bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Decision-Making Process for Electroconvulsive Therapy in Patients With Major Depressive Disorder and Their Relatives After Treatment
Authors: Rovers Jordy , Schönberger Lieke , Loef Dore , van Eijndhoven Philip , Verwijk Esmée , Somers Metten , Dols Annemiek , Tendolkar Indira
Published: February 2025

Objectives

Shared decision making is used for reaching medical decisions, also in the management of major depressive disorder (MDD). Electroconvulsive therapy (ECT) is an effective treatment option for patients with severe MDD. However, the decision-making process, specifically the exchange of evidence-based information, for ECT may be hampered by the controversy and stigma surrounding ECT. We aim to explore the experiences of the decision-making process of patients and their relatives who have chosen to receive ECT in order to guide optimization of shared decision making in ECT.

Methods

Semistructured interviews were conducted with MDD patients and their relatives who had voluntarily received ECT between 2018–2023 at the Radboud University Medical Center, the Netherlands. The interviews were analyzed by thematic analysis.

Results

Meaning saturation occurred after 16 interviews. The following 3 major themes emerged: 1) information is key, 2) empowering the decision, and 3) lived experiences with ECT. Participants emphasized the importance of accessible information presented in a calm and stepwise manner. They also identified gaps in desired information, particularly regarding memory loss and difficulty in retaining the given information. Factors empowering the decision included support from family, healthcare professionals, peers, and desperation, while negative factors included stigma, negative images, lack of support, and fear. Lived experiences with ECT might influence a future decision. Positive experiences were improved attitudes, treatment effects, and empathic and involved professionals, while negative aspects included cognitive side effects and lack of follow-up.

Conclusions

This study offers insights into factors influencing the decision-making process in patients with MDD that received ECT. It shows possibilities for improving the decision-making process in clinical practice.
Dietary Factors and Predominant Eye Diseases in Sub-Saharan African Populations: A Comprehensive Systematic Review Protocol
Authors: Duah Isaiah Osei , Akuffo Kwadwo Owusu , Ampong Josephine , Owiredu David , Danso-Appiah Anthony
Published: February 2025

Background

Evidence linking diet and ocular diseases is growing, yet variations persist, with a paucity of data in sub-Saharan Africa. The proposed review will systematically synthesize evidence on dietary factors associated with predominant eye disorders (cataracts, refractive error, glaucoma, diabetic retinopathy, age-related macular degeneration, and dry eye disease) in the sub-Saharan African population.

Methods

The systematic review and meta-analysis will follow the gold standard for reporting systematic reviews and meta-analysis, thus Preferred Reporting Items for Reporting Systematic Reviews and Meta-analysis (PRISMA), and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The study will identify all relevant studies published, unpublished, and pre-prints from PubMed, SciVerse Scopus, Web of Science, Google Scholar, Embase, Health Inter-Network Access to Research Initiative (HINARI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), African Journal of Science, Biomed Central, and Cochrane Library and relevant institutional databases without date restrictions. We will check the reference lists of all studies identified by the methods and contact experts for additional relevant studies. Data will be analyzed with the Review Manager (RevMan) software. The random effects model will be used to pool study effect estimates and robustness assessed through sensitivity analyses. Heterogeneity across studies will be assessed using the I2-statistic. Publication bias will be investigated graphically with a funnel plot and statistically with Egger’s regression intercept method or Begg’s rank correlation tests. All estimates will be reported with their confidence intervals, and statistical analysis will be set at a significance level of p<0.05. The results of the review will be presented based on the PRISMA guidelines.
Interplay of Type 2 Inflammation, Small Airway Dysfunction, and Patient-Reported Outcomes in Treatment-Naīve Uncontrolled Asthma: A Retrospective Primary Care Analysis
Authors: Nakano Yutaka , Nakano Rika , Yukawa Takuya , Arita Akihiro
Published: February 2025

Background: Effective initial asthma treatment in primary care requires a comprehensive assessment of airway inflammation and lung function impairment, including small airway dysfunction (SAD). We investigated the prevalence of type 2 (T2) inflammation and SAD in treatment-naīve patients with uncontrolled asthma who received primary care, and assessed the utility of the Asthma Control Questionnaire-5 (ACQ-5) as a potential indicator of these factors. Methods: This single-center retrospective study enrolled treatment-naīve adults who presented with uncontrolled asthma (ACQ-5 score ≥ 1.5) between April 2020 and March 2022. T2 inflammation was assessed using blood eosinophil count (bEOS), fractional exhaled nitric oxide (FeNO), and total immunoglobulin E (IgE) levels. Patients with bEOS ≥ 300 cells/μL and FeNO ≥ 50 ppb were designated "T2-high." SAD was defined as a forced expiratory flow between 25% and 75% of the vital capacity percentage predicted value (FEF25-75%pred) < 65%. Results: Among 192 patients, 87% exhibited an elevation in at least one T2 biomarker, with 47% meeting the T2-high criteria. An ACQ-5 score ≥ 3.0 significantly predicted T2-high status (odds ratio: 2.62, 95% confidence interval: 1.46-4.69, p = 0.00127). SAD was identified in 52% of patients, with ACQ-5 scores showing a strong negative correlation with FEF25-75%pred (ρ = -0.583, p < 0.0001), particularly for nocturnal awakening score (ρ = -0.728, p < 0.0001). Conclusions: Our findings revealed a high prevalence of T2 inflammation and SAD in treatment-naīve patients with uncontrolled asthma who received primary care. The ACQ-5 demonstrates potential as a practical screening tool for these pathophysiological features, offering valuable guidance for initial treatment decisions where advanced diagnostic capabilities may be limited.
Sex-dependent effects of a gestational ketogenic diet on offspring birth and lifespan
Authors: Zala Sarah M. , Santos Renata , Strasser Eva , Schadde Alice , Kugler Sarah , Strauss Verena , Kübber-Heiss Anna , Zala Diana
Published: February 2025

Low-carbohydrate, high-fat ketogenic diets (KDs) are used to treat drug-resistant epilepsy, and other potential benefits for treating neurological disorders, metabolic syndrome, and cancer are being explored. In addition to these and other medical applications, KDs have also become popular for rapid weight-loss and enhancing athletic performance. However, the effects of exposing developing offspring to KDs during pregnancy (gestational KD) are poorly understood, and especially their long-term health consequences. In this study, we investigated the effects of a partial gestational KD during the second half of pregnancy in mice and assessed the consequences on the offspring over their entire lifespan compared to offspring exposed to a control diet. We found that a gestational KD significantly reduced dams’ litter size and litter mass and altered the sex ratio at birth, reducing the proportion of female offspring, which also had lower body mass early in their life. In contrast, male offspring exposed to a gestational KD suffered a significantly reduced lifespan and a late-onset increase in body mass. We found no evidence that our KD diet influenced adult offspring behavior (locomotion, anxiety, depression, circadian rhythms, food and water consumption) or reproduction. These findings highlight the potential of even a partial maternal exposure to a KD to have surprisingly detrimental effects on offspring health and longevity, and thus raising concerns about its use during pregnancy.
Functional imaging of 3D bioprinted microalgal constructs and simulation of their photosynthetic performance
Authors: Murthy Swathi , Mosshammer Maria , Trampe Erik , Kühl Michael
Published: February 2025

The intricate three dimensional architecture at different spatial length scales affects the functionality and growth performance of immobilized photosynthesizing cells in biofilms and bioprinted constructs. Despite the tremendous potential of 3D bioprinting in precisely defining sample heterogeneity and composition in spatial context, cell metabolism is mostly measured in media surrounding the constructs or by destructive sample analyses. The exploration and application of non-invasive techniques for monitoring physico-chemical microenvironments, growth and metabolic activity of cells in 3D printed constructs is thus in strong demand. Here, we present a pipeline for the fabrication of 3D bioprinted microalgal constructs with a functionalized gelatin methacryloyl (GelMA)-based bioink for imaging O2dynamics within bioprinted constructs, as well as their characterization using various, non-invasive functional imaging techniques and numerical simulation of their photophysiological performance. This fabrication, imaging and simulation pipeline now enables investigation of the effect of structure and composition on photosynthetic efficiency of bioprinted constructs with microalgae or cyanobacteria. It can facilitate designing efficient construct geometries for enhanced light penetration and improved mass transfer of nutrients, CO2or O2between the 3D printed construct and the surrounding medium, thereby providing a mechanistic basis for the design of more efficient artificial photosynthetic systems.
Adaptation of visual responses in degeneratingrd10and healthy mouse retinas during ongoing electrical stimulation
Authors: Jalligampala Archana , Shabani Hamed , Zrenner Eberhart , Rathbun Daniel L. , Hosseinzadeh Zohreh
Published: February 2025

Objective

Visual adaptation is a physiological and perceptual process by which the visual system adjusts to changes in the environment or visual stimuli. This process is fundamental to how we perceive the world around us and allows our visual system to efficiently encode and process visual information. The retina incorporates adaptaion with its dozens of functionally distinct retinal ganglion cell types. Meanwhile, the field of retinal prostheses is increasing its understanding of electrical adaptation and cell-specific stimulation. However, very little is known about the interaction of visual and electrical stimulation on the adaptation of retinal ganglion cell types.

Methods/Approach

Recording with a microelectrode array (MEA), we presented an ON and OFF full-field, visual stimulus to characterize various visual response parameters in healthy and degeneratingrd10mouse retinas. We then evaluated visual response changes before and after blocks of monophasic voltage-controlled electrical pulse stimulation.

Main Results

A history of electrical stimulation strengthened visual responses in WT retina, even when changes attributable toin vitrovisual adaptation were taken into account. Inrd10retinas, electrical adaptation counteracted the baselinein vitrovisual adaptation. In all cases, adaptation often affected the ON and OFF visual response components differentially. Consequently, the ON/OFF classification of indiviual cells changed as a result of adaptation.

Significance

Electrical stimulation-induced changes in the retina should be considered in the encoding of visual stimuli by retinal prosthetic devices.In vitroinvestigations for bionic vision should strive to probe electrical responsiveness after adaptation to ongoing electrical stimulation has achieved a steady-state.
Prebreeding populations and the importance of life history for conserving the world’s imperiled seabirds
Authors: Taylor Liam U. , Gnam Eleanor
Published: February 2025

Seabird conservation often focuses on nestlings and breeding adults. Yet imperiled seabird populations also contain prebreeders, including juveniles and subadults, that wait several years before breeding at colonies. We use previously-published data on reproductive and survival rates for 84 species to quantify the conservation relevance of prebreeding seabirds. We find, first, that prebreeders average about half of seabird populations (median 47.4%, range 11.2%–66.7%). Second, while seabird population growth is much more sensitive to adult survival than prebreeder survival, human-driven changes may shift the importance of prebreeders for future population stability. Third, lowering the breeding age is a powerful, but underexplored, route to increasing population growth. Managing prebreeders could thus play a key role in protecting seabirds. This task may require answering fundamental questions about the behavior of young birds. Broadly, we suggest that life history characteristics (e.g., breeding age) actively shape both obstacles to, and opportunities for, successful conservation.
Decoding peripheral saccade targets from foveal retinotopic cortex
Authors: Kämmer Luca , Kroell Lisa M. , Knapen Tomas , Rolfs Martin , Hebart Martin N.
Published: February 2025

Human vision is characterized by frequent eye movements1. This causes continuous shifts in visual input, yet visual perception appears highly stable2–4. A potential mechanism behind this stability is foveal prediction, involving feedback from higher cortical areas during saccade preparation.5,6However, it remains unknown (1) whether information is fed back to early visual areas, (2) whether feedback is specific to stimulus features, and (3) which brain regions mediate this effect. To dissociate neural processes associated with stimulus presentation from those related to foveal feedback, we designed a gaze-contingent fMRI paradigm, where saccade targets are removed before they can be foveated. To determine the content of the neural representation, we used natural images as saccade targets and independently manipulated object shape and category. Multivariate analyzes revealed reliable decoding of stimuli from foveal retinotopic areas as early as V1, even though the stimulus never appeared in the fovea. Decoding was sensitive to shape but not semantic category, indicating that only low-to-mid-level information is fed back. Cross-decoding to a control condition with foveal stimulus presentation yielded reliable decoding, indicating a similar neural representation between foveal feedback and direct stimulation. Eccentricity-dependent analyzes showed a u-shaped decoding curve, confirming that these results are not explained by spillover of peripheral activity or large receptive fields. Moreover, fluctuations in foveal decodability correlated with activity in the intraparietal sulcus, a candidate region for driving this foveal feedback. These findings go beyond trans-saccadic remapping7,8by suggesting that peripheral saccade targets are encoded in the foveal cortex in a feature-specific representation5.

Highlights

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Saccade targets decodable from foveal early visual areas without foveal stimulation.

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Decoding accuracy is affected by stimulus shape, not semantic information.

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Peripheral stimuli are foveally represented similarly to direct foveal stimuli.

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Intraparietal sulcus activity is consistent with mediation of foveal feedback.
Multimodal characterization and optogenetic potential of the bistable Gi/o-coupled vertebrate ancient opsin from the flashlight fishAnomalops katoptron
Authors: Rohr Lennard , Zhornist Daniel , Bermann Ori , Ruse Christiane , Seidenthal Marius , Auger Genevieve Marie , Naber Caroline , Kirchhof Alina , Güers Caroline I. , Mark Melanie D. , Rudack Till , Soba Peter , Gottschalk Alexander , Shalev-Benami Moran , Siveke Ida , Herlitze Stefan
Published: February 2025

Vertebrate ancient long opsin, or VAL opsin, is a light-sensitive protein that is found within and outside the visual system in vertebrates. In accordance with its wide distribution in the retina, brain, testis and skin, VAL is suggested to play a role in light-dependent physiological processes that are beyond vision. However, many aspects of the physiological properties and specific functions of VAL remain unclear. Here we identified and characterized the VAL opsin from the flashlight fishAnomalops katoptron(AkVAL) and show that this opsin is bistable and reversibly converts between active and inactive states by responding to cycles of green and blue/UV lights. We further show thatAkVAL couples to the Gi/opathway and controls the activity of GIRK channels in a bistable manner. In line with this, we demonstrated thatAkVAL modulates neuronal activity in cerebellar Purkinje cells, where neuronal activity is reduced by UV/blue light and increased by green/red light illumination. In addition, upon thein vivoexpression ofAkVAL in neurons innervating body muscles ofCaenorhabditis elegansthe worm’s body movement can be bidirectionally controlled altering blue/UV and green illuminations. These data highlight the potential ofAkVAL as an optogenetic tool to control cellsin vitroandin vivo, in a bistable manner.
Designing new natural-mimetic phosphatidic acid: a versatile and innovative synthetic strategy for glycerophospholipid research
Authors: Schlichter Antoine , Wolf Alexander , Ferrand Thomas , Cocq Aurelien , Riachy Lina , Vertueux Steven , Beauvais Brice , Courvalet Marine , Henry Paul-Joël , Tanguy Emeline , Gonzales Louis , Ferlet Rémy , Laguerre Fanny , Decraene Charles , Pellissier Alexia , Sebban Muriel , Sabot Cyrille , Jeandel Lydie , Cianférani Sarah , Strub Jean-Marc , Bénard Magalie , Flon Victor , Peulon-Agasse Valérie , Cardinael Pascal , Ory Stéphane , Gasman Stéphane , Renard Pierre-Yves , Montero-Hadjadje Maïté , Vitale Nicolas , Balieu Sébastien
Published: February 2025

Glycerophospholipids (GPLs) play important roles in cellular compartmentalization and signaling. Among them, phosphatidic acids (PA) exist as many distinct species depending on acyl chain composition, each one potentially displaying unique signaling function. Although the signaling functions of PA have already been demonstrated in multiple cellular processes, the specific roles of individual PA species remain obscure due to a lack of appropriate tools. Indeed, current synthetic PA analogues fail to preserve all the functions of natural PA. To circumvent these limitations, we developed a novel synthetic approach to produce PA analogues without compromising structural integrity of acyl chains. Moreover, addition of a clickable moiety allowed flexible grafting of different molecules to PA analogues for various biological applications. Hence, this innovation also provides powerful tools to investigate specific biological activities of individual PA species, with potential applications in unraveling complex GPL-mediated signaling pathways.
Persistent dopamine-dependent remodeling of the neural transcriptome in response to pregnancy and postpartum
Authors: Chan Jennifer C , Di Salvo Giuseppina , Cunningham Ashley M , Dutta Sohini , Brindley Elizabeth A , Wan Ethan , Zhang Cindy , Maze Ian
Published: February 2025

Pregnancy and postpartum experiences represent transformative physiological states that impose lasting demands on the maternal body and brain, resulting in lifelong neural adaptations. However, the precise molecular mechanisms driving these persistent alterations remain poorly understood. Here, we used brain-wide transcriptomic profiling to define the molecular landscape of parity-induced neural plasticity, identifying the dorsal hippocampus (dHpc) as a key site of transcriptional remodeling. Combining single-cell RNA sequencing with a maternal-pup separation paradigm, we additionally demonstrated that chronic postpartum stress significantly disrupts dHpc adaptations by altering dopamine dynamics, leading to dysregulated transcription, altered cellular plasticity, and impaired behavior. We further established the sufficiency of dopamine modulation in the regulation of these parity-induced adaptations via chemogenetic suppression of dopamine release into dHpc, which recapitulated key transcriptional and behavioral features of parity in virgin females. In sum, our findings establish dopamine as a central regulator of parity-induced neuroadaptations, revealing a fundamental transcriptional mechanism by which female reproductive experiences remodel the maternal brain to sustain long-term behavioral adaptations.
Linking molecular pathways and islet cell dysfunction in human type 1 diabetes
Authors: dos Santos Theodore , Dai Xiao Qing , Jones Robert C , Spigelman Aliya F , Mummey Hannah M , Ewald Jessica D , Ellis Cara E , Lyon James G , Smith Nancy , Bautista Austin , Manning Fox Jocelyn E , Neff Norm F. , Detweiler Angela , Tan Michelle , Arrojo E Drigo Rafael , Xia Jianguo , Camunas-Soler Joan , Gaulton Kyle J , Quake Stephen , MacDonald Patrick E
Published: February 2025

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of most insulin-producing β-cells, along with dysregulated glucagon secretion from pancreatic α-cells. We conducted an integrated analysis that combines electrophysiological and transcriptomic profiling, along with machine learning, of islet cells from T1D donors to investigate the mechanisms underlying their dysfunction. Surviving β-cells exhibit altered electrophysiological properties and transcriptomic signatures indicative of increased antigen presentation, metabolic reprogramming, and impaired protein translation. In α-cells, we observed hyper-responsiveness and increased exocytosis, which are associated with upregulated immune signaling, disrupted transcription factor localization and lysosome homeostasis, as well as dysregulation of mTORC1 complex signaling. Notably, key genetic risk signals for T1D were enriched in transcripts related to α-cell dysfunction, including MHC class I which were closely linked with α-cell dysfunction. Our data provide novel insights into the molecular underpinnings of islet cell dysfunction in T1D, highlighting pathways that may be leveraged to preserve residual β-cell function and modulate α-cell activity. These findings underscore the complex interplay between immune signaling, metabolic stress, and cellular identity in shaping islet cell phenotypes in T1D.

Highlights

Surviving β-cells in T1D show disrupted electrical function linked to metabolic reprogramming and immune stress.

Transcripts associated with α-cell dysfunction are enriched in genetic risk alleles for T1D.

Upregulated MHC class I and impaired nuclear localization of key transcription factors associate with α-cell dysfunction in T1D.

T1D α-cells exhibit increased hyper-activity, lysosomal imbalance and impaired mTORC1 signaling, which promotes dysregulated glucagon secretion.
Inducible, virus-free direct lineage reprogramming enhances scalable generation of human inner ear hair cell-like cells
Authors: Rainey Robert N. , Houman Sam D. , Menendez Louise , Chang Ryan , Tao Litao , Bugacov Helena , McMahon Andrew P. , Kalluri Radha , Oghalai John S. , Groves Andrew K. , Segil Neil
Published: February 2025

Mammalian inner ear sensory hair cells are highly sensitive to environmental stress and do not regenerate, making hearing loss progressive and permanent. The paucity and extreme inaccessibility of these cells hinder the development of regenerative and otoprotective strategies, Direct lineage reprogramming to generate large quantities of hair cell-like cells in vitro offers a promising approach to overcome these experimental bottlenecks. Previously, we identified four transcription factors—Six1,Atoh1,Pou4f3, andGfi1(SAPG)—capable of converting mouse embryonic fibroblasts, adult tail tip fibroblasts, and postnatal mouse supporting cells into induced hair cell-like cells through retroviral or lentiviral transduction (Menendezet al., 2020). Here, we developed a virus-free, inducible system using a stable human induced pluripotent stem (iPS) cell line carrying doxycycline-inducible SAPG. Our inducible system significantly increases reprogramming efficiency compared to retroviral methods, achieving a ∼19-fold greater conversion to a hair cell fate in half the time. Immunostaining, Western blot, and single-nucleus RNA-seq analyses confirm the expression of hair cell-specific markers and activation of hair cell gene networks in reprogrammed cells. The reprogrammed hair cells closely resemble developing fetal hair cells, as evidenced by comparison with a human fetal inner ear dataset. Electrophysiological analysis reveals that the induced hair cell-like cells exhibit diverse voltage-dependent ion currents, including robust, quick-activating, slowly inactivating currents characteristic of primary hair cells. This virus-free approach improves scalability, reproducibility, and the modeling of hair cell differentiation, offering significant potential for hair cell regenerative strategies and preclinical drug discovery targeting ototoxicity and otoprotection.
Procurement of Pancreatic Islet Cells from Deceased Donors: Updated Data and Gaps in Reporting
Authors: Goldberg David S , Tewksbury Erin , Wadsworth Matthew
Published: February 2025

In 2020, CMS updated the ‘Final Rule’ for organ procurement organizations (OPO) in 2020 to include new metrics of OPO performance with a carveout whereby pancreata procured for research count as a “donor” to reward OPOs procuring pancreata for islet cell research or transplantation. Yet data suggested OPOs took advantage of this loophole, leading to updated guidance in 2024 to require OPOs classify whether procured research pancreata were “accepted for islet cell research.” Based on updated data using the new CMS codes, the increase in research pancreas procurement was nearly half previously reported, but far greater than prior to 2020. Importantly, the number of pancreata OPOs reported were accepted for islet cell research were an order of magnitude greater than what was used by the Integrated Islet Cell Distribution Program (IIDP) and the Network for Pancreatic Organ Donors with Diabetes (nPOD), the two largest sources of islet cell/pancreata for qualified researchers in the US. Inappropriate procurement of organs, and mislabeling them as being used for “islet cell research” raises questions of fraud, waste, and abuse that requires further investigation and transprancy.
Exploring intra-specific variation in photosynthesis of maize and sorghum
Authors: Almeida Rafael L. , Silveira Neidiquele M. , Sartori Heitor L. , Carvalho Camila C. , Scarpari Maximiliano S. , Duarte Aildson P. , Sawazaki Eduardo , Machado Eduardo C. , Ribeiro Rafael V.
Published: February 2025

Enhancing crop yield through improved photosynthesis is a key for feeding the global population and providing feedstock for a sustainable green economy. However, effectively linking photosynthetic performance and biomass production in C4species requires an integrative approach at plant canopy. This study aimed to characterize photosynthesis along the canopy of five maize (BM3069-PRO2, AG8701-PRO4, K7500-VIP3, DKB355-PRO3 and B2401-PWU) and sorghum (DKB560, Enforcer, IAC 7021, Brandelisa and Santa Elisa) cultivars, focusing on leaf gas exchange and chlorophyll fluorescence evaluations in three canopy strata: top; middle and bottom. Photosynthetic responses to increasing intercellular CO2concentration and light (A–CiandA–PAR curves, respectively) were performed and key photosynthetic traits estimated. We found a significant variability in the maximum photosynthetic rates across the canopies. Modern maize cultivars exhibited high CO2assimilation in the top and middle canopy leaves, demonstrating physiological adjustments for increasing canopy homogeneity in terms of photosynthesis. Such adjustments included high maximum quantum efficiency of CO2assimilation (ϕ), stomatal conductance, carboxylation rates of PEPC and Rubisco, and leaf nitrogen content (LNC) along the canopy. In contrast, sorghum cultivars showed significant interactions between canopy strata, with DKB560 and Brandelisa standing out for their enhanced CO2uptake and ϕ throughout the plant canopy. Our findings highlight maize as an efficient C4crop, characterized by a high photosynthetic capacity and relative uniform photosynthesis across the canopy. This is attributed to reduced stomatal limitation and higher stomatal conductance, carboxylation of Rubisco (Vcmax) and LNC in the top and middle canopy, along with higher ϕ in middle and bottom layers. Overall, physiological adjustments such as nitrogen redistribution to upper canopy leaves and the optimization of light-use efficiency in lower layers are key for enhancing canopy-level photosynthesis in maize and sorghum cultivars.
Co-adaptive training improves performance during fMRI decoded neurofeedback
Authors: Abdennour Najemeddine , Margolles Pedro , Soto David
Published: February 2025

A significant challenge for neurofeedback training research and related clinical applications, is participants’ difficulty in learning to induce specific brain patterns during training. Here, we address this issue in the context of fMRI-based decoded neurofeedback (DecNef). Arguably, discrepancies between the data used to construct the decoder and the data used for neurofeedback training, such as differences in data distributions and experimental contexts, neural and non-neural noise, are likely the cause of aforementioned participants’ difficulties. Hare, we developed a co-adaptation procedure using standard machine learning algorithms. The procedure involves an adaptive decoder algorithm that is updated in real time based on its predictions across neurofeedback trials. First, we tested the procedure via simulations using a previous DecNef dataset. We then collected real time fMRI data in a DecNef training procedure to provide proof of concept evidence that co-adaptation enhances participant’s ability to induce the target state during training. Thus, personalized decoders through co-adaptation can improve the precision and reliability of DecNef training protocols to target specific brain representations, with ramifications in translational research. The tools are made openly available to the scientific community.
Diurnal Bull Ants Navigating by Moonlight: Polarised Light Homing in Myrmecia tarsata
Authors: Freas Cody A , Cheng Ken
Published: February 2025

We present evidence that the faint polarised moonlight pattern of the sky can be detected and used for navigation in the diurnal bull ant Myrmecia tarsata, despite this species lacking the highly refined low-light visual specialisations of the nocturnal bull ant, Myrmecia midas. The position of celestial bodies such as the sun and moon can provide navigating animals directional information, yet direct observation can often be occluded. Animals can estimate positional information of solar and lunar cues via their polarised light pattern, present across the sky. The suns polarisation pattern is widely used in animals and a similar, yet much fainter pattern is produced by the moon, yet it is unknown how widespread moonlights use is in navigating animals. Here, we demonstrate that the bull ant Myrmecia tarsata, which forages throughout the day, returning home at sunset, can use both solar and lunar polarised light patterns to navigate. We compare these findings to the closely related M. midas navigating under identical light conditions, as this nocturnal bull ant is known to rely on these polarised light patterns as part of their celestial compass. While M. midas and M. tarsata can clearly use both the solar and lunar polarised light patterns to navigate, M. tarsata showed degraded performance under polarised moonlight as a function of lunar phase, decreasing performance as illumination decreased. M. midas in contrast, exhibited impressive attendance to the overhead lunar polarisation pattern throughout the lunar month, illustrating the highly specialised low-light-detection adaptations of bull ants.
Ultra-High Resolution TR-external EPIK with Deep Learning Image Reconstruction for Enhanced Characterisation of Cortical Depth-dependent Neural Activity
Authors: Yun Seong Dae , Cho Jaejin , Pais-Roldán Patricia , Shah N. Jon
Published: February 2025

The detection of neural signals using functional MRI at the laminar or columnar level enables non-invasive exploration of fundamental brain function processing and the interconnected pathways within intracortical tissues. The growing interest in this research area is driven by advancements in fMRI acquisition techniques that enhance spatial resolution for high-fidelity mapping. However, the submillimetre voxel sizes commonly employed in layer-specific fMRI studies raise concerns about relatively low signal-to-noise ratios and increased image artefacts in reconstructed images, ultimately limiting the precise delineation of cortical depth-dependent functional activities.

This work aims to address this issue by incorporating a deep learning technique for enhanced image reconstruction of the submillimetre fMRI data, acquired with echo-planar-imaging with keyhole (EPIK) combined with the repetition-time-external (TR-external) EPI phase correction scheme. Our network was trained in a self-supervised, scan-specific manner using the sampling strategy from zero-shot self-supervised learning (ZS-SSL) method, which has gained attention for high-resolution MR image reconstruction.

Healthy volunteers participated in this study, and the performance of the developed method was evaluated in direct comparison to the conventional reconstruction method using datasets acquired at 7T. The deep learning reconstruction produced reconstructed images with significantly higher SNR than the conventional method, which was further quantitatively validated through histogram analysis. This enhancement was consistent across all slice locations, demonstrating the reliability of the scan-specific deep learning technique.
N-terminal region of PetD is essential for cytochromeb6ffunction and controls STT7 kinase activity via STT7-dependent feedback loop phosphorylation
Authors: Zaeem Afifa , Milrad Yuval , Bütfering Simon , Stoffel Carolyne , Burlacot Adrien , Scholz Martin , Buchert Felix , Hippler Michael
Published: February 2025

The cytochromeb6fcomplex (b6f) links photosystem I (PSI) and photosystem II (PSII) in the photosynthetic electron transfer chain and is distributed across appressed and non-appressed thylakoid membranes. Theb6falso activates the state-transition 7 kinase (STT7), which phosphorylates light-harvesting complex proteins, triggering their migration to enable energy redistribution between PSII and PSI. STT7-dependent phosphorylation has also been observed at T4 in the N-terminal domain of theb6fsubunit-IV (PetD), though its functional significance has remained unclear. To investigate its role, we generated several chloroplast mutants. The phosphomimic mutation PetD T4E inhibited STT7 kinase activity, as indicated by the absence of STT7-dependent phosphorylation and the strain being locked in State 1. This reveals a novel feedback mechanism regulating phosphorylation facilitated by STT7. The deletion of five N-terminal amino acids resulted in a comparable inhibition of STT7 activity and, additionally, in the disruption of electron transfer which underscores a crucial role of the PetD N-terminus inb6ffunction.
Flagellin in the human gut microbiome is a diet-adjustable adjuvant for vaccination
Authors: Huus Kelsey E. ,   µHEAT Clinical Study Group, Tan Yi Han , Abo Hirohito , Keller Ronald , Atay Ezgi , Vu Dai Long , Dauser Silke , Prokipchuk Alina , Tyakht Alexander V. , Youngblut Nicholas , Chassaing Benoit , Kang Sang-Moo , Parsonnet Julie , Kremsner Peter G. , Maier Lisa , Gewirtz Andrew T. , Esen Meral , Ley Ruth E.
Published: February 2025

The intestinal microbiota is thought to modulate immune responsiveness to vaccines. Human studies on this topic, however, have yielded inconsistent results1,2. We hypothesized that the microbiome would influence innate immune responses, and thus vaccine reactogenicity, more directly than vaccine immunogenicity. To test this, we established the µHEAT (Microbial-Human Ecology And Temperature) study, which longitudinally profiled the fecal microbiota, oral body temperature and serum antibody responses of 171 healthy adults (18-40 years old) before and after vaccination for SARS-CoV-2. Increased temperature after vaccination (ΔT) was associated with habitual diet and with baseline metabolic and immune markers. The microbiomes of ΔT-high (ΔThi) participants were characterized by high expression of flagellin and an overabundance of the flagellated bacteriumWaltera. Fecal samples from ΔThiparticipants induced more inflammation in human cells and stronger post-vaccine temperature responses in mice compared to ΔTlosamples, suggesting a causal role for the microbiome. Moreover,Walteraflagellin replicated the inflammatory phenotypesin vitroand was modulable via a dietary additive. Overall, these data suggest that flagellin from the gut microbiome stimulates innate immunity and vaccine reactogenicity, and that this axis can be manipulated via diet. These findings have implications for improving human vaccine tolerance and immunogenicity.
Synthetic Diffusion Tensor Imaging Maps Generated by 2D and 3D Probabilistic Diffusion Models: Evaluation and Applications
Authors: Chattopadhyay Tamoghna , Jagad Chirag , Kush Rudransh , Desai Vraj Dharmesh , Thomopoulos Sophia I. , Villalón-Reina Julio E. , Ambite Jose Luis , Steeg Greg Ver , Thompson Paul M.
Published: February 2025

Diffusion tensor imaging (DTI) is a key neuroimaging modality for assessing brain tissue microstructure, yet high-quality acquisitions are costly, time-intensive, and prone to artifacts. To address data scarcity and privacy concerns – and to augment the available data for training deep learning methods – synthetic DTI generation has gained interest. Specifically, denoising diffusion probabilistic models (DDPMs) have emerged as a promising approach due to their superior fidelity, diversity, controllability, and stability compared to generative adversarial networks (GANs) and variational autoencoders (VAEs). In this work, we evaluate the quality, fidelity and added value for downstream applications of synthetic DTI mean diffusivity (MD) maps generated by 2D slice-wise and 3D volume-wise DDPMs. We evaluate their computational efficiency and utility for data augmentation in two downstream tasks: sex classification and dementia classification using 2D and 3D convolutional neural networks (CNNs). Our findings show that 3D synthesis outperforms 2D slice-wise generation in downstream tasks. We present a benchmark analysis of synthetic diffusion-weighted imaging approaches, highlighting key trade-offs in image quality, diversity, efficiency, and downstream performance.
Investigating the effectiveness of cannabidiol to mitigate the adverse consequences of exposure to neonatal procedural pain
Authors: Timmerman Brian , Honeycutt Jennifer A. , Skully Jordan , Patel Deep , Khan Waris , Neagu Alan , Baez Eshani , Battagliese Quinn , Brummelte Susanne
Published: February 2025

Repeated painful procedures are associated with a multitude of effects on neurodevelopment in preterm infants, and current methods of neonatal pain management are unable to prevent the distress and long-term changes induced by these procedures. Cannabidiol (CBD) may be particularly effective for neonatal pain management because it reduces pain unpleasantness ratings, mitigates biological stress responses, and has minimal side effects in adults. However, there is limited research on the effects of neonatal CBD exposure. The present study investigated the efficacy of CBD treatment in mitigating behavioral responses to neonatal pain exposure. This was measured acutely through changes in ultrasonic vocalization (USV) emissions, as well as across development on long-term behavioral outcomes. We show that neonatal pain exposure decreased USV emission and increased adult anxiety-like behavior in male rats. Neonatal CBD treatment also decreased USVs in male pups but was unable to rescue the increased anxiety-like behavior in adulthood. Additionally, neonatal CBD increased baseline corticosterone levels in adult male subjects and decreased adult female body weight. More research is needed to determine whether CBD may be a safe and effective neonatal pain management medication.

Highlights

CBD reduced USV emissions on PD 2 and 3 in males, but not on later days

Pain exposure increased adult anxiety-like behavior in males

Neonatal CBD exposure resulted in decreased adult female body weight.

CBD had no permanent effects on measurements of neurodevelopment or adult behavior

CBD does not seem to mitigate effects of neonatal pain exposure
Development and Characterization of aSf-1-Flp Mouse Model
Authors: Galvan Marco , Fujitani Mina , Heaselgrave Samuel R. , Thomas Shreya , Chen Bandy , Lee Jenny J. , Wyler Steven C. , Elmquist Joel K. , Fujikawa Teppei
Published: February 2025

The use of genetically engineered tools, including combinations of Cre-LoxP and Flp-FRT systems, enable the interrogation of complex biology. Steroidogenic factor-1 (SF-1) is expressed in the ventromedial hypothalamic nucleus (VMH). Development of genetic tools, such as mice expressing Flp recombinase (Flp) in SF-1 neurons (Sf-1-Flp), will be useful for future studies that unravel the complex physiology regulated by the VMH. Here, we developed and characterizedSf-1-Flp mice and demonstrated its utility. Flp sequence was inserted intoSf-1locus with P2A. This insertion did not affectSf-1mRNA expression levels andSf-1-Flp mice do not have any visible phenotypes. They are fertile and metabolically comparable to wild-type littermate mice. Optogenetic stimulation using adeno-associated virus (AAV)-bearing Flp-dependent channelrhodopsin-2 (ChR2) increased blood glucose and skeletal muscle PGC-1α inSf-1-Flp mice. This was similar to SF-1 neuronal activation usingSf-1-BAC-Cre and AAV-bearing Cre-dependent ChR2. Finally, we generatedSf-1-Flp mice that lackβ2-adrenergic receptors(Adrβ2) only in skeletal muscle with a combination of Cre/LoxP technology (Sf-1-Flp::SKMΔAdrβ2). Optogenetic stimulation of SF-1 neurons failed to increase skeletal muscle PGC-1α inSf-1-Flp::SKMΔAdrβ2mice, suggesting thatAdrβ2in skeletal muscle isrequiredfor augmented skeletal muscle PGC-1α by SF-1 neuronal activation. Our data demonstrate thatSf-1-Flp mice are useful for interrogating complex physiology.
Targeting the ferroptosis pathway: A novel compound, AZD1390, protects the brain after ischemic stroke
Authors: Lee Han Kyu , Lin Chao-Chieh , Dunn Denise E. , Chen Yubin , Chen Ssu-Yu , Marchuk Douglas A. , Floyd Scott R. , Chi Jen-Tsan
Published: February 2025

Background

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. This process has been implicated in various diseases, including ischemic stroke. Ischemic stroke leads to oxidative stress, iron overload, and reactive oxygen species (ROS) accumulation, which collectively may trigger ferroptotic neuronal cell death. However, the regulatory mechanisms of ferroptosis in stroke remain poorly understood. Previous studies have identified ataxia telangiectasia mutated (ATM), a DNA damage kinase, as a critical regulator of ferroptosis. However, the therapeutic potential of this discovery remains unknown.

Methods

We investigated the effect of ATM inhibitors, including the brain-penetrant AZD1390, on ferroptosis usingin vitro, ex vivo, andin vivomodels of ischemic stroke. Our analysis included assessments of cell viability, lipid peroxidation, ferroptosis marker expression, and infarct volume.

Result

ATM inhibitors significantly alleviated ferroptosis-induced cell death in cultured cells andex vivomurine brain slice cultures. In the oxygen-glucose deprivation (OGD) stroke model, treatment with AZD1390 reduced the expression of ferroptosis markers (xCT and PTGS2) and diminished neuronal cell death in rat and mouse brain slices. Furthermore, in a mouse model of ischemic stroke, AZD1390 decreased infarct volume confirming its therapeutic efficacyin vivo.

Conclusions

This study identifies ferroptosis as a critical mechanism in ischemic stroke-induced neuronal cell death and highlights ATM inhibition, particularly with AZD1390, as a promising therapeutic candidate for mitigating stroke-associated damage. Targeting ferroptosis may provide a translationally relevant strategy to mitigate neuronal injury and improve clinical outcomes for stroke patients.
Transcriptome differentiation inCryptomeria japonicatrees with different origins growing in the north and south of Japan
Authors: Ujino-Ihara Tokuko , Uchiyama Kentaro , Kanetani Seiichi , Suyama Yoshihisa , Tsumura Yoshihiko
Published: February 2025

Cryptomeria japonicais a coniferous species widely distributed throughout Japan and therefore adapted to various environments. To seek genes involved in the local adaptation of this species, individuals with different origins growing at three common gardens located in the south, central and north of Japan were subjected to transcriptome analysis. The transcriptome assembly, guided by whole-genome sequence ofC. japonica, resulted in 77,212 transcripts from 56,203 genes. Individuals were clustered into three genetic groups based on single nucleotide polymorphisms (SNPs) detected in 12,389 genes among them. Weighted gene co-expression network analysis (WGCNA) identified 25 gene modules. Comparison of representative gene expression patterns for each co-expression gene module with genetic differentiation predicted by SNPs revealed that one module exhibited a negative correlation and another a positive correlation across all three common gardens. While defense response genes were highly expressed in individuals from the Pacific Ocean side of Japan (omote-sugi), terpenoid metabolism genes were more expressed in individuals originating from the Sea of Japan side (ura-sugi). These results suggest that local adaptation associated with the alteration of gene regulation occurred in biotic stress response genes inC. japonica.
Assessing the impact of artifact correction and artifact rejection on the performance of SVM-based decoding of EEG signals
Authors: Zhang Guanghui , Luck Steven J.
Published: February 2025

Numerous studies have demonstrated that eyeblinks and other large artifacts can decrease the signal-to-noise ratio of EEG data, resulting in decreased statistical power for conventional univariate analyses. However, it is not clear whether eliminating these artifacts during preprocessing enhances the performance of multivariate pattern analysis (MVPA;decoding), especially given that artifact rejection reduces the number of trials available for training the decoder. This study aimed to evaluate the impact of artifact-minimization approaches on the decoding performance of support vector machines.

Independent component analysis (ICA) was used to correct ocular artifacts, and artifact rejection was used to discard trials with large voltage deflections from other sources (e.g., muscle artifacts). We assessed decoding performance in relatively simple binary classification tasks using data from seven commonly-used event-related potential paradigms (N170, mismatch negativity, N2pc, P3b, N400, lateralized readiness potential, and error-related negativity), as well as more challenging multi-way decoding tasks, including stimulus location and stimulus orientation. The results indicated that the combination of artifact correction and rejection did not improve decoding performance in the vast majority of cases. However, artifact correction may still be essential to minimize artifact-related confounds that might artificially inflate decoding accuracy. Researchers who are decoding EEG data from paradigms, populations, and recording setups that are similar to those examined here may benefit from our recommendations to optimize decoding performance and avoid incorrect conclusions.