bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interplay Between Breastfeeding and Autism Spectrum
Authors: Ben-Sasson Ayelet , Mimouni-Bloch Aviva , Samhat-Darawshi Sukaina , Ilann Keren , Gabis Lidia V. 
Published: January 2025

AbstractBackgroundEvidence supporting the association between breastfeeding patterns and ASD is inconsistent. This study examined sociodemographic and birth factors related to breastfeeding duration and ASD, compared to a typically developing (TD) cohort, using a data-driven approach based on electronic health and developmental records (EHR).MethodsDemographics, feeding preferences (breastfeeding, bottle or both), breastfeeding duration as reported by parents during routine baby wellness visits, were analyzed for a cohort of 11,766 (1.9%) children with ASD and a random subsample of 12,000 (2.03%) TD children. The designation of ASD versus TD was based on a national ASD registry and assigned after EHR were completed. Pre-term, very low birth weight, multiple births, and infants with complex medical comorbidities were excluded.ResultsInfants with ASD were breastfed for an average of 5.0 months, 1.5 months shorter than TD. Fewer ASD infants were exclusively breastfed in the first year of life. Two-way ANOVAs indicated a significant effect of socioeconomic status (SES) and ASD on breastfeeding duration, and a significant interaction with ASD. Post-hoc comparisons showed that the Low SES ASD and TD groups were breastfed longer than all other groups (p<.001). For the Low-Medium, Medium-High and High SES groups, infants with ASD were breastfed less than TD.ConclusionsShorter breastfeeding duration among ASD was confirmed in this representative cohort, calling for closer monitoring for ASD in infants with breastfeeding difficulties. These challenges were independent of birth parameters; however, influenced by socioeconomic factors.
Probabilistic classification of late treatment failure in uncomplicated malaria
Authors: Mehra Somya , Taylor Aimee R , Imwong Mallika , White Nicholas J , Watson James A 
Published: January 2025

AbstractDistinguishing treatment failure (recrudescence) from reinfection in uncomplicated falciparum malaria is essential for characterising antimalarial treatment efficacy in malaria endemic areas. Classification of recrudescence versus reinfection is usually based on a comparison of parasite allelic calls derived from PCR amplification and electrophoresis of individual polymorphic markers in the acute and recurrent isolates. Match-counting methods (e.g. 3/3 or 2/3 matching alleles) have usually been applied, but these do not account for multiple comparisons per-marker when infections are polyclonal. We show that when infections are polyclonal, as is common in high transmission settings, currently used match-counting and model-based methods have unacceptably high false-discovery rates leading to overestimation of treatment failure. We develop the softwarePfRecurwhich provides analytical Bayesian posterior probabilities of treatment failure in recurrent falciparum malaria. We use data from a recent study in Angola to demonstrate the potential utility of our model in resolving complex polyclonalP. falciparuminfections, thereby providing more accurate estimation of treatment failure rates.
Registered Report: The effect of systematic endurance training in treatment of women with lipedema - The LipidEx study
Authors: Sæther Julie Caroline , Nordeidet Ada Nilsen , Presthus Randi Merete , Undebakke Randi , Madsen Lise , Norberg Ina Lønnebakken , Kwapeng Sunniva , Owe Katrine Mari , Erbacher Gabriele , Bertsch Tobias , Dieterle Thomas , Nymo Siren , Giskeødegård Guro , Follestad Turid , Tjønna Arnt Erik , Bye Anja 
Published: January 2025

AbstractLipedema is a chronic adipose tissue disorder that primarily affects women. The etiology remains unclear and involves abnormal buildup of fat mainly in the lower limbs. It causes physical and psychological morbidity, often with negative impact on daily life. Effective treatment options are still limited, primarily involving conservative treatment such as compression therapy and pain reliever. As endurance training is shown to have beneficial effects on both pain and obesity management in patients suffering of other disorders, LipidEx aims to explore the potential of high-intensity interval training (HIIT) as a novel therapeutic option for women with lipedema. We will perform a cross-over randomized controlled trial (RCT) exploring the effects of 12 weeks of HIIT compared to a control period of usual care. The primary outcome is changes in pain, and secondary outcomes are changes in adipose tissue mass and quality of life.
Patterns of non-fatal overdose and injection-related bacterial infections during pregnancy and the postpartum year among New York State residents
Authors: Cooper Hannah LF , D’Souza Rohan R. , Chang Howard H. , Peterson Emily , Rogers Erin , Wien Simone , Blake Sarah C. , Kramer Michael R. 
Published: January 2025

AbstractObjectivesOverdoses are a leading cause of maternal mortality in the US, but limited evidence exists about patterns of nonfatal overdose, a key risk factor for subsequent fatal overdose, or of other drug-related harms. Here, we estimate prevalences of nonfatal overdose and injection-related endocarditis and abscesses/cellulitis across the 21 months spanning pregnancy and the postpartum year.MethodsAmong people who experienced an in-hospital birth in New York State between 9/1/2016 and 1/1/2018 (N=330,872), we estimated the prevalences of hospital-based diagnoses of nonfatal overdose and of injection-related bacterial infections (i.e., endocarditis, abscesses, and cellulitis) across these 21 months; by trimester and postpartum quarter; and by social position (e.g., race/ethnicity, rurality, payor).ResultsThe 21-month nonfatal overdose prevalence was 158/100,000 births (CI: 145/100,000, 172/100,000); the 21-month prevalence of injection-related bacterial infections was 56/100,000 births (CI: 49/100,000, 65/100,000). There was a trend such that rates of overdose and of injection-related bacterial infections declined as pregnancy progressed and rebounded postpartum. Rates of all outcomes were highest outside of large metropolitan areas and among publicly insured residents.Conclusions for PracticeThe trend toward diminished rates during pregnancy is supported by past qualitative studies. If confirmed by future research in other geographical regions and with larger sample sizes, this finding holds promise for programmatic and policy interventions. Interventions co-designed with people who use drugs could complement and support harm reduction efforts that pregnant people are already engaging in independently. Such efforts can help people who use drugs survive the pregnancy and postpartum year.Significance“What is already known on this subject?Fatal overdoses are a leading cause of maternal mortality in the US. Little evidence exists, however, about patterns of nonfatal overdose, a strong predictor of future fatal overdose, or about other serious injection-related bacterial infections.“What this study adds?We find trends suggesting that rates of nonfatal overdose and injection-related bacterial infections decline during pregnancy and then rebound postpartum. These findings, if confirmed in future research, suggest a clear path toward intervention development: partnering with people who use drugs to design interventions that complement and support their existing harm reduction interventions during pregnancy and in the postpartum period.
Time-dependent relationship between urinary biomarkers of nucleic acid oxidation and colorectal cancer risk
Authors: Zhao Yingya , Nogueira Marina S. , Milne Ginger L. , Gao Yu-Tang , Cai Qiuyin , Lan Qing , Yi Haoyang , Rothman Nathaniel , Shu Xiao-Ou , Zheng Wei , Chen Qingxia , Yang Gong 
Published: January 2025

ABSTRACTPURPOSERandomized controlled trials have failed to validate that neutralizing oxidative stress (OxS) through antioxidant supplementation reduces cancer risk. This study aims to prospectively investigate whether the relationship between systemic OxS and colorectal cancer (CRC) risk changes over the course of cancer development.METHODSThis study utilized a nested case-control design in two Shanghai cohorts for primary analysis and one US cohort for replication analysis. During a median follow-up of 15.1 years in the Shanghai cohorts, 1938 incident CRC cases were identified and matched to one control each. In the US cohort, 285 incident CRC cases were included with two matched controls per case. Systemic OxS was assessed by urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2’-deoxyguanosine [8-oxo-dG]) and RNA oxidation (7,8-dihydro-8-oxo-guanosine [8-oxo-Guo]) using UPLC-MS/MS assays. Multivariable-adjusted odds ratios (ORs) for CRC risk were calculated.RESULTSAfter adjusting for potential confounders, we observed an inversion association between OxS markers and CRC risk in the Shanghai cohorts, which was independently replicated in the US cohort. Moreover, the inverse association was time-dependent, manifesting only for CRC cases diagnosed within 5 years of enrollment. ORs (95% CI) for CRC at the 10th and 90th percentiles of 8-oxo-dG levels, relative to the median, were 1.87 (1.39 to 2.53) and 0.48 (0.37 to 0.63), respectively, demonstrating an approximate 4-fold difference in risk between the two groups, withPfor overall association of < 0.001. A similar pattern was observed for 8-oxo-Guo. No significant association was found for CRC diagnosed beyond 5 years of enrollment.CONCLUSIONThis novel finding of an inverse and time-dependent relationship between systemic OxS and CRC risk, if further confirmed, may provide a new perspective for revisiting redox-based chemoprevention.CONTEXTBackgroundAlmost all large randomized controlled trials have failed to validate the hypothesis that neutralizing oxidative stress through antioxidant supplementation can lower cancer risk, which has puzzled the public and researchers for decades.Key FindingsA reduced risk for colorectal cancer (CRC) with increasing systemic oxidative stress, measured by two urinary biomarkers of DNA and RNA oxidation, was observed in two large prospective cohort studies in Shanghai, China, and was replicated in an independent cohort in the United States. This association was time-dependent, with the inverse relationship strengthening as the biomarker assessment neared the time of CRC diagnosis.RelevanceOur study, for the first time, suggests an inverse and time-dependent relationship between systemic oxidative stress and CRC development, which, if further confirmed, may provide a new perspective for revisiting redox-based chemoprevention.
Revisiting the Need for mRNA Nucleoside Modification in CAR T Cell Engineering
Authors: Kahwaji Nourhan , Kotzian Niklas , Prinz Jasmin Melissa , Pu Yaolin , Kath Jonas , Picht Samira , Hiller Anna Luisa , Dunne Charlotte Maeve , Launspach Michael , Kleyer Arnd , Simon David Nils , Wagner Dimitrios Laurin , Pichon Chantal , Krönke Gerhard , Schmueck-Henneresse Michael , Volk Hans-Dieter , Gossen Manfred , Drzeniek Norman Michael 
Published: January 2025

AbstractmRNA-based chimeric antigen receptor (CAR)-T cells offer the promise of enhanced safety and simplified manufacturing. However, in vitro-transcribed (IVT) mRNA is known to trigger antiviral immune responses, inflammatory signaling, and apoptosis in transfected cells. To address these challenges and enable efficient IVT-mRNA expression, modified nucleosides, such as N1-methyl-pseudouridine (m1Ψ), have become the gold standard for CAR-T cell production, albeit at increased cost.In this study, immune responses to IVT-mRNA were evaluated across five primary human cell types, including T-cells. Unexpectedly, T-cells, unlike other immune and non-immune cell types tested, exhibited no immune activation in response to unmodified mRNA. T-cell viability and cytokine secretion patterns remained unaffected, regardless of whether unmodified mRNA was delivered via lipid nanoparticles (LNPs) or electroporation.Furthermore, CAR expression levels in T-cells were not influenced by mRNA modification with m1Ψ or 5-methoxy-uridine (5moU) nucleosides. The absence of nucleoside modifications did not compromise CAR-T cell cytotoxic potency, demonstrating that such modifications are not required for producing functional CAR-T cells.These findings eliminate the need for nucleoside modification in T-cell mRNA, simplifying and reducing the cost of CAR-T cell manufacturing while positioning IVT-mRNA as a highly efficient and minimally invasive tool for CAR-T cell engineering.
Periostin exon 17 skipping enhances the efficacy of local AAV-microdystrophin administration in a fibrotic model of Duchenne muscular dystrophy
Authors: Trundle Jessica , Boulinguiez Alexis , Lu-Nguyen Ngoc , March James , Malerba Alberto , Popplewell Linda 
Published: January 2025

AbstractDuchenne muscular dystrophy (DMD) is a severe, progressive genetic disorder primarily affecting boys, characterized by muscle degeneration due to mutations in the DMD gene encoding dystrophin, a crucial protein for muscle fiber integrity. The disease leads to significant muscle weakness and eventually to loss of ambulation. AAV-microdystrophin gene therapy shows promise in preclinical and clinical settings. However, muscle fibrosis, a consequence of chronic inflammation and extracellular matrix (ECM) remodeling, exacerbates disease progression and may hinder therapeutic efficacy. Periostin, a matricellular protein involved in fibrosis, is upregulated in DMD rodent models and correlates with collagen deposition. We previously developed an antisense oligonucleotide strategy to induce exon 17 skipping and so reduce periostin expression and collagen accumulation in the fibrotic D2.mdxmouse model of DMD. Here, we investigated the combined effects of periostin modulation and AAV-microdystrophin (AAV-MD1) treatment. We found that systemic periostin splicing modulation with intramuscular AAV-MD1 administration significantly improved muscle function, assessed by grip strength and treadmill performance, compared to either single treatment. Importantly, periostin exon skipping increases the microdystrophin protein expression. These findings suggest that targeting periostin in conjunction with microdystrophin therapy could represent a valid therapeutic strategy for DMD.
Loss of the autism associated geneTbr1disrupts prediction and encoding by prefrontal ensembles during socioemotional behaviors
Authors: Turner Marc , Robinson-Schwartz Sarah , Fazel-Darbandi Siavash , Rubenstein John L.R. , Sohal Vikaas S. 
Published: January 2025

ABSTRACTDisruptions in many genes linked to autism spectrum disorder (ASD) affect synaptic function and socioemotional behaviors in mice. However, exactly how synaptic dysfunction alters neural activity patterns underlying behavior remains unknown. We addressed this using mice lacking the high confidence ASD geneTbr1in cortical layer 5 (L5) projection neurons (Tbr1cKO mice). These mice have known deficits in synaptic input to L5 neurons and social behavior. We also find some abnormalities in anxiety-related avoidance. Calcium imaging of prefrontal L5 neurons revealed that despite reduced overall activity, cKO mice recruit normal numbers of neurons into prefrontal ensembles encoding social and anxiety-related behaviors. However, the stability, inter-neuronal coordination, and reactivation of social ensembles were diminished in cKO mice. Furthermore, in cKO mice, ensembles no longer predicted approach-avoidance decisions. These results reveal new aspects of how prefrontal ensembles encode socioemotional behaviors, and malfunction in the setting of ASD-linked gene disruption.
Is cultural context the crucial touch? Neurophysiological and self-reported responses to affective touch in women in South Africa and the United Kingdom
Authors: Hewitt Danielle , Besharati Sahba , Williams Victoria , Leal Michelle , McGlone Francis , Stancak Andrej , Henderson Jessica , Krahé Charlotte 
Published: January 2025

AbstractAffective touch, involving touch-sensitive C-tactile (CT-) afferent nerve fibres, is integral to human development and wellbeing. Despite presumed cultural differences, affective touch research typically includes ‘Western’, minority-world contexts, with findings extrapolated cross-culturally. We report the first cross-cultural study to experimentally investigate subjective and neurophysiological correlates of affective touch in women in South Africa (SA) and the United Kingdom (UK) using (1) subjective touch ratings, and (2) cortical oscillations for slow CT-optimal (vs. faster non-CT-optimal) touch on two body regions (arm, palm). Cultural context modulated affective touch experiences: SA (vs. UK) participants rated touch as more positive and less intense, with enhanced differentiation in sensorimotor beta band oscillations, especially during palm touch. UK participants differentiated between stroking speeds, with opposite directions of effects at arm and palm for frontal theta oscillations. Results highlight the importance of cultural context in subjective experience and neural processing of affective touch.
The Specific Genetic Markers to Diagnose Xanthomonads Infecting Pepper and Tomato Plants
Authors: Can Ahmet , Abdul-Baasit Abdul-Nasır , Belen Ilayda Nur , Capar Umran , Sener Burak , Basaran Ceyda C. , Sulu Serap Melike , Kusek Mustafa , Silme Ragip Soner , Baysal Omur 
Published: January 2025

ABSTRACTWe have improved a marker system to examine the genetic diversity in Xanthomonads species by using whole genome sequence analysis and repetitive regions in the bacterial genome. Specifically, we amplified microsatellite regions using PCR, and the resulting fragments were digested with specific enzymes. These fragment profiles served as molecular markers. Consequently, a more precise marker for bacterial identification was developed by combining the microsatellite and RFLP methods to differentiate Xanthomonads species. In Addition, we analysed the ancestral ordering of variousXanthomonasspecies’ genomes available in NCBI using Progressive Mauve Alignment. The data revealed unique collinear regions characteristic ofXanthomonasspecies. These regions were also associated with cut genomic fragments used as markers, enabling the discrimination ofXanthomonasspecies infecting tomato and pepper. We propose that these findings contribute to understanding the genetic diversity ofXanthomonasand rapidly diagnosis.
Carbon monoxide exposure stimulates growth and activity of primary producers in diverse soil ecosystems
Authors: Xu Yongfeng , Teng Ying , Liao Jing , Leung Pok Man , Dai Shixiang , Sun Yi , Hu Wenbo , Wang Hongzhe , Li Yanning , Huang Yuqi , Guo Zhiying , Pan Xianzhang , Dong Xiyang , Luo Yongming , Greening Chris 
Published: January 2025

AbstractCarbon monoxide (CO) is both a potent poison for many aerobic organisms and a desirable energy source for diverse microorganisms. Atmospheric emissions of this gas have increased since industrialization and their levels are highly elevated in many urban and natural environments; however, it is unresolved whether elevated levels of CO at environmentally relevant concentrations are primarily stimulatory or inhibitory to soil microbial communities. Here, we showed that CO exposure minimally affects microbial abundance, richness, and composition in diverse ecosystem soils, suggesting most microbes are tolerant of this gas. Genome-resolved metagenomic profiling showed that these soils harbored diverse bacteria capable of using CO an electron donor for aerobic respiration and carbon fixation. CO stimulated the growth of several of these putative CO-oxidizing bacteria in a dose-dependent manner, especially widespread proteobacterial and actinobacterial lineages. Additionally, we found a strong relationship between CO oxidation and carbon fixation and observed an enrichment of several carboxydotrophic MAGs capable of carbon fixation in most soil types. These findings highlight that environmentally relevant CO levels do not inhibit soil microbes, but instead foster the growth of distinct carboxydotrophic bacteria, suggesting a robust soil CO sink that could help mitigate anthropogenic CO emissions and contribute to carbon cycling in terrestrial ecosystems.
Multi-omics reveals global signaling rewiring and identifies Activin A-induced dysregulation of FOS/Activator Protein 1 as a novel target in Fibrodysplasia ossificans progressiva
Authors: Wits Marius , Gómez-Suárez Nerea , López Alexandre Deber , Farfán Nicole , Bekedam Fjodor , Sampadi Bharath , Rotman Sarah , López Daniel Rubiera , Márquez Judit Bestilleiro , Arendzen Christiaan , Freund Christian , Veelen Peter van , Valldeperas Aida Llucià , Man Frances de , Ventura Francesc , Goumans Marie-José , Sanchez-Duffhues Gonzalo 
Published: January 2025

AbstractBackgroundFibrodysplasia ossificans progressiva (FOP) is caused by an activating mutation (p.R206H) in the type I BMP receptor ALK2, leading to heterotopic ossification (HO) in soft connective tissues. While aberrant Activin A-induced SMAD signaling is central in FOP pathogenesis, global signaling alterations remain poorly understood.MethodsWe performed phosphoproteomics, transcriptomics and biochemical analyses in mesenchymal cells (MSCs) overexpressing wild-type ALK2WTor mutant ALK2R206Hreceptors and in induced-MSCs derived from FOP patient iPSCs. Findings were validated in vivo using FOP-like mouse models and in vitro via pharmacological interventions.ResultsMulti-omics analyses revealed previously unrecognized signaling networks in ALK2R206Hcells, including enhanced MAPK, mTOR, RUNX2 and RHO-mediated mechanotransduction pathways. Notably, we identified dysregulated Activator Protein-1 (AP-1) expression and function as a novel contributor to FOP. AP-1 factors were highly enriched in HO lesions in FOP-like animals. Pharmacological inhibition of AP-1 significantly reduced osteochondrogenic differentiation in vitro.ConclusionThis study highlights global signaling dysregulation in FOP and identifies AP-1 as a critical driver and potential therapeutic target for FOP.
Telemetry validation of dorsal scute microchemistry: complementary tools reconstruct the migratory life-history of an endangered population of Atlantic Sturgeon
Authors: Ingram Evan C. , Altenritter Matthew E. , Wilson Kylee B. , Frisk Michael G. , McCartin Kellie R. 
Published: January 2025

AbstractAn understanding of age-specific habitat requirements and the timing of critical ontogenetic transitions is essential to inform conservation and recovery efforts for Atlantic Sturgeon (Acipenser oxyrinchus). However, these are often difficult to assess due to the species’ cryptic nature and the consequent lack of temporal and spatial habitat data across life stages. Sampling and microchemistry analysis of dorsal scute apical spines (i.e., dorsal scutes) represents an innovative methodology to reconstruct past life-history events of endangered populations of Atlantic Sturgeon. Here, we establish the broad potential of dorsal scute sampling for wild-caught Atlantic Sturgeon and compare age-estimates and trace-element ratio patterns from dorsal scute with those from pectoral fin spines. We also evaluate microchemistry signatures from both structures to infer past habitat use and age at initial entry into marine waters and, importantly, validate these interpretations using known locations from acoustic telemetry detections. Major ontogenetic shifts in habitat use detected in the microchemistry signatures suggest our methodology was appropriate to identify the timing of initial juvenile migration into marine habitat, while providing additional information regarding the timing of transitions between freshwater and marine habitats that are essential to the management and conservation of this endangered species. As such, the collection of dorsal scute samples is suggested to complement ongoing research efforts for wild-populations and provides additional data points beyond those available from conventional tag-recapture methods alone, allowing researchers and managers to retrospectively identify environmental transitions and habitat use that occur prior to sampling encounters or outside of monitored areas.