bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review to identify research gaps in studies modeling vaccination strategies againstNeisseriainfections
Authors: Metelmann S , Thompson A , Donten A , Oke S , Sun S , Borrow R , Feng X , Vivancos R , Decraene V , Pellis L , Hall I 
Published: October 2024

AbstractThe genusNeisseriaincludes two major human pathogens:N. meningitidiscausing bacterial meningitis/septicemia andN. gonorrhoeaecausing gonorrhoea. Mathematical models have been used to simulate their transmission and control strategies, and the recent observation of a meningitis vaccine being partially effective against gonorrhoea has led to an increased modeling interest. Here we conducted a systematic review of the literature, focusing on studies that model vaccination strategies againstNeisseriaincidence and antimicrobial resistance. Using journal, preprint, and grey literature repositories, we identified 52 studies that we reviewed for validity, model approaches and assumptions. Most studies showed a good quality of evidence, and the variety of approaches along with their different modeling angles, was assuring especially for gonorrhoea studies. We identified options for future research, including the combination of both meningococcal and gonococcal infections in studies to have better estimates for vaccine benefits, and the spill over of gonorrhoea infections from the heterosexual to the MSM community and vice versa. Cost-effectiveness studies looking at at-risk and the wider populations can then be used to inform vaccine policies on gonorrhoea, as they have for meningococcal disease.
Distinct prostate cancer neuroendocrine subtypes predict prognosis and guide personalized prostate-specific membrane antigen-targeted therapy
Authors: Hong Yung-Chih , Tsai Cheng-Han , Hu Tze-Yun , Hsu Chih-Sin , Peng Yu-Ching , Chen Weber , Huang William J. , Lin Tzu-Ping , Chang Pei-Ching 
Published: October 2024

AbstractBackground and ObjectiveSecond-generation hormonal therapy inhibits castration-resistant prostate cancer (CRPC), but the tumor eventually recurs as neuroendocrine prostate cancer (NEPC) and turns lethal. Differentiating lineage plasticity that contributed to distinct NEPC subtypes aids in advancing treatments, particularly the recent FDA-approved177Lu-PSMA-617 radiopharmaceutical therapy.MethodsWe integrated single-cell RNA sequencing data from fresh human CRPC cases. This comprehensive approach allowed us to identify distinct NEPC subpopulations and their respective lineage with high confidence.Key Findings and LimitationsWe uncovered N-Myc and REST as key transcription factors driving distinct neuroendocrine subtypes among 5,797 neuroendocrine-like epithelial cells in CRPC: a REST-dependent subtype (NE I), an N-Myc-dependent subtype (NE II), and a combined N-Myc/REST subtype (NE I+II). These subtypes were validated using multiplex immunofluorescence staining. Trajectory analysis of single-cell RNA sequencing data, along with multi-omics time course analysis of publicly available transcriptomic data recapitulated N-Myc and REST lineages. Additionally, we observed PSMA loss in N-Myc lineage NEPC and identified STMN1 as a biomarker for PSMA-negative subtype. We validated the prognostic value of STMN1 using the TCGA dataset and 60 in-house CRPC tissues. Given that surgery is rarely performed in advanced CRPC, leading to limited sample availability, further validation in larger cohorts is needed.Conclusions and Clinical ImplicationsAdeno-to-neuroendocrine lineage transition in prostate cancer leads to resistance to new therapies. The lethal NEPC phenotype should be revealed earlier in the disease course of patients with CRPC, providing crucial clues for personalized precision medicine.
Seed specific overexpression of a modified wheatOrgene leads to enhanced β-carotene in rice and wheat grains
Authors: Sirohi Parul , Vishnoi Ritika , Baliyan Suchi , Gupta Bidya Bhushan , Demiwal Pratibha , Germain Hugo , Sircar Debabrata , Chauhan Harsh 
Published: October 2024

AbstractVitamin A deficiency is a major public health problem affecting up to 50% of the world’s population, as either wheat or rice, which are poor in many essential micronutrients such as vitamin A, are major staple food crops. Biofortification of cereal crops with β-carotene (provitamin A) through genetic engineering is a potential solution to overcome vitamin A deficiency. The Orange (Or) protein is involved in the regulation of carotenoid accumulation and previous studies demonstrated high carotenoid accumulation due to a single-nucleotide polymorphism (SNP) in the CDS leading to substitution of Arg to His in the OR protein results in carotenoid accumulation. In the present study, we showed that this substitution of a single amino acid at position 110 (Arg to His) of wild-type wheatTaOr(referred to asTaOrHis110) increased β-carotene accumulation in transgenic wheat and rice plants overexpressingTaOrHis110under the control of the seed-specific promoterGlu-1D1. HPLC analysis revealed increase in β-carotene content in rice grain up to 8-fold in case of TP309 (japonica) cultivar, 13-fold in case of IET10364 (indica) cultivar and 7-fold in wheat cv. CPAN1676. Additionally, most of the carotenoid biosynthetic pathway genes were found to be upregulated inTaOrHis110overexpressing seeds of TP309 and IET10364, which positively correlated with maximum increase in β-carotene content.
Chromosome-level genome assembly and annotation of the crested gecko,Correlophus ciliatus, a lizard incapable of tail regeneration
Authors: Gumangan Marc A , Pan Zheyu , Lozito Thomas P 
Published: October 2024

AbstractThe vast majority of gecko species are capable of tail regeneration, but singular geckos ofCorrelophus, Uroplatus, andNephrurusgenera are unable to regrow lost tails. Of these non-regenerative geckos, the crested gecko (Correlophus ciliatus) is distinguished by ready availability, ease of care, high productivity, and hybridization potential. These features makeC. ciliatusparticularly suited as a model for studying the genetic, molecular, and cellular mechanisms underlying loss of tail regeneration capabilities. We report a contiguous genome ofC. ciliatuswith a total size of 1.65 Gb, a total of 152 scaffolds, L50 of 6, and N50 of 109 Mb. Repetitive content consists of 40.41% of the genome, and a total of 30,780 genes were annotated. Assembly of the crested gecko genome provides a valuable resource for future comparative genomic studies between non-regenerative and regenerative geckos and other squamate reptiles.FindingsWe report genome sequencing, assembly, and annotation for the crested gecko,Correlophus ciliatus.
A post-injury immune challenge with lipopolysaccharide following adult traumatic brain injury alters neuroinflammation and the gut microbiome acutely, but has little effect on chronic outcomes
Authors: Rewell Sarah S.J. , Shad Ali , Chen Lingjun , Macowan Matthew , Chu Erskine , Gandasasmita Natasha , Casillas-Espinosa Pablo M. , Li Jian , O’Brien Terence J. , Semple Bridgette D. 
Published: October 2024

ABSTRACTPatients with a traumatic brain injury (TBI) are susceptible to hospital-acquired infections, presenting a significant challenge to an already-compromised immune system. The consequences and mechanisms by which this dual insult worsens outcomes are poorly understood. This study aimed to explore how a systemic immune stimulus (lipopolysaccharide, LPS) influences outcomes following experimental TBI in young adult mice. Male and female C57Bl/6J mice underwent controlled cortical impact or sham surgery, followed by 1 mg/kg i.p. LPS or saline-vehicle at 4 days post-TBI, before behavioral assessment and tissue collection at 6 h, 24 h, 7 days or 6 months. LPS induced acute sickness behaviors including weight loss, transient hypoactivity, and increased anxiety-like behavior. Early systemic immune activation by LPS was confirmed by increased spleen weight and serum cytokines. In brain tissue, gene expression analysis revealed a time course of inflammatory immune activation in TBI or LPS-treated mice (e.g., IL-1β, IL-6, CCL2, TNFα), which was exacerbated in TBI+LPS mice. This group also presented with fecal microbiome dysbiosis at 24 h post-LPS, with reduced bacterial diversity and changes in the relative abundance of key bacterial genera associated with sub-acute neurobehavioral and immune changes. Chronically, TBI induced hyperactivity and cognitive deficits, brain atrophy, and increased seizure susceptibility, similarly in vehicle and LPS-treated groups. Together, findings suggest that an immune challenge with LPS early after TBI, akin to a hospital-acquired infection, alters the acute neuroinflammatory response to injury, but has no lasting effects. Future studies could consider more clinically-relevant models of infection to build upon these findings.
Neurophysiological Dynamics of Metacontrol States: EEG Insights into Conflict Regulation
Authors: Wang Xi , Talebi Nasibeh , Zhou Xianzhen , Hommel Bernhard , Beste Christian 
Published: October 2024

AbstractUnderstanding the neural mechanisms underlying metacontrol and conflict regulation is crucial for insights into cognitive flexibility and persistence. This study employed electroencephalography (EEG), EEG-beamforming and directed connectivity analyses to explore how varying metacontrol states influence conflict regulation at a neurophysiological level. Metacontrol states were manipulated by altering the frequency of congruent and incongruent trials across experimental blocks in a modified flanker task, and both behavioral and electrophysiological measures were analyzed. Behavioral data confirmed the experimental manipulation’s efficacy, showing an increase in persistence bias and a reduction in flexibility bias during increased conflict regulation. Electrophysiologically, theta band activity paralleled the behavioral data, suggesting that theta oscillations reflect the mismatch between expected metacontrol bias and actual task demands. Alpha and beta band dynamics differed across experimental blocks, though these changes did not directly mirror behavioral effects. Post-response alpha and beta activity were more pronounced in persistence-biased states, indicating a neural reset mechanism preparing for future cognitive demands. By using a novel artificial neural networks method, directed connectivity analyses revealed enhanced inter-regional communication during persistence states, suggesting stronger top-down control and sensorimotor integration. Overall, theta band activity was closely tied to metacontrol processes, while alpha and beta bands played a role in resetting the neural system for upcoming tasks. These findings provide a deeper understanding of the neural substrates involved in metacontrol and conflict monitoring, emphasizing the distinct roles of different frequency bands in these cognitive processes.
GeTMoR: Simultaneous genomic, transcriptomic, and morphological profiling of rare single cells
Authors: Prabakar Rishvanth K. , Schmidt Michael J. , Kuhn Peter , Hicks James 
Published: October 2024

1AbstractCirculating tumor cells (CTCs), and circulating tumor related cells, are extremely rare cells that intravasate from the tumor into the circulatory system and can be captured via a liquid biopsy. Although CTCs contribute to the metastatic cascade, and diverse phenotypes of CTCs have been observed – including the cytokeratin expressing CTCs, CTC clusters, large polyploid CTCs, and CTCs undergoing epithelial to mesenchymal transition – little is known about their functionality. By virtue of CTCs being rare, a detection method that maximizes the information obtained per cell would be ideal to understand their biology and for use in diagnostic approaches. The challenge is that rare cell detection necessitates extensive processing steps, during which molecular content, such as RNA and DNA, needs to be preserved for downstream single cell analysis. We developed GEnomic, Transcriptomic, and MOrphological profiling of Rare cells (GeTMoR), a method that extends the High Definition Single Cell Assay for detecting rare cancer related cells to simultaneously image and profile the genome and transcriptome from single rare cells. We validated GeTMoR by spiking in cancer cell lines into whole blood to evaluate the quality of recovered gene expression and copy number profile from the same cell. The GeTMoR approach provides the ability to link the phenotype of rare cells, including CTCs, to their genome and transcriptome, thereby enabling insight into rare cell biology.
Exploring the link between extended red blood cell parameters and platelet indices in voluntary blood donors
Authors: De Ranita , Basavaraju Deepak Marballi , Stephen Leo , Lakshmi Kavitha , Mammen Joy , Edison Eunice Sindhuvi 
Published: October 2024

AbstractBackgroundAs regular blood donors are prone to iron deficiency, importance of extended red blood cell (eRBC) parameters in identifying donors with depleted iron stores was investigated. Thrombocytosis has been well documented in patients affected with IDA. Thus, significance of eRBC parameters in identifying iron deficiency associated thrombocytosis was also examined in this cohort.MethodsBlood samples were collected in EDTA tubes from consenting donors for analyses of routine haematological and eRBC parameters. Serum samples were isolated for estimation of iron parameters.ResultsIron deficient donors had significantly altered eRBC parameters. Among them, Ret-He with a cut-off of ≥32 pg had high AUC (0.822) and showed relatively high sensitivity & specificity in detecting iron deficiency. Combination of Ret-He with CCI increased sensitivity & specificity to 90.6% and 98.2%, in detection of donors affected with iron restricted erythropoiesis. This cohort had increased platelet counts, which showed significant association with Ret-He (β= -0.373), RBC-He (β= -0.384), CCI (β= 0.384), Hypo-He (β=0.494) and Micro-R (β= 0.299). Elevated platelet counts also showed significant correlations with these eRBC parameters, which was absent in iron replete donors.ConclusionseRBC parameters are sensitive indicators of non-anaemic iron deficiency, which may be enhanced by combining them. Their significant association with elevated platelet counts in iron deficient donors, highlights their importance in reflecting iron deficiency associated thrombocytosis.Impact StatementThe present study discusses utility of eRBC parameters in detecting non-anaemic iron deficiency, in regular voluntary blood donors. Previous reports have investigated the importance of these parameters in identifying IDA in blood donors. The present study is the first one which indicates combining different eRBC parameters such as Ret-He and CCI increases their accuracy of detection. They were also significantly associated with elevated platelet counts in iron deficient donors, which was absent in iron replete individuals. This link between eRBC parameters and higher platelet counts in healthy donors affected with non-anaemic iron deficiency has not been reported before.
Postpartum Tubal Sterilization in Sickle Cell Disease in the 2012-2019 National Inpatient Sample
Authors: Luo Amy , Gemmill Alison , Scott Jayla L , Burke Anne E. , Pecker Lydia H. 
Published: October 2024

ABSTRACTImportanceSickle cell disease (SCD) is associated with high-risk pregnancy and low rates of hormonal contraception use. Intersectional vulnerabilities among individuals with SCD in the United States (US) raise historically and socially contingent questions about tubal sterilization in individuals with SCD. However immediate postpartum tubal sterilization (TS) rates among individuals with SCD in the US are unknown.ObjectiveTo compare rates of TS in deliveries to people with SCD and without SCD, and to determine the modifying effect of severe maternal morbidity (SMM) on the odds of TS.Design, Setting, and ParticipantsThis repeated cross-sectional study used the 2012-2019 National Inpatient Sample to estimate the rate of TS among delivery hospitalizations to people with SCD, without SCD (non-SCD), Black people with and without SCD, and people with cystic fibrosis (CF). Logistic regression models estimated the odds of TS between SCD and non-SCD deliveries, SCD and non-SCD deliveries with Black race, and SCD and CF deliveries. We examined whether SMM modified the association between TS and SCD in interaction analyses.ExposureSCD, CFResultsAmong 29,822,518 deliveries, 6.7% underwent TS. Among 18,860 SCD deliveries, 8.8% underwent TS. Among 2,945 CF deliveries, 6.6% underwent TS. After adjusting for patient and hospital characteristics, SCD had higher odds of TS compared to non-SCD deliveries (aOR= 1.38 [1.06,1.79]) and in a stratified analysis of deliveries coded with Black race (aOR= 1.42 [1.06,1.90]). After adjusting for patient and hospital characteristics, there was no difference in the odds of TS between SCD or CF deliveries (aOR=1.0 [0.51,2.24]). SMM more than doubled the odds of TS in SCD deliveries (interaction: aOR=2.34 [1.57,3.47]; aOR= 2.14 [1.40,3.24] in deliveries coded with Black race).ConclusionEven after accounting for patient and hospital characteristics, people with SCD have higher odds of immediate postpartum TS compared to control groups. SMM at delivery increased the odds of TS in SCD compared to all non-SCD deliveries and compared to CF deliveries. Possibly SMM severity, patient preference, or clinician recommendations inform this finding. SMM is 3-7 times more common in SCD than non-SCD pregnancies and may be a modifiable risk factor for TS in SCD deliveries.KEY POINTSQuestionWhat are the national rates and associations of postpartum tubal sterilization (TS) among deliveries to people with sickle cell disease (SCD) compared to deliveries to people without SCD (non-SCD) and cystic fibrosis (CF)?FindingsFrom 2012-2019, the TS rate was significantly higher in SCD deliveries (88 per 1,000 deliveries) vs non-SCD (67 per 1,000 deliveries) and CF deliveries (66 per 1,000 deliveries). SCD was positively associated with TS. SMM modified the association between TS and SCD by two-fold.MeaningPostpartum TS rate in people with SCD is high; SMM during SCD deliveries significantly increases the odds of postpartum TS.
Estimating the trend of COVID-19 in Norway by combining multiple surveillance indicators
Authors: Rø Gunnar , Lyngstad Trude Marie , Seppälä Elina , Skodvin Siri Nærland , Trogstad Lill , White Richard Aubrey , Paulsen Arve , Paulsen Trine Hessevik , Ofitserova Trine Skogset , Langlete Petter , Madslien Elisabeth Henie , Nygård Karin , Freisleben de Blasio Birgitte 
Published: October 2024

AbstractBackgroundEstimating the trend of new infections was crucial for monitoring risk and for evaluating strategies and interventions during the COVID-19 pandemic. The pandemic revealed the utility of new data sources and highlighted challenges in interpreting surveillance indicators when changes in disease severity, testing practices or reporting occur.AimTo estimate the trend in new COVID-19 infections by combining estimates of growth rates from all available surveillance indicators in Norway.MethodsWe estimated growth rates from ten different surveillance indicators in Norway by using a negative binomial regression method and aligned the growth rates in time to hospital admissions by maximising correlations. Using a meta-analysis framework, we calculated overall growth rates and reproduction numbers including assessments of the heterogeneity between indicators.ResultsThe estimated growth rates reached a maximum of 25% per day in March 2020, but afterwards they were between -10% and 10% per day. The correlations between the growth rates estimated from different indicators were between 0.5 and 1.0. Growth rates from indicators based on wastewater, panel and cohort data can give up to 14 days earlier signals of trends compared to hospital admissions, while indicators based on positive lab tests can give signals up to 7 days earlier.ConclusionsCombining estimates of growth rates from multiple surveillance indicators provides a good description of the COVID-19 pandemic in Norway. This is a powerful technique for a holistic understanding of the trends of new COVID-19 infections and the technique can easily be adapted to new data sources and situations.
Change in brain molecular landscapes following electrical stimulation of the nucleus accumbens
Authors: Cai Chengwei , Gao Lingyun , Zhu Zhoule , Chen Wangyu , Zhang Fang , Yu Chaonan , Xu Kedi , Zhu Junming , Wu Hemmings 
Published: October 2024

ABSTRACTDeep brain stimulation (DBS) targeting the nucleus accumbens (NAc) is a promising therapeutic intervention for treatment-resistant neuropsychiatric disorders such as depression, anxiety, and addiction. However, the molecular mechanisms underlying the clinical efficacy of NAc DBS remain largely unknown. One approach to address this question is by performing spatial gene expression analysis on cells located in different regions of the same circuit following NAc DBS. In this study, we utilized high-resolution spatial transcriptomics (Stereo-seq) to investigate gene expression changes induced by NAc DBS in the mouse brain. Mice were randomly allocated to received continuous electrical stimulation (0.1 mA, 130 Hz) or sham treatment (electrode implanted, no electrical stimulation given) for one week, and subsequent Stereo-seq analysis identified differentially expressed genes (DEGs) across various brain regions. Our findings reveal widespread alterations in synaptic function and neuronal connectivity, particularly in glutamate receptor-expressing neurons in the NAc, which play a key role in the reward circuitry. Functional enrichment analysis highlighted changes in transporter activity and glutamate receptor binding in brain regions such as the anterior cingulate cortex and lateral septal nucleus. Single-cell resolution mapping further identified key molecular players, including Nlgn1, Snca, PDE10a, and Syt1, which are critical for synaptic plasticity and neurotransmitter release, and have been implicated in various psychiatric disorders. These findings shed light on the molecular underpinnings of NAc DBS and provide insights into its therapeutic potential in modulating neural circuits associated with neuropsychiatric disorders.
An unprecedented small RNA-riboswitch interaction controls expression of a bifunctional pump that is essential forStaphylococcus aureusinfection
Authors: González-Espinoza Gabriela , Prévost Karine , Hussain Fayyaz , Radin Jana N. , Valle Carlos D. Vega , Maucotel Julie , Barroso Marina Valente , Marteyn Benoît , Massé Eric , Romby Pascale , Kehl-Fie Thomas E. , Georg Jens , Lalaouna David 
Published: October 2024

SUMMARYMaintaining manganese and iron homeostasis is critical for the human pathogenStaphylococcus aureus. To counteract metal-based host defense strategies (e.g., nutritional immunity, metal poisoning),S. aureususes a combination of metal-sensing transcription factors and regulatory RNAs to maintain metal homeostasis. In this study, we uncovered an unprecedented interaction between a cis- and a trans-acting regulatory RNA controlling a conditionally essential gene,mntY, encoding a Mn efflux pump. This broadly conserved RNA-RNA interaction between a Fe-responsive sRNA and a Mn-sensing riboswitch allows the integration of Feand Mn-related stresses, notably encountered at the infection site, to fine-tunemntYexpression. Remarkably, deletion of themntYgene is strongly pleomorphic, causing growth defects, altering virulence factor expression, immune evasion, and survival during infection. We demonstrated that MntY is critical for the adaptation ofS. aureusto both low and high Mn environments, due to its dual role in metalation of Mn-dependent exoenzymes and Mn detoxification. These findings point to MntY as a promising new therapeutic target to combat multidrug-resistant staphylococcal infections.