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(searched for: doi:10.1371/*)
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Arkadiusz Sadowski, Monika Małgorzata Wojcieszak
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222576

Abstract: One of the trends in today’s tourism sector is the development of environmentally-friendly tourism activities which rely on natural resources of cultural heritage and on biodiversity. This is definitely the case for agritourism, a form of rural tourism. The purpose of this paper is to identify the development aspects of Polish agritourism with particular emphasis on natural and cultural attractiveness. To demonstrate the relationship between agritourism activities of Polish farms and the cultural and natural attractiveness, the Hellwig’s synthetic development indicator was used. As shown by research, the cultural and natural attractiveness of a destination is an important exogenous development factor. Another finding was that the intensified efforts undertaken by the farmers to access EU funds were not focused on areas with valuable natural or cultural resources and an untapped agritourism potential; instead, they were oriented at regions dominated by semi-subsistence or family farms. For a large part of farmers, the new form of support is about to become a source of additional incomes.
Mariko Carey, Jamie Bryant, Alison Zucca, Alix Hall, Alice Grady, Sophie Dilworth, Kerry Peek
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222107

Abstract: There is poor uptake of psychosocial interventions offered to people with cancer who record high scores on distress screening scales. Intervention uptake may be influenced by a mismatch between consumer (bottom-up) and professional (top-down) paradigms of wellbeing. The current research aims to compare cancer survivors’ ‘self-judgements’ about their levels of anxiety, depression and stress, to classifications derived via a professional-driven measure, the Depression, Anxiety and Stress Scale (DASS-21). A cross-sectional study was undertaken with haematological cancer survivors recruited from three population-based cancer registries in Australia. Consenting participants were mailed a questionnaire package; and non-responders received a second questionnaire package after 3-weeks and a reminder call after 6-weeks. The consumer-driven perspective was assessed via three separate single items asking survivors to self-classify their levels of anxiety, depression and stress over the past week on a scale from ‘normal’ to ‘extremely severe’. The professional-driven classification was assessed via the DASS-21. Kappa statistics were used to assess agreement between consumer- and professional-driven measures. Of 2,971 eligible haematological cancer survivors, 1,239 (42%) provided written consent and were mailed a questionnaire package. Of these, 984 (79%) returned a completed questionnaire. The simple kappa for agreement between the DASS-21 and self-classified measures for anxiety was 0.47 (95% CI: 0.39 to 0.54, p<0.0001). The weighted kappa for agreement between the DASS-21 and self-classified measures of depression was 0.60 (95% CI: 0.53 to 0.67, p<0.0001) and for measures of stress was 0.51 (95% CI: 0.44 to 0.59, p<0.0001). Moderate agreement between self-classification and professional-driven assessments was found. The value of screening is predicated on the assumption that those with identified needs will be offered and take up services that will benefit them. Our results suggest that to improve the utility of distress screening it may be important to include assessment of survivor views about their symptoms.
Stefanny Christie Monteiro Titon, Braz Titon, Adriana Maria Giorgi Barsotti, Fernando Ribeiro Gomes, Vania Regina Assis
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222856

Abstract: Immune responses have been mostly studied at a specific time in anuran species. However, time-changes related to immunomodulation associated with glucocorticoid (GC) alterations following stressors and GC treatment are complex. The present study describes time-related changes in immune response and corticosterone (CORT) plasma levels following restraint challenge, short, mid and long-term captivity, and CORT exogenous administration by transdermal application (TA) in Rhinella ornata toads. We observed increased neutrophil: lymphocyte ratios after restraint challenge and CORT TA, without changes following short and mid-term captivity. Plasma bacterial killing ability was sustained in all treatments, except long-term captivity, with decreased values after 90 days under such conditions. Phagocytic activity of peritoneal cells increased after mid-term captivity, and the phytohemagglutinin swelling response was impaired in those animals treated with CORT TA for 20 consecutive days. Plasma CORT levels increased or were sustained after restraint challenge (depending on initial values), decreased following mid and long-term captivity (for those animals showing high CORT in the field) and increased after 20 days of CORT TA. By performing assessments of time-changes in immune processes and CORT plasma levels in R. ornata, we demonstrate immuno-enhancing effects following restraint, short and mid-term stressors, while long-term stressors and CORT TA promoted immunosuppression in these toads.
Catriona Waitt, Catherine Orrell, Stephen Walimbwa, Yashna Singh, Kenneth Kintu, Bryony Simmons, Julian Kaboggoza, Mary Sihlangu, Julie-Anne Coombs, Thoko Malaba, et al.
Published: 20 September 2019
PLOS Medicine, Volume 16; doi:10.1371/journal.pmed.1002895

Abstract: The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3). In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28–36 weeks of gestation, age 26 (19–42), weight 67kg (45–119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3–8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum. Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy. clinicaltrials.gov NCT02245022
Erena A. Edae, Matthew N. Rouse
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0215492

Abstract: Many disease resistance genes that have been transferred from wild relatives to cultivated wheat have played a significant role in wheat production worldwide. Ae. umbellulata is one of the species within the genus Aegilops that have been successfully used as sources of resistance genes to leaf rust, stem rust and powdery mildew. The objectives of the current work was to validate the map position of a major QTL that confers resistance to the stem rust pathogen races Ug99 (TTKSK) and TTTTF with an independent bi-parental mapping population and to refine the QTL region with a bulk segregant analysis approach. Two F2 bi-parental mapping populations were developed from stem rust resistant Ae. umbellulata accessions (PI 298905 and PI 5422375) and stem rust susceptible accessions (PI 542369 and PI 554395). Firstly, one of the two populations was used to map the chromosome location of the resistance gene. Later on, the 2nd population was used to validate the chromosome location in combination with a bulk segregant analysis approach. For the bulk segregant analysis, RNA was extracted from a bulk of leaf tissues of 12 homozygous resistant F3 families, and a separate bulk of 11 susceptible homozygous F3 families derived from the PI 5422375 and PI 554395 cross. The RNA samples of the two bulks and the two parents were sequenced for SNPs identification. Stem rust resistance QTL was validated on chromosome 2U of Ae. umbellulata in the same region in both populations. With bulk segregant analysis, the QTL position was delimited within 3.2 Mbp. Although there were a large number of genes in the orthologous region of the detected QTL on chromosome 2D of Ae. tauschii, we detected only two Ae. umbellulata NLR genes which can be considered as a potential candidate genes.
Shikha Dixit, Vinod Kumar Jangid, Anita Grover
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222530

Abstract: Quantitative real-time PCR (qRT-PCR) is an efficient method to estimate the gene expression levels but the accuracy of its result largely depends on the stability of the reference gene. Many studies have reported considerable variation in the expression of reference genes (RGs) in different tissue and conditions. Therefore, screening for appropriate RGs with stable expression is crucial for functional analysis of the target gene. Two closely related crucifers Brassica juncea (cultivated) and Camelina sativa (wild) respond differently towards various abiotic and biotic stress where C. sativa exhibits higher tolerance to various stress. Comparative gene expression analysis of the target genes between two such species is the key approach to understand the mechanism of a plant’s response to stress. However, using an unsuitable RG can lead to misinterpretation of expression levels of the target gene in such studies. In this investigation, the stability of seven candidate RGs including traditional housekeeping genes (HKGs) and novel candidate RGs were identified across diverse sample sets of B. juncea and C. sativa representing- hormone treated, wounded, Alternaria brassicae inoculated and combination treated samples (exogenous hormone treatment followed by A. brassicae inoculation). In this investigation, we identified stable RGs in both the species and the most suitable RGs to perform an unbiased comparative gene expression analysis between B. juncea and C. sativa. Results revealed that TIPS41 and PP2A were identified as the overall best performing RGs in both the species. However, the most suitable RG for each sample subset representing different condition must be individually selected. In Hormone treated and wounded samples TIPS41 expressed stably in both the species and in A. brassicae inoculated and combination treatment performance of PP2A was the best. In this study, for the first time, we have identified and validated stable reference gene in C. sativa for accurate normalization of gene expression data.
Tiago Jessé Souza De Lima, Cicero Roberto Pereira, Ana Raquel Rosas Torres, Luana Elayne Cunha De Souza, Iara Maribondo Albuquerque
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222874

Abstract: Black and poor people are more frequently convicted of committing crimes. However, the specific role played by skin color and social class in convicting a person has yet to be clarified. This article aims to elucidate this issue by proposing that belonging to a lower social class facilitates the conviction of black targets and that this phenomenon is because information about social class dissimulates racial bias. Study 1 (N = 160) demonstrated that information about belonging to the lower classes increases agreement with a criminal suspect being sentenced to prison only when described as being black. Furthermore, Studies 2 (N = 170) and 3 (N = 174) show that the anti-prejudice norm inhibits discrimination against the black target when participants were asked to express individual racial prejudice, but not when they expressed cultural racial prejudice. Finally, Study 4 (N = 134) demonstrated that lower-class black targets were discriminated against to a greater degree when participants expressed either individual or cultural prejudice and showed that this occurs when racial and class anti-prejudice norms are salient. The results suggest that social class negatively affects judgments of black targets because judgment based on lower class mitigates the racist motivation of discrimination.
Meagan A. Bechel, Adam R. Pah, Hanyu Shi, Sanjay Mehrotra, Stephen D. Persell, Shayna Weiner, Richard G. Wunderink, Luís A. Nunes Amaral, Curtis H. Weiss
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222826

Abstract: Despite its efficacy, low tidal volume ventilation (LTVV) remains severely underutilized for patients with acute respiratory distress syndrome (ARDS). Physician under-recognition of ARDS is a significant barrier to LTVV use. We propose a computational method that addresses some of the limitations of the current approaches to automated measurement of whether ARDS is recognized by physicians. To quantify patient and physician factors affecting physicians’ tidal volume selection and to build a computational model of physician recognition of ARDS that accounts for these factors. In this cross-sectional study, electronic health record data were collected for 361 ARDS patients and 388 non-ARDS hypoxemic (control) patients in nine adult intensive care units at four hospitals between June 24 and December 31, 2013. Standardized tidal volumes (mL/kg predicted body weight) were chosen as a proxy for physician decision-making behavior. Using data-science approaches, we quantified the effect of eight factors (six severity of illness, two physician behaviors) on selected standardized tidal volumes in ARDS and control patients. Significant factors were incorporated in computational behavioral models of physician recognition of ARDS. Hypoxemia severity and ARDS documentation in physicians’ notes were associated with lower standardized tidal volumes in the ARDS cohort. Greater patient height was associated with lower standardized tidal volumes (which is already normalized for height) in both ARDS and control patients. The recognition model yielded a mean (99% confidence interval) physician recognition of ARDS of 22% (9%-42%) for mild, 34% (19%-49%) for moderate, and 67% (41%-100%) for severe ARDS. In this study, patient characteristics and physician behaviors were demonstrated to be associated with differences in ventilator management in both ARDS and control patients. Our model of physician ARDS recognition measurement accounts for these clinical variables, providing an electronic approach that moves beyond relying on chart documentation or resource intensive approaches.
Neire Niara Ferreira De Araujo, Hui Tzu Lin-Wang, Juliana De Freitas Germano, Pedro Silvio Farsky, Andre Feldman, Fabio Henrique Rossi, Nilo Mitsuru Izukawa, Maria De Lourdes Higuchi, Felicio Savioli Neto, Mario Hiroyuki Hirata, et al.
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222782

Abstract: Abdominal aortic aneurysm (AAA) is a pathological enlargement of infrarenal aorta close to the aortic bifurcation, and it is an important cause of mortality in the elderly. Therefore, the biomarker identification for early diagnosis is of great interest for clinical benefit. It is known that microRNAs (miRNAs) have important roles via target genes regulation in many diseases. This study aimed to identify miRNAs and their target genes involved in the pathogenesis of AAA. Tissue samples were obtained from patients who underwent AAA surgery and from organ donors (control group). Quantitative PCR Array was applied to assess 84 genes and 384 miRNAs aiming to identify differentially expressed targets (AAA n = 6, control n = 6), followed by validation in a new cohort (AAA n = 18, control n = 6) by regular qPCR. The functional interaction between validated miRNAs and target genes was performed by the Ingenuity Pathway Analysis (IPA) software. The screening cohort assessed by PCR array identified 10 genes and 59 miRNAs differentially expressed (≥2-fold change, p<0.05). Among these, IPA identified 5 genes and 9 miRNAs with paired interaction. ALOX5, PTGIS, CX3CL1 genes, and miR-193a-3p, 125b-5p, 150-5p maintained a statistical significance in the validation cohort. IPA analysis based on the validated genes and miRNAs revealed that eicosanoid and metalloproteinase/TIMP synthesis are potentially involved in AAA. Paired interactions of differentially expressed ALOX5, PTGIS, CX3CL1 genes, and miR-193b-3p, 125b-5p, 150-5p revealed a potentially significant role of the eicosanoid synthesis and metalloproteinase/TIMP pathways in the AAA pathogenesis.
Tatiana Jarret, Anika Stockert, Sonja A. Kotz, Barbara Tillmann
Published: 20 September 2019
PLOS ONE, Volume 14; doi:10.1371/journal.pone.0222385

Abstract: Previous research associated the left inferior frontal cortex with implicit structure learning. The present study tested patients with lesions encompassing the left inferior frontal gyrus (LIFG; including Brodmann areas 44 and 45) to further investigate this cognitive function, notably by using non-verbal material, implicit investigation methods, and by enhancing potential remaining function via dynamic attending. Patients and healthy matched controls were exposed to an artificial pitch grammar in an implicit learning paradigm to circumvent the potential influence of impaired language processing. Patients and healthy controls listened to pitch sequences generated within a finite-state grammar (exposure phase) and then performed a categorization task on new pitch sequences (test phase). Participants were not informed about the underlying grammar in either the exposure phase or the test phase. Furthermore, the pitch structures were presented in a highly regular temporal context as the beneficial impact of temporal regularity (e.g. meter) in learning and perception has been previously reported. Based on the Dynamic Attending Theory (DAT), we hypothesized that a temporally regular context helps developing temporal expectations that, in turn, facilitate event perception, and thus benefit artificial grammar learning. Electroencephalography results suggest preserved artificial grammar learning of pitch structures in patients and healthy controls. For both groups, analyses of event-related potentials revealed a larger early negativity (100–200 msec post-stimulus onset) in response to ungrammatical than grammatical pitch sequence events. These findings suggest that (i) the LIFG does not play an exclusive role in the implicit learning of artificial pitch grammars, and (ii) the use of non-verbal material and an implicit task reveals cognitive capacities that remain intact despite lesions to the LIFG. These results provide grounds for training and rehabilitation, that is, learning of non-verbal grammars that may impact the relearning of verbal grammars.
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