Tag: pubmed

PLoS One. 2021 Sep 8;16(9):e0256831. doi: 10.1371/journal.pone.0256831. eCollection 2021.

ABSTRACT

Current approach for the detection of cancer is based on identifying genetic mutations typical to tumor cells. This approach is effective only when cancer has already emerged, however, it might be in a stage too advanced for effective treatment. Cancer is caused by the continuous accumulation of mutations; is it possible to measure the time-dependent information of mutation accumulation and predict the emergence of cancer? We hypothesize that the mutation history derived from the tandem repeat regions in blood-derived DNA carries information about the accumulation of the cancer driver mutations in other tissues. To validate our hypothesis, we computed the mutation histories from the tandem repeat regions in blood-derived exomic DNA of 3874 TCGA patients with different cancer types and found a statistically significant signal with specificity ranging from 66% to 93% differentiating Glioblastoma patients from other cancer patients. Our approach and findings offer a new direction for future cancer prediction and early cancer detection based on information derived from blood-derived DNA.

PMID:34495981 | DOI:10.1371/journal.pone.0256831

PLoS One. 2021 Sep 8;16(9):e0256980. doi: 10.1371/journal.pone.0256980. eCollection 2021.

ABSTRACT

BACKGROUND: A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.

METHODOLOGY: This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.

RESULTS: In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.

CONCLUSIONS: This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.

PMID:34495988 | DOI:10.1371/journal.pone.0256980

PLoS One. 2021 Sep 8;16(9):e0256018. doi: 10.1371/journal.pone.0256018. eCollection 2021.

ABSTRACT

BACKGROUND: The Penn Alcohol Craving Scale (PACS) is an instrument with good psychometric properties that is widely used to assess alcohol craving. Based on the assumption that the experience of craving is independent of substance type, the Polish version of the PACS was modified to measure drug craving, thus creating the Penn Drug Craving Scale (PDCS). The analyses presented in the paper aim to verify the hypothesis that the PDCS has a unidimensional structure, is highly reliable and features longitudinal measurement invariance.

METHODS: The research was conducted in 14 inpatient and 13 outpatient randomly selected facilities that provide psychosocial therapy to people with substance use disorder (SUD) in Poland, during June 2018 -July 2019. The data used for the analyses came from 282 patients diagnosed on the basis of ICD-10 criteria (F11.2-F19.2). The paper presents analyses with the application of: [1] confirmatory factor analysis (CFA) conducted on the basis of a polychoric correlation matrix and the WLSMV estimator; [2] a reliability estimate using Cronbach’s alpha and coefficient omega; [3] verification of longitudinal measurement invariance between the beginning and end of therapy; [4] evaluation of criterion validity; [5] normalisation of the raw scores.

RESULTS: The CFA results confirmed a unidimensional PDCS structure (RMSEA = 0.047, 95% CI: 0.000-0.103; CFI = 0.999; TLI = 0.999) and a high reliability of the scale (ω = 0.93). Moreover, a strict longitudinal measurement invariance of the instrument was confirmed.

CONCLUSIONS: Accurate assessment of craving is possible only with valid and reliable instruments. Therefore, the psychometric properties of the PDCS were verified based on the latest statistical approaches. The scale is a valid and highly reliable tool featuring longitudinal measurement invariance and can be usefully used for research and clinical purposes. Thus, the Polish version of the PACS has been modified and successfully applied to the population of people with SUD.

PMID:34495966 | DOI:10.1371/journal.pone.0256018

PLoS Med. 2021 Sep 8;18(9):e1003727. doi: 10.1371/journal.pmed.1003727. Online ahead of print.

ABSTRACT

BACKGROUND: Seasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016.

METHODS AND FINDINGS: Case-control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3-59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%-50.9% and 38.9%-46.9% of controls and cases, respectively, were male. In all 7 individual case-control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29-42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: OR 0.90 (95% CI: 0.79, 0.96; p < 0.001) and 0.59 (95% CI: 0.34, 0.74; p < 0.001) for SMC 0-28 days and 29-42 days ago, respectively. Potential limitations include the possibility of residual confounding due to an association between exposure to malaria and access to SMC, or differences in access to SMC between patients attending a clinic and community controls; however, neighbourhood matching of cases and controls, and covariate adjustment, attempted to control for these aspects, and the observed decline in protection over time, consistent with expected trends, argues against a major bias from these sources.

CONCLUSIONS: SMC administered as part of routine national malaria control activities provided a very high level of personal protection against clinical malaria over 28 days post-treatment, similar to the efficacy observed in clinical trials. The case-control design used in this study can be used at intervals to ensure SMC treatments remain effective.

PMID:34495978 | DOI:10.1371/journal.pmed.1003727

PLoS One. 2021 Sep 8;16(9):e0255519. doi: 10.1371/journal.pone.0255519. eCollection 2021.

ABSTRACT

Advances in remote sensing and machine learning enable increasingly accurate, inexpensive, and timely estimation of poverty and malnutrition indicators to guide development and humanitarian agencies’ programming. However, state of the art models often rely on proprietary data and/or deep or transfer learning methods whose underlying mechanics may be challenging to interpret. We demonstrate how interpretable random forest models can produce estimates of a set of (potentially correlated) malnutrition and poverty prevalence measures using free, open access, regularly updated, georeferenced data. We demonstrate two use cases: contemporaneous prediction, which might be used for poverty mapping, geographic targeting, or monitoring and evaluation tasks, and a sequential nowcasting task that can inform early warning systems. Applied to data from 11 low and lower-middle income countries, we find predictive accuracy broadly comparable for both tasks to prior studies that use proprietary data and/or deep or transfer learning methods.

PMID:34495951 | DOI:10.1371/journal.pone.0255519

PLoS Biol. 2021 Sep 8;19(9):e3001385. doi: 10.1371/journal.pbio.3001385. Online ahead of print.

ABSTRACT

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or live Escherichia coli. PTL did not occur in LPS challenged rhesus macaques, while E. coli-infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli-infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in the E. coli group compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.

PMID:34495952 | DOI:10.1371/journal.pbio.3001385

Ying Yong Sheng Tai Xue Bao. 2020 Aug;31(8):2500-2506. doi: 10.13287/j.1001-9332.202008.008.

ABSTRACT

Tilia amurensis is one of (co-)dominant species in the broadleaved-conifer mixed forest in Northeast China, with high commercial and nectariferous values. We estimated the quantity of nectar secretion from individual trees to population or stand levels based on observation and statistical analysis. An equation for individual-tree nectar secretion was established, which was used to estimate nectar quantity at the stand level. We analyzed the relationships between nectar secretion and basal area or stem volume. The booming time for single flower was in average 6-8 days, with a nectar secretion period of about five days. The quantity for the entire period was estimated at 8.58 mg per flower. Sugar contents in the nectar, average 37.7%, showed diurnal variations, being high in the mid-noon and low in the early morning and late afternoon. The average diameter (DBH) of the species was approximately 40 cm, which was estimated to possess as much as 18×10⁴ single flowers and 1.56 kg (or pure sugar 0.588 kg) of nectar. At the stand level, the nectar production potential was 79-147 kg (or 0.0686-0.1285 m³, pure sugar 29.78-55.42 kg) per hectare. There was a close correlation between nectar quantity and basal area or timber volume at both individual and stand levels, which could be used to estimate the nectar quantity for macro-scale forest area based on inventory data.

PMID:34494770 | DOI:10.13287/j.1001-9332.202008.008

Ying Yong Sheng Tai Xue Bao. 2020 Aug;31(8):2663-2670. doi: 10.13287/j.1001-9332.202008.009.

ABSTRACT

The policy of natural forest protection project (NFPP) is of great significance to the protection and restoration of natural forests. It remains unclear about how to play the role of NFPP transfer payment in forest ecological benefits. Based on panel data of “China Forestry Statistical Yearbook” from 2011 to 2017, we used forest management area and forest tending area as indicators to measure forest ecological benefits, and used spatial lag model and intermediary effect model to analyze the impacts of the transfer payment funds of NFPP on the forest ecological benefits in key state-owned forest areas. The results showed that forest ecological benefits in the key state-owned forest areas in the second phase of NFPP had improved year by year. There was a significant spatial spillover effect of forest ecological benefits of forestry bureaus. The transfer funds of NFPP had a significant positive effect on the ecological benefits of forest resources in key state-owned forest areas. There was a partial intermediary effect between the improvement of human capital and the establishment of first-line management and protection stations. The central government should increase investment in the transfer payment funds of NFPP. Forest administrations should increase the proportion of funds used in improving human capital and establishing first-line management and protection stations.

PMID:34494789 | DOI:10.13287/j.1001-9332.202008.009

Aust J Rural Health. 2021 Sep 8. doi: 10.1111/ajr.12778. Online ahead of print.

ABSTRACT

INTRODUCTION: Rural-urban health inequities, exacerbated by deprivation and ethnicity, have been clearly described in the international literature. To date, the same inequities have not been as clearly demonstrated in Aotearoa New Zealand despite the lower socioeconomic status and higher proportion of Māori living in rural towns. This is ascribed by many health practitioners, academics and other informed stakeholders to be the result of the definitions of ‘rural’ used to produce statistics.

AIMS: To outline a protocol to produce a ‘fit-for-health purpose’ rural-urban classification for analysing national health data. The classification will be designed to determine the magnitude of health inequities that have been obscured by use of inappropriate rural-urban taxonomies.

METHODS: This protocol paper outlines our proposed mixed-methods approach to developing a novel Geographic Classification for Health. In phase 1, an agreed set of community attributes will be used to modify the new Statistics New Zealand Urban Accessibility Classification into a more appropriate classification of rurality for health contexts. The Geographic Classification for Health will then be further developed in an iterative process with stakeholders including rural health researchers and members of the National Rural Health Advisory Group, who have a comprehensive ‘on the ground’ understanding of Aotearoa New Zealand’s rural communities and their attendant health services. This protocol also proposes validating the Geographic Classification for Health using general practice enrolment data. In phase 2, the resulting Geographic Classification for Health will be applied to routinely collected data from the Ministry of Health. This will enable current levels of rural-urban inequity in health service access and outcomes to be accurately assessed and give an indication of the extent to which older classifications were masking inequities.

PMID:34494690 | DOI:10.1111/ajr.12778

Alzheimers Dement. 2021 Sep 8. doi: 10.1002/alz.12447. Online ahead of print.

ABSTRACT

INTRODUCTION: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer’s disease (AD).

METHODS: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.

RESULTS: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.

DISCUSSION: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

PMID:34494715 | DOI:10.1002/alz.12447