bluuebunny/crossref_metadata_2025 huggingface dataset:
Caring Enough to Counter Extinction: The Work of Volunteer Bat Carers and Educators in Tropical Queensland, Australia
Authors: Whitehouse Hilary
Published: June 2024

In the state of Queensland, volunteers perform much of the work needed to prevent the extinction of threatened species who are native and unique to this continent. Acting from an understanding of interspecies justice, caring people rescue and rehabilitate hundreds of thousands of wild animals every year. Many of these same people conduct informal environmental education to bring to community attention the problematics of extinction by seeking the material expression of an ethics of conviviality. Using a document case study approach, this paper narrates aspects of the kindship work of a network of carers and educators of flying foxes who undertake informal environmental education as part of their care practices. Volunteering to care and educate for Australian flying mammals is a form of activism in a nation with a mammalian extinction crisis that still fails to meet its obligations under the United Nations Sustainable Development Goal 15. This paper describes how volunteer run informal environmental education in far north Queensland is driven by a strong sense of multispecies care.
Changes in self-confidence in professional, personal, and scientific skills by gender during physician-scientist training at the University of Pittsburgh
Authors: Khouja Tumader , Proulx Chelsea N. , Nouraie S. Mehdi , Shah Ashti M. , Rao Rashmi J. , Steinman Richard A.
Published: June 2024

Introduction:

Persistence in physician-scientist careers has been suboptimal, particularly among women. There is a gender gap in self-confidence in medicine. We measured the impact of our physician-scientist training programs on trainee’s confidence in professional, personal, and scientific competencies, using a survey measuring self-rated confidence in 36 competencies across two timepoints.

Methods:

Results were analyzed for the full survey and for thematic subscales identified through exploratory factor analysis (EFA). A mixed effects linear model and a difference in differences (DID) design were used to assess the differential impact of the programing by gender and career level.

Results:

Analysis included 100 MD-PhD or MD-only medical student or resident/fellow trainees enrolled between 2020 and 2023. Five subscales were identified through EFA; career sustainability, science productivity, grant management, goal setting, and goal alignment (Cronbach’s alpha 0.85–0.94). Overall, mean scores increased significantly for all five subscales. Women significantly increased their confidence levels in all five areas, whereas men increased only in science productivity and grant management. Mixed effects models showed significant increases over time for women compared to men in career sustainability and goal alignment. Residents and fellows had greater increases than medical students across all subscales.

Conclusion:

Physician-scientist trainees fellows increased their confidence in personal, professional, and scientific skills during training. Training had a greater impact on women than men in building confidence in sustaining careers and aligning their goals with professional and institutional priorities. The magnitude of increased confidence among residents and fellows exceeded that in medical students.
SHEA position statement on pandemic preparedness for policymakers: introduction and overview
Authors: Hsu Vincent P. , Haessler Sarah , Banach David B. , Batshon Lynne Jones , Branch-Elliman Westyn , Dumyati Ghinwa , Jump Robin L. P. , Malani Anurag N. , Mathew Trini A. , Murthy Rekha K. , Pergam Steven A. , Shenoy Erica S. , Weber David J.
Published: June 2024

Throughout history, pandemics and their aftereffects have spurred society to make substantial improvements in healthcare. After the Black Death in 14th century Europe, changes were made to elevate standards of care and nutrition that resulted in improved life expectancy.1 The 1918 influenza pandemic spurred a movement that emphasized public health surveillance and detection of future outbreaks and eventually led to the creation of the World Health Organization Global Influenza Surveillance Network.2 In the present, the COVID-19 pandemic exposed many of the pre-existing problems within the US healthcare system, which included (1) a lack of capacity to manage a large influx of contagious patients while simultaneously maintaining routine and emergency care to non-COVID patients; (2) a “just in time” supply network that led to shortages and competition among hospitals, nursing homes, and other care sites for essential supplies; and (3) longstanding inequities in the distribution of healthcare and the healthcare workforce. The decades-long shift from domestic manufacturing to a reliance on global supply chains has compounded ongoing gaps in preparedness for supplies such as personal protective equipment and ventilators. Inequities in racial and socioeconomic outcomes highlighted during the pandemic have accelerated the call to focus on diversity, equity, and inclusion (DEI) within our communities. The pandemic accelerated cooperation between government entities and the healthcare system, resulting in swift implementation of mitigation measures, new therapies and vaccinations at unprecedented speeds, despite our fragmented healthcare delivery system and political divisions. Still, widespread misinformation or disinformation and political divisions contributed to eroded trust in the public health system and prevented an even uptake of mitigation measures, vaccines and therapeutics, impeding our ability to contain the spread of the virus in this country.3 Ultimately, the lessons of COVID-19 illustrate the need to better prepare for the next pandemic. Rising microbial resistance, emerging and re-emerging pathogens, increased globalization, an aging population, and climate change are all factors that increase the likelihood of another pandemic.4
A colorblind Christian country? How racial attitudes affect support for Christian nationalism and civil religion
Authors: Walker Brooklyn , Haider-Markel Donald P.
Published: June 2024

Can racial primes influence support for public expressions of religion? While a growing body of research demonstrates correlations between racial attitudes and support for public religion among White Americans, experimental tests of subconscious connections between the two concepts have been lacking. We utilize a novel survey experiment to prime racial considerations, and we find that Black racial primes raise support for Christian nationalism and civil religion among White Americans, compared to White racial primes. Moreover, our analysis indicates that these effects are attributable to racial animus, namely the evaluation that Black Americans are not prototypical members of the national community. The findings suggest that the preference for a Christian/religious America and a White America are subconsciously interwoven for many White Americans, providing the first experimental evidence, to our knowledge, of this relationship.
A New Phase Diagram for Fluid Invasion Patterns as a Function of Pore‐Scale Heterogeneity, Surface Roughness, and Wettability
Authors: Geistlinger Helmut , Golmohammadi Saeed , Zulfiqar Bilal , Kuechler Matthias , Reuter Danny , Schlueter Steffen , Segre Enrico , Holtzman Ran , Amro Mohd
Published: June 2024

Understanding how different flow patterns emerge at various macro‐ and pore scale heterogeneity, pore wettability and surface roughness is remains a long standing scientific challenge. Such understanding allows to predict the amount of trapped fluid left behind, of crucial importance to applications ranging from microfluidics and fuel cells to subsurface storage of carbon and hydrogen. We examine the interplay of wettability and pore‐scale heterogeneity including both pore angularity and roughness, by a combination of micro‐CT imaging of 3D grain packs with direct visualization of 2D micromodels. The micromodels are designed to retain the key morphological and topological properties derived from the micro‐CT images. Different manufacturing techniques allow us to control pore surface roughness. We study the competition between flow through the pore centers and flow along rough pore walls and corners in media of increasing complexity in the capillary flow regime. The resulting flow patterns and their trapping efficiency are in excellent agreement with previous μ‐CT results. We observe different phase transitions between the following flow regimes (phases): (a) Frontal/compact advance, (b) wetting and drainage Invasion percolation, and (c) Ordinary percolation. We present a heterogeneity‐wettability‐roughness phase diagram that predicts these regimes.
Discounting Water for Optimal Carbon Gain as a Basis of Stomatal Closure
Authors: Nakad Mazen
Published: June 2024

The exchange of carbon dioxide and water vapor between terrestrial ecosystems and the atmosphere is regulated by stomata (small pores in the leaves of plants). Unsurprisingly, environmental factors controlling the opening and closure of stomata has been sought as early as 1800. One approach, popularized in the early 1970s, is a stomatal optimization framework. This framework is based on the hypothesis that plants optimize carbon gain subject to water loss or water availability constraints. This constraint optimization problem was solved in various forms assuming instantaneous adjustments of stomatal aperture to maximize a reward function with no future foresight or legacy effects. Holtzman et al. (2024, https://doi.org/10.1029/2023av001113) offers a novel approach that can diagnose the effective timescale over which the reward function maximization must be time‐integrated. The developed method thus optimizes an integrated carbon gain function but adjusted by a discount factor subject to water availability in the root zone. The discount factor considers how the plant values carbon gain to save water and its timescale can be inferred from observations because the model is analytically tractable. The results suggest that the most important climate factor that determines this discount timescale is multi‐annual mean of the longest dry period during the growing season. The findings highlight how local climate traits influence the spatial variation in ecosystem‐level water use strategies. This sets the stage for expanding such a framework to cases where multiple constraints act in concert while operating at distinct time scales.
Dust Declines in Parts of Asia May Be Caused by the Warming Arctic
Authors: Ware Skyler
Published: June 2024

Rising Arctic temperatures have changed both wind patterns and precipitation in areas that carry dust to West and South Asia, but the change may not be permanent.
Seals Help Scientists Make Discoveries in Antarctica’s Bellingshausen Sea
Authors: Scharping Nathaniel
Published: June 2024

By analyzing hydrographic information gathered by seals and an undersea glider, researchers found new meltwater currents, as well as a new seafloor trough.
Global Ocean Mass Change Estimation Using Low‐Degree Gravity Field From Satellite Laser Ranging
Authors: Nie Yufeng , Chen Jianli , Peng Dongju
Published: June 2024

Satellite laser ranging (SLR) is a well‐established geodetic technique for measuring the low‐degree time‐variable gravity field for decades. However, its application in mass change estimation is limited by low spatial resolution, even for global mean ocean mass (GMOM) change which represents one of the largest spatial scales. After successfully correcting for signal leakage, for the first time, we can infer realistic GMOM changes using SLR‐derived gravity fields up to only degree and order 5. Our leakage‐corrected SLR GMOM estimates are compared with those from the Gravity Recovery and Climate Experiment (GRACE) for the period 2005 to 2015. Our results show that the GMOM rate estimates from SLR are in remarkable agreement with those from GRACE, at 2.23 versus 2.28 mm/year, respectively. This proof‐of‐concept study opens the possibility of directly quantifying GMOM change using SLR data prior to the GRACE era.
Inhalable Fungi and Opportunistic Pathogens During Haze and Haze‐Dust Events From Winter to Springtime in One Typical Inland City of Northern China
Authors: Wang Zhaowen , Liu Houfeng , Xu Pengju , Nie Changliang , Geng Xueyun , Chen Jianmin , Liu Siyu , Wei Min
Published: June 2024

Fungal aerosols, as significant biocomponents of inhalable particulate matter, encompass a variety of allergens and pathogens. However, comprehensive knowledge regarding their composition, sources, and opportunistic pathogens present in severe air pollution remains limited. In this study, PM2.5 samples were collected from January to March 2018 in a northern Chinese city, during the winter heating and spring sandstorm seasons. The fungal community characteristics within three distinct haze and haze‐dust composite pollution were examined. The concentration of fungal aerosols was found to be significantly higher in dust samples. This was evidenced by a strong positive correlation with Ca2+, temperature, and wind speed (p < 0.05). Human and animal pathogens, such as Candida, were more prevalent in haze samples. Conversely, allergens and plant pathogens, like Alternaria, were found in higher concentration in dust samples. The primary ecological function shifted from being saprophytic to becoming human‐animal pathogenic or plant‐animal pathogenic. This shift was observed from non‐pollution, haze, to haze‐dust composite pollution. The dispersion of fungal aerosols was influenced by factors such as dust events and meteorological conditions, including increased temperature and wind speed. In the spring dust episodes, dust‐related pollutants, such as soil Ca2+ and PM10, accounted for 51.39% of the variation in the fungal community. This research explored the dynamics of fungal communities, potential pathogens, and factors influencing fungal communities in regional air pollution. The insights garnered from this research provide a robust foundation for subsequent human health exposure assessments.
Deformable microlaser force sensing
Authors: Dalaka Eleni , Hill Joseph S. , Booth Jonathan H. H. , Popczyk Anna , Pulver Stefan R. , Gather Malte C. , Schubert Marcel
Published: June 2024

Mechanical forces are key regulators of cellular behavior and function, affecting many fundamental biological processes such as cell migration, embryogenesis, immunological responses, and pathological states. Specialized force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in vivo. However, current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue, reducing their application to 2D cell cultures and highly transparent biological tissue. Here, we introduce DEFORM, deformable microlaser force sensing, a spectroscopic technique that detects sub-nanonewton forces with unprecedented spatio-temporal resolution. DEFORM is based on the spectral analysis of laser emission from dye-doped oil microdroplets and uses the force-induced lifting of laser mode degeneracy in these droplets to detect nanometer deformations. Following validation by atomic force microscopy and development of a model that links changes in laser spectrum to applied force, DEFORM is used to measure forces in 3D and at depths of hundreds of microns within tumor spheroids and late-stage Drosophila larva. We furthermore show continuous force sensing with single-cell spatial and millisecond temporal resolution, thus paving the way for non-invasive studies of biomechanical forces in advanced stages of embryogenesis, tissue remodeling, and tumor invasion.
iPSC-derived hindbrain organoids to evaluate escitalopram oxalate treatment responses targeting neuropsychiatric symptoms in Alzheimer’s disease
Authors: Zivko Cristina , Sagar Ram , Xydia Ariadni , Lopez-Montes Alejandro , Mintzer Jacobo , Rosenberg Paul B. , Shade David M. , Porsteinsson Anton P. , Lyketsos Constantine G. , Mahairaki Vasiliki
Published: June 2024

Alzheimer’s disease (AD) is the most common cause of dementia, and the gradual deterioration of brain function eventually leads to death. Almost all AD patients suffer from neuropsychiatric symptoms (NPS), the emergence of which correlates with dysfunctional serotonergic systems. Our aim is to generate hindbrain organoids containing serotonergic neurons using human induced Pluripotent Stem Cells (iPSCs). Work presented here is laying the groundwork for the application of hindbrain organoids to evaluate individual differences in disease progression, NPS development, and pharmacological treatment response. Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 3), an AD patient without NPS (n = 1), and AD patients with NPS (n = 2) were reprogrammed into iPSCs and subsequently differentiated into hindbrain organoids. The presence of serotonergic neurons was confirmed by quantitative reverse transcription PCR, flow cytometry, immunocytochemistry, and detection of released serotonin (5-HT). We successfully reprogrammed PBMCs into 6 iPSC lines, and subsequently generated hindbrain organoids from 6 individuals to study inter-patient variability using a precision medicine approach. To assess patient-specific treatment effects, organoids were treated with different concentrations of escitalopram oxalate, commonly prescribed for NPS. Changes in 5-HT levels before and after treatment with escitalopram were dose-dependent and variable across patients. Organoids from different people responded differently to the application of escitalopram in vitro. We propose that this 3D platform might be effectively used for drug screening purposes to predict patients with NPS most likely to respond to treatment in vivo and to understand the heterogeneity of treatment responses.
The effect of combining primers and cements from different cement systems on the bond strength between zirconia and dentin
Authors: Le Minh , Papia Evaggelia , Larsson Christel
Published: June 2024

Objective

The aim of this study was to evaluate the influence of combining primers and cements from two different resin cement systems on the microtensile bond strength (μTBS) between zirconia and human dentin.

Materials and methods

A total of 120 specimens of zirconia cemented to dentin were allocated into eight groups based on cement type (RelyX Ultimate or Panavia V5) and primers (Tooth Primer, Clearfil Ceramic Primer and Scotchbond Universal Adhesive) combinations, applied to dentin or ceramic surfaces. Following artificial aging with 5000 thermocycles, μTBS tests were conducted. Statistical analysis was performed using One-way ANOVA and Tukey’s post hoc tests (p ≤ 0.05), and failure modes were assessed.

Results

The Panavia V5 cement system demonstrated the highest bond strength (19.4 ± 4.4 MPa), significantly higher than the other groups except when RelyX cement was used with Panavia primers (16.9 ± 3.7 MPa). Cohesive fractures within the cement layer were the predominant failure mode.

Conclusions

The combination of primers from different adhesive cement system brands may significantly affect the bonding effectiveness. Therefore, using products from a single product line of the same adhesive cement system, and following the manufacturer’s recommendations for indications and use, is crucial for a more predictable clinical outcome.
Probabilistic physics-integrated neural differentiable modeling for isothermal chemical vapor infiltration process
Authors: Akhare Deepak , Chen Zeping , Gulotty Richard , Luo Tengfei , Wang Jian-Xun
Published: June 2024

Chemical vapor infiltration (CVI) is a widely adopted manufacturing technique used in producing carbon-carbon and carbon-silicon carbide composites. These materials are especially valued in the aerospace and automotive industries for their robust strength and lightweight characteristics. The densification process during CVI critically influences the final performance, quality, and consistency of these composite materials. Experimentally optimizing the CVI processes is challenging due to the long experimental time and large optimization space. To address these challenges, this work takes a modeling-centric approach. Due to the complexities and limited experimental data of the isothermal CVI densification process, we have developed a data-driven predictive model using the physics-integrated neural differentiable (PiNDiff) modeling framework. An uncertainty quantification feature has been embedded within the PiNDiff method, bolstering the model’s reliability and robustness. Through comprehensive numerical experiments involving both synthetic and real-world manufacturing data, the proposed method showcases its capability in modeling densification during the CVI process. This research highlights the potential of the PiNDiff framework as an instrumental tool for advancing our understanding, simulation, and optimization of the CVI manufacturing process, particularly when faced with sparse data and an incomplete description of the underlying physics.
Spaceflight on the ISS changed the skeletal muscle proteome of two astronauts
Authors: Murgia Marta , Rittweger Jörn , Reggiani Carlo , Bottinelli Roberto , Mann Matthias , Schiaffino Stefano , Narici Marco V.
Published: June 2024

Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses.
An emission-state-switching radio transient with a 54-minute period
Authors: Caleb M. , Lenc E. , Kaplan D. L. , Murphy T. , Men Y. P. , Shannon R. M. , Ferrario L. , Rajwade K. M. , Clarke T. E. , Giacintucci S. , Hurley-Walker N. , Hyman S. D. , Lower M. E. , McSweeney Sam , Ravi V. , Barr E. D. , Buchner S. , Flynn C. M. L. , Hessels J. W. T. , Kramer M. , Pritchard J. , Stappers B. W.
Published: June 2024

Long-period radio transients are an emerging class of extreme astrophysical events of which only three are known. These objects emit highly polarized, coherent pulses of typically a few tens of seconds duration, and minutes to approximately hour-long periods. Although magnetic white dwarfs and magnetars, either isolated or in binary systems, have been invoked to explain these objects, a consensus has not emerged. Here we report on the discovery of ASKAP J193505.1+214841.0 (henceforth ASKAP J1935+2148) with a period of 53.8 minutes showing 3 distinct emission states—a bright pulse state with highly linearly polarized pulses with widths of 10–50 seconds; a weak pulse state that is about 26 times fainter than the bright state with highly circularly polarized pulses of widths of approximately 370 milliseconds; and a quiescent or quenched state with no pulses. The first two states have been observed to progressively evolve over the course of 8 months with the quenched state interspersed between them suggesting physical changes in the region producing the emission. A constraint on the radius of the source for the observed period rules out an isolated magnetic white-dwarf origin. Unlike other long-period sources, ASKAP 1935+2148 shows marked variations in emission modes reminiscent of neutron stars. However, its radio properties challenge our current understanding of neutron-star emission and evolution.
Co-expression analysis reveals distinct alliances around two carbon fixation pathways in hydrothermal vent symbionts
Authors: Mitchell Jessica H. , Freedman Adam H. , Delaney Jennifer A. , Girguis Peter R.
Published: June 2024

Most autotrophic organisms possess a single carbon fixation pathway. The chemoautotrophic symbionts of the hydrothermal vent tubeworm Riftia pachyptila, however, possess two functional pathways: the Calvin–Benson–Bassham (CBB) and the reductive tricarboxylic acid (rTCA) cycles. How these two pathways are coordinated is unknown. Here we measured net carbon fixation rates, transcriptional/metabolic responses and transcriptional co-expression patterns of Riftia pachyptila endosymbionts by incubating tubeworms collected from the East Pacific Rise at environmental pressures, temperature and geochemistry. Results showed that rTCA and CBB transcriptional patterns varied in response to different geochemical regimes and that each pathway is allied to specific metabolic processes; the rTCA is allied to hydrogenases and dissimilatory nitrate reduction, whereas the CBB is allied to sulfide oxidation and assimilatory nitrate reduction, suggesting distinctive yet complementary roles in metabolic function. Furthermore, our network analysis implicates the rTCA and a group 1e hydrogenase as key players in the physiological response to limitation of sulfide and oxygen. Net carbon fixation rates were also exemplary, and accordingly, we propose that co-activity of CBB and rTCA may be an adaptation for maintaining high carbon fixation rates, conferring a fitness advantage in dynamic vent environments.
Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs
Authors: Tomar A. , Gomez-Velazquez M. , Gerlini R. , Comas-Armangué G. , Makharadze L. , Kolbe T. , Boersma A. , Dahlhoff M. , Burgstaller J. P. , Lassi M. , Darr J. , Toppari J. , Virtanen H. , Kühnapfel A. , Scholz M. , Landgraf K. , Kiess W. , Vogel M. , Gailus-Durner V. , Fuchs H. , Marschall S. , Hrabě de Angelis M. , Kotaja N. , Körner A. , Teperino R.
Published: June 2024

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1–7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
MYCT1 controls environmental sensing in human haematopoietic stem cells
Authors: Aguadé-Gorgorió Júlia , Jami-Alahmadi Yasaman , Calvanese Vincenzo , Kardouh Maya , Fares Iman , Johnson Haley , Rezek Valerie , Ma Feiyang , Magnusson Mattias , Wang Yanling , Shin Juliana E. , Nance Karina J. , Goodridge Helen S. , Liebscher Simone , Schenke-Layland Katja , Crooks Gay M. , Wohlschlegel James A. , Mikkola Hanna K. A.
Published: June 2024

The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs1–3. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture. Lentivirus-mediated knockdown of MYCT1 prevented human fetal liver and cord blood (CB) HSPC expansion and engraftment. By contrast, restoring MYCT1 expression improved the expansion and engraftment of cultured CB HSPCs. Single-cell RNA sequencing of human CB HSPCs in which MYCT1 was knocked down or overexpressed revealed that MYCT1 governs important regulatory programmes and cellular properties essential for HSC stemness, such as ETS factor expression and low mitochondrial activity. MYCT1 is localized in the endosomal membrane in HSPCs and interacts with vesicle trafficking regulators and signalling machinery. MYCT1 loss in HSPCs led to excessive endocytosis and hyperactive signalling responses, whereas restoring MYCT1 expression balanced culture-induced endocytosis and dysregulated signalling. Moreover, sorting cultured CB HSPCs on the basis of lowest endocytosis rate identified HSPCs with preserved MYCT1 expression and MYCT1-regulated HSC stemness programmes. Our work identifies MYCT1-moderated endocytosis and environmental sensing as essential regulatory mechanisms required to preserve human HSC stemness. Our data also pinpoint silencing of MYCT1 as a cell-culture-induced vulnerability that compromises human HSC expansion.
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction
Authors: Schormair Barbara , Zhao Chen , Bell Steven , Didriksen Maria , Nawaz Muhammad S. , Schandra Nathalie , Stefani Ambra , Högl Birgit , Dauvilliers Yves , Bachmann Cornelius G. , Kemlink David , Sonka Karel , Paulus Walter , Trenkwalder Claudia , Oertel Wolfgang H. , Hornyak Magdolna , Teder-Laving Maris , Metspalu Andres , Hadjigeorgiou Georgios M. , Polo Olli , Fietze Ingo , Ross Owen A. , Wszolek Zbigniew K. , Ibrahim Abubaker , Bergmann Melanie , Kittke Volker , Harrer Philip , Dowsett Joseph , Chenini Sofiene , Ostrowski Sisse Rye , Sørensen Erik , Erikstrup Christian , Pedersen Ole B. , Topholm Bruun Mie , Nielsen Kaspar R. , Butterworth Adam S. , Soranzo Nicole , Ouwehand Willem H. , Roberts David J. , Danesh John , Burchell Brendan , Furlotte Nicholas A. , Nandakumar Priyanka ,   23andMe Research Team,   D.E.S.I.R. study group, Bonnefond Amélie , Potier Louis , Earley Christopher J. , Ondo William G. , Xiong Lan , Desautels Alex , Perola Markus , Vodicka Pavel , Dina Christian , Stoll Monika , Franke Andre , Lieb Wolfgang , Stewart Alexandre F. R. , Shah Svati H. , Gieger Christian , Peters Annette , Rye David B. , Rouleau Guy A. , Berger Klaus , Stefansson Hreinn , Ullum Henrik , Stefansson Kari , Hinds David A. , Di Angelantonio Emanuele , Oexle Konrad , Winkelmann Juliane
Published: June 2024

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82–0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
CD40 ligand antagonist dazodalibep in Sjögren’s disease: a randomized, double-blinded, placebo-controlled, phase 2 trial
Authors: St. Clair E. William , Baer Alan N. , Ng Wan-Fai , Noaiseh Ghaith , Baldini Chiara , Tarrant Teresa K. , Papas Athena , Devauchelle-Pensec Valerie , Wang Liangwei , Xu Wenjing , Pham Tuyet-Hang , Sikora Keith , Rees William A. , Alevizos Ilias
Published: June 2024

Sjögren’s disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren’s syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren’s Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, −6.3 ± 0.6; PBO, −4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, −1.8 ± 0.2; PBO, −0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164.
A global dataset for assessing nitrogen-related plant traits using drone imagery in major field crop species
Authors: Castilho Diogo , Tedesco Danilo , Hernandez Carlos , Madari Beata Emoke , Ciampitti Ignacio
Published: June 2024

Enhancing rapid phenotyping for key plant traits, such as biomass and nitrogen content, is critical for effectively monitoring crop growth and maximizing yield. Studies have explored the relationship between vegetation indices (VIs) and plant traits using drone imagery. However, there is a gap in the literature regarding data availability, accessible datasets. Based on this context, we conducted a systematic review to retrieve relevant data worldwide on the state of the art in drone-based plant trait assessment. The final dataset consists of 41 peer-reviewed papers with 11,189 observations for 11 major crop species distributed across 13 countries. It focuses on the association of plant traits with VIs at different growth/phenological stages. This dataset provides foundational knowledge on the key VIs to focus for phenotyping key plant traits. In addition, future updates to this dataset may include new open datasets. Our goal is to continually update this dataset, encourage collaboration and data inclusion, and thereby facilitate a more rapid advance of phenotyping for critical plant traits to increase yield gains over time.
In silico intravascular optical coherence tomography (IVOCT) for quality assured imaging with reduced intervention
Authors: Zhuo Haoyu , Huang Xianchen , Xiao Jie
Published: June 2024

In the clinical application of intravascular optical coherence tomography (IVOCT), it is necessary to flush opaque blood during image acquisition. However, there are no specific standards for how to perform low-dose but effective flushing. In this study, computational fluid dynamics (CFD) and optical models were integrated to numerically simulate the complete process of IVOCT, which includes blood flushing with normal saline followed by image acquisition. Moreover, an intermittent injection scheme was proposed, and its advantages over the conventionally adopted scheme of continuous injection were verified. The results show that intermittent injection can significantly reduce the dosage of normal saline (reduced by 44.4%) with only a slight sacrifice of image quality (reduced by 8.7%, but still acceptable). The developed model and key findings in this work can help surgeons practice optimized IVOCT operations and potentially lead to improved designs of the IVOCT equipment.
An interpretable ensemble structure with a non-iterative training algorithm to improve the predictive accuracy of healthcare data analysis
Authors: Izonin Ivan , Tkachenko Roman , Yemets Kyrylo , Havryliuk Myroslav
Published: June 2024

The modern development of healthcare is characterized by a set of large volumes of tabular data for monitoring and diagnosing the patient's condition. In addition, modern methods of data engineering allow the synthesizing of a large number of features from an image or signals, which are presented in tabular form. The possibility of high-precision and high-speed processing of such large volumes of medical data requires the use of artificial intelligence tools. A linear machine learning model cannot accurately analyze such data, and traditional bagging, boosting, or stacking ensembles typically require significant computing power and time to implement. In this paper, the authors proposed a method for the analysis of large sets of medical data, based on a designed linear ensemble method with a non-iterative learning algorithm. The basic node of the new ensemble is an extended-input SGTM neural-like structure, which provides high-speed data processing at each level of the ensemble. Increasing prediction accuracy is ensured by dividing the large dataset into parts, the analysis of which is carried out in each node of the ensemble structure and taking into account the output signal from the previous level of the ensemble as an additional attribute on the next one. Such a design of a new ensemble structure provides both a significant increase in the prediction accuracy for large sets of medical data analysis and a significant reduction in the duration of the training procedure. Experimental studies on a large medical dataset, as well as a comparison with existing machine learning methods, confirmed the high efficiency of using the developed ensemble structure when solving the prediction task.
Discrete element modeling and experimental study of biomechanical properties of cotton stalks in machine-harvested film-stalk mixtures
Authors: Zhang Jia , Xie Jianhua , Du Yakun , Li Yuanze , Yue Yong , Cao Silin
Published: June 2024

To address the current problems of low accuracy and poor reliability of the discrete element model of cotton stalks, as well as the difficulty of guiding the design and optimization of the equipment through simulations, the discrete element modeling and physical-mechanical tests of cotton stalks in machine harvested film-stalk mixtures are carried out. The peak tensile force $$F_{\rm j}^{\max }$$

F

j

max

, the peak pressure $$F_{\rm y}^{\max }$$

F

y

max

, the peak bending force $$F_{\rm w}^{\max }$$

F

w

max

, the peak shear force $$F_{\rm j}^{\max }$$

F

j

max

, and the force-displacement (F–x) curves of cotton stalks are obtained from the physical tests. The discrete element model of double-layer cotton stalks based on the flat-joint model is established with the PFC$$^{\rm 3D}$$

3
D

software. The $$F_{\rm y}^{\max }$$

F

y

max

is taken as the response value, and the microscopic parameters of the cotton stalk model are used as the test factors, then the Plackett–Burman test, the steepest climb test, and the Box–Behnken test are sequentially designed using Design-Expert software. The second-order regression model describing the relationship between the $$F_{\rm y}^{\max }$$

F

y

max

and the microscopic parameters is established. The optimal parameter combinations of the microscopic parameters are obtained, and then they are utilized to construct the compression, bending, and shear models of cotton stalks and to carry out the validation tests. The results confirm that the established discrete element model could accurately characterize the biomechanical properties of cotton stalks and that the parameter calibration method is reasonable, which could provide a reference for the discrete element modeling of cotton stalks and other stalks, and also offer a theoretical basis for the research of the crushing and separation mechanism of the film-stalk mixtures and the development of the equipment.
The beneficial effects of ethanolic extract of Sargassum serratifolium in DNCB-induced mouse model of atopic dermatitis
Authors: Kim Myeong-Jin , Ryu Heeyeon , Jeong Hyeon Hak , Van Ji Yun , Hwang Ji Young , Kim Ah-reum , Seo Jaeseong , Moon Kyoung Mi , Jung Won-Kyo , Lee Bonggi
Published: June 2024

Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.
Photocatalytic, antimicrobial and antibiofilm activities of MgFe2O4 magnetic nanoparticles
Authors: El-Khawaga Ahmed M. , Ayman Mohamed , Hafez Omar , Shalaby Rasha E.
Published: June 2024

This study reports the antibacterial and antibiofilm activities of Magnesium ferrite nanoparticles (MgFe2O4) against gram-positive and gram-negative bacteria. The photocatalytic degradation of Carbol Fuchsin (CF) dye (a class of dyestuffs that are resistant to biodegradation) under the influence of UV-light irradiation is also studied. The crystalline magnesium ferrite (MgFe2O4) nanoparticles were synthesized using the co-precipitation method. The morphology of the resulting nanocomposite was examined using scanning electron microscopy (SEM), while transmission electron microscopy (TEM) was employed for further characterization of particle morphology and size. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were utilized to analyze the crystalline structure, chemical composition, and surface area, respectively. Optical properties were evaluated using UV–Vis spectroscopy. The UV-assisted photocatalytic performance of MgFe2O4 nanoparticles was assessed by studying the decolorization of Carbol fuchsin (CF) azo dye. The crystallite size of the MgFe2O4 nanoparticles at the (311) plane, the most prominent peak, was determined to be 28.5 nm. The photocatalytic degradation of 10 ppm CF using 15 mg of MgFe2O4 nanoparticles resulted in a significant 96% reduction after 135 min at ambient temperature (25 °C) and a pH value of 9. Additionally, MgFe2O4 nanoparticles exhibited potent antibacterial activity against E. coli and S. aureus in a dose dependent manner with maximum utilized concentration of 30 µg/ml. Specifically, MgFe2O4 nanoparticles demonstrated substantial antibacterial activity via disk diffusion and microbroth dilution tests with zones of inhibition and minimum inhibitory concentrations (MIC) for E. coli (26.0 mm, 1.25 µg/ml) and S. aureus (23.0 mm, 2.5 µg/ml), respectively. Moreover, 10.0 µg/ml of MgFe2O4 nanoparticles elicited marked percent reduction in biofilm formation by E. coli (89%) followed by S. aureus (78.5%) after treatment. In conclusion, MgFe2O4 nanoparticles demonstrated efficient dye removal capabilities along with significant antimicrobial and antibiofilm activity against gram-positive and gram-negative bacterial strains suggesting their potential as promising antimicrobial and detoxifying agents.
SIR+ models: accounting for interaction-dependent disease susceptibility in the planning of public health interventions
Authors: Martignoni Maria M. , Raulo Aura , Linkovski Omer , Kolodny Oren
Published: June 2024

Avoiding physical contact is regarded as one of the safest and most advisable strategies to follow to reduce pathogen spread. The flip side of this approach is that a lack of social interactions may negatively affect other dimensions of health, like induction of immunosuppressive anxiety and depression or preventing interactions of importance with a diversity of microbes, which may be necessary to train our immune system or to maintain its normal levels of activity. These may in turn negatively affect a population’s susceptibility to infection and the incidence of severe disease. We suggest that future pandemic modelling may benefit from relying on ‘SIR+ models’: epidemiological models extended to account for the benefits of social interactions that affect immune resilience. We develop an SIR+ model and discuss which specific interventions may be more effective in balancing the trade-off between minimizing pathogen spread and maximizing other interaction-dependent health benefits. Our SIR+ model reflects the idea that health is not just the mere absence of disease, but rather a state of physical, mental and social well-being that can also be dependent on the same social connections that allow pathogen spread, and the modelling of public health interventions for future pandemics should account for this multidimensionality.