bluuebunny/crossref_metadata_2025 huggingface dataset:
GLP-1 Receptor Agonist Exposures Are Increasingly Common and Generally Associated with Mild Symptoms: A Single Poison Center Experience
Authors: Marshall Stacy , Ryan Erin , Rivera Jessica , Reynolds Lindy , Atti Suhkshant
Published: June 2024

Introduction

Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials indicate that gastrointestinal adverse effects are commonly experienced and severe hypoglycemia is rare; however, there is little data regarding glucagon-like peptide-1 receptor agonist in overdose.

Methods

We performed a retrospective chart review evaluating and characterizing glucagon-like peptide-1 receptor agonist exposures reported to a single poison center between 2006 and 2023. Patient demographics, circumstances of exposure, clinical effects, and outcomes were abstracted from charts. Descriptive statistics were utilized to summarize demographic information and clinical factor data.

Results

A total of 152 charts met inclusion criteria. Therapeutic errors accounted for 91% of exposures. Most patients (67%) reported no symptoms, although not all patients were followed to a definitive outcome. Nausea, vomiting, generalized weakness, and abdominal pain were the predominant symptoms reported. Most patients (62%) were monitored and closely followed in the home setting. Hypoglycemia was rare but occurred in the setting of a single agent glucagon-like peptide-1 receptor agonist exposure in two patients. Two additional patients who developed hypoglycemia involved co-administration of insulin. 21% of the exposures were related to errors on initial use of the pen.

Conclusion

Exposures to glucagon-like peptide-1 receptor agonist have increased substantially over the years. Effects from an exposure tended to be mild and primarily involve gastrointestinal symptoms. Hypoglycemia was rare. Therapeutic and administration errors were common. Education on pen administration may help to reduce errors.
A novel screw-type pyrolysis system for selectively producing value-added chemicals from lignocellulosic biomass
Authors: Altundoğan H. Soner , Tanyıldızı M. Şaban , Kalender Mehmet , Elçiçek Serhat , Pehlivan Dursun
Published: June 2024

In this study, a new unique screw-type (auger) reactor system was developed to selectively obtain valuable chemical-enriched liquid pyrolysis products. The new design has heating segments with increased temperature along the reactor tube and three-staged fractional condensing lines following pyrolysis gas ports at the end of each heating segment. To maximize liquid product yield, the effects of some parameters such as feeding rate, screw rate, and temperature profile were studied by the experiments designed with Response Surface Methodology (RSM). By fixing the maximum temperature at the last heating segment of a tubular reactor to 550 °C, the conditions for maximum liquid product yield were determined as feeder driver frequency of 21 Hz (13.6 rpm), auger driver frequency of 36 Hz (24.3 rpm), and ΔT (temperature difference between consecutive heating segments) of 66 °C. Biomass feeding rate and volumetric fullness ratio of the reactor at these conditions were 42 g min−1 and 0.58 (v/v), respectively. Under these conditions, total liquid, solid, and gas product yields were obtained as 57%, 19%, and 24%, respectively. In addition, analyses of the liquid fractions showed that valuable chemicals could be obtained selectively in a large extent by using the new design.
Antimicrobial Resistance in Migratory Paths, Refugees, Asylum Seekers and Internally Displaced Persons: A Narrative Review
Authors: Comelli Agnese , Gaviraghi Alberto , Cattaneo Paolo , Motta Leonardo , Bisoffi Zeno , Stroffolini Giacomo
Published: June 2024

Purpose of Review

Antimicrobial resistance (AMR) is a significant global health challenge, especially for populations with limited access to healthcare services and poor living conditions. This narrative review focuses on the determinants and figures related to AMR in the context of migration.

Recent Findings

Migrants face the risk of MDRO (multidrug resistant organisms) acquisition at every stage of their migration journey, from their country of origin to the transit centres and destination countries. While there is a lack of systematic data, the existing information justifies raising alertness among the global health community. Moreover, in recent years, a growing body of literature has reported that armed conflicts act as a magnifier of AMR spreading.

Targeted interventions at each stage of migration are urgently needed to limit the spread of the AMR pandemic, particularly among this vulnerable population.
Course of growth and nutritional status in Swiss children with food allergies
Authors: Gerber Rebekka , Meichtry Andre , van der Horst Klazine , Koehli Alice , Roduit Caroline , Bellutti Enders Felicitas , Skypala Isabel , Hickson Mary , Eisenblaetter Julia
Published: June 2024

Purpose

Studies suggest that children with immunoglobulin E (IgE)-mediated food allergies (FA) are at risk of impaired growth, especially those with cow’s milk or multiple FA. However, there is limited long-term data available on this topic. This analysis presents the growth of Swiss children for the first year after FA diagnosis.

Methods

This is a secondary analysis of data from a multicentered study following food allergic children (0–10 years) over 1 year post diagnosis, comparing those who received dietary counselling with those who did not. Growth z‑scores were calculated based on World Health Organization (WHO) standards, using data reported by caregivers. To analyze data, linear mixed models with between-subject factors related to dietary counselling, number of FA, and cow’s milk allergy were fitted to the data.

Results

In the 48 children (median age 16 months) studied, we observed an increasing prevalence of wasting (weight-for-length/height z‑score < 2; 2–10%) and a lower prevalence of stunting (length/height-for-age < 2; 0–2%) over the 1‑year period. Twelve months after diagnosis, all median z‑scores showed an increase. Linear mixed model analysis did not find any significant within-subject and between-subject effects on growth.

Conclusion

Children with IgE-mediated FA can have normal growth if children with cow’s milk allergy or multiple food allergies receive dietary counselling. Routine length/height and weight measurements should be taken to identify individual malnutrition and to initiate tailored nutritional interventions. Larger studies with longer duration are needed to assess further growth development in children with IgE-mediated food allergies.
Well-Tempered Power: ‘A Cultural Achievement of Universal Significance’
Authors: Krygier Martin
Published: June 2024

According to Laurent Pech, the rule of law was described as a “‘buzzword’ by [Hungary’s] justice minister; a fiction by a Fidesz MP; and a ‘magic word’ by the Fidesz-KDNP Delegation to the European Parliament. Not to be undone, a judge from Hungary’s (captured) constitutional court, has presented the rule of law ‘as a normative yardstick’ which is little more than an empty nineteenth century ideal and a political joker [sic] for all purposes” (Pech, Hague J Rule Law 14(2–3): 107-138, 2022 128). In contrast, the English historian, E.P. Thompson, notoriously and controversially called the rule of law ‘a cultural achievement of universal significance.’ With small amendments, I agree with Thompson. Each word in that phrase, I seek to demonstrate, deserves emphasis and respect. However, it makes a huge difference what one takes the rule of law to be about. What is universal is the notion and realisation of a state of affairs in which power is reliably tempered so as not to be available for arbitrary abuse. It is that which is a cultural achievement of universal significance. It is a mistake to identify it, as so many do, with any allegedly canonical arrangement of forms and institutions and rules that are enlisted or assumed to embody it. Many people make that mistake. Some do so, because they naively think that installation of familiar institutions they associate with ‘the rule of law’ is the same as generating the ideal itself. The disappointing history of rule of law promotion around the world shows that is not the case. On the other hand, modern illiberal, often populist, regimes are happy to endorse such a mistake and pretend that they are committed to the rule of law by making a show of conformity to legal forms, while systematically subverting and abusing the rule of law itself. Both the naïve and the malicious interpretations should be rejected.
Challenges and Issues in Implementing & Operationalising Big Data Analytics Capabilities in a major Australian Railway Organisation: A Case Study
Authors: Kortian Viken , Pal Souvik , Ghevondian Nejhdeh , Harrison Norma
Published: June 2024

This study examines the implementation of a Big Data Analytics (BDA) project within a major Australian freight and railway organisation. It also identifies the issues and challenges with data collection, data cleaning, data modelling, and data science software, and implements these models to deliver tangible business results. In addition, the project highlights the potential gains that a data analytics project, integrated with a data-driven culture, can provide through significant operational efficiencies and financial gains. Prior to 2019, the company had little exposure to Predictive Analytics. This study shows how the development of data science capability enables the creation of advanced predictive models, particularly in this case study, for the prediction of train wheel wear, and therefore a significant reduction in maintenance expenses Furthermore, a Data Analytics Maturity Assessment was conducted to determine the requirements to become a data-driven organisation. The outcome of the assessment was compared to recent global studies, and it was found that the organisation examined was significantly behind its counterparts in the areas of resources and analytic capabilities, and therefore required investment in these areas. Further studies to examine the degree of Data Analytics maturity within the Australian context are suggested. Organisations striving to become more data-driven need to plan and allocate resources for capability development in infrastructure, data management, employee quantitative skills, and governance.
The Association Between Cloud Droplet Number over the Summer Southern Ocean and Air Mass History
Authors: Mace Gerald G. , Benson Sally , Sterner Elizabeth , Protat Alain , Humphries Ruhi , Hallar A. Gannet
Published: June 2024

The cloud properties and governing processes in Southern Ocean marine boundary layer clouds have emerged as a central issue in understanding the Earth's climate sensitivity. While our understanding of Southern Ocean cloud feedbacks have evolved in the most recent climate model intercomparison, the background properties of simulated summertime clouds in the Southern Ocean are not consistent with measurements due to known biases in simulating cloud condensation nuclei concentrations. This paper presents several case studies collected during the Capricorn 2 and Marcus campaigns held aboard Australian research vessels in the Austral Summer of 2018. Combining the surface‐observed cases with MODIS data along forward and backward air mass trajectories, we demonstrate the evolution of cloud properties with time. These cases are consistent with multi‐year statistics showing that long trajectories of air masses over the Antarctic ice sheet are critical to creating high droplet number clouds in the high latitude summer Southern Ocean. We speculate that secondary aerosol production via the oxidation of biogenically derived aerosol precursor gasses over the high actinic flux region of the high latitude ice sheets is fundamental to maintaining relatively high droplet numbers in Southern Ocean clouds during Summer.
Numerical Studies on the Influence of Building Morphology on Urban Canopy Wind Speed
Authors: Sun Yong , Zhang Ning , Ao Xiangyu , Gao Ying
Published: June 2024

Buildings increase the urban surface roughness and reduce near‐surface wind speeds in the urban canopy due to the drag effect. Urban heat storage and other effects cause urban warming as well, which decreases the urban boundary layer stability and enhances the turbulence exchange between upper and lower layer. As upper momentum is transported downward, the wind speed of urban canopy increases. Quantitative descriptions of these mechanisms are still lacking currently. This paper presents high‐resolution numerical simulation results of a mega city, Shanghai, China from 2016 to 2020 using the building effect parameterization in WRF (WRF‐BEP) with urban morphological parameters. The dynamic and thermal effects of building morphology on urban canopy wind speed were separated and their quantitative expression functions were given. The results indicate that the influence of building morphology on urban canopy wind speed is mainly dynamic resulting in a wind speed attenuation of approximately 50% and nearly constant. The thermal effect of building morphology on urban canopy wind speed increases with the urban heat island intensity, and the thermal effect could increase urban canopy wind speed by about 30% under the condition of strong urban heat island. The relative contributions of the dynamic and thermal effects of building morphology to urban canopy wind speed change with the wind speed. As wind speed increases, the contribution of the thermal effect of building morphology to urban canopy wind speed gradually decreases. This paper provides a quantitative relationship between the urban canopy wind speed variation and urban morphology, as well as urban heat island intensity.
Regional Variation in Extratropical North Atlantic Air‐Sea Interaction 1960–2020
Authors: Latif Mojib , Martin Thomas , Bielke Inken
Published: June 2024

Air‐sea interaction in late boreal winter is studied over the extratropical North Atlantic (NA) during 1960–2020 by examining the relationship between sea‐surface temperature (SST) and total turbulent heat flux (THF). The two quantities are positively correlated on interannual timescales over the central‐midlatitude and subpolar NA, suggesting the atmosphere on average drives SST and THF variability is independent of SST. On decadal timescales and over the central‐midlatitude NA the correlation is negative, suggesting ocean processes on average drive SST and THF variability is sensitive to SST. The correlation is positive over the subpolar NA. There, interannual and decadal THF variability is governed by the North Atlantic Oscillation (NAO). During the major late 20th and early 21st century SST increase in the subpolar NA diminishing oceanic heat loss associated with a weakening NAO was observed. This study suggests that the atmosphere is more sensitive to SST over the central‐midlatitude than subpolar NA.
Microphysical Simulation of the 2022 Hunga Volcano Eruption Using a Sectional Aerosol Model
Authors: Li Chenwei , Peng Yifeng , Asher Elizabeth , Baron Alexandre A. , Todt Michael , Thornberry Troy D. , Evan Stephanie , Brioude Jerome , Smale Penny , Querel Richard , Rosenlof Karen H. , Zhou Luxi , Xu Jingyuan , Qie Kai , Bian Jianchun , Toon Owen B. , Zhu Yunqian , Yu Pengfei
Published: June 2024

Approximately 150 Tg of water vapor and 0.42 Tg of sulfur dioxide were injected directly into the stratosphere by the January 2022 Hunga volcanic eruption, which represents the largest water vapor injection in the satellite era. A comparison of numerical simulations to balloon‐borne and satellite observations of the water‐rich plume suggests that particle coagulation contributed to the Hunga aerosol's effective dry radius increase from 0.2 μm in February to around 0.4 μm in March. Our model suggests that the stratospheric aerosol effective radius is persistently perturbed for years by moderate and large‐magnitude volcanic events, whereas extreme wildfire events show limited impact on the stratospheric background particle size. Our analysis further suggests that both the particle optical efficiency and the aerosols' stratospheric lifetime explain Hunga's unusually large aerosol optical depth per unit of the SO2 injection, as compared with the Pinatubo eruption.
Responses of the Urban Atmospheric Thermal Environment to Two Distinct Heat Waves and Their Changes With Future Urban Expansion in a Chinese Megacity
Authors: Zhao Yang , Zhong Lei , Zhou Keqi , Liu Bin , Shu Weixi
Published: June 2024

This study investigates the responses of the urban atmospheric thermal environment to two distinct heat waves in Hefei, China, and explores potential changes associated with future urban expansion. During the Event 1, characterized by clear and dry conditions, the western Pacific subtropical high limits water vapor influx, resulting in a significant cooling effect in rural area due to higher surface latent heat flux. The urban heat island (UHI) intensity, calculated using surface temperature and 2‐m temperature, reaches 5.2°C and 1.7°C during the Event 1, respectively. Although Event 2, characterized by cloudy and humid conditions, exhibits weaker UHI and urban dry island effects, it remains highly unfavorable for human comfort. During distinct heat waves, the vertical extent of the warming effect induced by future urban expansion varies, which can be attributed to environmental factors, such as atmospheric stability and near‐surface wind speed.
The Longwave Cloud‐Radiative Feedback in Tropical Waves Derived by Different Precipitation Data Sets
Authors: Hsiao Wei‐Ting , Maloney Eric D.
Published: June 2024

Anomalous tropical longwave cloud‐radiative heating of the atmosphere is generated when convective precipitation occurs, which plays an important role in the dynamics of tropical disturbances. Defining the observed cloud‐radiative feedback as the reduction of top‐of‐atmosphere longwave radiative cooling per unit precipitation, the feedback magnitudes are sensitive to the observed precipitation data set used when comparing two versions of Global Precipitation Climatology Project, version 1.3 (GPCPv1.3) and the newer version 3.2 (GPCPv3.2). GPCPv3.2 contains larger magnitudes and variance of daily precipitation, which yields a weaker cloud‐radiative feedback in tropical disturbances at all frequencies and zonal wavenumbers. Weaker cloud‐radiative feedbacks occur in GPCPv3.2 at shorter zonal lengths on intraseasonal timescales, which implies a preferential growth at planetary scales for the Madden‐Julian oscillation. Phase relationships between precipitation, radiative heating, and other thermodynamic variables in eastward‐propagating gravity waves also change with the updated GPCPv3.2.
l-valine is a powerful stimulator of GLP-1 secretion in rodents and stimulates secretion through ATP-sensitive potassium channels and voltage-gated calcium channels
Authors: Modvig Ida Marie , Smits Mark M. , Galsgaard Katrine Douglas , Hjørne Anna Pii , Drzazga Anna Katarzyna , Rosenkilde Mette Marie , Holst Jens Juul
Published: June 2024

Background

We previously reported that, among all the naturally occurring amino acids, l-valine is the most powerful luminal stimulator of glucagon-like peptide 1 (GLP-1) release from the upper part of the rat small intestine. This makes l-valine an interesting target for nutritional-based modulation of GLP-1 secretion. However, the molecular mechanism of l-valine-induced secretion remains unknown.

Methods

We aimed to investigate the effect of orally given l-valine in mice and to identify the molecular details of l-valine stimulated GLP-1 release using the isolated perfused rat small intestine and GLUTag cells. In addition, the effect of l-valine on hormone secretion from the distal intestine was investigated using a perfused rat colon.

Results

Orally given l-valine (1 g/kg) increased plasma levels of active GLP-1 comparably to orally given glucose (2 g/kg) in male mice, supporting that l-valine is a powerful stimulator of GLP-1 release in vivo (P > 0.05). Luminal l-valine (50 mM) strongly stimulated GLP-1 release from the perfused rat small intestine (P < 0.0001), and inhibition of voltage-gated Ca2+-channels with nifedipine (10 μM) inhibited the GLP-1 response (P < 0.01). Depletion of luminal Na+ did not affect l-valine-induced GLP-1 secretion (P > 0.05), suggesting that co-transport of l-valine and Na+ is not important for the depolarization necessary to activate the voltage-gated Ca2+-channels. Administration of the KATP-channel opener diazoxide (250 μM) completely blocked the l-valine induced GLP-1 response (P < 0.05), suggesting that l-valine induced depolarization arises from metabolism and opening of KATP-channels. Similar to the perfused rat small intestine, l-valine tended to stimulate peptide tyrosine-tyrosine (PYY) and GLP-1 release from the perfused rat colon.

Conclusions

l-valine is a powerful stimulator of GLP-1 release in rodents. We propose that intracellular metabolism of l-valine leading to closure of KATP-channels and opening of voltage-gated Ca2+-channels are involved in l-valine induced GLP-1 secretion.
Structural basis of p53 inactivation by cavity-creating cancer mutations and its implications for the development of mutant p53 reactivators
Authors: Balourdas Dimitrios-Ilias , Markl Anja M. , Krämer Andreas , Settanni Giovanni , Joerger Andreas C.
Published: June 2024

The cavity-creating p53 cancer mutation Y220C is an ideal paradigm for developing small-molecule drugs based on protein stabilization. Here, we have systematically analyzed the structural and stability effects of all oncogenic Tyr-to-Cys mutations (Y126C, Y163C, Y205C, Y220C, Y234C, and Y236C) in the p53 DNA-binding domain (DBD). They were all highly destabilizing, drastically lowering the melting temperature of the protein by 8–17 °C. In contrast, two non-cancerous mutations, Y103C and Y107C, had only a moderate effect on protein stability. Differential stabilization of the mutants upon treatment with the anticancer agent arsenic trioxide and stibogluconate revealed an interesting proximity effect. Crystallographic studies complemented by MD simulations showed that two of the mutations, Y234C and Y236C, create internal cavities of different size and shape, whereas the others induce unique surface lesions. The mutation-induced pockets in the Y126C and Y205C mutant were, however, relatively small compared with that of the already druggable Y220C mutant. Intriguingly, our structural studies suggest a pronounced plasticity of the mutation-induced pocket in the frequently occurring Y163C mutant, which may be exploited for the development of small-molecule stabilizers. We point out general principles for reactivating thermolabile cancer mutants and highlight special cases where mutant-specific drugs are needed for the pharmacological rescue of p53 function in tumors.
Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway
Authors: Li Hongxia , Pan Wenlan , Li Chenqi , Cai Mengyu , Shi Wenjing , Ren Zifu , Lu Hongtao , Zhou Qicheng , Shen Hui
Published: June 2024

Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms that underlie this phenomenon have yet to be extensively investigated. The Morris water maze test was utilized to assess cognitive performance. RNA sequencing was employed to discover the primary regulators and pathological pathways involved in cognitive impairment caused by heat. Before heat exposure in vivo and in vitro, activation of the sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) was achieved by CDN1163. Hematoxylin-Eosin, Nissl staining, calcium imaging, transmission electron microscopy, western blot, and immunofluorescence were utilized to visualize histological changes, intracellular calcium levels, endoplasmic reticulum stress (ERS) markers, apoptosis, and synaptic proteins alterations. Heat stress (HS) significantly induced cognitive decline and neuronal damage in mice. By the transcriptome sequencing between control (n = 5) and heat stress (n = 5) mice in hippocampal tissues, we identified a reduction in the expression of the atp2a gene encoding SERCA, accompanied by a corresponding decrease in its protein level. Consequently, this dysregulation resulted in an excessive accumulation of intracellular calcium ions. Furthermore, HS exposure also activated ERS and apoptosis, as evidenced by the upregulation of p-PERK, p-eIF2α, CHOP, and caspase-3. Consistently, a reduction in postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) expressions indicated modifications in synaptic function. Notably, the impacts on neurons caused by HS were found to be mitigated by CDN1163 treatment both in vivo and in vitro. Additionally, SERCA-mediated ERS-induced apoptosis was attenuated by GSK2606414 treatment via inhibiting PERK-eIF2α-CHOP axis that not only curtailed the level of caspase-3 but also elevated the levels of PSD95 and SYN. These findings highlight the significant impact of heat stress on cognitive impairment, and further elucidate the underlying mechanism involving SERCA/PERK/eIF2α pathway.
Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs)
Authors: Schmitt Laura , Hoppe Julia , Cea-Medina Pablo , Bruch Peter-Martin , Krings Karina S. , Lechtenberg Ilka , Drießen Daniel , Peter Christoph , Bhatia Sanil , Dietrich Sascha , Stork Björn , Fritz Gerhard , Gohlke Holger , Müller Thomas J. J. , Wesselborg Sebastian
Published: June 2024

A key feature of cancer is the disruption of cell cycle regulation, which is characterized by the selective and abnormal activation of cyclin-dependent kinases (CDKs). Consequently, targeting CDKs via meriolins represents an attractive therapeutic approach for cancer therapy. Meriolins represent a semisynthetic compound class derived from meridianins and variolins with a known CDK inhibitory potential. Here, we analyzed the two novel derivatives meriolin 16 and meriolin 36 in comparison to other potent CDK inhibitors and could show that they displayed a high cytotoxic potential in different lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells. In a kinome screen, we showed that meriolin 16 and 36 prevalently inhibited most of the CDKs (such as CDK1, 2, 3, 5, 7, 8, 9, 12, 13, 16, 17, 18, 19, 20). In drug-to-target modeling studies, we predicted a common binding mode of meriolin 16 and 36 to the ATP-pocket of CDK2 and an additional flipped binding for meriolin 36. We could show that cell cycle progression and proliferation were blocked by abolishing phosphorylation of retinoblastoma protein (a major target of CDK2) at Ser612 and Thr82. Moreover, meriolin 16 prevented the CDK9-mediated phosphorylation of RNA polymerase II at Ser2 which is crucial for transcription initiation. This renders both meriolin derivatives as valuable anticancer drugs as they target three different Achilles’ heels of the tumor: (1) inhibition of cell cycle progression and proliferation, (2) prevention of transcription, and (3) induction of cell death.
Release of CD36-associated cell-free mitochondrial DNA and RNA as a hallmark of space environment response
Authors: Husna Nailil , Aiba Tatsuya , Fujita Shin-Ichiro , Saito Yoshika , Shiba Dai , Kudo Takashi , Takahashi Satoru , Furukawa Satoshi , Muratani Masafumi
Published: June 2024

A detailed understanding of how spaceflight affects human health is essential for long-term space exploration. Liquid biopsies allow for minimally-invasive multi-omics assessments that can resolve the molecular heterogeneity of internal tissues. Here, we report initial results from the JAXA Cell-Free Epigenome Study, a liquid biopsy study with six astronauts who resided on the International Space Station (ISS) for more than 120 days. Analysis of plasma cell-free RNA (cfRNA) collected before, during, and after spaceflight confirms previously reported mitochondrial dysregulation in space. Screening with 361 cell surface marker antibodies identifies a mitochondrial DNA-enriched fraction associated with the scavenger receptor CD36. RNA-sequencing of the CD36 fraction reveals tissue-enriched RNA species, suggesting the plasma mitochondrial components originated from various tissues. We compare our plasma cfRNA data to mouse plasma cfRNA data from a previous JAXA mission, which had used on-board artificial gravity, and discover a link between microgravity and the observed mitochondrial responses.
Astronaut omics and the impact of space on the human body at scale
Authors: Rutter Lindsay A. , Cope Henry , MacKay Matthew J. , Herranz Raúl , Das Saswati , Ponomarev Sergey A. , Costes Sylvain V. , Paul Amber M. , Barker Richard , Taylor Deanne M. , Bezdan Daniela , Szewczyk Nathaniel J. , Muratani Masafumi , Mason Christopher E. , Giacomello Stefania
Published: June 2024

Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.
Studying phonon coherence with a quantum sensor
Authors: Cleland Agnetta Y. , Wollack E. Alex , Safavi-Naeini Amir H.
Published: June 2024

Nanomechanical oscillators offer numerous advantages for quantum technologies. Their integration with superconducting qubits shows promise for hardware-efficient quantum error-correction protocols involving superpositions of mechanical coherent states. Limitations of this approach include mechanical decoherence processes, particularly two-level system (TLS) defects, which have been widely studied using classical fields and detectors. In this manuscript, we use a superconducting qubit as a quantum sensor to perform phonon number-resolved measurements on a piezoelectrically coupled phononic crystal cavity. This enables a high-resolution study of mechanical dissipation and dephasing in coherent states of variable size ($$\bar{n}\simeq 1-10$$

n

¯

≃
1
−
10
phonons). We observe nonexponential relaxation and state size-dependent reduction of the dephasing rate, which we attribute to TLS. Using a numerical model, we reproduce the dissipation signatures (and to a lesser extent, the dephasing signatures) via emission into a small ensemble (N = 5) of rapidly dephasing TLS. Our findings comprise a detailed examination of TLS-induced phonon decoherence in the quantum regime.
Observation of a spontaneous anomalous Hall response in the Mn5Si3 d-wave altermagnet candidate
Authors: Reichlova Helena , Lopes Seeger Rafael , González-Hernández Rafael , Kounta Ismaila , Schlitz Richard , Kriegner Dominik , Ritzinger Philipp , Lammel Michaela , Leiviskä Miina , Birk Hellenes Anna , Olejník Kamil , Petřiček Vaclav , Doležal Petr , Horak Lukas , Schmoranzerova Eva , Badura Antonín , Bertaina Sylvain , Thomas Andy , Baltz Vincent , Michez Lisa , Sinova Jairo , Goennenwein Sebastian T. B. , Jungwirth Tomáš , Šmejkal Libor
Published: June 2024

Phases with spontaneous time-reversal ($${{{{{{{\mathcal{T}}}}}}}}$$
T
) symmetry breaking are sought after for their anomalous physical properties, low-dissipation electronic and spin responses, and information-technology applications. Recently predicted altermagnetic phase features an unconventional and attractive combination of a strong $${{{{{{{\mathcal{T}}}}}}}}$$
T
-symmetry breaking in the electronic structure and a zero or only weak-relativistic magnetization. In this work, we experimentally observe the anomalous Hall effect, a prominent representative of the $${{{{{{{\mathcal{T}}}}}}}}$$
T
-symmetry breaking responses, in the absence of an external magnetic field in epitaxial thin-film Mn5Si3 with a vanishingly small net magnetic moment. By symmetry analysis and first-principles calculations we demonstrate that the unconventional d-wave altermagnetic phase is consistent with the experimental structural and magnetic characterization of the Mn5Si3 epilayers, and that the theoretical anomalous Hall conductivity generated by the phase is sizable, in agreement with experiment. An analogy with unconventional d-wave superconductivity suggests that our identification of a candidate of unconventional d-wave altermagnetism points towards a new chapter of research and applications of magnetic phases.
Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides
Authors: Claudio Quiros Adalberto , Coudray Nicolas , Yeaton Anna , Yang Xinyu , Liu Bojing , Le Hortense , Chiriboga Luis , Karimkhan Afreen , Narula Navneet , Moore David A. , Park Christopher Y. , Pass Harvey , Moreira Andre L. , Le Quesne John , Tsirigos Aristotelis , Yuan Ke
Published: June 2024

Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited by the cost and quality of annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels and operating via the automatic discovery of discriminatory features in image tiles. Tiles are grouped into morphologically similar clusters which constitute an atlas of histomorphological phenotypes (HP-Atlas), revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. These properties are maintained in a multi-cancer study.
Ultra-high spin emission from antiferromagnetic FeRh
Authors: Hamara Dominik , Strungaru Mara , Massey Jamie R. , Remy Quentin , Chen Xin , Nava Antonio Guillermo , Alves Santos Obed , Hehn Michel , Evans Richard F. L. , Chantrell Roy W. , Mangin Stéphane , Ducati Caterina , Marrows Christopher H. , Barker Joseph , Ciccarelli Chiara
Published: June 2024

An antiferromagnet emits spin currents when time-reversal symmetry is broken. This is typically achieved by applying an external magnetic field below and above the spin-flop transition or by optical pumping. In this work we apply optical pump-THz emission spectroscopy to study picosecond spin pumping from metallic FeRh as a function of temperature. Intriguingly we find that in the low-temperature antiferromagnetic phase the laser pulse induces a large and coherent spin pumping, while not crossing into the ferromagnetic phase. With temperature and magnetic field dependent measurements combined with atomistic spin dynamics simulations we show that the antiferromagnetic spin-lattice is destabilised by the combined action of optical pumping and picosecond spin-biasing by the conduction electron population, which results in spin accumulation. We propose that the amplitude of the effect is inherent to the nature of FeRh, particularly the Rh atoms and their high spin susceptibility. We believe that the principles shown here could be used to produce more effective spin current emitters. Our results also corroborate the work of others showing that the magnetic phase transition begins on a very fast picosecond timescale, but this timescale is often hidden by measurements which are confounded by the slower domain dynamics.
Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice
Authors: Masarapu Yuvarani , Cekanaviciute Egle , Andrusivova Zaneta , Westholm Jakub O. , Björklund Åsa , Fallegger Robin , Badia-i-Mompel Pau , Boyko Valery , Vasisht Shubha , Saravia-Butler Amanda , Gebre Samrawit , Lázár Enikő , Graziano Marta , Frapard Solène , Hinshaw Robert G. , Bergmann Olaf , Taylor Deanne M. , Wallace Douglas C. , Sylvén Christer , Meletis Konstantinos , Saez-Rodriguez Julio , Galazka Jonathan M. , Costes Sylvain V. , Giacomello Stefania
Published: June 2024

Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR).
Sopa: a technology-invariant pipeline for analyses of image-based spatial omics
Authors: Blampey Quentin , Mulder Kevin , Gardet Margaux , Christodoulidis Stergios , Dutertre Charles-Antoine , André Fabrice , Ginhoux Florent , Cournède Paul-Henry
Published: June 2024

Spatial omics data allow in-depth analysis of tissue architectures, opening new opportunities for biological discovery. In particular, imaging techniques offer single-cell resolutions, providing essential insights into cellular organizations and dynamics. Yet, the complexity of such data presents analytical challenges and demands substantial computing resources. Moreover, the proliferation of diverse spatial omics technologies, such as Xenium, MERSCOPE, CosMX in spatial-transcriptomics, and MACSima and PhenoCycler in multiplex imaging, hinders the generality of existing tools. We introduce Sopa (https://github.com/gustaveroussy/sopa), a technology-invariant, memory-efficient pipeline with a unified visualizer for all image-based spatial omics. Built upon the universal SpatialData framework, Sopa optimizes tasks like segmentation, transcript/channel aggregation, annotation, and geometric/spatial analysis. Its output includes user-friendly web reports and visualizer files, as well as comprehensive data files for in-depth analysis. Overall, Sopa represents a significant step toward unifying spatial data analysis, enabling a more comprehensive understanding of cellular interactions and tissue organization in biological systems.
Optimizing the design of spatial genomic studies
Authors: Jones Andrew , Cai Diana , Li Didong , Engelhardt Barbara E.
Published: June 2024

Spatial genomic technologies characterize the relationship between the structural organization of cells and their cellular state. Despite the availability of various spatial transcriptomic and proteomic profiling platforms, these experiments remain costly and labor-intensive. Traditionally, tissue slicing for spatial sequencing involves parallel axis-aligned sections, often yielding redundant or correlated information. We propose structured batch experimental design, a method that improves the cost efficiency of spatial genomics experiments by profiling tissue slices that are maximally informative, while recognizing the destructive nature of the process. Applied to two spatial genomics studies—one to construct a spatially-resolved genomic atlas of a tissue and another to localize a region of interest in a tissue, such as a tumor—our approach collects more informative samples using fewer slices compared to traditional slicing strategies. This methodology offers a foundation for developing robust and cost-efficient design strategies, allowing spatial genomics studies to be deployed by smaller, resource-constrained labs.
Strength dependency of frequency–magnitude distribution in earthquakes and implications for stress state criticality
Authors: Matsumoto Satoshi , Iio Yoshihisa , Sakai Shinichi , Kato Aitaro
Published: June 2024

Earthquake size distribution is characterized by the “b-value” of the power law decay, which exhibits spatiotemporal variations. These variations are sometimes evident before a large earthquake. Understanding spatiotemporal variations is key to developing a model for large-earthquake generation. Previous studies have shown that changes in the b-value are caused by the tectonic stress regime. Furthermore, lab experiments have demonstrated the b-value dependency of acoustic emissions on the criticality of the failure condition. However, the factors controlling the b-values during natural seismic activity are unclear. In this study, changes in the b-value in small earthquake sequences are investigated, focusing on failure criticality. Based on our high-precision focal mechanism dataset, we conclude that the b-value decreases as it nears a critical failure condition, providing a physical explanation for the reduction in b-value before a major earthquake. Our findings elucidate fault failure models, facilitating improvement in earthquake alerts and disaster mitigation.
An antiferromagnetic spin phase change memory
Authors: Yan Han , Mao Hongye , Qin Peixin , Wang Jinhua , Liang Haidong , Zhou Xiaorong , Wang Xiaoning , Chen Hongyu , Meng Ziang , Liu Li , Zhao Guojian , Duan Zhiyuan , Zhu Zengwei , Fang Bin , Zeng Zhongming , Bettiol Andrew A. , Zhang Qinghua , Tang Peizhe , Jiang Chengbao , Liu Zhiqi
Published: June 2024

The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.
An optical study on the enhanced light trapping performance of the perovskite solar cell using nanocone structure
Authors: Gu Xiaowei , Li Zeyu , E Rusli , Xu Xiaoxiao , Tao Zhi , Pan Jiangyong , Yu Xuechao , Yu Linwei , Mokkapati Sudha
Published: June 2024

Photon management strategies are crucial to improve the efficiency of perovskite thin film (PTF) solar cell. In this work, a nano-cone (NC) based 2D photonic nanostructure is designed and simulated aiming at achieve superior light trapping performance by introducing strong light scattering and interferences within perovskite active layer. Compared to the planar PTF solar cell, the NC nanostructured device with 45 degrees half apex angle obtains highest short-circuit current density, which improved over 20% from 15.00 mA/cm2 to 18.09 mA/cm2. This work offers an alternative design towards effective light trapping performance using 2D photonic nanostructure for PTF solar cell and could potentially be adopted as the nano-structuring strategy for the future perovskite solar cell industry.
Machine learning based urban sprawl assessment using integrated multi-hazard and environmental-economic impact
Authors: Sakti Anjar Dimara , Deliar Albertus , Hafidzah Dyah Rezqy , Chintia Adria Viola , Anggraini Tania Septi , Ihsan Kalingga Titon Nur , Virtriana Riantini , Suwardhi Deni , Harto Agung Budi , Nurmaulia Sella Lestari , Aritenang Adiwan Fahlan , Riqqi Akhmad , Hernandi Andri , Soeksmantono Budhy , Wikantika Ketut
Published: June 2024

The increasing demand for land development due to human activities has fueled urbanization. However, uncontrolled urban development in some regions has resulted in urban environmental problems arising from an imbalance between supply and demand. This study aims to develop an integrated model for evaluating and prioritizing the management of hazardous urban sprawl in the Bandung metropolitan region of Indonesia. The novelty of this study lies in its pioneering application of long-term remote sensing data-based and machine learning techniques to formulate an urban sprawl priority index. This index is unique in its consideration of the impacts stemming from human economic activity, environmental degradation, and multi-disaster levels as integral components. The analysis of hazardous urban sprawl across three distinct time periods (1985–1993, 1993–2008, and 2008–2018) revealed that the 1993–2008 period had the highest increase in human economic activity, reaching 172,776 ha. The 1985–1993 period experienced the highest level of environmental degradation in the study area. Meanwhile, the 1993–2008 period showed the highest concentration of multi-hazard locations. The combined model of hazardous urban sprawl, incorporating the three parameters, indicated that the highest priority for intervention was on the outskirts of urban areas, specifically in West Bandung Regency, Cimahi, Bandung Regency, and East Bandung Regency. Regions with high-priority indices require greater attention from the government to mitigate the negative impacts of hazardous urban sprawl. This model, driven by the urban sprawl priority index, is envisioned to regulate urban movement in a more sustainable manner. Through the efficient monitoring of urban environments, the study seeks to guarantee the preservation of valuable natural resources while promoting sustainable urban development practices.
Intersubject correlations in reward and mentalizing brain circuits separately predict persuasiveness of two types of ISIS video propaganda
Authors: Cohen Michael S. , Leong Yuan Chang , Ruby Keven , Pape Robert A. , Decety Jean
Published: June 2024

The Islamist group ISIS has been particularly successful at recruiting Westerners as terrorists. A hypothesized explanation is their simultaneous use of two types of propaganda: Heroic narratives, emphasizing individual glory, alongside Social narratives, which emphasize oppression against Islamic communities. In the current study, functional MRI was used to measure brain responses to short ISIS propaganda videos distributed online. Participants were shown 4 Heroic and 4 Social videos categorized as such by another independent group of subjects. Persuasiveness was measured using post-scan predictions of recruitment effectiveness. Inter-subject correlation (ISC) was used to measure commonality of brain activity time courses across individuals. ISCs in ventral striatum predicted rated persuasiveness for Heroic videos, while ISCs in mentalizing and default networks, especially in dmPFC, predicted rated persuasiveness for Social videos. This work builds on past findings that engagement of the reward circuit and of mentalizing brain regions predicts preferences and persuasion. The observed dissociation as a function of stimulus type is novel, as is the finding that intersubject synchrony in ventral striatum predicts rated persuasiveness. These exploratory results identify possible neural mechanisms by which political extremists successfully recruit prospective members and specifically support the hypothesized distinction between Heroic and Social narratives for ISIS propaganda.