bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyto- and genotoxicity evaluation of water samples collected from two rivers in the Kosovo
Authors: Asllani Fisnik H , Alija Avdulla J , Eckl Peter M , Bresgen Nikolaus 
Published: August 2024

Abstract
River water in Kosovo is exposed to various discharges from industrial and agricultural activities as well as to urban wastewater. Rivers Sitnica and Drenica are among the most affected ones and water samples drawn from these rivers show the presence of various toxic substances. Genotoxic effects are seen in fish living in these rivers indicating a cytotoxic and mutagenic potential of the river water. Aiming at substantiating these observations, we assessed the cyto- and genotoxic effects of water samples collected at different locations from the Drenica and Sitnica rivers. Samples drawn from Lake Badovc served for comparison. To address seasonal effects, samples were collected at different seasons/time points during the period of summer 2016—spring 2018. The water samples were analyzed employing primary rat hepatocytes as a reliable in vitro cell model for the assessment of cytotoxic effects (mitotic arrest and cell death) and DNA damage/genotoxicity (micronucleus assay and Comet assay). The results do not account for significant effects associated with specific locations but demonstrate seasonal differences of the genotoxic potential of the water samples collected along both rivers, which are accompanied by a limited cytotoxic potential. Our data provide substantial support to earlier observations and strongly warrant the need for continuous chemical as well as biological monitoring of the river water in Kosovo, focusing on improved toxicant profiling of the river water and investigations addressing the observed seasonal variations.
Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation
Authors: Rao Satyajeet , Andrs Martin , Shukla Kaustubh , Isik Esin , König Christiane , Schneider Stefan , Bauer Michael , Rosano Vinicio , Prokes Jiri , Müller Anne , Janscak Pavel 
Published: August 2024

Abstract
Replication forks stalled at co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage-religation cycles mediated by MUS81 endonuclease and DNA ligase IV (LIG4), which presumably relieve the topological barrier generated by the transcription-replication conflict (TRC) and facilitate ELL-dependent reactivation of transcription. Here, we report that the restart of R-loop-stalled replication forks via the MUS81-LIG4-ELL pathway requires senataxin (SETX), a helicase that can unwind RNA:DNA hybrids. We found that SETX promotes replication fork progression by preventing R-loop accumulation during S-phase. Interestingly, loss of SETX helicase activity leads to nascent DNA degradation upon induction of R-loop-mediated fork stalling by hydroxyurea. This fork degradation phenotype is independent of replication fork reversal and results from DNA2-mediated resection of MUS81-cleaved replication forks that accumulate due to defective replication restart. Finally, we demonstrate that SETX acts in a common pathway with the DEAD-box helicase DDX17 to suppress R-loop-mediated replication stress in human cells. A possible cooperation between these RNA/DNA helicases in R-loop unwinding at TRC sites is discussed.
Transposition with Tn3-family elements occurs through interaction with the host β-sliding clamp processivity factor
Authors: Tang Yu , Zhang Jianfeng , Guan Jiahao , Liang Wei , Petassi Michael T , Zhang Yumeng , Jiang Xiaofei , Wang Minggui , Wu Wenjuan , Ou Hong-Yu , Peters Joseph E 
Published: August 2024

Abstract
Tn3 family transposons are a widespread group of replicative transposons, notorious for contributing to the dissemination of antibiotic resistance, particularly the global prevalence of carbapenem resistance. The transposase (TnpA) of these elements catalyzes DNA breakage and rejoining reactions required for transposition. However, the molecular mechanism for target site selection with these elements remains unclear. Here, we identify a QLxxLR motif in N-terminal of Tn3 TnpAs and demonstrate that this motif allows interaction between TnpA of Tn3 family transposon Tn1721 and the host β-sliding clamp (DnaN), the major processivity factor of the DNA replication machinery. The TnpA-DnaN interaction is essential for Tn1721 transposition. Our work unveils a mechanism whereby Tn3 family transposons can bias transposition into certain replisomes through an interaction with the host replication machinery. This study further expands the diversity of mobile elements that use interaction with the host replication machinery to bias integration.
qPrimerDB 2.0: an updated comprehensive gene-specific qPCR primer database for 1172 organisms
Authors: Li Xiaodong , Meng Boyu , Zhang Zhi , Wei Lijuan , Chang Wei , Wang Yuhong , Zhang Kai , Li Tian , Lu Kun 
Published: August 2024

Abstract
High-quality primer design is essential for the success of all polymerase chain reaction (PCR)–based experiments. We previously developed a thermodynamics-based gene-specific quantitative PCR (qPCR) primer database for 147 organisms, which has been used extensively in gene expression studies. However, the number of organisms and the imperfection of function in the database limits its potential applications. Here, we improved the functionality of qPrimerDB to create a more comprehensive primer resource. Specifically, we (i) developed an improved primer design tool, qPrimer, building upon the previous qPrimerDB pipeline, to enhance the efficiency and simplicity of genome-scale qPCR primer design; (ii) pre-computed qPCR primer resources from 1 308 genomes of 1172 organisms and (iii) introduced a complete system for identifying, designing, checking, marking, and submitting qPCR primers. qPrimerDB 2.0 is freely available at https://qprimerdb.biodb.org. The qPrimer source code is available at https://github.com/swu1019lab/qPrimer.
Efficacy, biodistribution and safety comparison of chemically modified antisense oligonucleotides in the retina
Authors: Vázquez-Domínguez Irene , Anido Alejandro Allo , Duijkers Lonneke , Hoppenbrouwers Tamara , Hoogendoorn Anita D M , Koster Céline , Collin Rob W J , Garanto Alejandro 
Published: August 2024

Abstract
Antisense oligonucleotides (AONs) are a versatile tool for treating inherited retinal diseases. However, little is known about how different chemical modifications of AONs can affect their biodistribution, toxicity, and uptake in the retina. Here, we addressed this question by comparing splice-switching AONs with three different chemical modifications commonly used in a clinical setting (2′O-methyl-phosphorothioate (2-OMe/PS), 2′O-methoxyethyl-phosphoriate (2-MOE/PS), and phosphorodiamidite morpholino oligomers (PMO)). These AONs targeted genes exclusively expressed in certain types of retinal cells. Overall, studies in vitro and in vivo in C57BL/6J wild-type mouse retinas showed that 2-OMe/PS and 2-MOE/PS AONs have comparable efficacy and safety profiles. In contrast, octa-guanidine-dendrimer-conjugated in vivo PMO-oligonucleotides (ivPMO) caused toxicity. This was evidenced by externally visible ocular phenotypes in 88.5% of all ivPMO-treated animals, accompanied by severe alterations at the morphological level. However, delivery of unmodified PMO-AONs did not cause any toxicity, although it clearly reduced the efficacy. We conducted the first systematic comparison of different chemical modifications of AONs in the retina. Our results showed that the same AON sequence with different chemical modifications displayed different splicing modulation efficacies, suggesting the 2′MOE/PS modification as the most efficacious in these conditions. Thereby, our work provides important insights for future clinical applications.
Invention of circRNA promoting RNA to specifically promote circRNA production
Authors: He Zhilin , Ji Haofei , Xia Bei , Cao Xiuen , Huang Ying , Zhu Qubo 
Published: August 2024

Abstract
CircRNA, an essential RNA molecule involved in various biological functions and diseases, often exhibits decreased expression in tumor tissues, playing a role as a tumor suppressor, and suggesting therapeutic potential for cancer. However, current methods for promoting circRNA production are limited. This study introduces a novel approach for enhancing circRNA biogenesis, termed circRNA promoting RNA (cpRNA). CpRNA is designed to complement the flanking sequences of reverse complementary matches (RCMs) within pre-mRNA, thereby facilitating circRNA formation through improved exon circularization. Using a split-GFP reporter system, we demonstrated that cpRNA significantly enhance circGFP production. Optimization identified the best conditions for cpRNA to promote circRNA biogenesis, and these cpRNAs were then used to augment the production of endogenous circRNAs. These results indicate that cpRNAs can specifically increase the production of endogenous circRNAs with RCMs, such as circZKSCAN1 and circSMARCA5 in cancer cells, thereby inhibiting cell proliferation and migration by modulating circRNA-related pathways, showcasing the therapeutic potential of cpRNAs. Mechanistic studies have also shown that cpRNA promotes circRNA biogenesis, in part, by antagonizing the unwinding function of DHX9. Overall, these findings suggest that cpRNA represents a promising strategy for circRNA overexpression, offering a potential treatment for diseases marked by low circRNA levels.
Mitoclone2: an R package for elucidating clonal structure in single-cell RNA-sequencing data using mitochondrial variants
Authors: Story Benjamin , Velten Lars , Mönke Gregor , Annan Ahrmad , Steinmetz Lars 
Published: August 2024

Abstract
Clonal cell population dynamics play a critical role in both disease and development. Due to high mitochondrial mutation rates under both healthy and diseased conditions, mitochondrial genomic variability is a particularly useful resource in facilitating the identification of clonal population structure. Here we present mitoClone2, an all-inclusive R package allowing for the identification of clonal populations through integration of mitochondrial heteroplasmic variants discovered from single-cell sequencing experiments. Our package streamlines the investigation of this phenomenon by providing: built-in compatibility with commonly used tools for the delineation of clonal structure, the ability to directly use multiplexed BAM files as input, annotations for both human and mouse mitochondrial genomes, and helper functions for calling, filtering, clustering, and visualizing variants.
Latent Dirichlet allocation mixture models for nucleotide sequence analysis
Authors: Wang Bixuan , Mount Stephen M 
Published: August 2024

Abstract
Strings of nucleotides carrying biological information are typically described as sequence motifs represented by weight matrices or consensus sequences. However, many signals in DNA or RNA are recognized by multiple factors in temporal sequence, consist of distinct alternative motifs, or are best described by base composition. Here we apply the latent Dirichlet allocation (LDA) mixture model to nucleotide sequences. Using positions in an alignment of human or Drosophila splice sites as samples, we show that LDA readily identifies motifs, including such elusive cases as the intron branch site. Using whole sequences with positional k-mers as features, LDA can identify sequence subtypes enriched in long vs. short introns. LDA with bulk k-mers can reliably distinguish reading frame and species of origin in coding sequences from humans and Drosophila. We find that LDA is a useful model for describing heterogeneous signals, for assigning individual sequences to subtypes, and for identifying and characterizing sequences that do not fit recognized subtypes. Because LDA topic models are interpretable, they also aid the discovery of new motifs, even those present in a small fraction of samples. In summary, LDA can identify and characterize signals in nucleotide sequences, including candidate regulatory factors involved in biological processes.
Characterizing behavioural differentiation in gene regulatory networks with representation graphs
Authors: Viksna Juris , Cerans Karlis , Lace Lelde , Melkus Gatis 
Published: August 2024

AbstractWe introduce the formal notion of representation graphs, encapsulating the state space structure of gene regulatory network models in a compact and concise form that highlights the most significant features of stable states and differentiation processes leading to distinct stability regions. The concept has been developed in the context of a hybrid system-based gene network modelling framework; however, we anticipate that it can also be adapted to other approaches of modelling gene networks in discrete terms. We describe a practical algorithm for representation graph computation as well as two case studies demonstrating their real-world application and utility. The first case study presents models for three phage viruses. It shows that the process of differentiation into lytic and lysogenic behavioural states for all these models is described by the same representation graph despite the distinctive underlying mechanisms for differentiation. The second case study shows the advantages of our approach for modelling the process of myeloid cell differentiation from a common progenitor into different cell types. Both case studies also demonstrate the potential of the representation graph approach for deriving and validating hypotheses about regulatory interactions that must be satisfied for biologically viable behaviours.
Financial toxicity of oral chemotherapy in patients with primary brain tumors
Authors: Patel Mallika P , Affronti Mary Lou , Buckley Evan D , Herndon II James E , Mackowsky Emma M , Johnson Margaret O , Peters Katherine B 
Published: August 2024

Abstract

Background
Cancer treatment costs continue to rise with the development of new agents. Financial toxicity is defined as the quantifiable costs associated with cancer and cancer treatment in addition to the patient’s associated distress. This study’s rationale is to better understand the financial burden of oral chemotherapies from the perspective of patients with primary brain tumors.

Methods
After one cycle of oral chemotherapy, we requested patients to complete the financial toxicity-functional assessment of chronic illness therapy (COST-FACIT) survey and additional questions relevant to insurance and cost. We summarized responses with descriptive statistics within strata defined by on-label or off-label oral therapy.

Results
Sixty surveys were completed, with most patients (n = 53, 88%) receiving on-label therapy; only 7 patients (12%) received off-label oral agents. The mean overall financial toxicity score was 23.1 (SD = 11.3). When asked if their provider discussed treatment cost before initiation, 21 patients (35%) stated that they did, and 39 patients (65%) said they did not discuss cost or did not recall. However, in the off-label cohort, all 7 patients stated that their provider discussed the cost before prescribing. Most patients (70%) had copays. Nine (17%) in the on-label group and 3 (43%) in the off-label group had chemotherapy-associated costs that negatively affected their quality of life. A higher percentage of financial distress occurred in the off-label group.

Conclusions
Discussing medication costs with patients is an essential part of chemotherapy initiation and may mitigate undue psychosocial and financial distress.
Revisiting the effect of democracy on population health
Authors: Vu Trung V 
Published: August 2024

Abstract
I use a novel dichotomous measure of democracy to simulate a quasi-natural experiment and implement a difference-in-differences analysis to identify the heterogeneous treatment effect of democracy on population health across countries from 1960 to 2010. To counteract potential sources of bias resulting from unparallel and stochastic trends between treated and control units, I adopt a principal components difference-in-differences estimator that exploits factor proxies constructed from control units to account for unobserved trends. The main results indicate that countries that transitioned from non-democracy to democracy are more likely to experience health improvements, compared to countries retaining non-democratic institutions. However, the health-enhancing impact of democratization turns out to be much smaller in size than previously established. I posit that conventional estimates exaggerate the economic significance of the health returns to democratization due to inadequate attention to cross-border spillovers, global common shocks, and worldwide heterogeneity in the democracy-health nexus.
Addressing the urgent need for direct climate cooling: Rationale and options
Authors: Baiman Ron , Clarke Sev , Elsworth Clive , Field Leslie , MacCracken Michael , Macdonald John , Mitchell David , Oeste Franz Dietrich , Reed Suzanne , Salter Stephen , Simmens Herb , Tao Ye , Tulip Robert 
Published: August 2024

Abstract
Emissions reduction and removal are not proceeding at a pace that will limit global average warming to less than the Paris Agreement targets of 1.5°C or 2.0°C. Accelerating global warming is indicated by record high 2023–2024 monthly temperatures and annual 2023 global mean surface temperatures around 1.5°C above pre-industrial levels. Only direct climate cooling has the potential to avert continued temperature rise in the near term and moderate at least some projected climate change disruption including extreme weather, sea level rise, loss of sea ice, glacier and permafrost melting, and coral reef die-off. Strategically deployed at scale, starting in the near term, several cooling measures have the potential to reduce or reverse global warming. Others can exert local or regional cooling influences. The world needs an approach to climate change that extends beyond sole reliance on emission reductions and removal. We propose (i) researching, field testing and deploying one or more large-scale cooling influence(s) perhaps initially in polar regions and applying local and regional cooling measures that also support adaptation, (ii) accelerating emissions reductions with an early prioritization of short-lived climate drivers, and (iii) deploying large scale carbon removal to draw down legacy greenhouse gas. The authors make no attempt to determine what measures or mix of measures is optimal. That will depend on modeling and experimentation. Only by including properly researched emergency cooling “tourniquets,” in the near-term to our “bleeding” Earth can we slow and then reverse ongoing and increasingly severe climate change in the 21st Century.
AIDS and the End of the Soviet Union
Authors: Hearne Siobhán 
Published: August 2024

Abstract
In the mid-1980s, HIV and AIDS were initially dismissed in the Soviet press as infections that could only be contracted by individuals engaged in ‘deviant’ or ‘promiscuous’ sexual behaviour. However, in late 1988 a different narrative took hold when the mass nosocomial infection of children occurred in hospitals in Elista, Volgograd and Rostov-on-Don. These tragedies — and the Soviet government’s lack of action in their aftermath — crystallized the public perception that the spread of HIV and AIDS was primarily due to government negligence and the deficiencies of the Soviet system. In this context, civil society organizations sprang up across the USSR to critique the government’s AIDS response, address the country’s inadequate healthcare infrastructure, and formulate their own solutions. This article explores how this played out in Moscow and Riga in 1989–90, where grassroots AIDS action was inflected by the local political context and indicative of the broader disillusionment with the Soviet government. Because of the specific conditions of Soviet society, AIDS action was more centred on the collapse of the social contract between citizens and the government in a socialist welfare state, and less about the de-stigmatization and liberation of marginalized groups.
Indication of long-range correlations governing city size
Authors: Li Yunfei , Ural Deniz , Kantelhardt Jan W , Rybski Diego 
Published: August 2024

Abstract
City systems are characterized by the functional organization of cities on a regional or country scale. While there is a relatively good empirical and theoretical understanding of city size distributions, insights about their spatial organization remain on a conceptual level. Here, we analyze empirically the correlations between the sizes of cities (in terms of area) across long distances. Therefore, we (i) define city clusters, (ii) obtain the neighborhood network from Voronoi cells, and (iii) apply a fluctuation analysis along all shortest paths. We find that most European countries exhibit long-range correlations but in several cases these are anti-correlations. In an analogous way, we study a model inspired by Central Places Theory and find that it leads to positive long-range correlations, unless there is strong additional spatial disorder—contrary to intuition. We conclude that the interactions between cities extend over large distances reaching the country scale. Our findings have policy relevance as urban development or decline can affect cities at a considerable distance.
What is it to have an inquisitive attitude?
Authors: Gaultier Benoit 
Published: August 2024

Abstract
Following a common assumption, when one inquires into a question, one has an inquisitive attitude towards it. More precisely, I shall assume that there is an inquisitive attitude towards Q that all of those who inquire into Q have in common and in virtue of which they can be said to be in an inquisitive state of mind towards Q. This paper is about the nature of this attitude. I elucidate it by examining whether it boils down to doubt, curiosity, epistemic desire, or wondering. I shall do this by examining whether having these attitudes is necessary and sufficient for being in an inquisitive state of mind. The test will prove negative for the first three, but the case of wondering is more complex.
Major alteration of motor control during rapid eye movements sleep in mice models of sleep disorders
Authors: Grenot Maxime , Roman Alexis , Villalba Manon , Morel Anne-Laure , Fort Patrice , Arthaud Sébastien , Libourel Paul-Antoine , Peyron Christelle 
Published: August 2024

Abstract
Alteration of motor control during rapid eye movements (REM) sleep has been extensively described in sleep disorders, in particular in isolated REM sleep behavior disorder (iRBD) and narcolepsy type 1 (NT1). NT1 is caused by the loss of orexin/hypocretin (ORX) neurons. Unlike in iRBD, the RBD comorbid symptoms of NT1 are not associated with alpha-synucleinopathies. To determine whether the chronic absence of ORX neuropeptides is sufficient to induce RBD symptoms, we analyzed during REM sleep the EMG signal of the prepro-hypocretin knockout mice (ORX−/−), a recognized mouse model of NT1. Then, we evaluated the severity of motor alterations by comparing the EMG data of ORX−/− mice to those of mice with a targeted suppression of the sublaterodorsal glutamatergic neurotransmission, a recognized rodent model of iRBD. We found a significant alteration of tonic and phasic components of EMG during REM sleep in ORX−/− mice, with more phasic events and more REM sleep episodes without atonia compared to the control wild-type mice. However, these phasic events were fewer, shorter, and less complex in ORX−/− mice compared to the RBD-like ORX−/− mice. We thus show that ORX deficiency, as seen in NT1, is sufficient to impair muscle atonia during REM sleep with a moderate severity of alteration as compared to isolated RBD mice. As described in NT1 patients, we report a major interindividual variability in the severity and frequency of RBD symptoms in ORX-deficient mice.