogenic stroke and patent foramen ovale, aged 60 years or younger. The model was discounted at 2.0% and its cycle was one month. A willingness-to-pay threshold is set at $50,000 / quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio was evaluated. Then one-way sensitivity analyses as deterministic sensitivity analysis, and probabilistic sensitivity analyses were performed to assess data robustness.

RESULTS: Incremental quality-adjusted life years, incremental costs, and incremental cost-effectiveness ratio were 0.464, $13,562, and $29,208 per QALY gained, respectively. One-way sensitivity analysis showed that the stable state utility score difference between patent foramen ovale closure and medical therapy had the largest impact on incremental cost-effectiveness ratio. Patent foramen ovale closure is cost-effective at a stable state utility score difference of >0.051, compared with medical therapy. Probabilistic sensitivity analyses demonstrated that patent foramen ovale closure was 50.3% cost-effective.

CONCLUSIONS: Patent foramen ovale closure was cost-effective compared with medical therapy for Japanese patients with cryptogenic stroke who were ≤60 years.

PMID:35657973 | DOI:10.1371/journal.pone.0268690

PLoS One. 2022 Jun 3;17(6):e0269546. doi: 10.1371/journal.pone.0269546. eCollection 2022.

ABSTRACT

BACKGROUND: Service availability and readiness are critical for the delivery of quality and essential health care services. In Ghana, there is paucity of literature that describes general service readiness (GSR) of primary health care (PHC) facilities within the national context. This study therefore assessed the GSR of PHC facilities in Ghana to provide evidence to inform heath policy and drive action towards reducing health inequities.

METHODS: We analysed data from 140 Service Delivery Points (SDPs) that were part of the Performance Monitoring and Accountability 2020 survey (PMA2020). GSR was computed using the Service Availability and Readiness Assessment (SARA) manual based on four out of five components. Descriptive statistics were computed for both continuous and categorical variables. A multivariable binary logistic regression model was fitted to assess predictors of scoring above the mean GSR. Analyses were performed using Stata version 16.0. Significance level was set at p<0.05.

RESULTS: The average GSR index of SDPs in this study was 83.4%. Specifically, the mean GSR of hospitals was 92.8%, whereas health centres/clinics and CHPS compounds scored 78.0% and 64.3% respectively. The least average scores were observed in the essential medicines and standard precautions for infection prevention categories. We found significant sub-national, urban-rural and facility-related disparities in GSR. Compared to the Greater Accra Region, SDPs in the Eastern, Western, Upper East and Upper West Regions had significantly reduced odds of scoring above the overall GSR. Majority of SDPs with GSR below the average were from rural areas.

CONCLUSION: Overall, GSR among SDPs is appreciable as compared to other settings. The study highlights the existence of regional, urban-rural and facility-related differences in GSR of SDPs. The reality of health inequities has crucial policy implications which need to be addressed urgently to fast-track progress towards the achievement of the SDGs and UHC targets by 2030.

PMID:35657970 | DOI:10.1371/journal.pone.0269546