bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender and mental health of adolescents: a conceptual framework developed in a Delphi study
Authors: Alaze Anita , Grosser John , Razum Oliver , Miani Céline 
Published: January 2025

AbstractObjectiveAdolescence is one of the most neglected developmental phases, yet there are few phases in the life course when gender socialisation is as intense. So far, no framework or theory exists that theoretically conceptualises gender norms, gender attitudes and mental health outcomes. To address this gap, we aim to develop a conceptual framework that illustrates the interplay of key constructs in the gendered pathways of health, using the Delphi technique.MethodsWe carried out a Delphi study enrolling an international panel of 21 experts from different disciplines, with 43% of the respondents completing all three survey rounds. We asked the experts to identify core constructs (first round), suggest operationalisations of the constructs (second round), and to hypothesise about their relationships (third round). Items were included, excluded or adapted according to experts’ feedback. A 70% threshold was used for consensus.ResultsThe panelists consented on the following core constructs: gender norms (social environment), sex assigned at birth, gender attitudes, gender roles, competencies, and gender identity to the mental health of adolescents. They further consented on gender approaches, namely the intersectional, multidimensional and multilevel approach as well as the power relations lens. The operationalisation of the constructs in round two led to the inclusion of variables forming an intersectional lens and four social environment levels: the household, community, political and digital level. In round three, the experts formed 14 hypotheses about the relationships between the core constructs.ConclusionThe derived conceptual framework links the interplay of six key constructs, four gender approaches and four social environment levels to adolescent mental health. Future research should validate and apply the hypothesised relationships between the constructs to disentangle the gendered pathways to (mental) health in adolescence.
More than the sum of its parts? An analysis of the factors impacting the content of antenatal care consultations in the Democratic Republic of Congo
Authors: Han Rui , Hagedorn Brittany 
Published: January 2025

AbstractBackgroundPrevious studies have shown that in lower and middle-income countries, although antenatal care (ANC) coverage has increased significantly, maternal mortality remained high due to poor quality of care. Despite established protocols, recommended actions are not consistently completed and the causes are not well understood. We sought to unpack this by analyzing direct observations of ANC consultations from the Democratic Republic of Congo (DRC).MethodsWe conducted secondary analysis of data from the Health System Strengthening for Better Maternal and Child Health Results Project (2015-2022) evaluation. We examined completion rates of twenty recommended actions for a first ANC visit. We identified contributing factors using chi-squared tests on completion rates, in samples stratified by availability of essential items and provider characteristics. We used regressions to estimate the relative importance of facility, provider, and patient characteristics in determining completion rates and the effect of availability of the essential item for different care components.ResultsWe observed a statistically significant increase between baseline and endline in supply-side readiness (equipment and supplies) and quality of care for six recommended actions. While structural readiness was a significant predictor of quality, we found that provider qualifications and female gender had significant positive associations with completion rates, partially explaining the observed variation in care quality. For example, female A1 nurses prescribed tetanus vaccination for 70% of patients, male A1 nurses to 55%, and midwives to 51%. After decomposing the reasons for poor quality, we found that in addition to supply-side gaps (64% at baseline, 51% at endline), the know-do gap contributed to 30% of incompletions at baseline (21% at endline). Patient characteristics were rarely predictive of quality.ConclusionsWhile supply-side gaps continue to be important barriers to service quality for ANC visits, especially preventive treatments and diagnostics, addressing these alone is inadequate. This is especially true for the physical exam, where interpersonal and behavioral barriers persist and we see evidence of gendered differences in quality of care. Interventions to improve the performance of all providers is critical to ensure that every person receives the best possible care.
A clinical algorithm to identify people with the glucose-6-phosphate dehydrogenase p.Val68Met variant at risk for diabetes undertreatment
Authors: Pershad Yash , Breeyear Joseph H , Corty Robert W , Mosley Jonathan D , Giri Ayush , Roden Dan M , Edwards Todd L , Bick Alexander G 
Published: January 2025

AbstractPurposeTo develop an algorithm using routine clinical laboratory measurements to identify people at risk for systematic underestimation of glycated hemoglobin (HbA1c) due to p.Val68Met glucose-6-phosphate dehydrogenase (G6PD) deficiency.MethodsWe analyzed 122,307 participants of self-identified Black race across four large cohorts with blood glucose, HbA1c, and red cell distribution width measurements from a single blood draw. In UK Biobank, we used recursive partitioning to develop criteria for possible and likely G6PD deficiency. We validated the algorithm in NIH All of Us, Vanderbilt BioVU, and the Million Veterans Program. In Vanderbilt’s Synthetic Derivative, we created a cohort of 48,031 participants with type 2 diabetes and no genetic data to test whether predicted risk for G6PD deficiency was associated with incident diabetic retinopathy.ResultsG6PD deficiency predictions in hemizygous males showed precision/recall of 31%/81% for possible and 81%/10% for likely deficiency. In homozygous females, precision/recall was 6%/76% for possible and 34%/13% for likely deficiency. Diabetic patients with predicted possible deficiency demonstrated 1.4-fold higher 20-year retinopathy rates (14.3% vs 11.2%, P=0.003).ConclusionWe report a simple clinical algorithm that enables healthcare systems to identify people who may benefit from G6PD genotyping and glucose-based diabetes monitoring.
Household Air Pollution Exposures Over Pregnancy and Maternal Blood Pressure Trajectories through 8 Years Postpartum: Evidence from the Ghana Randomized Air Pollution and Health Study (GRAPHS)
Authors: Kaali Seyram , Li Michelle , Mujtaba Mohamed Nuhu , Colicino Elena , Awuni Sule , Wylie Blair , Osei Musah , Tsotetsi Kholiswa , Yussif Tawfiq , Chillrud Steve , Jack Darby , Asante Kwaku Poku , Lee Alison 
Published: January 2025

AbstractBackgroundHousehold air pollution is a major contributor to cardiovascular disease burden in women in Sub-Saharan Africa. However, little is known about exposures during pregnancy or the effect of clean cooking interventions on postpartum blood pressure trajectories.MethodsThe Ghana Randomized Air Pollution and Health Study (GRAPHS) randomized 1414 non-smoking women in the first and second trimesters to liquefied petroleum gas (LPG) or improved biomass stoves – vs control (traditional three-stone open fire). Personal exposure to carbon monoxide was measured at four prenatal timepoints and three times over the first postpartum year. Participants were prospectively followed with annual resting BP measurements at 2, 4, 5, 6, 7, and 8 years postpartum. We employed linear mixed effects models to determine effect of GRAPHS interventions on postpartum BP, and to examine associations between prenatal and postnatal CO and postpartum BP.ResultsLPG intervention was associated with 3.54mmHg (95% CI-5.55,-1.53) lower change in systolic BP from enrolment through 8 years postpartum, and 2.27mmHg (95% CI-3.61,-0.93) lower change in diastolic BP from enrolment through 8 years postpartum, as compared to control. In exposure-response analysis, average prenatal CO was positively associated with change in systolic BP from enrolment (β=0.71mmHg, 95% CI 0.08, 1.30, per doubling of CO)ConclusionsLPG cookstove intervention initiated in early pregnancy and maintained through the first postpartum year was associated with lower systolic and diastolic BP trajectories through 8 years postpartum. These findings support the need to integrate clean cooking solutions into existing antenatal care packages.
Behavioral investigation of allocentric and egocentric cognitive maps in human spatial memory
Authors: Nett Laura , Guth Tim A. , Büchel Philipp K. , Rungratsameetaweemana Nuttida , Kunz Lukas 
Published: January 2025

AbstractSpatial memory is a fundamental cognitive function that enables humans and other species to encode and recall the locations of items in their environments. Humans employ diverse strategies to support spatial memory, including the use of cognitive maps. Cognitive maps are mental representations of the environment that organize its content along two or more continuous dimensions. In allocentric cognitive maps, these dimensions form a Cartesian coordinate system referenced to the environment. In egocentric cognitive maps, the dimensions form a polar coordinate system centered on the subject. To better understand how humans employ allocentric and egocentric cognitive maps for spatial memory, we performed a behavioral study with a novel task designed to directly and explicitly assess both types of cognitive maps. During encoding periods, participants navigated through a virtual environment and encountered objects at different locations. During recall periods, participants aimed at remembering these locations in abstract allocentric and egocentric coordinate systems. Our results show that relationships between the objects and the environment, such as their distance to boundaries and corners, were associated with allocentric memory performance. Relationships between the objects and the participant, including their distance and orientation to the participant’s starting position, were linked to egocentric memory performance. Spatial feedback during recall supported performance within allocentric and egocentric domains, but not across domains. These findings are compatible with the notion that allocentric and egocentric cognitive maps operate as (partially) independent systems for spatial memory, each specialized in processing specific types of spatial relationships.
Protocol for the production of an Arenavirus and Hantavirus host-pathogen database: Project ArHa
Authors: Simons David , Rivero Ricardo , Guiote Ana Martinez-Checa , Gordon Harry , Milne Gregory C. , Rickard Grant , Redding David W. , Seifert Stephanie N. 
Published: January 2025

1AbstractArenaviruses and Hantaviruses, primarily hosted by rodents and shrews, represent significant public health threats due to their potential for zoonotic spillover into human populations. Despite their global distribution, the full impact of these viruses on human health remains poorly understood, particularly in regions like Africa, where data is sparse. Both virus families continue to emerge, with pathogen evolution and spillover driven by anthropogenic factors such as land use change, climate change, and biodiversity loss. Recent research highlights the complex interactions between ecological dynamics, host species, and environmental factors in shaping the risk of pathogen transmission and spillover. This underscores the need for integrated ecological and genomic approaches to better understand these zoonotic diseases. A comprehensive, spatially and temporally explicit dataset, incorporating host-pathogen dynamics and human disease data, is crucial for improving risk assessments, enhancing disease surveillance, and guiding public health interventions. Such a dataset (ArHa) would also support predictive modelling efforts aimed at mitigating future spillover events. This paper proposes the development of this unified database for small-mammal hosts of Arenaviruses and Hantaviruses, identifying gaps in current research and promoting a more comprehensive understanding of pathogen prevalence, spillover risk, and viral evolution.2Strengths and Limitations of this studyThis dataset combines detailed spatial and temporal information, providing a unique resource for understanding geographic and temporal trends in Arenavirus and Hantavirus host-pathogen relationships.By explicitly quantifying sampling biases and detection efforts, the dataset allows more robust and accurate asssessments of pathogen prevalence and distribution.The dataset offers a platform for linking ecological data with human health outcomes, supporting the identification of spillover hotspots.The dataset relies on published material, which may vary in terms of detail, accuracy and completeness. Missing or imprecise information may limit the reliability of subsequent analyses.The dataset will be produced as a static resource which could limit its relevance over time as emerging data will not be added.
Quantitative proteomics of infected macrophages reveals novelLeishmaniavirulence factors
Authors: Hagedorn Nicolas , Fradera-Sola Albert , Mitnacht Melina , Gold Tobias , Schleicher Ulrike , Butter Falk , Janzen Christian J. 
Published: January 2025

AbstractLeishmaniasis is a major public health problem, causing diseases ranging from self-healing skin lesions to life-threatening chronic infections. Understanding howLeishmaniaparasites evade the host defense system is crucial for understanding the different manifestations of the disease and for improving diagnostic tools and drug development. We performed high-resolution proteome profiling ofLeishmaniaspp. across three species during macrophage infection and identified distinct temporal expression patterns. Clustering analysis revealed unique protein expression profiles for eachLeishmaniaspecies, whereas pairwise enrichment analysis revealed specific up- and downregulation patterns at different infection stages. Our results confirmed known virulence factors and highlighted new ones, demonstrating the utility of our dataset. We validated the dataset by showing that deletion of putativeL. mexicanavirulence factors resulted in reduced stage differentiation capacity and infectivity. This novelLeishmaniainfectome database (LInfDB) is available online for further exploration (https://butterlab.imb-mainz.de/LInfDB), providing a valuable resource for future research.
Insights into the Absence of Lymphoma Despite Fulminant Epstein-Barr Virus Infection in Patients with XIAP Deficiency
Authors: Sun Yizhe , Chou Janet , Dong Kevin , Gygi Steven P. , Gewurz Benjamin E. 
Published: January 2025

AbstractX-linked Lymphoproliferative Syndromes (XLP), which arise from mutations in theSH2D1AorXIAPgenes, are characterized by the inability to control Epstein-Barr Virus (EBV) infection. While primary EBV infection triggers severe diseases in each, lymphomas occur at high rates with XLP-1 but not with XLP-2. Why XLP-2 patients are apparently protected from EBV-driven lymphomagenesis, in contrast to all other described congenital conditions that result in heightened susceptibility to EBV, remains a key open question. To gain insights, we cross-compared newly EBV infected versus immune stimulated B-cells from XLP-2 patients or upon XIAP CRISPR knockout, relative to healthy controls. XIAP perturbation impeded outgrowth of newly EBV-infected primary human B-cells, though had no impact on proliferation of B-cells stimulated by CD40 ligand and interleukin-21 or upon established EBV-immortalized lymphoblastoid cell lines (LCLs). B-cells from XLP-2 patients or in which XIAP was depleted by CRISPR editing exhibited a markedly lower EBV transformation efficiency than healthy control B-cells. Mechanistically, nascent EBV infection activated p53-mediated apoptosis signaling, whose effects on transforming B-cell death were counteracted by XIAP. In the absence of XIAP, EBV infection triggered high rates of apoptosis, not seen with CD40L/IL-21 stimulation. Moreover, inflammatory cytokines are present at high levels in XLP-2 patient serum with fulminant EBV infection, which heightened apoptosis induction in newly EBV-infected cells. These findings highlight the crucial role of XIAP in supporting early stages of EBV-driven B-cell immortalization and provide insights into the absence of EBV+ lymphoma in XLP-2 patients.Key pointsXIAP loss-of-function markedly impairs EBV+ B-cells outgrowth over the first week post-infection, particularly in the presence of IFN-γ.XIAP mutation impedes EBV-driven B-cell transformation by potentiating p53-driven caspase activation and apoptosis.
A High Throughput Assay for Measuring Secreted Protein Based on ade novoFluorescent Reporter Reveals Regulatory and Structural Insights inSalmonellaType Three Secretion System
Authors: Leach Samuel Alexander , Summers Jordan Scott , Wen Edward , Tullman-Ercek Danielle 
Published: January 2025

AbstractIntracellular protein production in bacteria is limited by the need for lysis and costly purification. A promising alternative is to engineer the host organism for protein secretion. While theSalmonella entericaserovar Typhimurium (S. Typhimurium) Type 3 Secretion System (T3SS) has been utilized for protein secretion, its study and eventual applicability for recombinant protein production is constrained by the lack of high-throughput assays to quantitatively measure secretion titer. Developing such assays is challenging, as proteins must remain unfolded for secretion, limiting the use of several common reporter proteins. In this work, we develop a high-throughput secretion assay using mini-Fluorescent Activating Protein (mFAP). mFAP forms a chromophore only upon addition of an exogenous substrate, allowing secretion and subsequent fluorescence detection. We demonstrate mFAP secretion via the T3SS with an N-terminal secretion tag and show that the fluorescent signal in the secreted fraction is rapid and linear over three orders of magnitude. Using this assay, we screenS. Typhimurium strains with secretion-enhancing mutations, identifying a constitutively active strain and reveal temporally controlled secretion dynamics. We also show that this assay may be applicable to other secretion systems, providing a universal tool for tracking heterologous protein secretion.
Comprehensive analysis of 37 composts: microbial indicators for soilborne disease suppression in three plant-pathogen systems
Authors: Logo Anja , Boppré Benedikt , Fuchs Jacques , Maurhofer Monika , Oberhänsli Thomas , Thürig Barbara , Widmer Franco , Flury Pascale , Mayerhofer Johanna 
Published: January 2025

AbstractSoilborne diseases pose a significant threat to crop production and their control remains a major challenge. Compost is a valuable soil amendment when it comes to suppressing soilborne pathogens, but the effectiveness of different composts varies and cannot yet be predicted. Microbial communities in compost play a key role in disease suppression, and therefore microbial taxa may serve as indicators for suppressive composts. In this study, we investigated 37 composts from seven commercial compost producers to analyze the association of their bacterial and fungal communities with disease-suppressive activity across three plant-pathogen systems: cress-Globisporanigum ultimum, cucumber-Globisporanigum ultimumand cucumber-Rhizoctonia solani. Our results underscore that compost suppressiveness is primarily pathogen-specific and, to a smaller extent, hostplant-specific. Suppressiveness was not found to be correlated to physicochemical properties or microbial activity, alpha- and beta-diversity of the composts. However, specific bacterial and a few fungal taxa were identified as potential indicators of suppression for each plant-pathogen system. Notably, forG. ultimum-suppression, bacteria from the generaLuteimonas,Sphingopyxis, andAlgoriphagusemerged as promising candidates. These findings provide a foundation for targeted microbial isolation, aiming to elucidate the role of microorganisms in compost-mediated disease suppression, and to predict and optimize suppressive activity.
Hypoxia-inducible factor 1 protects neurons from Sarm1-mediated neurodegeneration
Authors: Meraner Paul , Avetisyan Adel , Swift Kevin , Cheng Ya-Chen , Barria Romina , Freeman Marc R. 
Published: January 2025

AbstractThe Sarm1 NAD+hydrolase drives neurodegeneration in many contexts, but how Sarm1 activity is regulated remains poorly defined. Using CRISPR/Cas9 screening, we found loss of VHL suppressed Sarm1-mediated cellular degeneration. VHL normally promotes O2-dependent constitutive ubiquitination and degradation of hypoxia-inducible factor 1 (HIF-1), but during hypoxia, HIF-1 is stabilized and regulates gene expression. We observed neuroprotection after depletion of VHL or other factors required for HIF-1 degradation, and expression of a non-ubiquitinated HIF-1 variant led to even stronger blockade of axon degeneration in mammals andDrosophila. Neuroprotection required HIF-1 DNA binding, prolonged expression, and resulted in broad gene expression changes. Unexpectedly, stabilized HIF-1 prevented the precipitous NAD+loss driven by Sarm1 activation in neurons, despite NAD+hydrolase activity being intrinsic to the Sarm1 TIR domain. Our work argues hypoxia inhibits Sarm1 activity through HIF-1 driven transcriptional changes, rendering neurons less sensitive to Sarm1-mediated neurodegeneration when in a hypoxic state.Competing interestsMarc Freeman is co-founder of Nura Bio, a biotech startup pursuing novel neuroprotective therapies including SARM1 inhibition. The remaining authors declare no competing interests.
Conditioning electrical stimulation enhances functional rewiring in a mouse model of nerve transfer to treat chronic spinal cord injury
Authors: Jara Juan Sebastián , Soliman Marwa , Bernstein Amanda , di Grazia Paola , Ferguson Adam R. , Brown Justin M. , Torres-Espín Abel , Hollis Edmund R. 
Published: January 2025

AbstractNerve transfer surgery is a state-of-the-art surgical approach to restore hand and arm function in individuals living with tetraplegia, significantly impacting daily life. While nearly a third of all individuals with chronic SCI may benefit from this intervention, variability in outcomes can limit the functional impact. A bedside-to-bench approach was taken to address the variable response of tetraplegic individuals to nerve transfer surgery. We used a hierarchical multiple factor analysis to evaluate the effects of conditioning electrical stimulation (CES) on outcomes in a mouse model of nerve transfer to treat chronic cervical spinal cord injury. We found that CES of donor nerves one week prior to nerve transfer surgery enhanced anatomical and functional measures of innervation of targeted muscles. Furthermore, CES increased the rate of recovery of naturalistic behavior. While the model has some limitations due to the small size of the rodent, our results support the use of CES as an effective approach to improve outcomes in clinical nerve repair settings.