bluuebunny/crossref_metadata_2025 huggingface dataset:
Public services and the urban middling sort: the provision of water in Bristol, Chester and Ipswich, 1540–1640
Authors: Winter Mabel
Published: September 2023

This article examines the relationship between public services and the urban middling sort in provincial England from 1550 to 1640 through comparative case-studies of the finance and management of waterworks, the creation of new skilled roles and the cultural import of water systems in Bristol, Chester and Ipswich. It argues that the middling sort were vital in establishing public services and that water provision centred not only on its value as a material and financial resource, but also as an expanding source of patronage and social capital that shaped and entrenched the emergence of middling groups in society.
Automatic enrollment with a 12 percent default contribution rate
Authors: Beshears John , Guo Ruofei , Laibson David , Madrian Brigitte C. , Choi James J.
Published: September 2023

We study a retirement savings plan with a default contribution rate of 12 percent of income, which is much higher than previously studied defaults. Twenty-five percent of employees had not opted out of this default 12 months after hire; a literature review finds that the corresponding fraction in plans with lower defaults is approximately one-half. Because only contributions above 12 percent were matched by the employer, 12 percent was likely to be a suboptimal contribution rate for employees. Employees who remained at the 12 percent default contribution rate had average income that was approximately one-third lower than would be predicted from the relationship between salaries and contribution rates among employees who were not at 12 percent. Defaults may influence low-income employees more strongly in part because these employees face higher psychological barriers to active decision making.
Temporal Variations in Vertical Cloud Structure of Jupiter's Great Red Spot, Its Surroundings and Oval BA From HST/WFC3 Imaging
Authors: Anguiano‐Arteaga Asier , Pérez‐Hoyos Santiago , Sánchez‐Lavega Agustín , Sanz‐Requena José Francisco , Irwin Patrick G. J.
Published: September 2023

In this study, we present the evolution of the properties and vertical distribution of the hazes in Jupiter's Great Red Spot (GRS), its surroundings and Oval BA from 2015 to 2021. To retrieve the main atmospheric parameters, we model the spectral reflectivity of a number of dynamically and/or spectrally interesting regions with a radiative transfer tool that uses an optimal estimator scheme. The spectra of the selected regions are obtained from high‐resolution Hubble Space Telescope Wide Field Camera 3 images that cover the spectral range from 200 to 900 nm. The a priori model atmosphere used to describe the various Jovian regions is taken from Anguiano‐Arteaga et al. (2021, https://doi.org/10.1029/2021JE006996) for each corresponding area. We find that the biggest variations in the GRS occur in the optical thickness of the stratospheric and tropospheric haze layers starting in 2019 and in the mean size of the tropospheric haze particles in 2018. The absorption spectra of both hazes show little variations among the analyzed regions and years, with the stratospheric haze properties seeming compatible with the chromophore proposed by Carlson et al. (2016, https://doi.org/10.1016/j.icarus.2016.03.008). We report a color change of Oval BA from red to white during these years that, according to our models, can be mostly explained in terms of a decrease in the stratospheric haze optical depth.
Changes in Dissolved Inorganic Carbon Across Yangtze River Regulated by Dam and River‐Lake Exchange
Authors: Zhao Chu , Wang Chuan , Li Jianhong , Meng Lize , Xue Jingya , Gao Yang , Huang Tao , Bai Yixin , Li Shuaidong , Yang Hao , Shi Kun , Xu Yuanhui , Huang Changchun
Published: September 2023

The boom in dam construction and continuous river‐lake exchange has had a profound impact on the transmission and transformation of riverine dissolved inorganic carbon (DIC). An in‐depth understanding of the change mechanisms of DIC concentrations and sources driven by dam operation and lake recharge is crucial for regulating greenhouse gas emissions and evaluating the impact of DIC on the global carbon cycle. This study investigated dam‐ and lakes‐driven DIC via the concentration and δ13C of DIC, combined with anions, cations, δD and δ18O in the main stream of the Yangtze River. DIC showed a decreasing trend from upper reach (2,262.31 ± 113.69 μmol kg−1) to lower reach (1,771.61 ± 89.36 μmol kg−1). Carbonate dissolution proportion (from 36.45% to 28.44%) and atmospheric CO2 proportion (from 37.51% to 22.94%) of DIC decreased from upper reach to lower reach, whereas soil CO2 proportion of DIC (from 26.01% to 48.63%) increased. The control of dam operation on DIC biogeochemical process was revealed from different time scales. From the perspective of short‐term seasonal changes (from 2020 to 2021), the mineralization of organic matter in the dry season strengthened CO2 degassing and calcite precipitation, reducing the DIC and increasing the proportion of soil CO2. Meanwhile, longer periods of runoff retention provided sufficient time for water–rock reactions in the wet season and increased the DIC and carbonate dissolution source in the reservoir area. On a long‐term scale (from 2009 to 2021), a decrease in pH driven by sediment mineralization contributed to an annual increase in DIC in the reservoir. The flow of lakes mixed into the mainstream was revealed by the enrichment of δ18O, and river‐communicating recharge decreased the DIC and carbonate dissolution source. We show that dam operation and lake inflow change DIC concentrations and sources and therefore need to be considered in the transmission and transformation processes of DIC in the river‐ocean continuum.
Influence of the Thermal Structure on the Intensification of the Extreme Arctic Cyclone in August 2016
Authors: Qian Qian , Zhong Wei , Yao Yao , Zhang Deyuan
Published: September 2023

As one of the most dangerous weather systems affecting the Arctic region, Arctic cyclones (ACs) significantly affect Arctic shipping routes and navigation safety. This study investigates the evolution and structure characteristics of an extreme AC in August 2016 (AC16) based on the Arctic System Reanalysis version 2 (ASRv2) data set. The key factors affecting the development of AC16 are revealed by diagnosing the pressure tendency equation (PTE), with focus on the influence of thermal structure during two rapid intensification stages. It is found that PTE‐diagnosed results can well reproduce the evolution of AC16. The air‐column virtual temperature change is the decisive contributor decreasing the surface pressure and thus intensifying AC16, while the change in geopotential at upper boundary and the mass change caused by evaporation and precipitation have less effect. Further analysis indicates that at the initial rapid intensification stage, the middle‐lower‐level diabatic heating probably related to condensation latent heat and the upper‐level warm advection influenced by tropopause polar vortices (TPVs) have crucial effects on the air‐column warming, which leads to the AC16 rapid intensification initially. At the secondary rapid intensification stage, the upper‐level warm advection affected by TPVs further increases the air‐column virtual temperature, which is the dominant contributor to the AC16 secondary drastic intensification.
Seasonal and Diurnal Variations in XCO2 Characteristics in China as Observed by OCO‐2/3 Satellites: Effects of Land Cover and Local Meteorology
Authors: Zhao Hengheng , Gui Ke , Yao Wenrui , Shang Nanxuan , Zhang Xutao , Zhang Xinglu , Li Lei , Zheng Yu , Wang Zhili , Ren Hong‐Li , Wang Hong , Sun Junying , Li Jian , Che Huizheng , Zhang Xiaoye
Published: September 2023

Monitoring the dynamics of atmospheric CO2 is crucial for enhancing comprehension of the carbon cycle. Using column‐averaged dry‐air mole fraction of CO2 (XCO2) data collected by the Orbiting Carbon Observatory (OCO)‐2 and OCO‐3 satellites during 2020–2021, this study explored seasonal and diurnal variations in XCO2 characteristics in typical land cover biomes in China, and investigated their relationships with meteorological drivers. Results showed that XCO2 products retrieved by OCO‐2 and OCO‐3 have good agreement with Total Carbon Column Observing Network measurements, with average deviations of 0.8 and 1.2 ppm, respectively. The satellite observations revealed XCO2 hotpots located mainly in central and eastern China, and areas of low XCO2 values in western China, with a seasonal curve that was highest (lowest) in spring (summer). The largest seasonal cycle amplitude (∼9 ppm) of XCO2 was observed in forest areas, highlighting its key role in carbon exchange. Additionally, XCO2 was found to have a near‐sinusoidal diurnal pattern, characterized by rapid decrease in the early morning as photosynthesis resumed after sunrise, as indicated by the sun‐induced chlorophyll fluorescence (SIF), a peak at around midday, and subsequent decrease as SIF increased after mid‐afternoon. Urban regions had the highest diurnal cycle amplitude (∼6 ppm) among biomes. Statistical analyses revealed seasonal shift and nonlinear variation in the relationships between XCO2 and meteorological variables, suggesting that CO2 uptake is influenced by favorable humidity conditions. These relationships also provide insight into the sensitivity and adaptability of XCO2 to meteorological factors in diverse ecosystems such as savanna and grassland.
Double-edged sword: γδ T cells in mucosal homeostasis and disease
Authors: Kang In , Kim Yumin , Lee Heung Kyu
Published: September 2023

The mucosa is a tissue that covers numerous body surfaces, including the respiratory tract, digestive tract, eye, and urogenital tract. Mucosa is in direct contact with pathogens, and γδ T cells perform various roles in the tissue. γδ T cells efficiently defend the mucosa from various pathogens, such as viruses, bacteria, and fungi. In addition, γδ T cells are necessary for the maintenance of homeostasis because they select specific organisms in the microbiota and perform immunoregulatory functions. Furthermore, γδ T cells directly facilitate pregnancy by producing growth factors. However, γδ T cells can also play detrimental roles in mucosal health by amplifying inflammation, thereby worsening allergic responses. Moreover, these cells can act as major players in autoimmune diseases. Despite their robust roles in the mucosa, the application of γδ T cells in clinical practice is lacking because of factors such as gaps between mice and human cells, insufficient knowledge of the target of γδ T cells, and the small population of γδ T cells. However, γδ T cells may be attractive targets for clinical use due to their effector functions and low risk of inducing graft-versus-host disease. Therefore, robust research on γδ T cells is required to understand the crucial features of these cells and apply these knowledges to clinical practices.
Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation
Authors: Ryu Seungwon , Lim MinYeong , Kim Jinwoo , Kim Hye Young
Published: September 2023

Innate lymphoid cells (ILCs) are innate lymphocytes that do not express antigen-specific receptors and largely reside and self-renew in mucosal tissues. ILCs can be categorized into three groups (ILC1–3) based on the transcription factors that direct their functions and the cytokines they produce. Their signature transcription factors and cytokines closely mirror those of their Th1, Th2, and Th17 cell counterparts. Accumulating studies show that ILCs are involved in not only the pathogenesis of mucosal tissue diseases, especially respiratory diseases, and colitis, but also the resolution of such diseases. Here, we discuss recent advances regarding our understanding of the biology of ILCs in mucosal tissue health and disease. In addition, we describe the current research on the immune checkpoints by which other cells regulate ILC activities: for example, checkpoint molecules are potential new targets for therapies that aim to control ILCs in mucosal diseases. In addition, we review approved and clinically- trialed drugs and drugs in clinical trials that can target ILCs and therefore have therapeutic potential in ILC-mediated diseases. Finally, since ILCs also play important roles in mucosal tissue homeostasis, we explore the hitherto sparse research on cell therapy with regulatory ILCs. This review highlights various therapeutic approaches that could be used to treat ILC-mediated mucosal diseases and areas of research that could benefit from further investigation.
Invariant natural killer T cells in lung diseases
Authors: Jeong Dongjin , Woo Yeon Duk , Chung Doo Hyun
Published: September 2023

Invariant natural killer T (iNKT) cells are a subset of T cells that are characterized by a restricted T-cell receptor (TCR) repertoire and a unique ability to recognize glycolipid antigens. These cells are found in all tissues, and evidence to date suggests that they play many immunological roles in both homeostasis and inflammatory conditions. The latter include lung inflammatory diseases such as asthma and infections: the roles of lung-resident iNKT cells in these diseases have been extensively researched. Here, we provide insights into the biology of iNKT cells in health and disease, with a particular focus on the role of pulmonary iNKT cells in airway inflammation and other lung diseases.
Resuscitation, survival and morbidity of extremely preterm infants in California 2011–2019
Authors: Higgins Brennan V. , Baer Rebecca J. , Steurer Martina A. , Karvonen Kayla L. , Oltman Scott P. , Jelliffe-Pawlowski Laura L. , Rogers Elizabeth E.
Published: September 2023

Objective

To describe changes over time in resuscitation, survival, and morbidity of extremely preterm infants in California.

Study design

This population-based, retrospective cohort study includes infants born ≤28 weeks. Linked birth certificates and hospital discharge records were used to evaluate active resuscitation, survival, and morbidity across two epochs (2011–2014, 2015–2019).

Results

Of liveborn infants, 0.6% were born ≤28 weeks. Active resuscitation increased from 16.9% of 22-week infants to 98.1% of 25-week infants and increased over time in 22-, 23-, and 25-week infants (p-value ≤ 0.01). Among resuscitated infants, survival to discharge increased from 33.2% at 22 weeks to 96.1% at 28 weeks. Survival without major morbidity improved over time for 28-week infants (p-value < 0.01).

Conclusion

Among infants ≤28 weeks, resuscitation and survival increased with gestational age and morbidity decreased. Over time, active resuscitation of periviable infants and morbidity-free survival of 28-week infants increased. These trends may inform counseling around extremely preterm birth.
Fumarate hydratase (FH) and cancer: a paradigm of oncometabolism
Authors: Valcarcel-Jimenez Lorea , Frezza Christian
Published: September 2023

Fumarate hydratase (FH) is an enzyme of the Tricarboxylic Acid (TCA) cycle whose mutations lead to hereditary and sporadic forms of cancer. Although more than twenty years have passed since its discovery as the leading cause of the cancer syndrome Hereditary leiomyomatosis and Renal Cell Carcinoma (HLRCC), it is still unclear how the loss of FH causes cancer in a tissue-specific manner and with such aggressive behaviour. It has been shown that FH loss, via the accumulation of FH substrate fumarate, activates a series of oncogenic cascades whose contribution to transformation is still under investigation. In this review, we will summarise these recent findings in an integrated fashion and put forward the case that understanding the biology of FH and how its mutations promote transformation will be vital to establish novel paradigms of oncometabolism.
REPRESENT recommendations: improving inclusion and trust in cancer early detection research
Authors: Brockhoven Frederike , Raphael Maya , Currier Jessica , Jäderholm Christina , Mody Perveez , Shannon Jackilen , Starling Bella , Turner-Uaandja Hannah , Pashayan Nora , Arteaga Ignacia
Published: September 2023

Detecting cancer early is essential to improving cancer outcomes. Minoritized groups remain underrepresented in early detection cancer research, which means that findings and interventions are not generalisable across the population, thus exacerbating disparities in cancer outcomes. In light of these challenges, this paper sets out twelve recommendations to build relations of trust and include minoritized groups in ED cancer research. The Recommendations were formulated by a range of stakeholders at the 2022 REPRESENT consensus-building workshop and are based on empirical data, including a systematic literature review and two ethnographic case studies in the US and the UK. The recommendations focus on: Long-term relationships that build trust; Sharing available resources; Inclusive and accessible communication; Harnessing community expertise; Unique risks and benefits; Compensation and support; Representative samples; Demographic data; Post-research support; Sharing results; Research training; Diversifying research teams. For each recommendation, the paper outlines the rationale, specifications for how different stakeholders may implement it, and advice for best practices. Instead of isolated recruitment, public involvement and engagement activities, the recommendations here aim to advance mutually beneficial and trusting relationships between researchers and research participants embedded in ED cancer research institutions.
Wild jackdaws can selectively adjust their social associations while preserving valuable long-term relationships
Authors: Kings Michael , Arbon Josh J. , McIvor Guillam E. , Whitaker Martin , Radford Andrew N. , Lerner Jürgen , Thornton Alex
Published: September 2023

Influential theories of the evolution of cognition and cooperation posit that tracking information about others allows individuals to adjust their social associations strategically, re-shaping social networks to favour connections between compatible partners. Crucially, to our knowledge, this has yet to be tested experimentally in natural populations, where the need to maintain long-term, fitness-enhancing relationships may limit social plasticity. Using a social-network-manipulation experiment, we show that wild jackdaws (Corvus monedula) learned to favour social associations with compatible group members (individuals that provided greater returns from social foraging interactions), but resultant change in network structure was constrained by the preservation of valuable pre-existing relationships. Our findings provide insights into the cognitive basis of social plasticity and the interplay between individual decision-making and social-network structure.
Multi-scale dynamic imaging reveals that cooperative motility behaviors promote efficient predation in bacteria
Authors: Rombouts Sara , Mas Anna , Le Gall Antoine , Fiche Jean-Bernard , Mignot Tâm , Nollmann Marcelo
Published: September 2023

Many species, such as fish schools or bird flocks, rely on collective motion to forage, prey, or escape predators. Likewise, Myxococcus xanthus forages and moves collectively to prey and feed on other bacterial species. These activities require two distinct motility machines enabling adventurous (A) and social (S) gliding, however when and how these mechanisms are used has remained elusive. Here, we address this long-standing question by applying multiscale semantic cell tracking during predation. We show that: (1) foragers and swarms can comprise A- and S-motile cells, with single cells exchanging frequently between these groups; (2) A-motility is critical to ensure the directional movement of both foragers and swarms; (3) the combined action of A- and S-motile cells within swarms leads to increased predation efficiencies. These results challenge the notion that A- and S-motilities are exclusive to foragers and swarms, and show that these machines act synergistically to enhance predation efficiency.
Bacterial motility can govern the dynamics of antibiotic resistance evolution
Authors: Piskovsky Vit , Oliveira Nuno M.
Published: September 2023

Spatial heterogeneity in antibiotic concentrations is thought to accelerate the evolution of antibiotic resistance, but current theory and experiments have overlooked the effect of cell motility on bacterial adaptation. Here, we study bacterial evolution in antibiotic landscapes with a quantitative model where bacteria evolve under the stochastic processes of proliferation, death, mutation and migration. Numerical and analytical results show that cell motility can both accelerate and decelerate bacterial adaptation by affecting the degree of genotypic mixing and ecological competition. Moreover, we find that for sufficiently high rates, cell motility can limit bacterial survival, and we derive conditions for all these regimes. Similar patterns are observed in more complex scenarios, namely where bacteria can bias their motion in chemical gradients (chemotaxis) or switch between motility phenotypes either stochastically or in a density-dependent manner. Overall, our work reveals limits to bacterial adaptation in antibiotic landscapes that are set by cell motility.
Exploring non-equilibrium processes and spatio-temporal scaling laws in heated egg yolk using coherent X-rays
Authors: Anthuparambil Nimmi Das , Girelli Anita , Timmermann Sonja , Kowalski Marvin , Akhundzadeh Mohammad Sayed , Retzbach Sebastian , Senft Maximilian D. , Dargasz Michelle , Gutmüller Dennis , Hiremath Anusha , Moron Marc , Öztürk Özgül , Poggemann Hanna-Friederike , Ragulskaya Anastasia , Begam Nafisa , Tosson Amir , Paulus Michael , Westermeier Fabian , Zhang Fajun , Sprung Michael , Schreiber Frank , Gutt Christian
Published: September 2023

The soft-grainy microstructure of cooked egg yolk is the result of a series of out-of-equilibrium processes of its protein-lipid contents; however, it is unclear how egg yolk constituents contribute to these processes to create the desired microstructure. By employing X-ray photon correlation spectroscopy, we investigate the functional contribution of egg yolk constituents: proteins, low-density lipoproteins (LDLs), and yolk-granules to the development of grainy-gel microstructure and microscopic dynamics during cooking. We find that the viscosity of the heated egg yolk is solely determined by the degree of protein gelation, whereas the grainy-gel microstructure is controlled by the extent of LDL aggregation. Overall, protein denaturation-aggregation-gelation and LDL-aggregation follows Arrhenius-type time-temperature superposition (TTS), indicating an identical mechanism with a temperature-dependent reaction rate. However, above 75 °C TTS breaks down and temperature-independent gelation dynamics is observed, demonstrating that the temperature can no longer accelerate certain non-equilibrium processes above a threshold value.
Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes
Authors: Fan Qiao , Li Hengtong , Wang Xiaomeng , Tham Yih-Chung , Teo Kelvin Yi Chong , Yasuda Masayuki , Lim Weng Khong , Kwan Yuet Ping , Teo Jing Xian , Chen Ching-Jou , Chen Li Jia , Ahn Jeeyun , Davila Sonia , Miyake Masahiro , Tan Patrick , Park Kyu Hyung , Pang Chi Pui , Khor Chiea Chuan , Wong Tien Yin , Yanagi Yasuo , Cheung Chui Ming Gemmy , Cheng Ching-Yu
Published: September 2023

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ($$P \, < \, 1.19\times {10}^{-8}$$
P

<

1.19
×

10

−
8

). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; $$P=1.05\times {10}^{-6}$$
P
=
1.05
×

10

−
6

) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.
A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles
Authors: Chen Kangfu , Duong Bill T. V. , Ahmed Sharif U. , Dhavarasa Piriththiv , Wang Zongjie , Labib Mahmoud , Flynn Connor , Xu Jingya , Zhang Yi Y. , Wang Hansen , Yang Xiaolong , Das Jagotamoy , Zargartalebi Hossein , Ma Yuan , Kelley Shana O.
Published: September 2023

Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.
Single-molecule imaging reveals distinct elongation and frameshifting dynamics between frames of expanded RNA repeats in C9ORF72-ALS/FTD
Authors: Latallo Malgorzata J. , Wang Shaopeng , Dong Daoyuan , Nelson Blake , Livingston Nathan M. , Wu Rong , Zhao Ning , Stasevich Timothy J. , Bassik Michael C. , Sun Shuying , Wu Bin
Published: September 2023

C9ORF72 hexanucleotide repeat expansion is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the accumulation of toxic dipeptide repeat (DPR) proteins like poly-GA, GP and GR, produced by the noncanonical translation of the expanded RNA repeats. However, how different DPRs are synthesized remains elusive. Here, we use single-molecule imaging techniques to directly measure the translation dynamics of different DPRs. Besides initiation, translation elongation rates vary drastically between different frames, with GP slower than GA and GR the slowest. We directly visualize frameshift events using a two-color single-molecule translation assay. The repeat expansion enhances frameshifting, but the overall frequency is low. There is a higher chance of GR-to-GA shift than in the reversed direction. Finally, the ribosome-associated protein quality control (RQC) factors ZNF598 and Pelota modulate the translation dynamics, and the repeat RNA sequence is important for invoking the RQC pathway. This study reveals that multiple translation steps modulate the final DPR production. Understanding repeat RNA translation is critically important to decipher the DPR-mediated pathogenesis and identify potential therapeutic targets in C9ORF72-ALS/FTD.
Exploring the levodopa-paradox of freezing of gait in dopaminergic medication-naïve Parkinson’s disease populations
Authors: Jansen Jamie A. F. , Capato Tamine T. C. , Darweesh Sirwan K. L. , Barbosa Egberto R. , Donders Rogier , Bloem Bastiaan R. , Nonnekes Jorik
Published: September 2023

The relationship between dopaminergic treatment and freezing of gait (FOG) in Parkinson’s disease (PD) is complex: levodopa is the most effective symptomatic treatment for FOG, but long-term pulsatile levodopa treatment has also been linked to an increase in the occurrence of FOG. This concept, however, continues to be debated. Here, we compared the occurrence of FOG between a levodopa-naive PD cohort and a levodopa-treated cohort. Forty-nine treatment-naive patients and 150 levodopa-treated patients were included. The time since first motor symptoms was at least 5 years. Disease severity was assessed using the MDS-UPDRS part III. Occurrence of FOG was assessed subjectively (new freezing-of-gait-questionnaire) and objectively (rapid turns test and Timed Up-and-Go test). The presence of FOG was compared between the levodopa-treated and levodopa-naive groups using a chi-square test of homogeneity. We also performed a binomial Firth logistic regression with disease duration, disease severity, country of inclusion, location of measurement, and executive function as covariates. Subjective FOG was more common in the levodopa-treated cohort (n = 41, 27%) compared to the levodopa-naive cohort (n = 2, 4%, p < 0.001). The association between FOG and levodopa treatment remained after adjustment for covariates (OR = 6.04, 95%Cl [1.60, 33.44], p = 0.006). Objectively verified FOG was more common in the levodopa-treated cohort (n = 21, 14%) compared to the levodopa-naive cohort (n = 1, 2%, p = 0.02). We found an association between long-term pulsatile levodopa treatment and an increased occurrence of FOG. Future studies should further explore the role of nonphysiological stimulation of dopamine receptors in generating FOG, as a basis for possible prevention studies.
Potential value of high-throughput single-cell DNA sequencing of Juvenile myelomonocytic leukemia: report of two cases
Authors: Volchkov E. V. , Khozyainova A. A. , Gurzhikhanova M. Kh. , Larionova I. V. , Matveev V. E. , Evseev D. A. , Ignatova A. K. , Menyailo M. E. , Venyov D. A. , Vorobev R. S. , Semchenkova A. A. , Olshanskaya Yu. V. , Denisov E. V. , Maschan M. A.
Published: September 2023

Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of early childhood that develops due to mutations in the genes of the RAS-signaling pathway. Next-generation high throughput sequencing (NGS) enables identification of various secondary molecular genetic events that can facilitate JMML progression and transformation into secondary acute myeloid leukemia (sAML). The methods of single-cell DNA sequencing (scDNA-seq) enable overcoming limitations of bulk NGS and exploring genetic heterogeneity at the level of individual cells, which can help in a better understanding of the mechanisms leading to JMML progression and provide an opportunity to evaluate the response of leukemia to therapy. In the present work, we applied a two-step droplet microfluidics approach to detect DNA alterations among thousands of single cells and to analyze clonal dynamics in two JMML patients with sAML transformation before and after hematopoietic stem cell transplantation (HSCT). At the time of diagnosis both of our patients harbored only “canonical” mutations in the RAS signaling pathway genes detected by targeted DNA sequencing. Analysis of samples from the time of transformation JMML to sAML revealed additional genetic events that are potential drivers for disease progression in both patients. ScDNA-seq was able to measure of chimerism level and detect a residual tumor clone in the second patient after HSCT (sensitivity of less than 0.1% tumor cells). The data obtained demonstrate the value of scDNA-seq to assess the clonal evolution of JMML to sAML, response to therapy and engraftment monitoring.
Direct measurement of engineered cancer mutations and their transcriptional phenotypes in single cells
Authors: Kim Heon Seok , Grimes Susan M. , Chen Tianqi , Sathe Anuja , Lau Billy T. , Hwang Gue-Ho , Bae Sangsu , Ji Hanlee P.
Published: September 2023

Genome sequencing studies have identified numerous cancer mutations across a wide spectrum of tumor types, but determining the phenotypic consequence of these mutations remains a challenge. Here, we developed a high-throughput, multiplexed single-cell technology called TISCC-seq to engineer predesignated mutations in cells using CRISPR base editors, directly delineate their genotype among individual cells and determine each mutation’s transcriptional phenotype. Long-read sequencing of the target gene’s transcript identifies the engineered mutations, and the transcriptome profile from the same set of cells is simultaneously analyzed by short-read sequencing. Through integration, we determine the mutations’ genotype and expression phenotype at single-cell resolution. Using cell lines, we engineer and evaluate the impact of >100 TP53 mutations on gene expression. Based on the single-cell gene expression, we classify the mutations as having a functionally significant phenotype.
Nucleosome density shapes kilobase-scale regulation by a mammalian chromatin remodeler
Authors: Abdulhay Nour J. , Hsieh Laura J. , McNally Colin P. , Ostrowski Megan S. , Moore Camille M. , Ketavarapu Mythili , Kasinathan Sivakanthan , Nanda Arjun S. , Wu Ke , Chio Un Seng , Zhou Ziling , Goodarzi Hani , Narlikar Geeta J. , Ramani Vijay
Published: September 2023

Nearly all essential nuclear processes act on DNA packaged into arrays of nucleosomes. However, our understanding of how these processes (for example, DNA replication, RNA transcription, chromatin extrusion and nucleosome remodeling) occur on individual chromatin arrays remains unresolved. Here, to address this deficit, we present SAMOSA-ChAAT: a massively multiplex single-molecule footprinting approach to map the primary structure of individual, reconstituted chromatin templates subject to virtually any chromatin-associated reaction. We apply this method to distinguish between competing models for chromatin remodeling by the essential imitation switch (ISWI) ATPase SNF2h: nucleosome-density-dependent spacing versus fixed-linker-length nucleosome clamping. First, we perform in vivo single-molecule nucleosome footprinting in murine embryonic stem cells, to discover that ISWI-catalyzed nucleosome spacing correlates with the underlying nucleosome density of specific epigenomic domains. To establish causality, we apply SAMOSA-ChAAT to quantify the activities of ISWI ATPase SNF2h and its parent complex ACF on reconstituted nucleosomal arrays of varying nucleosome density, at single-molecule resolution. We demonstrate that ISWI remodelers operate as density-dependent, length-sensing nucleosome sliders, whose ability to program DNA accessibility is dictated by single-molecule nucleosome density. We propose that the long-observed, context-specific regulatory effects of ISWI complexes can be explained in part by the sensing of nucleosome density within epigenomic domains. More generally, our approach promises molecule-precise views of the essential processes that shape nuclear physiology.
A 10-m resolution impervious surface area map for the greater Mekong subregion from remote sensing images
Authors: Sun Genyun , Li Zheng , Zhang Aizhu , Wang Xin , Yan Kai , Jia Xiuping , Liu Qinhuo , Li Jing
Published: September 2023

High-resolution and multi-temporal impervious surface area maps are crucial for capturing rapidly developing urbanization patterns. However, the currently available relevant maps for the greater Mekong subregion suffer from coarse resolution and low accuracy. Addressing this issue, our study focuses on the development of accurate impervious surface area maps at 10-m resolution for this region for the period 2016–2022. To accomplish this, we present a new machine-learning framework implemented on the Google Earth Engine platform that merges Sentinel-1 Synthetic Aperture Radar images and Sentinel-2 Multispectral images to extract impervious surfaces. Furthermore, we also introduce a training sample migration strategy that eliminates the collection of additional training samples and automates multi-temporal impervious surface area mapping. Finally, we perform a quantitative assessment with validation samples interpreted from Google Earth. Results show that the overall accuracy and kappa coefficient of the final impervious surface area maps range from 92.75% to 92.93% and 0.854 to 0.857, respectively. This dataset provides comprehensive measurements of impervious surface coverage and configuration that will help to inform urban studies.
Analysis of compound health impacts of heatwave and COVID-19 in Korea from May to September in 2020
Authors: Park Haemin , Lee Sang-Min , Kim Woo Joong , Chae Yeora
Published: September 2023

The number of non-accidental deaths and heat-related illnesses due to the co-occurrence of heatwaves and COVID-19 has been identified to estimate compound health impacts between two risks. We have analyzed data from historical years (2013–2019) to calculate the baseline values of the number of non-accidental deaths and heat-related illness patients from May to September using a quasi-Poisson generalized linear model and compared them to data from 2020 in Korea. We also assessed the relative risk and absolute cumulative number of non-accidental deaths and heat-related illnesses in the summer of 2020 in Seoul, Daegu, and Gyeongnam region of Korea. In the Summer of 2020, Korea experienced 0.8% of non-accidental excess deaths, with the highest in August, and 46% of reduction was observed in heat-related throughout the study period, except in Daegu, where excess of heat-related illness occurred in August. The relative risk (RR) of non-accidental deaths at 33.1 °C, was 1.00 (CI 0.99–1.01) and 1.04 (CI 1.02–1.07) in 2013–2019 and 2020, respectively. The RR of heat-related illness at 33.1 °C, was 1.44 (CI 1.42–1.45) and 1.59 (CI 1.54–1.64) in 2013–2019 and 2020, respectively. The absolute cumulative trends of non-accidental deaths and heat-related illnesses were similar in the three regions, indicating increased non-accidental deaths and decreased heat-related illnesses at similar temperatures in 2020. During the COVID-19 pandemic, the fear of infection by the virus and the limited access to healthcare services led to changes in health-seeking behaviors. These results indicate social distancing could have had adverse impacts on other health conditions. A comprehensive health risk assessment is important when facing simultaneous risks, such as heatwaves and pandemics, in the implementation of effective countermeasures.
Automation of the control system for drying grain crops of the technological process for obtaining biodiesel fuels
Authors: Eremeeva Anzhelika M. , Ilyushin Yury V.
Published: September 2023

Process of grain drying is discussed by the authors, which is considered one of the preliminary stages in the technology of biodiesel production. The drying process has a number of disadvantages that affect the quality and cost of biodiesel fuel. The impossibility of uniform heating and maintaining the required temperature with minimal energy costs is considered one of the most important defects that deserve scientific research. The authors propose a method for changing the heating system and preheating raw materials, based on world experience. We carried out mathematical calculations, provided the change in the temperature field of the drying chamber over time, and we also performed industrial experiment. Based on our results we determined the optimal number of heating sources of raw materials, taking into account the dimensions of the drying chamber. The authors propose a technical solution with which a uniform temperature field can be obtained in the drying chamber. Thus, the uniformity of the chamber heating will be increased, and large operating costs associated with leakage of oil from the grains will be disappeared.
The benefits of early continuous renal replacement therapy in critically ill patients with acute kidney injury at high-altitude areas: a retrospective multi-center cohort study
Authors: Wang Bowen , Peng Mengjia , Wei Hui , Liu Chang , Wang Juan , Jiang Liheng , Fang Fei , Wang Yuliang , Shen Yuandi
Published: September 2023

Severe hypoxia would aggravate the acute kidney injury (AKI) in high-altitude areas and continuous renal replacement therapy (CRRT) has been used to treat critically ill patients with AKI. However, the characteristics and outcomes of CRRT in critically ill patients at AKI in high altitudes and the optimal timing of CRRT initiation remain unclear. 1124 patients were diagnosed with AKI and treated with CRRT in the ICU, comprising a high-altitude group (n = 648) and low-altitude group (n = 476). Compared with the low-altitude group, patients with AKI at high altitude showed longer CRRT (4.8 vs. 3.7, P = 0.036) and more rapid progression of AKI stages (P < 0.01), but without any significant minor or major bleeding episodes (P > 0.05). Referring to the analysis of survival and kidney recovery curves, a higher mortality but a lower possibility of renal recovery was observed in the high-altitude group (P < 0.001). However, in the high-altitude group, the survival rate of early CRRT initiation was significantly higher than that of delayed CRRT initiation (P < 0.001). The findings showed poorer clinical outcomes in patients undergoing CRRT for AKI at high altitudes. CRRT at high altitudes was unlikely to increase the adverse events. Moreover, early CRRT initiation might reduce the mortality and promote renal recovery in high-altitude patients.
Detecting potential causal relationship between inflammatory bowel disease and rosacea using bi-directional Mendelian randomization
Authors: Li Min , He Si Xian , He Yuan Xiong , Hu Xiao Han , Zhou Zhou
Published: September 2023

The association between rosacea and inflammatory bowel disease (IBD) has been studied in previous observational studies. It is unclear, however, whether the association is causal or not. Independent genetic variants for IBD were chosen as instruments from published Genome-wide association studies (GWAS) studies involving 38,155 cases with an IBD diagnosis and 48,485 controls in order to investigate the causal effect of IBD on rosacea. Summarized data for rosacea were gathered from various GWAS studies that included 1195 cases and 211,139 controls without rosacea. Reverse-direction Mendelian randomization (MR) analysis was done to investigate the relationship between genetically proxied rosacea and IBD. With the use of the inverse variance-weighted (IVW), MR-Egger, and weighted median approaches, a 2-sample Mendelian randomization study was carried out. Analysis of heterogeneity and sensitivity was performed to examine the pleiotropy and robustness of effect estimates. The forward-direction of the MR study was to reveal that genetic predisposition to IBD including its two main subtypes: Crohn’s disease (CD) and ulcerative colitis (UC) was associated with an increased risk of rosacea. The reverse-direction MR analyses did not demonstrate that a genetic predisposition to rosacea was associated with total IBD, UC and CD. Our findings provided evidence for a causal impact of IBD, UC, and CD on rosacea, but not vice versa. The elevated incidence of rosacea in patients with IBD should be recognized by doctors to make an early diagnosis and initiate specialized therapy.
Efficacy of hydroxyapatite-based skull base reconstruction for intraoperative high-flow cerebrospinal fluid leakage performed by less-experienced surgeons
Authors: Hong Inseo , Kim Kyung Hwan , Seo Youngbeom , Choo Yoon-Hee , Lee Han-Joo , Kim Seon-Hwan
Published: September 2023

Cerebrospinal fluid (CSF) leakage after endoscopic skull base surgery remains a challenge despite multilayer reconstruction including nasoseptal flap (NSF) has become a standard technique. Injectable hydroxyapatite (HXA) has shown promising results to prevent CSF leakage. This study aimed to validate the efficacy of HXA-based skull base reconstruction performed by less-experienced neurosurgeons who had short-term clinical experiences as independent surgeons. Between March 2018 and November 2022, 41 patients who experienced intraoperative high-flow CSF leakage following endoscopic endonasal surgery at two independent tertiary institutions were enrolled. Skull base reconstruction was performed using conventional multilayer techniques combined with or without HXA. The primary outcome was postoperative CSF leakage. The surgical steps and nuances were described in detail. The most common pathology was craniopharyngioma. Injectable HXA was used in 22 patients (HXA group) and conventional techniques were performed in 19 patients (control group). The HXA group achieved a significantly lower incidence of postoperative CSF leakage than the control group (0% vs. 26.3%, p = 0.016). No HXA-related complications were observed. The use of injectable HXA in skull base reconstruction was highly effective and safe. This technique and its favorable results might be readily reproduced by less-experienced neurosurgeons.
Effects of movement congruence on motor resonance in early Parkinson’s disease
Authors: Gentile Eleonora , Brunetti Antonio , Ricci Katia , Vecchio Eleonora , Santoro Carlo , Sibilano Elena , Bevilacqua Vitoantonio , Iliceto Giovanni , Craighero Laila , de Tommaso Marina
Published: September 2023

The observation of action seems to involve the generation of the internal representation of that same action in the observer, a process named motor resonance (MR). The objective of this study was to verify whether an experimental paradigm of action observation in a laboratory context could elicit cortical motor activation in 21 early Parkinson’s disease (PD) patients compared to 22 controls. Participants were instructed to simply observe (observation-only session) or to respond (Time-to-contact detection session) at the instant the agent performed a grasping action toward a graspable or ungraspable object. We used functional near-infrared spectroscopy with 20 channels on the motor and premotor brain areas and event-related desynchronization of alpha-mu rhythm. In both groups, response times were more accurate in graspable than ungraspable object trials, suggesting that motor resonance is present in PD patients. In the Time-to-contact detection session, the oxyhemoglobin levels and alpha-mu desynchronization prevailed in the graspable object trials rather than in the ungraspable ones. This study demonstrates the preservation of MR mechanisms in early PD patients. The action observation finalized to a consequent movement can activate cortical networks in patients with early PD, suggesting early rehabilitation interventions taking into account specific observation paradigms preceding motor production.
Quantifying the impact of Wolbachia releases on dengue infection in Townsville, Australia
Authors: Ogunlade Samson T. , Adekunle Adeshina I. , Meehan Michael T. , McBryde Emma S.
Published: September 2023

From October 2014 to February 2019, local authorities in Townsville, North Queensland, Australia continually introduced Wolbachia-infected mosquitoes to control seasonal outbreaks of dengue infection. In this study, we develop a mathematical modelling framework to estimate the effectiveness of this intervention as well as the relative dengue transmission rates of Wolbachia-infected and wild-type mosquitoes. We find that the transmission rate of Wolbachia-infected mosquitoes is reduced approximately by a factor of 20 relative to the uninfected wild-type population. In addition, the Townsville Wolbachia release program led to a 65% reduction in predicted dengue incidence during the release period and over 95% reduction in the 24 months that followed. Finally, to investigate the potential impact of other Wolbachia release programs, we use our estimates of relative transmissibility to calculate the relationship between the reproductive number of dengue and the proportion of Wolbachia-infected mosquitoes in the vector population.