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Nevin Manimala Statistics

The combination of the NS5A and cyclophilin inhibitors results in an additive anti-HCV inhibition in humanized mice without development of resistance

PLoS One. 2021 May 20;16(5):e0251934. doi: 10.1371/journal.pone.0251934. eCollection 2021.

ABSTRACT

We and others previously reported that the direct-acting agents (DAA) NS5A inhibitors (NS5Ai) and the host-targeting agents cyclophilin inhibitors (CypIs) inhibit HCV replication in vitro. In this study, we investigated whether the combination of NS5Ai and CypI offers a potent anti-HCV effect in vivo. A single administration of NS5Ai or CypI alone to HCV-infected humanized-mice inhibits HCV replication. The combination of NS5Ai with CypI suppresses HCV (GT1a, GT2a, GT3a and GT4a) replication in an additive manner. NS5Ai/CypI combinations provide a statistically more profound anti-HCV inhibition for GT2a and GT3a than GT1a and GT4a, leading to a fastest and deepest inhibition of GT2a and GT3a replications. Combining CypI with NS5Ai prevents the viral rebound normally observed in mice treated with NS5Ai alone. Results were confirmed in mice implanted with human hepatocytes from different donors. Therefore, the combination of NS5Ai with CypI may serve as a regimen for the treatment of HCV patients with specific genotypes and disorder conditions, which diminish sustain viral response levels to DAA, such as GT3a infection, cirrhosis, and DAA resistance associated with the selection of resistance-associated substitutions present at baseline or are acquired during treatment.

PMID:34014993 | DOI:10.1371/journal.pone.0251934

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Nevin Manimala Statistics

Impact of Enhanced Recovery After Surgery (ERAS) protocol versus standard of care on postoperative Acute Kidney Injury (AKI): A meta-analysis

PLoS One. 2021 May 20;16(5):e0251476. doi: 10.1371/journal.pone.0251476. eCollection 2021.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication with an incidence of nearly 15%. Relatively balanced fluid management, flexible use of vasoactive drugs, multimodal analgesia containing non-steroidal anti-inflammatory drugs are fundamental to ERAS protocols. However, these basic tenants may lead to an increased incidence of postoperative AKI.

METHODS: A search was done in the PubMed, Embase, Cochrane Library and reference lists to identify relevant studies from inception until May 2020 to be included in this study. Effects were summarized using pooled risk ratios (RRs), mean differences (MDs) and corresponding 95% confidence intervals (Cls) with random effect model. Heterogeneity assessment, sensitivity analysis, and publication bias were performed.

RESULTS: A systematic review of nineteen cohort studies covering 17,205 patients, comparing impact of ERAS with conventional care on postoperative AKI was performed. Notably, the ERAS regimen did not increase the incidence of postoperative AKI compared with standard care (RR: 1.21; 95% CI: 0.96 to 1.52; I2 = 53%). Both goal-directed fluid therapy (RR: 1.26; 95% CI: 0.99-1.61; I2 = 55%) and restrictive fluid management (RR: 1.06; 95% CI: 0.57-1.98; I2 = 60%) had no significant effect on the incidence of postoperative AKI. There was no significant statistical difference between different AKI diagnostic criteria (P = 0.43; I2 = 0%). ERAS group had significantly shorter hospital stay (MD: -1.54; 95% CI: -1.91 to -1.17; I2 = 66%). There was no statistical difference in 30-day readmission rate (RR: 0.98; 95% CI: 0.80 to 1.20; I2 = 42%), 30-day reoperation rate (RR: 0.98; 95% CI: 0.71 to 1.34; I2 = 42%) and mortality (RR: 0.81; 95% CI: 0.59 to 1.11; I2 = 0%) between the two groups.

CONCLUSIONS: This meta-analysis suggests that ERAS protocols do not increase readmission or reoperation rates and mortality while significantly reducing LOS. Most importantly, the ERAS protocol was shown to have no promoting effect on the incidence of postoperative AKI. Even GDFT and restrictive fluid management cannot avoid the occurrence of postoperative AKI, and the ERAS protocol is still worth recommending and its safety is further confirmed.

PMID:34015002 | DOI:10.1371/journal.pone.0251476

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Nevin Manimala Statistics

Temperament, character and decision-making characteristics of patients with major depressive disorder following a suicide attempt

PLoS One. 2021 May 20;16(5):e0251935. doi: 10.1371/journal.pone.0251935. eCollection 2021.

ABSTRACT

BACKGROUND: Multiple psychological factors of suicidal behaviour have been identified so far; however, little is known about state-dependent alterations and the interplay of the most prominent components in a suicidal crisis. Thus, the combined effect of particular personality characteristics and decision-making performance was observed within individuals who recently attempted suicide during a major depressive episode.

METHODS: Fifty-nine medication-free major depressed patients with a recent suicide attempt (within 72 h) and forty-five healthy control individuals were enrolled in this cross-sectional study. Temperament and character factors, impulsivity and decision-making performance were assessed. Statistical analyses aimed to explore between-group differences and the most powerful contributors to suicidal behaviour during a depressive episode.

RESULTS: Decision-making and personality differences (i.e. impulsivity, harm avoidance, self-directedness, cooperativeness and transcendence) were observed between the patient and the control group. Among these variables, decision-making, harm avoidance and self-directedness were shown to have the strongest impact on a recent suicide attempt of individuals with a diagnosis of major depressive disorder according to the results of the binary logistic regression analysis. The model was significant, adequately fitted the data and correctly classified 79.8% of the cases.

CONCLUSIONS: The relevance of deficient decision-making, high harm avoidance and low self-directedness was modelled in the case of major depressed participants with a recent suicide attempt; meaning that these individuals can be described with the myopia for future consequences, a pessimistic, anxious temperament; and a character component resulting in the experience of aimlessness and helplessness. Further studies that use a within-subject design should identify and confirm additional characteristics specific to the suicidal mind.

PMID:34015015 | DOI:10.1371/journal.pone.0251935

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Nevin Manimala Statistics

Pre-intervention characteristics of the mosquito species in Benin in preparation for a randomized controlled trial assessing the efficacy of dual active-ingredient long-lasting insecticidal nets for controlling insecticide-resistant malaria vectors

PLoS One. 2021 May 20;16(5):e0251742. doi: 10.1371/journal.pone.0251742. eCollection 2021.

ABSTRACT

BACKGROUND: This study provides detailed characteristics of vector populations in preparation for a three-arm cluster randomized controlled trial (RCT) aiming to compare the community impact of dual active-ingredient (AI) long-lasting insecticidal nets (LLINs) that combine two novel insecticide classes-chlorfenapyr or pyriproxifen-with alpha-cypermethrin to improve the prevention of malaria transmitted by insecticide-resistant vectors compared to standard pyrethroid LLINs.

METHODS: The study was carried out in 60 villages across Cove, Zangnanando and Ouinhi districts, southern Benin. Mosquito collections were performed using human landing catches (HLCs). After morphological identification, a sub-sample of Anopheles gambiae s.l. were dissected for parity, analyzed by PCR for species and presence of L1014F kdr mutation and by ELISA-CSP to identify Plasmodium falciparum sporozoite infection. WHO susceptibility tube tests were performed by exposing adult An. gambiae s.l., collected as larvae from each district, to 0.05% alphacypermethrin, 0.75% permethrin, 0.1% bendiocarb and 0.25% pirimiphos-methyl. Synergist assays were also conducted with exposure first to 4% PBO followed by alpha-cypermethrin.

RESULTS: An. gambiae s.l. (n = 10807) was the main malaria vector complex found followed by Anopheles funestus s.l. (n = 397) and Anopheles nili (n = 82). An. gambiae s.l. was comprised of An. coluzzii (53.9%) and An. gambiae s.s. (46.1%), both displaying a frequency of the L1014F kdr mutation >80%. Although more than 80% of people slept under standard LLIN, human biting rate (HBR) in An. gambiae s.l. was higher indoors [26.5 bite/person/night (95% CI: 25.2-27.9)] than outdoors [18.5 b/p/n (95% CI: 17.4-19.6)], as were the trends for sporozoite rate (SR) [2.9% (95% CI: 1.7-4.8) vs 1.8% (95% CI: 0.6-3.8)] and entomological inoculation rate (EIR) [21.6 infected bites/person/month (95% CI: 20.4-22.8) vs 5.4 (95% CI: 4.8-6.0)]. Parous rate was 81.6% (95%CI: 75.4-88.4). An. gambiae s.l. was resistant to alpha-cypermethrin and permethrin but, fully susceptible to bendiocarb and pirimiphos-methyl. PBO pre-exposure followed by alpha-cypermethrin treatment induced a higher 24 hours mortality compared to alphacypermethrin alone but not exceeding 40%.

CONCLUSIONS: Despite a high usage of standard pyrethroid LLINs, the study area is characterized by intense malaria transmission. The main vectors An. coluzzii and An. gambiae s.s. were both highly resistant to pyrethroids and displayed multiple resistance mechanisms, L1014F kdr mutation and mixed function oxidases. These conditions of the study area make it an appropriate site to conduct the trial that aims to assess the effect of novel dual-AI LLINs on malaria transmitted by insecticide-resistant vectors.

PMID:34014982 | DOI:10.1371/journal.pone.0251742

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Nevin Manimala Statistics

Analysis of climate factors and dengue incidence in the metropolitan region of Rio de Janeiro, Brazil

PLoS One. 2021 May 20;16(5):e0251403. doi: 10.1371/journal.pone.0251403. eCollection 2021.

ABSTRACT

Dengue is a re-emerging disease, currently considered the most important mosquito-borne arbovirus infection affecting humankind, taking into account both its morbidity and mortality. Brazil is considered an endemic country for dengue, such that more than 1,544,987 confirmed cases were notified in 2019, which means an incidence rate of 735 for every 100 thousand inhabitants. Climate is an important factor in the temporal and spatial distribution of vector-borne diseases, such as dengue. Thus, rainfall and temperature are considered macro-factors determinants for dengue, since they directly influence the population density of Aedes aegypti, which is subject to seasonal fluctuations, mainly due to these variables. This study examined the incidence of dengue fever related to the climate influence by using temperature and rainfall variables data obtained from remote sensing via artificial satellites in the metropolitan region of Rio de Janeiro, Brazil. The mathematical model that best fits the data is based on an auto-regressive moving average with exogenous inputs (ARMAX). It reproduced the values of incidence rates in the study period and managed to predict with good precision in a one-year horizon. The approach described in present work may be replicated in cities around the world by the public health managers, to build auxiliary operational tools for control and prevention tasks of dengue, as well of other arbovirus diseases.

PMID:34014989 | DOI:10.1371/journal.pone.0251403

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Nevin Manimala Statistics

Attitude towards diabetes mellitus among adult communities in Gondar city, Ethiopia

PLoS One. 2021 May 20;16(5):e0251777. doi: 10.1371/journal.pone.0251777. eCollection 2021.

ABSTRACT

BACKGROUND: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Diabetes and its complications can be reduced by enhancing the attitude of the community. However, there is limited information regarding attitude towards diabetes in northwest Ethiopia. Therefore, this study determined the attitude and associated factors of diabetes mellitus among adult non-diabetic participants in Gondar city.

METHODS: A community-based cross-sectional study was conducted in Gondar city. Systematic random sampling was employed to select 626 non-diabetic participants. The data were collected using a pre-tested structured questionnaire. Descriptive statistics, processing, and analysis were done using STATA version 14. Both bivariable and multivariable binary logistic regressions were used to identify the associated factors. An adjusted odds ratio with a 95% confidence interval was used to calculate a level of significance.

RESULTS: Of 626 participants, 572 (91.37%) study subjects heard about diabetes mellitus. Three hundred and fifteen participants (55.07%) (95% CI: 50.9% – 59.1%) had a favorable attitude towards diabetes mellitus. Having good knowledge about diabetes (adjusted odds ratio = 2.69, 95% CI: 1.88, 3.87), and higher educational status (adjusted odds ratio = 1.69, 95% CI: 1.04, 2.78) were positively associated with a favorable attitude towards diabetes mellitus. Female gender (adjusted odds ratio = 0.68, 95% CI: 0.47, 0.98), on the other hand, had poor attitude towards diabetes mellitus.

CONCLUSION: In this study, a favorable attitude towards diabetes was low among adult non-diabetic participants. Good knowledge, higher educational status, and being male were the factors associated with a favorable attitude towards diabetes.

PMID:34014991 | DOI:10.1371/journal.pone.0251777

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Nevin Manimala Statistics

Community-level women’s education and undernutrition among Indian adolescents: A multilevel analysis of a national survey

PLoS One. 2021 May 20;16(5):e0251427. doi: 10.1371/journal.pone.0251427. eCollection 2021.

ABSTRACT

BACKGROUND: Little research has explored the influence of social context on health of Indian adolescents. We conceptualized community-level women’s education (proxy for value placed on women’s wellbeing) as exerting contextual influence on adolescent hemoglobin level and body mass index (BMI).

METHODS: We derived our sample of more than 62,000 adolescent aged 15 through 17 years from the Indian National Family Health Survey 2015-16. The sample consisted of a total of 62648 adolescents (54232 girls and 8416 boys) for the hemoglobin, and 62846 adolescents (54383 girls and 8463 boys) for the BMI analysis. We fitted multilevel random intercepts linear regression models to test the association of village- and urban-ward-level-women’s education with hemoglobin level and BMI of adolescents, accounting for their own and their mother’s education; as well as relevant covariates.

FINDINGS: Our fully adjusted model estimated that if the 52% of communities with less than 20 percent of women having a tenth-grade education in our sample were to achieve 100 percent tenth-grade completion in women, hemoglobin would be 0·2 g/dl higher (p<0·001) and BMI would be 0·62 kg/m2 higher on average among all adolescents in such communities. Unexplained variance estimates at the contextual level remained statistically significant, indicating the importance of context on adolescent undernutrition.

INTERPRETATIONS: Adolescents are deeply embedded in their context, influenced by contextual factors affecting health. Promoting adolescent health therefore implies altering social norms related to adolescent health and health behaviors; along with structural changes creating a health-promoting environment. Integrating our empirical findings with theoretically plausible pathways connecting community-level women’s education with adolescent undernutrition, we suggest that enhancing community-level women’s education beyond high school is necessary to facilitate these processes.

IMPLICATIONS: Addressing contextual determinants of adolescent undernutrition might be the missing link in India’s adolescent anemia and undernutrition prevention efforts, which are currently focused heavily on individual-level biomedical determinants of the problem.

PMID:34014954 | DOI:10.1371/journal.pone.0251427

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Nevin Manimala Statistics

Analysis of the spatial association of geographical detector-based landslides and environmental factors in the southeastern Tibetan Plateau, China

PLoS One. 2021 May 20;16(5):e0251776. doi: 10.1371/journal.pone.0251776. eCollection 2021.

ABSTRACT

Steep canyons surrounded by high mountains resulting from large-scale landslides characterize the study area located in the southeastern part of the Tibetan Plateau. A total of 1766 large landslides were identified based on integrated remote sensing interpretations utilizing multisource satellite images and topographic data that were dominated by 3 major regional categories, namely, rockslides, rock falls, and flow-like landslides. The geographical detector method was applied to quantitatively unveil the spatial association between the landslides and 12 environmental factors through computation of the q values based on spatially stratified heterogeneity. Meanwhile, a certainty factor (CF) model was used for comparison. The results indicate that the q values of the 12 influencing factors vary obviously, and the dominant factors are also different for the 3 types of landslides, with annual mean precipitation (AMP) being the dominant factor for rockslide distribution, elevation being the dominant factor for rock fall distribution and lithology being the dominant factor for flow-like distribution. Integrating the results of the factor detector and ecological detector, the AMP, annual mean temperature (AMT), elevation, river density, fault distance and lithology have a stronger influence on the spatial distribution of landslides than other factors. Furthermore, the factor interactions can significantly enhance their interpretability of landslides, and the top 3 dominant interactions were revealed. Based on statistics of landslide discrepancies with respect to diverse stratification of each factor, the high-risk zones were identified for 3 types of landslides, and the results were contrasted with the CF model. In conclusion, our method provides an objective framework for landslide prevention and mitigation through quantitative, spatial and statistical analyses in regions with complex terrain.

PMID:34014965 | DOI:10.1371/journal.pone.0251776

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Nevin Manimala Statistics

Structural coordinates: A novel approach to predict protein backbone conformation

PLoS One. 2021 May 20;16(5):e0239793. doi: 10.1371/journal.pone.0239793. eCollection 2021.

ABSTRACT

MOTIVATION: Local protein structure is usually described via classifying each peptide to a unique class from a set of pre-defined structures. These classifications may differ in the number of structural classes, the length of peptides, or class attribution criteria. Most methods that predict the local structure of a protein from its sequence first rely on some classification and only then proceed to the 3D conformation assessment. However, most classification methods rely on homologous proteins’ existence, unavoidably lose information by attributing a peptide to a single class or suffer from a suboptimal choice of the representative classes.

RESULTS: To alleviate the above challenges, we propose a method that constructs a peptide’s structural representation from the sequence, reflecting its similarity to several basic representative structures. For 5-mer peptides and 16 representative structures, we achieved the Q16 classification accuracy of 67.9%, which is higher than what is currently reported in the literature. Our prediction method does not utilize information about protein homologues but relies only on the amino acids’ physicochemical properties and the resolved structures’ statistics. We also show that the 3D coordinates of a peptide can be uniquely recovered from its structural coordinates, and show the required conditions under various geometric constraints.

PMID:34014953 | DOI:10.1371/journal.pone.0239793

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Nevin Manimala Statistics

Small in size, big on taste: Metabolomics analysis of flavor compounds from Philippine garlic

PLoS One. 2021 May 20;16(5):e0247289. doi: 10.1371/journal.pone.0247289. eCollection 2021.

ABSTRACT

Philippine garlic (Allium sativum L.) is arguably known to pack flavor and aroma in smaller bulbs compared to imported varieties saturating the local market. In this study, ethanolic extracts of Philippine garlic cultivars were profiled using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF). γ-Glu dipeptides, oligosaccharides and lipids were determined in Philippine garlic cultivars through bioinformatics analysis in GNPS Molecular Networking Platform and fragmentation analysis. Multivariate statistical analysis using XCMS Online showed the abundance of γ-Glu allyl cysteine in Batanes-sourced garlic while γ-Glu propenyl cysteine, γ-Glu methyl cysteine, and alliin are enriched in the Ilocos cultivar. Principal component analysis showed that the γ-Glu dipeptides found in local garlic influenced their distinct separation across PC1 from imported varieties. This presence of high levels of γ-Glu dipeptides and probiotic oligosaccharides may potentially contribute to the superior flavor and nutritional benefits of Philippine garlic.

PMID:34014935 | DOI:10.1371/journal.pone.0247289