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Nevin Manimala Statistics

Population genomic evidence of Plasmodium vivax Southeast Asian origin

Sci Adv. 2021 Apr 28;7(18):eabc3713. doi: 10.1126/sciadv.abc3713. Print 2021 Apr.

ABSTRACT

Plasmodium vivax is the most common and widespread human malaria parasite. It was recently proposed that P. vivax originates from sub-Saharan Africa based on the circulation of its closest genetic relatives (P. vivax-like) among African great apes. However, the limited number of genetic markers and samples investigated questions the robustness of this hypothesis. Here, we extensively characterized the genomic variations of 447 human P. vivax strains and 19 ape P. vivax-like strains collected worldwide. Phylogenetic relationships between human and ape Plasmodium strains revealed that P. vivax is a sister clade of P. vivax-like, not included within the radiation of P. vivax-like By investigating various aspects of P. vivax genetic variation, we identified several notable geographical patterns in summary statistics in function of the increasing geographic distance from Southeast Asia, suggesting that P. vivax may have derived from a single area in Asia through serial founder effects.

PMID:33910900 | DOI:10.1126/sciadv.abc3713

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Online and telephone access to general practice: a cross sectional patient survey

BJGP Open. 2021 Apr 28:BJGPO.2020.0179. doi: 10.3399/BJGPO.2020.0179. Online ahead of print.

ABSTRACT

BACKGROUND: Improving access to primary healthcare in the United Kingdom has focused on the use of telephone and online access but little is known about how awareness of and use varies between different patient groups.

AIM: To determine how patients are interacting with telephone and online channels for accessing general practice services and information, and to analyse how this varies according to patient characteristics and health status.

DESIGN & SETTING: A cross sectional self-administered survey of adult patients in general practices across the West Midlands, UK.

METHOD: Descriptive statistics were used to show participants’ awareness of and interaction with online information sources and remote access. Multivariable logistic regression was used to model the relationships between demographic and health characteristics and awareness and use of online services and alternatives to face to face consultations (e.g. telephone).

RESULTS: 2789 patients (response rate 19.0%) from 43 general practices participated. 60.8% (1651/2715) of participants were aware of online services and 30.3% (811/2674) reported having used one. Daily internet usage and frequently visiting the GP showed the strongest associations with knowledge and use of online services.

CONCLUSION: We have shown that there is the potential for inequitable awareness and use of telephone and online services in general practice populations. Given that their use has greatly increased due to the COVID-19 pandemic future service design will need to ensure this is taken into account.

PMID:33910917 | DOI:10.3399/BJGPO.2020.0179

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Delayed antibiotic prescribing for respiratory tract infections: individual patient data meta-analysis

BMJ. 2021 Apr 28;373:n808. doi: 10.1136/bmj.n808.

ABSTRACT

OBJECTIVE: To assess the overall effect of delayed antibiotic prescribing on average symptom severity for patients with respiratory tract infections in the community, and to identify any factors modifying this effect.

DESIGN: Systematic review and individual patient data meta-analysis.

DATA SOURCES: Cochrane Central Register of Controlled Trials, Ovid Medline, Ovid Embase, EBSCO CINAHL Plus, and Web of Science.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials and observational cohort studies in a community setting that allowed comparison between delayed versus no antibiotic prescribing, and delayed versus immediate antibiotic prescribing.

MAIN OUTCOME MEASURES: The primary outcome was the average symptom severity two to four days after the initial consultation measured on a seven item scale (ranging from normal to as bad as could be). Secondary outcomes were duration of illness after the initial consultation, complications resulting in admission to hospital or death, reconsultation with the same or worsening illness, and patient satisfaction rated on a Likert scale.

RESULTS: Data were obtained from nine randomised controlled trials and four observational studies, totalling 55 682 patients. No difference was found in follow-up symptom severity (seven point scale) for delayed versus immediate antibiotics (adjusted mean difference -0.003, 95% confidence interval -0.12 to 0.11) or delayed versus no antibiotics (0.02, -0.11 to 0.15). Symptom duration was slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was similar for delayed versus no antibiotics. Complications resulting in hospital admission or death were lower with delayed versus no antibiotics (odds ratio 0.62, 95% confidence interval 0.30 to 1.27) and delayed versus immediate antibiotics (0.78, 0.53 to 1.13). A significant reduction in reconsultation rates (odds ratio 0.72, 95% confidence interval 0.60 to 0.87) and an increase in patient satisfaction (adjusted mean difference 0.09, 0.06 to 0.11) were observed in delayed versus no antibiotics. The effect of delayed versus immediate antibiotics and delayed versus no antibiotics was not modified by previous duration of illness, fever, comorbidity, or severity of symptoms. Children younger than 5 years had a slightly higher follow-up symptom severity with delayed antibiotics than with immediate antibiotics (adjusted mean difference 0.10, 95% confidence interval 0.03 to 0.18), but no increased severity was found in the older age group.

CONCLUSIONS: Delayed antibiotic prescribing is a safe and effective strategy for most patients, including those in higher risk subgroups. Delayed prescribing was associated with similar symptom duration as no antibiotic prescribing and is unlikely to lead to poorer symptom control than immediate antibiotic prescribing. Delayed prescribing could reduce reconsultation rates and is unlikely to be associated with an increase in symptoms or illness duration, except in young children.

STUDY REGISTRATION: PROSPERO CRD42018079400.

PMID:33910882 | DOI:10.1136/bmj.n808

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Validation of the Effectiveness of Neutrophil-to-lymphocyte Ratio (NLR) as a Predictive Factor in Patients Undergoing Prostate Biopsy With Prostate Specific Antigen (PSA) Between 4.0 and 10.0 ng/ml

In Vivo. 2021 May-Jun;35(3):1641-1646. doi: 10.21873/invivo.12422.

ABSTRACT

BACKGROUND/AIM: This study aimed to access the effectiveness of serum neutrophil-to-lymphocyte ratio (NLR) in patients undergoing prostate needle biopsy with a prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml.

PATIENTS AND METHODS: A total of 633 cases were eligible. We evaluated several factors including age, PSA, PSA-density (PSAD), platelet-to-lymphocyte ratio (PLR) and NLR in the presence or absence of prostate cancer (PCa), retrospectively. We evaluated statistically the associations between each factor and pathological findings or Gleason score.

RESULTS: A total of 201 were evaluated in this study. Regarding the presence or absence of prostate cancer, there were statistically significant differences in age, PSA levels, PSAD, the PLR and NLR. The mean NLR value of the patients with PCa was significantly lower compared to the entire cohort. Multivariate analysis showed that age, PSAD, and NLR were independent risk factors predicting PCa.

CONCLUSION: For patients having a PSA between 4.0 and 10.0 ng/ml, NLR was a predicting factor of PCa prior to prostate needle biopsy and an effective biomarker and useful tool for avoiding unnecessary biopsies.

PMID:33910847 | DOI:10.21873/invivo.12422

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Myocardial Fibrosis as a Predictor of Ventricular Arrhythmias in Patients With Non-ischemic Cardiomyopathy

In Vivo. 2021 May-Jun;35(3):1677-1685. doi: 10.21873/invivo.12427.

ABSTRACT

BACKGROUND/AIM: The aim of the study was to assess the relationship between myocardial fibrosis characteristics (percentage, localization, heterogeneity), evaluated by a non-invasive method such as cardiac magnetic resonance (CMR), with the extrasystolic ventricular arrhythmia in patients with non-ischemic cardiomyopathy.

PATIENTS AND METHODS: The study prospectively included 173 consecutive patients who underwent electrocardiogram Holter monitoring, transthoracic echocardiography and CMR with late gadolinium enhancement (LGE).

RESULTS: In univariate analysis, both the presence (OR=1.05, 95% CI=1.01-1.09; p=0.015), the percentage of fibrosis >15% (p=0.018), the septum size, the fibrosis in either lateral or septal walls (p=0.004), as well as fibrosis in the midwall (p=0.019) were statistically significant higher in the group with extrasystolic arrhythmia. After adjustment, the percentage of fibrosis >15%, had higher odds of extra systolic arrhythmia [OR=3.78 (95% CI=1.52-10.62, p=0.007)].

CONCLUSION: The presence, percentage, and localisation of left ventricle myocardial fibrosis characterized by LGE-CMR was associated with ventricular arrhythmias.

PMID:33910852 | DOI:10.21873/invivo.12427

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Impact of K-Ras Over-expression in Laryngeal Squamous Cell Carcinoma

In Vivo. 2021 May-Jun;35(3):1611-1615. doi: 10.21873/invivo.12418.

ABSTRACT

BACKGROUND/AIM: Oncogene up-regulation combined with suppressor gene down-regulation is a crucial genetic combination that promotes cell neoplastic phenotype and progressively malignant transformation in solid malignancies, including laryngeal squamous cell carcinoma (LSCC). Among oncogenes, the Kirsten ras oncogene homolog (K-Ras) is involved in LSCC onset and progression.

PATIENTS AND METHODS: Sixty (n=60) primary LSCC tissue sections were analyzed by immunohistochemistry (IHC). Digital image analysis (DIA) was also implemented for measuring K-Ras protein expression levels.

RESULTS: High K-Ras protein expression levels were observed in 20/60 (33.3%) LSCC tissue sections, whereas the rest of the cases (n=40; 66.7%) demonstrated low expression. Overall K-Ras expression was borderline significantly associated to the grade of the examined malignancies (p=0.048), whereas no other strong statistical correlations were identified. A progressive K-Ras overexpression was observed in all grades of the examined cases.

CONCLUSION: K-Ras over expression is correlated to a progressive dedifferentiation in LSCC.

PMID:33910843 | DOI:10.21873/invivo.12418

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Locally Optimizable Joint Embedding Framework to Design Nitrogen-Rich Molecules that are Similar but Improved

Mol Inform. 2021 Apr 28. doi: 10.1002/minf.202100011. Online ahead of print.

ABSTRACT

Deep learning has shown great potential for generating molecules with desired properties. But the cost and time required to obtain relevant property data have limited study to only a few classes of materials for which extensive data have already been collected. We develop a deep learning method that combines a generative model with a property prediction model to fuse small data of one class of molecules with larger data in another class. Common low-level physicochemical properties are jointly embedded into a latent space that can be used to design molecules in the smaller class. The chemical space around the molecules in the training set is explored through local gradient ascent optimization. Based on nine molecules from the original training set, nine new molecules are found to have improved properties while remaining structurally similar to the training molecules thereby easing requirements for entirely new synthesis routes. Validation is performed using an equilibrium thermochemistry code to verify the molecules and target properties. A specific example targeting the Chapman-Jouguet velocity and small data for nitrogen-rich molecules is shown. Despite the relative lack of nitrogen-rich molecule data, the results demonstrate that fusing and joint embedding with plentiful low nitrogen molecular data can produce higher generative performance than using the scarce data alone.

PMID:33909951 | DOI:10.1002/minf.202100011

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Essential oil chemical composition, antimicrobial, anticancer, and antioxidant effects of Thymus convolutus Klokov in Turkey

Z Naturforsch C J Biosci. 2021 Jan 19;76(5-6):193-203. doi: 10.1515/znc-2020-0070. Print 2021 May 26.

ABSTRACT

In this study, the chemical composition, antimicrobial, antioxidant, and anticancer effects of Thymus convolutus Klokov oil and its main compound camphor were investigated. The oil was isolated from T. convolutus using hydrodistillation method, analyzed by gas chromatography/mass spectrometry (GC-MS), and 66 compounds were identified. The main component was determined as camphor at 16.6%. The antioxidant properties were identified with the DPPH (2,2′-diphenyl-1-picrylhydrazyl) radical-scavenging method and, 33.39 ± 0.25% DPPH was scavenging in 1000 μg/mL of essential oil. The strong antimicrobial activity was observed against Escherichia coli, Enterobacter aerogenes, Proteus vulgaris, and Pseudomonas aeruginosa with MIC values of 125 μg/mL. Aspergillus flavus was more sensitive (28%) against T. convolutus essential oil than other fungi. The cytotoxic effect of oil was analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Camphor was effective on human hepatoma cells (Hep3B) at concentrations of 1 mg/mL, 500, 250, and 125 μg/mL, while essential oil of T. convolutus was found to be effective at concentrations of 250 and 125 μg/mL. A reduction in cell proliferation was observed in colon carcinoma cells (HT-29) treated with 500 μg/mL camphor for 48 h. No statistically significant effect was found in Umbilical Vein Endothelial Cells (HUVEC) treated with essential oil and camphor.

PMID:33909957 | DOI:10.1515/znc-2020-0070

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Effect of Air-Particle Abrasion Protocol and Primer on The Topography and Bond Strength of a High-Translucent Zirconia Ceramic

J Prosthodont. 2021 Apr 28. doi: 10.1111/jopr.13372. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate effect of air-particle abrasion protocol and primer on surface topography and bond strength of resin cement to high-translucent zirconia ceramics.

MATERIALS AND METHODS: Two hundred disk-shaped high-translucent zirconia specimens of 5Y-PSZ were prepared. The specimens were assigned to 5 groups in terms of particle type and air-particle abrasion pressure: (1) control (2) alumina with 0.2 MPa-air pressure [AB-0.2] (3) alumina with 0.4 MPa-air pressure [AB-0.4] (4) glass beads with 0.2 MPa-air pressure [GB-0.2] and (5) glass beads with 0.4 MPa-air pressure [GB-0.4]. Two different primers 1% MDP (Experimental) and MDP-silane primer (Clearfil Ceramic Primer Plus) was also tested. Stainless steel rods were bonded to the 5Y-PSZ specimens with PANAVIA V5. For each group, the tensile bond strength (TBS) was measured after 24h water storage (n = 10) and after 5,000 thermal-cycling (n = 10) at crosshead speed of 2 mm/min. The data were statistically analyzed using Weibull analysis. Surface roughness (Sa) was measured using a 3D-Laser Scanning Confocal Microscope (n = 5) and analyzed by t-test with Bonferroni correction. Surface topography using scanning electron microscopy (SEM) and surface elemental analysis using energy dispersion spectroscopy (EDX), and cross-section SEM at the interface with composite cement were also investigated.

RESULTS: In MDP-silane groups, the highest TBS was observed in AB-0.4 after 24h and GB-0.4 after thermal-cycling (p<0.05). In MDP groups, AB groups resulted in the significantly higher TBS than GB groups (p <0.05). AB-0.4 group showed the highest Sa value compared to all groups (p<0.005), meanwhile GB groups did not show different Sa compared to control (p>0.005).

CONCLUSION: Air-abrasion with different particle and blasting pressure can improve bonding to zirconia with proper primer selection. Particularly, glass beads abrasion followed by MDP-silane primer and alumina abrasion followed by MDP primer alone provided stable bond strength of resin cement to high-translucent zirconia after aging. High-translucent zirconia abraded with glass beads achieves a desirable bonding performance without creating surface microcracks which may hinder zirconia’s mechanical properties. This article is protected by copyright. All rights reserved.

PMID:33909938 | DOI:10.1111/jopr.13372

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Effects of Insoluble Cereal Fibre on Body Fat Distribution in the Optimal Fibre Trial (OptiFiT)

Mol Nutr Food Res. 2021 Apr 28:e2000991. doi: 10.1002/mnfr.202000991. Online ahead of print.

ABSTRACT

AIMS: The Optimal Fibre Trial investigated metabolic effects of insoluble cereal fibre in subjects with high-risk prediabetes. As the study shows dose-dependent moderate glycemic and anti-inflammatory benefits, especially in subjects with an obesity-related phenotype, the putative mechanism of action of this particular food component warrants clarification. A sub-group of the OptiFiT cohort received detailed body imaging throughout the study, permitting the analysis of effects on body fat distribution by fibre supplementation.

METHODS: 180 Caucasian participants with impaired glucose tolerance (IGT) received a blinded, randomized supplementation with insoluble cereal fibre or placebo for two years. Once a year, all subjects underwent fasting blood sampling, oGTT and full anthropometric measurements. A subgroup of 47 subjects additionally provided data from magnetic resonance imaging and spectroscopy for quantification of adipose tissue distribution and liver fat content. We compare these outcomes between fibre and placebo group and assess mechanistic connections to improvements in glucose metabolism and inflammation.

RESULTS: MR-assessed visceral and non-visceral body fat volume, fasting glucose, HbA1c, fasting insulin, insulin resistance and uric acid decreased in the fibre group, only. However, after adjustment for weight loss, there are no significant differences in changes of MR-derived measurements of body fat distribution between the intervention groups. There is a statistical trend for fibre-driven liver fat reduction in subjects with confirmed non-alcoholic fatty liver disease (NAFLD; n = 19). The entire MR subgroup shows the same pattern in metabolic improvements as the entire cohort.

CONCLUSIONS: Data and evidence on beneficial effects of insoluble cereal fibre on visceral and hepatic fat storage is limited, but warrants further research. Targetted trials assessing the usefulness of fibre in visceral obesity and NAFLD are required. This article is protected by copyright. All rights reserved.

PMID:33909947 | DOI:10.1002/mnfr.202000991