bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association Between Multilingual Experience Factors and Cognitive Functioning in Older Adults: A Lifelines Study
Authors: van den Berg Floor , Brouwer Jelle , Loerts Hanneke , Knooihuizen Remco , Keijzer, Merel
Published: January 2025

Objectives

The complex life experience of speaking two or more languages has been suggested to preserve cognition in older adulthood. This study aimed to investigate this further by examining the relationship between multilingual experience variables and cognitive functioning in a large cohort of older adults in the diversely multilingual north of the Netherlands.

Method

A total of 11,332 older individuals participating in the Lifelines Cohort Study completed a language experience questionnaire. From this cohort, a subset was selected (n = 3,972, aged 59–86) for whom complete demographic and cognitive data were available and who had learned at least two languages to evaluate the association between multilingual experience variables and cognitive functioning. Cognitive functioning was assessed using the Cogstate Brief Battery, which measures processing speed, attention, working memory, and recognition memory.

Results

A linear regression analysis revealed that a higher number of languages learned was related to better performance on all subtasks. In addition, a later onset of acquisition of the second language (L2) was associated with better attention. These effects were independent of demographic variables such as age, education level, income level, and country of birth.

Discussion

The results demonstrate that in our cohort only the experience factors of the number of languages learned and L2 onset of acquisition related to cognitive functioning. Our evidence supports the idea that there is a positive relationship between multilingual experiences and cognitive functioning in older adulthood, but more longitudinal work is needed to establish whether learning multiple languages can potentially promote healthy aging.
Evaluation and Modification of the Multifactorial Model of Driving Safety Among Older Adults
Authors: Tian Junyan , Mogle Jacqueline , Anstey Kaarin J , Ross Lesley A
Published: January 2025

Background and Objectives

Cognitive, visual, and physical performance are associated with driving safety. However, there are few comprehensive models that empirically evaluate how such factors together affect driving safety in older adults. The present study used structural equation modeling (SEM) to evaluate Anstey’s original Multifactorial Model of Driving Safety (MMDS) (2005) as well as a modified MMDS that incorporates recent research.

Research Design and Methods

We used the baseline data from the Advanced Cognitive Training for Independent and Vital Elderly study. Participants (n = 2,391) were drivers with a reported mean age of 73.28 (SD = 5.70; range 65–91), 75.7% White, and 73.3% women.

Results

Using SEM, Anstey’s original MMDS did not achieve adequate fit (CFI = 0.850, TLI = 0.777, RMSEA = 0.074). However, the modified MMDS had a good fit (CFI = 0.961, TLI = 0.934, RMSEA = 0.040). We found that better physical function was correlated with less driving avoidance (β = 0.28, p < .01) and a lower crash risk (β = −0.14, p < .01). Better cognitive abilities were associated with less driving avoidance (β = 0.08, p <.01) and better self-reported driving quality (β = 0.19, p < .01). Driving avoidance partially mediated the relationship between physical function and crash.

Discussion and Implications

This study highlights the importance of cognition and physical function in older adults safe driving. Implications for future directions and public policy considerations are discussed. Future research should examine possible dynamic changes between these predictors and driving in a longitudinal model.
xRead: a coverage-guided approach for scalable construction of read overlapping graph
Authors: Kong Tangchao , Wang Yadong , Liu Bo
Published: January 2025

Background

The development of long-read sequencing is promising for the high-quality and comprehensive de novo assembly for various species around the world. However, it is still challenging for assemblers to handle thousands of genomes, tens of gigabase-level assembly sizes, and terabase-level datasets efficiently, which is a bottleneck to large-scale de novo sequencing studies. A major cause is the read overlapping graph construction that state-of-the-art tools usually have to cost terabyte-level RAM space and tens of days for large genomes. Such lower performance and scalability are not suited to handle the numerous samples being sequenced.

Findings

Herein, we propose xRead, a novel iterative overlapping graph construction approach that achieves high performance, scalability, and yield simultaneously. Under the guidance of its coverage-based model, xRead converts read-overlapping to heuristic read-mapping and incremental graph construction tasks with highly controllable RAM space and faster speed. It enables the processing of very large datasets (such as the 1.28 Tb Ambystoma mexicanum dataset) with less than 64 GB RAM and obviously lower time costs. Moreover, benchmarks suggest that it can produce highly accurate and well-connected overlapping graphs, which are also supportive of various kinds of downstream assembly strategies.

Conclusions

xRead is able to break through the major bottleneck to graph construction and lays a new foundation for de novo assembly. This tool is suited to handle a large number of datasets from large genomes and may play important roles in many de novo sequencing studies.
Integration of multiomic data identifies core-module of inherited-retinal diseases
Authors: Singh Ajeet , Ratnapriya Rinki
Published: January 2025

Human diseases with similar phenotypes can be interconnected through shared biological pathways, genes, or molecular mechanisms. Inherited retinal diseases (IRDs) cause photoreceptor dysfunction due to mutations in approximately 300 genes, affecting visual transduction, photoreceptor morphogenesis, and transcription factors, suggesting common pathobiological mechanisms. This study examined the functional relationship between known IRDs genes by integrating binding sites and gene expression data from the key photoreceptor transcription factors (TFs), Crx and Nrl. We show that the targets of these TFs were enriched in IRDs causal genes. Co-expression network analysis revealed that IRD-centric networks were disrupted when Crx and Nrl were knocked out. Finally, we identified a highly connected core module comprising 14 IRD and 39 target genes, of which 29 were dysregulated in the rod photoreceptors of the four IRD mouse models. These findings offer a network-based interpretation of IRDs, aiding in the identification of common mechanisms, prioritizing genes for novel disease gene identification, and informing the development of gene-agnostic therapies for IRDs.
Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness
Authors: Pichichero Michael E , Gonzalez Eduardo , Cox Andrew , Thayer Terri C , Bajorski Peter
Published: January 2025

Introduction

We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness.

Methods

In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections.

Results

Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections.

Conclusion

When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.
The pathogenicity traits of avian pathogenic Escherichia coli O25-ST131 associated with avian colibacillosis in Georgia poultry and their genotypic and phenotypic overlap with other extraintestinal pathogenic E. coli
Authors: Runcharoon Klao , Favro Margaret E , Logue Catherine M
Published: January 2025

Aims

To characterize Escherichia coli O25 ST131 (O25-ST131) isolated from Georgia poultry—a “global high-risk” clonal strain.

Methods and results

Using multiplex PCR to detect target genes in 98 isolates of avian pathogenic E. coli (APEC) O25 recovered from avians diagnosed with colibacillosis (n = 87) and healthy chicks (n = 11) in Georgia, USA. Eighty-eight isolates were classified as sequence type ST131 clade b and 56% (n = 49) belong to the phylogenetic group B2. Overall, 17% were identified as uropathogenic E. coli (UPEC)–like and 94% of the isolates formed strong to moderate biofilms. The extended-spectrum β-lactamases encoding genes, blaCTX M-15 (24%), carbapenemases encoding genes, and blaOXA48 (16%) were also detected. The isolates harbored FIB (88%), FIC (28%), A/C (14%), and FIIA (6%) plasmid replicons. Interestingly, 78% of the isolates were found to be resistant to chicken serum and 92% showed capabilities for growth in human urine. The isolates showed phenotypic resistance to several antibiotics including chloramphenicol (63%), ciprofloxacin (57%), trimethoprim-sulfamethoxazole (28%), streptomycin (17%), and cefoxitin and meropenem (14%) using the national antimicrobial resistance monitoring system panel.

Conclusions

Overall, our study provides evidence of the virulence of these global “high-risk” clones in Georgia poultry with some isolates showing genotypic overlap between APEC and UPEC. Also, this clone harbored several virulence genes, antimicrobial-resistant genes, and plasmids. Interestingly, the majority of APEC O25-ST131 isolates can survive and grow in both chicken serum and human urine and warrant further investigation of their potential pathogenicity for both chickens and humans.
The effect of a combined mHealth and community health worker intervention on HIV self-management
Authors: Dos Santos Fabiana Cristina , Batey D Scott , Kay Emma S , Jia Haomiao , Wood Olivia R , Abua Joseph A , Olender Susan A , Schnall Rebecca
Published: January 2025

Objective

To identify demographic, social, and clinical factors associated with HIV self-management and evaluate whether the CHAMPS intervention is associated with changes in an individual’s HIV self-management.

Method

This study was a secondary data analysis from a randomized controlled trial evaluating the effects of the CHAMPS, a mHealth intervention with community health worker sessions, on HIV self-management in New York City (NYC) and Birmingham. Group comparisons and linear regression analyses identified demographic, social, and clinical factors associated with HIV self-management. We calculated interactions between groups (CHAMPS intervention and standard of care) over time (6 and 12 months) following the baseline observation, indicating a difference in the outcome scores from baseline to each time across groups.

Results

Our findings indicate that missing medical appointments, uncertainty about accessing care, and lack of adherence to antiretroviral therapy are associated with lower HIV self-management. For the NYC site, the CHAMPS showed a statistically significant positive effect on daily HIV self-management (estimate = 0.149, SE = 0.069, 95% CI [0.018 to 0.289]). However, no significant effects were observed for social support or the chronic nature of HIV self-management. At the Birmingham site, the CHAMPS did not yield statistically significant effects on HIV self-management outcomes.

Discussion

Our study suggests that CHAMPS intervention enhances daily self-management activities for people with HIV at the NYC site, indicating a promising improvement in routine HIV care.

Conclusion

Further research is necessary to explore how various factors influence HIV self-management over time across different regions.
Intuitive and feasible geometric representation of airfoil using variational autoencoder
Authors: Kang Yu-Eop , Lee Dawoon , Yee Kwanjung
Published: January 2025

Airfoil shape optimization is crucial for improving aerodynamic performance in advanced aircraft designs. Given the extensive functional evaluations required for optimization, surrogate modeling is widely used to alleviate computational burden. However, greater flexibility in airfoil parameterization often requires a larger number of design variables, leading to the challenge known as the curse of dimensionality in surrogate modeling. In recent years, generative models such as generative adversarial networks and variational autoencoders have shown potential to represent large design spaces with compact design variables. However, these models still exhibit limited feasibility and intuitiveness due to their high model capacity, which in turn degrades the efficiency of design optimization. To address this issue, we have developed a novel airfoil parameterization method using a variational autoencoder. The proposed method improves feasibility by using architecture modeling to separate the generation of thickness and camber distributions, resulting in smooth and nonintersecting airfoils. It also improves intuitiveness by using a physics loss function that aligns latent dimensions with geometric features of the airfoils. Notably, extensive comparative analyses validate the effectiveness of our method in terms of flexibility, parsimony, feasibility, and intuitiveness, leading to increased efficiency in aerodynamic design optimization.
Disparities in cervical cancer elimination time frames in the United States: a comparative modeling study
Authors: Burger Emily A , Jansen Erik E L , de Bondt Daniël , Killen James , Spencer Jennifer C , Regan Mary Caroline , Smith Megan A , Sy Stephen , Canfell Karen , de Kok Inge M C M , Kim Jane J , Hontelez Jan A C
Published: January 2025

Population-level estimates in time frames for reaching cervical cancer elimination (ie, <4 cases per 100 000 women) in the United States may mask potential disparities in achieving elimination among subpopulations. We used 3 independent Cancer Intervention and Surveillance Modeling Network models to estimate differences in the time to cervical cancer elimination across 7 strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared with the average population, elimination was achieved at least 22 years earlier for the high-uptake strata and at least 27 years later for the most extreme low-uptake strata. Accounting for correlated uptake impacted the population average time frame by no more than 1 year. Consequently, national average elimination time frames mask substantial disparities in reaching elimination among subpopulations. Addressing inequalities in cervical cancer control could shorten elimination time frames and would ensure more equitable elimination across populations. Furthermore, country-level elimination monitoring could be supplemented by monitoring progress in subpopulations.
Arab domination and fiscal tensions in the Delta under the Marwānids: An official investigation regarding the punishment of a reluctant taxpayer
Authors: Maghraby Ahmed Nabil , Tillier Mathieu
Published: January 2025

From the end of the seventh century CE, Egypt was increasingly destabilised by taxpayer protests, which culminated in significant armed revolts in the following century. In this article, we present the edition, translation, and analysis of papyrus P. Utah Inv. 114 that uniquely documents an incident in the northern Delta, dating to the late seventh or the early eighth century CE. The death of a taxpayer, at the hands of a Christian official in a case of tax evasion, triggered an administrative investigation by the Arab-Muslim authorities. The resulting report not only shows how local authorities addressed cases of tax resistance, but offers new insights into the legal procedures implemented by provincial authorities. The document also allows for a better understanding of Arabic administrative terminology. Finally, it contains the earliest recorded use of the term ‘Arabs’ to refer to the group of conquerors, attributing a moral and religious significance to the term.
Solving quantified modal logic problems by translation to classical logics
Authors: Steen Alexander , Sutcliffe Geoff , BenzmÜller Christoph
Published: January 2025

This article describes an evaluation of Automated Theorem Proving (ATP) systems on problems taken from the Quantified Modal Logics Theorem Proving (QMLTP) library of first-order modal logic problems. Principally, the problems are translated to both typed first-order and higher-order logic (HOL) in the TPTP language using an embedding approach, and solved using first-order resp. HOL ATP systems and model finders. Additionally, the results from native modal logic ATP systems are considered, and compared with the results from the embedding approach. The findings are that the embedding process is reliable and successful when state-of-the-art ATP systems are used as backend reasoners, the first- and higher-order embeddings perform similarly, native modal logic ATP systems have comparable performance to classical systems using the embedding for proving theorems, native modal logic ATP systems are outperformed by the embedding approach for disproving conjectures and the embedding approach can cope with a wider range of modal logics than the native modal systems considered.
Ameliorative Potential of Carvedilol Versus Platelet-Rich Plasma Against Paclitaxel-Induced Femoral Neuropathy in Wistar Rats: A Light and Electron Microscopic Study
Authors: Fekry Ereny , Refaat George Nagi , Hosny Sara Adel
Published: January 2025

Paclitaxel, a chemotherapeutic drug, induces sensorimotor peripheral neuropathy. Carvedilol, a nonselective β-adrenoreceptor blocker, has been shown to exert antioxidant activity. Platelet-rich plasma (PRP) has supra-physiological levels of growth factors (GFs), enhances biosynthesis of antioxidant enzymes, and suppresses oxidative stress. This study compared the ameliorative effects of carvedilol and PRP on paclitaxel-induced femoral neuropathy. Eighty-eight adult male albino rats were equally randomized into four groups: group I served as the control; group II received paclitaxel (16 mg/kg intraperitoneally, weekly); group III received carvedilol (10 mg/kg daily, orally) concomitant with paclitaxel; and group IV received PRP (0.5 mL/kg subcutaneously, twice weekly) concomitant with paclitaxel. After 5 weeks, femoral nerve conduction velocity was measured, and blood samples were collected to assess catalase and superoxide dismutase levels. All animals were sacrificed, and gene expression of miR-21 was quantified. Tissue sections were stained with hematoxylin and eosin and toluidine blue. Then, the ultrathin sections were examined by transmission electron microscopy. Both carvedilol and PRP reversed paclitaxel-induced changes in the peripheral nerve, but PRP demonstrated a stronger antioxidant effect and a more pronounced presence of GFs, as evidenced by electron microscopy. PRP may represent a promising therapeutic approach for paclitaxel-induced neuropathy.
Hip Region Stress Fracture in South Korean Military Recruits: Private’s Fracture
Authors: Kim Jong Seop , Ahn Byung Hyun , Won Yoo-Sun , Kwak Woo Kyoung , Min Tae-Hong , Ha Cheungsoo
Published: January 2025

Introduction

This study aims to analyze the characteristics of hip region stress fractures (HSFs) within a South Korean military cohort and identify the associated risk factors to provide insights for treatment and prevention strategies. Additionally, we will report the epidemiologic data and clinical outcomes of treating HSF within the second largest military hospital.

Materials and Methods

Between January 2022 and December 2023, this retrospective case series revised all HSF patients’ medical records to analyze demographic and epidemiologic data and clinical progress. The incidence rate was calculated using the number of conscripted soldiers based on publicly open available statistics from government institution.

Results

A total of 95 hips from 60 patients were included in this study, and 35 patients (58.3%) exhibited bilaterality. The seasonal variation of HSF patients showed a bimodal distribution, with peaks from April to June and October to December. The incidence rate per 100,000 person-years is estimated to be between 55.3 in 2022 and 67.9 in 2023.

Conclusions

Hip region stress fractures can also be termed as “private’s fractures,” which accurately describe their nature. It is crucial to identify cases that necessitate early diagnosis and surgical intervention. Epidemiologically, HSF demonstrates high bilaterality and a bimodal distribution throughout the year. During this period, unit commanders and military doctors should be cautious of HSF among soldiers and conduct appropriate screenings.
ΛCDM model against cosmography: a possible deviation after DESI 2024
Authors: Pourojaghi Saeed , Malekjani Mohammad , Davari Zahra
Published: January 2025

In this study, we present an analysis of the standard flat-$\Lambda$CDM (Lambda cold dark matter) model using a cosmographic approach, incorporating recent Dark Energy Survey Instrument (DESI) baryon acoustic oscillation (BAO) observations and Type Ia Supernova (SNIa) catalogues, including Dark Energy Survey Supernova 5 Year Release (DES-SN5YR) and Pantheon + compilations. We find full consistency between the standard model and the cosmographic approach when considering DESI BAO and SNIa catalogues independently. When combining DESI BAO with SNIa data, we examine the impact of the Planck prior on the sound horizon at the drag epoch, $r_d$, and the Cepheid prior on the absolute magnitude, M. Applying the Planck prior on $r_d$ alone yields an $H_0$ value consistent with the Planck measurement, while applying the Cepheid prior on M alone results in an $H_0$ value consistent with the SH0ES measurement. Without any priors, the $H_0$ value obtained has a large error margin, reconciling the Planck and SH0ES measurements. In all cases where individual priors are applied, we observe no significant tension between the flat-$\Lambda$CDM model and the cosmographic approach. However, when both Planck and Cepheid priors are applied simultaneously, significant tensions arise between the model and cosmography. This tension is even more pronounced when excluding LRG1 and LRG2 from the DESI measurements. These results indicate that the standard model cannot simultaneously reconcile high-redshift Planck cosmic microwave background observations and local Cepheid measurements. This discrepancy supports the possibility of new physics beyond the standard model or, alternatively, the presence of unrecognized systematic errors in the observational data.
The impact of cosmic-ray heating on the cooling of the low-metallicity interstellar medium
Authors: Brugaletta Vittoria , Walch Stefanie , Naab Thorsten , Girichidis Philipp , Rathjen Tim-Eric , Seifried Daniel , Nürnberger Pierre Colin , Wünsch Richard , Glover Simon C O
Published: January 2025

Low-metallicity environments are subject to inefficient cooling. They also have low dust-to-gas ratios and therefore less efficient photoelectric (PE) heating than in solar-neighbourhood conditions, where PE heating is one of the most important heating processes in the warm neutral interstellar medium (ISM). We perform magnetohydrodynamic simulations of stratified ISM patches with a gas metallicity of 0.02 Z$_\odot$ as part of the SILCC project. The simulations include non-equilibrium chemistry, heating, and cooling of the low-temperature ISM as well as anisotropic cosmic-ray (CR) transport, and stellar tracks. We include stellar feedback in the form of far-ultraviolet and ionizing (FUV and extreme ultraviolet, EUV) radiation, massive star winds, supernovae, and CR injection. From the local CR energy density, we compute a CR heating rate that is variable in space and time. In this way, we can compare the relative impact of PE and CR heating on the metal-poor ISM and find that CR heating can dominate over PE heating. Models with a uniform CR ionization rate of $\zeta$  = 3 $\times$ 10$^{-17}$ s$^{-1}$ suppress or severely delay star formation, since they provide a larger amount of energy to the ISM due to CR heating. Models with a variable CR ionization rate form stars predominantly in pristine regions with low PE heating and CR ionization rates where the metal-poor gas is able to cool efficiently. Because of the low metallicity, the amount of formed stars in all runs is not enough to trigger outflows of gas from the mid-plane.
On the Owing to in Owing Duties to Self
Authors: Schofield Paul
Published: January 2025

Philosophical discussions of self-directed duties concern not merely those duties one has regarding oneself, but those one owes specifically to oneself. In this paper, I take up the question of what it even means to owe something to oneself in the first place. A proper appreciation of what it means, I argue, will help answer skeptics who doubt the coherence of duties to self.
Respect, Self-Respect, and Self-Knowledge
Authors: Cholbi Michael
Published: January 2025

Knowledge and respect exhibit a puzzling self-other asymmetry: Self-respect generates an imperative to know oneself, but as the objectionability of paternalism and privacy violations illustrate, respect for others can require that we avoid acquiring, or making use of, knowledge we have about them. This article elaborates this asymmetry and offers a solution to it, rooted in the distinctive importance that self-knowledge has for self-respecting rational agents: Self-respecting agents have reasons to have others defer to their ‘surfaces’ or self-presentations in order to inhibit making themselves vulnerable to others in ways that undermine their self-respect by subordinating their wills to the wills of others, as well as to ensure that self-knowledge can play its desired role in the lives of self-respecting agents.
A Funny Thing Happened on the Way to Self-Knowledge
Authors: MacKenzie Jordan
Published: January 2025

What moral value, if any, is there to unsuccessful self-scrutiny? I answer this question by drawing on Kant’s discussion of the duty of self-knowledge in the Metaphysics of Morals. On my interpretation, the duty of self-knowledge is a demand to understand the generic structure of our moral agency: fulfilling it requires that we appreciate ourselves as fundamentally flawed, but also fundamentally morally worthy. This interpretation renders the duty consistent with Kant’s claims about moral self-opacity and explains why Kant called self-knowledge the ‘First Command’ of all duties. But this interpretation has value beyond the exegetical: by appreciating the value of generic moral self-knowledge, we can understand why self-scrutiny can be worthwhile even when it does not yield particular self-knowledge.
Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex
Authors: Baral Saroj , Chakraborty Sagnik , Steinbach Peter J , Paul Debamita , Min Jung-Hyun , Ansari Anjum
Published: January 2025

Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair. T-jump measurements, together with a novel and rigorous comparison with equilibrium FRET, uncovered conformational dynamics spanning multiple timescales and revealed key differences between Rad4-specific and non-specific DNA. AT-rich non-specific sites (matched or mismatched) exhibited dynamics primarily within the T-jump observation window, albeit with some amplitude in ‘missing’ fast (<20 μs) kinetics. These fast-kinetics amplitudes were dramatically larger for specific sites (CCC/CCC and TTT/TTT), which also exhibited ‘missing’ slow (>50 ms) kinetics at elevated temperatures, unseen in non-specific sites. We posit that the rapid (μs–ms) intrinsic DNA fluctuations help stall a diffusing protein at AT-rich/damaged sites and that the >50-ms kinetics in specific DNA reflect a propensity to adopt unwound/bent conformations resembling Rad4-bound DNA structures. These studies provide compelling evidence for sequence/structure-dependent intrinsic DNA dynamics and deformability that likely govern damage sensing by Rad4.
The pathway to resolve dimeric forms distinguishes plasmids from megaplasmids in Enterobacteriaceae
Authors: Fournes Florian , Campos Manuel , Cury Jean , Schiavon Caroline , Pagès Carine , Touchon Marie , Rocha Eduardo P C , Rousseau Philippe , Cornet François
Published: January 2025

Bacterial genomes contain a plethora of secondary replicons of divergent size. Circular replicons must carry a system for resolving dimeric forms, resulting from recombination between sister copies. These systems use site-specific recombinases. Among these, the XerCD recombinase resolves dimers of chromosomes and certain plasmids, using different modes of regulation. We have analyzed the dimer resolution functions in enterobacterial secondary replicons and show that, in addition to the main chromosomes, XerCD is preferentially used by small plasmids and by the largest secondary replicons, megaplasmids and secondary chromosomes. Indeed, all replicons longer than 250 kb host an active XerCD recombination site. These sites, in contrast to those of small plasmids, use the same control as chromosomes, coupled to cell division by the FtsK protein. We conclude that a chromosome-like mode of dimer resolution is mandatory for the faithful inheritance of large plasmids and chromids, its acquisition being a prerequisite for the genesis of secondary chromosomes from plasmids.
A cross-species inducible system for enhanced protein expression and multiplexed metabolic pathway fine-tuning in bacteria
Authors: Li Yang , Wu Yaokang , Xu Xianhao , Liu Yanfeng , Li Jianghua , Du Guocheng , Lv Xueqin , Li Yangyang , Liu Long
Published: January 2025

Inducible systems are crucial to metabolic engineering and synthetic biology, enabling organisms that function as biosensors and produce valuable compounds. However, almost all inducible systems are strain-specific, limiting comparative analyses and applications across strains rapidly. This study designed and presented a robust workflow for developing the cross-species inducible system. By applying this approach, two reconstructed inducible systems (a 2,4-diacetylphloroglucinol-inducible system PphlF3R1 and an anhydrotetracycline-inducible system Ptet2R2*) were successfully developed and demonstrated to function in three model microorganisms, including Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum. To enhance their practicality, both inducible systems were subsequently placed on the plasmid and genome for detailed characterization to determine the optimal expression conditions. Furthermore, the more efficient inducible system Ptet2R2* was employed to express various reporter proteins and gene clusters in these three strains. Moreover, the aTc-inducible system Ptet2R2*, combined with T7 RNA polymerase and dCas12a, was utilized to develop a single-input genetic circuit that enables the simultaneous activation and repression of gene expression. Overall, the cross-species inducible system serves as a stringent, controllable and effective tool for protein expression and metabolic pathway control in different bacteria.
A mobile genetic element-derived primase-polymerase harbors multiple activities implicated in DNA replication and repair
Authors: Fu Pan , Wang Yuwei , Liu Yanqiu , Han Zhenhao , Peng Zhangzhong , Liu Linfeng , Han Wenyuan
Published: January 2025

Primase-polymerases (PrimPols) play divergent functions from DNA replication to DNA repair in all three life domains. In archaea and bacteria, numerous and diverse PPs are encoded by mobile genetic elements (MGEs) and act as the replicases for their MGEs. However, their varying activities and functions are not fully understood. In this study, we characterized a group of PrimPols that are genetically associated with prokaryotic argonaute proteins (pAgos). The pAgo-associated PrimPol (AgaPP) is likely derived from a MGE. AgaPP has polymerase and primase activities and physically interacts with a helicase encoded by its downstream gene, suggesting that they constitute a functional replication module. Further, AgaPP performs translesion DNA synthesis, terminal transfer and microhomology-mediated end joining (MMEJ), showing striking similarity to human DNA repair polymerase θ. AgaPP can promote the MMEJ repair of Cas9-induced double-stranded DNA breaks and increase cell survival post DNA damage in Escherichia coli. In addition, the MMEJ activity of AgaPP can be repurposed to assist DNA assembly in vitro. Together, the findings reveal dual role of AgaPP in both DNA replication and repair.
Dent disease: clinical practice recommendations
Authors: Bökenkamp Arend , Ariceta Gema , Böckenhauer Detlef , Devuyst Olivier , Emma Francesco , van Bennekom David , Levtchenko Elena , Sayer John , Servais Aude , Vargas Rosa , Zaniew Marcin , Prikhodina Larisa
Published: January 2025

Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the third and fifth decades of life in 30%–80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic-range proteinuria which may be misinterpreted and cause diagnostic delay. Due to its rarity, there is limited evidence to guide diagnosis and management. These clinical practice recommendations summarize the current knowledge on Dent disease and provide guidance for diagnosis and management. The recommendations are based on a systematic search of the literature and were endorsed by a Delphi procedure among stakeholders in the field as well as the respective ERA and ESPN working groups.
Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma
Authors: Martell Emma , Kuzmychova Helgi , Senthil Harshal , Chawla Ujala , Kaul Esha , Grewal Akaljot , Banerji Versha , Anderson Christopher M , Venugopal Chitra , Miller Donald , Werbowetski-Ogilvie Tamra E , Singh Sheila K , Sharif Tanveer
Published: January 2025

Background

The mitochondrial pyruvate carrier (MPC), a central metabolic conduit linking glycolysis and mitochondrial metabolism, is instrumental in energy production. However, the role of the MPC in cancer is controversial. In particular, the importance of the MPC in glioblastoma (GBM) disease progression following standard temozolomide (TMZ) and radiation therapy (RT) remains unexplored.

Methods

Leveraging in vitro and in vivo patient-derived models of TMZ-RT treatment in GBM, we characterize the temporal dynamics of MPC abundance and downstream metabolic consequences using state-of-the-art molecular, metabolic, and functional assays.

Results

Our findings unveil a disease stage-specific role for the MPC, where in posttreatment GBM, but not therapy-naïve tumors, the MPC acts as a central metabolic regulator that suppresses differentiation. Temporal profiling reveals a dynamic metabolic rewiring where a steady increase in MPC abundance favors a shift towards enhanced mitochondrial metabolic activity across patient GBM samples. Intriguingly, while overall mitochondrial metabolism is increased, acetyl-CoA production is reduced in posttreatment GBM cells, hindering histone acetylation and silencing neural differentiation genes in an MPC-dependent manner. Finally, the therapeutic translations of these findings are highlighted by the successful pre-clinical patient-derived orthotopic xenograft trials utilizing a blood-brain-barrier permeable MPC inhibitor, MSDC-0160, which augments standard TMZ-RT therapy to mitigate disease relapse and prolong animal survival.

Conclusion

Our findings demonstrate the critical role of the MPC in mediating GBM aggressiveness and molecular evolution following standard TMZ-RT treatment, illuminating a therapeutically-relevant metabolic vulnerability to potentially improve survival outcomes for GBM patients.
Prevalence of and factors associated with formula feeding among mothers with infants 0–6 months of age in Ethiopia: a systematic review and meta-analysis
Authors: Gebreegziabher Zenebe Abebe , Semagn Birhan Ewunu , Walle Agmasie Damtew , Tilahun Werkneh Melkie , Belay Mahider Awoke , Wondie Wubet Tazeb , Gedefaw Gezahagn Demsu , Dejene Tadesse Mamo , Mohammed Fitsum Zekarias
Published: January 2025

Context

Inconsistent results have been reported regarding the prevalence of and factors associated with formula feeding in Ethiopia.

Objective

This study aimed to determine the pooled prevalence of and factors associated with formula feeding among mothers with infants 0–6 months of age in Ethiopia.

Data Sources

A comprehensive systematic search was conducted across 3 databases (PubMed, EMBASE, and ScienceDirect) and the Google Scholar search engine to identify relevant studies published up to April 2, 2024.

Data Extraction

After assessing the quality of each study using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies, data were independently extracted by 2 authors using pre-designed forms in an Excel spreadsheet. Any disagreements were resolved through discussion and consultation with additional authors.

Data Analysis

Statistical heterogeneity across studies was assessed using the I2 statistic. A random-effects meta-analysis was used to pool the proportions, due to high heterogeneity, while a fixed-effect meta-analysis was used to pool associated factors with low heterogeneity. A sensitivity analysis was performed to assess the potential impact of outlier studies on the overall estimates. Five studies, with a combined sample size of 2344 participants, were included. The pooled prevalence of formula feeding was 34.0% (95% CI: 23.0%, 44.0%). Factors significantly associated with formula feeding included cesarean delivery (POR [pooled odds ratio] = 4.72, 95% CI: 3.32, 6.71) compared with vaginal delivery, a positive attitude toward formula feeding (POR = 2.26, 95% CI: 1.45, 3.53) compared with a negative attitude, initiation of breastfeeding more than 1 hour after delivery (POR = 2.27, 95% CI: 1.25, 4.13) compared with initiation within 1 hour, and receiving information about formula feeding from friends or family (POR = 2.47, 95% CI: 1.46, 4.20) compared with receiving information from health-care professionals.

Conclusion

The prevalence of formula feeding in Ethiopia is significant. Cesarean delivery, a positive attitude toward formula feeding, late initiation of breastfeeding, and receiving formula feeding-related information from friends and family were positively associated with formula feeding. Given these findings, the authors recommend that public health interventions in Ethiopia target these key determinants to decrease the high prevalence of formula feeding practices observed in the country. Strategies addressing factors such as promoting vaginal delivery, improving attitudes toward breastfeeding, encouraging early breastfeeding initiation, and limiting the influence of social networks on formula-feeding decisions may be beneficial.
Hepatitis C Virus Seroprevalence, Incidence, and Screening Patterns in Ontario Preexposure Prophylaxis Users
Authors: McGarrity Matthew W , Lisk Ryan , MacPherson Paul , Knox David , Woodward Kevin S , Reinhart Jeff , MacLeod John , Bogoch Isaac I , Clatworthy Deanna , Biondi Mia J , Sullivan Sean T , Li Alan T W , Burchell Ann N , Tan Darrell H S
Published: January 2025

Background

Hepatitis C virus (HCV) has emerged as a sexually transmitted infection in gay, bisexual, and other men who have sex with men (GBM). We estimated the seroprevalence and incidence of HCV infection and examined patterns of HCV testing among GBM using human immunodeficiency virus preexposure prophylaxis (PrEP) in Ontario, Canada.

Methods

We analyzed data from the Ontario PrEP Cohort Study (ON-PrEP), a prospective cohort of PrEP users from 10 Ontario clinics. Participants completed an online questionnaire and study staff collected clinical information into a study database biannually for 2 years. We estimated the baseline seroprevalence and incidence of HCV infection and examined patterns of HCV testing during follow-up. We further explored differences in sociodemographic/clinical variables between those with and without prevalent/incident HCV infection through bivariate analysis.

Results

Among 557 eligible PrEP users, 382 (68.6%) underwent baseline HCV antibody testing, of whom 5 tested HCV seropositive, giving a seroprevalence of 1.3% (95% confidence interval [CI], .43%–3.03%). Only 245 (43.9%) participants underwent HCV antibody testing after baseline, and median time to participants’ first follow-up test was 245 days. During follow-up, 2 participants tested newly HCV seropositive, giving an incidence of 0.47/100 person-years (95% CI, .06–1.69) over 428.9 years of follow-up. Participants with prevalent/incident HCV infection during the study appeared more likely to report giving money, drugs, gifts, or services for sex in the 3 months preceding enrollment compared to those who never tested HCV seropositive (P = .02).

Conclusions

HCV seroprevalence and incidence were low but not negligible among Ontario PrEP users. HCV antibody and RNA testing were suboptimal.
Cycling Dof Factor 3 mediates light-dependent ascorbate biosynthesis by activating GDP-l-galactose phosphorylase in Rosa roxburghii fruit
Authors: Huang Qianmin , Yan Yali , Zhang Xue , Cao Xuejiao , Ludlow Richard , Lu Min , An Huaming
Published: January 2025

Light plays an important role in determining the l-ascorbate (AsA) pool size in plants, primarily through the transcriptional regulation of AsA metabolism-related genes. However, the specific mechanism of transcriptional induction responsible for light-dependent AsA biosynthesis remains unclear. In this study, we used a promoter sequence containing light-responsive motifs from GDP-L-galactose phosphorylase 2 (RrGGP2), a key gene involved in AsA overproduction in Rosa roxburghii fruits, to identify participating transcription factors. Among these factors, Cycling Dof Factor 3 (RrCDF3) was highly responsive to variations in light intensity, quality, and photoperiod, leading to alterations in RrGGP2 expression. Further yeast one-hybrid and dual-luciferase assays confirmed that RrCDF3 acts as a transcriptional activator of RrGGP2 by binding specifically to its promoter. Modulating the expression of RrCDF3 in fruits through transient overexpression and silencing resulted in significant changes in RrGGP2 expression and AsA synthesis. Additionally, the stable overexpression of RrCDF3 in R. roxburghii calli and Solanum lycopersicum plants resulted in a significant increase in AsA content. Notably, the well-known photo-signal transcription factor ELONGATED HYPOCOTYL5 (RrHY5) directly interacted with the RrCDF3 promoter, enhancing its transcription. These findings reveal a special mechanism involving the RrHY5-RrCDF3-RrGGP2 module that mediates light-induced AsA biosynthesis in R. roxburghii fruit.
Chromatin accessibility mediated by CHROMATIN REMODELING 11 promotes chilling tolerance in rice
Authors: Li Jing , Liu He , Qian Hanying , Lu Shan , Wu Yufeng , Hua Jian , Zou Baohong
Published: January 2025

Chromatin remodeling plays a crucial role in controlling gene transcription by modifying chromatin structure. However, the involvement of chromatin remodeling in plant stress responses, especially cold tolerance, through chromatin accessibility remains largely unexplored. Here, we report that rice (Oryza sativa L.) CHROMATIN REMODELING 11 (OsCHR11) positively regulates chilling tolerance by enhancing chromatin accessibility and facilitating changes in gene expression. Loss-of-function mutants of OsCHR11 exhibited increased susceptibility to chilling stress compared to wild-type rice plants. Transcriptome analysis revealed that the chr11 mutant displays diminished transcriptomic responses to chilling. Additionally, assay for transposase-accessible chromatin indicated that chilling treatment increases chromatin accessibility in the promoter regions, and this process depended on OsCHR11 function. Chromatin immunoprecipitation sequencing showed that OsCHR11 is physically associated with the promoters of cold-responsive genes. Integrated multiomics analysis further demonstrated a correlation between OsCHR11 enrichment and chromatin accessibility, as well as a correlation between chromatin accessibility and gene expression. Furthermore, OsCHR11 is required for the full expression of key cold-response genes, including those involved in trehalose biosynthesis. The exogenous application of trehalose partially rescued the chilling-susceptible phenotype of the chr11 mutant, suggesting that trehalose biosynthesis contributes to the chilling tolerance promoted by OsCHR11. Collectively, these findings indicate that OsCHR11 enhances cold tolerance in plants, likely by increasing chromatin accessibility and elevating the expression levels of cold-response genes in response to chilling.
Steering the future: expert knowledge and stakeholder voices in autonomous vehicle policy reports
Authors: Hicks Diana , Kingsley Gordon , Isett Kimberley R
Published: January 2025

The anticipated arrival of autonomous vehicles has created considerable uncertainty for US states because they govern roads. In response, states activated their policy advisory systems. While policy advising at the national level has been studied, less is known about the sub-national level. Similarly, more is known about the use of scientific knowledge by policymakers than about the full range of knowledge deployed in policy advising. This study analyzes reports written for states to help them make sense of an emerging technology in preparation for governance. Committees, university researchers, staff at Department of Transportation, and legislative staff produced different types of reports, for example, more and less academic, focused more or less on topics associated with governance or engineering. Our analysis reveals that state policy advisory systems used two types of processes—convening and expert—and employed three types of expertise—academic, practical, and political—to help prepare to govern this emerging technology. The study provides insight into how states mobilized expertise to address uncertainty around an emerging technology, showing how different actors balanced the need for credible technical knowledge with legitimate stakeholder engagement.