bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed rhegmatogenous retinal detachment post macular surgery – a multicentric study
Authors: Singh Sumit Randhir , Boscia Francesco , Boscia Giacomo , Romano Mario R , Ferrara Mariantonia , Menzio Sara , Veritti Daniele , Sarao Valentina , Lanzetta Paolo , Arevalo J. Fernando , Parolini Barbara , Kuppermann Baruch , Singh Rishi , Hassan Tarek , Rezaei Kourous , Wu Lihteh , Israilevich Rachel , Starr Matthew R , Chhablani Jay
Published: February 2025

Purpose:

To report the anatomic and visual outcomes of eyes developing delayed rhegmatogenous retinal detachment (RRD) post macular surgery.

Methods:

This was a retrospective, multicentric study including eyes undergoing RRD repair at least 3 months after macular surgery for either full-thickness macular hole (FTMH) or epiretinal membrane (ERM). Anatomic and functional assessment, i.e., pre- and post-operative best corrected visual acuity (BCVA), indications and details of macular and RRD surgery, time interval from macular surgery to RRD, intraocular tamponade, location, extent of RRD, and nature of retinal break was performed.

Results:

Sixteen out of 2906 eyes (0.55%) undergoing macular surgery developed RRD after 8.4 ± 5.8 months (mean±SD). Intra-operative peripheral retina evaluation showed missed/de-novo break (11 eyes; 68.75%), no identifiable break i.e., probable microbreak (2 eyes; 12.5%), giant retinal tear (2 eyes; 12.5%), and retinoschisis related break (1 eye; 6.25%). Anatomical success i.e., attached retina after one surgery was seen in 14 eyes (87.5%). BCVA worsened from 0.6±0.3 logMAR (Snellen equivalent 20/80) at baseline to 0.9±0.8 logMAR (20/160) through the last visit (p<0.001).

Conclusion:

RRD post-macular surgery occurs predominantly via missed/de-novo retinal breaks. A significant percentage (50%) of eyes showed worse visual acuity compared to baseline despite successful retinal reattachment.
Multimodal imaging of a case of intraretinal silicone oil in an eye with retinochoroidal coloboma: Insights into possible routes of migration
Authors: Bidasaria Amit , Bhattacharya Sampurna , Juneja Aarzoo , Paul Pragati , Sen Ahana , Majumdar Bristi , Chowdhury Ruchira , Saurabh Kumar , Sinha Sourav , Roy Rupak
Published: February 2025

Purpose:

We report multimodal imaging of intraretinal silicone oil in a case operated for coloboma-associated retinal detachment (RD) and provide imaging based anatomical insights of the route on entry of intraretinal emulsified silicone oil droplets.

Method:

A 19-year-old male presented with gradual onset diminution of vision in right eye for several years with worsening for 1 month. The patient was evaluated with examination, multimodal imaging, including fundus photography, optical coherence tomography, multicolor imaging, and green reflectance imaging.

Result:

The right eye showed large inferonasal chorioretinal coloboma sparing the fovea, with dull foveal reflex on color fundus photography, loss of foveal contour with multiple hyperreflective dots predominantly collected in the outer nuclear layer in the foveal region on optical coherence tomography, greenish hue in the foveal region with feather-like projections on multicolor imaging, and crystalline deposits on green reflectance imaging. This was diagnosed as collection of intraretinal silicone oil post-RD surgery in a case of chorioretinal coloboma.

Conclusion:

We highlight a possible pathway for the intraretinal entry of emulsified silicone oil particles in a case of chorioretinal coloboma.
Modelling inflammation-induced peripheral sensitization in a dish—more complex than expected?
Authors: Li Yuening , Lock Amy , Fedele Laura , Zebochin Irene , Sabate Alba , Siddle Matthew , Cainarca Silvia , Röderer Pascal , Montag Katharina , Tarroni Paola , Brüstle Oliver , Shaw Tanya , Taams Leonie , Denk Franziska
Published: February 2025

Peripheral sensitization of nociceptors is believed to be a key driver of chronic pain states. Here, we sought to study the effects of a modified version of inflammatory soup on the excitability of human stem cell–derived sensory neurons. For this, we used a preexisting and a novel stem cell line, modified to stably express the calcium sensor GCamP6f. Upon treatment with inflammatory soup, we observed no changes in neuronal transcription or functional responses upon calcium imaging and only a very minor increase in resting membrane potential (RMP) via whole cell patch clamping: control RMP (−71.31 ± 1.1 mV) vs inflammatory soup RMP (−67.74 ± 1.29 mV), uncorrected 2-tailed independent samples t test, P = 0.0383. Similarly, small changes were observed when treating mouse primary sensory neurons with inflammatory soup. A semi-systematic reexamination of past literature further indicated that observed effects of inflammatory mediators on dissociated sensory neuron cultures are generally small. We conclude that modelling inflammation-induced peripheral sensitization in vitro is nontrivial and will require careful selection of mediators and/or more complex, longitudinal multicellular setups. Especially in the latter, our novel GCamP6f-induced pluripotent stem cell line may be of value.
Preinjury functional status is associated with functional status after hip fracture in older adults without preinjury perceived social support
Authors: Zhang Yan , Kolam Isaac , Tumin Dmitry
Published: February 2025

We investigated if preinjury perceived social support moderated the association between pre- and postinjury functional status after hip fracture in older adults. Using data from the longitudinal Health and Retirement Study (biennial interviews from 1998 to 2018), we analyzed perceived social support measured preinjury and functional status [activities of daily living (ADL) or instrumental activities of daily living (IADL) limitations] measured at pre- and postinjury interviews. Among 709 respondents, 61% anticipated social support from friends or family if they required future assistance with personal care, 16% had difficulty with ADL preinjury, and 9% had difficulty with IADL preinjury. Among 1697 postinjury follow-up interviews (mean follow-up time: 2.8 years), ADL limitations and IADL limitations were reported in 752 and 683 interviews, respectively. During follow-up, any preinjury IADL limitations were associated with more postinjury IADL limitations among people without social support [adjusted incidence rate ratio (aIRR): 2.505, 95% confidence interval (CI): 1.765–3.555] but not among people with preinjury perceived social support (aIRR: 1.355, 95% CI: 0.950–1.940, interaction P = 0.016). Any preinjury ADL limitations were associated with more postinjury ADL limitations among people with (aIRR: 1.471, 95% CI: 1.124–1.925) or without (aIRR: 2.084, 95% CI: 1.563–2.778) preinjury perceived social support. Preinjury perceived social support moderates the association between pre- and postinjury functional status in older adults experiencing a hip fracture. Older adults experiencing pre-existing IADL limitations without social support are at high risk for continued or increased activity limitations.
Content Analysis of Social Determinants of Health Accelerator Plans Using Artificial Intelligence: A Use Case for Public Health Practitioners
Authors: DePriest Kelli , Feher John , Gore Kailen , Glasgow LaShawn , Grant Clint , Holtgrave Peter , Hacker Karen , Chew Robert
Published: February 2025

Context:

Public health practice involves the development of reports and plans, including funding progress reports, strategic plans, and community needs assessments. These documents are valuable data sources for program monitoring and evaluation. However, practitioners rarely have the bandwidth to thoroughly and rapidly review large amounts of primarily qualitative data to support real-time and continuous program improvement. Systematically examining and categorizing qualitative data through content analysis is labor-intensive. Large language models (LLMs), a type of generative artificial intelligence (AI) focused on language-based tasks, hold promise for expediting content analysis of public health documents, which, in turn, could facilitate continuous program improvement.

Objectives:

To explore the feasibility and potential of using LLMs to expedite content analysis of real-world public health documents. The focus was on comparing semiautomated outputs from GPT-4o with human outputs for abstracting and synthesizing information from health improvement plans.

Design:

Our study team conducted a content analysis of 4 publicly available community health improvement plans and compared the results with GPT-4o’s performance on 20 data elements. We also assessed the resources required for both methods, including time spent on prompt engineering and error correction.

Main outcome measure(s):

Accuracy of data abstraction and time required.

Results:

GPT-4o demonstrated abstraction accuracy of 79% (n = 17 errors) compared to 94% accuracy by the study team for individual plans, with 8 instances of falsified data. Out of the 18 synthesis data elements, GPT-4o made 9 errors, demonstrating an accuracy of 50%. On average, GPT-4o abstraction required fewer hours than study team abstraction, but resource savings diminished when accounting for time for developing prompts and identifying/correcting errors.

Conclusions:

Public health professionals who explore the use of generative AI tools should approach the method with cautious curiosity and consider the potential tradeoffs between resource savings and data accuracy.
Metastasis of Urothelial Carcinoma to the Wrist
Authors: Ghorbani Hamidreza , Saber Tanha Amin , Ataei Naime , Ataei Reza , Zare Ali
Published: February 2025

A 65-year-old man presented with painless hematuria and a bladder mass, diagnosed as high-grade papillary urothelial carcinoma following transurethral resection. Considering negative metastasis workup, he was scheduled for radical cystectomy. During follow-up, he reported chronic wrist pain. A whole-body 99mTc-Methylene diphosphonate (MDP) scan showed focal uptake in the wrist, misinterpreted as arthritis and overlooked as inconsequential. Three months later, x-ray imaging revealed a lytic wrist lesion, later confirmed as metastatic carcinoma through biopsy. Immunohistochemical analysis supported the diagnosis, highlighting the importance of careful interpretation of imaging findings in patients with bladder cancer.
Prenatal sex determination illuminates the unusual adult sex ratio of a group-living lemur
Authors: Pethig Leonie , Ozgul Arpat , Heistermann Michael , Fichtel Claudia , Kappeler Peter M.
Published: February 2025

Most mammals, including humans, exhibit even or slightly male-biased birth sex ratios (BSRs) and female-biased adult sex ratios (ASRs) much later in life due to higher male mortality rates. The group-living primates of Madagascar are unusual in this respect because they lack female-biased ASRs, but it is unknown whether this is the result of skewed BSRs or sex-specific disappearance patterns. Using long-term demographic data from wild red-fronted lemurs (
Eulemur rufifrons
), we analysed their sex ratio dynamics across the lifespan. We assessed BSR via prenatal sex determination using maternal faecal oestrogen metabolite measurements during late pregnancy, confirming a visually determined equal sex ratio three months after birth, and indicating no early sex-specific mortality. Demographic analyses additionally disclosed higher female disappearance within the first 8 years of age, likely associated with reproductive effort early in life. Thereby, adult male survival had the greatest positive effect on the ASR. Our study offers a rare perspective on the dynamics of age- and sex-specific disappearance in a wild primate population, whose sex-reversed patterns may also contribute to a more general understanding of the mechanisms generating sex-biased mortality.
Hierarchical TiO
2
nanotube arrays enhance mesenchymal stem cell adhesion and regenerative potential through surface nanotopography
Authors: Tasdemir Nur Kubra , Kilicarslan Bogac , Imren Gozde , Karaosmanoglu Beren , Taskiran Ekim Z. , Bayram Cem
Published: February 2025

The concept of preconditioning mesenchymal stem cells (MSCs) under different stress conditions or with bioactive molecules is introduced to optimize their therapeutic potential. This study investigates the physicochemical effect of hierarchical TiO
2
nanotube arrays, a versatile and easy-to-prepare nanosurface, on MSC behaviour. By precisely controlling the nanotopography through anodization, we demonstrate the significant influence of surface properties on MSC adhesion, proliferation and differentiation. Electrostatic interactions between surface charge and proteins play a crucial role in these cellular responses. In addition, preconditioning MSCs under specific conditions enhances their therapeutic potential by optimizing paracrine signalling and homing properties. Higher surface charges and increasing spiky character of surface roughness of titania samples after anodization at 60 V significantly upregulated chemokine receptor type 4 (CXCR4) and vascular endothelial growth factor A (VEGFA), indicating the enhanced migratory and angiogenic potential of MSCs. The study reveals the mechanotransductive effects of nanotopography on MSC differentiation, suggesting that tailored surface features can direct cellular fate. These findings highlight the potential of hierarchical TiO
2
nanotube arrays as a promising platform for regenerative medicine, offering a novel approach to improve tissue engineering and therapeutic outcomes.
Prolonged coccidioidomycosis transmission seasons in a warming California: a Markov state transition model of shifting disease dynamics
Authors: Camponuri Simon K. , Head Jennifer R. , Collender Philip A. , Weaver Amanda K. , Heaney Alexandra K. , Colvin Kate A. , Bhattachan Abinash , Sondermeyer-Cooksey Gail , Vugia Duc J. , Jain Seema , Remais Justin V.
Published: February 2025

Coccidioidomycosis, an emerging fungal disease in the southwestern United States, exhibits pronounced seasonal transmission, yet the influence of current and future climate on the timing and duration of transmission seasons remains poorly understood. We developed a distributed-lag Markov state transition model to estimate the effects of temperature and precipitation on the timing of transmission season onset and end, analysing reported coccidioidomycosis cases (
n
= 72 125) in California from 2000 to 2023. Using G-computation substitution estimators, we examined how hypothetical changes in seasonal meteorology impact transmission season timing. Transitions from cooler, wetter conditions to hotter, drier conditions were found to significantly accelerate season onset. Dry conditions (10th percentile of precipitation) in the spring shifted season onset an average of 2.8 weeks (95% CI: 0.43–3.58) earlier compared with wet conditions (90th percentile of precipitation). Conversely, transitions back to cooler, wetter conditions hastened season end, with dry autumn conditions extending the season by an average of 0.69 weeks (95% CI: 0.37–1.41) compared with wet conditions. When dry conditions occurred in the spring and autumn, the transmission season extended by 3.70 weeks (95% CI: 1.23–4.22). With prolonged dry seasons expected in California with climate change, our findings suggest this shift will extend the period of elevated coccidioidomycosis risk.
Could a female athlete run a 4-minute mile with improved aerodynamic drafting?
Authors: da Silva Edson Soares , Hoogkamer Wouter , Kipp Shalaya , Kram Rodger
Published: February 2025

In 2023, Faith Kipyegon set the female world record for running one mile (4:07.64). Here, we quantitatively explore if improved aerodynamic drafting could allow her to run just 3.19% faster and thus break the 4-minute mile barrier. Drafting involves other athletes (pacers) running in formation around a designated athlete to reduce the aerodynamic drag force acting on the designated runner. Drafting allows the designated athlete to run faster at the same rate of metabolic energy consumption. Our overall approach was to estimate Kipyegon’s metabolic energy consumption during her mile world record performance. Then, we used empirically established relationships between horizontal resistive force, running velocity and metabolic power to estimate how much faster she could run at the same metabolic power if the aerodynamic force was reduced via drafting. Our calculations suggest that Kipyegon could run ~3:59.37 with drafting provided by one pacer in front and one in back who change out with two other pacers at 800 m.
In situ
characterisation of slip-band behaviour in ferrite under mechanical loading
Authors: Koko Abdalrhaman
Published: February 2025

This study investigates the behaviour of slip bands, terminated mid-grain in the ferrite grains of age-hardened stainless steel, under different conditions, to understand their dislocation activity and response to varying loads. The full Nye lattice curvature tensor was measured
in situ
using high-resolution electron backscatter diffraction (HR-EBSD) to estimate the total geometrically necessary dislocation (GND) density and individual mobile and immobile dislocation activity at the slip-band scale. We found that slip bands primarily consist of edge dislocations, marked by a ‘blooming zone’ at their tip, indicating significant shear deformation and loss of mobile dislocations. The blooming zone expands as the load increases while the slip-band thickness remains constant. Coupled with the correlation between mobile and immobile dislocations within the loaded slip bands observed
in situ
, we observed that the dislocation activities at the slip bands were mainly from immobile edge dislocations to maintain the geometrical distortion of the slip band.
Museum ‘dark data’ show variable impacts on deep-time biogeographic and evolutionary history
Authors: Dean Christopher D. , Thompson Jeffrey R.
Published: February 2025

The age of digitally accessible datasets has transformed palaeontology, enabling previously impossible macroevolutionary insights. However, a substantial reservoir of generally inaccessible ‘dark data’ resides within museum collections, which may alter our understanding of ancient groups and their ecological and evolutionary history. We demonstrate how the addition of data held exclusively in museums impacts our macroevolutionary understanding of an entire taxonomic group, using a dataset of Palaeozoic echinoids containing the majority of museum occurrences for the clade. We find that museum ‘dark data’ shows clear differences in composition compared to data available in the published literature and strongly impacts biogeographic patterns, increasing the average geographic range size of taxa by 35%. Global model results assessing drivers of diversity are also significantly affected by the addition of museum-only data. Conversely, ‘dark data’ have a more limited impact on the temporal ranges of taxa or estimates of overall diversity and are impacted by similar socio-geographic biases as the published record. These findings show that unpublished museum data are necessary to obtain a complete understanding of macroevolutionary patterns in deep-time, illustrating the importance of the collection, curation, digitization and continued care of ‘dark data’ in the age of ‘Big Data’ in palaeobiology.
Disease from leaves to landscapes: viral hotspots are determined by spatial arrangement and phytochemistry of host plants in specialist caterpillars
Authors: Christensen Tara , Smilanich Angela M. , Carper Adrian , Peechatt Victoria , Bowers M. Deane , Forister Matthew L. , Teglas Mike B. , Hurtado Paul , Dyer Lee A.
Published: February 2025

Although infectious diseases play a critical role in population regulation, our knowledge of complex drivers of disease for insects is limited. We conducted a field study on Baltimore checkerspot caterpillars (
Euphydryas phaeton
), chemical specialists on plants containing iridoid glycosides (IGs), to investigate the roles of host plant, phytochemistry, ontogeny and spatial associations in determining viral prevalence. We analysed individuals for viral presence and loads, quantified leaf IG concentrations from their native and novel host plants, and sequestered IGs in caterpillars. We found proximate caterpillar groups had greater similarity in infection prevalence, with areas of high prevalence indicating viral hotspots. Underlying variation in host plant chemistry corresponded to differences in viral prevalence. Furthermore, we used structural equation modeling to examine causal drivers of infection prevalence and loads. Advanced ontogeny was associated with increased viral prevalence and loads, as well as decreased sequestration of IGs. Infection loads were lower on the novel host plant, but prevalence was slightly higher, partially explained by decreased sequestration of IGs. Altogether, our findings reveal that spatial proximity, ontogeny, host plant species and secondary phytochemistry can all contribute to structuring infection risk, and thus offer insight into causal drivers of disease prevalence in complex plant–insect systems.
Vogesella oryzagri sp. nov., isolated from the rhizosphere of rice and in silico genome mining for the prediction of biosynthetic gene clusters
Authors: Huq Md. Amdadul , Kim Yeon-Ju , Rahman M. Mizanur , Alam Md. Morshedul , Srinivasan Sathiyaraj , Kang Kwon-Kyoo , Akter Shahina
Published: February 2025

A Gram-stain-negative, aerobic, rod-shaped, motile and flagellated novel bacterial strain, designated MAHUQ-64T, was isolated from the rhizosphere of rice. The colonies were observed to be creamy white-coloured, smooth, spherical and 0.5–1.1 mm in diameter when grown on Reasoner’s 2A agar medium for 2 days. Strain MAHUQ-64T was able to grow at 10–40 °C, at pH 5.0–9.5 and in the presence of 0–2.0% NaCl (w/v). The strain was positive for both catalase and oxidase tests. The strain was positive for hydrolysis of l-tyrosine. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Vogesella and is closely related to Vogesella oryzae L3B39T (98.6% sequence similarity) and Vogesella facilis TTM-24T (98.2%). The novel strain MAHUQ-64T has a draft genome size of 3 827 146 bp (22 contigs), annotated with 3612 protein-coding genes, 74 tRNA and 4 rRNA genes. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain MAHUQ-64T and its closest member V. oryzae L3B39T were 86.5 and 33.4%, respectively. In silico genome mining revealed several biosynthetic gene clusters in the genome of the novel strain MAHUQ-64T. The genomic DNA G+C content was determined to be 63.4 mol%. The predominant isoprenoid quinone was ubiquinone-8. The major fatty acids were identified as summed feature 3 (comprising C16  :  1
ω7c and/or C16  :  1
ω6c) and C16  :  0. Based on dDDH, ANI value, genotypic analysis and chemotaxonomic and physiological data, strain MAHUQ-64T represents a novel species within the genus Vogesella, for which the name Vogesella oryzagri sp. nov. is proposed, with MAHUQ-64T (=KACC 22245T=CGMCC 1.19000T) as the type strain.
Multi-view gene panel characterization for spatially resolved omics
Authors: Kim Daniel , Ding Wenze , Shaw Akira Nguyen , Torkel Marni , Turtle Cameron J , Yang Pengyi , Yang Jean
Published: February 2025

Spatially resolved transcriptomics has transformed our ability to study complex tissues at the cellular and subcellular resolution. However, targeted spatial technologies require pre-selected gene panels, which are typically curated based on existing biological knowledge and prior research hypotheses. While current methods often prioritize capturing cell type information, we argue that an effective gene panel should also capture cell type diversity, cell states, pathway-level information, and minimize redundancy. To address these broader requirements, we developed a gene panel characterization platform that characterizes panels across multiple perspectives, thus allowing us to compare panels comprehensively. Notably, computationally constructed gene panels performed competitively in capturing major cell types when compared to our in-house manually curated panel. However, refined manual curation offered distinct advantages, particularly in capturing minor and rare cell types and exhibited lower information redundancy comparatively. Building on this framework, we integrated these metrics into a deep learning platform, panelScope, leveraging them as a loss function to design holistic gene panels. Using an acute myeloid leukemia (AML) dataset with 42 well-defined cell types and the 5K Xenium panel from 10X Genomics, we demonstrate the utility of our framework in comprehensively characterizing gene panels, enabling the design of tailored panels that address diverse research needs.
Integration of CA attention and KAN algorithm to predict EGFR mutation status in lung cancer
Authors: Jia Nan , Xing Junfeng , Tang Siyuan , Liu Liang , Guo Jingxia , Wu Yan , Bai Jiniu , Li Yan
Published: February 2025

Epidermal Growth Factor Receptor (EGFR) mutations are critical biomarkers for targeted therapies in non-small cell lung cancer (NSCLC). However, conventional diagnostic methods rely on invasive tissue biopsies, which are costly, time-consuming, and pose significant limitations. As an alternative, non-invasive approaches using lung CT imaging to predict EGFR mutation status have gained attention for their rapid and user-friendly nature. This study explores EGFR mutation prediction by analyzing seven distinct 2D regions of interest (ROI): the nodule itself, 2-pixel, 4-pixel, and 6-pixel extensions around the nodule, CT slices containing the nodule, single-lung segmented images with the nodule, and bilateral lung segmented images with the nodule. We developed a deep learning model combining EfficientNet-B0 with a Coordinate Attention (CA) mechanism, replacing the traditional MLP classifier with a KAN classifier. Results show that analyzing single-lung images containing the nodule captures additional relevant information, achieving the highest predictive performance. This suggests that regions surrounding the nodule contain valuable discriminatory biomarkers. The model achieved 92.73% accuracy on the single-lung test set with only 6.82M parameters, demonstrating its potential as a clinical tool to optimize targeted treatment decision-making.
The vaginal microbiota composition influences cervicovaginal and systemic inflammation induced byChlamydia trachomatisinfection
Authors: Adapen Cindy , Réot Louis , Nunez Natalia , Cannou Claude , Marlin Romain , Lemaitre Julien , Lakoum Sabrine , Diry Ségolène , d’Agata Léo , Gros Wesley , Gallouët Anne-Sophie , Leonec Marco , Bossevot Laetitia , Dereuddre-Bosquet Nathalie , Le Grand Roger , Nugeyre Marie-Thérèse , Menu Elisabeth
Published: February 2025

Background

Chlamydiosis, a sexually transmitted infection (STI) induced byChlamydia trachomatis(CT), increases local inflammation (cytokine production, recruitment of immune cells such as neutrophils). Few is known on the impact of CT infection on the phenotype of cervicovaginal neutrophils. Vaginal microbiota (VM) is a key factor in the regulation of local immune responses and STI acquisition whereLactobacillus sppare associated with protection. In this study, the VM of cynomolgus macaques was enriched withLactobacillus crispatusafter local metronidazole treatment followed by repeated intravaginal inoculations of CT. VM composition, CT infection and local and systemic inflammation were monitored.

Results

First, we observed that metronidazole treatment induced drastic modifications of the VM by reducing the abundance of several anaerobes and increasing the number of naturalLactobacillus spp(Lactobacillus johnsoniiand its prophage mainly) as well as opportunistic bacteria (Streptococcus sppandStaphylococcus spp). After CT exposure ofL. crispatustreated or not animals, a non-persisting CT infection and no association betweenL. crispatusenrichment and a lower susceptibility to CT infection were detected. However, the production of serum specific anti-CT IgG was higher inL. crispatustreated animals. Moreover, the production of anti-CT IgG was associated with various bacterial species. An increased production of peripheral blood cytokines after CT infection was observed in untreated animals, whereasL. crispatustreated animals exhibited an increased production of cervicovaginal cytokines. Peripheral blood neutrophils were more mature and activated after CT infection/inoculation in both groups. Very few alterations of the cervicovaginal neutrophil phenotype were noticed after CT infection. Markers expressed on neutrophils were associated with bacterial species and differences were detected according to groups.

Conclusion

These results suggest a better local immune response as well as a better control on systemic inflammation upon CT infection inL. crispatustreated animals compared to untreated animals. Indeed, it highlight an impact of VM composition on the local and systemic immune responses induced by CT infection. This study confirmed that VM composition can be a powerful tool to modulate local inflammation and STI susceptibility.
Calcium starvation leads to strain-specific gene regulation of lipid and carotenoid production inMucor Circinelloides
Authors: Baalsrud HT , Byrtusova D , To TH , Larsen IE , Bøe VA , Grønvold L , Fu J , Árnyasi M , Shapaval V , Sandve SR
Published: February 2025

Abstract

Fungi are pivotal in transitioning to a bio-based, circular economy due to their ability to transform organic material into valuable products such as organic acids, enzymes, and drugs.Mucor circinelloidesis a model organism for studying lipogenesis and it particularly promising for its metabolic capabilities in producing oils like TAGs and carotenoids, influenced by environmental factors such as nutrient availability. Notably, strains VI04473 and FRR5020 have been identified for their potential in producing single-cell oils and carotenoids, respectively. Calcium starvation have previously been shown to have strain-specific effects, with VI04473 accumulating more lipids and FRR5020 producing more carotenoids. Here we used genome sequencing, comparative genomics, transcriptomics, and metabolite phenotyping to explore the genetic basis of lipid and carotenoid production under calcium starvation in these strains. We found extensive genomic rearrangements between these strains, as well as low conservation of gene regulatory responses to calcium depletion. This lack of conservation also applies to genes involved in lipid and carotenoid production, i.e. the lipidome. Several pathways show divergent regulation between strains, which explains the phenotypic divergence between VI04473 and FRR5020. The complex gene family evolution of several lipidome genes probably also affected specialization of these strains to calcium stress. Our study sheds light on the complexity of the evolution of metabolic networks inM. circinelloides. Understanding these genetic underpinnings can optimize the industrial use ofM. circinelloides, enhancing lipid productivity and stress tolerance, and tailoring metabolic profiles for specific applications. This research advances our knowledge on complexity of fungal lipid metabolism and the role of calcium in regulating metabolic pathways.
PEAKQC: Periodicity Evaluation in scATAC-seq data for quality assessment
Authors: Detleffsen Jan , Kuenne Carsten , Bentsen Mette , Looso Mario
Published: February 2025

ATAC-seq is a common protocol to identify regulatory regions in the genome. While quality control (QC) standards are well-established for bulk ATAC-seq, application to single-cell ATAC-seq remains challenging due to data sparsity, noise, and a lack of consensus on effective QC metrics and thresholds. Existing methods, such as fragment length ratio offer limited resolution and fail to fully utilize fragment length distribution (FLD) patterns. We present PEAKQC, a Python-based tool designed to assess single-cell ATAC-seq data quality using a wavelet-based convolution of FLD patterns. Benchmarking PEAKQC against established QC metrics demonstrates an overall more consistent, linear quality assessment of ATAC data. PEAKQC improves downstream analyses by effectively filtering low-quality cells while preserving biologically meaningful data. When combined with other metrics, such as the ratio of fragments in peaks and total counts, PEAKQC enhances clustering accuracy and cell-type identification. The tool is modular, easily installable via Python Package Index, and integrates seamlessly into Python-based single-cell analysis frameworks. PEAKQC provides a robust and scalable solution for single-cell ATAC-seq QC, addressing current gaps in the field and suggesting FLD patterns as a new standard for data quality assessment.
Cytokine-Induced Transcriptional Changes in Human Neutrophils Reveal Immune Regulatory Plasticity
Authors: Thomas Huw B , Edwards Steven W , Wright Helen L
Published: February 2025

Neutrophils are the major cellular constituent of blood leukocytes and play a central role in the inflammatory response, producing an array of destructive molecules and antimicrobial proteases that characterise the cells as front-line defenders of the innate immune system, crucial to host defence. It is now appreciated that neutrophils produce and respond to a variety of inflammatory signals and are able to regulate both the innate and adaptive immune responses. However, the mechanisms by which neutrophils respond to different inflammatory signals to regulate their own function and the functions of other immune cells are incompletely defined. In this study, we performed RNA sequencing with bioinformatics analysis of healthy human neutrophils exposed for 1h to a range of pro-inflammatory cytokines. GM-CSF and TNFα induced significant changes in expression in the most transcripts including activation of genes regulating apoptosis and genes encoding cytokines and chemokines that can drive the differentiation and activation of CD4 T cells. Stimulation of neutrophils with G-CSF, IFNα, IFN γ, IL-1β, or IL-8 resulted in expression of discrete gene sets and differential activation of signalling pathways including changes in cell adhesion and migration, immune receptor expression, apoptosis, and production of pro-inflammatory prostaglandins. This work defines the differential gene expression patterns in neutrophils exposed to different regulatory cytokines. This is important in both increasing our understanding of the role of neutrophils in driving innate and adaptive immune responses and, importantly, for deconvoluting the neutrophil gene expression signatures observed in inflammatory diseases.
THE INFLUENCE OF FOOD ABUNDANCE CHANGE ON SEARCH AND ATTACK BEHAVIOR OF INSECTIVOROUS BIRD IN THE MONTE DESERT, ARGENTINA
Authors: Guerra-Navarro Carolina , Cueto Victor R
Published: February 2025

Bird foraging is a combination of two behaviors, the search movements to locate preys and the attack maneuvers to catch them. However, the first behavior is poorly studies. Hear we determine the searching movements and attack maneuvers of three species of insectivorous birds in the central Monte desert, Argentina and evaluate if these two components of the foraging behavior change as a function of interannual variation in the availability of food resources. During three years we studied the search movements and attack maneuvers of three insectivorous bird species in the foliage of Neltuma flexuosa trees and simultaneously evaluated the abundance and biomass of their prey. We found that arthropod abundance increased in the last year, although biomass was low, due to the greater number of small arthropods (less than 0.2 mg) in that year. During the first and second year the main capture maneuver of Grey-crowned Tyrannulet (Serpophaga griseicapilla) was sally-hover and it moved among the foliage using flight movements, but in the third year a greater use of gleaning maneuvers was observed and its main foraging movements were jumping on the branches. Greater Wagtail-tyrant (Stigmatura budytoides) used both sally-hovering and gleaning maneuvers in the first and second years, however it used glean more frequently and performed more jumping movements in the third year Ringed Warbling-Finch (Microspingus torquata) showed very stereotyped behavior throughout the study period, using only gleaning and jumping as foraging strategies. The increase of small prey in the last year could have determined the changes in attack maneuvers and searching movements of Grey-crowned Tyrannulet and Greater Wagtail-tyrant. The gleaning maneuver might be more suitable for capturing small prey, probably because birds detect them better at close range, and moving with short movements such as jumping might allow them to explore branches and foliage in greater detail. For Ringed Warbling-Finch, given the characteristics of its feeding behavior, the above-mentioned changes did not influence the way it search and attack prey. The interannual changes observed in searching and capture behavior provide valuable information about ecological flexibility of insectivorous birds that may be advantageous when they confront variable climates and food fluctuations such as in desert environments.
A spontaneous mutation in a key C4pathway gene significantly alters leaf δ13C uncoupling its relationship with WUE and photosynthetic performance inZea mays
Authors: Twohey Robert J. , Crawford Joseph D , Runyon Matthew M. , Xie Jiayang , Leakey Andrew D B , Cousins Asaph B. , Studer Anthony J.
Published: February 2025

Increases in global temperature and drought are negatively impacting the yields of major crops. Therefore, targeted improvements to intrinsic water use efficiency (WUEi) are needed to reduce the water required for agricultural production. While it is very time-consuming to directly measureWUEi, stable carbon isotope ratios (δ13C) are a reliable high throughput proxy trait for quantifyingWUEiin C3species. While genetic studies have improved our understanding of the relationship betweenWUEiand δ13C in C4species, the knowledge needed to implement δ13C in breeding schemes is incomplete. Using aZea maysline with an extremely negative δ13C value, a quantitative genetics approach was used to identify a large deletion in carbonic anhydrase1 (cah1). Carbonic anhydrase is the first enzymatic step of the C4photosynthetic pathway and is known to affect δ13C. Surprisingly, the line with the mutant allele has significantly higher carbonic anhydrase activity with a concurrent reduction in δ13C, opposite of what would be expected based on C4carbon isotope fractionation theory. These observed decouple δ13C andWUEi, which calls for further investigation into carbon isotope discrimination in C4species.
Multi-omic subtypes of Alzheimer’s dementia are differentially associated with psychological traits
Authors: Zammit Andrea R. , Yu Lei , Poole Victoria N. , Arfanakis Konstantinos , Schneider Julie A. , Petyuk Vladislav A. , De Jager Philip L. , Kaddurah-Daouk Rima , Iturria-Medina Yasser , Bennett David A.
Published: February 2025

Importance

Psychological traits reflecting neuroticism, depressive symptoms, loneliness, and purpose in life are risk factors of AD dementia; however, the underlying biologic mechanisms of these associations remain largely unknown.

Objective

To examine whether one or more multi-omic brain molecular subtypes of AD is associated with neuroticism, depressive symptoms, loneliness, and/or purpose in life.

Design

Two cohort-based studies; Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP), both ongoing longitudinal clinical pathological studies that began enrollment in 1994 and 1997.

Setting

Older priests, nuns, and brothers from across the U.S. (ROS) and older adults from across the greater Chicago metropolitan area (MAP).

Participants

822 decedents with multi-omic data from the dorsolateral prefrontal cortex.

Exposure(s)

Pseudotime, representing molecular distance from no cognitive impairment (NCI) to AD dementia, and three multi-omic brain molecular subtypes of AD dementia representing 3 omic pathways from no cognitive impairment (NCI) to AD dementia that differ by their omic constituents.

Main outcome(s) and measure(s)

We first ran four separate linear regressions with neuroticism, depressive symptoms, loneliness, purpose in life as the outcomes, and pseudotime as the predictor, adjusting for age, sex and education. We then ran four separate analyses of covariance (ANCOVAs) with Bonferroni-corrected post-hoc tests to test whether the three multi-omic AD subtypes are differentially associated with the four traits, adjusting for the same covariates.

Result

Pseudotime was positively associated (p<0.05) with neuroticism and loneliness. AD subtypes were differentially associated with the traits: AD subtypes 1 and 3 were associated with neuroticism; AD subtype 2 with depressive symptoms; AD subtype 3 with loneliness, and AD subtype 2 with purpose in life.

Conclusions and Relevance

Three multi-omic brain molecular subtypes of AD dementia differentially share omic features with four psychological risk factors of AD dementia. Our data provide novel insights into the biology underlying well-established associations between psychological traits and AD dementia.

Key points

Question

Are three distinct multi-omic brain molecular subtypes of Alzheimer’s disease (AD) dementia associated with four well-established psychological AD risk factors (neuroticism, depressive symptoms, loneliness and purpose in life)?

Findings

We found differential associations: AD subtypes 1 and 3 were associated with neuroticism, AD subtype 2 was associated with depressive symptoms, AD subtype 3 was associated with loneliness; and AD subtype 2 was associated with purpose in life.

Meaning

Psychological risk factors might be associated with AD dementia via shared multi-omic molecular pathways.
Penetration of Inner Scleral Fibers into Peripapillary Sclera Revealed by Polarization-Sensitive OCT
Authors: Xiong Jianping , Lu Hongshuang , Zhou Nan , Wu Yijin , Yamanari Masahiro , Takahashi Hiroyuki , Okamoto Michiaki , Sugisawa Keigo , Yoshida Takeshi , Chen Changyu , Wang Yining , Wang Ziye , Ohno-Matsui Kyoko
Published: February 2025

Purpose

To determine the structural characteristics of the peripapillary sclera in myopic eyes using polarization-sensitive optical coherence tomography (PS-OCT).

Methods

Patients with myopia who underwent PS-OCT imaging between April and June 2023 were studied. The intensity, optic axis, and birefringence of PS-OCT images were analyzed to determine the surface of the lamina cribrosa (LC). The direction and arrangement of the scleral collagen fibers in the peripapillary region and scleral ridge were determined.

Results

One hundred and ten eyes of 59 patients with myopia (mean axial length, 30.00 ± 1.98 mm) were studied. The scleral fibers around the optic nerve were arranged circularly in all eyes regardless of the presence or size of the peripapillary atrophy. Inner scleral fibers that penetrated beneath this circular arrangement were detected in 98 eyes (89.1%). There was a Y-shaped split at the point of penetration in 77 eyes (70.0%). The integrity of the circular arrangement and penetrating scleral fiber complexes remained intact even in cases of severe peripapillary scleral deformation. A scleral ridge was identified in 27 eyes (24.5%), and it appeared as a full-thickness protrusion composed primarily of outer scleral fibers. The ridge was consistently located outside the circular arrangement.

Conclusions

The penetration of the radial inner scleral fibers into the circular arrangement and extension to the LC suggest that they act as stabilizing anchors for the circular structure. The differences of the scleral ridges from those in eyes with dome-shaped macula suggest that unique mechanisms cause the scleral differences.
Dysregulation of the actin cytoskeleton and FMRP causes polar body protrusion defects in human fragile X premutation and aged oocytes
Authors: Gerhardt Jeannine , McCarter Kelly , Deshpande Madhura , Romanski Phillip , Stratopoulou Christina Anna , Zaninovic Nikica , Tareen Momina , Al-Mousawi Razan , James Daylon , Madireddy Advaitha , Rosenwaks Zev
Published: February 2025

Women carrying the fragile X premutation (55-200 CGG repeat expansion, PM) are at risk for developing fragile X-associated primary ovarian insufficiency (FXPOI), which is preceded by fragile X-associated diminished ovarian reserve (FXDOR). So far, the cause of FXDOR/FXPOI could not be comprehensively examined due to the scarcity of human ovarian tissue and oocytes. From studies in model systems, it was proposed that molecular abnormalities within the ovaries or a diminished primordial follicle pool cause FXDOR/FXPOI. To elucidate the defects instigating FXDOR/FXPOI, we examined human oocytes obtained from PM carriers undergoing in vitro fertilization (IVF). We found that the primordial follicle pool was not affected but the number of MII oocytes was reduced suggesting that the maturation of the oocytes is constrained in PM carriers. Furthermore, immature PM oocytes contained abnormal inclusions, irregular ubiquitin levels and DNA breaks. Despite these defects PM oocytes passed the DNA damage checkpoints. However, in anaphase I PM oocytes failed to initiate the protrusion of the first polar body. In addition, these oocytes amassed bundle actin structures, lacked an actin cap and had elevated profilin1 level. Profilin1 limits the formation of branched actin structures which are necessary for actin cap formation and membrane protrusions. Surprisingly, our results suggest that in PM oocytes an increase in FMRP elevates the profilin1 translation, which leads to the cytoskeleton defects and deficiencies in formation of the first polar body. We also analyzed the decline of MII oocytes in aging human ovaries. Similar, we found that the profilin1 expression and formation of the actin cytoskeleton were dysregulated due to appearance of cytoplasmatic FMRP foci in aged human oocytes. Thus, these results reveal that defects during anaphase I hinder the maturation of human oocytes resulting in FXDOR/FXPOI in PM carriers and a reduction in mature oocytes in women with advanced maternal age.
Estimating Direct and Spillover Vaccine Effectiveness with Partial Interference under Test-Negative Design Sampling
Authors: Jiang Cong , Fang Fei , Talbot Denis , Schnitzer Mireille E
Published: February 2025

The Test-Negative Design (TND), which involves recruiting care-seeking individuals who meet predefined clinical case criteria, offers valid statistical inference for Vaccine Effectiveness (VE) using data collected through passive surveillance, making it cost-efficient and timely. Infectious disease epidemiology often involves interference, where the treatment and/or outcome of one individual can affect the outcomes of others, rendering standard causal estimands ill-defined; ignoring such interference can bias VE evaluation and lead to ineffective vaccination policies. This article addresses the estimation of causal estimands for VE in the presence of partial interference using TND samples. Partial interference means that the vaccination of units within the same group/cluster may influence the outcomes of other members of the cluster. We define the population direct, spillover, total, and overall effects using the geometric risk ratio, which are identifiable under TND sampling. We investigate various stochastic policies for vaccine allocation in a counterfactual scenario, and identify policy-relevant VE causal estimands. We propose inverse-probability weighted (IPW) estimators for estimating the policy-relevant VE causal estimands with partial interference under the TND, and explore the statistical properties of these estimators.