Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a non-target strategy for evaluation of potential biological effects of inhalable aerosols generated during purposeful room conditioning using an in vitro inhalation model

Abstract Objectives: An integrated in vitro inhalation approach was outlined to estimate potential adverse acute inhalation effects of aerosols from commercial nebulizer applications used for purposeful room conditioning such as disinfection, scenting or others. Aerosol characterization, exposure estimation and evaluation of acute biological effects by in vitro inhalation were included to generate dose-response data, allowing for determination of in vitro lowest observable adverse effect levels (LOAELs). Correlation of these to estimates of human lung deposition was included for quantitative in vitro to in vivo extrapolation approach (QIVIVE) for acute effects during human exposure. Methods: To test the proposed approach, a case study was undertaken using two realistic test materials. An acute in vitro inhalation setup with air-liquid interface A549-cells in an optimized exposure situation (P.R.I.T.® ExpoCube®) was used to expose cells and analysis of relevant biological effects (viability, mitochondrial membrane potential, stress, IL-8 release) was carried out. Results: The observed dose-responsive effects in a sub-toxic dose-range could be attributed to the main component of one test material and its presence in the aerosol phase of the nebulized material. QIVIVE resulted in a factor of at least 256 between the in vitro LOAEL and the estimated acute human lung exposure for this test material. Conclusions: The case-study shows the value of the non-target in vitro inhalation testing approach especially in case of a lack of knowledge on complex product composition. It is expected that approaches like this will be of high value for product safety and environmental health in the future. HIGHLIGHTS Design of a routine in vitro inhalation approach to estimate biological effects of nebulized products. Application in a case study on a potential real product for purposeful room conditioning by use of a commercial nebulizer. Combining results from aerosol characterization and in vitro inhalation experiments allowed for comprehensive correlation of product composition, aerosol properties and biological effects. Assignment of sub-toxic biological effects to a specific product component enabled identification of a product composition with potentially even less biological effect. Combined in vivo exposure estimation and in vitro LOAEL determination enabled a QIVIVE approach.
SwissParam 2023: A Modern Web-Based Tool for Efficient Small Molecule Parametrization

Most steps of drug discovery are now routinely supported and accelerated by computer-aided drug design tools. Among them, structure-based approaches use the three-dimensional structure of the targeted biomacromolecule as a major source of information. When it comes to calculating the interactions of small molecules with proteins using the equations of molecular mechanics, topologies, atom typing, and force field parameters are required. However, generating parameters for small molecules remains challenging due to the large number of existing chemical groups. The SwissParam web tool was first released in 2011 with the aim of generating parameters and topologies for small molecules based on the Merck molecular force field (MMFF) while being compatible with the CHARMM22/27 force field. Here, we present an updated version of SwissParam, providing various new features, including the possibility to setup covalent ligands. Molecules can now be imported from different file formats or via a molecular sketcher. The MMFF-based approach has been updated to provide parameters and topologies compatible with the CHARMM36 force field. An option was added to generate small molecule parametrizations following the CHARMM General Force Field via the multipurpose atom-typer for CHARMM (MATCH) approach. Additionally, SwissParam now generates information on probable alternative tautomers and protonation states of the query molecule so that the user can consider all microspecies relevant to its compound. The new version of SwissParam is freely available at www.swissparam. ch and can also be accessed through a newly implemented command-line interface.
Velocity evaluation using least squares prestack migration

Kirchhoff least squares prestack migration (LSPSM) attenuates acquisition artifacts resulted from the irregularities or sparseness in the seismic data sampling and improves the image resolution. This study shows that this improvement needs an accurate subsurface velocity information. It is shown that the improvement in the resolution of the resulted LSPSM, convergence rate of the least squares conjugate gradient (LSCG) iterations, and the ability of a good data reconstruction by LSPSM are the three factors that strongly depend on the accuracy of the background velocity and can be used as effective tools for ensuring the accuracy of the velocity model.
A cross-sectional study of nutritional status in healthy, young, physically-active German omnivores, vegetarians and vegans reveals adequate vitamin B12 status in supplemented vegans

Abstract Background/Objective Plant-based diets reduce the risk of cardiovascular disease but also increase the risk of certain micronutrient deficiencies, particularly, of vitamin B12 (B12). The extent to which the unsupervised use of oral nutrient supplements is sufficient to prevent these deficiencies is not well established. We analyzed nutrient intake, laboratory biomarkers, supplementation behavior, and B12 status adequacy amongst young, healthy, physically active omnivores, lacto-ovo-vegetarians and vegans from Germany. Methods We recruited 115 participants (n = 40 omnivores; n = 37 lacto-ovo-vegetarians, and n = 38 vegans) with comparable age, sex, marital status, physical activity and educational levels through online advertisements and local newspapers in Freiburg, Germany. Results Energy intake and macronutrient distribution were comparable across diets. Major differences included intake of fiber, cholesterol, and several vitamins. Vegans had the lowest intake of B12 from foods (0.43 (0.58) µg/d), compared to omnivores (2.14 (2.29) µg/d) and lacto-ovo-vegetarians (0.98 (1.34) µg/day). Multivariate analysis of 36 blood biomarkers revealed that three major classes of biomarkers contributed the most to the clustering of individuals by dietary group, namely, biomarkers of B12 status (B12, holoTC, Hcy), iron (iron, ferritin, transferrin) and lipid metabolism (vitamin A, HDL, LDL, total cholesterol, TAG). This suggests that nutrients that modify the metabolic pathways represented by these biomarkers have the most penetrating effect on health status across diets. Analysis of B12 status (including 4cB12) revealed adequacy in omnivores and vegans, and a poorer B12 status amongst lacto-ovo-vegetarians. Fewer lacto-ovo-vegetarians used B12 supplements compared to vegans (51% versus 90%). Conclusions Even amongst homogeneously healthy Germans, each diet manifested with measurable differences in dietary intakes and biomarkers of health. Plant-based diets, in particular the vegan diet, exhibited the most favorable patterns of lipid metabolism and glycemic control, but the lowest food intake of B12. Supplementation of healthy vegans with B12 (median 250 µg B12/day, over 2 years) secured an adequate B12 status that was comparable to that of healthy omnivores. Clinical Trial Registry: German Clinical Trial register number: DRKS00027425
APPLICATION OF AN AUTOMATIC CALIBRATION SCHEME FOR URBAN RAINFALL - RUNOFF MODELS IN MOUSE

This study presents an automatic calibration procedure applicable specially for urban rainfall - runoff models. The shuffled complex evolution (SCE) method is used as an optimisation algorithm to estimate the model parameters of the MOUSE software package. The surface runoff model is exemplified by the time/area model. The comparison of calibration results of automatic and manual calibration procedures is discussed. The calibration results show the potential of an applied automated calibration scheme as a viable alternative to the manual approach.
Analysis of the impact of COVID-19 pandemic and response on routine childhood vaccination coverage and equity in Northern Nigeria: a mixed methods study

Background Based on 2021 data, Nigeria had the second largest number of zero-dose children globally estimated at over 2.25 million, concentrated in the northern part of the country due to factors some of which are sociocultural. This study analysed the impact of the COVID-19 pandemic and response on childhood vaccination in Northern Nigeria. Methods Using a mixed methods sequential study design in the most populous northern states of Kaduna and Kano, quantitative routine immunisation data for the period 2018–2021 and qualitative data collected through 16 focus group discussions and 40 key informant interviews were used. An adaptation of the socioecological model was used as a conceptual framework. Mean vaccination coverages and test of statistical difference in childhood vaccination data were computed. Qualitative data were coded and analysed thematically. Results Mean Penta 1 coverage declined in Kaduna from 69.88% (SD=21.02) in 2018 to 59.54% (SD=19.14%) by 2021, contrasting with Kano where mean Penta 1 coverage increased from 51.87% (SD=12.61) to 56.32% (SD=17.62%) over the same period. Outreaches and vaccination in urban areas declined for Kaduna state by 10% over the pandemic period in contrast to Kano state where it showed a marginal increase. The two states combined had an estimated 25% of the country’s zero-dose burden in 2021. Lockdowns, lack of transport and no outreaches which varied across the states were some of the factors mentioned by participants to have negatively impacted childhood vaccination. Special vaccination outreaches were among the recommendations for ensuring continued vaccination through a future pandemic. Conclusion While further interrogating the accuracy of denominator estimates for the urban population, incorporating findings into pandemic preparedness and response will ensure uninterrupted childhood vaccination during emergencies. Addressing the identified issues will be critical to achieving and sustaining universal childhood vaccination in Nigeria.
Alloantigen Infusion Activates the Transcriptome of Type 2 Conventional Dendritic Cells

Abstract Recent studies have revealed novel molecular mechanisms by which innate monocytic cells acutely recognize and respond to alloantigen with significance to allograft rejection and tolerance. What remains unclear is the single-cell heterogeneity of the innate alloresponse, particularly the contribution of dendritic cell (DC) subsets. To investigate the response of these cells to exposure of alloantigen, C57BL/6J mice were administered live allogenic BALB/cJ splenic murine cells versus isogenic cells. In parallel, we infused apoptotic allogenic and isogenic cells, which have been reported to modulate immunity. Forty-eight hours after injection, recipient spleens were harvested, enriched for DCs, and subjected to single-cell mRNA sequencing. Injection of live cells induced a greater transcriptional change across DC subsets compared with apoptotic cells. In the setting of live cell infusion, type 2 conventional DCs (cDC2s) were most transcriptionally responsive with a Ccr2+ cDC2 subcluster uniquely responding to the presence of alloantigen compared with the isogenic control. In vitro experimentation confirmed unique activation of CCR2+ cDC2s following alloantigen exposure. Candidate receptors of allorecognition in other innate populations were interrogated and A type paired Ig-like receptors were found to be increased in the cDC2 population following alloexposure. These results illuminate previously unclear distinctions between therapeutic infusions of live versus apoptotic allogenic cells and suggest a role for cDC2s in innate allorecognition. More critically, these studies allow for future interrogation of the transcriptional response of immune cells in the setting of alloantigen exposure in vivo, encouraging assessment of novel pathways and previously unexamined receptors in this setting.
Recent changes in the glaciers of Heard Island

ABSTRACT Heard Island, a heavily glacierized volcanic island in the Southern Ocean, is 80% ice-covered, with glaciers descending from 2,400 m to sea level: major glaciers are up to 7 km long with areas exceeding 10 km. Much of the island was photographed from the air in 1947 and again in early 1980. Photographs and limited ground surveys record changes (mostly retreats) in glacier fronts. Retreat is most marked on the eastern flanks where former tidewater glaciers are now grounded inland. Glaciers on northern and windward western flanks still end in ice cliffs but have narrowed; glaciers and ice caps on Laurens Peninsula (maximum elevation 710 m) are up to 65% smaller. Nearby lies Kerguelen and other southern islands with long climatic records have warrned significantly since the early 1960s. Surface and upper-air climatic data from Heard Island 1947–54 and records from automatic weather stations 1980–82 suggest that Heard too has warmed slightly, concurrently with a possible northward shift of low-pressure system tracks in this region. Temperatures have remained above average through the early 1980s and glacier retreat is expected to continue.
CDK4/6 inhibitors induce breast cancer senescence with enhanced anti‐tumor immunogenic properties compared with DNA‐damaging agents

Since therapy‐induced senescence (TIS) can either support or inhibit cancer progression, identifying which types of chemotherapeutic agents can produce the strongest anti‐tumor TIS is an important issue. Here, cyclin‐dependent kinase4/6 inhibitors (CDK4/6i)‐induced senescence was compared to the TIS induced by conventional DNA‐damaging agents. Despite both types of agents eliciting a similar degree of senescence, we observed increased expression of the senescence‐associated secretory phenotype (SASP) and ligands related to pro‐tumor immunity (IL6, CXCL8, TGFβ, CD274, and CEACAM1) and angiogenesis (VEGFA) mainly in TIS induced by DNA‐damaging agents rather than by CDK4/6i. Additionally, although all agents increased the expression of anti‐tumor immunomodulatory proteins related to antigen presentation (MHC‐I, B2M) and T cell chemokines (CXCL9, 10, 11), CDK4/6i‐induced senescent cells still maintained this expression at a similar or even higher intensity than cells treated with DNA‐damaging agents, despite the absence of nuclear factor‐kappa‐B (NF‐κB) and p53 activation. These data suggest that in contrast with DNA‐damaging agents, which augment the pro‐tumorigenic microenvironment via pro‐inflammatory SASP, CDK4/6i can generate TIS only with antitumor immunomodulatory proteins.
Effects of wet deposition on the abundance and size distribution of black carbon in East Asia

An improved understanding of the variations in the mass concentration and size distribution of black carbon (BC) in the free troposphere (FT) over East Asia, where BC emissions are very high, is needed to reliably estimate the radiative forcing of BC in climate models. We measured these parameters and the carbon monoxide (CO) concentration by conducting the Aerosol Radiative Forcing in East Asia (A‐FORCE) 2013W aircraft campaign in East Asia in winter 2013 and compared these data with measurements made in the same region in spring 2009. The median BC concentrations in the FT originating from North China (NC) and South China (SC) showed different seasonal variations, which were primarily caused by variations in meteorological conditions. CO concentrations above the background were much higher in SC than in NC in both seasons, suggesting a more active upward transport of CO. In SC, precipitation greatly increased from winter to spring, leading to an increased wet deposition of BC. As a result, the median BC concentration in the FT was highest in SC air in winter. This season and region were optimal for the effective transport of BC from the planetary boundary layer to the FT. The count median diameters of the BC size distributions generally decreased with altitude via wet removal during upward transport. The altitude dependence of the BC size distributions was similar in winter and spring, in accord with the similarity in the BC mixing state. The observed BC concentrations and microphysical properties will be useful for evaluating the performance of climate models.
Motor actions are spatially organized in motor and dorsal premotor cortex

Frontal motor areas are central to controlling voluntary movements. In non-human primates, the motor areas contain independent, somatotopic, representations of the forelimb (i.e., motor maps). But are the neural codes for actions spatially organized within those forelimb representations? Addressing this question would provide insight into the poorly understood structure–function relationships of the cortical motor system. Here, we tackle the problem using high-resolution optical imaging and motor mapping in motor (M1) and dorsal premotor (PMd) cortex. Two macaque monkeys performed an instructed reach-to-grasp task while cortical activity was recorded with intrinsic signal optical imaging (ISOI). The spatial extent of activity in M1 and PMd was then quantified in relation to the forelimb motor maps, which we obtained from the same hemisphere with intracortical microstimulation. ISOI showed that task-related activity was concentrated in patches that collectively overlapped <40% of the M1 and PMd forelimb representations. The spatial organization of the patches was consistent across task conditions despite small variations in forelimb use. Nevertheless, the largest condition differences in forelimb use were reflected in the magnitude of cortical activity. Distinct time course profiles from patches in arm zones and patches in hand zones suggest functional differences within the forelimb representations. The results collectively support an organizational framework wherein the forelimb representations contain subzones enriched with neurons tuned for specific actions. Thus, the often-overlooked spatial dimension of neural activity appears to be an important organizing feature of the neural code in frontal motor areas.
Combined effect of ozone and household air pollution on COPD in people aged less than 50 years old

Objectives Air pollution has been suggested as an important risk factor for chronic obstructive pulmonary disease (COPD); however, evidence of interactive effects on COPD between different factors was sparse, especially for young adults. We aimed to assess the combined effects of ambient ozone (O3) and household air pollution on COPD in young individuals. Methods We conducted a population-based study of residents aged 15–50 years in the low-income and middle-income regions of western China. We used multivariable logistic regression models to examine the associations between long-term ozone exposure and COPD in young individuals. Results A total of 6537 young cases were identified among the participants, with a COPD prevalence rate of 7.8 (95% CI 7.2% to 8.5%), and most young COPD individuals were asymptomatic. Exposure to household air pollution was associated with COPD in young patients after adjustment for other confounding factors (OR 1.82, 95% CI 1.41 to 2.37). We also found positive associations of COPD with O3 per IQR increase of 20 ppb (OR 1.92, 95% CI 1.59 to 2.32). The individual effects of household air pollution and O3 were 1.68 (95% CI 1.18 to 2.46) and 1.55 (95% CI 0.99 to 2.43), respectively, while their joint effect was 3.28 (95% CI 2.35 to 4.69) with the relative excess risk due to interaction of 1.05 (95% CI 0.33 to 1.78). Conclusions This study concludes that exposure to ambient O3 and household air pollution might be important risk factors for COPD among young adults, and simultaneous exposure to high levels of the two pollutants may intensify their individual effects.
Metacognition, public health compliance, and vaccination willingness

Significance Metacognition, the ability to reflect upon, and evaluate our own beliefs, can help us avoid making decisions based on unreliable evidence. Here, we provide empirical tests of the importance of human metacognition during the COVID-19 pandemic. Results demonstrate the predictive power of metacognitive sensitivity—our insight into the accuracy and fallibility of own COVID-19 beliefs—for reported compliance with recommended public health measures and vaccination willingness, above and beyond the accuracy of these beliefs. However, results provide only mixed evidence for the predictivity of metacognitive insight, controlling for the absolute confidence citizens had in their COVID-19 beliefs. This research highlights how behavior during the pandemic may relate to metacognitive self-reflection, not only to critical evaluation of external information.
A Web based geospatial application for disaster preparedness in Uganda

The power of Geospatial technologies in first world countries is increasingly being harnessed to manage disasters; this is not the same case for Uganda a disaster prone country in East Africa. For regions in the blankets of Mt. Rwenzori in the west and Mt. Elgon in the east, every year brings with it new challenges in the field of disaster management. When disasters happen in Uganda, government agencies and different Humanitarian Organizations run to the aid of the affected, relief is provided and rehabilitation activities carried out, but there remains little usable GI of the affected areas (Farthing & Ware, 2010). If disaster preparedness and management is dependent on accurate analysis and mapping of vulnerability and susceptibility of communities to risk (Office of the Prime Minister, 2010) and there exists data gaps and challenges (NEMA/UBOS, n.d.) in the country, how then can disaster managers carry out vulnerability assessment of communities? This thesis examines the possibility of providing disaster managers the means to assess the vulnerability of communities to risk by suggesting a solution for data acquisition and developing a web application based on interoperable modular components to act as a platform where this analysis can be performed.