bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell atlas of BAL from preschool cystic fibrosis reveals key inflammatory pathways modified by the CFTR modulator ivacaftor in the early life lung
Authors: Maksimovic Jovana , Shanthikumar Shivanthan , Howitt George , Dixit Gunjan , Hickey Peter F , Anttila Casey , Brown Daniel V. , Senabouth Anne , Amann-Zalcenstein Daniela , Powell Joseph E. , Ranganathan Sarath C. , Oshlack Alicia , Neeland Melanie R. 
Published: February 2025

ABSTRACTAberrant inflammation and structural lung damage occurs early in life for people with cystic fibrosis (CF). Even in the era of CFTR modulators, anti-inflammatory therapy may still be needed to prevent establishment and lifelong consequences of bronchiectasis. In this study, we integrated transcriptome-wide single-cell RNA sequencing data, highly multiplexed surface protein expression, and functional pathway analysis to create a comprehensive paediatric lower airway atlas of 44 immune and epithelial cell populations in bronchoalveolar lavage (BAL). We then analysed this atlas to investigate inflammatory cell responses in children with CF to show widespread dysregulation of macrophage function in the preschool CF lung. This included alterations in pathways associated with SARS-COV and influenza responses, TNF/IFN signalling, cholesterol homeostasis, and pulmonary fibrosis that were further altered by the early development of bronchiectasis. We showed that the CFTR modulator ivacaftor restores some of these macrophage-related functional deficits and reduces expression of pathways associated with neutrophil infiltration, however the modulator lumacaftor/ivacaftor was not associated with any detectable change in transcriptional response. This work represents a comprehensive, multi-omic single-cell analysis of bronchoalveolar lavage from preschool children and the results inform the future development of anti-inflammatory therapy for children with CF.
Machine Learning-Based Drug Response Prediction Identifies Novel Therapeutic Candidates for Colorectal Cancer Cell Line KM-12
Authors: Chanchabi Cyrine , Paul Conception , Coulon Vincent , Cicalini Ilaria , Pierogostino Damiana , Vishwakarma Sachin , Hernández-Hernández Saiveth , Ballester Pedro J. , Hahne Michael 
Published: February 2025

AbstractOne major hurdle in the discovery of new drugs is the limited capacity of traditional screening methods to efficiently explore the immense space of drug candidates. To bypass this difficulty, computational approaches such as virtual screening (VS) have been developed supported by Machine Learning (ML) models to predict the activities of drug-like molecules on a given target. We developed a ML model for VS of a library of 25 million highly-diverse synthesis-on-demand molecules against the KM-12 colorectal cancer (CRC) cell line. By combining different biological readouts, we discovered compounds with a novel chemical scaffold, not yet described in the context of CRC, with either a prominent cytotoxic or cytostatic effect. This finding underpins the strength of our ML-guided VS protocol in discovering promising CRC drug leads triggering altered biological responses.
Fitness and Exercise Effects on Brain Age: A Randomized Clinical Trial
Authors: Wan Lu , Molina-Hidalgo Cristina , Crisafio Mary E. , Grove George , Leckie Regina L. , Kamarck Thomas W. , Kang Chaeryon , DeCataldo Mia , Marsland Anna L. , Muldoon Matthew F. , Scudder Mark R. , Rasero Javier , Gianaros Peter J. , Erickson Kirk I. 
Published: February 2025

AbstractObjectivesExamine the effect of aerobic exercise on structural brain age and explore potential mediators.MethodsIn a single-blind, 12-month randomized clinical trial, 130 healthy participants aged 26-58 years were randomized into a moderator-to-vigorous intensity aerobic exercise group or a usual-care control group. The exercise group attended 2 supervised 60-minute sessions per week in a laboratory setting plus home-based exercise to achieve 150 minutes of exercise per week. Brain-predicted age difference (brain-PAD) and cardiorespiratory fitness (CRF) were assessed at baseline and 12 months. Intention-to-treat (ITT) and completers analyses were performed.ResultsThe 130 participants (67.7% female) had a mean (SD) age of 41.28 (9.93) years. At baseline, higher CRF (VO2peak) was associated with smaller brain-PAD (β=-0.309, p=0.012). After the intervention, the exercise group showed a decrease in brain-PAD (estimated mean difference (EMD) =-0.60; 95% CI: -1.15 to -0.04; p=0.034) compared to the control group (EMD=0.35; 95% CI: -0.21 to 0.92; p=0.22); time×group interaction (between-group difference (BGD)= -0.95; 95% CI: -1.72 to -0.17; p=0.019). VO2peakimproved in the exercise group (EMD=1.60; 95% CI: 0.29 to 2.90; p=0.017) compared to the control group (EMD=-0.78; 95% CI: -2.17 to 0.60; p=0.26); time×group interaction (BGD=2.38; 95% CI: 0.52 to 4.25; p=0.015). Body composition, blood pressure, and brain-derived neurotrophic factor levels were unaffected. None of the proposed pathways statistically mediated the effect of exercise on brain-PAD. The results from completers were similar.ConclusionEngaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults. The pathways by which these effects occur remain unknown.Summary BoxWhat is already known on this topicMidlife risk factors influence brain aging, with physical activity conferring protective benefits, yet evidence for the effect of exercise on midlife brain age and underlying mechanisms remains limited.What this study addsParticipation in a 12-month aerobic exercise intervention significantly reduced a neuroimaging marker of brain age. Higher cardiorespiratory fitness was also associated with younger brain age.How this study might affect research, practice or policyFindings of this study complement the scarce literature examining the effects of exercise on early-to-midlife brain health and confirm the neuroprotective effects of aerobic exercise against accelerated brain aging in early-to-midlife adults.
Quantitative T1 mapping indicates elevated white matter myelin in children with RASopathies
Authors: Plank Julia R. , Gozdas Elveda , Bruno Jennifer , McGhee Chloe A. , Wu Hua , Raman Mira M. , Saggar Manish , Green Tamar 
Published: February 2025

AbstractBackgroundEvidence suggests pathological roles of myelination in neurodevelopmental disorders, but our understanding is limited. We investigated quantitative T1 mapping (QT1) as a clinically feasible tool for measuring myelination in children with neurodevelopmental disorders of the RAS-MAPK signaling pathway (RASopathies).MethodsWe collected QT1, diffusion-weighted, and structural MRI scans from 72 children (49 RASopathies, 23 typical developing (TD)). QT1 measures of myelin content included the macromolecular tissue volume (MTV) in white matter and R1 (1/T1 relaxation) of the cortex. For white matter, we assessed between-groups differences across 39 tracts. For cortical R1, we used principal components analysis to reduce dimensionality and capture myelination patterns across 360 regions. A multivariate ANOVA assessed differences across principal components. Finally, a support vector machine (SVM) identified the most discriminative features between TD and RASopathies.ResultsThirty-four of 39 tracts were higher in MTV in RASopathies relative to TD (pFDR<.05), indicating widespread elevation in myelination. Our MANOVA revealed a group effect on cortical R1 (p=.002,η2=.028), suggesting cortical myelination differences between-groups. SVM yielded an accuracy of 87% and identified cognitive and cortical R1 features as the most discriminant between-groups.ConclusionsWe found widespread elevated myelin in white matter tracts and region-dependent patterns of cortical myelination in children with RASopathies. QT1 enabled us to leverage preclinical models showing oligodendrocyte dysfunction to uncover the myelination patternin vivoin the developing human brain. Using QT1, myelin represents a promising treatment target that can be identified and monitored in neurodevelopmental disorders, offering significant potential for advancing current therapeutic strategies.
Post-stroke Urinary Tract Infections and Their Outcome: A Clinico-microbiological and Epidemiological Analysis based on A Stroke Registry
Authors: Hosseinzadeh Naeimeh , Khabbaz Aytak , Ahmadi Somayeh , Hejazian Seyyed Sina , Salehi-Pourmehr Hanieh , Hasani Roqaiyeh , Tahmasbi Fateme , Mehdizadeh Robab , Torabi Saba , Farhoudi Mehdi , Hasani Alka 
Published: February 2025

AbstractBackgroundUrinary tract infections (UTIs) are common among hospitalized stroke patients, leading to increased hospital stays and patient discomfort. While it’s known that post-stroke infections generally worsen outcomes, specific factors contributing to UTIs after stroke remain unclear.MethodsThis study aimed to investigate the incidence of post-stroke UTI (PSUTI) in patients admitted to the Hospitals from September 2020 to June 2021. The study included patients with a suspected diagnosis of stroke at the time of initial visit by a specialist. The final diagnosis was approved by an experienced neurologist and radiologist according to their brain CT scan. Data was collected from patients’ files, including demographics, comorbidities, drug history, smoking history, admission unit, clinical manifestations, systolic and diastolic blood pressure, type of stroke, etiology, laboratory findings, admission unit, in-hospital stay duration, therapies, use of NG tubes, urinary catheters, CV lines, brain drain, intratracheal tube, chest tube, dialysis catheter, and their durations.ResultsA study involving 612 patients found that PSUTI-positive patients had worse conditions at admission, with ischemic stroke being more common. They had longer stays in the ward or ICU, and were more likely to have a death outcome. The most common pathogen was Escherichia coli, followed by Staphylococcus epidermidis, Enterococcus spp, and Pseudomonas aeruginosa. In-hospital complications were more prevalent in PSUTI-positive patients, except for hydrocephalus and pulmonary embolism. Positive history of diabetes, falling symptoms, urinary catheter, and intubation were independent risk factors for post-stroke UTI.ConclusionThe study highlights the impact of urinary tract infections (UTIs) on stroke outcomes, revealing severe clinical profiles, comorbidities, longer hospital stays, and increased invasive interventions. Key risk factors like diabetes and urinary catheter use highlight the need for vigilant monitoring and tailored management strategies.
Precision in Spinal Cord Injury Research: A Novel Electromagnetic Impactor for a Consistent Porcine Model
Authors: Steger Leonard , Smit Constantin , Robinson Kayla , Leadingham Kelley M. Kempski , Davidar Daniel , Routkevitch Denis , Weber-Levine Carly , Jiang Kelly , Quiroz Victor , Bauer Stuart , Liang Ruixing , Suk Ian , Tyler Betty , Doloff Joshua C. , Theodore Nicholas , Manbachi Amir 
Published: February 2025

AbstractPurposeReplicating spinal cord injury (SCI) in large animals is necessary for evaluating therapeutics for potential human translation, yet there is currently no commercial, standardized device for inducing SCI. We present the fabrication and testing of a custom impactor device for producing repeatable contusion SCI in porcine models.MethodsWe first designed and built the device. Mechanical modeling was subsequently utilized to calibrate our benchtop testing setup. Benchtop verification was performed to measure impact force post calibration. We then used the device to generate a contusion SCI model in 2 pigs and the results were compared to an uninjured pig. Intraoperative ultrasound was used to visualize a hematoma in the injured spinal cord. Hematoxylin-eosin (H&E) and Masson’s trichrome staining were used to confirm injury presence onex vivospinal cord samples.ResultsMechanical modeling forces matched benchtop impact forces within 1.4 N, indicating successful calibration of the testing setup. Our device demonstrated repeatability and the potential for modulating injury severity on the benchtop. Impactor forces were demonstrated across a range from 12.8 to 67.6 N, with variability remaining within 0.2 to 0.7 N standard deviation. The device induced two contusion injuries of different severityin vivo, confirmed by intraoperative ultrasound imaging and post-excision histology of the spinal cord.ConclusionOur impactor device is a major advancement towards producing repeatable and titratable contusions in large animal SCI models.
Identification of the Lipid Oxygen Radical Defense pathway and its epigenetic control
Authors: Mesquita Francisco S. , Abrami Laurence , Forey Romain , Kunz Béatrice , Raclot Charlène , Bracq Lucie , Martins Filipe , Milovanovic Danica , Planet Evarist , Rosspopoff Olga , Trono Didier , van der Goot F. Gisou 
Published: February 2025

ABSTRACTMembrane phospholipids are vulnerable to oxidative radicals, and uncontrolled lipid peroxidation can compromise cell viability. To mitigate lipid damage, cells have evolved defense mechanisms, the genetic regulation of which is not fully understood. Here, we identify the Lipid Oxygen Radical Defense (LORD) pathway. Under normal conditions, the pathway is epigenetically repressed by a complex comprising the KRAB-zinc finger protein ZNF354A, the scaffold protein KAP1/TRIM28, the histone methyltransferase SETDB1, and the transcriptional activator ATF2. In response to lipid peroxide accumulation, ATF2, KAP1, and ZNF354A undergo p38- and JNK-dependent phosphorylation, and the repressive complex disassembles, releasing ZNF354A from specific DNA loci. A protective gene network is subsequently activated, comprising targets of the major redox regulator NRF2 and modulating cellular sensitivity to oxidative stress and ferroptosis. These findings reveal a novel layer of epigenetic regulation in the cellular defense against lipid damage but also position the LORD pathway as a promising therapeutic target for diseases linked to chronic inflammation, neurodegeneration and cancer.
Racism in public health authorities – a scoping review and situational analysis
Authors: Wandschneider Lisa , Stieglitz Sigsten , Altmiks Theresa , Razum Oliver , Zielke Julia , Namer Yudit 
Published: February 2025

AbstractBackgroundWhile racism in health care services is increasingly well-researched, public health services and public health authorities (PHA) have been neglected as relevant contexts. Yet, public health authorities play an essential role in protecting and promoting population health at a local and national level.MethodWith a scoping review, we mapped the academic discourse on racism in PHA. We searched in PubMed, Embase, PsycINFO and CINAHL as well as the reference list of included academic literature. We included literature assessing racism in interactions between all stakeholders involved or in the actions (not) taken by PHA, while we excluded literature exclusively focusing on health care facilities.FindingsWe identified 55 publications that include survey and intervention studies as well as opinion pieces. Most of the literature focuses on the US, Australia and New Zealand. The Tuskegee experiment has been discussed extensively acknowledging the political and historical elements of the racist, inhumane practices and policies in PHA. More recent literature explores anti-racism approaches and how they can facilitate access for racialized, socially multiply stigmatized groups (e.g. screening uptake in racialized queer people).DiscussionThe literature on racism in PHA is limited, mostly processing historical policies. Studies on how racism affects equitable access to PHA and the associated health inequities are lacking. Positive examples highlight the importance of a) building the services in PHA on anti-racism and equity-driven principles and b) integrating and amplifying the voices of racialized community. Public health research on racism needs to extend the scope from health care services to the under researched public health services and authorities.
Compassion as a guiding framework for digital mental health implementation: an interview study with clients and professionals
Authors: van Lotringen Charlotte M. , Zirnheld Alec , Kelders Saskia M. , Westerhof Gerben J. , Noordzij Matthijs L. 
Published: February 2025

AbstractBackgroundDigital mental health interventions are often described in terms of their contribution to cost-effectiveness or innovation. Instead, many clients and professionals in mental healthcare seem to value the human connection highly. To implement technology in ways that align with values held by clients and professionals, a value-based framework for technology use in mental healthcare could be promising. The current study explores whether values of clients and professionals in mental healthcare match a framework of compassion, and whether this framework could be a suitable foundation for the implementation of digital mental health interventions.MethodWe conducted semi-structured interviews with 5 (former) clients and 15 professionals in mental healthcare. Values of both clients and professionals were analyzed inductively, and deductively linked to a compassion framework. Professionals were asked whether their values were congruent with their organization’s approach to technology. We coded their answers as matches and mismatches, and described the themes identified in both categories.ResultsValues held by clients and professionals showed many connections with the compassion framework. Clients highly valued feeling heard and understood, humanity, and openness from the professional. Professionals highly valued helping people, personalization, and offering transparency. Examples of how technology use could enhance or detract from compassion according to participants were also identified. Professionals experienced a match with their values if they felt that their organizations focused the adoption of technology on the client’s autonomy or meeting treatment needs. They experienced a mismatch if they felt that their organizations were more focused on financial benefit or a technology push.ConclusionCompassion seems a promising framework for integrating technology in mental healthcare in value-sensitive ways.
Macrogenetic atlas of prokaryotes
Authors: Yang Chao , Huang Hao , Wang Naike , Didelot Xavier , Yang Ruifu , Cui Yujun , Falush Daniel 
Published: February 2025

AbstractMacrogenetics investigates the patterns and predictors of intraspecific genetic variation across diverse taxa, offering a framework to address longstanding evolutionary hypotheses. Here, we present a comprehensive macrogenetic atlas of prokaryotes (MAP), integrating genomic data (summarized by 30 parameters in 12 categories) from 15,235 prokaryotic species and population genetic data (35 parameters in 7 categories) from 786 species with phylogenetic, phenotypic, and ecological data. We illustrate the power and potential of the MAP by addressing a series of fundamental questions. For example, we provide evidence that genome size in prokaryotes depends on a balance between deletion bias and the beneficial effects of additional genes. Moreover, we show that long-range and short-range linkage disequilibrium represent quite different features of evolutionary dynamics and contribute independently to genetic diversity. Notably, we show that as within-species diversity increases, selection becomes an increasingly strong force structuring diversity, for example creating convergent ecospecies structures inStreptococcus mitisandS. oralis. Overall, our atlas represents a widely applicable resource and offers novel insights into the drivers of macroevolution and the life-cycle of prokaryotic species.
Immunogenicity and protective efficacy of an intranasal neuraminidase-based influenza virus vaccine adjuvanted with bacterial cell membrane-derived adjuvants
Authors: Vasilev Kirill , Hoxie Irene , Puente-Massaguer Eduard , Yueh Joshua , Bhavsar Disha , Singh Maya , Mallett Corey P. , Zimmermann Joseph , Krammer Florian 
Published: February 2025

AbstractInfluenza virus neuraminidase (NA) has emerged as a promising vaccine candidate due to its relatively stable antigenic structure and the ability of NA-specific antibodies to provide cross-protection within influenza virus subtypes. Since the influenza virus causes respiratory infections in humans, developing mucosal vaccines to protect the entry site of the virus is of high importance. Recombinant NA requires adjuvants to induce a protective immune response after mucosal administration. In the current study, we analyze the immunogenicity and protective efficacy of a recombinant NA-based influenza virus vaccine administered intranasally in combination with adjuvants consisting of outer membrane proteins fromNeisseria meningitidiscomplexed with exogenous lipopolysaccharides (LPS) fromShigella flexnerior endogenous LPS fromN. meningitidis. We evaluated the local and systemic humoral and cellular immune responses to adjuvanted recombinant N1 NA, analyzing the dynamics of local follicular T-helper (Tfh) cells and germinal center B cells (GCB) in nasal-associated lymphoid tissue (NALT) and tissue-resident memory T cells in lungs, as well as the levels of IgA and IgG in the upper and lower respiratory tracts. Finally, we performed a heterologous challenge study to test the ability of the investigated vaccine formulations to induce cross-protection. The study demonstrates that bacterial cell membrane-derived adjuvants significantly improve the immunogenicity and protective efficacy of the recombinant N1 NA-based influenza vaccine leading to protection against clade 2.3.4.4b H5N1 challenge. This finding supports the potential of these adjuvanted vaccines in providing effective mucosal immunity against influenza virus.
High-Throughput Conjugation Reveals Strain Specific Recombination Patterns Enabling Precise Trait Mapping in Escherichia coli
Authors: Corneloup Thibault , Bellengier Juliette , Magnan Mélanie , Chavan Arsh , Gachet Benoit , Dixit Zoya , Pintard Coralie , Baron Alexandra , Toko Doreen , Lambert Amaury , Choudhury Alaksh , Tenaillon Olivier 
Published: February 2025

AbstractGenetic exchange is a cornerstone of evolutionary biology and genomics, driving adaptation and enabling the identification of genetic determinants underlying phenotypic traits. InEscherichia coli, horizontal gene transfer via conjugation and transduction not only promotes diversification and adaptation but has also been instrumental in mapping genetic traits. However, the dynamics and variability of bacterial recombination remain poorly understood, particularly concerning the patterns of recombined DNA fragments. To elucidate these patterns and simultaneously develop a tool for trait mapping, we designed a high-throughput conjugation method to generate recombinant libraries. Recombination profiles were inferred through whole-genome sequencing of individual clones and populations after selection of a marker from the donor strain in the recipient. This analysis revealed an extraordinary range of recombined fragment sizes, spanning less than ten kilobases to over a megabase—a pattern that varied across the three tested strains. Mathematical modelling indicated that this diversity in recombined fragment size enables precise identification of selected loci following genetic crosses. Consistently, population sequencing pinpointed a selected marker at kilobase-scale accuracy, offering a robust tool for identifying subtle genetic determinants that could include point mutations in core genes. These findings challenge the conventional view that conjugation always transfers large fragments, suggesting that even short recombined segments, traditionally attributed to transduction, may originate from conjugation.