julilili42/papers huggingface dataset:
“Progressing Backwards”: Rural Outsider Figures in Richard Jefferies, W.H. Hudson and Edward Thomas
2021-11-18

This paper explores representations of rural outsider figures in Richard Jefferies, W.H. Hudson and Edward Thomas. It begins by suggesting that there has been limited recognition of these authors before moving on to explore Raymond Williams' critique of various ways of representing the countryside that can be found in their writing: including the fetishisation of the past and the creation of an overly simplistic binary between country and city. Against this it is proposed that Williams' objection to texts that falsely idealise rural life may be seen to reflect a progress-oriented ideological bias, which in the context of the present environmental crisis might be viewed as problematic. This paper subsequently returns to these three authors in order to determine whether their representations of rural outsider figures can be seen to offer an indirect critique of the left's adoption of the capitalistic fantasy of progress, or whether they should indeed be viewed as a reactionary defence of a largely imaginary idealised past.
Microplastic Contamination in the Human Gastrointestinal Tract and Daily Consumables Associated with an Indonesian Farming Community
2021-11-19

Plastic is one of the most abundant pollutants in the environment. As a result of natural physical processes, large plastic waste is degraded into microsized particles (&lt;5 mm) called microplastics. Because of their size, abundance, and durability, microplastics are widely distributed in the environment, contaminating food and water intended for human consumption. The extent of microplastic contamination in the human body is still unclear because there are few studies concerning microplastic contamination in human specimens and, in most studies, data were collected from city dwellers. Despite having the fourth largest population and being the fourth largest plastic waste producer in the world and second largest plastic polluter in the ocean, there are currently no data with respect to microplastic exposure for the Indonesian population. Several studies have reported on microplastic contamination in seafood and freshwater organisms from Indonesia, and it is likely that microplastics have contaminated the gastrointestinal tracts of Indonesians. Using Raman spectroscopy, we detected microplastic contamination in 7 out of 11 analyzed stool samples collected from a farming community in the highland village of Pacet, East Java, Indonesia. Polypropylene (PP) was the most abundant and prevalent type of microplastic observed, and it was found in four of the positive samples with an average concentration of 10.19 microgram per gram of feces (μg/g). Microplastics were also detected at high concentrations in tempeh (soybean cake, a staple protein source for Indonesians), table salts, and toothpaste, which were regularly consumed and used by the study participants. PP was particularly high in table salts (2.6 μg/g) and toothpaste (15.42 μg/g), suggesting that these products might contribute to the gastrointestinal contamination in the studied population. This pilot study indicated microplastic contamination in the rural Indonesian population and in their daily consumables, demonstrating the far-reaching extent of microplastic pollution beyond urban areas.
Enrichment of SARM1 alleles encoding variants with constitutively hyperactive NADase in patients with ALS and other motor nerve disorders
2021-11-19

SARM1, a protein with critical NADase activity, is a central executioner in a conserved programme of axon degeneration. We report seven rare missense or in-frame microdeletion human SARM1 variant alleles in patients with amyotrophic lateral sclerosis (ALS) or other motor nerve disorders that alter the SARM1 auto-inhibitory ARM domain and constitutively hyperactivate SARM1 NADase activity. The constitutive NADase activity of these seven variants is similar to that of SARM1 lacking the entire ARM domain and greatly exceeds the activity of wild-type SARM1, even in the presence of nicotinamide mononucleotide (NMN), its physiological activator. This rise in constitutive activity alone is enough to promote neuronal degeneration in response to otherwise non-harmful, mild stress. Importantly, these strong gain-of-function alleles are completely patient-specific in the cohorts studied and show a highly significant association with disease at the single gene level. These findings of disease-associated coding variants that alter SARM1 function build on previously reported genome-wide significant association with ALS for a neighbouring, more common SARM1 intragenic single nucleotide polymorphism (SNP) to support a contributory role of SARM1 in these disorders. A broad phenotypic heterogeneity and variable age-of-onset of disease among patients with these alleles also raises intriguing questions about the pathogenic mechanism of hyperactive SARM1 variants.
Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis
2021-11-19

Abstract Context Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. Objective This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. Methods A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. Results We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. Conclusion Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.
What difference does multiple imputation make in longitudinal modeling of EQ-5D-5L data? Empirical analyses of simulated and observed missing data patterns
2021-11-19

Abstract Purpose Although multiple imputation is the state-of-the-art method for managing missing data, mixed models without multiple imputation may be equally valid for longitudinal data. Additionally, it is not clear whether missing values in multi-item instruments should be imputed at item or score-level. We therefore explored the differences in analyzing the scores of a health-related quality of life questionnaire (EQ-5D-5L) using four approaches in two empirical datasets. Methods We used simulated (GR dataset) and observed missingness patterns (ABCD dataset) in EQ-5D-5L scores to investigate the following approaches: approach-1) mixed models using respondents with complete cases, approach-2) mixed models using all available data, approach-3) mixed models after multiple imputation of the EQ-5D-5L scores, and approach-4) mixed models after multiple imputation of EQ-5D 5L items. Results Approach-1 yielded the highest estimates of all approaches (ABCD, GR), increasingly overestimating the EQ-5D-5L score with higher percentages of missing data (GR). Approach-4 produced the lowest scores at follow-up evaluations (ABCD, GR). Standard errors (0.006–0.008) and mean squared errors (0.032–0.035) increased with increasing percentages of simulated missing GR data. Approaches 2 and 3 showed similar results (both datasets). Conclusion Complete cases analyses overestimated the scores and mixed models after multiple imputation by items yielded the lowest scores. As there was no loss of accuracy, mixed models without multiple imputation, when baseline covariates are complete, might be the most parsimonious choice to deal with missing data. However, multiple imputation may be needed when baseline covariates are missing and/or more than two timepoints are considered.
Heart rate as an early warning parameter and proxy for subsequent mortality in Danio rerio embryos exposed to ionisable substances
2021-11-19

Environmental risk assessments of organic chemicals usually do not consider pH as a key factor. Hence, most substances are tested at a single pH only, which may underestimate the toxicity of ionisable substances with a pK<sub>a</sub> in the range of 4-10. Thus, the ability to consider the pH-dependent toxicity would be crucial for a more realistic assessment. Moreover, there is a tendency in acute toxicity tests to focus on mortality only, while little attention is paid to sublethal endpoints. We used Danio rerio embryos exposed to ten ionisable substances (the acids diclofenac, ibuprofen, naproxen and triclosan and the bases citalopram, fluoxetine, metoprolol, propranolol, tramadol and tetracaine) at four external pH levels, investigating the endpoints mortality (LC<sub>50</sub>) and heart rate (EC<sub>20</sub>). Dose-response curves were fitted with an ensemble-model to determine the true uncertainty and variation around the mean endpoints. The ensemble considers eight (heart rate) or twelve (mortality) individual models for binominal and Poisson distributed data, respectively, selected based on the Akaike Information Criterion (AIC). In case of equally good models, the mean endpoint of all models in the ensemble was calculated, resulting in more robust EC<sub>x</sub> estimates with lower 'standard errors' as compared to randomly selected individual models. We detected a high correlation between mortality (LC<sub>50</sub>) at 96 hpf and reduced heart rate (EC<sub>20</sub>) at 48 hpf for all compounds and all external pH levels (r = 0.98). Moreover, the observed pH-dependent effects were strongly associated with log D and thus, likely driven by differences in uptake (toxicokinetic) rather than internal (toxicodynamic) processes. Prospectively, the a priori consideration of pH-dependent effects of ionisable substances might make testing at different pH levels redundant, while the endpoint of mortality might even be replaced by a reliable sublethal proxy that would reduce the exposure, accelerating the evaluation process.
Hypofractionated preoperative radiotherapy for high risk soft tissue sarcomas in a geriatric patient population
2021-11-19

Abstract Background Standard therapy for localised, resectable high risk soft tissue sarcomas consists of wide excision and radiotherapy over several weeks. This treatment schedule is hardly feasible in geriatric and frail patients. In order not to withhold radiotherapy from these patients, hypofractionated radiotherapy with 25 Gy in 5 fractions was evaluated in a geriatric patient population. Patients and methods A retrospective analysis was performed of 18 geriatric patients with resectable high risk soft tissue sarcomas of extremities and thoracic wall. Wound healing and short term oncologic outcome were analysed. In addition, dose constraints for radiotherapy of the extremities were transferred from normofractionated to hypofractionated radiotherapy regimens. Results Feasibility was good with 17/18 patients completing treatment as planned. Wound healing complication rate was in the range of published data. Two patients developed local and distant recurrence, two patients isolated distant recurrences. No isolated local recurrences were observed. Keeping the constraints was possible in all cases without compromising the coverage of the target volume. Conclusions Hypofractionated radiotherapy and surgery was well tolerated even in this specific patient population. With feasibility concerning early wound healing problems and adapted constraints, which allow for the treatment of most resectable extremity tumours, the concept warrants further evaluation in patients unfit for standard radiotherapy.
Dynamic DNA Methylation Changes in the COMT Gene Promoter Region in Response to Mental Stress and Its Modulation by Transcranial Direct Current Stimulation
2021-11-19

Changes in epigenetic modifications present a mechanism how environmental factors, such as the experience of stress, can alter gene regulation. While stress-related disorders have consistently been associated with differential DNA methylation, little is known about the time scale in which these alterations emerge. We investigated dynamic DNA methylation changes in whole blood of 42 healthy male individuals in response to a stressful cognitive task, its association with concentration changes in cortisol, and its modulation by transcranial direct current stimulation (tDCS). We observed a continuous increase in COMT promotor DNA methylation which correlated with higher saliva cortisol levels and was still detectable one week later. However, this lasting effect was suppressed by concurrent activity-enhancing anodal tDCS to the dorsolateral prefrontal cortex. Our findings support the significance of gene-specific DNA methylation in whole blood as potential biomarkers for stress-related effects. Moreover, they suggest alternative molecular mechanisms possibly involved in lasting behavioral effects of tDCS.
Preparation of Cationic Amphiphilic Nanoparticles with Modified Chitosan Derivatives for Doxorubicin Delivery
2021-11-19

Polymeric micelle-like nanoparticles have demonstrated effectiveness for the delivery of some poorly soluble or hydrophobic anticancer drugs. In this study, a hydrophobic moiety, deoxycholic acid (DCA) was first bonded on a polysaccharide, chitosan (CS), for the preparation of amphiphilic chitosan (CS-DCA), which was further modified with a cationic glycidyltrimethylammounium chloride (GTMAC) to form a novel soluble chitosan derivative (HT-CS-DCA). The cationic amphiphilic HT-CS-DCA was easily self-assembled to micelle-like nanoparticles about 200 nm with narrow size distribution (PDI 0.08–0.18). The zeta potential of nanoparticles was in the range of 14 to 24 mV, indicating higher positive charges. Then, doxorubicin (DOX), an anticancer drug with poor solubility, was entrapped into HT-CS-DCA nanoparticles. The DOX release test was performed in PBS (pH 7.4) at 37 °C, and the results showed that there was no significant burst release in the first two hours, and the cumulative release increased steadily and slowly in the following hours. HT-CS-DCA nanoparticles loaded with DOX could easily enter into MCF-7 cells, as observed by a confocal microscope. As a result, DOX-loaded HT-CS-DCA nanoparticles demonstrated a significant inhibition activity on MCF-7 growth without obvious cellular toxicity in comparison with blank nanoparticles. Therefore, the anticancer efficacy of these cationic HT-CS-DCA nanoparticles showed great promise for the delivery of DOX in cancer therapy.
Toward an X-ray inventory of nearby neutron stars
2021-11-19

Context. The X-ray emission of neutron stars enables a probe of their temperatures, geometries and magnetospheric properties. The current number of X-ray emitting pulsars is insufficient to rule out observational biases that may arise from poorly known distance, age, or location of the neutron stars. One approach to overcome such biases is to create a distance-limited sample with sufficiently deep observations. Aims. With the aim of better sampling of the nearby (≲2 kpc) population of neutron stars, we started an XMM-Newton survey of pulsars to measure their X-ray fluxes or derive respective constraining upper limits. Methods. We investigated 14 nearby pulsars for potential X-ray counterparts using different energy bands and detectors. In addition to our new XMM-Newton data, we also considered archival data and catalogs. We discuss source properties and also check for alternative counterparts to the X-ray sources. Results. In our new XMM-Newton data, we found two pulsar counterpart candidates with significance above 4 σ and one candidate with 3.5 σ by combining EPIC camera detection likelihoods. We also report the detection of potential X-ray counterparts to eight radio pulsars in the 4XMM-DR10 catalog which have not been reported in the literature.
Dataset for Urban, Agouti historiography: the problem of widespread lexical forms and deep linguistic history in Central and South America
2021-11-19

This is the entire dataset underlying the article "Agouti historiography: the problem of widespread lexical forms and deep linguistic history in Central and South America" by Matthias Urban, which will appear in Faits de Langues.
Higher-level Inferences in the Strong-Kleene Setting: A Proof-theoretic Approach
2021-11-20

Abstract Building on early work by Girard (1987) and using closely related techniques from the proof theory of many-valued logics, we propose a sequent calculus capturing a hierarchy of notions of satisfaction based on the Strong Kleene matrices introduced by Barrio et al. (Journal of Philosophical Logic 49:93–120, 2020) and others. The calculus allows one to establish and generalize in a very natural manner several recent results, such as the coincidence of some of these notions with their classical counterparts, and the possibility of expressing some notions of satisfaction for higher-level inferences using notions of satisfaction for inferences of lower level. We also show that at each level all notions of satisfaction considered are pairwise distinct and we address some remarks on the possible significance of this (huge) number of notions of consequence.
The Muslim Brotherhood in Jordan. By Joas Wagemakers
2021-11-20

The six chapters of this book, arranged in two parts, offer a thorough analysis of the history and evolution of the Muslim Brotherhood in the Middle East and North Africa (MENA), Jordan in particular. Its main contribution, I believe, is in its second part. Using Freeden’s history of concept theory, Wagemakers presents a unique exploration into the causes of ideological shifts within the group and in Jordan and how its members justified such shifts using Islamic texts and concepts, thereby ‘show[ing] how early Islamic thought continues to be a source of contested and de-contested ideological concepts for highly diverse yet ideologically connected contemporary Islamist thinkers and organisations’ (p. 19). By focusing on the discourse of the group, as theoretical framework and methodology, Wagemakers seems to adopt a constructivist approach to analyse the reasons—constructed over time—for the ideological shift of the Muslim Brotherhood in Jordan. He links the process to domestic...
Historical comparisons show evolutionary changes in drought responses in European plant species after two decades of climate change
2021-11-21

Plants must continuously respond to environmental changes, and a timely question is whether and how populations respond to ongoing global warming and increased drought frequencies and intensities. Plants can either respond through migration or through phenotypic plasticity or their populations can adapt evolutionarily, which encompasses the evolution of trait means and of trait plasticity. One way to detect such evolutionary changes within plant populations is through historical comparisons where plants grown from seeds collected in the past (“ancestors”) are compared to freshly collected seeds from the same populations (“descendants”) in common garden experiments. We used 21- to 26-year-old seeds stored in seed banks for two multi-species experiments that investigated changes in phenotypic traits and their plasticity conferring drought tolerance in early life stages of European plant species. In the first experiment, we used seedlings of four Mediterranean species, ceased watering and recorded their day of mortality. In the second experiment, we studied phenotypic responses to drought in juvenile plants of nine species originating from temperate regions in Europe. In one of four species in the first experiment, descendants survived significantly longer without watering and were smaller than their ancestors. In the second experiment, descendant plants were generally taller under well-watered conditions but smaller under drought than their ancestors, thus showing stronger plasticity. Our historical comparisons suggest that some populations have likely evolved through changes in trait means and plasticity in ways consistent with adaptation to increased drought. Using seed bank material for historical comparisons has several weaknesses, such as unknown sampling protocols or invisible fractions. However, we show how accurately sampled and stored seed bank collections can be used similar to the resurrection approach for investigating rapid evolutionary processes in early life stages of plants under climate change.
Activating endogenous resolution pathways by soluble epoxide hydrolase inhibitors for the management of COVID‐19
2021-11-21

Abstract Anti‐inflammatory, specialized proresolving mediators such as resolvins, protectins, maresins, and lipoxins derived from polyunsaturated acids may play a potential role in lung diseases as they protect different organs in animal disease models. Polyunsaturated fatty acids are an important resource for epoxy fatty acids (EET, EEQ, and EDP) that mediate a broad array of anti‐inflammatory and proresolving mechanisms, such as mitigation of the cytokine storm. However, epoxy fatty acids are rapidly metabolized by soluble epoxide hydrolase (sEH). In animal studies, administration of sEH inhibitors (sEHIs) increases epoxy fatty acid levels, reduces lung inflammation, and improves lung function, making it a viable COVID‐19 treatment approach. Thus, using sEHIs to activate endogenous resolution pathways might be a novel method to minimize organ damage in severe cases and improve outcomes in COVID‐19 patients. This review focuses on the use of sEH inhibitors to activate endogenous resolution mechanisms for the treatment of COVID‐19.
Too much water: How salinisation transformed Australia’s ‘food bowl’, 1945–2017
2021-11-21

Australia's 'food bowl', its largest irrigation region-the Goulburn-Murray Irrigation District (GMID) in Northern Victoria, in the south-east of the Murray-Darling Basin-was transformed dramatically between 1945 and 1994.The reason was salinisation, a result of 'too much water'.Unsustainable irrigation practices caused what in 1987 was called 'Australia's greatest environmental threat'.While the environmental degradation brought about by salinisation caused a variety of social conflicts between rural communities about access to water and 'rights' to pollute rivers, and undermined many farmers' productive base, its story is also one of hope and self-organisation.Concerned people in Kerang and Shepparton founded research farms and action committees that collaborated with government departments to develop ways of farming in a saline environment and encourage environmental awareness.After the Victorian government launched a long-term strategy in 1988, this brought about some success.However, the decisive event was the 'Millennium Drought', from 1996 to 2010, which drastically reduced the water table levels and brought the GMID a reprieve from salinisation.Therefore, while this story is instructive to study environment-society interactions during a time of degradation, it also vividly shows how the natural world shapes the conditions under which humans act, even in a highly modified, anthropogenic environment.