bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment of TRiC chaperonin in rotavirus viroplasms directly associates with virus replication
Authors: Vetter Janine , Papa Guido , Tobler Kurt , Kley Manuel , Myers Michael , Wiesendanger Mahesa , Schraner Elisabeth M. , Burrone Oscar R. , Fraefel Cornel , Eichwald Catherine 
Published: December 2022

AbstractRotavirus replication takes place in the viroplasms, cytosolic inclusions that allow the synthesis of virus genome segments and their encapsidation in the core shell followed by the addition of the second layer of the virion. The viroplasms are composed of several viral proteins, including NSP5, which is the main building block. Microtubules, lipid droplets, and miRNA-7 are among the host components recruited in viroplasms. To investigate the relationship between rotavirus proteins and host components of the viroplasms, we performed a pull-down assay of lysates from rotavirus-infected cells expressing NSP5-BiolD2. Subsequent tandem mass spectrometry identified all eight subunits of the TRiC complex, a cellular chaperonin responsible for folding at least 10% of the cytosolic proteins. Our validated results show that TRiC is recruited in viroplasms and specifically surrounds newly formed double-layered particles (DLPs). Chemical inhibition of TRiC and silencing of its subunits drastically reduced virus progeny production. Interestingly, TRiC-inhibited RV-infected cells lacked triple-layered particles (TLPs) but harbored empty DLPs. Through sequence-specific direct RNA nanopore sequencing, we show that TRiC is critical for RV replication by controlling dsRNA genome segment synthesis, particularly (-)ssRNA. Moreover, TRiC associates and regulates the folding of VP2, a cofactor allowing dsRNA synthesis. This study provides in-cell culture evidence of the regulatory mechanism by which dsRNA genome segment replication is controlled and coordinated in the rotavirus viroplasms.ImportanceThe replication of rotavirus takes place in cytosolic inclusions termed viroplasms. In these inclusions, the eleven double-stranded RNA genome segments are synthesized and packaged individually into the newly generated virus particles. In this study, we show for the first time that the TRiC complex, a cellular chaperonin responsible for the folding of at least 10% of the cytosolic proteins, is a component of viroplasms and is required for the synthesis of the viral (-)ssRNA. Specifically, TRiC interacts and assists in folding VP2, the cofactor involved in RNA replication. Our study adds a new component to the current model of rotavirus replication, where TRiC is recruited in viroplasm to assist replication.
Acceleration of genome replication uncovered by single-cell nascent DNA sequencing
Authors: van den Berg Jeroen , van Batenburg Vincent , van Oudenaarden Alexander 
Published: December 2022

AbstractIn a human cell thousands of replication forks simultaneously coordinate the duplication of the entire genome. The rate at which this process occurs, might depend on the epigenetic state of the genome and vary between, or even within, cell types. To accurately measure DNA replication speeds, we developed a technology to detect recently replicated DNA using single-cell sequencing. Replication speed is not constant but increases during S-phase of the cell cycle. Using genetic and pharmacological perturbations we are able to alter this acceleration of replication and conclude that DNA damage inflicted by the process of transcription limits the speed of replication during early S-phase. In late S-phase, during which less transcription occurs, replication accelerates and approaches its maximum speed.
Compensatory mechanisms enables intelligibility in prodromal Parkinson’s disease
Authors: Thies Tabea , Mücke Doris , Geerts Nuria , Seger Aline , Fink Gereon R. , Barbe Michael T. , Sommerauer Michael 
Published: December 2022

AbstractBackgroundSpeech impairment is already present on the acoustic level in speakers with isolated rapid eye movement sleep behavior disorder (iRBD). The aim of this study was to determine whether speech changes are already present on the articulatory level and if how these differ from healthy control speakers and speakers with Parkinson’s disease (PD).MethodsKinematic data were collected from 68 age and sex-matched subjects: healthy control speakers (n=23), patients with iRBD (n=22), and patients with PD (n=23). All participants were recorded with electromagnetic articulography (AG 501) to capture articulatory movements of the lower lip, the tongue tip and the tongue body. Movement amplitudes, durations and average speeds were calculated per articulator. In addition, naïve listeners rated the intelligibility of the speech sampled produced by the participants.ResultsThe results of the production experiment indicate changes between the control and the iRBD group as well as between the iRBD and the PD group. Movement durations increase from the control group to the iRBD group and further to the PD group. In contrary, movement amplitudes increase in prodromal PD and decreased from PD onwards. This relationship was reflected by preserved articulatory speed in iRBD patients, but articulatory slowdown in PD. Intelligibility is lower in speakers with PD, but does not differ between the control and the iRBD group.ConclusionSpeakers with iRBD adjust underlying articulatory movement patterns to maintain their intelligibility level.
Burden of insomnia on healthcare utilization in children with autism spectrum disorder
Authors: Solomon Shirley , Meiri Gal , Michaelovski Analya , Sadaka Yair , Ilan Michal , Faroy Michal , Dinstein Ilan , Menashe Idan 
Published: December 2022

AbstractInsomnia is frequently reported in children with autism spectrum disorder (ASD) and is associated with the severity of hyperactivity, irritability, sensory sensitivities, and related symptoms. The aim of this study was to examine the extent of healthcare utilization associated with insomnia in children with ASD. We conducted a retrospective, cross-sectional study of 541 children with ASD registered at the National Autism Database of Israel (NADI). Parents of all children completed the Children’s Sleep Habits Questionnaire (CSHQ) and insomnia was defined as a total CSHQ score ≥48. We compared sociodemographic characteristics, ASD diagnostic measures, chronic comorbidities, medication usage, hospitalizations, visits to the emergency room (ER), and visits to specialists between ASD children with and without insomnia. Finally, we assessed the independent association of insomnia with clinical characteristics and healthcare utilization using multivariate logistic regression models. Of the 541 children with ASD, 257 (47.5%) had insomnia. Children with insomnia compared to children without insomnia exhibited higher rates of comorbidities within the symptoms, signs, and ill-defined conditions (ICD-9[780–789]) category (aOR=1.70; 95%CI=1.04-2.77; p=0.033) and were prescribed more medications for chronic comorbidities (aOR=1.47; 95%CI=1.01-2.15; p=0.046). Finally, ASD children with insomnia were 1.75 and 2.82 times more likely to visit the ER and be hospitalized than their counterparts (aOR=1.75; 95%CI=1.17-2.62; p=0.007 and aOR=2.82; 95%CI=1.43-5.56; p=0.003, respectively). Our findings demonstrate that insomnia is associated with greater healthcare utilization among children with ASD. Thus, treating insomnia in children with ASD may have a broad clinical impact beyond specific improvements in sleep disturbances.
Improving cardiovascular health in patients with an abdominal aortic aneurysm: Development of the Cardiovascular risk reduction in patients with aneurysms (CRISP) behaviour change intervention
Authors: Withers T. M. , Greaves C. J. , Bown M. J. , Saratzis A. 
Published: December 2022

ABSTRACTObjectivesAbdominal aortic aneurysm (AAA) is an important cardiovascular health problem. Ultrasound screening is proven to reduce AAA-mortality and programmes have been implemented in some healthcare systems. Those who are identified as having a small AAA in screening enter into a surveillance programme to monitor AAA-size. Individuals in AAA-surveillance are at elevated risk of cardiovascular events, which is not currently addressed sufficiently. We aimed to develop a simple intervention to reduce cardiovascular risk, which could be embedded in AAA surveillance-pathways.DesignIntervention mapping methods were used to co-develop the interventionParticipantsIndividuals with AAA, families/carers, and healthcare staff.SettingAAA screening and surveillance programmes in the United KingdomOutcome measuresWe identified “targets for change” by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We conducted a series of workshops to identify barriers to and facilitators of change, and used taxonomies of behaviour change theories and techniques to match intervention strategies to each target. Further stakeholder involvement work helped refine the intervention.ResultsThe developed intervention focusses on assessment and individually tailored discussion of risk factors, exchanging information, building motivation and action planning, followed by review of progress and problem-solving. Workbooks covering physical activity, diet, stress management, alcohol, smoking, blood pressure and mental health are provided to support behaviour change. The intervention is facilitated by trained healthcare professionals during the patient’s AAA screening appointment for the duration that they are in surveillance.ConclusionsThe developed intervention will now be tested to assess whether it can be integrated with the current AAA screening programme. The developed intervention is a novel approach to reducing cardiovascular disease in the AAA population, it is also the first intervention which tries to do this in this population.
Incivility in the workplace: A study of nursing and midwifery staff in Northern Ghana
Authors: Boo Alipitio , Dzomeku Veronica Millicent , Diji Abigail Kusi-Amponsah , Bonsu Adwoa Bemah , Apiribu Felix 
Published: December 2022

AbstractIntroductionThe purpose of this study was to assess the prevalence, sources and effect of incivility in a tertiary hospital in Northern Ghana.MethodsA descriptive cross-sectional survey was conducted among 321 nurses at a tertiary-level hospital in Northern Ghana. Between October and November 2022, participating nurses responded to an online or self-administered questionnaire using the 43-item incivility scale developed by Guidroz and colleagues. Data collected was cleaned in Microsoft Excel and transported into SPSS version 21 for further statistical analysis.ResultsTwo-fifths of the participants (n=131, 40.8%) were aged 31-35 years. Over 50% of the participants were males (n=161), married (n=187) and had a Bachelor’s degree (n=166). A little over 30% of the participants had worked in the nursing profession for more than 8 years.ConclusionThe participants reported an average incidence of 54.5% of incivility sometimes, most of the time, and all the time. Moreover, in terms of incivility reported under the subscales, the average greatest prevalence recorded was displaced frustration under patients/relations, with a rate of 78.9%. The least average prevalence rate indicated under the subscales was from abusive supervision under direct supervisors with a rate of 30.7%.The existence of incivility in healthcare settings does not support a setting where healthcare workers and patients may operate safely. Therefore, it is advised that frequent in-service training sessions on what constitutes incivility is held for nurses and the hospital’s general staff in order to raise awareness of the negative impacts of incivility.
A multiomics approach reveals RNA dynamics promote cellular sensitivity to DNA hypomethylation
Authors: Ge Alex Y. , Arab Abolfazl , Dai Raymond , Navickas Albertas , Fish Lisa , Garcia Kristle , Asgharian Hosseinali , Goudreau Jackson , Lee Sean , Keenan Kathryn , Pappalardi Melissa B. , McCabe Michael T. , Przybyla Laralynne , Goodarzi Hani , Gilbert Luke A. 
Published: December 2022

SUMMARYThe search for new approaches in cancer therapy requires a mechanistic understanding of cancer vulnerabilities and anti-cancer drug mechanisms of action. Problematically, some effective therapeutics target cancer vulnerabilities that have poorly defined mechanisms of anti-cancer activity. One such drug is decitabine, a frontline therapeutic approved for the treatment of high-risk acute myeloid leukemia (AML). Decitabine is thought to kill cancer cells selectively via inhibition of DNA methyltransferase enzymes, but the genes and mechanisms involved remain unclear. Here, we apply an integrated multiomics and CRISPR functional genomics approach to identify genes and processes associated with response to decitabine in AML cells. Our integrated multiomics approach reveals RNA dynamics are key regulators of DNA hypomethylation induced cell death. Specifically, regulation of RNA decapping, splicing and RNA methylation emerge as important regulators of cellular response to decitabine.
Chaotic signatures in host-microbe interactions
Authors: Sella Yehonatan , Broderick Nichole A , Stouffer Kaitlin , McEwan Deborah L , Ausubel Frederick M. , Casadevall Arturo , Bergman Aviv 
Published: December 2022

AbstractHost-microbe interactions constitute dynamical systems that can be represented by mathematical formulations that determine their dynamic nature, and are categorized as deterministic, stochastic, or chaotic. Knowing the type of dynamical interaction is essential for understanding the system under study. Very little experimental work has been done to determine the dynamical characteristics of host-microbe interactions and its study poses significant challenges. The most straightforward experimental outcome involves an observation of time to death upon infection. However, in measuring this outcome, the internal parameters, and the dynamics of each particular host-microbe interaction in a population of interactions are hidden from the experimentalist. To investigate whether a time-to-death (time to event) dataset provides adequate information for searching for chaotic signatures, we first determined our ability to detect chaos in simulated data sets of time-to-event measurements and successfully distinguished the time-to-event distribution of a chaotic process from a comparable stochastic one. To do so, we introduced aninversion measureto test for a chaotic signature in time-to-event distributions. Next, we searched for chaos, in time-to-death ofCaenorhabditis elegansandDrosophila melanogasterinfected withPseudomonas aeruginosaorPseudomonas entomophila, respectively. We found suggestions of chaotic signatures in both systems, but caution that our results are preliminary and highlight the need for more fine-grained and larger data sets in determining dynamical characteristics. If validated, chaos in host-microbe interactions would have important implications for the occurrence and outcome of infectious diseases, the reproducibility of experiments in the field of microbial pathogenesis and the prediction of microbial threats.ImportanceIs microbial pathogenesis a predictable scientific field? At a time when we are dealing with Coronavirus Disease 2019 (COVID-19) there is intense interest in knowing about the epidemic potential of other microbial threats and new emerging infectious diseases. To know whether microbial pathogenesis will ever be a predictable scientific field requires knowing whether a host-microbe interaction follows deterministic, stochastic, or chaotic dynamics. If randomness and chaos are absent from virulence, there is the hope for prediction in the future regarding the outcome of microbe-host interactions. Chaotic systems are inherently unpredictable although it is possible to generate shortterm probabilistic models, as is done in applications of stochastic processes and machine learning to weather forecasting. Information on the dynamics of a system is also essential for understanding the reproducibility of experiments, a topic of great concern in biological sciences. Our study finds preliminary evidence for chaotic dynamics in infectious diseases.
Effects of DNA extraction, DNA integrity, and laboratory on the precision of qPCR-based telomere length measurement - a multi-lab impartial study
Authors: Lin Jue , Verhulst Simon , Alonso Camilo Fernandez , Dagnall Casey , Gadalla Shahinaz , Hastings Waylon J. , Lai Tsung-Po , Shalev Idan , Wang Ying , Zheng Yun-Ling , Epel Elissa , Drury Stacy 
Published: December 2022

AbstractMeasuring telomere length (TL) with high precision is challenging. Currently there is insufficient understanding of the causes of variation in measurement precision, particularly for qPCR-based measurement. To better understand how DNA extraction protocols and laboratory-specific analytical factors influence qPCR-based TL measurement precision, we conducted a multi-laboratory study involving four labs and six DNA extraction protocols assaying the same blinded human whole blood samples. DNA extraction protocols differed in underlying principles (magnetic beads, salting out, silica membrane) and commercial kits. A fifth lab performed Telomere Restriction Fragment (TRF) analysis using Southern Blot technique with one DNA extraction protocol. All labs performed TL measurement using their standard procedures on two sets of fifty double blinded samples. Data was sent to a central point for unblinding and statistical analyses. Precision was quantified using the Intraclass Correlation Coefficient (ICC). Correlations with TRF measurements were also calculated. Repeated qPCR-based measurements of the same DNA extraction yielded ICC values ranging from 0.24 to 0.94. ICC values calculated over measurements of repeated DNA extractions were on average 0.23 lower and ranged from 0.02 to 0.83. The latter ICC estimates more strongly predicted the association between qPCR- and Southern blot-based measurements across the protocol / lab combinations (R2=0.56 vs. R2=0.93). We conclude that ICC calculated over measurements on repeated DNA extractions reliably indicates measurement precision, while ICC calculated over multiple measurements of the same DNA extraction overestimates measurement precision. Variation in ICC was driven by variation between laboratories, with few consistent DNA extraction protocol effects. Values of DNA integrity and purity generally characterized as reflecting high sample quality, (e.g. OD 260/280 of 1.8 and OD 260/230 of 2.0) were associated with qPCR-based measurement precision, but did not always predict higher ICCs.
Niche overlap between two large herbivores across landscape variability using dietary eDNA metabarcoding
Authors: Mas-Carrió Eduard , Churski Marcin , Kuijper Dries , Fumagalli Luca 
Published: December 2022

AbstractUnderstanding the relationship between a species feeding strategy and its environment (trophic ecology) is critical to assess environmental requirements and improve management policies. However, measuring trophic interactions remains challenging. Among the available methods, quantifying the plant composition of a species’ diet indicates how species use their environment and their associated niche overlap. Nevertheless, most studies focusing on herbivore trophic ecology ignore the influence that landscape variability may have. Here, we explored how landscape variability influences diet composition through niche overlap. We used eDNA metabarcoding to quantify the diet composition of two large herbivores of the Bialowieza Forest, Red deer (Cervus elaphus) and European bison (Bison bonasus) to investigate how increasing habitat quality (i.e. higher abundance of deciduous forage species) and predation risk (i.e. density of wolf in the area) influence their diet composition and niche partitioning. Our findings indicate diet composition is non-homogeneous across the landscape, both within and between species. Red deer showed greater diet variability and lower niche overlap within species compared to bison. We detected a reduction of niche overlap for red deer with increasing predation risk, leading to more dissimilar diets, suggesting their feeding behaviour is affected by wolf presence. This correlation was not found for bison, which are rarely predated by wolf. Higher habitat quality was associated with higher niche overlap only within bison, probably due to their suboptimal feeding strategy as browsers. These results show the importance of integrating environment-induced diet variation in studies aimed at determining the landscape usage or niche overlap of a species. Niche overlap can therefore be a powerful tool for inferring predation risk for red deer, and estimating predator abundance or its perception. This approach has enormous potential for wildlife management in areas where predator estimates are unknown or difficult to quantify.
A novel LC-MS/MS method development and validation for the determination of tezepelumab in rat plasma and its application in rat pharmacokinetic studies
Authors: Nimmakayala Madhusudhana Reddy , Kolli Deepti , Kumar J.V. Shanmukha 
Published: December 2022

AbstractBy developing a quick, accurate, reproducible, and straightforward LC-MS/MS system and employing trastuzumab as an internal standard (IS), tezepelumab (TZP)’s quantification was achieved. This study explores the most recent advancement in bioanalytical LC-MS/MS technologies utilizing a 150×4.6 mm, 3.5µ Waters Symmetry C18 column that was set for isocratic mode at ambient temperature. Methanol (MeoH): 0.1% Formic acid (FA) in 40:60 v/v at 1.0 ml/min was utilized as the mobile phase. The injection volume and runtime were 10 µl and 5 minutes, respectively. TZP’s retention time (RT) was 1.944 Minutes, and a chromatographic duration total of 5.0 min. With a correlation value (r2) of 0.99971, the technique was validated for Tezepelumab throughout a linear range of 6.00–120.00 ng/mL. Findings for precision, accuracy, recovery, matrix effect, and stability all occurred within acceptable limits. Below visual abstract is the concise summary of the article.Abstract Figure
Identification of structurally diverse FSP1 inhibitors that sensitize cancer cells to ferroptosis
Authors: Hendricks Joseph M. , Doubravsky Cody , Wehri Eddie , Li Zhipeng , Roberts Melissa A. , Deol Kirandeep , Lange Mike , Lasheras-Otero Irene , Dixon S.J. , Bersuker Kirill , Schaletzky Julia , Olzmann James A. 
Published: December 2022

ABSTRACTFerroptosis is a regulated form of cell death associated with the iron-dependent accumulation of lipid peroxides. Inducing ferroptosis is a promising approach to treat therapy resistant cancer. Ferroptosis suppressor protein 1 (FSP1) promotes ferroptosis resistance in cancer by generating the antioxidant form of coenzyme Q10 (CoQ). Despite the important role of FSP1, few molecular tools exist that target the CoQ-FSP1 pathway. Exploiting a series of chemical screens, we identify several structurally diverse FSP1 inhibitors. The most potent of these compounds, ferroptosis sensitizer 1 (FSEN1), is an uncompetitive inhibitor that acts selectively through on target inhibition of FSP1 to sensitize cancer cells to ferroptosis. Furthermore, a synthetic lethality screen reveals that FSEN1 synergizes with endoperoxide-containing ferroptosis inducers, including dihydroartemisinin, to trigger ferroptosis. These results provide new tools that catalyze the exploration of FSP1 as a therapeutic target and highlight the value of combinatorial therapeutic regimes targeting FSP1 and additional ferroptosis inducers.