bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a selection assay for small guide RNAs that drive efficient site-directed RNA editing
Authors: Diaz Quiroz Juan Felipe , Ojha Namrata , Shayhidin Elnur E , De Silva Dasuni , Dabney Jesse , Lancaster Amy , Coull James , Milstein Stuart , Fraley Andrew W , Brown Christopher R , Rosenthal Joshua J C 
Published: February 2023

AbstractA major challenge confronting the clinical application of site-directed RNA editing (SDRE) is the design of small guide RNAs (gRNAs) that can drive efficient editing. Although many gRNA designs have effectively recruited endogenous Adenosine Deaminases that Act on RNA (ADARs), most of them exceed the size of currently FDA-approved antisense oligos. We developed an unbiased in vitro selection assay to identify short gRNAs that promote superior RNA editing of a premature termination codon. The selection assay relies on hairpin substrates in which the target sequence is linked to partially randomized gRNAs in the same molecule, so that gRNA sequences that promote editing can be identified by sequencing. These RNA substrates were incubated in vitro with ADAR2 and the edited products were selected using amplification refractory mutation system PCR and used to regenerate the substrates for a new round of selection. After nine repetitions, hairpins which drove superior editing were identified. When gRNAs of these hairpins were delivered in trans, eight of the top ten short gRNAs drove superior editing both in vitro and in cellula. These results show that efficient small gRNAs can be selected using our approach, an important advancement for the clinical application of SDRE.
When translation elongation is impaired, the mRNA is uniformly destabilized by the RNA degradosome, while the concentration of mRNA is altered along the molecule
Authors: Duviau Marie-Pierre , Chen Fan , Emile Anthony , Cocaign-Bousquet Muriel , Girbal Laurence , Nouaille Sébastien 
Published: February 2023

AbstractmRNA sits at the crossroads of transcription, translation and mRNA degradation. Many questions remain about the coupling of these three processes in Escherichia coli and, in particular, how translation may have an effect on mRNA degradation and transcription. To characterize the interplay between mRNA degradation and translation while accounting for transcription, we altered the translation initiation or elongation and measured the effects on mRNA stability and concentration. Using a mapping method, we analysed mRNA concentration and stability at the local scale all along the transcript. We showed that a decrease in translation initiation efficiency destabilizes the mRNA and leads to a uniform decrease in mRNA concentration throughout the molecule. Prematurely terminating translation elongation by inserting a stop codon is associated with a drop in local mRNA concentration downstream of the stop codon, due to the uncoupling of transcription and translation. In contrast, this translation alteration uniformly destabilizes the coding and ribosome-free regions, in a process triggered by RNase E activity, and its ability to form the RNA degradome. These results demonstrate how ribosomes protect mRNA molecules and highlight how translation, mRNA degradation and transcription are deeply interconnected in the quality control process that avoids unproductive gene expression in cells.
Structural insights into the binding of bS1 to the ribosome
Authors: D’Urso Gaetano , Chat Sophie , Gillet Reynald , Giudice Emmanuel 
Published: February 2023

Abstract
The multidomain ribosomal protein bS1 is the biggest and the most flexible and dynamic protein in the 30S small subunit. Despite being essential for mRNA recruitment and its primary role in the accommodation of the start codon within the decoding centre, there has not yet been a high-resolution description of its structure. Here, we present a 3D atomic model of OB1 and OB2, bS1’s first two N-terminal domains, bound to an elongation-competent 70S ribosome. Our structure reveals that, as previously reported, bS1 is anchored both by a π-stacking to the 30S subunit and via a salt bridge with the Zn2+ pocket of bS1. These contacts are further stabilized by other interactions with additional residues on OB1. Our model also shows a new conformation of OB2, interacting with the Shine–Dalgarno portion of the mRNA. This study confirms that OB1 plays an anchoring role, but also highlights a novel function for OB2, which is directly involved in the modulation and support of mRNA binding and accommodation on the ribosome.
Beyond human capital: how does parents’ direct influence on their sons’ earnings vary across eight OECD countries?
Authors: Bonomi Bezzo Franco , Raitano Michele , Vanhuysse Pieter 
Published: February 2023

Abstract
This article asks to what degree the association between parents’ education and sons’ earnings is mediated by various forms of sons’ human capital across eight large OECD countries. We exploit the OECD Program for the International Assessment of Adult Competencies (PIAAC) database, which provides information on four dimensions of human capital (educational attainment, field of study, cognitive skills, and proxies of non-cognitive skills). We find that the intergenerational transmission process is wholly mediated just by sons’ formal educational attainment in Germany, Norway, and the USA. By contrast, in France, Italy, Spain, Poland, and the UK, a significant residual association remains after we control for all dimensions of sons’ human capital. While we cannot exclude that this residual association is due to unobservable background-related skills sons might have, this also points to family origin factors unrelated to human capital accumulation—such as social ties—that might play a role in the intergenerational transmission of labour market advantages in these countries.
Doing the Job! Expectations of Police Recruits (Pre- and Post- Graduate Entry)
Authors: McCanney John , Taylor Julie 
Published: February 2023

AbstractThis research explores the views of police recruits from cohorts pre and post the introduction of the graduate entry scheme. Recruits at the end of their initial training period were asked about their role and their expectations of policing. The views of recruits from these different cohorts are compared to understand whether the new graduate programme inculcated different views than the previous training programme. This research suggests that there are few differences between student officers who have completed the graduate training programme and those that did not. The findings suggest that there are deeply entrenched barriers and resistance to the change process. If change is to be achieved, it will require that the commitment of several stakeholders including the graduate officers themselves.
Trust in the police in Latin America: A multilevel analysis of institutional and experiential models
Authors: Salazar-Tobar Felipe , Rengifo Andres F 
Published: February 2023

AbstractThis paper explores two models of preference-formation of trust in the police in Latin America and the Caribbean: An institutional model that highlights the role of broad assessments of government performance and legitimacy and an experiential approach focussed on more narrow experiences of victimization and police contact. We examine these frameworks based on theory and analysis of administrative data and surveys from the Americas Barometer 2014 (N = 34,798 respondents T = 22 countries). Findings show that respondents with higher confidence in their government also indicate higher ratings of trust in the police. Similarly, trust is higher among individuals who had not experienced victimization or bribery or who anticipated faster police response times. At the country level, our results suggest that trust is negatively related to economic development but positively related to rule of law. We draw on these findings to outline an integrative model that combines both institutional and experiential perspectives.
Central nervous system manifestations of dengue infection: data from a tertiary care Centre in South India
Authors: George John Titus , Lenin Audrin , Koshy Maria , Vignesh C V , Sathyendra Sowmya 
Published: February 2023

AbstractBackgroundDengue fever is the second most common mosquito-borne disease affecting human beings and neurological manifestations (NMs) of this arboviral infection are increasingly being reported.MethodsIn this retrospective study, conducted in a tertiary care centre in south India, we sought to describe the spectrum of NMs of dengue fever. The records of all patients admitted in the Department of Internal Medicine over 8 years, with a diagnosis of dengue—based on clinical symptoms and the detection of dengue IgM antibodies or detection of NS1 antigen or nucleic acid by reverse transcriptase–polymerase chain reaction (RT-PCR); with Glasgow coma score (GCS) ≤14, neck stiffness, focal neurological signs, seizures, or visual disturbances—were explored.ResultsOf 1121 patients admitted with dengue fever, 341 (30%) had severe dengue and 23 (2%) had NMs. Encephalopathy was seen in 9 patients (39%), encephalitis in 6 (27%), cerebellitis in 4 (17%), acute disseminated encephalomyelitis (ADEM) in 2 (9%), ischaemic stroke in 1 (4%) patient, and neuro-ophthalmological manifestations in 1 (4%) patient. The median duration of hospital stay was 7 days. Nine (39% of) patients required intensive care unit (ICU) admission and 5 (22%) had fatal outcomes. There was no association between thrombocytopenia, metabolic acidosis, transaminitis, hyponatremia, the type of dengue infection, and the various NMs described.ConclusionsThe NMs of dengue infection are varied, and a high index of suspicion is needed to identify them in patients who present with lethargy or altered sensorium on the background of an acute febrile illness suggestive of dengue.
Increased rhinovirus/enterovirus infections including Ev-D68 in the United States, a challenge for healthcare providers amidst influenza virus infection and the COVID-19 pandemic
Authors: Abdul-Rahman Toufik , Nazir Abubakar , Khater Bashar , Pyrpyris Nikolaos , Wireko Awuah A , Miteu David G , Patel Heli , Sikora Vladyslav 
Published: February 2023

Abstract
In March 2020, WHO declared SARS-CoV-2 a global pandemic and lockdowns were enforced in most of the United States. Self-protective measures and travel restrictions were implemented, and schools/universities initiated online learning. Consequently, the global incidence and hospitalization rates of seasonal respiratory infections decreased significantly up to early 2021. Despite the decrease in hospitalization rates due to respiratory illnesses other than Covid-19, hospitals and healthcare providers faced huge stressors regarding workload dueto the pandemic. Furthermore, higher vaccination rates across the United States decreased non pharmaceutical interventions (NPI) implementation increasing the risk of major seasonal viral outbreaks. This editorial discusses the increased Rhinovirus/Enterovirus infections in the United States, challenges faced by healthcare providers and provides recommendations to address the issue.
The effect of a 5-minute body scan mindfulness intervention on healthier food choices
Authors: Hopfer Kaylea B , Fang Di , Zabelina Darya L , Hung Yung , Upshaw Joshua D , Nayga Rodolfo M 
Published: February 2023

AbstractThe effects of mindfulness interventions on food purchases and consumption are popular topics. Recent studies focus on mindfulness interventions that target overweight and obese populations. We measure the effects of a guided 5-minute body scan mindfulness intervention on ‘healthier’ food purchases in an online experiment. Specifically, we use a choice experiment approach with a between-subject design to evaluate participants’ choices of unhealthy/healthier foods. Results revealed the mindfulness intervention effectively increased state mindfulness in the treatment group. The treatment had a positive and significant effect on the overweight subsample. Additionally, we found nutrition knowledge to have a positive and significant effect on ‘healthier’ food choices across three regression models and various subsamples. Our findings suggest that mindfulness interventions may be a useful, low-cost alternative to current weight loss strategies, especially for overweight and obese individuals. In addition, our findings point to the importance of nutrition knowledge in promoting ‘healthier’ food choices.
EVALUATION OF EXISTING PUBLIC DOSE LIMITS APPLIED TO RECREATIONAL SPACEFLIGHT
Authors: Long Michael A , Hayes Robert B 
Published: February 2023

Abstract
Establishing realistic radiation dose limits with a solid scientific basis is a key component of the ‘as low as reasonably achievable’ (ALARA) principle. Although existing occupational dose limits have been established for civil astronauts, with the rise in popularity and technological maturation of the ‘space tourism’ sector, there does not appear to be considerable discussion on the subject of non-occupational astronaut dose limits. The necessity to come to a collective decision on dose limits and radiation safety procedures for recreational spaceflight is urgent and imperative to maintain ALARA goals, as existing federal dose limits to the public cannot be adequately or universally applied to the space tourism sector. Development of an entirely new set of regulations and guidelines should also provide long-term benefits in public perception as evidence of safety commitments from decision makers and the community in protecting passengers from radiological risks balanced with other spaceflight hazards.
Cross-cultural Differences in Hallucinations: A Comparison Between Middle Eastern and European Community-Based Samples
Authors: Khaled Salma M , Brederoo Sanne G , Yehya Arij , Alabdulla Majid , Woodruff Peter W , Sommer Iris E C 
Published: February 2023

AbstractBackground and HypothesisWhile literature indicates that culture modulates phenomenological characteristics of hallucinations in schizophrenia-spectrum disorders, little is known about the extent culture modulates these characteristics in nonclinical samples.Study DesignWe compared lifetime prevalence, age of onset, and phenomenology of hallucinations as assessed with the Questionnaire for Psychotic Experiences between samples of nonclinical participants used from the Netherlands (N = 2999) and Qatar (N = 2999). While participant recruitment differed between the 2 countries, the samples were relatively equal in terms of demographic factors.Study ResultsOur findings indicate that the lifetime prevalence of tactile and olfactory hallucinations are the same across countries. However, the prevalence of auditory hallucinations (AH) and visual hallucinations (VH) were twice as high in the Dutch sample. The reported age of onset for auditory and tactile hallucinations was younger for the Dutch sample. Findings from the measurement invariance supported cross-cultural comparisons with exception for duration, distress, and insight. Qatar’s and Dutch participants reported similar valence and extent of interaction with AH and VH. However, compared to those in the Netherlands, participants from Qatar reported significantly more impact on daily functioning and a higher prevalence of receiving commands from hallucinations in the past week.ConclusionsWhile AH and VH were more often reported in the Dutch sample, participants in Qatar generally had higher mean factor scores for past week AH and VH than in the Netherlands. The phenomenology of hallucinations in the Qatar sample was of greater clinical relevance, with potentially important implications for early screening and prevention.
Oxytocin mediated excitation of hypoglossal motoneurons: implications for treating obstructive sleep apnea
Authors: Dergacheva Olga , Polotsky Vsevolod Y , Mendelowitz David 
Published: February 2023

AbstractClinical studies have shown that oxytocin administered intranasally (IN) decreased the incidence and duration of obstructive events in patients with obstructive sleep apnea (OSA). Although the mechanisms by which oxytocin promotes these beneficial effects are unknown, one possible target of oxytocin could be the excitation of tongue-projecting hypoglossal motoneurons in the medulla, that exert central control of upper airway patency. This study tested the hypothesis that IN oxytocin enhances tongue muscle activity via the excitation of hypoglossal motoneurons projecting to tongue protrudor muscles (PMNs). To test this hypothesis we performed in vivo and in vitro electrophysiological studies in C57BL6/J mice as well as fluorescent imaging studies in transgenic mice in which neurons that express oxytocin receptors co-express fluorescent protein. IN oxytocin significantly increased the amplitude of inspiratory-related tongue muscle activity. This effect was abolished by severing the medial branch of hypoglossal nerve that innervates PMNs of the tongue. Oxytocin receptor-positive neurons were more prevalent in the population of PMNs than in retractor-projecting hypoglossal motoneurons (RMNs). Oxytocin administration increased action potential firing in PMNs, but had no significant effect on firing activity in RMNs. In conclusion, IN oxytocin stimulates respiratory-relating tongue muscle activity likely acting on central hypoglossal motoneurons that provide tongue protrusion and upper airway opening. This mechanism may play a role in oxytocin-induced reductions in upper airway obstructions in patients with OSA.
Factors Influencing the Efficacy of Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury
Authors: Purcell Elisha , Nguyen Timothy , Smith Madeleine , Penny Tayla , Paton Madison C B , Zhou Lindsay , Jenkin Graham , Miller Suzanne L , McDonald Courtney A , Malhotra Atul 
Published: February 2023

AbstractIntroductionWe have previously described preclinical literature which supports umbilical cord blood-derived cell (UCBC) therapy as an efficacious treatment for perinatal brain injury. However, efficacy of UCBCs may be influenced by different patient population and intervention characteristics.ObjectivesTo systematically review the effects of UCBCs on brain outcomes in animal models of perinatal brain injury across subgroups to better understand the contribution of model type (preterm versus term), brain injury type, UCB cell type, route of administration, timing of intervention, cell dosage, and number of doses.MethodsA systematic search of MEDLINE and Embase databases was performed to identify studies using UCBC therapy in animal models of perinatal brain injury. Subgroup differences were measured by chi2 test where possible.ResultsDifferential benefits of UCBCs were seen across a number of subgroup analyses including intraventricular hemorrhage (IVH) vs. hypoxia ischemia (HI) model (apoptosis white matter (WM): chi2 = 4.07; P = .04, neuroinflammation-TNF-α: chi2 = 5.99; P = .01), UCB-derived mesenchymal stromal cells (MSCs) vs. UCB-derived mononuclear cells (MNCs) (oligodendrocyte WM: chi2 = 5.01; P = .03, neuroinflammation-TNF-α: chi2 = 3.93; P = .05, apoptosis grey matter (GM), astrogliosis WM), and intraventricular/intrathecal vs. systemic routes of administration (microglial activation GM: chi2 = 7.51; P = .02, astrogliosis WM: chi2 = 12.44; P = .002). We identified a serious risk of bias and overall low certainty of evidence.ConclusionsPreclinical evidence suggests UCBCs to show greater efficacy in the injury model of IVH compared to HI, the use of UCB-MSCs compared to UCB-MNCs and the use of local administrative routes compared to systemic routes in animal models of perinatal brain injury. Further research is needed to improve certainty of evidence and address knowledge gaps.
Cigarette smoke and tumor microenvironment copromote aggressiveness of human breast cancer cells
Authors: Benoit Louise , Tomkiewicz Celine , Delit Maxime , Khider Hanna , Audouze Karine , Kowandy Flavie , Bortoli Sylvie , Barouki Robert , Coumoul Xavier , Koual Meriem 
Published: February 2023

AbstractBreast cancer is a major public health issue and the role of pollutants in promoting breast cancer progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor the aggressivity of breast cancer cells. We also evaluated the impact of the tumor microenvironment, largely represented by adipocytes, in mediating this modification of cell phenotype. Breast cancer cells lines, MCF-7 were cultured using a transwell coculture model with preadipocytes hMADS cells or were cultured alone. Cells were treated with cigarette smoke extract (CSE) and the four conditions: control, treated by CSE, coculture, and coexposure (coculture and CSE) were compared. We analyzed morphological changes, cell migration, resistance to anoikis, stemness, epithelial-to-mesenchymal transition (EMT), and the presence of hormonal receptors in each condition. A complete transcriptomic analysis was carried out to highlight certain pathways. We also assessed whether the aryl hydrocarbon receptor (AhR), a receptor involved in the metabolism of xenobiotics, could mediate these modifications. Several hallmarks of metastasis were specific to the coexposure condition (cell migration, resistance to anoikis, stemness characterized by CD24/CD44 ratios and ALDH1A1 and ALDH1A3 rates) whereas others (morphological changes, EMT, loss of hormonal receptors) could be seen in the coculture condition and were aggravated by CSE (coexposure). Moreover, MCF-7 cells presented a decrease in hormonal receptors, suggesting an endocrine treatment resistance. These results were confirmed by the transcriptomic analysis. We suggest that the AhR could mediate the loss of hormonal receptor and the increase in cell migration
H9N2 avian influenza virus dispersal along Bangladeshi poultry trading networks
Authors: Carnegie L , Hasan M , Mahmud R , Hoque M A , Debnath N , Uddin M H , Lewis N S , Brown I , Essen S , Giasuddin Md , Pfeiffer D U , Samad M A , Biswas P , Raghwani J , Fournié G , Hill S C 
Published: February 2023

AbstractAvian influenza virus subtype H9N2 is endemic in Bangladesh’s poultry population. The subtype affects poultry production and poses a potential zoonotic risk. Insufficient understanding of how the poultry trading network shapes the dissemination of avian influenza viruses has hindered the design of targeted interventions to reduce their spread. Here, we use phylodynamic analyses of haemagglutinin sequences to investigate the spatial spread and dispersal patterns of H9N2 viruses in Bangladesh’s poultry population, focusing on its two largest cities (Dhaka and Chattogram) and their poultry production and distribution networks. Our analyses suggest that H9N2 subtype avian influenza virus lineage movement occurs relatively less frequently between Bangladesh’s two largest cities than within each city. H9N2 viruses detected in single markets are often more closely related to viruses from other markets in the same city than to each other, consistent with close epidemiological connectivity between markets. Our analyses also suggest that H9N2 viruses may spread more frequently between chickens of the three most commonly sold types (sunali—a cross-bred of Fayoumi hen and Rhode Island Red cock, deshi—local indigenous, and exotic broiler) in Dhaka than in Chattogram. Overall, this study improves our understanding of how Bangladesh’s poultry trading system impacts avian influenza virus spread and should contribute to the design of tailored surveillance that accommodates local heterogeneity in virus dispersal patterns.