bluuebunny/crossref_metadata_2025 huggingface dataset:
Varieties of felt presence? Three surveys of presence phenomena and their relations to psychopathology
Authors: Alderson-Day Ben , Moseley Peter , Mitrenga Kaja , Moffatt Jamie , Lee Rebecca , Foxwell John , Hayes Jacqueline , Smailes David , Fernyhough Charles
Published: March 2022

Background

Experiences of felt presence (FP) are well documented in neurology, neuropsychology and bereavement research, but systematic research in relation to psychopathology is limited. FP is a feature of sensorimotor disruption in psychosis, hypnagogic experiences, solo pursuits and spiritual encounters, but research comparing these phenomena remains rare. A comparative approach to the phenomenology of FP has the potential to identify shared and unique processes underlying the experience across these contexts, with implications for clinical understanding and intervention.

Methods

We present a mixed-methods analysis from three online surveys comparing FP across three diverse contexts: a population sample which included people with experience of psychosis and voice-hearing (study 1, N = 75), people with spiritual and spiritualist beliefs (study 2, N = 47) and practitioners of endurance/solo pursuits (study 3, N = 84). Participants were asked to provide descriptions of their FP experiences and completed questionnaires on FP frequency, hallucinatory experiences, dissociation, paranoia, social inner speech and sleep. Data and code for the study are available via OSF.

Results

Hierarchical linear regression analysis indicated that FP frequency was predicted by a general tendency to experience hallucinations in all three studies, although paranoia and gender (female > male) were also significant predictors in sample 1. Qualitative analysis highlighted shared and diverging phenomenology of FP experiences across the three studies, including a role for immersive states in FP.

Conclusions

These data combine to provide the first picture of the potential shared mechanisms underlying different accounts of FP, supporting a unitary model of the experience.
Coping with COVID: risk and resilience factors for mental health in a German representative panel study
Authors: Riepenhausen Antje , Veer Ilya M. , Wackerhagen Carolin , Reppmann Zala C. , Köber Göran , Ayuso-Mateos José Luis , Bögemann Sophie A. , Corrao Giovanni , Felez-Nobrega Mireia , Abad Josep Maria Haro , Hermans Erno , van Leeuwen Judith , Lieb Klaus , Lorant Vincent , Mary-Krause Murielle , Mediavilla Roberto , Melchior Maria , Mittendorfer-Rutz Ellenor , Compagnoni Matteo Monzio , Pan Kuan-Yu , Puhlmann Lara , Roelofs Karin , Sijbrandij Marit , Smith Pierre , Tüscher Oliver , Witteveen Anke , Zerban Matthias , Kalisch Raffael , Kröger Hannes , Walter Henrik
Published: March 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare.

Methods

In a stratified random sample of the German household population (n= 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting.

Results

PHQ-4 scores in 2020 (M= 2.45) and 2021 (M= 2.21) were elevated compared to 2019 (M= 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes.

Conclusions

We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.
Paediatric and adult congenital cardiology education and training in Europe
Authors: McMahon Colin J. , Heying Ruth , Budts Werner , Cavigelli-Brunner Anna , Shkolnikova Maria , Michel-Behnke Ina , Kozlik-Feldmann Rainer , Wåhlander Håkan , DeWolf Daniel , Difilippo Sylvie , Kornyei Laslo , Russo Maria Giovanna , Kaneva-Nencheva Anna , Mesihovic-Dinarevic Senka , Vesel Samo , Oskarsson Gylfi , Papadopoulos George , Petropoulos Andreas C. , Cevik Berna Saylan , Jossif Antonis , Doros Gabriela , Krusensjerna-Hafstrom Thomas , Dangel Joanna , Rahkonen Otto , Albert-Brotons Dimpna C. , Alvares Silvia , Brun Henrik , Janousek Jan , Pitkänen-Argillander Olli , Voges Inga , Lubaua Inguna , Sendzikaite Skaiste , Magee Alan G. , Rhodes Mark J. , Blom Nico A. , Bu’Lock Frances , Hanseus Katarina , Milanesi Ornella
Published: March 2022

Background:

Limited data exist on training of European paediatric and adult congenital cardiologists.

Methods:

A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries.

Results:

Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87–9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63–10.72 million), and one training centre per 4.29 million population (range 1.63–10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1–17), and duration of training was 3 years (range 2–5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41).

Conclusion:

Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.
Democracy, Terror, and Utopia in Dickens'sA Tale of Two Cities
Authors: Lamouria Lanya
Published: March 2022

This essay reads Charles Dickens'sA Tale of Two Cities(1859) as a previously unrecognized contribution to Victorian discourses around democracy. Approaching the novel through the parliamentary reform debate of the late 1850s and through Dickens's earlier writings about American democracy, I argue that this historical narrative of the French Revolution elaborates Victorian liberals’ fears that democracy will, on one hand, devalue individuality and produce a world of sameness or, on the other, overvalue individual sovereignty, giving way to isolating difference and social fragmentation. Despite his deep ambivalence about democratic reform, Dickens uses the novel to imagine alternative forms of political representation. The motif of “echoing footsteps” is one key example of the utopian democratic fantasy that the novel develops. In the “echoing footsteps” passages, Dickens appropriates the theories of Charles Babbage for political purposes, proposing that the earth's atmosphere is a medium that contains a complete democratic record of all the sounds made by every individual in existence. In this respect, the novel anticipates a concept of democracy as individual expression that today increasingly threatens democratic institutions.
Binge-Watching, Self-Determination, and Well-Being
Authors: Erdmann Elena , Dienlin Tobias
Published: March 2022

Abstract. Binge-watching is a highly relevant new media phenomenon. An increasing number of people watch multiple episodes of their favorite series online, a process often spanning several hours. Granow et al. (2018) showed that binge-watching is accompanied by both positive as well as negative psychological experiences. Because it is one of the most important studies on the topic, we conducted a direct replication of Granow et al. (2018) . We also extended the original study by including additional variables derived from self-determination theory. We conducted an online questionnaire with 668 respondents. Results showed that we could not reproduce the exact model that was reported. We also needed to adapt several of the originally tested measures to achieve satisfactory model fit. After introducing these changes, results showed that we replicated 67% of all effects in terms of significance (i.e., originally significant effects were also significant in the replication, and vice versa). When looking at effect size (i.e., originally reported effects fell into the replication’s 95% confidence interval), we replicated 42%. Our study represents a partial replication of Granow et al. (2018) . In our extension, we found two further positive links between binge-watching and well-being: Binge-watching was associated not only with greater autonomy, but also with increased feelings of competence and relatedness. Competence and relatedness were related to increased well-being, which included vitality, recovery experience, and media enjoyment. In line with Granow et al. (2018) , we found that binge-watching is related to self-determined media use and improved psychological well-being.
Large CO2 Emitters as Seen From Satellite: Comparison to a Gridded Global Emission Inventory
Authors: Chevallier Frédéric , Broquet Grégoire , Zheng Bo , Ciais Philippe , Eldering Annmarie
Published: March 2022

Using the multiyear archive of the two Orbiting Carbon Observatories (OCO) of NASA, we have retrieved large fossil fuel CO2 emissions (larger than 1.0 ktCO2 h−1 per 10−2 square degree grid cell) over the globe with a simple plume cross‐sectional inversion approach. We have compared our results with a global gridded and hourly inventory. The corresponding OCO emission retrievals explain more than one third of the inventory variance at the corresponding cells and hours. We have binned the data at diverse time scales from the year (with OCO‐2) to the average morning and afternoon (with OCO‐3). We see consistent variations of the median emissions, indicating that the retrieval‐inventory differences (with standard deviations of a few tens of percent) are mostly random and that trends can be calculated robustly in areas of favorable observing conditions, when the future satellite CO2 imagers provide an order of magnitude more data.
Structure of Sea Surface Temperature Anomaly Induced by Mesoscale Eddies in the North Pacific Ocean
Authors: Lv Mingkun , Wang Fan , Li Yuanlong , Zhang Zhengguang , Zhu Yanan
Published: February 2022

Sea surface temperature anomalies (SSTAs) induced by oceanic mesoscale eddies trigger mesoscale air‐sea interactions and modulate large‐scale climate systems. Yet, how eddies drive SSTAs has not been firmly established; particularly, the relative importance of lateral stirring and vertical pumping remains a debated issue. This study investigates characteristics and generation mechanisms of mesoscale eddy SSTAs in three eddy‐enriched domains of the North Pacific Ocean: the Kuroshio Extension (KET), the Subtropical Countercurrent (STCC), and the North Equatorial Countercurrent (NECC). Analysis of satellite observational data reveals quasi‐monopole eddy SSTAs in the KET and NECC and dipole‐like eddy SSTAs in the STCC. By investigating spatial and seasonal variations and performing sensitivity experiments using an idealized model, we demonstrate that lateral stirring plays a more important role than vertical pumping in causing mesoscale eddy SSTAs. The eastward transport by the strong background current UC (∼0.6 and ∼0.4 m s−1 in the KET and the NECC, respectively) and the westward eddy translation UT (∼−0.2 m s−1 in the NECC) can dramatically modify the structure of SSTA. The pure stirring effect of eddy rotation velocities generates strong dipole‐like SSTAs. Owing to the eastward UC and the westward UT, the western SSTA pole tends to approach the eddy center, while the eastern SSTA pole departs from the eddy and scatters along the eddy trajectory. These effects reduce the eddy SSTA amplitude and favor the emergence of quasi‐monopole structure. This work provides a useful benchmark for model simulations of mesoscale SST variability and air‐sea interaction.
Energetically Informed Niche Models of Hydrogenotrophs Detected in Sediments of Serpentinized Fluids of the Samail Ophiolite of Oman
Authors: Howells Alta E. G. , Leong James A. M. , Ely Tucker , Santana Michelle , Robinson Kirt , Esquivel‐Elizondo Sofia , Cox Alysia , Poret‐Peterson Amisha , Krajmalnik‐Brown Rosa , Shock Everett L.
Published: February 2022

A geochemical gradient established by mixing between reduced, hyperalkaline (pH > 11), H2‐rich fluids generated through the process of serpentinization and surrounding surface water (pH ∼ 8) in the Samail Ophiolite of Oman provides an opportunity to characterize the geochemical and biological factors that influence the distribution of H2 oxidizing chemotrophs, hydrogenotrophs. In this study, 16S rRNA gene amplicon sequencing was implemented to characterize hydrogenotrophs in sediments underlying surface expressed serpentinized fluids in Oman. Hydrogenotroph phylotype distribution was evaluated as functions of chemical energy supplies for their given metabolic redox reactions. Through this approach, it was discovered that hydrogenotrophic taxa are likely constrained to sediments with overlying fluids that have <∼60 μm O2, including microorganisms of the genus, Hydrogenophaga. Sulfate reducers of the family, Thermodesulfovibrionaceae, likely require >∼10 μm SO4−2 for survival. In sediments with fluids having >∼10 μm SO4−2, sulfate reducers likely outcompete microorganisms of the methanogen genus, Methanobacterium, for H2. Additionally, differences in distribution between Thermodesulfovibrionaceae and Methanobacterium may be driven by the availability of electron acceptors and the redox reaction that is most energy yielding in the fluid. Taken together, observations from the Oman geochemical gradient result in a hydrogenotroph niche model that can be used to evaluate global distribution patterns of hydrogenotrophs in continental serpentinized fluids. On a global scale, based on previous studies, Methanobacterium is constrained to fluids that have <∼10 μm SO4−2.
Feedforward and feedback interactions between visual cortical areas use different population activity patterns
Authors: Semedo João D. , Jasper Anna I. , Zandvakili Amin , Krishna Aravind , Aschner Amir , Machens Christian K. , Kohn Adam , Yu Byron M.
Published: March 2022

Brain function relies on the coordination of activity across multiple, recurrently connected brain areas. For instance, sensory information encoded in early sensory areas is relayed to, and further processed by, higher cortical areas and then fed back. However, the way in which feedforward and feedback signaling interact with one another is incompletely understood. Here we investigate this question by leveraging simultaneous neuronal population recordings in early and midlevel visual areas (V1–V2 and V1–V4). Using a dimensionality reduction approach, we find that population interactions are feedforward-dominated shortly after stimulus onset and feedback-dominated during spontaneous activity. The population activity patterns most correlated across areas were distinct during feedforward- and feedback-dominated periods. These results suggest that feedforward and feedback signaling rely on separate “channels”, which allows feedback signals to not directly affect activity that is fed forward.
Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment
Authors: Vanuytsel Kim , Villacorta-Martin Carlos , Lindstrom-Vautrin Jonathan , Wang Zhe , Garcia-Beltran Wilfredo F. , Vrbanac Vladimir , Parsons Dylan , Lam Evan C. , Matte Taylor M. , Dowrey Todd W. , Kumar Sara S. , Li Mengze , Wang Feiya , Yeung Anthony K. , Mostoslavsky Gustavo , Dries Ruben , Campbell Joshua D. , Belkina Anna C. , Balazs Alejandro B. , Murphy George J.
Published: March 2022

The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, hematopoietic stem cells in the fetal liver undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. Here, we profile 26,407 fetal liver cells at both the transcriptional and protein level including ~7,000 highly enriched and functional fetal liver hematopoietic stem cells to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression reveals a generalizable signature defining functional fetal liver hematopoietic stem cells and allows for the stratification of enrichment strategies with high translational potential. More precisely, our integrated analysis identifies CD201 (endothelial protein C receptor (EPCR), encoded by PROCR) as a marker that can specifically enrich for engraftment potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers. As such, it serves as a useful resource for the field and forms the basis for further biological exploration of strategies to retain the engraftment potential of hematopoietic stem cells ex vivo or induce this potential during in vitro hematopoietic stem cell generation.
Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma
Authors: Smith Lorey K. , Parmenter Tiffany , Kleinschmidt Margarete , Kusnadi Eric P. , Kang Jian , Martin Claire A. , Lau Peter , Patel Riyaben , Lorent Julie , Papadopoli David , Trigos Anna , Ward Teresa , Rao Aparna D. , Lelliott Emily J. , Sheppard Karen E. , Goode David , Hicks Rodney J. , Tiganis Tony , Simpson Kaylene J. , Larsson Ola , Blythe Benjamin , Cullinane Carleen , Wickramasinghe Vihandha O. , Pearson Richard B. , McArthur Grant A.
Published: March 2022

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy.
Massive interstitial solid solution alloys achieve near-theoretical strength
Authors: Liu Chang , Lu Wenjun , Xia Wenzhen , Du Chaowei , Rao Ziyuan , Best James P. , Brinckmann Steffen , Lu Jian , Gault Baptiste , Dehm Gerhard , Wu Ge , Li Zhiming , Raabe Dierk
Published: March 2022

Interstitials, e.g., C, N, and O, are attractive alloying elements as small atoms on interstitial sites create strong lattice distortions and hence substantially strengthen metals. However, brittle ceramics such as oxides and carbides usually form, instead of solid solutions, when the interstitial content exceeds a critical yet low value (e.g., 2 at.%). Here we introduce a class of massive interstitial solid solution (MISS) alloys by using a highly distorted substitutional host lattice, which enables solution of massive amounts of interstitials as an additional principal element class, without forming ceramic phases. For a TiNbZr-O-C-N MISS model system, the content of interstitial O reaches 12 at.%, with no oxides formed. The alloy reveals an ultrahigh compressive yield strength of 4.2 GPa, approaching the theoretical limit, and large deformability (65% strain) at ambient temperature, without localized shear deformation. The MISS concept thus offers a new avenue in the development of metallic materials with excellent mechanical properties.
Aragonite dissolution protects calcite at the seafloor
Authors: Sulpis Olivier , Agrawal Priyanka , Wolthers Mariette , Munhoven Guy , Walker Matthew , Middelburg Jack J.
Published: March 2022

In the open ocean, calcium carbonates are mainly found in two mineral forms. Calcite, the least soluble, is widespread at the seafloor, while aragonite, the more soluble, is rarely preserved in marine sediments. Despite its greater solubility, research has shown that aragonite, whose contribution to global pelagic calcification could be at par with that of calcite, is able to reach the deep-ocean. If large quantities of aragonite settle and dissolve at the seafloor, this represents a large source of alkalinity that buffers the deep ocean and favours the preservation of less soluble calcite, acting as a deep-sea, carbonate version of galvanization. Here, we investigate the role of aragonite dissolution on the early diagenesis of calcite-rich sediments using a novel 3D, micrometric-scale reactive-transport model combined with 3D, X-ray tomography structures of natural aragonite and calcite shells. Results highlight the important role of diffusive transport in benthic calcium carbonate dissolution, in agreement with recent work. We show that, locally, aragonite fluxes to the seafloor could be sufficient to suppress calcite dissolution in the top layer of the seabed, possibly causing calcite recrystallization. As aragonite producers are particularly vulnerable to ocean acidification, the proposed galvanizing effect of aragonite could be weakened in the future, and calcite dissolution at the sediment-water interface will have to cover a greater share of CO2 neutralization.
Subnanometric alkaline-earth oxide clusters for sustainable nitrate to ammonia photosynthesis
Authors: Li Jieyuan , Chen Ruimin , Wang Jielin , Zhou Ying , Yang Guidong , Dong Fan
Published: March 2022

The limitation of inert N2 molecules with their high dissociation energy has ignited research interests in probing other nitrogen-containing species for ammonia synthesis. Nitrate ions, as an alternative feedstock with high solubility and proton affinity, can be facilely dissociated for sustainable ammonia production. Here we report a nitrate to ammonia photosynthesis route (NO3−RR) catalyzed by subnanometric alkaline-earth oxide clusters. The catalyst exhibits a high ammonia photosynthesis rate of 11.97 mol gmetal−1 h−1 (89.79 mmol gcat−1 h−1) with nearly 100% selectivity. A total ammonia yield of 0.78 mmol within 72 h is achieved, which exhibits a significant advantage in the area of photocatalytic NO3−RR. The investigation of the molecular-level reaction mechanism reveals that the unique active interface between the subnanometric clusters and TiO2 substrate is beneficial for the nitrate activation and dissociation, contributing to efficient and selective nitrate reduction for ammonia production with low energy input. The practical application of NO3−RR route in simulated wastewater is developed, which demonstrates great potential for its industrial application. These findings are of general knowledge for the functional development of clusters-based catalysts and could open up a path in the exploitation of advanced ammonia synthesis routes with low energy consumption and carbon emission.
Tree functional traits, forest biomass, and tree species diversity interact with site properties to drive forest soil carbon
Authors: Augusto Laurent , Boča Antra
Published: March 2022

Forests constitute important ecosystems in the global carbon cycle. However, how trees and environmental conditions interact to determine the amount of organic carbon stored in forest soils is a hotly debated subject. In particular, how tree species influence soil organic carbon (SOC) remains unclear. Based on a global compilation of data, we show that functional traits of trees and forest standing biomass explain half of the local variability in forest SOC. The effects of functional traits on SOC depended on the climatic and soil conditions with the strongest effect observed under boreal climate and on acidic, poor, coarse-textured soils. Mixing tree species in forests also favours the storage of SOC, provided that a biomass over-yielding occurs in mixed forests. We propose that the forest carbon sink can be optimised by (i) increasing standing biomass, (ii) increasing forest species richness, and (iii) choosing forest composition based on tree functional traits according to the local conditions.
Prenatal and early life exposure to air pollution and the incidence of Kawasaki disease
Authors: Kuo Ni-Chun , Lin Chien-Heng , Lin Ming-Chih
Published: March 2022

Kawasaki disease (KD) is the most common form of acquired pediatric cardiac disease in the developed world. However, its etiology is still unclear. Epidemiological studies have shown that air pollution is a plausible risk factor in stimulating oxidative stress, inducing inflammation and causing autoimmune diseases. This study aims to assess the connections between prenatal and early life air pollution exposure to the incidence of KD. The main data source of this nationwide longitudinal study was the National Health Insurance Research Database (NHIRD) of Taiwan. NHIRD was linked with Taiwan Maternal and Child Health Database to establish the link between mothers and children. In total, 4192 KD cases involving children under 6 years of age were identified between January 2004 and December 2010. Children in the control group were randomly selected at a 1:4 ratio and matched using their age and index year. Integrated data for the air pollutants were obtained from 71 Environmental Protection Agency monitoring stations across Taiwan. Patients who had main admission diagnosis of KD and subsequently received intravenous immunoglobulin treatment were defined as incidence cases. Ambient exposure, including pollutant standards index (PSI), carbon monoxide (CO), nitric oxide (NO), nitric dioxide (NO2), and nitrogen oxide (NOx) during pregnancy were all positively associated with KD incidence. Conversely, ozone (O3) exposure had a negative correlation. Exposure to CO, NO, NO2, and NOx after childbirth remained consistent with regards to having a positive association with KD incidence. Exposure to PSI and O3 after delivery displayed no significant association with KD. Both prenatal and postnatal cumulative CO, NO, NO2, and NOx exposure had a dose dependent effect towards increasing KD incidence. Certain prenatal and early life air pollutant exposure may increase the incidence of KD.
Transposase-CRISPR mediated targeted integration (TransCRISTI) in the human genome
Authors: Rezazade Bazaz Mahere , Ghahramani Seno Mohammad M. , Dehghani Hesam
Published: March 2022

Various methods have been used in targeted gene knock-in applications. CRISPR-based knock-in strategies based on homology-independent repair pathways such as CRISPR HITI have been shown to possess the best efficiency for gene knock-in in mammalian cells. However, these methods suffer from the probability of plasmid backbone insertion at the target site. On the other hand, studies trying to combine the targeting ability of the Cas9 molecule and the excision/integration capacity of the PB transposase have shown random integrations. In this study, we introduce a new homology-independent knock-in strategy, Transposase-CRISPR mediated Targeted Integration (TransCRISTI), that exploits a fusion of Cas9 nuclease and a double mutant piggyBac transposase. In isogenic mammalian cell lines, we show that the TransCRISTI method demonstrates higher efficiency (72%) for site-specific insertions than the CRISPR HITI (44%) strategy. Application of the TransCRISTI method resulted in site-directed integration in 4.13% and 3.69% of the initially transfected population in the human AAVS1and PML loci, respectively, while the CRISPR HITI strategy resulted in site-directed integration in the PML locus in only 0.6% of cells. We also observed lower off-target and random insertions in the TransCRISTI group than the CRISPR HITI group. The TransCRISTI technology represents a great potential for the accurate and high-efficiency knock-in of the desired transposable elements into the predetermined genomic locations.
Association between chronic kidney disease and open-angle glaucoma in South Korea: a 12-year nationwide retrospective cohort study
Authors: Ro Jun-Soo , Moon Jong Youn , Park Tae Kwann , Lee Si Hyung
Published: March 2022

Various non-intraocular pressure factors have been identified as possible risk factors for open-angle glaucoma (OAG). However, there is still controversy around the association between OAG and chronic kidney disease (CKD). In this study, we used a nationwide cohort to investigate the risk of OAG in the 12 years following a diagnosis of CKD. This retrospective cohort study included 1,103,302 subjects from the Korean National Health Insurance Service National Sample Cohort database. The CKD group (n = 1318) included patients who were initially diagnosed with CKD between 2003 and 2008. The subjects in the comparison group were matched at a 1:5 ratio using propensity scores. In multivariate Cox regression analysis, a diagnosis of CKD was significantly associated with an increased incidence of OAG (hazard ratio [HR] = 1.546, 95% confidence interval [CI] 1.363–1.754, p < 0.001). Further analysis revealed that the risk of OAG increased with the severity of CKD (mild to moderate CKD [CKD stage 1–3]: HR = 1.280, 95% CI 1.077–1.521, p = 0.005; advanced CKD [CKD stage 4–5]: HR = 1.861, 95% CI 1.589–2.180, p < 0.001). In subgroup analysis, female CKD patients had a greater risk of developing OAG than males, and subjects with CKD aged ≥ 40 years were more likely to develop OAG compared with those aged < 40 years. Our study demonstrates that CKD is a significant risk factor for OAG and that severe CKD is associated with an increased risk of developing OAG.
A quantitative study on the impact of working environment on the well-being of teachers in China’s private colleges
Authors: Chen Jinping , Cheng Hongyan , Zhao Dan , Zhou Fuyu , Chen Yuan
Published: March 2022

Teacher well-being is a prominent issue in policy and public debates. Those teachers working in private schools deserve concern given concerns about their working environment. Focus of this study: to learn about the level and main characteristics of teacher well-being in private schools and to explore the impact of working environment on their well-being. Methodology: The data were collected via an online questionnaire among 1161 language teachers at 58 China’s private colleges in 22 provinces, and were quantitatively analyzed with SPSS 23.0. Findings: These teachers have an intermediate level of overall well-being. Performance evaluation, student academic foundation, and pressure of research work are the main negative impacting factors; while social support from leaders and colleagues, work autonomy, training and development opportunities, and appraisal feedback guide are key resources enhancing their well-being. Discussions: The impacting factors of working environment on teacher well-being in private schools are unique due to the special scenarios. Implications: The results of this study may apply to similar private schools, suggesting pertinent stakeholders to take targeted measures, to guarantee enough economic input into running school, and to put democratic and professional leadership into practice for promoting teacher well-being in the private education sector.
DNA repair phenotype and cancer risk: a systematic review and meta-analysis of 55 case–control studies
Authors: Wu Hui-Chen , Kehm Rebecca , Santella Regina M. , Brenner David J. , Terry Mary Beth
Published: March 2022

DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity. We included 55 case–control studies that evaluated 12 different cancers using 10 different DNA repair assays. The pooled OR of cancer risk (all cancer types combined) was 2.92 (95% Confidence Interval (CI) 2.49, 3.43) for the lowest DNA repair. Lower DNA repair was associated with all studied cancer types, and pooled ORs (95% CI) ranged from 2.02 (1.43, 2.85) for skin cancer to 7.60 (3.26, 17.72) for liver cancer. All assays, except the homologous recombination repair assay, showed statistically significant associations with cancer. The effect size ranged from 1.90 (1.00, 3.60) for the etoposide-induced double-strand break assay to 5.06 (3.67, 6.99) for the γ-H2AX assay. The consistency and strength of the associations support the use of these phenotypic biomarkers; however large-scale prospective studies will be important for understanding their use related to age and screening initiation.
Preterm birth buccal cell epigenetic biomarkers to facilitate preventative medicine
Authors: Winchester Paul , Nilsson Eric , Beck Daniel , Skinner Michael K.
Published: March 2022

Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. The current study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). An epigenome-wide association study (EWAS) was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p < 1e−04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes. Observations identify a potential paternal germline contribution for preterm birth and identify the potential epigenetic inheritance of preterm birth susceptibility for the female child later in life. Although expanded clinical trials and preconception trials are required to optimize the potential epigenetic biomarkers, such epigenetic biomarkers may allow preventative medicine strategies to reduce the incidence of preterm birth.
Initial measurement of ion nonextensive parameter with geodesic acoustic mode theory
Authors: Qiu Huibin , Xiao Donghua , Wu Junjie , Wu Shengfa , Zhong Chengjie , Li Xiaobin , Peng Xingkun , Yuan Youlong , Cai Qilong , Chang Jinming , Hu Tianyi , Hu Zuozhi , Zhu Yuqing
Published: March 2022

The consideration of nonextensivity effects is crucial to the accurate diagnosis of plasma parameters; common plasma nonextensive parameters include electron nonextensive parameter and ion nonextensive parameter, and the former can be measured, while the ion nonextensive parameter cannot be measured yet. Here we show the measurement of ion nonextensive parameter of plasma based on the theory of nonextensive geodesic acoustic modes. We assume that the plasma to be measured can be described by nonextensive statistical mechanics, and on this basis, the nonextensive geodesic acoustic mode theory is established. Utilizing this theory, we have measured the ion nonextensive parameter $${{q}_{{{F}_{\mathrm {i}}}}}= 1.565$$

q

F
i

=
1.565

which cannot be diagnosed even by a nonextensive single electric probe. Our research points out that the proposed measurement method of ion nonextensive parameter may play a role in plasma diagnosis and will help us to grasp the nonextensivity of plasma more precisely. We hope the proposed method of ion nonextensive parameter diagnosis based on the nonextensive geodesic acoustic mode theory can be the starting point of more complex ion nonextensive parameter diagnosis methods. In addition, the measurement of ion nonextensive parameter is closely related to the study of various plasma waves, instabilities, turbulence and abnormal transport, and a defined and quantitative test of nonextensive geodesic acoustic mode theory will bound up deeply with such developments.
GC–MS and molecular docking analyses of phytochemicals from the underutilized plant, Parkia timoriana revealed candidate anti-cancerous and anti-inflammatory agents
Authors: Ralte Laldinfeli , Khiangte Laldinliana , Thangjam Nurpen M. , Kumar Awadhesh , Singh Y. Tunginba
Published: March 2022

Plants are excellent sources of functionally bioactive compounds and essential nutrients. The phytochemical constituents have enormous potential in treating both plant and human diseases. Parkia timoriana (Yongchak/Zawngtah), one of the most important underutilized plants popularly consumed in Manipur and Mizoram states of Northeastern region of India, is known for its ethnobotanical and ethnomedicinal values. A significant DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), and Phosphomolybdate scavenging activity corresponding to high antioxidant potentials was shown by the extracts from different edible parts of P. timoriana. P. timoriana extract showed significant antibacterial potential against Bacillus pumilus, Bacillus subtillis, Escherichia coli and Pseudomonas aeruginosa. Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry (GC–MS) analyses of the extracts revealed the functional groups and bioactive compounds present in different edible parts of the plant. Characteristic peaks of phenols, carboxylic acids, alkenes, glycogen, alkyl halides, halogen, aliphatic amines, primary and secondary amines, esters, ether, aromatics, lipids, triglycerides, nitro compounds that had antimicrobial, anti-cancer and anti-inflammatory properties etc. were observed. The GC–MS analysis also revealed the occurrence of 49 bioactive compounds that are known to possess a variety of pharmacological activities. Subsequently, in silico molecular docking studies of the identified bioactive compounds predicted potential anticancer and anti-inflammatory properties. To the best of our knowledge, this is the first-hand report on the bioactive compounds of edible parts of P. timoriana extracts showing antioxidant, antimicrobial and pharmacological significance. This study can lead to the production of new herbal medicines for various diseases employing P. timoriana and perhaps leading to the creation of new medications.
Transgenic manipulation of triacylglycerol biosynthetic enzymes in B. napus alters lipid-associated gene expression and lipid metabolism
Authors: Liao Pan , Lechon Tamara , Romsdahl Trevor , Woodfield Helen , Fenyk Stepan , Fawcett Tony , Wallington Emma , Bates Ruth E. , Chye Mee-Len , Chapman Kent D. , Harwood John L. , Scofield Simon
Published: March 2022

Oilseed rape (Brassica napus) is an important crop that is cultivated for the oil (mainly triacylglycerol; TAG) it produces in its seeds. TAG synthesis is controlled mainly by key enzymes in the Kennedy pathway, such as glycerol 3-phosphate acyltransferase (GPAT), lysophosphatidate acyltransferase (LPAT) and diacylglycerol acyltransferase (DGAT) but can also be produced from phosphoglycerides such as phosphatidylcholine (PC) by the activity of the enzyme phospholipid: diacylglycerol acyltransferase (PDAT). To evaluate the potential for these enzymes to alter oil yields or composition, we analysed transgenic B. napus lines which overexpressed GPAT, LPAT or PDAT using heterologous transgenes from Arabidopsis and Nasturtium and examined lipid profiles and changes in gene expression in these lines compared to WT. Distinct changes in PC and TAG abundance and spatial distribution in embryonic tissues were observed in some of the transgenic lines, together with altered expression of genes involved generally in acyl-lipid metabolism. Overall our results show that up-regulation of these key enzymes differentially affects lipid composition and distribution as well as lipid-associated gene expression, providing important information which could be used to improve crop properties by metabolic engineering.
Local genetic variation of inflammatory bowel disease in Basque population and its effect in risk prediction
Authors: Garcia-Etxebarria Koldo , Merino Olga , Gaite-Reguero Adrián , Rodrigues Pedro M. , Herrarte Amaia , Etxart Ane , Ellinghaus David , Alonso-Galan Horacio , Franke Andre , Marigorta Urko M. , Bujanda Luis , D’Amato Mauro
Published: March 2022

Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract. Although its aetiology remains unknown, environmental and genetic factors are involved in its development. Regarding genetics, more than 200 loci have been associated with IBD but the transferability of those signals to the Basque population living in Northern Spain, a population with distinctive genetic background, remains unknown. We have analysed 5,411,568 SNPs in 498 IBD cases and 935 controls from the Basque population. We found 33 suggestive loci (p < 5 × 10−6) in IBD and its subtypes, namely Crohn’s Disease (CD) and Ulcerative Colitis (UC), detecting a genome-wide significant locus located in HLA region in patients with UC. Those loci contain previously associated genes with IBD (IL23R, JAK2 or HLA genes) and new genes that could be involved in its development (AGT, BZW2 or FSTL1). The overall genetic correlation between European populations and Basque population was high in IBD and CD, while in UC was lower. Finally, the use of genetic risk scores based on previous GWAS findings reached area under the curves > 0.68. In conclusion, we report on the genetic architecture of IBD in the Basque population, and explore the performance of European-descent genetic risk scores in this population.
Using contact tracing from interlocking diaries to map mood contagion along network chains
Authors: Fu Yang-chih , Chan Ta-Chien , Chu Yen-Hua , Hwang Jing-Shiang
Published: March 2022

Both viruses and moods are transmitted through interpersonal contacts, but it has been extremely difficult to track each unique chain of contacts through which particular moods diffuse. By analyzing 56,060 contact records from 113 interlocking, yearlong diaries collected through a web-based platform in Taiwan, we traced mood states before and after each specific contact along a triplet of persons where B contacts C and subsequently contacts A. Multilevel analyses show that both positive and negative emotions are contagious, but the two paths diverge markedly in how the diffusion stops. Positive contact between C and B (which leads to improved mood for B) spreads to A through B’s contact with A, making A feel better afterward, regardless of whether B’s mood deteriorated between the two interactions. Negative contact between C and B (which leads to worsened mood for B) also spreads to A, making A feel worse after the contact with B. However, the spread of a negative mood discontinues if B’s mood improved between the two contacts. The different patterns of diffusion suggest that a negative mood is harder to disperse, probably because people generally make efforts to keep their negative emotions from spreading to others.
Structural and functional characterization of an achromatopsia-associated mutation in a phototransduction channel
Authors: Zheng Xiangdong , Li Huan , Hu Zhengshan , Su Deyuan , Yang Jian
Published: March 2022

Numerous missense mutations in cyclic nucleotide-gated (CNG) channels cause achromatopsia and retinitis pigmentosa, but the underlying pathogenic mechanisms are often unclear. We investigated the structural basis and molecular/cellular effects of R410W, an achromatopsia-associated, presumed loss-of-function mutation in human CNGA3. Cryo-EM structures of the Caenorhabditis elegans TAX-4 CNG channel carrying the analogous mutation, R421W, show that most apo channels are open. R421, located in the gating ring, interacts with the S4 segment in the closed state. R421W disrupts this interaction, destabilizes the closed state, and stabilizes the open state. CNGA3_R410W/CNGB3 and TAX4_R421W channels are spontaneously active without cGMP and induce cell death, suggesting cone degeneration triggered by spontaneous CNG channel activity as a possible cause of achromatopsia. Our study sheds new light on CNG channel allosteric gating, provides an impetus for a reevaluation of reported loss-of-function CNG channel missense disease mutations, and has implications for mutation-specific treatment of retinopathy.
Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
Authors: Bost Jeremy P. , Ojansivu Miina , Munson Michael J. , Wesén Emelie , Gallud Audrey , Gupta Dhanu , Gustafsson Oskar , Saher Osama , Rädler Julia , Higgins Stuart G. , Lehto Taavi , Holme Margaret N. , Dahlén Anders , Engkvist Ola , Strömstedt Per-Erik , Andersson Shalini , Edvard Smith C. I. , Stevens Molly M. , Esbjörner Elin K. , Collén Anna , El Andaloussi Samir
Published: March 2022

The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.