bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale network mechanisms underlying postoperative cognitive improvement after spine surgery
Authors: Antonenko Daria , Leroy Sophie , Müller Jonas , Behr Frederik , Fromm Anna E. , von Dincklage Falk , Fleischmann Robert
Published: January 2025

Background:

The outcome of major surgery is determined not only by the success of the procedure itself but also by its neurocognitive effects. We previously reported improved cognition following spine surgery (Müller et al. 2023 Spine), but the mechanisms underlying these changes remain unknown.

Materials and methods:

We analyzed resting-state functional magnetic resonance images of 79 patients (mean/SD age: 71/7 years) acquired at baseline in this previously published trial. For 26 patients, data was additionally available at 3-months follow-up visits. To delineate large-scale connectivity, we calculated functional connectivity (FC) within and between three core neural networks, the central executive network (CEN), the salience network (SAL), and the default mode network (DMN).

Results:

FC between CEN and SAL predicted cognitive improvement (beta = 0.36, 95%-CI 0.28 to 0.45, P = 0.033). Average FC between all nodes of the CEN showed changes toward an increase after surgery (beta = 0.057, 95%-CI −0.01 to 0.123, P = 0.086). Further seed-based FC analyses revealed that this increase was most pronounced in the functional coupling between left dorsolateral prefrontal and right posterior parietal cortex (beta = 0.10, T(24) = 2.73, P
unc = 0.012, P
FDR = 0.035). The increase of CEN-FC correlated with individual enhancements of executive scores (beta = 0.34, 95%-CI 0.32 to 0.36, P = 0.034).

Conclusion:

Integration of activity between the CEN and SAL networks predicted postoperative cognitive improvements, suggesting that less segregated large-scale functional networks may facilitate beneficial cognitive changes following surgery. Postoperative increases in functional coupling may serve as a biomarker for individual improvements in executive functions. These results indicate that surgery should not be routinely deferred in elderly patients due to concerns about postoperative neurocognitive complications. Moreover, our findings highlight potential targets for non-invasive brain stimulation interventions aimed at preventing neurocognitive complications.
Use of Artificial Intelligence in Lower Gastrointestinal and Small Bowel Disorders
Authors: Parikh Mili , Tejaswi Sooraj , Girotra Tavishi , Chopra Shreya , Ramai Daryl , Tabibian James H. , Jagannath Soumya , Ofosu Andrew , Barakat Monique T. , Mishra Rajnish , Girotra Mohit
Published: January 2025

Machine learning and its specialized forms, such as Artificial Neural Networks and Convolutional Neural Networks, are increasingly being used for detecting and managing gastrointestinal conditions. Recent advancements involve using Artificial Neural Network models to enhance predictive accuracy for severe lower gastrointestinal (LGI) bleeding outcomes, including the need for surgery. To this end, artificial intelligence (AI)-guided predictive models have shown promise in improving management outcomes. While much literature focuses on AI in early neoplasia detection, this review highlights AI’s role in managing LGI and small bowel disorders, including risk stratification for LGI bleeding, quality control, evaluation of inflammatory bowel disease, and video capsule endoscopy reading. Overall, the integration of AI into routine clinical practice is still developing, with ongoing research aimed at addressing current limitations and gaps in patient care.
Topical Protection of Esophageal Mucosa as a New Treatment of GERD
Authors: Savarino Vincenzo , Visaggi Pierfrancesco , Marabotto Elisa , Bertin Luisa , Pasta Andrea , Calabrese Francesco , Zentilin Patrizia , Ghisa Matteo , Ribolsi Mentore , Mari Amir , Tolone Salvatore , de Bortoli Nicola , Savarino Edoardo V.
Published: January 2025

Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients. Accordingly, the reinforcement of protective mechanisms of esophageal mucosa by topical therapies has become a novel treatment target. Alginate, the combination of hyaluronic acid+chondroitin sulphate and Poliprotect have been shown to adhere to esophageal mucosa and to have good protective properties. Several placebo-controlled clinical trials have shown that these compounds, given alone or as add-on therapy for short periods, enable to relieve symptoms and to improve the quality of life in NERD patients. Further studies are needed to confirm the above results and to find new mucosal protectants in order to improve the management of NERD patients.
Home Medication Regimen Complexity in Newly Diagnosed Pediatric Oncology Patients
Authors: Skipper K. Elizabeth , Wadhwa Aman , Rice Marti , York Jocelyn , Bhatia Smita , Landier Wendy
Published: January 2025

Background

Parents of children newly diagnosed with cancer require specialized education to provide care for their child at home, including the management of complex medication regimens.

Objective

To assess the complexity of home medication regimens in a cohort of newly diagnosed pediatric oncology patients.

Methods

We inventoried and categorized all discharge medications for each patient and used the Medication Regimen Complexity Index (MRCI) to quantify the complexity of the prescribed medication regimens. We used logistic regression to identify patient sociodemographic and clinical characteristics significantly (P < .05) associated with higher medication burden (ie, higher total MRCI scores).

Results

The cohort consisted of 105 newly diagnosed pediatric oncology patients initially hospitalized between December 2016 and February 2019 (61.9% male, 65.7% non-Hispanic White, 65.7% leukemia or lymphoma; median [range] age at diagnosis, 7.1 [0.4-17.7] years; median [range] number of discharge medications, 9 [1-14]). The proportion of patients prescribed ≥1 medication in each pharmacologic category was as follows: antiemetics, 94.3%; antimicrobials, 93.3%; pain management, 88.6%; oral care, 86.7%; stool softeners/laxatives, 81.0%; gastrointestinal protectants, 60.0%; cancer-directed therapy, 51.5%, other supportive therapies, 49.5%, other, 27.6%. Characteristics associated with ≥ median (≥33.0) MRCI score included a diagnosis of leukemia or lymphoma (odds ratio, 2.7; 95% confidence interval, 1.1-6.6; P = .027; comparison: solid tumor) and older age (odds ratio, 1.1 per year; 95% confidence interval, 1.0-1.2; P = .020).

Conclusions

Most children newly diagnosed with cancer are discharged with complex medication regimens that parents/caregivers must manage at home.

Implications for Practice

Nurses can use these findings to develop tailored medication education plans for parents/caregivers of newly diagnosed pediatric oncology patients.
Predictors of Palliative Care Self-efficacy Among Health Care Professionals in Vietnam
Authors: Huynh Nhien Thi Thuy , To Nghi Minh , Hoang Huyen Thi Mong , Lam Hoa Thanh , Kao Chi-Yin
Published: January 2025

This study aimed to investigate predictors of palliative care self-efficacy among Vietnamese health care professionals. An online descriptive cross-sectional survey was conducted at 1 hospital in Vietnam. Participants completed survey questionnaires including demographics, professional experience, Palliative Care Self-Efficacy, Palliative Care Quiz for Nursing, Frommelt Attitudes Toward Care of the Dying–Form B, Santa Clara Brief Compassion Scale, and Self-Compassion Scale–Short Form. After data collection, descriptive statistics and stepwise regression were applied for data analysis. A total of 128 nurses and 42 physicians completed the survey. The mean score for palliative care self-efficacy was 27.6 ± 10.6 out of 48. The results indicated that compassion for others, self-compassion, and palliative care knowledge explained 17.8% of health care professionals' self-efficacy levels. This study supports the positive relationship between self-efficacy, compassion for others, and self-compassion among health care professionals, underscoring the need for incorporating compassion training into the curriculum and the training program.
State-space modelling using wastewater virus and epidemiological data to estimate reported COVID-19 cases and the potential infection numbers
Authors: Kadoya Syun-suke , Li Yubing , Wang Yilei , Katayama Hiroyuki , Sano Daisuke
Published: January 2025

The current situation of COVID-19 measures makes it difficult to accurately assess the prevalence of SARS-CoV-2 due to a decrease in reporting rates, leading to missed initial transmission events and subsequent outbreaks. There is growing recognition that wastewater virus data assist in estimating potential infections, including asymptomatic and unreported infections. Understanding the COVID-19 situation hidden behind the reported cases is critical for decision-making when choosing appropriate social intervention measures. However, current models implicitly assume homogeneity in human behaviour, such as virus shedding patterns within the population, making it challenging to predict the emergence of new variants due to variant-specific transmission or shedding parameters. This can result in predictions with considerable uncertainty. In this study, we established a state-space model based on wastewater viral load to predict both reported cases and potential infection numbers. Our model using wastewater virus data showed high goodness-of-fit to COVID-19 case numbers despite the dataset including waves of two distinct variants. Furthermore, the model successfully provided estimates of potential infection, reflecting the superspreading nature of SARS-CoV-2 transmission. This study supports the notion that wastewater surveillance and state-space modelling have the potential to effectively predict both reported cases and potential infections.
Structure of WzxE the lipid III flippase for Enterobacterial Common Antigen polysaccharide
Authors: Le Bas Audrey , Clarke Bradley R. , Teelucksingh Tanisha , Lee Micah , El Omari Kamel , Giltrap Andrew M. , McMahon Stephen A. , Liu Hui , Beale John H. , Mykhaylyk Vitaliy , Duman Ramona , Paterson Neil G. , Ward Philip N. , Harrison Peter J. , Weckener Miriam , Pardon Els , Steyaert Jan , Liu Huanting , Quigley Andrew , Davis Benjamin G. , Wagner Armin , Whitfield Chris , Naismith James H.
Published: January 2025

The enterobacterial common antigen (ECA) is conserved in Gram-negative bacteria of the
Enterobacterales
order although its function is debated. ECA biogenesis depends on the Wzx/Wzy-dependent strategy whereby the newly synthesized lipid-linked repeat units, lipid III, are transferred across the inner membrane by the lipid III flippase WzxE. WzxE is part of the Wzx family and required in many glycan assembly systems, but an understanding of its molecular mechanism is hindered due to a lack of structural evidence. Here, we present the first X-ray structures of WzxE from
Escherichia coli
in complex with nanobodies. Both inward- and outward-facing conformations highlight two pairs of arginine residues that move in a reciprocal fashion, enabling flipping. One of the arginine pairs coordinated to a glutamate residue is essential for activity along with the C-terminal arginine rich tail located close to the entrance of the lumen. This work helps understand the translocation mechanism of the Wzx flippase family.
Dynamic colour change in zebrafish (
Danio rerio
) across multiple contexts
Authors: Ackroyd Ella J. , Heathcote Robert J. P. , Ioannou Christos C.
Published: January 2025

Many animals are capable of rapid dynamic colour change, which is particularly well represented in fishes. The proximate mechanisms of dynamic colour change in fishes are well understood; however, less attention has been given to understanding its ecological relevance. In this study, we investigate dynamic colour change in zebrafish (
Danio rerio
) across multiple contexts, using a protocol to image the colouration of live fish without anaesthesia under standardized conditions. We show that zebrafish respond to different visual environments by darkening their overall colouration in a dark environment and lightening in a light environment. This is consistent with crypsis through background matching as a function of dynamic colour change. Additionally, we find that zebrafish use dynamic colour change to increase the internal contrast of their striped patterning in the presence of conspecifics. We speculate that this may function in social signalling and/or dazzle colouration. We find no effect of a predator stimulus on dynamic colour change. Finally, we discuss the potential for zebrafish to use multiple colouration strategies simultaneously as distance-dependent effects, considering the typical viewing distances of zebrafish and their predators.
Cranial osteology and neuroanatomy of the late Permian reptile
Milleropsis pricei
and implications for early reptile evolution
Authors: Jenkins Xavier A. , Benson Roger B. J. , Ford David P. , Browning Claire , Fernandez Vincent , Griffiths Elizabeth , Choiniere Jonah , Peecook Brandon R.
Published: January 2025

Millerettidae are a group of superficially lizard-like Permian stem reptiles originally hypothesized as relevant to the ancestry of the reptile crown group, and particularly to lepidosaurs and archosaurs. Since the advent of cladistics, millerettids have typically been considered to be more distant relatives of crown reptiles as the earliest-diverging parareptiles and therefore outside of ‘Eureptilia’. Despite this cladistic consensus, some conspicuous features of millerettid anatomy invite reconsideration of their relationships. We provide a detailed description of the late Permian millerettid
Milleropsis pricei
using synchrotron X-ray phase-contrast micro-computed tomography focusing on the cranial anatomy of three individuals known from a burrow aggregation. Our data reveal a suite of neuroanatomical features
Milleropsis
shares with neodiapsids that are absent both in other ‘parareptiles’ and in early diverging groups of ‘eureptiles’. Traits shared between Milleropsis and neodiapsids include: the presence of a tympanic emargination on the quadrate, quadratojugal and squamosal, the loss of epipterygoid contribution to the basicranial articulation suggesting a more kinetic palatoquadrate, the absence of a sphenethmoid and the pathway of the abducens nerve through the braincase. Our findings suggest that the early reptile neurocranium, a region poorly sampled in phylogenetic analyses due to relative visual inaccessibility and poor preservation, has the potential to inform the phylogenetic relationships of early reptiles.
Phylogenomic resolution of lampreys reveals the recent evolution of an ancient vertebrate lineage
Authors: Hughes Lily C. , Bloom Devin D. , Piller Kyle R. , Lang Nicholas , Mayden Richard L.
Published: January 2025

Jawless vertebrates once dominated Palaeozoic waters, but just two lineages have persisted to the present day: lampreys and hagfishes. Living lampreys are a relatively small clade, with just over 50 species described, but knowledge of their evolutionary relationships has always been based on either a few mitochondrial genes or a small number of taxa. Biogeographers have noted the disjunct antitropical distribution of living lamprey families. Here, we present a comprehensive phylogenomic analysis of living and fossil lampreys, sampling 36 species with phylogenomic data and 46 in total with genetic data. We present new divergence time estimates based on comprehensive nuclear data and analysis of their diversification dynamics. Our analysis indicates a central role for extreme global warming during the Late Cretaceous Cenomanian–Turonian Boundary Event as a likely cause for the antitropical distribution of living lampreys, and a notable increase in lineage diversification in Northern Hemisphere lampreys during the Miocene corresponding with a period of global cooling.
Large-scale sampling of potential breeding sites in male ruffs
Authors: Kempenaers Bart , Valcu Mihai , Piersma Theunis , Santema Peter , Vervoort Raf
Published: January 2025

The traditional narrative of the life cycle of migratory birds is that individuals perform long-distance movements between a breeding and a wintering site, but are largely resident at those sites. Although this pattern may apply to socially monogamous species with biparental care, in polygamous systems, the sex that only provides gametes may benefit from continuing to move and sample several potential breeding sites during a single breeding season. Such behaviour would blur the distinction between migration and breeding. We used satellite telemetry to study movements during the breeding season of males of the ruff
Calidris pugnax
, a lekking wader with a polygynous mating system and female-only parental care. Ruffs have a unique life-history, with three distinct genetically determined male mating strategies: aggressive ‘independents’, submissive ‘satellites’, and female-mimicking ‘faeders’. Within the breeding season, ruff males visited up to 23 sites (median: 11) and travelled up to 9029 km (median: 4435 km) covering a considerable part of their known breeding range. All three male morphs displayed breeding site sampling, indicating that they might gain similar benefits from this behaviour. Our findings suggest that large-scale breeding range sampling may be a common feature of migratory species with female-only care and strong male-male competition.
Aquatic–terrestrial linkages drive contrasting biodiversity patterns in tropical and temperate forests
Authors: Nash Liam N. , Recalde Fátima C. , Chambers Timothy , Saito Victor S. , Romero Gustavo Q. , Kratina Pavel
Published: January 2025

Riparian ecosystems harbour unique biodiversity because of their close interconnections with adjacent aquatic ecosystems. Yet, how aquatic ecosystems influence terrestrial biodiversity over different spatial scales is poorly understood, particularly in the tropics. We conducted field campaigns to collect 235 terrestrial invertebrate assemblages along 150 m transects from 47 streams in both Brazil and the UK, compiling one of the largest known datasets of riparian invertebrate community composition at multiple spatial scales. Invertebrate densities increased towards water in both regions. In Brazil, this was driven by an increase in spiders, with a corresponding decrease in non-predators, resulting in higher predator : prey ratios near water. In the UK, non-predator densities increased towards water, decreasing predator : prey ratios. While pairwise dissimilarity increased with distance from water in both regions, β-diversity was significantly higher in tropical assemblages, with more β-diversity explained by turnover. Spider community composition was significantly structured by distance from water in the Brazilian sites, suggesting tropical assemblages were influenced more by emerging aquatic prey, with a distinct spider community replacing other predators, with possible top–down control of terrestrial prey. High turnover-driven dissimilarity among tropical assemblages suggests that Brazilian riparian ecosystems are better managed at the landscape scale, with an emphasis on in-stream measures preventing disruption of aquatic resource subsidies.
Spur-winged lapwings show spatial behavioural types with different mobility and exploration between urban and rural individuals
Authors: Bar-Ziv Michael , Ziv Hilla , Breuer Mookie , Arnon Eitam , Uzan Assaf , Spiegel Orr
Published: January 2025

Understanding how wildlife responds to the spread of human-dominated habitats is a major challenge in ecology. It is still poorly understood how urban areas affect wildlife space-use patterns and consistent intra-specific behavioural differences (i.e. behavioural types; BTs), which in turn shape various ecological processes. To address these questions, we investigated the movements of a common resident wader, the spur-winged lapwing (
Vanellus spinosus
), hypothesizing that urban individuals will be more mobile than rural ones. We used an ATLAS tracking system to track many (
n 
= 135) individuals at a high resolution over several months each. We first established that daily movement indices show consistent differences among individuals, acting as spatial-BTs. Then focusing on the two main principle components of lapwings’ daily movements—mobility and position along the exploration–exploitation gradient—we investigated how these BTs are shaped by urbanization, season (nesting versus non-nesting) and sex. We found that urban lapwings were indeed more mobile in both seasons. Furthermore, urban females were less explorative than rural females, especially during the nesting season. These results highlight how urbanization affects wildlife behaviour, even of apparently urban-resilient avian residents. This underscores the need to consider possible behavioural consequences that are only apparent through advanced tracking methods.
Ubiquitin-like modifier-activating enzyme 1 interacts with Zika virus NS5 and promotes viral replication in the infected cell
Authors: Rodrigo Imanol , Albentosa-González Laura , Romero de Ávila María Jos , Bassi Maria Rosaria , Sempere Raquel Navarro , Clemente-Casares Pilar , Arias Armando
Published: January 2025

Translation errors, impaired folding or environmental stressors (e.g. infection) can all lead to an increase in the presence of misfolded proteins. These activate cellular responses to their removal, including intracellular protein degradation activities. Protein ubiquitylation is involved in two major degradation pathways, the ubiquitin-proteasome system and selective autophagy. In humans, the ubiquitin-like modifier-activating enzyme 1 (UBA1) is the primary E1 enzyme in the ubiquitin conjugation cascade. Viruses have evolved to exploit protein degradation pathways to complete their infection cycles. Zika virus (ZIKV) is an emerging orthoflavivirus causing serious neurologic disorders in neonates (congenital microcephaly) and adults (Guillain–Barré syndrome). Non-structural protein 5 (NS5), the largest and most conserved protein in the orthoflaviviruses, catalyses the synthesis and capping of new viral genomes. In addition to viral RNA replication in the cytoplasm, ZIKV NS5 is translocated into the nucleus to interfere with host antiviral responses. Here, we demonstrate that ZIKV NS5 co-immunoprecipitates with cellular UBA1. Immunofluorescence assays suggest that this interaction takes place primarily in the nucleus of an infected cell, although colocalization of both proteins is also detected in the cytosol. RNA interference-mediated depletion of UBA1 leads to reduced virus titres in the infected cells, while transient overexpression of UBA1 favours faster replication kinetics, with higher virus titres and protein levels detected. Moreover, UBA1-targeting drugs cause significant drops in virus infectivity. These results support a proviral role for UBA1 during ZIKV infection and encourage the potential use of inhibitors against this enzyme or its NS5-interacting epitopes as potential therapeutic targets.
HIV-1 Vpr alters cellular transcription by targeting the PAF1 complex
Authors: Biguet Maximilien , Marno Kelly , Oliveira Nidia , Gibbons Joseph M , Pade Corinna , Jones Christopher E , Branco Miguel R , McKnight Aine
Published: January 2025

Innate immunity represents the first line of defence against viral infections, and successful pathogens like HIV-1 have evolved mechanisms to bypass these barriers. The PAF1 complex (PAF1c) has emerged as a key regulator of antiviral innate immune responses, inhibiting the replication of various viruses, including HIV-1. While its role in transcription regulation is well documented, little is known about how PAF1c inhibits HIV-1 and how HIV-1 circumvents this antiviral activity. Here we demonstrate that Vpr induces the rapid and transient downmodulation of PAF1c shortly after infection, a process that correlates with significant transcriptomic changes within the host cell. Transcriptomic profiling reveals that PAF1 knockdown mirrors many of the gene expression changes induced by HIV-1 infection, indicating that Vpr antagonism of PAF1c is a means by which HIV-1 may modulate host gene expression to favour replication. Further, we show that the loss of PAF1c leads to the suppression of interferon-stimulated genes (ISGs) and several known HIV-1 restriction factors. Overall, the evidence supports the emerging role of PAF1 as a regulator of a broad antiviral transcriptional program, but also suggests a specific anti-HIV activity that is countered by HIV-1 Vpr.
Valence-dependent sensory-rhythmic neural entrainment modulates cortico-subcortical dynamics, attention, and memory
Authors: Hoyer R.S. , Bernier M-F. , Martineau L. , Lessard Bonaventure P. , Labelle C. , Borderie A. , Blanchette I. , Blumenthal A. , Albouy P.
Published: January 2025

Recent studies have shown that sensory rhythmic stimulation can enhance executive functions by synchronizing, entraining, oscillations within higher-order cortical networks. However, whether this entrainment extends to subcortical structures and shapes human behavior remains unclear. In a first experiment, we used intracranial EEG recordings in epileptic patients during a visual search task. While neutral stimulation induced moderate entrainment, we demonstrated that 5 Hz negative-valence stimulation can significantly entrain theta oscillations in a widespread task-related cortico-subcortical network, with increased synchrony in the ventral visual stream, the hippocampus, and the dorsolateral prefrontal cortex. In a second behavioral experiment in healthy individuals, visual search performance improved under both stimulation conditions, but memory for target images, assessed through an additional recognition task, was significantly enhanced after negative stimulation. These findings unravel the role of valence in modulating subcortical brain activity and behaviors through rhythmic sensory stimulation and pave the way for its further application in clinical intervention.
Three-dimensional quantitative characterization ofCoxiella burnetiiinfection using focused ion beam-scanning electron microscopy
Authors: Botting Jack M. , Steiner Samuel , Graham Morven , Liu Xinran , Roy Craig R. , Liu Jun
Published: January 2025

Coxiella burnetiiis a highly virulent intracellular pathogen that causes acute and chronic Q fever in humans. The bacterium utilizes a Dot/Icm type IV secretion system (T4SS) to translocate over 100 effectors into host cells to facilitate biogenesis ofCoxiella-containing vacuoles (CCVs), which are specialized lysosome-derived organelles that support bacterial replication. During replication in CCVs,C. burnetiiundergoes a unique biphasic developmental cycle defined by two distinct cellular forms: the infectious and metabolically dormant small cell variant (SCV) that converts to a replicative large cell variant (LCV). This developmental cycle was believed to be intimately coupled with biogenesis of CCVs, but the underlying mechanisms remained unclear. Here, we combine advanced focused ion beam-scanning electron microscopy (FIB-SEM) with machine learning-based data analyses to visualize host cells infected byC. burnetii. We reveal significant pleiomorphism of both the bacteria and CCVs in three dimensions. We show that this technology can be leveraged to characterize CCV biogenesis defects displayed byC. burnetiimutants that are unable to generate the large CCV displayed by wild-typeC. burnetii. Analysis of HeLa cells infected with acig2::Tn mutant confirmed that this mutant creates vacuoles that have a defect in homotypic fusion but that the proportions of SCV to LCV in vacuoles in which this mutant resides are nearly identical to CCVs containing wild-typeC. burnetii, which indicates the vacuole biogenesis defect displayed by thecig2::Tn mutant did not impact the developmental cycle intracellularly. Collectively, this study provides unprecedented three-dimensional images of the complex intracellular lifestyle ofC. burnetii. This imaging technology also provides unique insights into the biphasic developmental cycle and will be a powerful approach to dissect CCV biogenesis defects displayed by mutantC. burnetii.
Antidepressants reactivate developmental plasticity through remodeling of extracellular matrix
Authors: Nguyen Phi T , Tamura Shogo , Sun Emily , Shi Yuecheng , Xiao Yang , Lacefield Clay , Turi Gergely , Hen Rene
Published: January 2025

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders, yet their molecular mechanisms of action remain poorly understood. Here, we show that chronic treatment with the SSRI fluoxetine reinstates a developmental plasticity program in the dentate gyrus (DG) by remodeling the extracellular matrix (ECM). Fluoxetine elicited a robust transcriptomic response in the DG, where mature granule cells adopted a juvenile-like profile. This shift was characterized by upregulation of the transcription factor SOX11 and the neurotrophic factor BDNF, as well as decreased ECM and enhanced structural remodeling of granule cell axon terminals. Direct enzymatic degradation of ECM in the DG reactivated SOX11 in mature granule cells. At the behavioral level, fluoxetine mitigated stress-induced fear generalization, an endophenotype of mood and anxiety disorders. This effect was phenocopied by ECM degradation, suggesting that ECM remodeling and granule cell rejuvenation are key mechanisms underlying the effects of fluoxetine, and possibly other antidepressants, on fear generalization.
Tumour suppressor WT1 and its interacting protein RNA helicase DDX5 regulate the microRNA let7/Igf1r axis in the kidney mesenchyme
Authors: Dey Sourav , Slight Joan , Aitken Stuart , Joseph Iwin , Bhore Utkarsh , vonKriegshiem Alex , Petrovich Giulia , Charlton Jocelyn , Stancheva Viktoriya , Mohapatra Debasis , Essafi Abdelkader , Pritchard-Jones Kathy , Hastie Nicholas D , Bharathavikru Ruthrothaselvi
Published: January 2025

Germline mutations in tumour suppressor, Wilms Tumour 1 (WT1) as well as somatic and germline mutations in microRNA processing genes (MIRPG) have been identified in Wilms’ Tumours (WT), where upregulation of IGF2 through genetic and/or epigenetic mechanisms is commonly seen. Whether these different epigenetic and genetic causes converge on common targets is still unclear. WT1 is also involved in RNA binding and regulates the stability of these developmental mRNAs. We now show that WT1 interacts with microRNA let-7 and proteins involved in microRNA processing wherein DDX5 is found to be an important regulator. WT1 absence results in decreased microRNA levels in cell lines and kidney mesenchyme, which is further downregulated in a WT1 and DDX5 double knockdown, ultimately modulatingIgf1rexpression. These findings suggest a plausible mechanism by whichWT1mutations lead to WT, and converge on microRNA pathway and IGF signalling pathway, which are important contributing factors in the aetiology of WT.
Regulation of transcription elongation anticipates alternative gene expression strategies across the cell cycle
Authors: Maya-Miles Douglas , García-Martínez José , Cases Ildefonso , Pasión Rocío , de la Cruz Jesús , Pérez-Ortín José E. , de la Cruz Muñoz-Centeno María , Chávez Sebastián
Published: January 2025

Increasing evidence supports that the activity of RNA polymerase II (RNA pol II) during transcription elongation can be regulated to control transcription rates. Using genomic run-on (GRO) and RNA pol II chromatin immunoprecipitation (RPCC), we have respectively measured active and total RNA pol II present in the body of genes at 3 different stages of the mitotic cell cycle ofSaccharomyces cerevisiae: G1, S and G2/M. Comparison of active and total RNA pol II values at these three points defined different patterns of transcription elongation control across the cell cycle. Previously characterized cycling genes were found associated to some of these elongation patterns. A cluster of genes with very divergent GRO and RPCC patterns was significantly enriched in genes functionally related to ribosome biogenesis (RiBi) and the structural components of the ribosome. We confirmed that RiBi mRNA expression upregulates after START but decreases after mitosis. Finally, we analysed the contribution of mRNA stability to each cluster and found that concerted control of RNA pol II activity and mRNA decay is needed to fully understand alternative strategies of gene expression across the cell cycle.
Performance of the VISITECT® CD4 Test for Rapid Identification of Advanced HIV Disease at AHF-Supported Sites in Zambia: A Diagnostic Accuracy Analysis in a Zambian Population
Authors: Mulumba Eric Mpoyi , Kayembe Mazinga F. , Chewe Webster C. , Chanda Chitalu , Dube Nduduzo , Chituta Clifford , Hamooya Benson M. , Kasweka Freddy T. , Matabishi Martin , Assani Muyungila Bob
Published: January 2025

Background

Advanced HIV disease (AHD), defined as a CD4 count below 200 cells/mm³ or the presence of WHO Stage 3 or 4 clinical conditions, poses significant diagnostic challenges in resource-limited settings such as Zambia. Early identification of AHD is essential for improving outcomes for recipients of care (ROCs). The VISITECT® CD4 test, a point-of-care tool, offers potential for addressing these challenges; however, its diagnostic performance in Zambia remains under-evaluated. This study aimed to assess the sensitivity and specificity of the VISITECT® CD4 test for identifying AHD among ROCs at five AIDS Healthcare Foundation (AHF)-supported clinics in Zambia.

Methodology

A cross-sectional study was conducted between January 8 to May 31, 2024, at five AHF-supported clinics in Zambia. Participants included individuals who were newly diagnosed with HIV, re-engaging in HIV care, or presenting with unsuppressed HIV viral loads. Baseline clinical and demographic data were collected, and the diagnostic performance of the VISITECT® CD4 test was compared to the flow cytometry CD4 test (the gold standard) using STATA v15 to determine sensitivity, specificity, and other diagnostic accuracy metrics.

Results

Among 231 participants, 24.7% (57/231) had AHD based on the flow cytometry CD4 test, whereas 47.6% (110/231) were classified with AHD by the VISITECT® CD4 test. The VISITECT® CD4 test demonstrated a sensitivity of 96.5% and a specificity of 68.4%. The Negative Predictive Value was 98.4%, and the Positive Predictive Value was 50.0%. The overall diagnostic accuracy, as indicated by the area under the curve, was 0.82 (95% CI: 0.78, 0.87). AHD was significantly associated with age according to flow cytometry (p=0.029) but not according to the VISITECT® CD4 test (p=0.277). A significantly higher proportion of individuals with anemia had AHD across both tests (p<0.05).

Conclusion

The VISITECT® CD4 test demonstrated strong diagnostic accuracy for detecting AHD, making it a valuable rapid point-of-care tool in resource-limited settings. Its wider implementation could enhance early AHD detection and facilitate timely clinical interventions, warranting further exploration.
Non-Contact Optical Blood Pressure Biometry Using AI-Based Analysis of Non-Mydriatic Fundus Imaging
Authors: Bressler Idan , Dollberg Dolev , Aviv Rachelle , Margalit Danny , Harris Alon , Siesky Brent , Ianchulev Tsontcho , Dvey-Aharon Zack
Published: January 2025

Background

This study was developed to determine whether a machine learning model could be developed to assess blood pressure with accuracy comparable to arm cuff measurements.

Methods

A deep learning model was developed based on the UK Biobank dataset and was trained to detect both systolic and diastolic pressure. The hypothesis was formulated after data collection and before the development of the model. Comparison was conducted between arm cuff measurements, as ground truth, and results from the model, using Mean Absolute Error, Mean Squared Error, and Coefficient of Determination (R^2).

Results

Systolic pressure was measured with 9.81 Mean Absolute Error, 165.13 Mean Squared Error and 0.36 R^2. Diastolic pressure was measured with 6.00 Mean Absolute Error, 58.21 and 0.30 R^2.

Conclusions

This model improves on existing research and shows errors comparable to the variability of hand cuff measurements. The use of fundus images to assess blood pressure may be more indicative of long-term hypertension. Additional trials in clinical settings may be necessary, as well as additional prospective studies to validate results.
HD2Net: A Deep Learning Framework for Simultaneous Denoising and Deaberration in Fluorescence Microscopy
Authors: Hou Xuekai , Li Yue , Hobson Chad M. , Shroff Hari , Guo Min , Liu Huafeng
Published: January 2025

Fluorescence microscopy is essential for biological research, offering high-contrast imaging of microscopic structures. However, the quality of these images is often compromised by optical aberrations and noise, particularly in low signal-to-noise ratio (SNR) conditions. While adaptive optics (AO) can correct aberrations, it requires costly hardware and slows down imaging; whereas current denoising approaches boost the SNR but leave out the aberration compensation. To address these limitations, we introduce HD2Net, a deep learning framework that enhances image quality by simultaneously denoising and suppressing the effect of aberrations without the need for additional hardware. Building on our previous work, HD2Net incorporates noise estimation and aberration removal modules, effectively restoring images degraded by noise and aberrations. Through comprehensive evaluation of synthetic phantoms and biological data, we demonstrate that HD2Net outperforms existing methods, significantly improving image resolution and contrast. This framework offers a promising solution for enhancing biological imaging, particularly in challenging aberrating and low-light conditions.
Carbon monoxide exposure in pregnant women in the UK – results from the IPPCO study
Authors: Place Elsie , Wareing Hilary , Herigstad Mari
Published: January 2025

Carbon monoxide (CO) is a colourless, odourless gas that poses a threat to life at concentrations of just a few hundred ppm. The developing foetus is particularly vulnerable to CO exposure, and maternal exposure to much lower levels of the gas is associated with adverse outcomes such as low birth weight. This study aimed to quantify CO exposure in pregnant women’s homes and assess whether breath CO levels could be linked to home-based CO exposure and sociodemographic factors.

CO levels were monitored continuously over two weeks in 161 households selected for indicators of lower socio-economic status and proximity to gas appliances, a risk factor for environmental CO exposure. Exhaled breath CO measurements were taken before and after the monitoring period. Of the households monitored, 57.8% had detectable CO levels, with 31.7% experiencing levels above 4ppm and 14.3% above 10ppm. CO exposure varied significantly across households, with both chronic low-level and intermittent high-level exposures observed. Six households included in the study exceeded current World Health Organisation recommended limits of 3.5ppm for ≥24 hours, and three exceeded the limit of 9ppm for ≥8 hours. Higher CO levels in the household were associated with the use of gas for cooking. Higher exhaled CO levels were associated with number of smokers in the household and eligibility for the UK government NHS Healthy Start scheme. Following the monitoring period, exhaled CO levels were only associated with number of smokers in the household, suggesting an intervention effect.

This study indicates that a high proportion of pregnant women are exposed to CO within the home, albeit predominantly within current recommended limits, and that exposure may be linked to socio-economic factors in addition to smoking. This study highlights the need for improved CO monitoring and mitigation strategies, particularly in vulnerable populations, to protect maternal and foetal health.
Unraveling the molecular mechanism underlying the anticancer activity of CISD2/NAF-144-67
Authors: Rowland Linda , Alfoni Itai , Neumann Ehud , Karmi Ola , Nechushtai Rachel , Mittler Ron
Published: January 2025

We recently reported on the development of a unique cancer-targeting peptide called NAF-144-67(derived from CISD2/NAF-1). NAF-144-67selectively permeates the plasma membrane (PM) of cancer cells, but not healthy cells, causing the activation of apoptotic and ferroptotic cell death pathways specifically in cancer cells. NAF-144-67also targets and shrinks human breast and ovarian cancer tumors in a xenograft mice model system without any apparent side effects. Although the specific permeation of NAF-144-67through cancer cell PMs was studied, and its cancer killing effects validatedin vitroandin vivo, little is known about how NAF-144-67exerts its biological activity once it enters cancer cells. Here, we report that NAF-144-67targets the CISD2/NAF-1 protein of cancer cells and disrupts its homodimeric structure. We further reveal that a peptide derived from the same domain of the human CISD1 (mitoNEET; mNT19-42) protein, a close family member to CISD2, has no killing activity towards cancer cells, and that dimers of NAF-144-67(at two different orientations) have higher anticancer activity compared to monomeric NAF-144-67. Our findings shed new light on the biological activity of NAF-144-67and bring it closer to becoming a potential new anticancer drug.
PROTAC molecule-mediated SpCas9 protein degradation for precise genome editing
Authors: Sun Shengnan , Sun Renhong , Tan Minkang , Kip Maarten , Yang Xiaobao , Pang Baoxu
Published: January 2025

CRISPR (clustered regularly interspaced short palindromic repeats) technology has revolutionized both fundamental research and genomic medicine. The need for precise control of SpCas9-based CRISPR genome editing has resulted in a number of methods to control the function and activity of Cas9 proteins to minimize off-target editing effects. Proteolysis-targeting chimeras (PROTACs) are an emerging technology using the ubiquitin-proteasome system to selectively degrade the target proteins. Here, we developed CASPROTAC 6, a reversible and cell-permeable degrader directly targeting SpCas9 proteins for degradation. The warhead of CASPROTACs was derived by bridging a known SpCas9 binder BRD7087 with an S-substituted Lenalidomide cereblon (CRBN) ligand via the 6-carbon alkyl linker. Our data showed that CASPROTAC 6 is a broad-spectrum degrader of SpCas9 and SpCas9 variants such as dCas9 and Cas9 nickases. The CASPROTAC 6 degraded SpCas9 and the SpCas9-guide-RNA complex via the proteasome system by ∼50%. As a result, the CASPROTAC 6 molecule can reduce the CRISPR/Ca9-mediated genome editing by 30%. The CASPROTAC 6 molecules could be used to regulate the CRISPR/SpCas9-associated nucleases for precise genome editing to reduce off-target effects and strengthen biosafety.
Cell-death induced immune response and coagulopathy promote cachexia inDrosophila
Authors: Singh Ankita , Hu Yanhui , Lopes Raphael Fragoso , Lane Liz , Woldemichael Hilina , Xu Charles , Udeshi Namrata D. , Carr Steven A. , Perrimon Norbert
Published: January 2025

Tumors can exert a far-reaching influence on the body, triggering systemic responses that contribute to debilitating conditions like cancer cachexia. To characterize the mechanisms underlying tumor-host interactions, we utilized a BioID-based proximity labeling method to identify proteins secreted by YkiactadultDrosophilagut tumors into the bloodstream/hemolymph. Among the major proteins identified are coagulation and immune-responsive factors that contribute to the systemic wasting phenotypes associated with Ykiacttumors. The effect of innate immunity factors is mediated by NFκB transcription factors Relish, dorsal, and Dif, which in turn upregulate the expression of the cachectic factors Pvf1, Impl2, and Upd3. In addition, Ykiacttumors secrete Eiger, a TNF-alpha homolog, which activates the JNK signaling pathway in neighboring non-tumor cells, leading to cell death. The release of damage-associated molecular patterns (DAMPs) from these dying cells presumably amplifies the inflammatory response, exacerbating systemic wasting. Targeting the inflammatory response, the JNK pathway, or the production of cachectic factors could potentially alleviate the debilitating effects of cancer cachexia.
LncPTPred: Predicting lncRNA-Protein Interaction based on Crosslinking and Immunoprecipitation (CLIP-Seq) Data
Authors: Das Gourab , Das Troyee , Ghosh Zhumur
Published: January 2025

Long non-coding RNA (lncRNA)-Protein Interaction (LPI) across diverse biological systems directly and indirectly regulates various cellular processes. Experimental assays to recognize the protein binding partners of lncRNAs is highly time consuming and expensive.In-silicopredictive approaches involving pattern recognition technique provides a promising alternative to it by reducing the search space. Our work identifies such hidden pattern from within the Cross-linking immunoprecipitation sequencing (CLIP-Seq) data which aids to overcome the problem of obtaining real negative dataset and thus offers a state-of-the-art machine learning (ML) based prediction algorithm to predict LPI. Initial phase of this work involves preparation of the training dataset and the next phase is devoted towards developing the ML based model to perform prediction operation. In order to show the efficacy of our model, its performance has been compared against that of the contemporary prediction tools, where the result clearly shows the outperformance of our model. Moreover it also provides the segments of interaction within the lncRNA loci which acts as a roadmap for precise designing of the validation experiment. The LncPTPred tool has been provided in terms of web server as well as standalone version in github.

Web server Link:http://bicresources.jcbose.ac.in/zhumur/lncptpred/

Github Link:https://github.com/zglabDIB/lncptpred.git
Calcium-triggered apoplastic ROS bursts balance gravity and mechanical signals to navigate soil
Authors: Kulich Ivan , Vladimirtsev Dmitrii , Randuch Marek , Gao Shiqiang , Citterico Matteo , Konrad Kai R. , Nagel Georg , Wrzaczek Michael , Friml Jiri
Published: January 2025

Reactive oxygen species (ROS) have been implicated repeatedly in multiple signaling processes in plants but the underlying mechanisms and roles remain enigmatic. Here, we developed live imaging of apoplastic ROS at the root surface. Different signals, including auxin, extracellular ATP and RALF1 peptide, all induce cytosolic calcium transients and apoplastic ROS bursts. Genetic and optogenetic manipulations identified calcium transients as necessary and sufficient for ROS bursts via activation of NADPH oxidases RBOHC and RBOHF. Apoplastic ROS bursts are not required but rather limit the gravity-induced root bending. Root bending is sensed by stretch-activated calcium channel MCA1 leading to NADPH oxidase activation at the stretched side. The resulting ROS production stiffens cell wall for better soil penetration. Apoplastic ROS thus provides a means to balance tissue flexibility and stiffness to efficiently navigate soil.