Nevin Manimala

PLoS One. 2021 Jul 30;16(7):e0255282. doi: 10.1371/journal.pone.0255282. eCollection 2021.

ABSTRACT

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use and more cost-effective method for administration of vaccines when compared to the needle and syringe. Since MAPs deliver vaccine to the dermis and epidermis, a degree of local immune response at the site of application is expected. In a phase 1 clinical trial (ACTRN 12618000112268), the Vaxxas high-density MAP (HD-MAP) was used to deliver a monovalent, split inactivated influenza virus vaccine into the skin. HD-MAP immunisation led to significantly enhanced humoral responses on day 8, 22 and 61 compared with IM injection of a quadrivalent commercial seasonal influenza vaccine (Afluria Quadrivalent®). Here, the aim was to analyse cellular responses to HD-MAPs in the skin of trial subjects, using flow cytometry and immunohistochemistry. HD-MAPs were coated with a split inactivated influenza virus vaccine (A/Singapore/GP1908/2015 [H1N1]), to deliver 5 μg haemagglutinin (HA) per HD-MAP. Three HD-MAPs were applied to the volar forearm (FA) of five healthy volunteers (to achieve the required 15 μg HA dose), whilst five control subjects received three uncoated HD-MAPs (placebo). Local skin response was recorded for over 61 days and haemagglutination inhibition antibody titres (HAI) were assessed on days 1, 4, 8, 22, and 61. Skin biopsies were taken before (day 1), and three days after HD-MAP application (day 4) and analysed by flow-cytometry and immunohistochemistry to compare local immune subset infiltration. HD-MAP vaccination with 15 μg HA resulted in significant HAI antibody titres compared to the placebo group. Application of uncoated placebo HD-MAPs resulted in mild erythema and oedema in most subjects, that resolved by day 4 in 80% of subjects. Active, HA-coated HD-MAP application resulted in stronger erythema responses on day 4, which resolved between days 22-61. Overall, these erythema responses were accompanied by an influx of immune cells in all subjects. Increased cell infiltration of CD3+, CD4+, CD8+ T cells as well as myeloid CD11b+ CD11c+ and non-myeloid CD11b- dendritic cells were observed in all subjects, but more pronounced in active HD-MAP groups. In contrast, CD19+/CD20+ B cell counts remained unchanged. Key limitations include the use of an influenza vaccine, to which the subjects may have had previous exposure. Different results might have been obtained with HD-MAPs inducing a primary immune response. In conclusion, influenza vaccine administered to the forearm (FA) using the HD-MAP was well-tolerated and induced a mild to moderate skin response with lymphocytic infiltrate at the site of application.

PMID:34329337 | DOI:10.1371/journal.pone.0255282

PLoS One. 2021 Jul 30;16(7):e0255124. doi: 10.1371/journal.pone.0255124. eCollection 2021.

ABSTRACT

OBJECTIVE: A screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women.

METHODS: This cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18-29, 30+ years), HIV status, Pap smear results and tested for statistical significance.

RESULTS: Of 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear.

CONCLUSION: South African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women <30 years, both populations found to have high prevalence of HR-HPV. HPV-based primary screening from 25 years could improve outcomes.

PMID:34329334 | DOI:10.1371/journal.pone.0255124

PLoS One. 2021 Jul 30;16(7):e0255327. doi: 10.1371/journal.pone.0255327. eCollection 2021.

ABSTRACT

BACKGROUND: Delayed tuberculosis diagnosis and treatment increase morbidity, mortality, expenditure, and transmission in the community. Early diagnosis and initiation of treatment are essential for effective TB control. Therefore, the main objective of this study was to assess the magnitude and factors associated with patient delay among tuberculosis patients in Gamo Zone, Southern Ethiopia.

METHODS: A cross-sectional study was conducted in Gamo Zone, Southern Ethiopia from February to April 2019. Fifteen health facilities of the study area were selected randomly and 255 TB patients who were ≥18 years of age were included. Data were collected using a questionnaire through face-to-face interviews and analyzed using SPSS version 20.0. Patient delay was analyzed using the median as the cut-off value. Multivariable logistic regression analysis was fitted to identify factors associated with patient delay. A p-value of ≤ 0.05 with 95% CI was considered to declare a statistically significant association.

RESULTS: The median (inter-quartile range) of the patient delay was 30 (15-60) days. About 56.9% of patients had prolonged patients’ delay. Patient whose first contact were informal provider (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI] 1.29, 3.86), presenting with weight loss (AOR: 2.53; 95%CI: 1.35, 4.74) and fatigue (AOR: 2.38; 95%CI: 1.36, 4.17) and body mass index (BMI) categories of underweight (AOR: 1.74; 95%CI: 1.01, 3.00) were independently associated with increased odds of patient delay. However, having good knowledge about TB (AOR: 0.44; 95% CI: 0.26, 0.76) significantly reduce patients’ delay.

CONCLUSION: In this study, a significant proportion of patients experienced more than the acceptable level for the patient delay. Knowledge about TB, the first action to illness, presenting symptoms, and BMI status were identified factors associated with patient delay. Hence, raising public awareness, regular training, and re-training of private and public healthcare providers, involving informal providers, and maintenance of a high index of suspicion for tuberculosis in the vulnerable population could reduce long delays in the management of TB.

PMID:34329333 | DOI:10.1371/journal.pone.0255327

PLoS One. 2021 Jul 30;16(7):e0255532. doi: 10.1371/journal.pone.0255532. eCollection 2021.

ABSTRACT

The environmental footprint of courier, express, and parcel (CEP) logistics is significant and growing, owing to increased e-commerce. Consumer willingness to participate in the green logistics of CEPs, however, has been understudied. This study addresses this knowledge gap by surveying 155 Chinese consumers about their willingness to participate in CEP green logistics. Additionally, this research identifies some technical issues with previous survey research. Three main factors were extracted after the data were tested for reliability and validity using exploratory factor analysis with principal axis factor extraction and confirmatory factor analysis with diagonally weighted least squares. Consumer willingness is positively correlated with economic (8 items), operational (3 items), and social (3 items) factors, with a statistical significance of p < 0.001. Of all the factors, the strongest correlation, 0.67 (95% CI = 0.57, 0.75; p < 0.001; N = 155), exists between economic factors and consumer willingness. The results of a multinomial logistic regression analysis suggest that all consumers are highly unlikely to participate in economic factors, while they are highly likely to positively commit to operational and social factors. Therefore, it is recommended that the government provides monetary incentives to CEP companies to adopt green logistics, such as tax reductions and subsidies, to reduce the costs of green logistics. Meanwhile, the CEP industry could provide some direct and indirect incentives to consumers to re-use, recycle, and share materials, and to spend time learning about express enterprises’ green logistics, to increase consumer participation in economic factors.

PMID:34329331 | DOI:10.1371/journal.pone.0255532

PLoS One. 2021 Jul 30;16(7):e0254785. doi: 10.1371/journal.pone.0254785. eCollection 2021.

ABSTRACT

The association between physical appearance and income has been of central interest in social science. However, most previous studies often measured physical appearance using classical proxies from subjective opinions based on surveys. In this study, we use novel data, called CAESAR, which contains three-dimensional (3D) whole-body scans to mitigate possible reporting and measurement errors. We demonstrate the existence of significant nonclassical reporting errors in the reported heights and weights by comparing them with measured counterparts, and show that these discrete measurements are too sparse to provide a complete description of the body shape. Instead, we use a graphical autoencoder to obtain intrinsic features, consisting of human body shapes directly from 3D scans and estimate the relationship between body shapes and family income. We also take into account a possible issue of endogenous body shapes using proxy variables and control functions. The estimation results reveal a statistically significant relationship between physical appearance and family income and that these associations differ across genders. This supports the hypothesis on the physical attractiveness premium in labor market outcomes and its heterogeneity across genders.

PMID:34329322 | DOI:10.1371/journal.pone.0254785

PLoS One. 2021 Jul 30;16(7):e0253043. doi: 10.1371/journal.pone.0253043. eCollection 2021.

ABSTRACT

Studies published over the last decade have reached contrasting conclusions regarding the impact of climate change on conflict among the Classic Maya (ca. 250-900 CE). Some researchers have argued that rainfall declines exacerbated conflict in this civilisation. However, other researchers have found that the relevant climate variable was increasing summer temperatures and not decreasing rainfall. The goal of the study reported here was to test between these two hypotheses. To do so, we collated annually-resolved conflict and climate data, and then subjected them to a recently developed Bayesian method for analysing count-based times-series. The results indicated that increasing summer temperature exacerbated conflict while annual rainfall variation had no effect. This finding not only has important implications for our understanding of conflict in the Maya region during the Classic Period. It also contributes to the ongoing discussion about the likely impact of contemporary climate change on conflict levels. Specifically, when our finding is placed alongside the results of other studies that have examined temperature and conflict over the long term, it is clear that the impact of climate change on conflict is context dependent.

PMID:34329320 | DOI:10.1371/journal.pone.0253043

Sci Rep. 2021 Jul 29;11(1):15408. doi: 10.1038/s41598-021-94516-7.

ABSTRACT

The ubiquity of smartphones, with their increasingly sophisticated array of sensors, presents an unprecedented opportunity for researchers to collect longitudinal, diverse, temporally-dense data about human behavior while minimizing participant burden. Researchers increasingly make use of smartphones for “digital phenotyping,” the collection and analysis of raw phone sensor and log data to study the lived experiences of subjects in their natural environments using their own devices. While digital phenotyping has shown promise in fields such as psychiatry and neuroscience, there are fundamental gaps in our knowledge about data collection and non-collection (i.e., missing data) in smartphone-based digital phenotyping. In this meta-study using individual-level data from six different studies, we examined accelerometer and GPS sensor data of 211 participants, amounting to 29,500 person-days of observation, using Bayesian hierarchical negative binomial regression with study- and user-level random intercepts. Sensitivity analyses including alternative model specification and stratified models were conducted. We found that iOS users had lower GPS non-collection than Android users. For GPS data, rates of non-collection did not differ by race/ethnicity, education, age, or gender. For accelerometer data, Black participants had higher rates of non-collection, but rates did not differ by sex, education, or age. For both sensors, non-collection increased by 0.5% to 0.9% per week. These results demonstrate the feasibility of using smartphone-based digital phenotyping across diverse populations, for extended periods of time, and within diverse cohorts. As smartphones become increasingly embedded in everyday life, the insights of this study will help guide the design, planning, and analysis of digital phenotyping studies.

PMID:34326370 | DOI:10.1038/s41598-021-94516-7

Sci Rep. 2021 Jul 29;11(1):15418. doi: 10.1038/s41598-021-93847-9.

ABSTRACT

Several studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT < 2 years, 2 ≤ MHT < 5 years, MHT ≥ 5 years. During the 9-year study period, a total of 4905 participants developed ESRD. The participants who had a history of MHT use were found to have a 30% reduced risk of developing ESRD. Results from the subgroup analyses were similar to that of the primary study. The findings in this study demonstrate the beneficial effects of MHT on the development of ESRD in postmenopausal women. Based on results, our study may offer suggestions for further studies to investigate the therapeutic options on kidney disease.

PMID:34326358 | DOI:10.1038/s41598-021-93847-9

Sci Rep. 2021 Jul 29;11(1):15431. doi: 10.1038/s41598-021-92176-1.

ABSTRACT

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.

PMID:34326355 | DOI:10.1038/s41598-021-92176-1

Pain. 2021 Jul 28. doi: 10.1097/j.pain.0000000000002415. Online ahead of print.

ABSTRACT

Efforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. The present study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194 839 adolescents and adults who initiated opioid prescription in 2010-2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17 582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60-120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12-1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1-30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.

PMID:34326295 | DOI:10.1097/j.pain.0000000000002415