bluuebunny/crossref_metadata_2025 huggingface dataset:
The Thousand-Pulsar-Array programme on MeerKAT XVII: Discovery of beating radio emission variability in PSR J1514−4834
Authors: Hsu J A , Weltevrede P , Wright G , Keith M J , Oswald L S , Song X , Wang H
Published: February 2025

We present a comprehensive analysis of the complex subpulse modulation patterns in PSR J1514−4834 (B1510−48) using L-band data from the Thousand-Pulsar-Array (TPA) programme, complemented with further MeerKAT UHF-band data. We demonstrate that periodic drifting subpulses and rapid amplitude modulation with a period of about 2 pulse periods coexist. It is established that these two periodic emission patterns interfere in the form of a beat system, giving rise to multiple spectral features. We develop a new methodology which confirms the expected correlations in the complex phase of the beat features in a 2D Fourier Transform of the data. Therefore, a relatively simple beat system can explain the complex single-pulse behaviour of this pulsar. The simultaneous coexistence of multiple subpulse modulation periodicities is rare in the population and points to poorly understood intricate dynamics within pulsar magnetospheres. A comparison with PSR B0943+10 is made, for which the coexistence of multiple periodicities has been argued to be a natural consequence of a rotating carousel. However, our observations of PSR J1514−4834 require a different explanation, involving time-delayed interactions between separate regions of the magnetosphere. The developed phase correlation methodology opens up the route for underlying beat systems in the modulation patterns of more pulsars.
Fast dynamic ejecta in neutron star mergers
Authors: Rosswog Stephan , Sarin Nikhil , Nakhar Ehud , Diener Peter
Published: February 2025

The ejection of neutron-rich matter is one of the most important consequences of a neutron star merger. While the bulk of the matter is ejected at fast, but non-relativistic velocities (∼0.2c), a small amount of mildly relativistic dynamic ejecta have been seen in a number of numerical simulations. Such ejecta can have far reaching observational consequences ranging from the shock breakout burst of gamma-rays promptly after the merger, to an early (∼1 hour post-merger) blue kilonova precursor signal, to synchrotron emission years after the merger (‘kilonova afterglow’). These all potentially carry the imprint of the binary system parameters and the equation of state. By analyzing Lagrangian simulations in full General Relativity, performed with the code SPHINCS_BSSN, we identify two ejection mechanisms for fast ejecta: i) about 30% of the ejecta with v > 0.4c are ‘sprayed out’ from the shear interface between the merging stars and escape along the orbital plane and ii) the remaining ∼ 70% of the fast ejecta result from the central object ‘bouncing back’ after strong, general-relativistic compression. This ‘bounce component’ is ejected in a rather isotropic way and reaches larger velocities (by ∼0.1c) so that its faster parts can catch up with and shock slower parts of the spray ejecta. Even for a case that promptly collapses to a black hole, we find fast ejecta with similar properties to the non-collapsing case, while slower matter parts are swallowed by the forming black hole. We discuss observational implications of these fast ejecta, including shock breakout and kilonova afterglow.
Constraints on optical and near-infrared variability in the localisation of the long-period radio transient GLEAM-X J1627–52
Authors: Lyman J D , Dhillon V S , Kamann S , Chrimes A A , Levan A J , Pelisoli I , Steeghs D T H , Wiersema K
Published: February 2025

GLEAM-X J1627–52 was discovered as a periodic (∼18 min) radio signal over a duration of three months in 2018. It is an enigmatic example of a growing population of ‘long-period radio transients’ consistent with Galactic origins. Their nature is uncertain, and leading models invoke magnetic neutron stars or white dwarfs, potentially in close binary systems, to power them. GLEAM-X J1627–52 resides in the Galactic plane with a comparatively coarse localisation (≃2 arcsecond). Here we study the localisation region to search for spectrophotometric signatures of a counterpart using time-domain searches in optical and near-infra-red imaging, and MUSE integral field spectroscopy. No sources in the localisation display clear white dwarf spectral signatures, although at the expected distance we can only provide modest limits on their presence directly. We rule out the presence of hot sub-dwarfs in the vicinity. We found no candidate within our search for variability or periodic behaviour in the light curves. Radial velocity curves additionally show only weak evidence of variation, requiring any realistic underlying system to have very low orbital inclination (i ≲ 5 deg). Two Balmer emission line sources are reminiscent of white dwarf pulsar systems, but their characteristics fall within expected M-dwarf chromospheric activity with no signs of being in a close binary. Currently the white dwarf pulsar scenario is not supported, although longer baseline data and data contemporaneous with a radio active epoch are required before stronger statements. Isolated magnetars, or compact binaries remain viable. Our limits highlight the difficulty of these searches in dense environments at the limits of ground-based data.
Early compensatory increase in single kidney estimated GFR after unilateral nephrectomy is associated with a lower long-term risk of estimated GFR decline
Authors: van der Weijden Jessica , Mazhar Faizan , Fu Edouard L , van Londen Marco , Evans Marie , Berger Stefan P , De Borst Martin H , Carrero Juan J
Published: February 2025

Background and hypothesis

A more pronounced short-term increase in single-kidney GFR (ΔskGFR) has been associated with better long-term kidney function in living kidney donors. Whether this also applies to non-donors is unknown. We evaluated if ΔskGFR is associated with long-term risk of eGFR decline in individuals undergoing unilateral nephrectomy.

Methods

This study included 1777 participants from the SCREAM cohort who underwent radical unilateral nephrectomy in Stockholm between 2006–2021. The ΔskGFR was calculated as the early (1–6 months) post-nephrectomy eGFR minus 50% of the pre-nephrectomy eGFR. Multivariable Cox regression was used to study the association between Δsk-GFR and the subsequent risk of progressive eGFR decline, defined as composite of an eGFR decline > 30% compared to the early (6 months) post-nephrectomy eGFR or kidney failure.

Results

Mean age at nephrectomy was 68 ± 11 years, 40% were female, 92% had kidney cancer, and median (IQR) pre-nephrectomy eGFR was 76 (61–89) mL/min/1.73m2. Median Δsk-GFR was 11 (7–20) mL/min/1.73m2. Pre-nephrectomy determinants of Δsk-GFR were age (inverse association) and pre-nephrectomy eGFR (positive association). During a median follow-up of 5 years (range 0.6–15 years), 178 participants developed progressive eGFR decline. Individuals with a Δsk-GFR above the median had a lower rate of progressive eGFR decline (adjusted HR: 0.58, 95% CI: 0.42–0.80), compared to those with a Δsk-GFR below the median, independent of baseline eGFR and age.

Conclusions

A stronger increase in single-kidney eGFR early after unilateral nephrectomy was associated with a lower long-term risk of progressive eGFR decline. Evaluation of Δsk-GFR could help identify patients at higher risk of progressive kidney function decline following unilateral nephrectomy.
Global access to management of primary hyperoxaluria: a survey on behalf of OxalEurope, G&K working group of the ERA, and ESPN
Authors: Deesker Lisa J , Oubram Laila , Almardini Reham , Baum Michelle A , Bonilla-Felix M , Figueres Lucile , Garrelfs Sander F , Groothoff Jaap W , Ekulu Pépé M , Müller Roman-Ulrich , Oosterveld Michiel J S , Qian Shen , Sayer John A , Soliman Neveen , Moochhala Shabbir H , Bacchetta Justine
Published: February 2025

Background and hypothesis

Primary hyperoxaluria (PH) is a rare disorder with significant morbidity and mortality if left untreated. Given the rarity, global inequities in diagnostics and treatment are expected. Recently introduced RNA interference therapeutics (RNAi) have dramatically changed the outcome for PH patients, potentially disproportionately affecting low-resource regions. Understanding these disparities is crucial for implementing measures, ensuring equitable healthcare access for PH patients worldwide. This study aims to evaluate the current global health situation for PH patients upon the introduction of targeted therapeutics.

Methods

An international cross-sectional questionnaire study was conducted among healthcare providers involved in PH care. Responses were gathered between March 2023 and April 2024 and distributed by email via various international nephrology networks. Meta-analysis (mixed random effects model with inverse-variance weighting) was used to analyze data and adjust for subgroup differences.

Results

We gathered 136 responses from 57 countries, representing all World Bank regions. Overall access to genetic analysis diagnostics was 82% (CI, 77–91%) and to urinary oxalate measurement 97% (93–100%). Significant differences (P < 0.05) between low- and high-income countries were found for most diagnostics including genetic testing, plasma oxalate, plasma and urinary glycolate. Conservative therapies (e.g. pyridoxine and alkalinizing agents) were highly available globally (98% and 95%), but significant differences in access to peritoneal dialysis, kidney- and liver transplantation were reported (P < 0.05). Access to RNA interference therapeutic lumasiran was limited to high- and middle-income countries, with 53% (40–66%) of all countries having access (78% high-income versus 56% middle-income). Even in high-income countries, RNAi was not always accessible.

Conclusions

We found global disparities in access to optimal management of PH patients, disproportionately affecting low-income countries, but even existing between high-income countries. These results may provide support for initiatives to improve the outcome of PH patients worldwide in an era of new targeted therapeutic treatments.
A volumetric analysis of timing and duration of T2/FLAIR changes on MRI following radiation therapy in patients with Low-Grade IDH-Mutant Glioma
Authors: Sutherland Isabella , Ulano Adam , Thomas Alissa A
Published: February 2025

Background

Patients with IDH-mutant low-grade glioma (LGG) can achieve many years of survival with radiation (RT) and chemotherapy. There is risk of overtreatment and negative treatment side-effects if these patients are unnecessarily retreated due to perceived tumor progression in the absence of true tumor regrowth. Better understanding of volumetric post-radiation FLAIR changes will help with clinical interpretation of disease progression/treatment effect and will help guide management decisions. We conducted this research to characterize the changes in MRI FLAIR hyperintensity that occur in LGG patients following RT, to better understand the radiation-treatment effects or “pseudoprogression” that occurs in absence of true tumor regrowth.

Methods

Serial MRI scans of patients with LGG were reviewed, including pre-RT and for 2.5 years post-RT. Segmentation for volumetric analysis was performed with manual supervision using ITK-SNAP (open-source segmentation software). Descriptive statistics are reported.

Results

Sixteen patients with histologic grade 2 gliomas were included. 159 MRI scans were segmented using ITK-SNAP (median 9.5 MRIs/patient). Nine of 16 MRIs showed decreasing FLAIR volume immediately post-RT, while 7/16 showed increasing FLAIR volume. After the initial post-RT MRI, 12/16 patients had MRIs with an increase in FLAIR volume sometime during the first year. The FLAIR volume stabilized or decreased a median of 18.4 months and mean of 15.0 months post-RT.

Conclusion

FLAIR hyperintensity changes on MRI are highly variable in the first 1.5 years post-RT in low-grade glioma, but after 1.5 years, FLAIR volumes stabilize and decrease, likely indicating the inflection point where post-RT pseudoprogression stabilizes.
Generative Artificial Intelligence: A Historical Perspective
Authors: He Ran , Cao Jie , Tan Tieniu
Published: February 2025

Generative Artificial Intelligence (GAI) has recently achieved significant success, enabling anyone to create texts, images, videos, and even computer codes while providing insights that might not be possible with traditional tools. To stimulate future research, this work provides a brief summary of the ongoing and historical developments in GAI over the past 70 years. The achievements are grouped into four categories: (i) rule-based generative systems that follow specialized rules and instructions, (ii) model-based generative algorithms that produce new content based on statistical or graphical models, (iii) deep generative methodologies that utilize deep neural networks to learn how to generate new content from data, and (iv) foundation models that are trained on extensive datasets and capable of performing a variety of generative tasks. This paper also reviews successful generative applications and identifies open challenges posed by remaining issues. In addition, this paper describes potential research directions aimed at better utilizing, understanding, and harnessing GAI technologies.
Breaking Kasha's rule for photoswitchable reactive oxygen species generation in carbonylated carbon nitride
Authors: Zhao Jun , Li Hui , Li Zhihao , Jiang Shenlong , Guan Manqin , Zhang Peng , Shang Shu , Zhao Zhi , Wang Hui , Zhang Qun , Zhang Xiaodong , Xie Yi
Published: February 2025

Photoswitchable catalysis enables the non-invasive regulation of light-to-chemical energy conversion, where catalysts with wavelength-dependent photoexcitation behaviors are typically required. However, as for semiconductors, the ultrafast hot-excited-species cooling, depicted as Kasha's rule, tends to induce the accumulation of photoinduced species on the lowest excited states, which brings about a detrimental effect on achieving photoswitchable catalysis. Herein, by taking polymeric carbon nitride as an example, we demonstrate photoswitchable molecular oxygen activation to be achieved by incorporating carbonyl groups into the matrix: in the range of 300–400 nm, hydroxyl radical and singlet oxygen are identified as the dominant reactive oxygen species under high- and low-energy excitations, respectively. Photoluminescence and ultrafast transient absorption measurements confirm the breakdown of Kasha's rule in carbonylated carbon nitride, where the obstructed relaxation of hot excited species leads to nontrivial wavelength-dependent photophysical properties. And this anti-Kasha behavior is attributed to carbonyl-induced spin–orbit coupling, where the mixing of singlet and triplet states would lead to robust leaps/relaxations between these states, which in turn affects the cooling process of hot photoinduced species. This work deepens the understanding of modulating hot-excited-species relaxation for gaining versatile semiconductor-based photocatalysis.
Atmospheric inversions for carbon dioxide and methane at national scale
Authors: Chevallier Frédéric , Broquet Grégoire
Published: February 2025

This paper outlines the current state of national-scale atmospheric inversion, at a time when not only the volume of observational data, but also institutional expectations, are increasing considerably.
Space environment adaptability of two-dimensional semiconductor materials
Authors: Yu Lingxiao , Sun Shiran , Jia Yi , Kang Feiyu , Lv Ruitao
Published: February 2025

Two-dimensional semiconductors demonstrate unprecedented stability in extreme space conditions, enabling next-generation electronics for advanced space technologies in harsh cosmic environments.
Differences in e-cigarette use behaviors and device and liquid characteristics of U.S. adults by sexual and gender identity
Authors: Crespi Elizabeth , Hardesty Jeffrey J , Nian Qinghua , Cohen Joanna E
Published: February 2025

Background

E-cigarette use behaviors and device and liquid characteristics have addiction, cessation, and health implications. E-cigarettes may exacerbate or reduce existing tobacco and nicotine product disparities by sexual and gender identity. We examine e-cigarette device and liquid characteristics and tobacco and nicotine product use by sexual and gender identity.

Methods

Data are from the VAPER study (wave 5: Feb-Apr 2023), an online cohort of U.S. adults (≥21 years) using e-cigarettes ≥5 days per week. Participants (n=1186) reported on tobacco and nicotine product use and submitted photos of their most used e-cigarette device and liquid. Rao-Scott Chi-square tests with Bonferroni corrections were used to cross-sectionally assess differences in tobacco and nicotine product use behaviors and e-cigarette device and liquid characteristics by sexual and gender identity.

Results

A greater percentage of bisexual women vs. heterosexual and gay men used disposable devices (54% vs. 31% and 19%) and nicotine concentrations ≥20 mg/mL (77% vs 59% and 34%). A higher proportion of heterosexual women than men used disposable devices (42% vs 31%). A greater percentage of bisexual (20%) than heterosexual (9%) women never smoked cigarettes (p<0.05). A higher proportion of heterosexual (9.4%) and bisexual (16.4%) men vs. heterosexual women (3%) used nicotine pouches (p<0.05).

Conclusions

E-cigarette characteristics, which have implications for addiction, health, and cessation, and tobacco and nicotine product use behaviors vary by sexual and gender identity. Targeted interventions may be needed to alleviate and prevent health disparities. Agencies must consider potential variation in regulatory impacts by sexual and gender identity.

Implications

This study of adults frequently using e-cigarettes highlights differences in e-cigarette device and liquid characteristics and tobacco and nicotine product use by sexual and gender identity. For example, a greater percentage of bisexual and heterosexual women than heterosexual men used disposable e-cigarette devices. Given the variation in how e-cigarettes and other tobacco and nicotine products are used, researchers and regulators must consider how health outcomes, cessation behaviors, and responses to interventions or regulatory actions associated with e-cigarette use may vary by sexual and gender identity.
Spontaneous bilateral basal ganglia hemorrhage: an unusual clinical scenario
Authors: Sunil Bhatta , Hemant Ojha , Sukriti Pandit
Published: February 2025

The most significant threat factor for intracerebral hemorrhage (ICH) is hypertension, which frequently results in solitary hematoma. Bilateral basal ganglia simultaneous hypertensive intracerebral hemorrhages are exceedingly rare. Few case reports of concomitant hypertensive ICH in the bilateral basal ganglia region exist in the literature. The majority of documented patients received conservative care and had dreadful prognoses. We report a case of a 43-year-old male, who presented to our emergency room with concurrent hypertensive bilateral hemorrhages within both basal ganglia. He was managed conservatively and attained a recoverable state. We would like to report this case because of the clinical rarity, paucity of published case reports, and the widespread dispute on its management.
An incidental finding of Cor Triatriatum in an adult with left ventricular dysfunction and atrial flutter
Authors: Meel Ruchika , Sothoane Keitumetsi Lucy , Variava Ebrahim
Published: February 2025

The global incidence of Cor Triatriatum ranges from 0.1% to 0.4 globally. It is a rare diagnosis, with only a few cases reported in Africa. This case report outlines the first presentation of Cor Triatriatum in a 34-year-old female previously diagnosed with post-partum cardiomyopathy. The purpose of this case report was to raise awareness about the presence of congenital heart disease in adulthood as a potential cause of heart failure. Additionally, it emphasizes the importance of detailed echocardiography using advanced imaging techniques for evaluating defects and co-existing lesions.
Prolonged extrapyramidal syndrome due to metoclopramide overdose: a rare case report
Authors: Malakian Abdollah , Omrani Alireza , Omrani Arshia , Ramzani Yasin , Zakariaei Zakaria
Published: February 2025

Metoclopramide is a useful antiemetic drug that is widely used in medical emergencies. This drug can cause extrapyramidal side effects that are worrying. An 18-year-old girl student unintentionally consumed a large dose (60 mg) of metoclopramide, exceeding the recommended therapeutic dose, for the management of nausea and vomiting. Approximately six hours after the ingestion of the medication, she developed neck dystonia and upward deviation of the eyes. Seeing these symptoms and worrying about their child’s physical condition, the parents took her to the local medical center in northern Iran. With the diagnosis of the extrapyramidal syndrome and intramuscular administration of biperiden 5 mg ampoule twice at 12-h intervals, unfortunately, the symptoms did not improve and finally he was referred to our hospital. Dystonic reactions caused by metoclopramide can be misdiagnosed and it is necessary to be monitored and treated appropriately to reduce the family’s concern about its unpleasant side effects.
A neural network study of the phase transitions of the two-dimensional antiferromagnetic q-state Potts models on the square lattice
Authors: Tseng Yuan-Heng , Jiang Fu-Jiun
Published: February 2025

The critical phenomena of the two-dimensional antiferromagnetic q-state Potts model on the square lattice with q = 2, 3, 4 are investigated using the techniques of neural networks (NN). In particular, an unconventional supervised NN which is trained using no information about the physics of the considered systems is employed. In addition, conventional unsupervised autoencoders (AECs) are used in our study as well. Remarkably, while the conventional AECs either fail or only work partially to uncover the critical phenomena of the systems associated with q = 3 and q = 4 investigated here, our unconventional supervised NN correctly identifies the critical behaviors of all the three considered antiferromagnetic q-state Potts models. The results obtained in this study suggest convincingly that the applicability of our unconventional supervised NN is broader than one anticipates. In particular, when a new system is studied with our NN, it is likely that there is not necessary to conduct any training, and one only needs to examine whether an appropriate reduced representation of the original raw configurations exists, so that the same already trained NN can be employed to explore the related phase transition efficiently.
A Monetary-Fiscal Theory of Sudden Inflations
Authors: Bassetto Marco , Miller David S
Published: February 2025

This paper posits an information channel as an explanation for sudden inflations. Households saving via nominal government bonds face a choice whether to acquire costly information about future government surpluses. They trade off the cost of acquiring information about the surpluses that back bond repayment against the benefit of a more informed saving decision. Through the information channel, small changes in the economic environment can trigger large responses in consumers’ behavior and prices. This setting explains why there can be long stretches of time during which government surpluses have large movements with little inflation response; yet, at some point, something snaps, and a sudden inflation takes off that is strongly responsive to incoming fiscal news.
A co-designed program for better sleep in Australian First Nations adolescents: Protocol for the Let’s Yarn About Sleep adolescent sleep health program
Authors: Fatima Y , Von Senden R , Bucks R S , Ashby C , Sullivan D P , Smith S S , Blunden S , Yiallourou S , Eastwood P R , Mamun A A , McDaid L , Walsh J , Kinghorn M , Potia A H , Varela S , King S , Solomon S , Fanti M , Skinner T C
Published: February 2025

The first-ever comprehensive report on the sleep health of Aboriginal and Torres Strait Islander peoples (hereafter referred to as First Nations Australians) highlighted an 18% prevalence of poor sleep in First Nations youth. While sleep health is important across the lifespan, adolescence is a critical life stage with increased vulnerability to poor sleep. In adolescents, pubertal changes, social and academic commitments, and peer pressure significantly increase the risk of poor sleep, which often results in social and emotional well-being (SEWB) issues. In First Nations adolescents, high rates of SEWB issues demand effective prevention and management strategies. Evidence from non-First Nations adolescents suggests that timely prevention, identification, diagnosis, and management of poor sleep help reduce the risk and severity of SEWB issues in First Nations adolescents.
Fructose induces inflammatory activation in macrophages and microglia through the nutrient‐sensing ghrelin receptor
Authors: Shen Zheng , Liu Zeyu , Wang Hongying , Landrock Danilo , Noh Ji Yeon , Zang Qun Sophia , Lee Chih‐Hao , Farnell Yuhua Z. , Chen Zheng , Sun Yuxiang
Published: February 2025

High fructose corn syrup (HFCS) is a commonly used sweetener in soft drinks and processed foods, and HFCS exacerbates inflammation when consumed in excess. Fructose, a primary component of HFCS; however, it is unclear whether fructose directly activates inflammatory signaling. Growth hormone secretagogue receptor (GHSR) is a receptor of the nutrient‐sensing hormone ghrelin. We previously reported that GHSR ablation mitigates HFCS‐induced inflammation in adipose tissue and liver, shifting macrophages toward an anti‐inflammatory spectrum. Since inflammation is primarily governed by innate immune cells, such as macrophages in the peripheral tissues and microglia in the brain, this study aims to investigate whether GHSR autonomously regulates pro‐inflammatory activation in macrophages and microglia upon fructose exposure. GHSR deletion mutants of RAW 264.7 macrophages and the immortalized microglial cell line (IMG) were generated using CRISPR‐Cas9 gene editing. After treating the cells with equimolar concentrations of fructose or glucose for 24 h, fructose increased mRNA and protein expression of GHSR and pro‐inflammatory cytokines (Il1β, Il6, and Tnfα) in both macrophages and microglia, suggesting that fructose activates Ghsr and induces inflammation directly in macrophages and microglia. Remarkably, GHSR deletion mutants (Ghsrmutant) of macrophages and microglia exhibited reduced inflammatory responses to fructose, indicating that GHSR mediates fructose‐induced inflammation. Furthermore, we found that GHSR regulates fructose transport and fructose metabolism and mediates fructose‐induced inflammatory activation through CREB–AKT‐NF‐κB and p38 MAPK signaling pathways. Our results underscore that fructose triggers inflammation, and reducing HFCS consumption would reduce disease risk. Moreover, these findings reveal for the first time that the nutrient‐sensing receptor GHSR plays a crucial role in fructose‐mediated inflammatory activation, suggesting that targeting GHSR may be a promising therapeutic approach to combat the immunotoxicity of foods that contain fructose.
Bird occurrence and trophic interactions vary across gradients of tree diversity and microclimate in a planted forest
Authors: Coyne Sophie , Osorio Eriberto , Bennett Shelley K. , Kirchgraber Aidan , Parker John D. , Nowakowski A. Justin
Published: February 2025

Deforestation reshuffles communities across landscapes with myriad consequences for ecosystem function. Following deforestation, rapid exposure to novel microclimates can act as a strong environmental filter, favoring warm-adapted species and decoupling trophic interactions. Forest restoration may partly reverse this process through increased habitat structure, food resources, and buffering of microclimates – each potentially modified by tree diversity. Despite growing evidence that tree diversity and cool microclimates help maintain animal diversity in natural forests, less is known about how these factors shape species assemblages or multitrophic dynamics in restoration areas. Here, using surveys and two field experiments within a long-term tree planting experiment, we assessed the relative effects of tree diversity, forest structure, and associated microclimate on fine-scale space use by birds and their top-down impacts on insects. Surveys showed that fine-scale occurrences of birds increased in cooler plots, which were associated with higher tree diversity and structural complexity. The strength of microclimate effects on bird occurrences was strongest for species that are forest specialists. To assess risk to insect herbivores from avian predation, we used a sentinel prey experiment and found that predation risk increased in warmer plots, counter to our expectations based on bird surveys. Last, we examined top-town effects of bird exclusion on leaf herbivory, finding that skeletonizing patterns of herbivory increased in exclosures and in cooler plots. Taken together, these results suggest that microclimate resulting from variation in forest structure shapes space use of birds at fine scales with complex outcomes for bird-herbivore-tree interactions in planted forests. Active restoration methods that enhance below-canopy cooling may improve biodiversity outcomes and help maintain species interactions that underlie many ecosystem functions.
Resolution ofin situinflammation in human lupus nephritis into principal immune cell trajectories
Authors: Casella Gabriel , Torcasso Madeleine , Ai Junting , Cao Thao , Hara Satoshi , Andrade Michael , Ghosh Deepjyoti , Chang Anthony , Ko Kichul , Chong Anita S. , Giger Maryellen , Clark Marcus R.
Published: February 2025

In human lupus nephritis (LuN), tubulointerstitial inflammation (TII) is prognostically more important than glomerular inflammation. However, a comprehensive understanding of both TII complexity and heterogeneity is lacking. Herein, we used high-dimensional confocal microscopy and specialized computer vision techniques to quantify immune cell populations and localize these within normal and diseased renal cortex structures. With these tools, we compared LuN to renal allograft rejection (RAR) and normal kidney. In both LuN and RAR, the 33 characterized immune cell populations formed discrete subgroups whose constituents co-varied in prevalence across biopsies. In both diseases, these co-variant immune cell subgroups organized into the same unique niches. Therefore, inflammation could be resolved into trajectories representing the relative prevalence and density of cardinal immune cell members of each co-variant subgroup. Indeed, in any one biopsy, the inflammatory state could be characterized by quantifying constituent immune cell trajectories. Remarkably, LuN heterogeneity could be captured by quantifying a few myeloid immune cell trajectories while RAR was more complex with additional T cell trajectories. Our studies identify rules governing renal inflammation and thus provide an approach for resolving LuN into discrete mechanistic categories.

Abstract Figure

Graphical Abstract
Non-invasive approach for endoluminal biopsy coupled with single-cell proteomics allows for immune characterization of intracranial aneurysms
Authors: Antonios J. , Gultekin B. , Theriault B. , Yalcin K. , Miyagishima D. , Adenu-Mensah N. , Sujijantarat N. , Koo A. , Haynes J. , Cedeno P. , Johnson M. , Hebert R. , Matouk C. , Barak T. , Gunel M.
Published: February 2025

The immune regulatory mechanisms driving the stability, growth, and rupture of intracranial aneurysms (IAs) remain incompletely understood. In this study, we employ endoluminal biopsy with single-cell proteomics to comprehensively profile the immune landscape of IAs across their pathologic states. Our findings reveal distinct immune signatures associated with aneurysm states. Stable, i.e. non-growing unruptured, IAs exhibit a balanced immune cell composition. Ruptured IAs are marked by significant neutrophil predominance. Notably, we highlight key immune markers in aneurysm instability, offering new insights into immune drivers of aneurysm progression. These findings provide a foundation for immune-targeted, non-invasive therapeutic strategies aimed at targeting IAs and preventing rupture.
Non-invasive and unbiased assessment of thermogenesis in mice through thermal gradient ring
Authors: Melo Paulo De , Pereira Nayara , Araujo Rafaela Braun , Festuccia William T. , Cunha Thiago Mattar , Leiria Luiz Osório
Published: February 2025

Accurately assessing whole-body heat production requires reliable thermometry methods. In mice, common approaches include rectal temperature (RT) measurement, infrared (IR) thermography, and implanted probes. However, factors such as stress, handling, surgery, and variability limit their applicability for evaluating thermogenesis. The Thermal Gradient Ring (TGR), widely used in neuropathic pain and ion channel studies, consists of a circular structure with twelve temperature zones and an integrated IR camera for real-time behavior monitoring. This system allows precise analysis of preferred temperature (PT), heat tolerance, locomotion, and zone occupancy over time, thereby offering a behavioral perspective beyond traditional thermometric methods, which provides only temperature data. In this study, we evaluated TGR as a non-invasive tool for detecting thermogenic changes. Since mice with higher thermogenesis prefer cooler zones, while those with reduced thermogenesis seek warmth, TGR provides a sensitive readout of metabolic behavior. Using models with both enhanced and impaired thermogenesis, we demonstrated TGR’s ability to detect thermogenic status under different conditions. These findings suggest that TGR is a valuable tool for metabolic research, offering a reliable alternative for assessing thermogenesis in mice.
Mifepristone alone and in combination with scAAV9-SMN1 gene therapy improves disease phenotypes in Smn2B/- spinal muscular atrophy mice
Authors: Sutton Emma R , McCallion Eve , Hoolachan Joseph M , Cetin Ozge , Pacheco-Torres Paloma , Bouhmidi Sihame , Churchill Lauren , Scaife Taylor , Chaytow Helena , Huang Yu-Ting , Duguez Stephanie , Schneider Bernard L , Gillingwater Thomas H , Dimitriadi Maria , Bowerman Melissa
Published: February 2025

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene. SMA is characterised by alpha motor neuron loss in the spinal cord and subsequent muscle atrophy. There are currently three approved SMN-directed therapies for SMA patients. While these therapies have transformed what was once a life-limiting condition into one that can be managed and even improved, they are unfortunately not cures, highlighting the need for additional supporting second-generation therapies. These should not only target the neuromuscular system but also peripheral and metabolic perturbations that are present in both SMA models and patients. Kruppel-like factor 15 (Klf15) is a transcription factor that maintains metabolic homeostasis and is involved in the glucocorticoid-glucocorticoid receptor (GR) signalling pathway, in several peripheral and metabolic tissues in SMA mice. Here, we used murine and human cellular models as well as SMA mice and Caenorhabditis Elegans (C. elegans) to assess the therapeutic potential of reducing Klf15 activity with mifepristone, a glucocorticoid antagonist, combined with SMN-targeted gene therapy. We report that mifepristone reduces Klf15 expression across several in vitro models, ameliorates neuromuscular pathology in SMA smn-1(ok355) C. elegans and improves survival of SMA Smn2B/- mice. Furthermore, we show that combining mifepristone with an approved SMN-directed gene therapy (scAAV9-SMN1) results in improved tissue- and sex-specific responses to treatment. Our study demonstrates that a multi-tissue targeting SMN-independent drug, alone and in combination with an approved SMN-dependent therapy, has the potential to improve SMA disease pathology.
NRGRank: Coarse-grained structurally-informed ultra-massive virtual screening
Authors: Descoteaux Thomas , Najmanovich Rafael
Published: February 2025

NRGRank is a coarse-grained structurally-informed software capable of performing ultra-massive virtual screening with accuracy comparable to docking-based methodologies but with 100 fold speed increase. NRGRank is based on a coarse-grained evaluation of pairwise atom-type pseudo-energy interactions that implicitly accounts for compound and side-chain flexibility as well as limited backbone movements. We compare NRGRank to docking-based virtual screening software Glide, Autodock Vina and DOCK 3.7 on the DUD-E virtual screening benchmark using enrichment factors at 1% (EF1). We observe broad variations of EF1 values across targets, structural models and methods. For apo form or AlphaFold2 models, out of a subset of 37 targets from DUD-E, NRGRank has better EF1 values than Glide for 12 and 13 targets respectively. Even in holo form, where the accuracy of docking software increases, NRGRank has better EF1 values than 13, 10 and 5 targets out of 37 compared to AutoDock Vina, DOCK 3.7 and Glide respectively. Comparing the rank of true binders in Glide and NRGRank shows that true binders ranked in the top 1% are complementary between methods irrespective of the target form (AlphaFold, apo or holo). That is, utilizing NRGRank detects binders that are missed by Glide (and presumably other methods), whereas those found by Glide are missed by NRGRank. Furthermore, we observe that most hits found by NRGRank within the top 50 predictions remain once the top 1% of predictions when re-scored with Glide, but the hit rate within the top 50 predictions increase. NRGRank can evaluate one molecule in 0.3 s on average, enabling a modern laptop with 8 cores to screen 1,000,000 molecules in 24 hours, up to two orders of magnitude faster than the reported speed of DOCK 3.7, AutoDock Vina running on GPUs and Glide. NRGRank occupies a unique niche among tools for virtual screening being insensitive to structural inaccuracies but with comparable accuracy as state-of-the-art docking methods and fast as AI-based methods but without the dangers of overfitting as it is based on 780 pseudo-energy parameters. Combined with the fact that NRGRank does not require extensive or expensive computational resources or expert pre-processing of targets, it is unique in making high-performance ultra-massive virtual screening accessible to all.
In vitrocellular phenotypes of cortical neurons from R255XMECP2knock-in mice are improved by either expression of wildtype MeCP2 or ‘read-through’ with G418
Authors: Xu Xin , Merritt Jonathan , Gray Steven J. , Neul Jeffrey , Pozzo-Miller Lucas
Published: February 2025

Approximately 60% of individuals with Rett syndrome (RTT) carry a nonsense variant in theMECP2gene; thus, there is an unmet need to identify novel nonsense suppression compound(s) that can restore full length MeCP2 protein levels and function. Here, we characterized neuronal phenotypes in cultured cortical neurons from newborn knock-in mice harboring theMECP2R255X variant. After 2 weeksin vitro, R255X mutant neurons showed smaller cell bodies, shorter dendrites, fewer dendritic branches, and a lower density of excitatory synapses when compared to wildtype (WT) neurons. Transduction of AAV9-MeCP2-GFP in R255X mutant neurons made these cellular phenotypes similar to those in WT neurons, including soma size, dendritic length and branching, and excitatory synapse density. As proof of principle for the potential clinical use of ‘read-through’ compounds, cultured R255X mutant neurons treated with the aminoglycoside G418 for 72hin vitroshowed cell body size and excitatory synapse density similar to WT neurons. We expect these combined approaches will identify effective compounds to suppress translation termination at a premature termination codon, which can be moved to further preclinical functional and behavioral studies in R255XMECP2knock-in mice.

Summary Statement

Expression of wildtypeMECP2or treatment with G418in vitrorestored cell body size, dendritic length, and dendritic spine density in cortical neurons from R255XMECP2knock-in mice to levels comparable to wildtype neurons.
Agent-based modeling of cellular dynamics in adoptive cell therapy
Authors: Wang Yujia , Casarin Stefano , Daher May , Mohanty Vakul , Dede Merve , Shanley Mayra , Başar Rafet , Rezvani Katayoun , Chen Ken
Published: February 2025

Adoptive cell therapies (ACT) leverage tumor-immune interactions to cure cancer. Despite promising phase I/II clinical trials of chimeric-antigen-receptor natural killer (CAR-NK) cell therapies, molecular mechanisms and cellular properties required to achieve clinical benefits in broad cancer spectra remain underexplored. Whilein vitroandin vivoexperiments are required in this endeavor, they are typically expensive, laborious, and limited to targeted investigations. Here, we present ABMACT (Agent-Based Model for Adoptive Cell Therapy), anin silicoapproach employing agent-based models (ABM) to simulate the continuous course and dynamics of an evolving tumor-immune ecosystem, consisting of heterogeneous “virtual cells” created based on knowledge and omics data observed in experiments and patients. Applying ABMACT in multiple therapeutic context indicates that to achieve optimal ACT efficacy, it is key to enhance immune cellular proliferation, cytotoxicity, and serial killing capacity. With ABMACT,in silicotrials can be performed systematically to inform ACT product development and predict optimal treatment strategies.
Universal orthologs infer deep phylogenies and improve genome quality assessments
Authors: Alam Md Nafis Ul , Román-Palacios Cristian , Copetti Dario , Wing Rod A.
Published: February 2025

Universal single-copy orthologs are the most conserved components of genomes. Although they are routinely used for studying evolutionary histories and assessing new assemblies, current methods do not incorporate information from available genomic data. Here, we first determine the influence of evolutionary history on universal gene content in plants, fungi and animals. We find that across 11,098 genomes comprising 2,606 taxonomic groups, 215 groups significantly vary from their respective lineages in terms of their BUSCO (Benchmarking Universal Single Copy Orthologs) completeness. Additionally, 169 groups display an elevated complement of duplicated orthologs, likely as an artifact of whole genome duplication events. Secondly, we investigate the extent of taxonomic congruence in BUSCO-derived whole-genome phylogenies. For 275 suitable families out of 543 tested, sites evolving at higher rates produce at most 23.84% more taxonomically concordant, and at least 46.15% less terminally variable phylogenies compared to lower-rate sites. We find topological differences between BUSCO concatenated and coalescent trees to be marginal and conclude that higher rate sites from concatenated alignments produce the most congruent and least variable phylogenies. Finally, we show that BUSCO misannotations can lead to misrepresentations of assembly quality. To overcome this issue, we filter a Curated set of BUSCOs (CUSCOs) that provide up to 6.99% fewer false positives compared to the standard BUSCO search and introduce novel methods for comparing assemblies using BUSCO synteny. Overall, we highlight the importance of considering evolutionary histories during assembly evaluations and release the phyca software toolkit that reconstructs consistent phylogenies and reports phylogenetically informed assembly assessments.
A comprehensive identification and annotation of mobile LINE-1 retrotransposons across human reference and personal genomes
Authors: Ferrasa Adriano , Herai Roberto H.
Published: February 2025

LINE-1 (L1) is a type of mobile genetic element (retrotransposon) that can self-copy into distinct parts of its host genome by dynamically shaping its content. In humans, misregulation of these elements have been associated as the potential cause of distinct types of pathologies and neurodevelopmental disorders, including cancer, Rett syndrome and Aicardi Goutierrez disease. However, the precise annotation of these 6 kb long nucleotide sequence is a challenging task due to the high similarity between their internal regions (coding and non-coding) for distinct L1 families. Current L1 reference annotations such as RepeatMasker still lack sequence details and also provide confounding annotated information, that includes thousands of incomplete L1 sequences annotated as representative full-length, and missing information on their regulatory and coding regions (5’UTR, ORF1, intron, ORF2 and 3’UTR). Additionally, current L1 resources also provide annotations based on consensus reference genomes and does not include individual genome information at allele-level and nucleotide-level resolution. Here, we present L1Farm as a complementary databank and annotation resource that contains a comprehensive analysis and annotation of L1 subfamilies identified in the current human reference genome (build Hg38) and in two individual Asian and Caucasian genomes at allele-level and nucleotide-level resolution. L1 elements sequences were also annotated with genomiclociand ranked according to their full-length content and similarity.
JAK inhibitors remove innate immune barriers to allow viral propagation
Authors: Ravlo Erlend , Ianevski Aleksandr , Skipperstøen Marius Nårstad , Lysvand Hilde , Schjølberg Jørn-Ove , Vapalahti Olli , Smura Teemu , Vauhkonen Hanna , Oksenych Valentyn , Weber Friedemann , Strand Mårten , Evander Magnus , Malmring Janne Fossum , Afset Jan Egil , Bjørås Magnar , Kainov Denis E.
Published: February 2025

Janus kinase (JAK) inhibitors are small-molecule therapeutics that reduce inflammation in autoimmune and inflammatory diseases by modulating the JAK-STAT pathway. While effective in alleviating immune-mediated conditions, JAK inhibitors can impair antiviral defences by suppressing interferon (IFN) responses, potentially increasing susceptibility to viral infections. This study investigates the pro-viral mechanism of JAK inhibitors, focusing on baricitinib, across various cell lines, retinal organoids, and viral strains, including a recombinant IFN-sensitive Rift Valley fever (rRVFV), influenza A (rIAV), SARS-CoV-2 (rSARSCoV-2) reporter viruses, and wild type adenovirus (AdV). Our findings demonstrate that baricitinib suppresses transcription of IFN-stimulated genes in non-infected cells (ISGs) which is triggered by type I IFNs produced by infected cells, facilitating viral propagation. The pro-viral effects were influenced by viral load, inhibitor concentration, and structural characteristics of the compound. These results underscore the dual effects of JAK inhibitors: reducing inflammation while potentially exacerbating viral infections. Additionally, the findings highlight opportunities to leverage JAK inhibitors for viral research, vaccine production, and drug screening.