Tag: pubmed

J Chem Phys. 2022 May 14;156(18):184501. doi: 10.1063/5.0088388.

ABSTRACT

The effect of trimethylamine-N-oxide (TMAO) on hydrophobic solvation and hydrophobic interactions of methane has been studied with Molecular Dynamics simulations in the temperature range between 280 and 370 K at 1 bar ambient pressure. We observe a temperature transition in the effect of TMAO on the aqueous solubility of methane. At low temperature (280 K), methane is preferentially hydrated, causing TMAO to reduce its solubility in water, while above 320 K, methane preferentially interacts with TMAO, causing TMAO to promote its solubility in water. Based on a statistical-mechanical analysis of the excess chemical potential of methane, we find that the reversible work of creating a repulsive methane cavity opposes the solubility of methane in TMAO/water solution more than in pure water. Below 320 K, this solvent-excluded volume effect overcompensates the contribution of methane-TMAO van der Waals interactions, which promote the solvation of methane and are observed at all temperatures. These van der Waals interactions with the methyl groups of TMAO tip the balance above 320 K where the effect of TMAO on solvent-excluded volume is smaller. We furthermore find that the effective attraction between dissolved methane solutes increases with the increasing TMAO concentration. This observation correlates with a reduction in the methane solubility below 320 K but with an increase in methane solubility at higher temperatures.

PMID:35568566 | DOI:10.1063/5.0088388

J Chem Phys. 2022 May 14;156(18):184304. doi: 10.1063/5.0088017.

ABSTRACT

Gaussian process (GP) emulator has been used as a surrogate model for predicting force field and molecular potential, to overcome the computational bottleneck of ab initio molecular dynamics simulation. Integrating both atomic force and energy in predictions was found to be more accurate than using energy alone, yet it requires O((NM)³) computational operations for computing the likelihood function and making predictions, where N is the number of atoms and M is the number of simulated configurations in the training sample due to the inversion of a large covariance matrix. The high computational cost limits its applications to the simulation of small molecules. The computational challenge of using both gradient information and function values in GPs was recently noticed in machine learning communities, whereas conventional approximation methods may not work well. Here, we introduce a new approach, the atomized force field model, that integrates both force and energy in the emulator with many fewer computational operations. The drastic reduction in computation is achieved by utilizing the naturally sparse covariance structure that satisfies the constraints of the energy conservation and permutation symmetry of atoms. The efficient machine learning algorithm extends the limits of its applications on larger molecules under the same computational budget, with nearly no loss of predictive accuracy. Furthermore, our approach contains an uncertainty assessment of predictions of atomic forces and energies, useful for developing a sequential design over the chemical input space.

PMID:35568561 | DOI:10.1063/5.0088017

J Chem Phys. 2022 May 14;156(18):184118. doi: 10.1063/5.0085006.

ABSTRACT

We derive a systematic and general method for parameterizing coarse-grained molecular models consisting of anisotropic particles from fine-grained (e.g., all-atom) models for condensed-phase molecular dynamics simulations. The method, which we call anisotropic force-matching coarse-graining (AFM-CG), is based on rigorous statistical mechanical principles, enforcing consistency between the coarse-grained and fine-grained phase-space distributions to derive equations for the coarse-grained forces, torques, masses, and moments of inertia in terms of properties of a condensed-phase fine-grained system. We verify the accuracy and efficiency of the method by coarse-graining liquid-state systems of two different anisotropic organic molecules, benzene and perylene, and show that the parameterized coarse-grained models more accurately describe properties of these systems than previous anisotropic coarse-grained models parameterized using other methods that do not account for finite-temperature and many-body effects on the condensed-phase coarse-grained interactions. The AFM-CG method will be useful for developing accurate and efficient dynamical simulation models of condensed-phase systems of molecules consisting of large, rigid, anisotropic fragments, such as liquid crystals, organic semiconductors, and nucleic acids.

PMID:35568534 | DOI:10.1063/5.0085006

J Clin Hypertens (Greenwich). 2022 May 14. doi: 10.1111/jch.14500. Online ahead of print.

ABSTRACT

The authors aimed to explore the association between visit-to-visit blood pressure variability (BPV) in pregnant women and adverse neonatal outcomes. The study included 52 891 pregnant women. BPV was calculated as standard deviation (SD) and coefficient of variation (CV) of systolic blood pressure (SBP) or diastolic blood pressure (DBP). All participants were divided into four groups by the quartiles of BPV. When comparing the highest quartiles to the lowest quartiles of DBP SD in all participants, the fully adjusted ORs were 1.19 (95% CI 1.11-1.27, p for trend < .001) for fetal distress, 1.32 (95% CI 1.14-1.54, p for trend < .001) for small for gestational age, 1.32 (95% CI 1.06-1.63, p for trend = .003) for 1-min Apgar score ≤ 7. When comparing the highest quartiles to the lowest quartiles of DBP CV, ORs were 1.22 (95% CI 1.14-1.30, p for trend < .001) for fetal distress, 1.38 (95% CI 1.17-1.61, p for trend < .001) for small for gestational age, 1.43 (95% CI 1.14-1.79, p for trend < .001) for 1-min Apgar score ≤ 7. ORs for preterm birth and 5-min Apgar score ≤ 7 were not statistically significant. However, in participants with gestational hypertension or preeclampsia, ORs for preterm birth were 2.80 (95% CI 1.99-3.94, p for trend < .001) in DBP SD and 3.25 (95% CI 2.24-4.72, p for trend < .001) in DBP CV when extreme quartiles were compared. In conclusion, higher visit-to-visit BPV was associated with adverse neonatal outcomes.

PMID:35567772 | DOI:10.1111/jch.14500

Diagn Cytopathol. 2022 May 14. doi: 10.1002/dc.24978. Online ahead of print.

ABSTRACT

BACKGROUND: The histological classifications of invasive lung adenocarcinoma subtypes are considered to predict patient prognosis after surgical treatment. The objectives of this study were to evaluate cytomorphological characteristics and proliferative activities among the histological predominant patterns by performing cytomorphometric and flow cytometric analyses using liquid-based cytology materials.

METHODS: Cytological samples fixed by liquid-based cytology preservatives from 53 surgically-resected lung adenocarcinoma specimens were obtained between August 2018 and November 2019. The Papanicolaou-stained and paired Ki-67-stained slides were analyzed for calculating nuclear morphology (nuclear area, nuclear perimeter and nuclear circularity) and Ki-67 labeling index using software. The cell proliferation index (CPIx) was calculated and cellular information including cell cycle stage of tumor cells was obtained by flow cytometry.

RESULTS: The 53 cases included papillary (n = 29), acinar (n = 8), lepidic (n = 5), and solid (n = 4) subtypes, and invasive mucinous adenocarcinoma (n = 7) were also included. In the lepidic pattern, nuclear area (79.6 ± 28.8 μm² ) and perimeter (34.1 ± 6.1 μm) were relatively larger and longer than those of the other predominant patterns. The Ki-67 labeling index of the solid pattern (27.9 ± 12.5%) was highest compared with those of other predominant patterns. There were statistically significant differences in the lepidic versus solid patterns and the papillary versus solid patterns (p = .013 and p = .039, respectively). The calculated mean CPIx of the lepidic and the acinar patterns were approximately two-fold higher than those of the other predominant patterns.

CONCLUSION: By revealing the differences of cytomorphological characteristics, these methodologies might be used for diagnosing cytopathological materials using digital cytopathology.

PMID:35567786 | DOI:10.1002/dc.24978

Cardiovasc Drugs Ther. 2022 May 14. doi: 10.1007/s10557-022-07346-8. Online ahead of print.

ABSTRACT

AIMS: This study attempts to identify predictors associated with bleeding and stroke and systemic embolism (SSE) in Singaporean Asians taking rivaroxaban and apixaban.

METHODS: A total of 134 Singaporean patients on either rivaroxaban or apixaban for non-valvular atrial fibrillation were included for this study. Baseline characteristics were recorded at recruitment while bleeding and SSE events were recorded during a 1-year follow-up. Peak and trough drug plasma concentrations were collected based on the dosing interval and pharmacokinetics of the drugs and quantified using high performance liquid chromatography. Characteristics of patients with or without bleeds were compared using relevant statistical tests. Multivariable regression that included covariates with p < 0.1 from an initial univariable regression was performed to analyse predictors that resulted in higher risk of bleeding in patients.

RESULTS: Median creatinine clearance (CrCl) was significantly lower in patients on rivaroxaban who experienced bleeds as compared to patients who did not experience bleeds (61.5 vs 70.8 mL/min, p = 0.047), while concomitant simvastatin use was found to be independently associated with a sixfold increased risk of bleeding (adjusted OR = 6.14 (95% CI: 1.18-31.97), p = 0.031) for rivaroxaban after controlling for body mass index, CrCl and having experienced a previous SSE.

CONCLUSION: Our findings suggest that concomitant use of simvastatin with rivaroxaban may be associated with bleeding events in an Asian cohort. Further studies using physiologically based pharmacokinetic modelling are required to investigate the drug-drug interactions between these drugs.

PMID:35567727 | DOI:10.1007/s10557-022-07346-8

J Patient Rep Outcomes. 2022 May 14;6(1):49. doi: 10.1186/s41687-022-00456-9.

ABSTRACT

BACKGROUND: Clostridioides difficile infection (CDI) is associated with high recurrence rates impacting health-related quality of life (HrQOL). However, patient-reported data are lacking particularly in the outpatient setting. We assessed changes in HrQOL over time in patients treated with bezlotoxumab at US infusion centers and determined clinical factors associated with HrQOL changes.

METHODS: The HrQOL survey was conducted in adult patients with CDI, who received bezlotoxumab in 25 US outpatient infusion centers. The survey was adapted from the Cdiff32 instrument to assess anxiety-related changes to HrQOL and completed on the day of infusion (baseline) and at 90 days post bezlotoxumab (follow-up). Demographics, disease history, CDI risk factors, and recurrence of CDI (rCDI) at 90-day follow-up were collected. Changes in HrQOL scores were calculated and outcomes assessed using a multivariable linear regression model with P < 0.05 defined as statistically significant.

RESULTS: A total of 144 patients (mean age: 68 ± 15 years, 63% female, median Charlson index: 4, 15.9% rCDI) were included. The overall mean baseline and follow-up HrQOL scores were 26.4 ± 11.5 and 56.4 ± 25.0, respectively. At follow-up, this score was significantly higher for patients who had primary CDI (34.5 ± 21.7) compared to those with multiple rCDI (24.7 ± 21.0; P = 0.039). The mean HrQOL change at follow-up was significantly higher for patients without rCDI (34.1 ± 28.8 increase) compared to patients with rCDI (6.7 ± 19.5 increase; P < 0.001), indicating improvement in anxiety.

CONCLUSIONS: Using the Cdiff32 instrument, we demonstrated that HrQOL worsened significantly in patients with further rCDI. These findings support the use of Cdiff32 in assessing CDI-related humanistic outcomes.

PMID:35567724 | DOI:10.1186/s41687-022-00456-9

Sports Med. 2022 May 14. doi: 10.1007/s40279-022-01682-3. Online ahead of print.

ABSTRACT

BACKGROUND: Research has shown the effectiveness of sedentary behaviour interventions on reducing sedentary time. However, no systematic review has studied where the reduced sedentary time after such interventions is displaced to.

OBJECTIVE: Our objective was to synthesize the evidence from interventions that have reduced sedentary behaviour and test the displacement of sedentary time into physical activity (light physical activity [LPA], moderate-to-vigorous physical activity [MVPA], standing, and stepping).

METHODS: Two independent researchers performed a systematic search of the EBSCOhost, PubMed, Scopus, and Web of Science electronic databases. Meta-analyses were performed to examine the time reallocated from sedentary behaviour to physical activity during working time and the whole day in intervention trials (randomized/non-randomized controlled/non-controlled).

RESULTS: A total of 36 studies met all the eligibility criteria and were included in the systematic review, with 26 studies included in the meta-analysis. Interventions showed a significant overall increase in worksite LPA (effect size [ES] 0.24; 95% confidence interval [CI] 0.05 to 0.43; P < 0.013) and daily LPA (ES 0.62; 95% CI 0.34 to 0.91; P = 0.001). A statistically significant increase in daily MVPA was observed (ES 0.47; 95% CI 0.26 to 0.67; P < 0.001). There was a significant overall increase in worksite standing time (ES 0.76; 95% CI 0.56 to 0.95; P < 0.001), daily standing time (ES 0.52; 95% CI 0.38 to 0.65; P < 0.001), and worksite stepping time (ES 0.12; 95% CI 0.04 to 0.20; P = 0.002).

CONCLUSIONS: Effective interventions aimed at reducing sedentary behaviour result in a consistent displacement of sedentary time to LPA and standing time, both at worksites and across the whole day, whereas changes in stepping time or MVPA are dependent on the intervention setting. Strategies to reduce sedentary behaviour should not be limited to worksite settings, and further efforts may be required to promote daily MVPA.

TRIAL REGISTRATION: PROSPERO registration number CRD42020153958.

PMID:35567719 | DOI:10.1007/s40279-022-01682-3

Int Ophthalmol. 2022 May 14. doi: 10.1007/s10792-022-02312-7. Online ahead of print.

ABSTRACT

PURPOSE: To report the prevalence of undiagnosed glaucoma, as well as demographic characteristics and risk factors among glaucoma suspects who were detected in a publicly promoted intraocular pressure (IOP) based glaucoma screening event.

METHODS: A total of 2468 subjects older than 18 years participated in the glaucoma screening event in Zagreb, in 2014, which included a medical interview and IOP measurement using Icare tonometer. 256 subjects (10.37%) were identified as glaucoma suspects, out of which 125 (5.06%) subjects underwent further detailed ophthalmic examination and were classified into five diagnostic groups.

RESULTS: The prevalence of all types of newly diagnosed glaucoma was 1.175%, while the prevalence of ocular hypertension (OH), primary open-angle glaucoma (POAG), primary angle closure (PAC) and secondary glaucoma (SG) was 0.16%, 0.89%, 0.16% and 0.12%, respectively. The prevalence of newly diagnosed glaucoma in glaucoma suspects was 23.2%. 17.60% of glaucoma suspects were diagnosed as POAG. Older age was statistically significantly associated with POAG (p = 0.001) and PAC (p = 0.029). At the univariate level, refractive errors were a statistically significant predictor of POAG, and those with hyperopia had more than three times larger odds for POAG. At the multivariate level, none of the predictors reached statistical significance.

CONCLUSION: Successful cooperation between healthcare institutions and media can be a useful way of increasing awareness and detection of individuals at an increased risk for developing glaucoma.

PMID:35567692 | DOI:10.1007/s10792-022-02312-7

J Community Health. 2022 May 14. doi: 10.1007/s10900-022-01098-0. Online ahead of print.

ABSTRACT

Understanding changes in substance use in a small population state is challenging. Many national datasets restrict data to reduce the probability of identifying persons. Alaska is a small population state (731,000 residents) with a large geographic region (25% the size of the lower 48), a diverse population, and highly variable seasons, with fewer than 10% of the state being road accessible. Given the uniqueness of Alaska, this project sought to understand what could be learned about addiction and its relationships with unemployment and median income in Alaska. National Survey on Drug Use and Health, State and Small Area Estimates (1999-2020) data were analyzed to measure prevalence changes. Outcome prevalence were independently correlated with median income and annual unemployment rate as the annual collection periods varied. Analyses were limited to simple bivariate analyses due to the data restrictions. Median income was found to have stronger correlational relationships and significant relationships with more negative outcomes compared to unemployment. While annual unemployment rates had statistically significant relationships with substance use outcomes, negative mental health outcomes appeared more related to unemployment than median income. Alcohol use in the past month, cigarette and tobacco use, and pain reliever misuse declined while binge drinking in the past month and illicit drug use increased. More people reported depression, serious mental illness, and suicidal ideation and planning over time peaking in the last year of data collection. While NSDUH data provide some idea of the changes in drug use over time, their effectiveness in Alaska is unknown. Many data sources claim they are nationally representative, but these statements cannot be objectively measured. We will use these outcomes and data as a baseline for future studies where we will explore state specific data sources.

PMID:35567711 | DOI:10.1007/s10900-022-01098-0