Nevin Manimala

ALTEX. 2022 Mar 30. doi: 10.14573/altex.2012022. Online ahead of print.

ABSTRACT

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies – thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.

PMID:35353900 | DOI:10.14573/altex.2012022

Mod Rheumatol. 2022 Mar 30:roac022. doi: 10.1093/mr/roac022. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the changes in knee pain, a dominant cause of physical disability, following the coronavirus disease (COVID-19) pandemic, and to identify factors affecting the changes in knee pain.

METHODS: We analyzed the pre- and post-COVID-19 longitudinal dataset of the Nagahama Study. Knee pain was assessed using the Knee Society Score (KSS). The estimated KSS from the age and sex using regression model in the pre- and post-COVID-19 dataset was compared. Factors including the activity score, educational level, and various impacts of COVID-19 were analyzed for correlation analyses with changes in KSS.

RESULTS: Data collected from 6409 participants showed statistically significant differences in KSS, pre- (mean = 22.0; SD = 4.4) and post-COVID-19 (mean = 19.5; SD = 6.4). Low activity score (p = 0.008), low educational level (p < 0.001) and undesirable financial impact (p = 0.030) were independently associated with knee pain exacerbation.

CONCLUSION: The harmful effects of the COVID-19 pandemic on knee pain were suggested. People should be encouraged to engage in physical activities, such as walking, even despite the state of emergency. Furthermore, social support for economically disadvantaged groups may improve healthcare access, preventing the acute exacerbations of knee pain.

PMID:35353896 | DOI:10.1093/mr/roac022

Plant Cell Physiol. 2022 Mar 30:pcac041. doi: 10.1093/pcp/pcac041. Online ahead of print.

ABSTRACT

ATTED-II (https://atted.jp) is a gene coexpression database for nine plant species based on publicly available RNAseq and microarray data. One of the challenges in constructing condition-independent coexpression data based on publicly available gene expression data is managing the inherent sampling bias. Here, we report ATTED-II version 11, wherein we adopted a coexpression calculation methodology to balance the samples using principal component analysis and ensemble calculation. This approach has two advantages. First; omitting principal components with low contribution rates reduces the main contributors of noise. Second; balancing large differences in contribution rates enables considering various sample conditions entirely. In addition, based on RNAseq- and microarray-based coexpression data, we provide species-representative, integrated coexpression information to enhance the efficiency of inter-species comparison of the coexpression data. These coexpression data are provided as a standardized z-score to facilitate integrated analysis with different data sources. We believe that with these improvements, ATTED-II is more valuable and powerful for supporting inter-species comparative studies and integrated analyses using heterogeneous data.

PMID:35353884 | DOI:10.1093/pcp/pcac041

Int J Neuropsychopharmacol. 2022 Mar 30:pyac023. doi: 10.1093/ijnp/pyac023. Online ahead of print.

ABSTRACT

BACKGROUND: Around 3% of the population suffers a first episode of psychosis (FEP) and a high percentage of these patients subsequently relapse. As the clinical course following a FEP is hard to predict, it is of interest to identify cognitive and biological markers that will help improve the diagnosis, treatment and outcome of such events, and to define new therapeutic targets. Here we analyzed the plasma oxytocin and prolactin levels during a FEP, assessing their correlation with clinical and cognitive features.

METHODS: The oxytocin and prolactin in plasma was measured in 120 FEP patients and 106 healthy controls, all of whom were subjected to a clinical and neuropsychological assessment. Most patients were under antipsychotics. Statistical analyses aimed to identify factors associated with the FEP and to search for associations between the variables.

RESULTS: FEP patients had less oxytocin, more prolactin, a poor premorbid-IQ and they performed worse in sustained attention. Male patients with higher prolactin levels experienced more severe psychotic symptoms and required higher doses of antipsychotics. Low oxytocin was associated with poor sustained attention in women, whereas low oxytocin and high prolactin in men correlated with better performance in sustained attention.

CONCLUSION: Low oxytocin, high prolactin, and poor premorbid-IQ and sustained attention are factors associated with a FEP, representing potential therapeutic targets in these patients. These biological factors and cognitive domains might play an important role during a FEP, which could help us to develop new strategies that improve the outcomes of this disorder and that should perhaps be gender specific.

PMID:35353882 | DOI:10.1093/ijnp/pyac023

PLoS One. 2022 Mar 30;17(3):e0266127. doi: 10.1371/journal.pone.0266127. eCollection 2022.

ABSTRACT

BACKGROUND: City-wide lockdowns and school closures have demonstrably impacted COVID-19 transmission. However, simulation studies have suggested an increased risk of COVID-19 related morbidity for older individuals inoculated by house-bound children. This study examines whether the March 2020 lockdown in New York City (NYC) was associated with higher COVID-19 hospitalization rates in neighborhoods with larger proportions of multigenerational households.

METHODS: We obtained daily age-segmented COVID-19 hospitalization counts in each of 166 ZIP code tabulation areas (ZCTAs) in NYC. Using Bayesian Poisson regression models that account for spatiotemporal dependencies between ZCTAs, as well as socioeconomic risk factors, we conducted a difference-in-differences study amongst ZCTA-level hospitalization rates from February 23 to May 2, 2020. We compared ZCTAs in the lowest quartile of multigenerational housing to other quartiles before and after the lockdown.

FINDINGS: Among individuals over 55 years, the lockdown was associated with higher COVID-19 hospitalization rates in ZCTAs with more multigenerational households. The greatest difference occurred three weeks after lockdown: Q2 vs. Q1: 54% increase (95% Bayesian credible intervals: 22-96%); Q3 vs. Q1: 48% (17-89%); Q4 vs. Q1: 66% (30-211%). After accounting for pandemic-related population shifts, a significant difference was observed only in Q4 ZCTAs: 37% (7-76%).

INTERPRETATION: By increasing house-bound mixing across older and younger age groups, city-wide lockdown mandates imposed during the growth of COVID-19 cases may have inadvertently, but transiently, contributed to increased transmission in multigenerational households.

PMID:35353857 | DOI:10.1371/journal.pone.0266127

PLoS One. 2022 Mar 30;17(3):e0264676. doi: 10.1371/journal.pone.0264676. eCollection 2022.

ABSTRACT

BACKGROUND: Appropriate and prompt health care seeking by parents or caretakers can reduce morbidity and mortality among under-five year children. Although remarkable progress has been made in the reduction of under-five mortality, still the under-five mortality rate is high in Nepal. There are few studies on health care seeking behavior among caretakers in Nepal. Therefore, this study was conducted to determine the prevailing health care seeking behavior of caretakers on common childhood illness of under five year children and to identify the association of socio demographic, economic, illness related and health system related factors with health care seeking behavior in 2018.

METHODS: A community based descriptive cross-sectional study was conducted from September to November 2018. Data were collected using a pretested semi-structured interview schedule. Both descriptive and inferential statistics were used to present the data. Bivariate and multivariate logistic regression analysis was used to identify the factors associated with health care seeking behavior.

RESULTS: A total of 387 caretakers participated in the study. Of these, 84.8% sought any type of care and 15.2% did nothing. Amongst those who sought care 42.4% visited the pharmacy directly, 25.3% visited the health facility. Amongst those who visited a health facility, 37.2% of caretakers sought prompt health care. Common danger sign stated by caretakers was fever in children (92.4%). Secondary education(AOR = 0.357, 95%CI = 0.142-0.896), involvement in service as an occupation(AOR = 3.533, 95%CI = 1.096-11.384), distance to reach nearest health facility(0.957, 95%CI = 0.923-0.993) and perceived severity of illness; moderate severity (7.612, 95%CI = 2.127-27.242), severe severity (AOR = 15.563, 95%CI = 3.495-69.308) were found to be significantly associated with health care seeking behavior.

CONCLUSION: Strong policies and regulations should be formulated and implemented at Birendranagar municipality of Surkhet district to prevent direct purchase of medicines from pharmacies without any consultation. It is essential to conduct the health awareness program at community level on early recognition of danger signs and importance of consulting health facilities.

PMID:35353836 | DOI:10.1371/journal.pone.0264676

PLoS One. 2022 Mar 30;17(3):e0265269. doi: 10.1371/journal.pone.0265269. eCollection 2022.

ABSTRACT

BACKGROUND: There are limited data on the epidemiology of HPV in different anatomical sites of female sex workers (FSW). We investigated the prevalence and concordance of cervical, vulval, oral and anal HPV among FSW in Ibadan, Nigeria.

METHODS: FSWs aged 18-45 years were enrolled in a cross-sectional survey. After interview and clinical examination, samples were collected from mouth, cervix, vulva and anus. HPV genotyping was done with Anyplex II 28HPV assay. Multivariable analyses were performed to explore associated risk factors and concordance of HPV infections across sites.

RESULTS: In total, 315 FSWs participated in the study with a mean age of 30-6.5 years. The prevalence of any HPV infection was 88% in the vulva, 84% in the cervix, 75% in the anus and 24% in the oral cavity. HPV 35 was the most prevalent and concordant high-risk type in the four sites. The risk factors for HPV infection by anatomic site varied.

CONCLUSION: This large study showed a high prevalence and concordance of HPV infections of cervical, vulval, oral and anal HPV among FSWs in Nigeria. The potential to acquire and transmit HPV is high in this population, and we highlighted the urgency to protect young women through HPV vaccination.

PMID:35353833 | DOI:10.1371/journal.pone.0265269

PLoS One. 2022 Mar 30;17(3):e0261056. doi: 10.1371/journal.pone.0261056. eCollection 2022.

ABSTRACT

The relationship between nature contact and mental well-being has received increasing attention in recent years. While a body of evidence has accumulated demonstrating a positive relationship between time in nature and mental well-being, there have been few studies comparing this relationship in different locations over long periods of time. In this study, we analyze over 1.5 million tweets to estimate a happiness benefit, the difference in expressed happiness between in- and out-of-park tweets, for the 25 largest cities in the US by population. People write happier words during park visits when compared with non-park user tweets collected around the same time. While the words people write are happier in parks on average and in most cities, we find considerable variation across cities. Tweets are happier in parks at all times of the day, week, and year, not just during the weekend or summer vacation. Across all cities, we find that the happiness benefit is highest in parks larger than 100 acres. Overall, our study suggests the happiness benefit associated with park visitation is on par with US holidays such as Thanksgiving and New Year’s Day.

PMID:35353831 | DOI:10.1371/journal.pone.0261056

PLoS One. 2022 Mar 30;17(3):e0262722. doi: 10.1371/journal.pone.0262722. eCollection 2022.

ABSTRACT

Note that identifying Mild Cognitive Impairment (MCI) is crucial to early detection and diagnosis of Alzheimer’s disease (AD). This work explores how classification features and experimental algorithms influence classification performances on the ADNI database. Based on structural Magnetic Resonance Images (sMRI), two features including gray matter (GM) volume and lateralization index (LI) are firstly extracted through hypothesis testing. Afterward, several classifier algorithms including Random Forest (RF), Decision Tree (DT), K-Nearest Neighbor(KNN) and Support Vector Machine (SVM) with RBF kernel, Linear kernel or Polynomial kernel are established to realize binary classification among Normal Control (NC), Early Mild Cognitive Impairment (EMCI), Late Mild Cognitive Impairment (LMCI) and AD groups. The main experimental results are as follows. (1) The classification performance in the feature of LI is poor compared with those in the feature of GM volume or the combined feature of LI and GM volume, i.e., the classification accuracies in the feature of LI are relatively low and unstable for most classifier models and subject groups. (2) Comparing with the classification performances in the feature of GM volume and the combined feature of LI and GM volume, the classification accuracy of NC group versus AD group is relatively stable for different classifier models, moreover, the accuracy of AD group versus NC group is almost the highest, with the most classification accuracy of 98.0909%. (3) For different subject groups, the SVM classifier algorithm with Polynomial kernel and the KNN classifier algorithm show relatively stable and high classification accuracy, while DT classifier algorithm shows relatively unstable and lower classification accuracy. (4) Except the groups of EMCI versus LMCI and NC versus EMCI, the classification accuracies are significantly enhanced by emerging the LI into the original feature of GM volume, with the maximum accuracy increase of 5.6364%. These results indicate that various factors of subject data, feature types and experimental algorithms influence classification performances remarkably, especially the newly introduced feature of LI into the feature of GM volume is helpful to improve classification results in some certain extent.

PMID:35353825 | DOI:10.1371/journal.pone.0262722

PLoS Genet. 2022 Mar 30;18(3):e1010129. doi: 10.1371/journal.pgen.1010129. Online ahead of print.

ABSTRACT

Over 1,500 variants in the ABCA4 locus cause phenotypes ranging from severe, early-onset retinal degeneration to very late-onset maculopathies. The resulting ABCA4/Stargardt disease is the most prevalent Mendelian eye disorder, although its underlying clinical heterogeneity, including penetrance of many alleles, are not well-understood. We hypothesized that a share of this complexity is explained by trans-modifiers, i.e., variants in unlinked loci, which are currently unknown. We sought to identify these by performing exome sequencing in a large cohort for a rare disease of 622 cases and compared variation in seven genes known to clinically phenocopy ABCA4 disease to cohorts of ethnically matched controls. We identified a significant enrichment of variants in 2 out of the 7 genes. Moderately rare, likely functional, variants, at the minor allele frequency (MAF) <0.005 and CADD>25, were enriched in ROM1, where 1.3% of 622 patients harbored a ROM1 variant compared to 0.3% of 10,865 controls (p = 2.41E04; OR 3.81 95% CI [1.77; 8.22]). More importantly, analysis of common variants (MAF>0.1) identified a frequent haplotype in PRPH2, tagged by the p.Asp338 variant with MAF = 0.21 in the matched general population that was significantly increased in the patient cohort, MAF 0.25, p = 0.0014. Significant differences were also observed between ABCA4 disease subgroups. In the late-onset subgroup, defined by the hypomorphic p.Asn1868Ile variant and including c.4253+43G>A, the allele frequency for the PRPH2 p.Asp338 variant was 0.15 vs 0.27 in the remaining cohort, p = 0.00057. Known functional data allowed suggesting a mechanism by which the PRPH2 haplotype influences the ABCA4 disease penetrance. These associations were replicated in an independent cohort of 408 patients. The association was highly statistically significant in the combined cohorts of 1030 cases, p = 4.00E-05 for all patients and p = 0.00014 for the hypomorph subgroup, suggesting a substantial trans-modifying role in ABCA4 disease for both rare and common variants in two unlinked loci.

PMID:35353811 | DOI:10.1371/journal.pgen.1010129