bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges
Authors: Espinoza Miranda Suyen Solange , Abbaszade Gorkhmaz , Hess Wolfgang R. , Drescher Knut , Saliba Antoine-Emmanuel , Zaburdaev Vasily , Chai Liraz , Dreisewerd Klaus , Grünberger Alexander , Westendorf Christian , Müller Susann , Mascher Thorsten 
Published: January 2025

SUMMARY
The development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.
Overexpression of the RNA-binding protein NrdA affects global gene expression and secondary metabolism in
Aspergillus
species
Authors: Kadooka Chihiro , Izumitsu Kosuke , Asai Teigo , Hiramatsu Kentaro , Mori Kazuki , Okutsu Kayu , Yoshizaki Yumiko , Takamine Kazunori , Goto Masatoshi , Tamaki Hisanori , Futagami Taiki 
Published: January 2025

ABSTRACT

RNA-binding protein Nrd1 plays a role in RNA polymerase II transcription termination. In this study, we showed that the orthologous NrdA is important in global mRNA expression and secondary metabolism in
Aspergillus
species. We constructed an
nrdA
conditional expression strain using the Tet-On system in
Aspergillus luchuenesis
mut.
kawachii
. Downregulation of
nrdA
caused a severe growth defect, indicating that NrdA is essential for the proliferation of
A. kawachii
. Parallel RNA-sequencing and RNA immunoprecipitation-sequencing analysis identified potential NrdA-interacting transcripts, corresponding to 32% of the predicted protein-coding genes of
A. kawachii
. Subsequent gene ontology analysis suggested that overexpression of NrdA affects the production of secondary metabolites. To clarify this, we constructed
Aspergillus nidulans
,
Aspergillus fumigatus
, and
Aspergillus oryzae
strains overexpressing NrdA in the early developmental stage. Overexpression of NrdA reduced the production of sterigmatocystin and penicillin in
A. nidulans
, as well as that of helvolic acid and pyripyropene A in
A. fumigatus
. Moreover, it increased the production of kojic acid and reduced the production of penicillin in
A. oryzae
. These effects were accompanied by almost consistent changes in the mRNA levels of relevant genes. Collectively, these results suggest that NrdA is the essential RNA-binding protein, which plays a significant role in global gene expression and secondary metabolism in
Aspergillus
species.

IMPORTANCE

Nrd1, a component of the Nrd1–Nab3–Sen1 complex, is an essential RNA-binding protein involved in transcriptional termination in yeast. However, its role in filamentous fungi has not been studied. In this study, we characterized an orthologous NrdA in the
Aspergillus
species, identified potential NrdA-interacting mRNA, and investigated the effect of overexpression of NrdA on mRNA expression in
Aspergillus luchuensis
mut.
kawachii
. The results indicated that NrdA controls global gene expression involved in versatile metabolic pathways, including the secondary metabolic process, at least in the early developmental stage. We demonstrated that NrdA overexpression significantly affected the production of secondary metabolites in
Aspergillus nidulans
,
Aspergillus oryzae
, and
Aspergillus fumigatus
. Our findings are of importance to the fungal research community because the secondary metabolism is an industrially and clinically important aspect for the
Aspergillus
species.
Gender affirming hormone therapy for individuals with gender dysphoria aged <26 years: a systematic review and meta-analysis
Authors: Miroshnychenko Anna , Ibrahim Sara , Roldan Yetiani , Kulatunga-Moruzi Chan , Montante Steven , Couban Rachel , Guyatt Gordon , Brignardello-Petersen Romina 
Published: January 2025

ObjectiveIn this systematic review and meta-analysis, we assessed and summarised the certainty of the evidence about the effects of gender affirming hormone therapy (GAHT) in individuals with gender dysphoria (GD).MethodsWe searched Medline, Embase, PsychINFO, Social Sciences Abstracts, LGBTQ+ Source and Sociological Abstracts from inception to September 2023. We included studies comparing GAHT with no GAHT in individuals aged <26 years with GD. Outcomes of interest included psychological and physical effects. Pairs of reviewers independently screened articles, abstracted data and assessed the risk of bias in the included studies. We performed meta-analyses and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsWe included 24 studies. Comparative observational studies (n=9) provided mostly very low certainty evidence regarding GD, global function and depression. One comparative observational study reported that the odds of depression may be lower (OR 0.73 (95% CI 0.61 to 0.88), n (number of studies)=1, low certainty) in individuals who received GAHT compared with those who did not. Before–after studies (n=13) provided very low certainty evidence about GD, global function, depression and bone mineral density. Case series studies (n=2) provided high certainty evidence that the proportion of individuals with cardiovascular events 7–109 months after receiving GAHT was 0.04 (95% CI 0.03 to 0.05, n=1, high certainty).ConclusionThere is considerable uncertainty about the effects of GAHT and we cannot exclude the possibility of benefit or harm. Methodologically rigorous prospective studies are needed to produce higher certainty evidence.Trial registration numberPROSPERO CRD42023452171.
Association of arterial stiffness and eye disease: a systematic review and meta-analysis
Authors: Beros Angela L , Sluyter John D , Scragg Robert 
Published: January 2025

BackgroundThis systematic review and meta-analysis assesses the association of arterial stiffness with age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO) and retinopathy (diabetic and hypertensive).MethodsMedline and Embase were systematically searched for observational studies of arterial stiffness and eye disease. Cohort studies were included if they estimated arterial stiffness using any measures based on the arterial waveform, with cross-sectional and case-control studies limited to measures of pulse wave velocity. We assessed the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation.ResultsThe systematic review of 61 studies (six for AMD, ten for glaucoma, six for RVO and 39 for retinopathy) showed that arterial stiffness overall was higher in people with eye disease than people without eye disease. Forty-four cross-sectional and case-control studies were included in the meta-analysis. Arterial stiffness estimated by way of pulse wave velocity was associated with AMD (mean difference: 0.92 m/s, 95% CI 0.37 to 1.46; 2 studies; n=381; low certainty evidence), glaucoma (mean difference: 0.97 m/s, 95% CI 0.31 to 1.64; 7 studies; n=3418; low certainty evidence), RVO (mean difference: 2.79 m/s, 95% CI 2.02 to 3.55; 5 studies; n=414; very low certainty evidence) and retinopathy (1.48 m/s, 95% CI 0.1.16 to 1.81; 22 studies; n=10 074; low certainty evidence). The 19 cohort studies identified (five for AMD, three for glaucoma, one for RVO and 10 for retinopathy) indicated overall that increased arterial stiffness was associated with the future development of eye disease.ConclusionsHigher arterial stiffness is associated with AMD, glaucoma, RVO and retinopathyPROSPERO registration numberCRD42019129563.
Fermionic entanglement in the presence of background electric and magnetic fields
Authors: Kaushal Shagun 
Published: January 2025

Abstract
In this study, we investigate the fermionic Schwinger effect in the presence of a constant magnetic field within

$$(1+3)$$

(
1
+
3
)

-dimensional Minkowski spacetime, considering both constant and pulsed electric fields. We analyze the correlations between Schwinger pairs for the vacuum and maximally entangled states of two fermionic fields. The correlations are quantified using entanglement entropy and Bell’s inequality violation for the vacuum state, while Bell’s inequality violation and mutual information are used for the maximally entangled state. One can observe the variation of the entanglement produced for fermionic modes with respect to different parameters. Additionally, we discuss the key differences from the behaviour of scalar fields in this context. This study offers deeper insights into quantum field theory and the dynamics of entanglement in the fermionic Schwinger effect.
Spinning waveforms of scalar radiation in quadratic modified gravity
Authors: Falkowski Adam , Marinellis Panagiotis 
Published: January 2025

Abstract
We study scalar–tensor gravitational theories using on-shell amplitude methods. We focus on theories with gravity coupled to a massless scalar via the Gauss–Bonnet and Chern–Simons terms. In this framework, we calculate the waveforms for classical scalar radiation emitted in scattering of macroscopic objects, including spin effects. To this end, we use the Kosower–Maybee–O’Connell formalism, with the 5-particle amplitude for scalar emission in matter scattering calculated at tree level using the unitarity-factorization bootstrap techniques. We also discuss in detail the dependence of that amplitude on the contact terms of the intermediate 4-particle scalar-graviton-matter amplitude. Finally, we discuss the conditions for resolvability of classical scalar radiation.
Quasi-topological fractons: a 3D dipolar gauge theory
Authors: Bertolini Erica , Blasi Alberto , Maggiore Nicola 
Published: January 2025

Abstract
We consider the theory of a generic rank-2 tensor field in three spacetime dimensions, which involves a symmetric tensor field transforming under infinitesimal diffeomorphisms, and a vector field, whose gauge transformation depends on a local vector parameter. The gauge fixing shows a non-trivial structure, and some non-intuitive possibilities are listed. Despite the fact that the theory is not topological, the energy-momentum tensor vanishes on-shell, which justifies the “quasi-topological” appellation we give to this theory. We show that the theory has three degrees of freedom. Moreover, we find an interesting physical interpretation, which consists in a generalized planar electromagnetism and in the emergence of two vector charges with restricted mobility. These are typical fractonic behaviours which can be related to the so-called traceless scalar and vector charge theories.
Correlation and autocorrelation of data on complex networks
Authors: Arthur Rudy 
Published: January 2025

Abstract
Networks where each node has one or more associated numerical values are common in applications. This work studies how summary statistics used for the analysis of spatial data can be applied to non-spatial networks for the purposes of exploratory data analysis. We focus primarily on Moran-type statistics and discuss measures of global autocorrelation, local autocorrelation and global correlation. We introduce null models based on fixing edges and permuting the data or fixing the data and permuting the edges. We demonstrate the use of these statistics on real and synthetic node-valued networks.
Closed-Form Solution to Vibration and Stability of Non-Prismatic and Axially Functionally Graded Beams
Authors: Zhao Xingwei , Jiang Wenhao , Ma Jiaqi , Zhao Ying 
Published: January 2025

The closed-form solution for the free vibration and buckling of non-prismatic and axially functionally graded beams is derived in this paper. Classical beam-column theory is applied to thin and slender beams. The governing differential equations, which contain variable coefficients, are solved exactly by introducing appropriate auxiliary functions. The method facilitates the derivation of closed-form solutions to exact mode shapes for free vibration and buckling, addressing a gap in existing methods for analyzing non-prismatic and axially functionally graded beams under various boundary conditions. The exact mode shapes for free vibration are identified as either hyperbolic trigonometric or hyperbolic functions, depending on the natural frequency. For buckling, the mode shapes are characterized by regularized confluent hypergeometric functions. The closed-form formulations enable efficient calculation of natural frequencies and critical buckling loads as eigenvalue problems, offering a straightforward method for identifying optimal design values. This approach eliminates the need for extensive series expansions common in many analytical methods and avoids the large number of elements required by finite element methods. To illustrate the effectiveness and accuracy of the method, several examples with various boundary conditions are provided.
How Does Virtual Reality Exposure Treatment Change the Brain Function of Acrophobia Patients? A Randomized Controlled Trial
Authors: Guo Meilin , Chen Yongjun , Xie Ya , Zhang Yumin , Xu Aoran , Zhang Guojia , Kong Jingya , Zhong Yuan , Wang Chun 
Published: January 2025

Background: Virtual reality exposure therapy (VRET), an innovative form of exposure therapy (ET), has been demonstrated to be effective in treating acrophobia. However, its neural mechanisms of action and how it differs from traditional imaginal exposure therapy (IET) remain unclear. This study utilized resting‐state functional magnetic resonance imaging (fMRI) to investigate the effects of VRET on brain activity in acrophobic patients and to explore the potential mechanisms underlying its therapeutic action.Method: Fifty patients with acrophobia were randomly assigned to either an experimental group (25 patients) or a control group (25 patients) based on different treatments. The experimental group received VRET, while the control group received conventional IET. A mixed‐design repeated‐measures analysis of variance (ANOVA) was performed on the whole brain to identify brain regions affected by the intervention. Both groups of patients underwent treatment twice a week for 3 weeks. fMRI scans were performed for all patients at baseline and after treatment to facilitate a comparison of clinical effects at the end of the treatment period. The degree centrality (DC) values of the blood oxygenation level dependent signals across the entire brain were analyzed. A mixed‐design repeated‐measures ANOVA was conducted on the pre‐ and post‐intervention data to identify brain regions affected by the intervention. The degree of symptom improvement was assessed using self‐report measures, including the Acrophobia Questionnaire (AQ), the Attitude Toward Heights Questionnaire, the Behavior Avoidance Test, and the 7‐item Generalized Anxiety Disorder Scale. These assessments were correlated with pre‐ and post‐intervention differences in brain activity. Additionally, a functional connectivity (FC) analysis was conducted to identify any atypical connectivity patterns following the ET.Results: There was a significant positive correlation between the change in scores on the AQ and the right middle temporal gyrus (MTG) (r = 0.442, p = 0.045). After VRET, DC values in the right calcarine, MTG, cuneus, and precuneus were decreased (p < 0.005), while DC values in the postcentral gyrus decreased after IET (p < 0.05). Additionally, reduced FC between the right MTG and both the right medial superior frontal gyrus and the left MTG was observed in acrophobia patients following VRET. In the IET group, reduced FC between the left MTG and the left superior temporal gyrus was found (p < 0.005).Conclusion: Preliminary results suggest that VRET may improve abnormal brain activity in acrophobia by modulating the activity of the default mode network and the primary visual cortex.
Targeting TUT1 Depletes Tri-snRNP Pools to Suppress Splicing and Inhibit Pancreatic Cancer Cell Survival
Authors: Guo Ziwei , Huang Junran , Lu Zhi J. , Shi Yongsheng , David Charles J. , Chen Mo 
Published: January 2025

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and lacks effective therapeutic options. Cancer cells frequently become more dependent on splicing factors than normal cells due to increased rates of transcription. Terminal uridylyltransferase 1 (TUT1) is a specific terminal uridylyltransferase for U6 small nuclear RNA (snRNA), which plays a catalytic role in the spliceosome. Here, we found that TUT1 was required for the survival of PDAC cells but not for normal pancreatic cells. In PDAC cells, the uridylylation activity of TUT1 promoted tri-snRNP assembly by facilitating the binding of LSM proteins to U6 snRNA and subsequent tri-snRNP assembly. PDAC cells required higher amounts of tri-snRNP to efficiently splice pre-mRNA with weak splice sites to support the high transcriptional output. Depletion of TUT1 in PDAC cells resulted in inefficient splicing of exons in a group of highly expressed RNAs containing weak splice sites, thereby resulting in the collapse of an mRNA processing circuit and consequently dysregulating splicing required by PDAC cells. Overall, this study unveiled an interesting function of TUT1 in regulating splicing by modulating tri-snRNP levels and demonstrated a distinct mechanism underlying splicing addiction in pancreatic cancer cells.
Vvax001, a Therapeutic Vaccine, for Patients with HPV16-Positive High-grade Cervical Intraepithelial Neoplasia: A Phase II Trial
Authors: Eerkens Anneke L. , Esajas Martha D. , Brummel Koen , Vledder Annegé , van Rooij Nienke , Plat Annechien , Avalos Haro Stefany B. , Paijens Sterre T. , Slagter-Menkema Lorian , Schuuring Ed , Werner Naomi , Kosterink Jos G.W. , Kroesen Bart-Jan , Wilschut Jan C. , Daemen Toos , Bart Joost , Nijman Hans W. , de Bruyn Marco , Yigit Refika 
Published: January 2025

Abstract

Purpose:
Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. In this study, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia (CIN) grade 3 (CIN3).

Patients and Methods:
Patients with newly diagnosed HPV16-positive CIN3 were eligible for participation. Patients received three immunizations of Vvax001 (5 × 107 infectious particles) at a 3-week interval. Up to 19 weeks after the last immunization, patients were monitored for regression of CIN3 by colposcopy. A colposcopy-guided biopsy was taken at the last visit, and a standard-of-care loop excision was performed only in case of remaining CIN grade 2/CIN3. Histopathologic response rates, HPV16 clearance, treatment-related adverse events, and vaccine-induced immune responses were assessed.

Results:
A total of 18 patients were enrolled and fully immunized. Colposcopic examination revealed a reduction in CIN3 lesion sizes in 17/18 (94%) patients already evident from 3 weeks onward after the last immunization. A histopathologic complete response (regression to CIN grade 1 or no dysplasia) was observed in 9/18 patients (50%) and HPV16 clearance in 10/16 patients (63%). Vvax001 did not induce clearance of other HPV types. To date, no recurrences have been observed, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious adverse events were observed.

Conclusions:
Treatment with Vvax001 is safe and feasible and shows preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions.
The Role of WDR77 in Cancer: More than a PRMT5 Interactor
Authors: Silverman Isaac , Shaykevich Aaron , Maitra Radhashree 
Published: January 2025

Abstract
WD repeat domain 77 protein (WDR77), a WD-40 domain–containing protein, is a crucial regulator of cellular pathways in cancer progression. Although much of the past research on WDR77 has focused on its interaction with protein arginine methyltransferase 5 (PRMT5) in histone methylation, WDR77’s regulatory functions extend beyond this pathway, influencing diverse mechanisms such as mRNA translation, chromatin assembly, cell-cycle regulation, and apoptosis. WDR77 is a key regulator of cell-cycle progression, regulating the transition from the G1 phase. WDR77 regulates many signaling pathways such as TGFβ in which its role in these cellular pathways underscores its broad oncogenic potential. WDR77 also assists and promotes certain transcription factors such as E2F. Furthermore, in certain cancers, WDR77 enhances steroid hormone receptor activity, uniquely linking it to hormone-driven malignancies. WDR77 often translocates between the nucleus and the cytoplasm, with its location dictating its role in the cell. WDR77 has the ability to adapt its function depending on its location that emphasizes its dynamic role in both promoting and inhibiting tumor growth, depending on cellular context. This dual function makes WDR77 an attractive therapeutic target, as disrupting its interactions with critical signaling pathways or modulating its translocation could yield novel strategies for cancer treatment. Given WDR77’s role in oncogenic pathways independent of PRMT5, further exploration of WDR77 and its non-PRMT5-related activities may reveal additional therapeutic opportunities in an array of cancers.