bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontiers of cervical cancer research: an analysis from the top 100 most influential articles in the field
Authors: Liang Lei , Song Chuangxiu , Chang Chun , Chen Shichao , Yang Bo , Sun Li 
Published: November 2024

AbstractBackgroungCervical cancer (CC) is one of the common gynecological malignancies, which has a serious negative impact on the quality of life of patients, and brings huge economic pressure and burden to society. The most effective treatment for CC has become an important issue worldwide.MethodIn order to determine the current research hotspots and development trends in a particular field, we conducted a bibliometric analysis of the top 100 cited papers. To achieve this, we searched for the top 100 most cited papers on the Science Citation Index Expanded (SCI Expanded) on the Web of Science (WOS), based on the CCS (citation count score). We then reviewed relevant literature from different years, countries/regions, institutions, authors, keywords, and references. Using VOS viewer and Cite Space software, we constructed a knowledge map, and finally compiled the relevant information we retrieved from the literature using Excel. Through this process, we were able to make predictions about the current focus and trends in the field.ResultsBetween 2013 and 2023, numerous journals published the top 100 cited research papers. The International Agency for Research on Cancer and the American Cancer Society were the most cited institutions. The United States contributed the most papers, followed by France and England. The top 5 keyword co-occurrences were cervical cancer, women, human papillomavirus, United States, and colorectal cancer. Cluster analysis results suggest that future research in CCS may focus on prophylaxis and HPV vaccination.ConclusionBibliometric analysis can quickly and intuitively identify the focus and boundaries of cervical cancer research. Our findings suggest that prophylaxis and HPV vaccination may be the focus and trend for future research on cervical cancer.
Exploring influenza vaccination coverage and determinants through digital participatory surveillance
Authors: Kelley Kathleen , Gozzi Nicolò , Mazzoli Mattia , Paolotti Daniela 
Published: November 2024

AbstractBackground:Vaccination is key for mitigating the impact of recurring seasonal influenza epidemics. Despite the efficacy and safety of influenza vaccines, achieving optimal vaccination uptake remains a challenge. This study aimed to explore the determinants of influenza vaccination uptake using data from Influweb, the Italian node of the InfluenzaNet participatory surveillance network, and to compare self-reported vaccination rates with data from official sources.MethodsThis study utilizes a longitudinal dataset of self-reported vaccination statuses from Italian participants across the 2011-2021 flu seasons. Logistic regression models were used to identify factors associated with vaccination uptake, while vaccination coverage of the Influweb population was compared with national data. Post-stratification weights were applied to account for demographic differences between the Influweb sample and the general population.ResultsThe analysis reveals that individuals using public transport, those living with minors, and residents of the Islands macro-region are less likely to receive the influenza vaccination. On the other hand, university-educated individuals, and those on medication for chronic diseases are more likely to be vaccinated. Age also plays a role: individuals aged 44 and under are less likely to vaccinate compared to those aged 45-65, while those over 65 are more likely to do so. Furthermore, higher cumulative influenza-like illness incidence rates within a macro-region are associated with increased vaccination uptake, suggesting that local epidemic dynamics may influence individual decisions. Finally, the impact of COVID-19 pandemic was associated with an increase in influenza vaccination uptake. Comparison of the Influweb data to nationally reported vaccination rates revealed higher coverage for self-reported vaccination. This could be linked to the voluntary nature of the survey, possibly attracting a more health-conscious cohort.ConclusionsOur study found that individuals living with minors and those relying on public transportation have lower odds of being vaccinated, despite having a higher documented risk of respiratory virus exposure. These findings highlight the importance of continued public health efforts targeting vulnerable groups and raising awareness about the risks of forgoing vaccination. The complex interplay of socioeconomic, demographic, and public health context significantly shapes vaccination decisions, emphasizing the need for tailored public health campaigns.
Mental Tasks Induce Common Modulations of Oscillations in Cortex and Spinal Cord
Authors: Ofner Patrick , Farina Dario , Mehring Carsten 
Published: November 2024

ABSTRACTWe investigated whether power modulations of cortical oscillations induced by mental tasks are paralleled by the same modulations in spinal motor neurons. We recruited 15 participants and recorded high-density electromyography signals (HD-EMG) from the tibialis anterior muscle, as well as electroencephalography (EEG) signals. The cumulative spike train (CST) was computed from the activity of spinal motor neurons decoded from HD-EMG signals. The participants performed sustained dorsiflexion concurrent with foot motor imagery, hand motor imagery, mental arithmetic, or no specific mental task. We found significant power correlations between CST and EEG across trials irrespective of the mental task and across mental tasks at the intra-muscular coherence peak (τtrial= 0.08 ± 0.10,τtask= 0.33 ± 0.19, respectively; mean ± std. dev.). CST power in beta and low-gamma bands could provide a novel control signal for neural interface applications, as power changes in these bands are not translated into actual force changes. To evaluate the potential of CST bands as a control signal, we classified the mental tasks from CST bandpower with a linear classifier and obtained classification accuracies slightly but significantly above chance level (30% ± 5%; chance level = 25%). These results show for the first time that mental tasks can modulate the power of cortical and spinal oscillations concurrently. This supports the notion that movement-unrelated oscillations can leak down from the cortex to the spinal level. We further show that mental tasks can be classified from CST, although further research is necessary to boost the classification performance to an adequate level for neural interface applications.Significance StatementSpike trains of spinal motor neurons have frequency components below 10 Hz that are translated into muscle force changes. These spike trains also contain oscillations above 10 Hz that do not directly produce force changes, and currently lack a clear functional interpretation. Our findings indicate that these oscillations can, at least in part, be remnants of force-unrelated cortical oscillations that propagate down to spinal motor neurons. This propagation enables the decoding of modulations of cortical oscillations evoked by mental tasks at the level of spinal motor neurons. We evaluate the decoding of these oscillation modulations for potential neural interface applications.
Exploring Mechanisms of Action in Combinatorial Therapies through Solubility Alterations: Advancing AML Treatment
Authors: Gholizadeh Elham , Zangene Ehsan , Vadadokhau Uladzislau , Ritz Danilo , Miettinen Juho J. , Soliymani Rabah , Baumann Marc , Wilhelm Mathias , Heckman Caroline A. , Saei Amir A. , Jafari Mohieddin 
Published: November 2024

AbstractAcute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. Although treatments like allogeneic hematopoietic stem cell transplantation and high-dose chemotherapy can potentially cure younger patients in some cases, challenges such as relapse and treatment-related toxicities remain significant. Combination therapy has been a cornerstone in AML treatment, offering enhanced efficacy by leveraging the synergistic effects of multiple agents. However, high toxicity levels and the genetic heterogeneity of AML complicate the identification of effective and universally applicable drug regimens. To address these challenges, we introduce CoPISA workflow (Proteome Integral Solubility/Stability Alteration Analysis for Combinations), an innovative method designed to study drug-target interactions specifically within combination therapies. CoPISA detects changes in protein solubility/stability that occur only when two drugs are used together, revealing cooperative mechanisms that single-drug treatments cannot achieve. We applied this method to two highly effective and low-toxicity drug combinations in AML, previously introduced by our group: LY3009120-sapanisertib (LS) and ruxolitinib-ulixertinib (RU). CoPISA workflow utilizes advanced proteomic tools to investigate both primary and secondary target effects, providing a deeper understanding of how combination therapies influence multiple signaling pathways to overcome resistance. Furthermore, we propose a novel concept termed “conjunctional inhibition”, where the combined action of drugs induces biological responses that cannot be achieved by individual agents. This approach introduces a transformation in designing combinatorial therapies and offers new directions for more effective treatments in AML and other complex diseases.
Cell fate determination is associated with changes in competing transcriptional units in the humanGATA1andGATA2lineage-determining transcription factors
Authors: Anderson Erik M , Li Hongchuan , Ruesch Michael , Wright Paul W , Freud Aharon G , Anderson Stephen K 
Published: November 2024

AbstractThe GATA1 and GATA2 transcription factors play a central role in early cell fate decisions in hematopoietic progenitor cells. Although the switch from GATA2 to GATA1 occupancy at GATA-binding sites in erythroblast-specific genes has been extensively studied, the underlying molecular mechanisms controlling this switch are not fully elucidated. An antisense promoter in the 5’ region of theGATA2gene produces a long non-coding RNA that has been shown to affectGATA2transcription and erythroblast differentiation. The recent identification of an antisense promoter in the first intron of theGATA1gene indicates that similar promoter competition mechanisms operate in these genes, potentially controlling GATA1/GATA2 levels in a probabilistic manner. In the current study we perform a comprehensive evaluation ofGATA1andGATA2transcripts in human CD34+progenitors either freshly isolated or differentiated in vitro and the human leukemia cell lines K562 and HL60. The ratio of competing sense and antisense transcripts varied significantly with differentiation status, suggesting that promoter competition controls cell fate decisions. Treatment of HL60 cells with differentiating agents resulted in significant changes in the ratio ofGATA2sense to antisense promoter activity, in agreement with previous results showing that sense and antisense transcription are associated with distinct cellular phenotypes.
Enhancement and validation of the antibiotic resistance prediction performance of a cloud-based genetics processing platform for Mycobacteria
Authors: Westhead Jeremy , Baker Catriona S , Brouard Marc , Colpus Matthew , Constantinides Bede , Hall Alexandra , Knaggs Jeff , Lopes Alves Marcela , Spies Ruan , Thai Hieu , Surrell Sarah , Govender Kumeren , Peto Timothy EA , Crook Derrick W , Omar Shaheed V , Turner Robert , Fowler Philip W 
Published: November 2024

AbstractTuberculosis remains a global health problem. Making it easier and quicker to identify which antibiotics an infection is likely to be susceptible to will be a key part of the solution. Whilst whole-genome sequencing offers many advantages, the processing of the genetic reads to produce the relevant public health and clinical information is, surprisingly, often the responsibility of the end user which inhibits uptake. Here we describe our Mycobacterial genetics processing pipeline and its deployment in a cloud-based platform. For antibiotic resistance prediction we have implemented the second edition of the WHO catalogue of resistance-associated variants. We validate the resistance prediction performance by constructing and processing a diverse dataset of 2,663 publicly-availableM. tuberculosissamples with published drug susceptibility testing (DST) data and find that identifying a sample as resistant if it contains a minor allele known to be associated with resistance increases sensitivity. By only considering high confidence DST results we are able to show that both isoniazid and rifampicin achieve sensitivities and specificities in excess of 95%.
Influenza Virus Enhances Bacterial Growth in the Lungs through Weakening Capsule Receptor-Mediated Bacterial Capture by Neutrophils
Authors: Fang Yujie , Ma Wenxia , Qian Chenyun , Hu Jiao , Tian Xianbin , Huang Xueting , Lai Wenlong , Wu Li , An Haoran , Zhang Jing-Ren 
Published: November 2024

ABSTRACTCertain serotypes of encapsulated bacteria are more associated with severe pneumonia than others, but the biological reason behind this association has remained largely unknown. This study has uncovered a causal relationship between capsule serotype and virulence phenotype ofStreptococcus pneumoniae, a leading cause of community-acquired pneumonia, in mice using isogenic bacteria. Certain high-virulence (HV) serotypes persist in the lungs and lead to severe pneumonia, whereas the low-virulence (LV) serotypes are effectively cleared. The capsule type-dependent difference in virulence is determined by the capsule-binding receptors, which recognize the capsular polysaccharides of the LV serotypes (but not the HV serotypes) and enable pathogen capture by neutrophils through complement activation. The capsule receptor-driven immunity of lung neutrophils is significantly compromised by pre-infection of influenza virus, which enhances the survival and virulence of the LVS. pneumoniaeserotypes, and recurs in the heightened pathogenicity ofHaemophilus influenzae. This study not only unravels the long-sought mechanistic mystery of serotype-dependent virulence in bacterial lung infections, but also provides an explanation for the well-known pathogenesis synergism between influenza virus and respiratory bacteria.Graphical abstract
CHARACTERIZATION OF RECOMBINASE ACTIVITY ACROSS CELLULAR GROWTH PHASES
Authors: Gonzalez-Colell M. , Macia J. 
Published: November 2024

ABSTRACTRecombinases, which are enzymes that catalyze targeted DNA modifications, hold significant potential in synthetic biology. Their capacity to precisely manipulate genetic material enables the construction of complex genetic circuits that can be dynamically reconfigured in response to environmental stimuli. Such capabilities are essential for developing synthetic organisms tailored for specific functions, including biosensing, bioremediation, and pharmaceutical production. Therefore, characterizing the dynamics of recombinases is crucial for the innovative design of cellular devices. A deeper understanding of how recombinases interact with DNA in various conditions can improve the efficiency and control of genetic modifications, thereby enhancing both the functionality and reliability of synthetic biological systems.This study presents a detailed examination of the dynamics and efficiency of the serine recombinase Bxb1, focusing on its behavior under controlled expression inEscherichia coli. It highlights the significant influence of cellular growth phases (exponential and stationary) on the efficiency of recombinase-mediated gene expression. Our findings show that recombinase activity is maintained during stationary phase, which is critical to ensure ongoing recombination without the need for the continuous presence of an inducer.In experiments, we quantified the recombination efficiency of Bxb1 by monitoring expression of green fluorescent protein (GFP) as a reporter. Optimal expression of Bxb1, which maximized the recombination efficiency, occurred during exponential phase. However, once the culture reached stationary phase, accumulated Bxb1 continued to facilitate recombination, although GFP expression levels plateaued due to reduced cellular activity.These insights are relevant for synthetic biology applications where precise control of genetic functions is necessary.
Contrasted viral communities betweenAedes albopictusandCulex quinquefasciatusin La Réunion Island
Authors: François S. , Antoine-Lorquin A. , Mutuel D. , Makoundou P. , Perriat-Sanguinet M. , Unal S. , Sobry H. , Gosselin-Grenet A.S. , Ogliastro M. , Sicard M. , Weill M. , Atyame C. , Boëte C. 
Published: November 2024

AbstractMosquitoes are major vectors of arboviruses, and host a wide diversity of insect viruses. Recent studies highlighted the impacts of mosquito-associated insect-specific viruses on the transmission of arboviruses. However, we still lack knowledge on the biotic and abiotic factors impacting the distribution dynamics of mosquito specific viruses, although such information has the potential to inform arbovirus surveillance efforts. To gain knowledge on the distribution of mosquito viruses in islands, we collected 13Aedes albopictusand 9Culex quinquefasciatuspooled larvae samples in the Réunion Island, described their whole viral communities at the family level by a viromic approach, and tested the impacts of mosquito species and spatial distance on the structure of their viral communities.Our study show that the composition of viral communities is more strongly linked to mosquito species than to the geographic origin of samples. Spatial disparities were only observed inAedes albopictusviromes. Finally, we described the genomes of five virus taxa (an iflavirus, an ambidensovirus and three potentially novel microvirus species). Notably, we detected the presence of a mosquito-infecting ambidensovirus, named CpDV, inAedes albopictus. It was previously only reported inCulex pipiens, implying that this densovirus may have a broader host range than currently estimated.Overall these results bring insights into the diversity and the distribution of mosquito viruses; their unexplored interactions with two major vectors of arboviral diseases warrant further studies.
The C-terminus of the TlpD cytoplasmic chemoreceptor promotes polar localization and function
Authors: Lopez-Magaña Raymondo , Ottemann Karen M. 
Published: November 2024

AbstractBacteria localize proteins to distinct subcellular locations. One family of proteins with distinct cellular placement are chemoreceptors, which frequently localize to the bacterial pole. Although some polarity-promoting mechanisms have been described, there are many chemoreceptors that lack clear routes to becoming polar. The TlpD chemoreceptor ofHelicobacter pyloriis one such protein.H. pyloriis a chemotactic bacterial pathogen with four chemoreceptors. Its cytoplasmic chemoreceptor, TlpD, localizes to the pole in a manner that is independent of the other chemoreceptors. In this work, we evaluated the role of TlpD domains in its function. Truncated proteins were created that lacked different amounts of the N- or C-termini and expressed inH. pyloriin place of nativetlpDor as the sole chemoreceptor. These TlpD variants were examined for expression, protein localization, association with chemotaxis signaling proteins, and effect on motility. TlpD that lacked any portion of the N-terminal 104 amino acids did not produce detectable protein. In contrast, TlpD retained expression with loss of the C-terminal 45 amino acids. TlpD variants lacking the last 45 amino acids (TlpDΔC4) preserved the ability to interact with CheW and CheV proteins based on bacterial two-hybrid analysis but were unable to localize to the pole either on their own or in the presence of other chemoreceptors. TlpDΔC4 was found diffuse in the cytoplasm, and recruited detectable CheV1, CheV2, and CheV3 to this location but not CheW. TlpDΔC4 did not confer chemotactic abilities. These findings suggest the C-terminal end of TlpD plays a previously unappreciated role in promoting TlpD polar localization. The mechanism by which TlpD drives polar localization could translate to soluble cytoplasmic chemoreceptors in other bacterial pathogens.Author SummaryAlthough bacteria are small, they still place their proteins in specific locations that are required for the proteins to function. One such place is the bacterial end, or pole, where numerous proteins head to. How the bacterial cell identifies which proteins go to the pole is not fully understood. In this work, we dissect parts of a protein called TlpD that naturally goes to the pole. We find that mutants lacking one end of TlpD lose their polar placement. TlpD is part ofH. pylori’schemotaxis system, an ability that allows the bacteria to direct their motility towards beneficial situations and away from harmful ones. This ability is critical for infection inH. pyloriand numerous other pathogens. When TlpD loses its polar placement, the protein no longer functions, laying the foundation for future studies that can translate into therapies to treat or preventH. pyloriinfection.
Toxoplasma gondiiinfection of neurons alters the production and content of extracellular vesicles altering astrocyte phenotype and contributing to the loss of GLT-1 in the infected brain
Authors: Tabaie Emily Z. , Gao Ziting , Gomez Stacey , Bergersen Kristina , Zhong Wenwan , Wilson Emma H. 
Published: November 2024

AbstractToxoplasma gondii (T. gondii)cyst formation in the central nervous system only occurs in neurons allowing the parasite to remain latent for the lifetime of the host. Astrocytes are fundamental to neuronal health by providing nutrients and structural support and help regulate neurotransmitters by continuous communication with neurons. It is not yet known how infection and the presence of intracellular cysts, disrupts the crucial relationship between these cells. Extracellular vesicles (EVs) function in intracellular communication and can contain proteins, lipids, DNA, miRNA, and other RNA subtypes. EVs are produced by all cells including neurons and play an important role in neuronal-astrocyte interactions including the regulation of glutamate receptors on astrocytes. Previous work has demonstrated Toxoplasma infection reduces astrocytic expression of the primary glutamate transporter, GLT-1. Here we tested if cyst infection of neurons alters the production and content of EVs. EVs were isolated from uninfected and infected primary murine cortical neurons and their size, concentration, and characterization were confirmed with nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), CD63 ELISA, liquid chromatography (LC)-mass spectrometry (MS)/MS, and microRNA Sequencing. Analysis reveals that infection of neurons reduced neuronal production of EVs and altered their protein and miRNA content. EVs from infected neurons contained secreted Toxoplasma proteins GRA1, GRA2, GRA7, MAG1 and MAG2 associated with cyst formation. Following incubation of neuronal EVs with primary astrocytes, a proportion of EVs colocalize to the nucleus. EVs from infected neurons altered gene expression of astrocytes leading to a downregulation of GLT-1 protein expression and an increase in pro-inflammatory transcriptional signatures. These results demonstrate the ability of a parasitic infection in the brain to alter EV production and the fundamental communication between neurons and astrocytes.