bluuebunny/crossref_metadata_2025 huggingface dataset:
Edema description in pediatric critical care: terms, patterns, and clinical characteristics
Authors: Gaetani Melany , See Emily , Satkumaran Saravanan , Gelbart Ben
Published: August 2023

Background

No validated methods are currently available to objectively quantify edema in critical illness. Therefore, the frequency, timing of onset, and association between edema and outcomes are unknown. Since clinicians document the presence of edema based on physical examination in the medical record, natural language processing techniques could be used to better understand its epidemiology. The objectives of this study were to describe the patterns of edema documentation by clinicians and to compare clinical characteristics and outcomes of children with and without edema.

Methods

An observational cohort study was conducted in a quaternary, university-affiliated pediatric intensive care unit (ICU). Eligible patients were aged 0–18 years and admitted to ICU for a minimum of 12 h.

Results

A total of 7884 patient admissions were studied, and a cumulative total of 211,122 notes were evaluated. Approximately, 40% of patient admissions had documented edema, of which 49% occurred before day 2 of ICU stay. The most commonly documented term across all provider types was “edema”. In multivariable regression analysis, patients who were mechanically ventilated and those with NIV, ECMO support, RRT, and vasoactive support had an increased odds of edema documentation throughout ICU stay. There was also an adjusted increased odds of death of (aOR 1.6, 95% CI of 1.1–2.2) in those with edema documented.

Conclusions

Edema is documented frequently and early in ICU stay. Children with edema documented were younger, required more invasive therapies, and, in addition to greater duration of intensive care stay, had higher mortality rates.
Errors and fallibility in radiology: X-ray readings and expert radiologists, 1947–1960
Authors: Lysen Flora
Published: August 2023

This article traces the historical emergence of a new understanding of radiologists as fallible expert observers from the late 1940s, a conception that was shaped by new technologies and techniques, but also prepared the ground for promises of automation and artificial intelligence in the field of medical imaging. Reports of radiologists’ unreliable performance prompted investigations in many countries into ‘observer variability’ and ‘observer error’. Towards the end of the 1950s, scientists could conceive of radiologists as imperfect medical decision makers, while they concurrently developed a new model for ‘logical analysis’ of the diagnostic process that would limit errors. As well as technological solutions to flawed X-ray readers, researchers proposed ‘double-reading’ practices (a second independent reading) as a way to mitigate the ‘human factor’. Yet these ideas did not find widespread resonance due to concerns about feasibility and debates about radiological expertise, and also because of a discrepancy between experimental models and real-world practices. A genealogy of the fallible trained observer helps us understand persistent worries about – and solutions to – radiologists’ ‘error problem’ and contributes to a better understanding of current discourses on AI in medical imaging.
The effect of the spatial variation of the evaporative flux on the deposition from a thin sessile droplet
Authors: D'Ambrosio Hannah-May , Wilson Stephen K. , Wray Alexander W. , Duffy Brian R.
Published: August 2023

A mathematical model for the effect of the spatial variation of the local evaporative flux on the evaporation of and deposition from a thin pinned particle-laden sessile droplet is formulated and solved. We then analyse the behaviour for a one-parameter family of local evaporative fluxes with the free parameter

$n \, (>-1)$

that exhibits qualitatively different behaviours mimicking those that can be obtained by, for example, surrounding the droplet with a bath of fluid or using a mask with one or more holes in it to achieve a desired pattern of evaporation enhancement and/or suppression. We show that when

$-1< n<1$

(including the special cases

$n=-1/2$

of diffusion-limited evaporation into an unbounded atmosphere and

$n=0$

of spatially uniform evaporation), all of the particles are eventually advected to the contact line, and so the final deposit is a ring deposit at the contact line, whereas when

$n>1$

all of the particles are eventually advected to the centre of the droplet, and so the final deposit is at the centre of the droplet. In particular, the present work demonstrates that a singular (or even a non-zero) evaporative flux at the contact line is not an essential requirement for the formation of a ring deposit. In addition, we calculate the paths of the particles when diffusion is slower than both axial and radial advection, and show that in this regime all of the particles are captured by the descending free surface before eventually being deposited onto the substrate.
A Romancastellumat Chott Chergui (Algeria)
Authors: Djeradi Mustapha Ameur
Published: August 2023

Roman remains were discovered by chance at Saf-Saf Lakhdara in the Chott Chergui (Algeria). This article attempts to demonstrate that these ruins are part of a Roman fortification in the south of Caesarian Mauretania, far from the Severanlimes, the course of which has been confirmed by numerous archaeologists. A historical-comparative study has been carried out to confirm that the ruins of Saf-Saf Lakhdar are those of acastellum. The corpus of graphic and photographic records and the ‘Khnag ‘Azzir’ inscription, combined with theoretical sources on Roman defensive architecture, confirmed that the fortifications at Saf-Saf Lakhdar were part of acastellum. The ‘Khnag ‘Azzir’ inscription revealed three main facts: it is dedicated to deities to commemorate the victory over the Berber tribes of the Saharan Atlas; it mentions Caius Octavius Pudens, who was procurator during the reign of the emperor Septimius Severus; and it mentions the conflicts between Rome and the Bavarians, a tribe from the ancient Maghreb. We urgently need to protect the site and carry out excavations in the hope of finding pottery or other objects that could shed light on and support this discovery.
Rumination in bipolar disorder associated with brain network and behavioural measures of inhibitory executive control
Authors: Chou Tina , Dougherty Darin D. , Nierenberg Andrew A. , Ghaznavi Sharmin
Published: August 2023

Objective:

Rumination is a passive form of negative self-focused cognition that predicts depressive episodes for individuals with bipolar disorder (BD). Individuals with BD also have impaired inhibitory executive control; rumination in BD may therefore reflect executive dysfunction. We investigated the relationship between a neural measure of executive functioning (functional connectivity between the frontoparietal control network [FPCN] and the default mode network [DMN] during an effortful task), behavioural measures of executive functioning (the Behavior Rating Inventory of Executive Function) and rumination (the Ruminative Responses Scale).

Methods:

Fifteen individuals with BD and fifteen healthy controls underwent MRI scans during mental distraction. Using CONN toolbox, between-network FPCN-DMN connectivity values were calculated. We conducted Pearson’s r bivariate correlations between connectivity values, BRIEF and RRS scores.

Results:

RRS scores were positively correlated with BRIEF Behavioral Regulation Index (BRI) scores. In individuals with BD, there was a positive correlation between FPCN-DMN functional connectivity during distraction and BRIEF BRI scores. FPCN-DMN functional connectivity was also positively correlated with RRS ruminative brooding scores. Healthy controls did not show significant correlations between these behavioural and neural measures of executive functioning and rumination.

Conclusion:

For individuals with BD, the greater the tendency to ruminate and the higher the executive dysfunction, the stronger the connectivity between an executive control network and a network involved in rumination during an unrelated cognitive task. This could reflect continual attempts to inhibit ruminative thinking and shift back to the distraction task. Therefore, engagement in rumination may reflect failed inhibitory executive control.
Pressure anisotropy and viscous heating in weakly collisional plasma turbulence
Authors: Squire J. , Kunz M.W. , Arzamasskiy L. , Johnston Z. , Quataert E. , Schekochihin A.A.
Published: August 2023

Pressure anisotropy can strongly influence the dynamics of weakly collisional, high-beta plasmas, but its effects are missed by standard magnetohydrodynamics (MHD). Small changes to the magnetic-field strength generate large pressure-anisotropy forces, heating the plasma, driving instabilities and rearranging flows, even on scales far above the particles’ gyroscales where kinetic effects are traditionally considered most important. Here, we study the influence of pressure anisotropy on turbulent plasmas threaded by a mean magnetic field (Alfvénic turbulence). Extending previous results that were concerned with Braginskii MHD, we consider a wide range of regimes and parameters using a simplified fluid model based on drift kinetics with heat fluxes calculated using a Landau-fluid closure. We show that viscous (pressure-anisotropy) heating dissipates between a quarter (in collisionless regimes) and half (in collisional regimes) of the turbulent-cascade power injected at large scales; this does not depend strongly on either plasma beta or the ion-to-electron temperature ratio. This will in turn influence the plasma's thermodynamics by regulating energy partition between different dissipation channels (e.g. electron and ion heat). Due to the pressure anisotropy's rapid dynamic feedback onto the flows that create it – an effect we term ‘magneto-immutability’ – the viscous heating is confined to a narrow range of scales near the forcing scale, supporting a nearly conservative, MHD-like inertial-range cascade, via which the rest of the energy is transferred to small scales. Despite the simplified model, our results – including the viscous heating rate, distributions and turbulent spectra – compare favourably with recent hybrid-kinetic simulations. This is promising for the more general use of extended-fluid (or even MHD) approaches to model weakly collisional plasmas such as the intracluster medium, hot accretion flows and the solar wind.
Understanding the disease and economic impact of avirulent avian paramyxovirus type 1 (APMV-1) infection in Great Britain
Authors: Reid Scott M. , Skinner Paul , Sutton David , Ross Craig S. , Drewek Karolina , Weremczuk Natalia , Banyard Ashley C. , Mahmood Sahar , Mansfield Karen L , Mayers Jo , Thomas Saumya S. , Brookes Sharon M. , Brown Ian H.
Published: August 2023

Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the ‘testing to exclude’ scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.
Dosimetric case study of 3-D FiF vs. VMAT techniques in the treatment of H/N tumour
Authors: Xie Zhaohui
Published: August 2023

A case study comparing three-dimensional conformal radiation therapy with field-in-field (FiF) technique and volumetric-modulated arc therapy (VMAT) for head/neck (H/N) irradiation, evaluating the differences in the treatment techniques and low doses to critical structures. Compared to VMAT plan, 3D FIF plan offers similar planning target volume coverage and acceptable organs at risk dose. Therefore, 3D FIF is still a feasible alternative for some centres unqualified for IMRT/VMAT worldwide.
Obstacles and Limitations in the Use of Protocols Responding Intimate Partner Violence Against Women from the Health System in Spain
Authors: Badenes-Sastre Marta , Lorente Acosta Miguel , Beltrán-Morillas Ana M. , Expósito Francisca
Published: August 2023

Intimate partner violence against women (IPVAW) is a public health problem that affects women worldwide. Consequently, victims frequently go to healthcare centers, usually with a cover reason. To address this problem, national and autonomic protocols to respond to IPVAW in health systems have been developed in Spain. In this regard, the role of primary care physicians (PCPs) will be essential for addressing IPVAW, but they could encounter obstacles in doing so. The purpose of this study was to explore how IPVAW is addressed in healthcare centers in Spain. This study synthesized the information available in the protocols to address IPVAW among health care workers in Spain and analyzed it according to World Health Organization (WHO) guidelines. Additionally, PCPs’ perspectives on these protocols and the nature of IPVAW attention from healthcare centers were explored through a focus group. The findings displayed that, although the protocols mostly conform to WHO guidelines, they are insufficient to address IPVAW. Generally, PCPs were unaware of the existence of the protocols and referred to the lack of training in IPVAW and protocol use as one of the main obstacles to intervening, along with a lack of time and feelings as well as cultural, educational, and political factors. The adoption of measures to ensure that PCPs apply these protocols correctly and to approach PCPs’ obstacles for addressing IPVAW in consultations will be crucial for the care of victims.
Multi‐Band Periodic Poleward‐Moving Auroral Arcs at the Postdawn Sector: A Case Study
Authors: Yin Ze‐Fan , Zhou Xu‐Zhi , Hu Ze‐Jun , Zong Qiu‐Gang , Liu Jian‐Jun , Yue Chao , Wang Shan , Zhao Xing‐Xin , Yang Hui‐Gen , Li Bin
Published: August 2023

Poleward‐moving auroral arcs (PMAAs) with recurrence periods on the order of minutes have been established as a distinct form of auroral activities. Their origin and characteristics, especially those on the dayside, are less understood due to the paucity of observations. Here, we investigate a periodic PMAA event at the postdawn sector based on optical measurements from the high‐latitude Yellow River Station and magnetic measurements from multiple ground‐based stations. The optical observations demonstrate a long duration (∼2.5 hr) of the periodic auroral arcs at not only the well‐established red‐line but also the green‐ and the blue‐lines. This multi‐band feature, together with images at far‐ultraviolet wavelengths, demonstrates a wide energy range of precipitating electrons from hundreds of eV to several keV, with a characteristic energy of ∼2 keV. The auroral luminosity variations at different wavebands show a consistent periodicity within 1.67–3 mHz, which is also shown in the ground‐based magnetic pulsations. The auroral arc and magnetic field observations display signatures of field line resonance, which are likely driven by perturbations at the magnetopause boundary layer. These results complement our knowledge of the dayside periodic PMAAs and improve our understanding of their relationship with ultra‐low frequency waves.
Are Upwelling Systems an Underestimated Source of Long Chain Omega‐3 in the Ocean? The Case of the Southern Benguela Upwelling System
Authors: Puccinelli Eleonora , Fawcett Sarah E. , Flynn Raquel F. , Burger Jessica M. , Delebecq Gaspard , Duquesne Nolwenn , Lambert Christophe , Little Hazel , Pecquerie Laure , Sardenne Fany , Wallschuss Sina , Soudant Philippe
Published: August 2023

The Benguela upwelling system (BUS) is one of the world's most productive ecosystems, supporting globally relevant fisheries. The BUS marine community is modulated by the availability of nutrients and omega‐3 long chain polyunsaturated fatty acid (hereafter, LC omega‐3). Phytoplankton growth in the BUS can be supported by upwelled nitrate, a new nitrogen (N) source to the surface, or by recycled N such as ammonium. Preferential assimilation of one N source over another may yield differences in LC omega‐3 production between high and low food‐quality species. To evaluate how upwelling and the N source(s) consumed by phytoplankton influence LC omega‐3 production, we sampled a BUS anchor station daily for 10 days. Upwelling on days 5–7 supplied high concentrations of nutrients to the surface, while pre‐ and post‐upwelling, surface waters were stratified and nutrient concentrations were low. LC omega‐3 and phytoplankton concentrations were near‐zero during upwelling, and elevated pre‐ and post‐upwelling. Throughout our sampling, nanoplankton (2.7–10 µm) dominated primary production (30–95%), relying mainly on nitrate to support their growth. Surface LC omega‐3 concentrations reached peaks of 215 and 175 µg L−1 pre‐ and post‐upwelling, up to 10 times higher than previous measurements from the BUS (<5 µg L−1). Pre‐upwelling, non‐diatom trophic markers (18:1n − 9, 18:4n − 3, 18:5n − 3) were dominant, with a switch over just two days to diatom trophic markers post‐upwelling (16:1n − 7, 16:2n − 4, 16:2n − 7, 16:3n − 4, 16:4n − 1). This study reveals the key role of upwelling in promoting phytoplankton LC omega‐3 production, which is tightly coupled to the supply of new nitrate. Additionally, the high observed LC omega‐3 concentrations suggest that global LC omega‐3 production is underestimated.
PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway
Authors: Cheng Ming , Cao Hongyi , Yao Peifeng , Guan Jingqian , Wu Peihong , Ji Hairu , Jiang Siyu , Yuan Yinan , Fu Lin , Zheng Qianqian , Li Qingchang
Published: August 2023

At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan–Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2’-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.
Identifying and preventing degradation in flavin mononucleotide-based redox flow batteries via NMR and EPR spectroscopy
Authors: Hey Dominic , Jethwa Rajesh B. , Farag Nadia L. , Rinkel Bernardine L. D. , Zhao Evan Wenbo , Grey Clare P.
Published: August 2023

While aqueous organic redox flow batteries (RFBs) represent potential solutions to large-scale grid storage, their electrolytes suffer from short lifetimes due to rapid degradation. We show how an understanding of these degradation processes can be used to dramatically improve performance, as illustrated here via a detailed study of the redox-active biomolecule, flavin mononucleotide (FMN), a molecule readily derived from vitamin B2. Via in-situ nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) we identify FMN hydrolysis products and show that these give rise to the additional plateau seen during charging of an FMN-cyanoferrate battery. The redox reactions of the hydrolysis product are not reversible, but we demonstrate that capacity is still retained even after substantial hydrolysis, albeit with reduced voltaic efficiency, FMN acting as a redox mediator. Critically, we demonstrate that degradation is mitigated and battery efficiency is substantially improved by lowering the pH to 11. Furthermore, the addition of cheap electrolyte salts to tune the pH results in a dramatic increase in solubility (above 1 M), this systematic improvement of the flavin-based system bringing RFBs one step closer to commercial viability.
Material symmetry recognition and property prediction accomplished by crystal capsule representation
Authors: Liang Chao , Rouzhahong Yilimiranmu , Ye Caiyuan , Li Chong , Wang Biao , Li Huashan
Published: August 2023

Learning the global crystal symmetry and interpreting the equivariant information is crucial for accurately predicting material properties, yet remains to be fully accomplished by existing algorithms based on convolution networks. To overcome this challenge, here we develop a machine learning (ML) model, named symmetry-enhanced equivariance network (SEN), to build material representation with joint structure-chemical patterns, to encode important clusters embedded in the crystal structure, and to learn pattern equivariance in different scales via capsule transformers. Quantitative analyses of the intermediate matrices demonstrate that the intrinsic crystal symmetries and interactions between clusters have been exactly perceived by the SEN model and critically affect the prediction performances by reducing effective feature space. The mean absolute errors (MAEs) of 0.181 eV and 0.0161 eV/atom are obtained for predicting bandgap and formation energy in the MatBench dataset. The general and interpretable SEN model reveals the potential to design ML models by implicitly encoding feature relationship based on physical mechanisms.
Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans
Authors: Possik Elite , Klein Laura-Lee , Sanjab Perla , Zhu Ruyuan , Côté Laurence , Bai Ying , Zhang Dongwei , Sun Howard , Al-Mass Anfal , Oppong Abel , Ahmad Rasheed , Parker Alex , Madiraju S.R. Murthy , Al-Mulla Fahd , Prentki Marc
Published: August 2023

Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients.
Electron counting detectors in scanning transmission electron microscopy via hardware signal processing
Authors: Peters Jonathan J. P. , Mullarkey Tiarnan , Hedley Emma , Müller Karin H. , Porter Alexandra , Mostaed Ali , Jones Lewys
Published: August 2023

Transmission electron microscopy is a pivotal instrument in materials and biological sciences due to its ability to provide local structural and spectroscopic information on a wide range of materials. However, the electron detectors used in scanning transmission electron microscopy are often unable to provide quantified information, that is the number of electrons impacting the detector, without exhaustive calibration and processing. This results in arbitrary signal values with slow response times that cannot be used for quantification or comparison to simulations. Here we demonstrate and optimise a hardware signal processing approach to augment electron detectors to perform single electron counting.
Impact of inherent energy barrier on spin-orbit torques in magnetic-metal/semimetal heterojunctions
Authors: Gao Tenghua , Qaiumzadeh Alireza , Troncoso Roberto E. , Haku Satoshi , An Hongyu , Nakayama Hiroki , Tazaki Yuya , Zhang Song , Tu Rong , Asami Akio , Brataas Arne , Ando Kazuya
Published: August 2023

Spintronic devices are based on heterojunctions of two materials with different magnetic and electronic properties. Although an energy barrier is naturally formed even at the interface of metallic heterojunctions, its impact on spin transport has been overlooked. Here, using diffusive spin Hall currents, we provide evidence that the inherent energy barrier governs the spin transport even in metallic systems. We find a sizable field-like torque, much larger than the damping-like counterpart, in Ni81Fe19/Bi0.1Sb0.9 bilayers. This is a distinct signature of barrier-mediated spin-orbit torques, which is consistent with our theory that predicts a strong modification of the spin mixing conductance induced by the energy barrier. Our results suggest that the spin mixing conductance and the corresponding spin-orbit torques are strongly altered by minimizing the work function difference in the heterostructure. These findings provide a new mechanism to control spin transport and spin torque phenomena by interfacial engineering of metallic heterostructures.
Weakened AMOC related to cooling and atmospheric circulation shifts in the last interglacial Eastern Mediterranean
Authors: Levy Elan J. , Vonhof Hubert B. , Bar-Matthews Miryam , Martínez-García Alfredo , Ayalon Avner , Matthews Alan , Silverman Vered , Raveh-Rubin Shira , Zilberman Tami , Yasur Gal , Schmitt Mareike , Haug Gerald H.
Published: August 2023

There is limited understanding of temperature and atmospheric circulation changes that accompany an Atlantic Meridional Overturning Circulation (AMOC) slowdown beyond the North Atlantic realm. A Peqi’in Cave (Israel) speleothem dated to the last interglacial period (LIG), 129–116 thousand years ago (ka), together with a large modern rainfall monitoring dataset, serve as the base for investigating past AMOC slowdown effects on the Eastern Mediterranean. Here, we reconstruct LIG temperatures and rainfall source using organic proxies (TEX86) and fluid inclusion waterd-excess. The TEX86data show a stepwise cooling from 19.8 ± 0.2° (ca. 128–126 ka) to 16.5 ± 0.6 °C (ca. 124–123 ka), whiled-excessvalues decrease abruptly (ca. 126 ka). Thed-excessshift suggests that rainfall was derived from more zonal Mediterranean air flow during the weakened AMOC interval. Decreasing rainfalld-excesstrends over the last 25 years raise the question whether similar atmospheric circulation changes are also occurring today.
Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice
Authors: Lee Jiyeon , Dimitry Julie M. , Song Jong Hee , Son Minsoo , Sheehan Patrick W. , King Melvin W. , Travis Tabor G. , Goo Young Ah , Lazar Mitchell A. , Petrucelli Leonard , Musiek Erik S.
Published: August 2023

Alzheimer’s disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a core circadian clock protein which also serves as a nuclear receptor and transcriptional repressor involved in lipid metabolism and macrophage function. Global REV-ERBα deletion has been shown to promote microglial activation and mitigate amyloid plaque formation. However, the cell-autonomous effects of microglial REV-ERBα in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deletion enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male microglia. These events impair microglial tau phagocytosis, which can be partially rescued by blockage of LD formation. In vivo, microglial REV-ERBα deletion exacerbates tau aggregation and neuroinflammation in two mouse tauopathy models, specifically in male mice. These data demonstrate the importance of microglial lipid droplets in tau accumulation and reveal REV-ERBα as a therapeutically accessible, sex-dependent regulator of microglial inflammatory signaling, lipid metabolism, and tauopathy.
Propensity of selecting mutant parasites for the antimalarial drug cabamiquine
Authors: Stadler Eva , Maiga Mohamed , Friedrich Lukas , Thathy Vandana , Demarta-Gatsi Claudia , Dara Antoine , Sogore Fanta , Striepen Josefine , Oeuvray Claude , Djimdé Abdoulaye A. , Lee Marcus C. S. , Dembélé Laurent , Fidock David A. , Khoury David S. , Spangenberg Thomas
Published: August 2023

We report an analysis of the propensity of the antimalarial agent cabamiquine, a Plasmodium-specific eukaryotic elongation factor 2 inhibitor, to select for resistant Plasmodium falciparum parasites. Through in vitro studies of laboratory strains and clinical isolates, a humanized mouse model, and volunteer infection studies, we identified resistance-associated mutations at 11 amino acid positions. Of these, six (55%) were present in more than one infection model, indicating translatability across models. Mathematical modelling suggested that resistant mutants were likely pre-existent at the time of drug exposure across studies. Here, we estimated a wide range of frequencies of resistant mutants across the different infection models, much of which can be attributed to stochastic differences resulting from experimental design choices. Structural modelling implicates binding of cabamiquine to a shallow mRNA binding site adjacent to two of the most frequently identified resistance mutations.
MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia
Authors: Crump Nicholas T. , Smith Alastair L. , Godfrey Laura , Dopico-Fernandez Ana M. , Denny Nicholas , Harman Joe R. , Hamley Joseph C. , Jackson Nicole E. , Chahrour Catherine , Riva Simone , Rice Siobhan , Kim Jaehoon , Basrur Venkatesha , Fermin Damian , Elenitoba-Johnson Kojo , Roeder Robert G. , Allis C. David , Roberts Irene , Roy Anindita , Geng Huimin , Davies James O. J. , Milne Thomas A.
Published: August 2023

Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.
Persistent dynamic magnetic state in artificial honeycomb spin ice
Authors: Guo J. , Ghosh P. , Hill D. , Chen Y. , Stingaciu L. , Zolnierczuk P. , Ullrich C. A. , Singh D. K.
Published: August 2023

Topological magnetic charges, arising due to the non-vanishing magnetic flux on spin ice vertices, serve as the origin of magnetic monopoles that traverse the underlying lattice effortlessly. Unlike spin ice materials of atomic origin, the dynamic state in artificial honeycomb spin ice is conventionally described in terms of finite size domain wall kinetics that require magnetic field or current application. Contrary to this common understanding, here we show that a thermally tunable artificial permalloy honeycomb lattice exhibits a perpetual dynamic state due to self-propelled magnetic charge defect relaxation in the absence of any external tuning agent. Quantitative investigation of magnetic charge defect dynamics using neutron spin echo spectroscopy reveals sub-ns relaxation times that are comparable to the relaxation of monopoles in bulk spin ices. Most importantly, the kinetic process remains unabated at low temperature where thermal fluctuation is negligible. This suggests that dynamic phenomena in honeycomb spin ice are mediated by quasi-particle type entities, also confirmed by dynamic Monte-Carlo simulations that replicate the kinetic behavior. Our research unveils a macroscopic magnetic particle that shares many known traits of quantum particles, namely magnetic monopole and magnon.
Occipital transcranial direct current stimulation in episodic migraine patients: effect on cerebral perfusion
Authors: Pohl Heiko , Sandor Peter S. , Moisa Marius , Ruff Christian C. , Schoenen Jean , Luechinger Roger , O’Gorman Ruth , Riederer Franz , Gantenbein Andreas R. , Michels Lars
Published: August 2023

Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.

Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017).
Upcycling polyethylene terephthalate wastes for enhancing the performance of polyester from rice straw polyol in HDPE-composites
Authors: Shafik Emad S. , Lotfy Vivian F. , Basta Altaf H.
Published: August 2023

Upscaling the utilization of polymer wastes together with the valorization of undesirable waste rice straw (RS) will minimize the environmental impact of waste disposal by traditional tools. This present work assesses the utilization of polyethylene terephthalate wastes in enhancing the production of polyester-(high density polyethylene) HDPE from Rice straw polyol composites. In this respect, the polyester from rice straw polyol in hybrid with glycolysis polyethylene terephthalate wastes (Gly-WPET) was assessed in comparison with that resulted from RS-polyol, using FTIR, non-isothermal analysis, and mechanical tests. The data showed the positive role of Gly-WPET in hybrid with RS-polyol in production polyester with high thermal stability and mechanical properties. It provided an increase in activation energy of degradation, elongation, Young's Modulus, and modulus of toughness from 184.5 to 1201 kJ/mole, from 4.7 to 9.8%, from 47.5 to 66.5 MPa, and from ~ 4.0 to 23 J/m3, respectively. This behavior was reflected in the properties of HDPE-polyester polyol (PEPO) composites, especially in improving elongation (from 55.4 to 72%). These promising data persuade us to recommend the influential role of Gly-WPET in using PEPO from liquefied RS as a plasticizer.
Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans
Authors: Martinez Francisco J. , Guillotte-Blisnick Micheline , Huon Christèle , England Patrick , Popovici Jean , Laude Hélène , Arowas Laurence , Ungeheuer Marie-Noëlle , Reimer Jenny M. , Carter Darrick , Reed Steve , Mukherjee Paushali , Chauhan Virander S. , Chitnis Chetan E.
Published: August 2023

The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate. Here, we have evaluated the immunogenicity of recombinant PvDBPII formulated with the adjuvants Matrix-M and GLA-SE in mice. Analysis of the antibody responses revealed comparable ELISA recognition titres as well as similar recognition of native PvDBP in P. vivax schizonts by immunofluorescence assay. Moreover, antibodies elicited by the two adjuvant formulations had similar functional properties such as avidity, isotype profile and inhibition of PvDBPII-DARC binding. Furthermore, the anti-PvDBPII antibodies were able to block the interaction of DARC with the homologous PvDBPII SalI allele as well as the heterologous PvDBPII PvW1 allele from a Thai clinical isolate that is used for controlled human malaria infections (CHMI). The cross-reactivity of these antibodies with PvW1 suggest that immunization with the PvDBPII SalI strain should neutralize reticulocyte invasion by the challenge P. vivax strain PvW1.
Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments
Authors: Findlay-Wilson Stephen , Easterbrook Linda , Smith Sandra , Pope Neville , Aldridge Matthew , Humphries Gareth , Schuhmann Holger , Ngabo Didier , Rayner Emma , Otter Ashley , Coleman Thomas , Hicks Bethany , Halkerston Rachel , Apostolakis Kostis , Taylor Stephen , Fotheringham Susan , Horton Amanda , CanoCejas Irene , Wand Matthew , Tree Julia A. , Sutton Mark , Graham Victoria , Hewson Roger , Dowall Stuart
Published: August 2023

The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab′)2 fragments. These preparations were evaluated for in vitro activity and demonstrated to be strongly neutralising against a range of SARS-CoV-2 strains, including Omicron B2.2. In addition, their protection against disease manifestations and viral loads were assessed using a hamster SARS-CoV-2 infection model. Results demonstrated protective effects of both IgG and F(ab′)2, with the latter requiring sequential dosing to maintain in vivo activity due to rapid clearance from the circulation.
Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats
Authors: Wang Xue , Xiong Yu , Zheng Xinxin , Zeng Liang , Chen Jinglin , Chen Lizhen , Zhong Liping , Liu Zhigang , Xu Jia , Jin Youhong
Published: August 2023

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-l-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-l-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.
Routine hypercapnic challenge after cervical spinal hemisection affects the size of phrenic motoneurons
Authors: Kawamura Kenta , Kobayashi Masaaki , Tomita Kazuhide
Published: August 2023

After an individual experiences a cervical cord injury, the cell body's adaptation to the smaller size of phrenic motoneurons occurs within several weeks. It is not known whether a routine hypercapnic load can alter this adaptation of phrenic motoneurons. We investigated this question by using rats with high cervical cord hemisection. The rats were divided into four groups: control, hypercapnia, sham, and sham hypercapnia. Within 72 h post-hemisection, the hypercapnia groups began a hypercapnic challenge (20 min/day, 4 times/week for 3 weeks) with 7% CO2 under awake conditions. After the 3-week challenge, the phrenic motoneurons in all of the rats were retrogradely labeled with horseradish peroxidase, and the motoneuron sizes in each group were compared. The average diameter, cross-sectional area, and somal surface area of stained phrenic motoneurons as analyzed by software were significantly smaller in only the control group compared to the other groups. The histogram distribution was unimodal, with larger between-group size differences for motoneurons in the horizontal plane than in the transverse plane. Our findings indicate that a routine hypercapnic challenge may increase the input to phrenic motoneurons and alter the propensity for motoneuron adaptations.
A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study
Authors: Ou Huiting , Kawaguchi Shuji , Sonomura Kazuhiro , Kawaguchi Takahisa , Kitada Seri , Yoshiji Satoshi , Brial François , Gauguier Dominique , Xia Jianguo , Matsuda Fumihiko
Published: August 2023

Gut-microbiota derived metabolites are important regulators of host biology and metabolism. To understand the impacts of the microbial metabolite 4-cresol sulfate (4-CS) on four chronic diseases [type 2 diabetes mellitus, metabolic syndrome (MetS), non-alcoholic fatty liver disease, and chronic kidney disease (CKD)], we conducted association analyses of plasma 4-CS quantified by liquid chromatography coupled to mass spectrometry (LC–MS) in 3641 participants of the Nagahama study. Our results validated the elevation of 4-CS in CKD and identified a reducing trend in MetS. To delineate the holistic effects of 4-CS, we performed a phenome-wide association analysis (PheWAS) with 937 intermediate biological and behavioral traits. We detected associations between 4-CS and 39 phenotypes related to blood pressure regulation, hepatic and renal functions, hematology, sleep quality, intraocular pressure, ion regulation, ketone and fatty acid metabolisms, disease history and dietary habits. Among them, 19 PheWAS significant traits, including fatty acids and 14 blood pressure indices, were correlated with MetS, suggesting that 4-CS is a potential biomarker for MetS. Consistent associations of this gut microbial-derived metabolite on multiple endophenotypes underlying distinct etiopathogenesis support its role in the overall host health, with prospects of probiotic-based therapeutic solutions in chronic diseases.
Natural mega disturbances drive spatial and temporal changes in diversity and genetic structure on the toadfish Aphos porosus
Authors: Vásquez Cynthia , Vera-Escalona Iván , Brante Antonio , Silva Francisco , Hernández-Miranda Eduardo
Published: August 2023

Natural disturbances can modify extinction-colonization dynamics, driving changes in the genetic diversity and structure of marine populations. Along Chilean coast (36°S, 73°W), a strong hypoxic-upwelling event in 2008, and a mega earthquake-tsunami in 2010 caused mass mortality within the Aphos porosus population, which is a vulnerable species with low dispersal potential. We evaluated the effects of these two major disturbances on the diversity and spatial-temporal genetic structure of Aphos porosus in two neighboring areas that were impacted on different levels (High level: Coliumo Bay; Low level: Itata Shelf). Thirteen microsatellites (from 2008 to 2015) amplified in individuals collected from both locations were used to evaluate the effects of the two disturbances. Results showed that after the strong hypoxic-upwelling event and the mega earthquake-tsunami, Aphos porosus populations exhibited lower genetic diversity and less effective population sizes (Ne < 20), as well as asymmetries in migration and spatial-temporal genetic structure. These findings suggest a rise in extinction-recolonization dynamics in local Aphos porosus populations after the disturbances, which led to a loss of local genetic diversity (mainly in Coliumo Bay area impacted the most), and to greater spatial-temporal genetic structure caused by drift and gene flow. Our results suggest that continuous genetic monitoring is needed in order to assess potential risks for Aphos porosus in light of new natural and anthropogenic disturbances.