Nevin Manimala

Trends Pharmacol Sci. 2022 Apr 27:S0165-6147(22)00059-1. doi: 10.1016/j.tips.2022.03.009. Online ahead of print.

ABSTRACT

Researchers, regulatory agencies, and the pharmaceutical industry are moving towards precision pharmacovigilance as a comprehensive framework for drug safety assessment, at the service of the individual patient, by clustering specific risk groups in different databases. This article explores its implementation by focusing on: (i) designing a new data collection infrastructure, (ii) exploring new computational methods suitable for drug safety data, and (iii) providing a computer-aided framework for distributed clinical decisions with the aim of compiling a personalized information leaflet with specific reference to a drug’s risks and adverse drug reactions. These goals can be achieved by using ‘smart hospitals’ as the principal data sources and by employing methods of precision medicine and medical statistics to supplement current public health decisions.

PMID:35490032 | DOI:10.1016/j.tips.2022.03.009

J Chem Phys. 2022 Apr 28;156(16):164105. doi: 10.1063/5.0090055.

ABSTRACT

Feature selection (FS) methods often are used to develop data-driven descriptors (i.e., features) for rapidly predicting the functional properties of a physical or chemical system based on its composition and structure. FS algorithms identify descriptors from a candidate pool (i.e., feature space) built by feature engineering (FE) steps that construct complex features from the system’s fundamental physical properties. Recursive FE, which involves repeated FE operations on the feature space, is necessary to build features with sufficient complexity to capture the physical behavior of a system. However, this approach creates a highly correlated feature space that contains millions or billions of candidate features. Such feature spaces are computationally demanding to process using traditional FS approaches that often struggle with strong collinearity. Herein, we address this shortcoming by developing a new method that interleaves the FE and FS steps to progressively build and select powerful descriptors with reduced computational demand. We call this method iterative Bayesian additive regression trees (iBART), as it iterates between FE with unary/binary operators and FS with Bayesian additive regression trees (BART). The capabilities of iBART are illustrated by extracting descriptors for predicting metal-support interactions in catalysis, which we compare to those predicted in our previous work using other state-of-the-art FS methods (i.e., least absolute shrinkage and selection operator + l₀, sure independence screening and sparsifying operator, and Bayesian FS). iBART matches the performance of these methods yet uses a fraction of the computational resources because it generates a maximum feature space of size O(10²), as opposed to O(10⁶) generated by one-shot FE/FS methods.

PMID:35490030 | DOI:10.1063/5.0090055

J Chem Phys. 2022 Apr 28;156(16):161101. doi: 10.1063/5.0087586.

ABSTRACT

In this Communication, we assess a panel of 18 double-hybrid density functionals for the modeling of the thermochemical and kinetic properties of an extended dataset of 449 organic chemistry reactions belonging to the BH9 database. We show that most of DHs provide a statistically robust performance to model barrier height and reaction energies in reaching the “chemical accuracy.” In particular, we show that nonempirical DHs, such as PBE0-DH and PBE-QIDH, or minimally parameterized alternatives, such as ωB2PLYP and B2K-PLYP, succeed to accurately model both properties in a balanced fashion. We demonstrate, however, that parameterized approaches, such as ωB97X-2 or DSD-like DHs, are more biased to only one of both properties.

PMID:35490016 | DOI:10.1063/5.0087586

J Chem Phys. 2022 Apr 28;156(16):164104. doi: 10.1063/5.0086640.

ABSTRACT

We present our blind predictions for the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL), ninth challenge, focusing on the binding of WP6 (carboxy-pillar[6]arene) with ammonium/diammonium cationic guests. Host-guest binding free energies have been calculated using the recently developed virtual double system single box approach, based on the enhanced sampling of the bound and unbound end-states followed by fast switching nonequilibrium alchemical simulations [M. Macchiagodena et al., J. Chem. Theory Comput. 16, 7160 (2020)]. As far as Pearson and Kendall coefficients are concerned, performances were acceptable and, in general, better than those we submitted for calixarenes, cucurbituril-like open cavitand, and beta-cyclodextrines in previous SAMPL host-guest challenges, confirming the reliability of nonequilibrium approaches for absolute binding free energy calculations. In comparison with previous submissions, we found a rather large mean signed error that we attribute to the way the finite charge correction was addressed through the assumption of a neutralizing background plasma.

PMID:35490003 | DOI:10.1063/5.0086640

J Fr Ophtalmol. 2022 Apr 27:S0181-5512(21)00473-3. doi: 10.1016/j.jfo.2021.06.007. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effect of systemic anti-androgen drugs on tear function tests and the ocular surface.

METHODS: Sixty-four male subjects were included in this study. Subjects who were on anti-androgen treatment for prostate cancer (Group A, n: 31) and those who had received only surgical treatment for prostate cancer (Group B, n: 17) were recruited from the department of urology. Age-matched subjects who had never received anti-androgen treatment (Group C, n: 16) constituted the control group. Group A was divided into two subgroups according to the number of anti-androgen drugs used (Group A1: one drug, Group A2: two drugs). All cases underwent a complete ocular examination, including tear film break up time (TBUT), corneal and conjunctival staining, Schirmer 1 test, conjunctival impression cytology, and ocular surface disease index (OSDI) questionnaire.

RESULTS: The mean Schirmer’s values were 6.87mm, 11.41mm, and 13.03mm in Groups A, B, and C, respectively (P=0.001). TBUT was 5.45±2.01, 9.85±2.52 and 9.81±1.96seconds in Groups A, B, and C, respectively (P=0.001). Schirmer and TBUT were significantly lower, and corneal staining and OSDI questionnaire scores were higher in Group A compared to groups B and C (P<0.01). Conjunctival impression cytology results according to the Nelson grading system revealed no statistically significant difference between the groups (P=0.422).

CONCLUSION: Anti-androgen drugs alter tear function tests, cause increased corneal and conjunctival staining scores and worsen complaints of dry eye in patients with prostate cancer.

PMID:35489988 | DOI:10.1016/j.jfo.2021.06.007

Matern Child Nutr. 2022 Apr 30:e13368. doi: 10.1111/mcn.13368. Online ahead of print.

ABSTRACT

The introduction of fluids other than breast milk during the first few days of life or later neonatal period has been identified as a risk factor for suboptimal breastfeeding (BF) outcomes in numerous studies using varying study designs. However, the relationship between early introduction of fluids other than breast milk and BF outcomes has not been systematically assessed using only prospective studies that can establish temporality, which is critical for determining whether observed associations are causal. We conducted a systematic review and meta-analysis of prospective studies to assess if there is a difference in BF outcomes as a result of the introduction of: (a) milk-based prelacteals, (b) water-based prelacteals and (c) breast milk substitutes (BMS) between 4 days and 4 weeks postpartum. We searched PubMed, Lilacs, Web of Science and other repositories for original research investigating the relationship between early introduction of prelacteals and/or BMS and BF outcomes. Forty-eight studies met the inclusion criteria for the systematic review. Of the 39 prelacteal feeding studies, 27 had the prerequisite statistical information for inclusion in the meta-analysis. Findings from the meta-analysis showed a relationship between prelacteals and exclusive BF cessation (RR 1.44; 1.29-1.60) and any BF cessation (2.23; 1.63-3.06) among infants under 6 months old. Nine studies focusing on the introduction of BMS during the neonatal period identified this practice as a statistically significant risk factor for a shorter BF duration. Effective interventions are needed to prevent the introduction of unnecessary milk-based prelacteals and BMS during the perinatal and neonatal periods to improve BF outcomes.

PMID:35489107 | DOI:10.1111/mcn.13368

Phys Ther Sport. 2022 Apr 22;55:196-204. doi: 10.1016/j.ptsp.2022.04.010. Online ahead of print.

ABSTRACT

PURPOSE: To determine the proportion of adolescents at moderate/high risk for Persistent Postconcussion Symptoms (PPCS) who develop PPCS when randomized to early aerobic exercise or standard-of-care and examine exercise volume/intensity between groups.

METHODS: Using a randomized clinical trial design, we enrolled patients 10-18 years of age who obtained a “Predicting/Preventing Postconcussive Problems in Pediatrics” (5P) risk score ≥6 and enrolled/tested ≤ one-week post-concussion (mean = 5.5 ± 1.5 days post-concussion). Participants were randomized to “Exercise” (5 days/week, 20 min/day aerobic exercise at individualized intensity [80% HR at exercise test cessation]) or “Standard-of-Care” (no exercise recommendations). They returned for re-testing one-month post-concussion, and we remotely monitored exercise between assessments.

RESULTS: Sixteen participants enrolled (intervention: n = 9, 56% female, 14.2 ± 2.1 years; standard-of-care: n = 7, 57% female, 13.6 ± 1.7 years). A smaller proportion of the early aerobic exercise group developed PPCS when compared to the standard-of-care group (44% vs. 86%; relative risk = 0.52; 95% confidence interval = 0.34-1.36; number-needed-to-treat = 2.4).

CONCLUSION: We observed that participants randomized to early aerobic exercise had a lower risk of PPCS compared to standard-of-care. Although not statistically significant, these results suggest early/individualized aerobic exercise among those at moderate/high PPCS risk may be effective at reducing that risk, and early aerobic exercise is not detrimental to recovery outcomes.

PMID:35489100 | DOI:10.1016/j.ptsp.2022.04.010

Iran J Kidney Dis. 2022 Mar;16(2):88-95.

ABSTRACT

INTRODUCTION: Cardiovascular disease (CVD) may accompany chronic kidney disease (CKD), resulting in additional complications and increased death rate. This study was performed to evaluate cardiac structure and function and several risk factors in hospitalized CKD children.

METHODS: Seventy-four children with CKD were enrolled in this cross-sectional descriptive study. Two-dimensional and M-mode ultrasonography, Doppler flow velocity and Tissue Doppler Imaging (TDI) were used to evaluate cardiac chamber size, left ventricular mass (LVM) and echocardiographic indices of ventricular function.

RESULTS: Advanced stages of CKD showed statistically insignificant increased LVM and LVM indexed to height2.7 (LVMI), and mildly reduced diastolic function. Hypertensive patients had an insignificant increase in the incidence of left ventricular hypertrophy (LVH) defined as LVMI greater than 95th percentile for age and sex and LVH2 as LVMI2 more than 95 gr/m2 for girls and more than 115gr/ m2 for boys older than 8 years. Patients with LVH had lower left ventricular ejection fraction (LVEF) and abnormal right ventricular (RV) function based on the tricuspid valve systolic velocity (TV S’) survey. LVH2 cases, however, revealed decreased LV systolic function according to ejection fraction (EF) and abnormal mitral valve systolic velocity (MV S’).

CONCLUSION: LVH related to hypertension and mild systolic and diastolic dysfunction were more prevalent in advanced CKD cases, however TDI showed no statistically significant difference in the prevalence of MV S’ and TV S’. We recommend strict blood pressure control and prevention of renal function deterioration as effective tools for cardiac protection in CKD children. DOI: 10.52547/ijkd.6643.

PMID:35489077

Dev Med Child Neurol. 2022 Apr 30. doi: 10.1111/dmcn.15252. Online ahead of print.

ABSTRACT

AIM: To identify 5-week pain intensity trajectories and their association with physical and psychological well-being in children/young people with cerebral palsy (CP).

METHOD: A cohort study was conducted with 101 Canadian children/young people with CP, of whom 49 were female, with an overall mean age of 12 years 11 months (SD 3 years 1 month), range of 8 to 18 years, and classified in any Gross Motor Function Classification System level. Self-reported pain intensity (Faces Pain Scale – Revised) was collected weekly for 5 weeks and physical and psychological well-being (KIDSCREEN-27) at baseline and 5 weeks. Statistical analyses included latent class growth and general linear models.

RESULTS: All Gross Motor Function Classification System levels were represented (I = 40.6%; II = 15.8%; III = 20.8%; IV = 13.9%; V = 8.9%). Five pain intensity trajectories were identified. Three trajectories had very low (35.4%), low (32.4%), or high (4.9%) mean stable pain. Two trajectories had moderate changing pain (16.8%) and high pain decreasing to moderate levels (10.5%) respectively. Trajectory participants with stable high pain had the lowest physical well-being (adjusted β = -10.01; 95% confidence interval [CI] = -19.37 to -0.66). Those in the three trajectories with the highest mean baseline pain intensity (>3 out of 10) had the lowest psychological well-being (adjusted β = -8.27, 95% CI = -14.84 to -1.70; β = -6.74, 95% CI = -12.43 to -1.05; β = -5.82, 95% CI = -15.34 to 3.71).

INTERPRETATION: Almost one-third of participants had moderate-to-high pain intensity trajectories. Membership in the higher pain intensity trajectories was associated with lower physical and psychological well-being.

PMID:35489074 | DOI:10.1111/dmcn.15252

J Med Entomol. 2022 Apr 30:tjac033. doi: 10.1093/jme/tjac033. Online ahead of print.

ABSTRACT

Host feeding patterns and the prevalence of infection with Rickettsia parkeri were determined for the primary vector, Amblyomma maculatum Koch as well as sympatric tick species A. americanum (Linnaeus) and Dermacentor variabilis (Say) collected from a reconstructed prairie in the Piedmont region of North Carolina during 2011 and 2012. The occurrence of R. parkeri among A. maculatum adults and nymphs was 36.9% (45/122) and 33.3% (2/6), respectively. Rickettsia parkeri was detected in a single male A. americanum 2.3% (1/43). A PCR-reverse line blot hybridization assay of a 12S rDNA fragment amplified from remnant larval and nymphal bloodmeals of host-seeking ticks was used to identify bloodmeal hosts. Of the tick samples tested, bloodmeal host identification was successful for 29.3% (12/41) of adult A. americanum and 39.2% (20/51) of adult D. variabilis. For A. maculatum, bloodmeal host identification was successful for 50% (61/122) of adults collected from vegetation and 100% (4/4) of nymphs removed from cotton rats (Sigmodon hispidus Say and Ord). The cotton rat was the most common bloodmeal host with 59.0% (36/61) identified for adult A. maculatum. No statistically significant association was observed, however, between bloodmeal host and pathogen prevalence for any tick species. While the cotton rat was an important bloodmeal host for A. maculatum nymphs, this vertebrate did not appear to be the primary source of R. parkeri infection for A. maculatum.

PMID:35489062 | DOI:10.1093/jme/tjac033