julilili42/papers huggingface dataset:
Acute and chronic inflammation alter immunometabolism in a cutaneous delayed-type hypersensitivity reaction (DTHR) mouse model
2022-11-15

Abstract T-cell-driven immune responses are responsible for several autoimmune disorders, such as psoriasis vulgaris and rheumatoid arthritis. Identification of metabolic signatures in inflamed tissues is needed to facilitate novel and individualised therapeutic developments. Here we show the temporal metabolic dynamics of T-cell-driven inflammation characterised by nuclear magnetic resonance spectroscopy-based metabolomics, histopathology and immunohistochemistry in acute and chronic cutaneous delayed-type hypersensitivity reaction (DTHR). During acute DTHR, an increase in glutathione and glutathione disulfide is consistent with the ear swelling response and degree of neutrophilic infiltration, while taurine and ascorbate dominate the chronic phase, suggesting a switch in redox metabolism. Lowered amino acids, an increase in cell membrane repair-related metabolites and infiltration of T cells and macrophages further characterise chronic DTHR. Acute and chronic cutaneous DTHR can be distinguished by characteristic metabolic patterns associated with individual inflammatory pathways providing knowledge that will aid target discovery of specialised therapeutics.
Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia
2022-11-15

Abstract Introduction We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline
Monitoring and Integrating the Changes in Vegetated Areas with the Rate of Groundwater Use in Arid Regions
2022-11-15

Frequent water table measurements are crucial for sustainable groundwater management in arid regions. Such monitoring is more important in areas that are already facing an acute problem with excessive groundwater withdrawal. In the majority of these locations, continuous readings of groundwater levels are lacking. Therefore, an approximate estimate of the rate of increase or decrease in water consumption over time may serve as a proxy for the missing data. This could be achieved by tracking the changes in vegetated areas that generally correlate with changes in the rate of water use. The technique proposed in this paper is based on two remote sensing datasets: Landsat 7 and 8 from 2001 to 2021, and Sentinel 2A from 2015 to 2021, as well as five vegetation indices: Normalized Difference Vegetation Index (NDVI), Renormalized Difference Vegetation Index (RDVI), Soil Adjusted Vegetation Index (SAVI), Enhanced Vegetation Index (EVI), and Transformed Vegetation Index (TVI). The findings have shown that the datasets chosen performed best for small-scale land farms at the research location, which was chosen to be the El-Qaa plain, in the southwestern corner of the Sinai Peninsula in Egypt. Landsat 7 data with a resolution of 30 m revealed a substantial increase in land farms from 2.9 km2 in 2001 to 23.3 km2 in 2021. By using the five indices based on Sentinel 2A data, vegetated areas were categorized as heavy, moderate, or light. In addition, the expansion of each class area from 2015 to 2021 was tracked. Additionally, the NDVI index was modified to better reflect the arid environment (subsequently naming this new index as the Arid Vegetation Index: AVI). Rough scenarios of the increase in water consumption rate at the research site were generated by observing the increase in vegetated areas and collecting rough information from the farmers regarding the crop types.
Universal Categories, Single Language Realisations: Aspectuality in French and other Romance Languages
2022-11-15

Aspect and Aktionsart are both categories that codify information on the internal temporal structure of states of affairs. In traditional studies on aspectuality, a very strict distinction between them is usually made. Aspect is an obligatory grammatical (morphosyntactic) verbal category, which must therefore be expressed in all languages whose verbal systems allow it. Aktionsart is a lexical verbal category and is not subject to such restraints in individual languages. This “bidimensional” perspective – widespread in Linguistics and even more so in Romance Linguistics (see, among many others, Bertinetto 1986; Smith 1991; Squartini 1998) – contrasts with a less common “unidimensional” approach (De Miguel 1999; Verkuyl 1972, 1993). The latter advocates the semantic identity of what, in terms of the linguistic analysis of individual languages, is considered either grammatical or lexical aspect.In this paper, an analysis of aspectuality as a semantic-functional category comprising both aspect and Aktionsart will be introduced by means of a new unidimensional model, which has an onomasiological background and is based on frame semantics (see Dessì Schmid 2014, 2019). In accordance with many studies on cognitive semantics, aspectuality is defined as the structuring of states of affairs through delimitation or bounding (see, e.g., Smith 1997; Bickel 1997; Langacker 1987, 2006; Talmy 1996, 2000); this delimitation principle is further developed and applied in a highly extended and structured way.The paper will focus on French examples but will also consider some data from other Romance languages, although it is applicable to any individual language.
Probing the role of bounding, definiteness and other factors: bare noun and determiner use in Guianese French Creole
2022-11-15

From a cognitive‐semantic perspective, two important conceptual schemas underlie determiner use and the count/mass distinction in languages such as English and French, namely bounding and definiteness. This paper investigates to what extent these concepts are related to noun phrase marking in Guianese French Creole (GFC). The corpus‐based analysis shows that GFC uses bare nouns not only with unbounded entities and in non‐referential and generic contexts, but also for representing singular and plural indefinite and definite referents. At the same time, GFC shows a clear count/mass distinction and also has definite and indefinite determiners. However, in contrast to article languages such as English and French, bounding and definiteness need to be examined alongside semantic‐pragmatic and discourse‐informational criteria in order to explain the use of determiners and bare nouns in GFC. Thus, determiner use as a grammatical individuation strategy clearly has a different weight in GFC, which does not fit into cross‐linguistic typologies of articleless and article languages (e.g. Chierchia 1998). The comparative results on GFC, French and English also serve to evaluate two recent typological claims: while they confirm Le Bruyn et al.’s (2017) hypothesis on a correlation between the richness of the article system and the freedom of bare noun use, Abraham et al.’s (2007) claim of a universally complementary distribution of articles and grammatical aspect distinctions in the verb phrase is not supported by the data.
Publication activities relating to digital teaching and learning in the GMS Journal for Medical Education – a descriptive analysis (1984–2020)
2022-11-15

Aims and objectives: Digital teaching, learning and assessment have been part of medical education and continuing education for decades. The objective of this review paper is to highlight developments and perspectives in these areas in the GMS Journal for Medical Education (GMS JME). Methodology: In the spring of 2020, we conducted a systematic literature search of the Journal for Medical Education (JME) and analysed the articles with regard to different categories such as article type, digital tools used or mode of data collection. Results: Of the 132 articles analysed, 78 were digital interventions (53 of which were exploratory-descriptive), 28 were project descriptions, 16 were surveys of needs or equipment and 10 were concept papers. About one-third of the studies and project reports each dealt with virtual patients or case-based learning, whereas no articles were published on trends such as serious games or virtual reality. Overall, our analysis shows that in many respects, the studies on digital teaching were more broadly based, especially between 2006 and 2010, after which this trend tended to decline again. Conclusions: Our analysis shows that publications in the JME consider some key aspects of digital teaching in medical education and continuing education, such as educational videos or virtual patients. The variability of information and methods of presentation advocate the use of guidelines to optimise the quality of scientific papers. Furthermore, clues for future research topics and experimental study designs are identified.
Recovery of systemic hyperinflammation in patients with severe SARS-CoV-2 infection
2022-11-15

Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19. Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled and received a cardiological assessment at study entry and during follow-up visit. Inclusion criteria of our study were age older than 18 years, presence of CVD, and acute SARS-CoV-2 infection. The median age of the patient cohort was 69 (IQR 55–79) years. 12 (52.2%) patients were men. Peripheral monocytes and chemokine/cytokine profiles were analysed. Numbers of classical and non-classical monocytes were significantly decreased during acute SARS-CoV-2 infection compared to 3-month recovery. While classical monocytes reached the expected level in peripheral blood after 3 months, the number of non-classical monocytes remained significantly reduced. All three monocyte subsets exhibited changes of established adhesion and activation markers. Interestingly, they also expressed higher levels of pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF) at the time of recovery, although MIF was only slightly increased during the acute phase. Changes of monocyte phenotypes and increased MIF expression after 3-month recovery from acute SARS-CoV-2 infection may indicate persistent, possibly long-lasting, pro-inflammatory monocyte function in CVD patients.
Differential Expression of C/Ebpa and Its Stem Cell-Specific Targets in Congenital Neutropenias and Cyclic Neutropenias
2022-11-15

Severe congenital neutropenias (CN) and cyclic neutropenias (CyN) are disorders of hematopoiesis that differ markedly in disease severity. Mutations in ELANE are considered responsible for most cases of CyN and CN. ELANE mutations lead to accelerated apoptosis of myeloid progenitor cells due to the production of misfolded elastase protein and subsequent elevated unfolded protein response (UPR). In CyN at the peak of the cycle up to 10 % of the CD34+ cells were immature CD49f+ HSC that did not express mutated ELANE and therefore escaped from UPR (escaper cells). The proliferation and differentiation of CD49f+ cells during the ascending arm of the cycle led to increased neutrophils at the peak of the cycle stimulated by G-CSF, C/EBPA, HLF, MLL1, HOXA9 and MEIS1. At the peak of the cycle, CD34+ cells comprising the high percentage of CD49f+ cells, expressed up to 8-fold more C/EBPA, MLL1, HOXA9, MEIS1, and HLF levels as compared to cells from untreated healthy controls. This ensured sufficient neutrophil numbers in CyN at the peak. However, the mutated neutrophil elastase protein released by the high numbers of neutrophils at the peak of the cycle caused negative feedback of granulopoiesis by proteolytic digestion of G-CSF. Since G-CSF was not available anymore, CD34+ cells including CD49f+ cells did not proliferate and differentiate anymore during the downward arm of the cycle leading to neutropenia. CD34+ cells from CN patients contained only low percentages of CD49f+ cells and there was defective or no expression of C/EBPA, HLF, MLL1, HOXA9, and MEIS1.
A System-Level Study Reveals That a Defective Thymic Niche Accelerates the T-ALL Initiation
2022-11-15

The ontogeny of T-cell acute lymphoblastic leukemia (T-ALL) is unknown. In humans and mice, T-ALL is diagnosed when malignant T cells are detectable in the peripheral blood, i.e., at a stage when disease development is complete. Therefore, the malignant processes in the thymus - where the T cells develop - are an unexplored "black box". We took an interdisciplinary approach combining in vivo experiments with computational modeling to investigate the role of the thymic niche in disease manifestation. We focused on the role of interleukin 7 (IL-7) in the thymus, as approximately 70-80% of T-ALL patients have either increased IL-7 receptor (IL-7R) expression or gain-of-function mutations in this gene. In addition, autocrine production of IL-7 by T-ALL blasts has been detected in some patients. Using our recently developed "virtual thymus" model (Aghaallaei et al., Science Advances, 2021), we first simulated more than 200 scenarios to find out the conditions that lead to massive expansion of a single clone in the thymus. We then genetically engineered thymocytes and thymic epithelial cells (TECs) in medaka fish based on in silico predictions. Consistent with our computational model, we found that manipulation of thymocytes or TECs alone resulted in only 25% (N=36) and 10% (N=29) T-ALL development, respectively, in the thymus of Medaka larvae after five days; however, this frequency was accelerated to 54% (N=45) when both cell types were manipulated simultaneously. Our results strongly suggest that defective thymic niche has a strong impact on T-ALL development. Taken together, we propose a previously unknown mechanism that may trigger T-ALL initiation in the thymus. In addition, we introduce the "virtual thymus" as a new versatile in silico model that can predict the outcome of conditions for the development or treatment of T-ALL.
Effect-based monitoring to integrate the mixture hazards of chemicals into water safety plans
2022-11-16

Abstract Water safety plans (WSPs) are intended to assure safe drinking water (DW). WSPs involve assessing and managing risks associated with microbial, chemical, physical and radiological hazards from the catchment to the consumer. Currently, chemical hazards in WSPs are assessed by targeted chemical analysis, but this approach fails to account for the mixture effects of the many chemicals potentially present in water supplies and omits the possible effects of non-targeted chemicals. Consequently, effect-based monitoring (EBM) using in vitro bioassays and well plate-based in vivo assays are proposed as a complementary tool to targeted chemical analysis to support risk analysis, risk management and water quality verification within the WSP framework. EBM is frequently applied to DW and surface water and can be utilised in all defined monitoring categories within the WSP framework (including ‘system assessment’, ‘validation’, ‘operational’ and ‘verification’). Examples of how EBM can be applied within the different WSP modules are provided, along with guidance on where to apply EBM and how frequently. Since this is a new area, guidance documents, standard operating procedures (SOPs) and decision-making frameworks are required for both bioassay operators and WSP teams to facilitate the integration of EBM into WSPs, with these resources being developed currently.
Emergent quantum correlations and collective behavior in noninteracting quantum systems subject to stochastic resetting
2022-11-16

We investigate the dynamics of a noninteracting spin system, undergoing coherent Rabi oscillations, in the presence of stochastic resetting. We show that resetting generally induces long-range quantum and classical correlations both in the emergent dissipative dynamics and in the nonequilibrium stationary state. Moreover, for the case of conditional reset protocols - where the system is reinitialized to a state dependent on the outcome of a preceding measurement - we show that in the thermodynamic limit, the spin system can feature collective behavior which results in a phenomenology reminiscent of that occurring in nonequilibrium phase transitions. The discussed reset protocols can be implemented on quantum simulators and quantum devices that permit fast measurement and readout of macroscopic observables, such as the magnetization. Our approach does not require the control of coherent interactions and may therefore highlight a route towards a simple and robust creation of quantum correlations and collective nonequilibrium states, with potential applications in quantum enhanced metrology and sensing.
Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment
2022-11-16

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&amp;D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.
Dissimilar micro beam welding of titanium to Nitinol and stainless steel using biocompatible filler materials for medical applications
2022-11-16

Abstract In the present investigation, thin sheet geometries of commercially pure titanium (cp, grade 4) are butt-welded to AISI 316L stainless steel as well as Nitinol by means of micro electron beam welding using filler materials. In order to avoid mixing of the base materials, the refractory metals tantalum, niobium and hafnium are applied as intermediate layers. Owing to the biocompatibility of these filler materials, the final products are suitable for medical technology applications. In combination with low energy inputs and precise beam alignments, it is demonstrated that high-quality and crack-free joints can be produced using micro electron beam welding. The welded joints are analysed using nanoindentation to identify critical weld areas, e.g. high concentrations of intermetallic compounds, and to evaluate the compatibility of the base and filler materials. To correlate the hardness mappings with the microstructural evolution of the welds, an exemplary joint is analysed by means of electron backscatter diffraction and energy dispersive X-ray spectroscopy with special emphasis on intermixing and the formation of intermetallic compounds. Based on the generated hardness mappings as well as the ultimate tensile strengths of the joints, it will be concluded which filler material provides the most promising results for the given material combinations.
Elevated platelet–leukocyte complexes are associated with, but dispensable for myocardial ischemia–reperfusion injury
2022-11-16

Abstract Aims P-selectin is an activatable adhesion molecule on platelets promoting platelet aggregation, and platelet–leukocyte complex (PLC) formation. Increased numbers of PLC are circulating in the blood of patients shortly after acute myocardial infarction and predict adverse outcomes. These correlations led to speculations about whether PLC may represent novel therapeutic targets. We therefore set out to elucidate the pathomechanistic relevance of PLC in myocardial ischemia and reperfusion injury. Methods and results By generating P-selectin deficient bone marrow chimeric mice, the post-myocardial infarction surge in PLC numbers in blood was prevented. Yet, intravital microscopy, flow cytometry and immunohistochemical staining, echocardiography, and gene expression profiling showed unequivocally that leukocyte adhesion to the vessel wall, leukocyte infiltration, and myocardial damage post-infarction were not altered in response to the lack in PLC. Conclusion We conclude that myocardial infarction associated sterile inflammation triggers PLC formation, reminiscent of conserved immunothrombotic responses, but without PLC influencing myocardial ischemia and reperfusion injury in return. Our experimental data do not support a therapeutic concept of selectively targeting PLC formation in myocardial infarction.
Affix substitution in Indonesian: A computational modeling approach
2022-11-16

Abstract Indonesian has two noun-forming prefixes, PE- and PEN- , that often stand in a paradigmatic relation to verbal base words with the prefixes BER- and MEN- . The central question addressed in the present study is whether the form similarities between PEN- and MEN- make PEN- easier to learn compared to PE- . To address this question, we made use of a computational model, the ‘discriminative lexicon’ (DL) model. We trained this model on 2,517 word forms that were inflected or derived variants of 99 different base words. Of these word forms, 109 were nouns with PE- and 221 words were nouns with PEN- . Both the production and the comprehension networks of the model performed with high accuracy for both prefixes. However, the model was able to provide more precise predictions for PE- as compared to PEN- , implying that PE- should have a processing advantage compared to PEN- . There are two reasons for why PE- is learned more robustly than PEN- . First, PE- words tend to be longer and hence have more discriminative triphones. Second, due to cue competition with MEN- , the prefixal triphones of PEN- are less effective cues than those of PE- . A measure of functional load is proposed that helps clarify the relative importance of the triphones in the prefixes and those straddling the boundary between prefix and stem. Our results shed further light on the productivity paradox, role of junctural phonotactics, and (dis)functionality of affix substitution.