bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Age And Endovascular Treatment Outcomes: Binational Registry Of 9941 EVT Cases From Korea And Taiwan
Authors: Kim Beom Joon , Tang Sung-Chun , Hsieh Yi-Chen , Chen Chih-Hao , Kim Yong Soo , Lin Chun-Jen , Park Jong-Moo , Sung Pi-Shan , Kang Kyusik , Chen Yu-Wei , Lee Soo Joo , Lin Kuan-Hung , Cha Jae-Kwan , Tang Chih-Wei , Park Tai Hwan , Chu Hai-Jui , Lee Kyungbok , Fu Chuan-Hsiu , Lee Jun , Chou Chao-Liang , Hong Keun-Sik , Lin Ching-Huang , Yu Kyung-Ho , Wei Cheng-Yu , Kim Dong-Eog , Yen Shang-Yih , Kim Joon-Tae , Chen Po-Lin , Choi Jay Chol , Chan Lung , Kwon Jee Hyun , Shin Dong-Ick , Sohn Sung-Il , Chiou Hung-Yi , Kim Chulho , Park Kwang-Yeol , Kim Chi Kyung , Lien Li-Ming , Heo Sung Hyuk , Lee Jiunn-Tay , Bae Hee-Joon , Jeng Jiann-Shing
Published: January 2025

Background and Purpose

As populations age, there is an increasing need to optimize endovascular treatment (EVT) for acute ischemic stroke. We harmonized prospective stroke registries from Korea and Taiwan to enable direct comparisons of patient characteristics and clinical outcomes, with a particular focus on the impact of advanced age.

Methods

Prospective stroke registries in South Korea (CRCS-K) and Taiwan (TREAT-AIS) were harmonized to form a unified dataset of patients treated with EVT. EVT outcomes included 3-month modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (SICH), and successful recanalization. We assessed the association between age and outcomes in the overall population and in those aged ≥80 years, adjusting for relevant covariates.

Results

A total of 9941 EVT cases (7835 from Korea and 2106 from Taiwan) were included. Patients had a mean age of 70.1 ± 12.9 years (57.6% male, median NIHSS: 14 [IQR: 9–19]). Compared to Korean patients, Taiwanese patients had a higher prevalence of vascular risk factors and more severe strokes, contributing to lower rates of favorable 3-month outcomes. Increasing age was associated with poorer EVT results; among patients ≥80 years, only 18% achieved mRS 0–2, compared to 47% of younger patients. However, the risk of SICH did not significantly increase with age (adjusted OR per year: 1.00 [0.99–1.01]; adjusted OR ≥80 years: 1.05 [0.85–1.29]). Pre-stroke functional independence and bridging thrombolysis were identified as key modifiers of better outcomes even in the oldest patients.

Conclusion

Taiwanese EVT patients had more risk factors and worse outcomes than Korean patients. Advanced age is associated with poorer functional recovery, yet selected older patients—particularly those who were functionally independent before the stroke or received bridging thrombolysis—demonstrated meaningful benefit. These results underscore the importance of individualized treatment strategies and careful patient selection, especially as populations continue to age.
Antimicrobial Resistance Pattern among Organisms Isolated from Tertiary Care Hospital in Chennai
Authors: Moses G. F , Subhasri B , Sakthi Abirami R , Kalpana Devi V , Durga shree U , Rithika A , Bannari Amruth G
Published: January 2025

Background

The findings will help guide the development of targeted antimicrobial stewardship programs and enhance public health strategies to address resistance.

Aim

This study aimed to identify common antimicrobial-resistant organisms and their resistance profiles in clinical specimens from a tertiary care hospital.

Settings and Design

A cross-sectional study was conducted at ACS Medical College and Hospital, Chennai, from November 2023 to May 2024, involving 346 participants.

Materials and Methods

Clinical specimens, including urine, blood, sputum, and wound swabs, were collected from patients in various hospital wards. Demographic details of participants were documented, and patients who had received antimicrobial therapy within the previous month or provided tissue samples were excluded. The specimens were analyzed in the central laboratory for microbial growth and antimicrobial resistance profiles. Isolated were tested by Kirby-Bauer disc diffusion method and breakpoint minimum inhibitory concentration for susceptibility against standard antibiotics.

Results

Among the 346 specimens analyzed, 264 (76.3%) showed microbial growth. The most commonly isolated organisms were Escherichia coli (28.8%), Klebsiella species (26.9%). High level resistance was observed, especially to Polymyxin B (98.7%), Cefoperazone/Sulbactam (97.4%), and Cefotaxime (92.1%).

Conclusion

antimicrobial resistance requires coordinated action across healthcare, policy, and public sectors. By enforcing stricter regulations, enhancing surveillance, and investing in new treatments, we can slow resistance and preserve the effectiveness of antibiotics, safeguarding public health for future generations.
High magnitude of lung function decline among heroin users attending Medication-Assisted Therapy clinic at Muhimbili National Hospital, Tanzania
Authors: Nkongoki Alex , Balandya Emmanuel , Mamuya Simon , Mbwambo Jessie
Published: January 2025

Heroin users have a high burden of respiratory morbidity, including premature lung function decline at age of 41 years. This early decline in lung function has been attributed to exposure to multiple risk factors. Further, methadone treatment has been found to aggravate lung function decline and independently cause asthma. However, the lung function status among heroin users on Medication-Assisted Therapy clinic in Tanzania is yet to be studied. This study aimed to assess the magnitude, pattern, and factors associated with lung function decline among heroin users attending MAT clinic at the Muhimbili National Hospital in Dar-es-salaam, Tanzania. This was a quantitative, analytical cross-sectional study conducted between May, 2022 – July, 2023. Individuals aged 18 years or above with heroin use disorder on the maintenance phase of treatment were recruited into the study. Data were collected using a questionnaire, and lung functions were measured using a portable spirometer. Lung function decline was defined as the percentage of participants with FEV1 <70%. The association between socio-demographic characteristics, substance use history and comorbidities with lung function decline was assessed via binary logistic regression. We enrolled 302 participants into the study (mean age of 42.78±7.56 years), whereby 95.7% were male. Of the study participants, 28.5% had lung function decline with mean age at onset of 44±8 years. Restrictive lung disease was the commonest pattern of lung function decline with a proportion of 13.2%. Independent predictors of lung function decline were being underweight (aOR 4.73, 95% CI 2.61-8.59, p<0.001), living with HIV infection (aOR 2.61, 95% CI 1.20-5.66, p=0.016) and having a history of pulmonary TB (aOR 2.48, 95% CI 1.48-4.17, p=0.001). Heroin users on methadone therapy in Dar-es-salaam have high magnitude of lung function decline compared to the general population. Routine lung function testing is recommended.
Automated Monitoring of Clinical Practice Guideline Adherence Using FHIR and OMOP: A Multi-Center Study in Intensive Care Units
Authors: Lichtner Gregor , Schiefenhövel Fridtjof , Gashi Bora , Martin Ingrid , Jurth Carlo , Vasiljewa Lisa , Kleimeier Dana , Gibb Sebastian , Heim Markus , Brugger Jürgen , Lohr Johannes , Feig Martin A. , Speidel Saya , Bienert Thomas , Abramovich Igor , Kaspar Mathias , Sindel Anja , Mehringer Laurenz , Hinske Ludwig Christian , Simon Philipp , Heller Axel R , Kranke Peter , Meybohm Patrick , Balzer Felix , Spies Claudia , Schneider Gerhard , Hahnenkamp Klaus , Waltemath Dagmar , Boeker Martin , von Dincklage Falk
Published: January 2025

Background

Clinical practice guidelines are important tools for clinical decision support, but monitoring guideline adherence manually is highly resource-intensive. Therefore, we developed an automated system for evaluating guideline adherence based on computer-interpretable representations of guidelines. We implemented the system across multiple university hospitals and assessed its validity and performance by comparing its guideline adherence evaluations to those conducted by medical professionals.

Methods

We selected six representative clinical guideline recommendations from across 41 intensive care guidelines and translated these text-based recommendations into a computer-interpretable, Fast Healthcare Interoperability Resources (FHIR)-based format using an iterative consensus approach. Clinical data from five university hospitals were transformed into the Observational Medical Outcomes Partnership (OMOP) common data model. A decision support system was developed to interpret FHIR-encoded recommendations and apply them to OMOP-formatted patient data. We evaluated the system retrospectively on intensive care data covering 3.5 years and validated its performance by comparing system-generated decisions with human decisions in three hospitals. We created and iteratively refined a user interface for individual and ward-level adherence visualization.

Findings

We expert-reviewed more than 18,000 patient days to assess the applicability of and adherence to the recommendations. The system demonstrated 97.0% accuracy in identifying guideline applicability and adherence, with significantly higher accuracy than human reviewers (accuracy 86.6%, p<0.001, McNemar’s Test). The automated system processed more than 2000 patient days per second for a total of 2,200,000 patient days across 82,000 intensive care episodes, compared to humans’ two patient days per minute.

Interpretation

We demonstrate that an automated adherence monitoring system outperforms human reviewers in both accuracy and time efficiency. Using FHIR-encoded recommendations enables flexibility and scalability across hospitals with different data infrastructures. Future work should focus on integrating unstructured patient data and expanding the range of encoded recommendations.

Funding

Federal Ministry of Education and Research of Germany.
Emergence and Rising Prevalence of Artemisinin Partial Resistance Marker Kelch13 P441L in a Low Malaria Transmission Setting in Southern Zambia
Authors: Martin Anne C. , Sadler Jacob M. , Simkin Alfred , Musonda Michael , Katowa Ben , Matoba Japhet , Schue Jessica , Simulundu Edgar , Bailey Jeffrey A. , Moss William J. , Juliano Jonathan J. , Fola Abebe A.
Published: January 2025

Increasing artemisinin partial resistance (ArtR) due to mutations in the gene encoding Kelch13 (Pfk13) protein in eastern Africa is of urgent concern, and mutations, such asPfk13P441L, continue to emerge. We used an amplicon deep-sequencing panel to estimate the prevalence of ArtRPfk13mutations in samples collected between 2018 and 2023 in southern Zambia.Pfk13P441L was present in 30 of 501 samples (6%), and prevalence increased over time (0% to 7.2%). Further studies of the P441L mutation are needed to document its geographical origin, distribution and impact on treatment outcomes.
Comparison of Machine Learning Models in Predicting Mental Health Sequelae Following Concussion in Youth
Authors: Peng Jin , Chen Jiayuan , Yin Changchang , Zhang Ping , Yang Jingzhen
Published: January 2025

Youth who experience concussions may be at greater risk for subsequent mental health challenges, making early detection crucial for timely intervention. This study utilized Bidirectional Long Short-Term Memory (BiLSTM) networks to predict mental health outcomes following concussion in youth and compared its performance to traditional models. We also examined whether incorporating social determinants of health (SDoH) improved predictive power, given the disproportionate impact of concussions and mental health issues on disadvantaged populations. We evaluated the models using accuracy, area under the curve (AUC) of the receiver operating characteristic (ROC), and other performance metrics. Our BiLSTM model with SDoH data achieved the highest accuracy (0.883) and AUC-ROC score (0.892). Unlike traditional models, our approach provided real-time predictions at each visit within 12 months of the index concussion, aiding clinicians in making timely, visit-specific referrals for further treatment and interventions.
PREVALENCE AND FACTORS ASSOCIATED WITH NON-ADHERENCE TO ANTIRETROVIRAL THERAPY IN HIV PATIENTS AT KIBUNGO REFERRAL HOSPITAL, IN RWANDA
Authors: Niyonsenga Phocas Mukezamfura , Habimana Amos , Nsanzabera Charles
Published: January 2025

Background

It has been demonstrated that antiretroviral therapy improves health and lengthens the life of HIV positive individuals. For those living with HIV, attaining optimal adherence is turning out to be the largest obstacle. The purpose of this research was to determine how often antiretroviral therapy non-adherence is among HIV patients who visit Rwanda’s Kibungo Referral Hospital.

Methods

This study utilized a quantitative, cross-sectional design. Data collection was conducted from March 25thto April 30, 2024, with a sample size of 396 HIV patients on ART at Kibungo Referral Hospital. Inclusion criteria included patients aged 18 years and older who had been on ART for six months, while exclusion criteria included lack of consent and hospitalized patients. A structured questionnaire was used. The Fisher exact test and logistic regression were employed to analyze associations, with significance set at p < 0.05 and 95% CI.

Findings

The findings showed that the overall non-adherence rate to ART was 13% while the adherence rate was 87%. Also, patients without tertiary education are significantly more likely to be non-adherent to ART compared to those with tertiary education (AoR: 8.232, 95% CI: 4.124-17.217, P-value: <0.001). Patients who experience stigma are more likely to be non-adherent to ART (AoR: 2.148, 95% CI: 1.032-6.689, P-value: 0.015). Patients who perceive ART as ineffective are significantly more likely to be non-adherent (AoR: 9.333, 95% CI: 2.108-20.638, P-value: <0.001. Patients who do not integrate ART into their daily routines are significantly more likely to be non-adherent (AoR: 11.180, 95% CI: 5.879-28.338, P-value: <0.001). There is no significant association between not setting an alarm and non-adherence.

In conclusion

The study found a high non-adherence rate to ART among HIV patients at Kibungo Referral Hospital, linked to factors such as younger age, lack of tertiary education, stigma, and perceived ineffectiveness of ART. It recommends implementing structured support systems and targeted interventions to improve adherence and health outcomes for these patients.
Challenges in the medical oxygen ecosystem of Peru: a political economy analysis
Authors: Garcia Patricia J. , Kitutu Freddy Eric , Guzman Jehnette M. , Najarro Lizzette , Ssengooba Freddie , King Carina
Published: January 2025

Background

Medical oxygen is essential in the management of several human disease conditions including acute respiratory conditions across the life course, and yet access remains unequal in many low- and middle-income countries, including Peru. This study explores Peru’s challenges in ensuring reliable oxygen supplies, with a focus on those laid bare or exacerbated by the COVID-19 pandemic, to inform strategies for improving medical oxygen access.

Methodology and Principal Findings

Using a political economy analysis, we conducted 13 key informant interviews with stakeholders involved in oxygen policy, supply, and health care, supported by reviews of 117 academic and grey literature sources, including policy documents. Before the COVID-19 pandemic, Peru’s requirement for medical oxygen to be >99% pure restricted competition, consolidating control of a few large liquid oxygen suppliers on the oxygen market and blocking smaller, affordable providers due to high compliance costs. Although pre-pandemic oxygen supplies were reportedly adequate, the pandemic exposed severe limitations including market constraints, slow government response, and lack of data management, resulting in an acute oxygen crisis. Civil society and private organizations stepped in, donating medical oxygen generator plants, but many of these are now unused due to insufficient planning for maintenance and operation.

Conclusions and Significance

This study underscores the urgent need for a National Oxygen System in Peru to oversee supply, distribution, and maintenance, and strengthen resilience for future health emergencies. Solutions include reducing reliance on a small number of external suppliers, infrastructure investments, dedicated funding for maintenance, and training for personnel to ensure continuous oxygen access nationwide. This research highlights systemic vulnerabilities in Peru’s health system and calls for coordinated policies to ensure equitable oxygen access and preparedness for future crises.
Blood Pressure and Hypertension After Hypertensive Disorders of Pregnancy
Authors: Urrutia Rachel Peragallo , Loop Matthew Shane , Johnson Jasmine D , Wang Tracy Y , Price Thomas M , Daubert Melissa A
Published: January 2025

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality for women. Timely diagnosis of hypertension after a hypertensive disorder of pregnancy (HDP) provides an opportunity for CVD prevention. We assessed the association between blood pressure (BP) 15-90 days postpartum and incident hypertension after an HDP.

Methods

This was a retrospective cohort study of women with an HDP between January 2014 and December 2017 at two health systems in the southeastern U.S. Cox proportional hazards models assessed the association of postpartum BP and incident hypertension 12 months postpartum. Covariates included type of HDP, gestational age at diagnosis, timing of measurement, comorbidities, and structural determinants of health. We excluded people with preexisting hypertension and without a BP measurement 15-90 days postpartum.

Results

Out of 5657 women, only 2514 (44%) met the inclusion criteria as almost 40% (2125) did not have a BP check at 15-90 days postpartum. The hazards of incident hypertension were significantly higher for those with elevated systolic postpartum BP (1.70, 95% CI: 1.37 - 2.12) and more severe HDPs. The estimated cumulative incidence of hypertension among participants with postpartum BP of 110/65 mmHg was 4.7% (CI, 2.0% - 7.4%) and for those with BP 140/90, it was 13.0% (CI 5.6% - 19.8%).

Conclusions

The risk of incident hypertension after an HDP is high in the first year postpartum. Despite this, for many participants, BP was not even measured within 15-90 days postpartum despite. Opportunities exist to improve care for individuals with HDPs.
Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking
Authors: Loughran Ryan M. , Arora Gurpreet K. , Sun Jiachen , Llorente Alicia , Crabtree Sophia , Ly Kyanh , Huynh Ren-Li , Cho Wonhwa , Emerling Brooke M.
Published: January 2025

In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport. In this study, we investigate a previously underexplored function of PI5P4Ks, which catalyzes the conversion of PI(5)P to PI(4,5)P2at intracellular membranes. Our findings reveal that PI5P4Ks play a key role in facilitating lysosomal cholesterol transport, regulating lysosome positioning, and sustaining growth signaling via the mTOR pathway. While PI5P4Ks have previously been implicated in mTOR signaling and tumor proliferation in p53-deficient contexts, this work elucidates an upstream mechanism that unifies these earlier observations.
Studying sleep orthologs in Epsilonproteobacteria through an evolutionary lens: Investigating sleep mysteries through phylogenomics
Authors: Pandi-Perumal Seithikurippu R , Saravanan Konda Mani , Paul Sayan , Warren Spence David , Chidambaram Saravana Babu
Published: January 2025

The current study employed phylogenomic methods to examine the evolutionary role and significance of sleep-related genes inSulfurimonas paralvinellaeof the Epsilonproteobacteria class. This has facilitated the identification of conserved sleep orthologs, including DnaK, serine hydroxymethyltransferase, and potassium channel family proteins, exhibiting sequence similarities ranging from 39.13% to 61.45%. These findings align with prior research indicating that chaperones and ion channels are conserved during sleep. This was demonstrated by the observation that proteins with fewer domains exhibited more significant conservation than others, such as adenylate kinase, which is substantial under selective pressure. Distinct adaptations in bifunctional protein - serine/threonine kinases and phosphatases were linked toS. paralvinellae, an extremophilic organism adapted to high-pressure and/or high-temperature conditions, indicating functional divergence influenced by the organism’s environment. The Gene Ontology study results indicated catalytic activity, potassium channel function, and cellular processes, underscoring the significance of ion channels in regulating the sleep-wake cycle. Furthermore, the categories not recognized as particularly significant for the over-represented genes encompassed metabolic and signal transduction categories, suggesting enhanced functional flexibility within this protein subfamily. The findings emphasize that orthologous interactions are complex and influenced by subfunctionalization and neofunctionalization of ecology and evolution. These findings enhance the existing understanding of the evolution of sleep-related genes and their association with metabolic and environmental changes, providing a foundation for subsequent experimental investigations and cross-taxonomic comparisons.
From Nets to Molecules: A Comparative Study of Stream Fish Diversity Recovery Using Different Sampling Methods in Eastern Amazonia
Authors: Rosa Fabricio dos Anjos Santa , Carvalho Cintia Oliveira , Queiroz Anna Karolina Oliveira de , Silva Derlan José Ferreira , Barreto Silvia Britto , Thorbek Birgitte Lisbeth Graae , Sales João Bráullio de Luna , Mauvisseau Quentin , de Boer Hugo , Ready Jonathan Stuart
Published: January 2025

The Neotropical freshwaters of South America host an exceptional level of ichthyofaunal diversity with over 5,160 species, making it the richest continental fauna worldwide. Despite their richness, these freshwater ecosystems face severe threats from human activities, leading to significant declines in fish populations. Traditional fish sampling techniques, such as netting, have been fundamental to ichthyology, offering insights into species richness and abundance. However, the complexity of stream environments limits the effectiveness of conventional sampling tools. As a result, more elusive or niche species are often missed. In recent years, water environmental DNA (eDNA) has emerged as a complementary method to traditional sampling. It allows for detection of aquatic organisms from water samples, expanding the scope of biodiversity assessments. Nevertheless, eDNA filtration faces challenges, especially in turbid waters, including the likelihood of co-extracting inhibitors that can affect amplification and detection processes, as well as the downstream flow of eDNA signals, which means that samples predominantly detect upstream fauna. To address these limitations, the use of bulk samples, such as stomach contents, provides a robust alternative by directly analyzing biological tissues and leveraging the bidirectional mobility of organisms within the stream, enabling the detection of taxa from both upstream and downstream regions. Given these issues, this study combines traditional netting, water eDNA analysis, and dietary metabarcoding to assess the fish biodiversity in three Neotropical streams in the Capim River basin, Pará, Brazil. The integration of multiple sampling techniques offers a more accurate picture of biodiversity, helping to overcome the limitations of each individual method and providing essential insights for conservation efforts.
Brain-Guided Convolutional Neural Networks Reveal Task-Specific Representations in Scene Processing
Authors: Hansen Bruce C. , Greene Michelle R. , Lewinsohn Henry A.S. , Kris Audrey E. , Smyth Sophie , Tang Binghui
Published: January 2025

Scene categorization is the dominant proxy for visual understanding, yet humans can perform a large number of visual tasks within any scene. Consequently, we know little about how different tasks change how the scene is processed, represented, and its features ultimately used. Here, we developed a novel brain-guided convolutional neural network (CNN) where each convolutional layer was separately guided by neural responses taken at different time points while observers performed two different tasks on the same set of images. We then reconstructed each layer’s activation maps via deconvolution to spatially assess how different features were used as a function of task. The brain-guided CNN made use of image features that human observers identified as being crucial to complete each task starting around 244 ms and persisted to 402 ms. Critically, because the same images were used across the two tasks, the CNN could only succeed if the neural data captured task-relevant differences. Our analyses of the activation maps across layers revealed that the brain’s spatiotemporal representation of local image features evolves systematically over time. This underscores how distinct image features emerge at different stages of processing, shaped by the observer’s goals and behavioral context.
Genome-wide analysis of DtxR and HrrA regulons reveals novel targets and a high level of interconnectivity between iron and heme regulatory networks inCorynebacterium glutamicum
Authors: Krüger Aileen , Weber Ulrike , Frunzke Julia
Published: January 2025

Iron is an essential trace element required by nearly all organisms as a cofactor in enzymes, regulatory proteins, and cytochromes of the respiratory chain. Maintaining iron homeostasis is crucial, since elevated levels cause oxidative stress through the formation of reactive oxygen species. InCorynebacterium glutamicum, iron and heme homeostasis are tightly interconnected and controlled by the global regulators DtxR and HrrA. While DtxR senses intracellular Fe2+, the two-component system HrrSA is activated by heme, functioning as a global regulator of heme homeostasis. This study provides the first genome-wide analysis of DtxR and HrrA binding dynamics under varying iron and heme conditions using chromatin affinity purification sequencing (ChAP-seq). Our conditional ChAP- Seq approach revealed 25 novel DtxR targets and 210 previously unrecognized HrrA targets. Among these,metH,encoding homocysteine methyltransferase, andxerC,encoding a tyrosine recombinase, were bound by DtxR exclusively under heme conditions, underscoring condition-dependent variation in DtxR binding. Activation ofmetHby DtxR links iron metabolism to methionine synthesis, potentially relevant for the mitigation of oxidative stress. Beyond novel targets, this study highlights the interconnected nature of the DtxR and HrrA regulons, identifying 16 shared targets with in some cases overlapping operator sequences. Strikingly, we provide several examples for weak ChAP-Seq peaks, often disregarded in global approaches, that feature a significant impact of the regulator on differential gene expression. These findings emphasize the importance of genome-wide profiling under different conditions to uncover novel targets and shed light on the complexity and dynamic nature of bacterial regulatory networks.

Importance

The trace element iron is essential for life, but elevated levels can rapidly cause cellular damage through oxidative stress. Bacteria, likeCorynebacterium glutamicum, tightly regulate iron and heme homeostasis via the global regulators DtxR and HrrA. This study provides the first analysis of the genome-wide binding patterns of these two regulators demonstrating significant differences in binding dependent on the tested iron regimes. Overall, we identified 25 new DtxR targets and 210 previously unknown HrrA targets, including genes with crucial roles in central metabolism and DNA repair. Notably, DtxR was shown to link iron metabolism to methionine synthesis, which might be important to protect the cell from oxidative stress. Our findings highlight the interconnected nature of DtxR and HrrA networks and underscore the value of condition-specific analysis to deepen the understanding of how bacteria adapt to environmental changes.
Estimating the distribution of fitness effects in aye-ayes (Daubentonia madagascariensis), accounting for population history as well as mutation and recombination rate heterogeneity
Authors: Soni Vivak , Versoza Cyril J. , Pfeifer Susanne P. , Jensen Jeffrey D.
Published: January 2025

The distribution of fitness effects (DFE) characterizes the range of selection coefficients from which new mutations are sampled, and thus holds a fundamentally important role in evolutionary genomics. To date, DFE inference in primates has been largely restricted to haplorrhines, with limited data availability leaving the other suborder of primates, strepsirrhines, largely under-explored. To advance our understanding of the population genetics of this important taxonomic group, we here map exonic divergence in aye-ayes (Daubentonia madagascariensis) – the only extant member of the Daubentoniidae family of the Strepsirrhini suborder. We further infer the DFE in this highly-endangered species, utilizing a recently published high-quality annotated reference genome, a well-supported model of demographic history, as well as both direct and indirect estimates of underlying mutation and recombination rates. The inferred distribution is generally characterized by a greater proportion of deleterious mutations relative to humans, providing evidence of a larger long-term effective population size. In addition however, both immune-related and sensory-related genes were found to be amongst the most rapidly evolving in the aye-aye genome.
Endothelial Sensitivity to Pro-Fibrotic Signals Links Systemic exposure to Pulmonary Fibrosis
Authors: Möbus Lena , Ylä-Outinen Laura , Mannino Luca , Migliaccio Giorgia , Kosunen Karoliina , D’Alessandro Nicoletta , Serra Angela , Greco Dario
Published: January 2025

Pulmonary fibrosis (PF) is a life-threatening condition characterised by excessive extracellular matrix deposition and tissue scarring. While much of PF research has focused on alveolar epithelial cells and fibroblasts, endothelial cells have emerged as active contributors to the disease initiation, especially in the context of systemic exposure to pro-fibrotic substances. Here, we investigate early transcriptomic and secretory responses of human umbilical vein endothelial cells (HUVEC) to subtoxic doses of bleomycin, a known pro-fibrotic agent, and TGF-beta, a key cytokine in fibrosis. Bleomycin exposure induced a rapid and extensive shift in the endothelial transcriptional programme, including signatures of endothelial to mesenchymal transition, cellular senescence, and immune cell recruitment. These findings suggest endothelial cells as early initiators of pro-fibrotic signals, independent of contributions from other cell types. In contrast, TGF-beta effects were limited and transient, indicating its pro-fibrotic action may require another initial stimulus and interplay with other cells like fibroblasts. This study highlights the sensitivity of endothelial cells to systemic pro-fibrotic exposure and provides a blueprint of early pro-fibrotic mechanisms, emphasising their pivotal role in PF pathogenesis.
Iron retention coupled with trade-offs in localized symbiotic effects confers tolerance to combined iron deficiency and drought in soybean
Authors: Hasan Md Rokibul , Thapa Asha , Kabir Ahmad H.
Published: January 2025

Iron (Fe) and water availability are closely interlinked, with deficiencies in both adversely affecting soybean growth. However, the strategies employed by soybean to tolerate such conditions remain poorly understood. This study elucidates the interactions of physiological adjustments, host factors, and microbial associations in soybean using multi-omics approaches in Clark (tolerant) and Arisoy (sensitive) genotypes exposed to Fe deficiency and drought. Clark demonstrated stress resilience by maintaining osmotic balance, nutritional status, and photosynthetic efficiency, whereas these were severely affected in Arisoy. Furthermore, Fe retention in Clark, accompanied by the upregulation of ferritin-like proteins, may mitigate oxidative stress by reducing Fenton reactions. Interestingly, the elevated jasmonic acid and salicylic acid in the roots of Clark, compared to the lower levels in Arisoy, may contribute to differential physiological adjustments for stress adaptations. RNA-seq analysis revealed 818 and 500 upregulated, along with 931 and 361 downregulated genes, in roots of Clark and Arisoy, respectively, under stress. We observed the upregulation of symbiotic genes, such asChalcone-flavonone isomerase1 andSWEET10, accompanied by increased rhizosphere siderophore and root flavonoid in Clark. This indicates a significant microbial role in driving differential stress tolerance. Amplicon sequencing revealed distinct root and nodule microbiome dynamics, with Clark recruiting beneficial microbes such asVariovoraxandPaecilomyces, known for promoting plant growth, whereas Arisoy displayed an opposite pattern. In addition, Clark maintainedBradyrhizobiumand tissue nitrogen status, supported by ammonium retention and induction ofAmmonium transporter1 in the roots. Furthermore,in vitrocompatibility betweenV. paradoxusand P. lilacinussuggests a synergistic interaction, with their localized signals benefiting Clark. Remarkably, enriched microbiomes significantly improved growth parameters, accompanied by elevated rhizosphere siderophore in sensitive genotypes under stress. This study is the first to uncover mechanisms of dual stress tolerance in soybean that may advance breeding and biofertilizer strategies for climate resilience.
The microtubule-severing enzyme spastin regulates spindle dynamics to promote chromosome segregation inTrypanosoma brucei
Authors: Souza Onofre Thiago , Zhou Qing , Li Ziyin
Published: January 2025

Microtubule-severing enzymes play essential roles in regulating diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching protozoan parasiteTrypanosoma brucei, microtubule-severing enzymes are involved in cytokinesis and flagellum length control during different life cycle stages, but none of them have been found to regulate mitosis in any life cycle form. Here, we report the biochemical and functional characterization of the microtubule-severing enzyme spastin in the procyclic form ofT. brucei. We demonstrate that spastin catalyzes microtubule severingin vitroand ectopic overexpression of spastin disrupts spindle microtubulesin vivoin trypanosome cells, leading to defective chromosome segregation. Knockdown of spastin impairs spindle integrity and disrupts chromosome alignment in metaphase and chromosome segregation in anaphase. We further show that the function of spastin requires the catalytic AAA-ATPase domain, the microtubule-binding domain, and the microtubule interacting and trafficking domain, and that the association of spastin with spindle depends on the microtubule-binding domain. Together, these results uncover an essential role for spastin in chromosome segregation by regulating spindle dynamics in this unicellular eukaryote.
Maternal type 2 immunity promotes a microchimeric transfer of systemic type 2 immunity to offspring
Authors: Gabier Malika , Darby Matthew , Chetty Alisha , Taliep Aisha , Cook Peter , Ryffel Bernhard , Dewals Benjamin , Oudhoff Menno , Cunningham Adam , Hickey Emer , Horsnell William
Published: January 2025

During maternity mothers undergo an immune pivot to a type 2 immune phenotype which is independent of any antigen experience. In this study we present this maternal Type 2 immunity as a key enabler of optimal maternally-driven microchimeric transfer of immunity to helminth infection in offspring.

To demonstrate that maternal type 2 immunity dictates offspring immunity we nursed wildtype (WT) offspring on WT or IL-4Rα-/-foster mothers. WT offspring nursed on IL-4Ra-/-mothers acquired a reduced type 2 immune signature compared to WT offspring nursed on WT mothers. This demonstrated maternal IL-4Rα imprints type 2 immunity in offspring. This increased type 2 immunity in offspring related to a maternal IL-4Rα dependent increased frequency of maternal microchimeric cells (MMc) being detected in offspring. Higher worm burdens were detected in offspring nursed on IL-4Rα-/-mothers, demonstrating that an antigen independent promotion of maternal type 2 immunity provides offspring with protective immunity against a helminth infection. To establish the contribution of increased MMc in offspring nursed on WT mothers in the control of infection, we undertook an antibody mediated depletion of MMc cells in WT offspring. This MMc depletion impaired the control of infection and reduced the magnitude of offspring type 2 immune response against a helminth infection. These findings present antigen independent maternal IL-4Rα driven type 2 immunity during pregnancy as critical for imparting a profound immune influence via MMc on offspring immunity to infection.
Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation
Authors: Kwaku Geneva N. , Jensen Kirstine Nolling , Simaku Patricia , Floyd Daniel J. , Saelens Joseph W. , Reardon Christopher M. , Ward Rebecca A. , Basham Kyle J. , Hepworth Olivia W. , Vyas Tammy D. , Zamith-Miranda Daniel , Nosanchuk Joshua D. , Vyas Jatin M. , Brown Harding Hannah
Published: January 2025

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted byCandida albicanstrigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway. Here, we show that despite sharing similar properties of morphology and internal DNA content, the interactions between EVs and the innate immune system differ according to the parental fungal species. EVs secreted byC. albicans,Saccharomyces cerevisiae, Cryptococcus neoformans,andAspergillus fumigatusare endocytosed at different rates by murine macrophages triggering varied cytokine responses, innate immune signaling, and subsequent immune cell recruitment. Notably, cell wall constituents that decorateC. neoformansandA. fumigatusEVs inhibit efficient internalization by macrophages and dampen innate immune activation. Our data uncover the transcriptional and functional consequences of the internalization of diverse fungal EVs by immune cells and reveal novel insights into the early innate immune response to distinct clinically significant fungal pathogens.
DNA supercoiling modulates eukaryotic transcription in a gene-orientation dependent manner
Authors: Morao Ana Karina , Chervova Almira , Zhao Yuya , Ercan Sevinc , Cecere Germano
Published: January 2025

Transcription introduces torsional stress in the DNA fiber causing it to transition from a relaxed to a supercoiled state that can propagate across several kilobases and modulate the binding and activity of DNA-associated proteins. As a result, transcription at one locus has the potential to impact nearby transcription events. In this study, we asked how DNA supercoiling affects histone modifications and transcription of neighboring genes in the multicellular eukaryoteCaenorhabditis elegans. We acutely depleted the two major topoisomerases and measured nascent transcription by Global Run-on sequencing (GRO-seq), RNA Polymerase II occupancy by ChIP-seq, gene expression by RNA-seq and four transcription-associated histone modifications by Cut & Tag. Depletion of topoisomerases I and II led to genome-wide changes in transcription dynamics, with minor disruptions to the histone modification landscape. Our results showed thatC. eleganstopoisomerase I is required for transcription elongation and is partially redundant with topoisomerase II. Analysis of transcription changes with respect to neighboring genes suggest that negative supercoiling promotes the transcription of genes with a divergent neighbor and positive supercoiling suppresses transcription of convergent genes. Additionally, topoisomerase depletion caused coordinated changes in the expression of divergent gene pairs, suggesting that negative supercoiling drives their synchronized expression. Conversely, the coordinated expression of convergent genes was disrupted, suggesting that excessive positive supercoiling inhibits transcription. Overall, our data supports a model in which DNA supercoiling generated by transcription at one site propagates along the eukaryotic chromatin fiber, influencing nearby transcription in an orientation-dependent manner.
Structural basis of directionality control in large serine integrases
Authors: Shin Heewhan , Pigli Ying , Peña Reyes Tania , Fuller James R. , Olorunniji Femi J. , Rice Phoebe A.
Published: January 2025

Large serine integrases (LSIs) catalyze unidirectional site-specific DNA recombination reactions, yet those reactions are reversed by the presence of a cognate recombination directionality factor (RDF). Mechanistic understanding of directionality control has been hampered by a lack of structural information. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of six SPbeta integrase—DNA complexes along the integrative (-RDF) and excisive (+RDF) reaction pathways, at 4.16-7.18Å resolution. Our findings reveal how RDF-mediated repositioning of an integrase subdomain (1) dictates which pairs of DNA sites can be assembled into a synaptic complex to initiate recombination and (2) dictates which product complexes will be conformationally locked, preventing the back reaction. These mechanistic insights provide a conceptual framework for engineering efficient and versatile genome editing tools.
Precise evaluation of time-varying quadrupole field errors through closed-orbit measurements in the J-PARC main ring
Authors: Asami Takashi , Hotchi Hideaki , Igarashi Susumu , Koseki Tadashi , Sato Yoichi , Yamamoto Noboru , Yasui Takaaki
Published: January 2025

In the main ring (MR) of the Japan Proton Accelerator Research Complex, one of the primary sources of beam loss is the betatron resonance. A factor determining the strength of betatron resonances is the symmetry of optics, which relies on the quadrupole field errors in the ring. In the beam tuning of the MR, correcting quadrupole field errors plays a significant role in reducing beam loss. This paper introduces and examines a precise method to evaluate time-varying quadrupole field errors at individual quadrupole magnets around the ring through closed-orbit measurements in the MR. By applying this method, we experimentally determined substantial quadrupole field errors due to eddy currents on the vacuum ducts during acceleration. The methods developed in this paper are employed in the beam tuning for the user operations of the MR.

Published by the American Physical Society
2025
Multitwist Trajectories and Decoupling Zeros in Conformal Field Theory
Authors: Homrich Alexandre , Simmons-Duffin David , Vieira Pedro
Published: January 2025

Conformal Regge theory predicts the existence of analytically continued conformal field theory data for complex spin. How could this work when there are so many more operators with large spin compared to small spin? Using planar N=4 SYM as a test ground, we find a simple physical picture. Operators do organize themselves into analytic families but the continuation of the higher families have zeros in their structure operator product expansion constants for lower integer spins. They thus decouple. Newton’s interpolation series technique is perfectly suited to this physical problem and will allow us to explore the complex spin half-plane.

Published by the American Physical Society
2025
Dynamical quantum maps for single-qubit gates under universal non-Markovian noise
Authors: Sánchez Velázquez J. M. , Steiner A. , Freund R. , Guevara-Bertsch M. , Marciniak Ch. D. , Monz T. , Bermudez A.
Published: January 2025

Noise is both ubiquitous and generally deleterious in settings where precision is required. This is especially true in the quantum technology sector where system utility typically decays rapidly under its influence. Understanding the noise in quantum devices is thus a prerequisite for efficient strategies to mitigate or even eliminate its harmful effects. However, this requires resources that are often prohibitive, such that the typically used noise models rely on simplifications that sometimes depart from experimental reality. Here we derive a compact microscopic error model for single-qubit gates that only requires a single experimental input—the noise power spectral density. Our model goes beyond standard depolarizing or Pauli-twirled noise models, explicitly including non-Clifford and non-Markovian contributions to the dynamical error map. We gauge our predictions for experimentally relevant metrics against established characterization techniques run on a trapped-ion quantum computer. In particular, we find that experimental estimates of average gate errors measured through randomized benchmarking and reconstructed via quantum process tomography are tightly lower-bounded by our analytical estimates, while the depolarizing model overestimates the gate error. Our noise modeling including non-Markovian contributions can be readily applied to established frameworks such as dynamical decoupling and dynamically corrected gates, or to provide more realistic thresholds for quantum error correction.

Published by the American Physical Society
2025
crystchemlib: a Python library and GUI for analysis of crystal structure datasets
Authors: Rashchenko Sergey V.
Published: January 2025

The problem of extracting basic (e.g. bond lengths and angles) and advanced (e.g. polyhedron volumes and effective coordination numbers) crystal chemical parameters from large datasets of CIFs in a quick and flexible way is addressed by a lightweight Python library with a graphical user interface (GUI). A description of library functionality in the GUI and scripting modes followed by examples based on open-access data demonstrate its advantages for crystallographers working with pressure-, temperature- and chemistry-induced structural variations, as well as with analysis of structural databases.