bluuebunny/crossref_metadata_2025_split huggingface dataset:
CpG island turnover events predict evolutionary changes in enhancer activity
Authors: Kocher Acadia A. , Dutrow Emily V. , Uebbing Severin , Yim Kristina M. , Rosales Larios María F. , Baumgartner Marybeth , Nottoli Timothy , Noonan James P. 
Published: May 2023

AbstractGenetic changes that modify the function of transcriptional enhancers have been linked to the evolution of biological diversity across species. Multiple studies have focused on the role of nucleotide substitutions, transposition, and insertions and deletions in altering enhancer function. Here we show that turnover of CpG islands (CGIs), which contribute to enhancer activation, is broadly associated with changes in enhancer activity across mammals, including humans. We integrated maps of CGIs and enhancer activity-associated histone modifications obtained from multiple tissues in nine mammalian species and found that CGI content in enhancers was strongly associated with increased histone modification levels. CGIs showed widespread turnover across species and species-specific CGIs were strongly enriched for enhancers exhibiting species-specific activity across all tissues and species we examined. Genes associated with enhancers with species-specific CGIs showed concordant biases in their expression, supporting that CGI turnover contributes to gene regulatory innovation. Our results also implicate CGI turnover in the evolution of Human Gain Enhancers (HGEs), which show increased activity in human embryonic development and may have contributed to the evolution of uniquely human traits. Using a humanized mouse model, we show that a highly conserved HGE with a large CGI absent from the mouse ortholog shows increased activity at the human CGI in the humanized mouse diencephalon. Collectively, our results point to CGI turnover as a mechanism driving gene regulatory changes potentially underlying trait evolution in mammals.
Building synthetic chromosomes from natural DNA
Authors: Coradini Alessandro L.V. , Ne Ville Christopher , Krieger Zachary A. , Roemer Joshua , Hull Cara , Yang Shawn , Lusk Daniel T. , Ehrenreich Ian M. 
Published: May 2023

AbstractDe novo chromosome synthesis is costly and time-consuming, limiting its use in research and biotechnology. Building synthetic chromosomes from natural components is an unexplored alternative with many potential applications. In this paper, we report CReATiNG (Cloning,Reprogramming, andAssemblingTiledNaturalGenomic DNA), a method for constructing synthetic chromosomes from natural components in yeast. CReATiNG entails cloning segments of natural chromosomes and then programmably assembling them into synthetic chromosomes that can replace the native chromosomes in cells. We used CReATiNG to synthetically recombine chromosomes between strains and species, to modify chromosome structure, and to delete many linked, non-adjacent regions totaling 39% of a chromosome. The multiplex deletion experiment revealed that CReATiNG also enables recovery from flaws in synthetic chromosome design via recombination between a synthetic chromosome and its native counterpart. CReATiNG facilitates the application of chromosome synthesis to diverse biological problems.
Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study
Authors: Yang Jingyan , Andersen Kathleen M. , Rai Kiran K. , Tritton Theo , Mugwagwa Tendai , Reimbaeva Maya , Tsang Carmen , McGrath Leah J. , Payne Poppy , Backhouse Bethany , Mendes Diana , Butfield Rebecca , Naicker Kevin , Araghi Mary , Wood Robert , Nguyen Jennifer L. 
Published: May 2023

ABSTRACTObjectivesTo quantify healthcare resource utilisation (HCRU) and costs to the National Health Service (NHS) associated with acute COVID-19 in adults in England.DesignPopulation-based retrospective cohort study, using Clinical Practice Research Datalink (CPRD) Aurum primary care electronic medical records linked when available to Hospital Episode Statistics (HES) secondary care administrative data.SettingPatients registered to primary care practices in England.Population1,706,368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13,105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1,693,263 within the primary care cohort indexed between August 2020 and January 2022.Main outcome measuresPrimary and secondary care HCRU and associated costs during the acute phase of COVID-19 (≤4 weeks following positive test), stratified by age group, risk of severe COVID-19 and immunocompromised status.ResultsAmong the hospitalised cohort, average total length of stay, as well as in critical care wards, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75 – 84 (£8,942) and ≧85 years (£8,835) than in those aged <50 years (£7,703). Whilst few (6.0%) patients in critical care required mechanical ventilation, its use was higher in older adults (50 – 74 years: 8.3%; <50 years: 4.3%). HCRU and associated costs were often greater in those at higher risk of severe COVID-19 when compared to the overall cohort, although minimal differences in HCRU were found across the three different high-risk definitions implemented. Among the primary care cohort, GP or nurse consultations were more frequent among older adults and the immunocompromised.ConclusionsCOVID-19 related hospitalisations in older adults, particularly critical care admissions, were the primary drivers of high resource use of COVID-19 in England. These findings may inform health policy decisions and resource allocation in the prevention and management of COVID-19.
A Retrospective Study to Determine the Impact of Psychedelic Therapy for Dimensional Measures of Wellness: A Quantitative Analysis
Authors: Di Virgilio Victoria , Minerbi Amir , Deol Jagpaul Kaur , Aggerwal Salena , Safi Toufik , Gupta Gaurav 
Published: May 2023

AbstractBackgroundThe World Health Organization (WHO) defines wellness as the optimal state of health of individuals and groups. No study to date has identified the impact of psychedelic medicines on optimizing wellness using a dimensional approach. Using this approach, treatment effects can be measured more broadly using a composite score of participants’ global perceptions of change for pain, function, and mood scores. Given the precedence in previous work for retrospective studies of participants’ self-medicating with these substances, the nature of this study design allows for a safe way to develop further evidence in this area of care, with wellness as the broad indication.Methods65 civilian or military veterans above the age of 18, self-identifying as having used psychedelic medicines for non-recreational purposes in the last 3 years were recruited. Participants completed the following standardized questionnaires: Patient Global Impression of Change (PGIC) scale, Pain, Enjoyment of Life and General Activity (PEG) scale, Anxiety and Depression scale (ADS), and Disability Index (DI) scale. The analysis focused on reported PGIC outcomes and correlations between subscales. Given the nature of the study, a comparison to the baseline could not be made.ResultsOn average, participants reported improvement in all domains (pain, mental health, function, and overall quality of life), regardless of the medicine. Perceived improvement was highest in mental health and overall quality of life, and lowest in pain. Kendall correlation showed a highly significant association between the perceived changes in all domains. Correlation coefficients were highest between the perceived change in function, quality of life, and mental health.DiscussionThe use of various psychedelic medicines may be associated with a broad range of changes that could help clarify the mechanism of how they impact wellness in the future. Pain, mental health, function, and overall quality of life accordingly improved after the use of these medicines. Minor differences between the drugs were not found as significant, indicating that the perceived benefits seemed to be specific to the psychedelic class. Numerous limitations exist to this type of study which was relatively small in size, retrospective and anonymous in nature.ConclusionThe wellness of individuals or groups is not simply an absence of disease, symptoms, or impairments. Instead, it is an outcome that is shaped by a myriad of personal characteristics, psychophysiology, and choices, expressed throughout one’s lifespan, unfolding in dynamic interaction with a complicated sociocultural and physical environment.
Transcriptional and epigenomic profiling identifies YAP signaling as a key regulator of intestinal epithelium maturation
Authors: Pikkupeura Laura M. , Bressan Raul B. , Guiu Jordi , Chen Yun , Maimets Martti , Mayer Daniela , Schweiger Pawel J. , Hansen Stine L. , Maciag Grzegorz J. , Larsen Hjalte L. , Lõhmussaar Kadi , Pedersen Marianne Terndrup , Teves Joji M. Yap , Bornholdt Jette , Benes Vladimir , Sandelin Albin , Jensen Kim B. 
Published: May 2023

AbstractDuring intestinal organogenesis, equipotent epithelial progenitors mature into phenotypically distinct stem cells that are responsible for life-long maintenance of the tissue. While the morphological changes associated with the transition are well-characterized, the molecular mechanisms underpinning the maturation process are not fully understood. Here, we leverage intestinal organoid cultures to profile transcriptional, chromatin accessibility, DNA methylation and 3D chromatin conformation landscapes defining fetal and adult epithelial cells. We observed prominent differences in gene expression and enhancer activity, accompanied by changes in 3D organization and local changes in DNA accessibility and methylation, between the two cellular states. Using integrative analyses, we identified sustained YAP transcriptional activity as a major gatekeeper of the immature fetal state. We found the YAP-associated transcriptional network to be regulated at various levels of chromatin organization, and likely to be coordinated by changes in extracellular matrix composition. Altogether, our work highlights the value of unbiased profiling of regulatory landscapes for the identification of key mechanisms underlying tissue maturation.
A population intrinsic timer controlsHoxgene expression and cell dispersion during progenitor addition to the body axis
Authors: Busby Lara , Nájera Guillermo Serrano , Steventon Ben 
Published: May 2023

AbstractDuring embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where the progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled, post-ingression through the primitive streak. The delayed exit of older cells from this state correlates with expression of posteriorHoxgenes. Using grafting and explant culture, we find that bothHoxgene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. Therefore, we demonstrate that cell dispersion is controlled by a population intrinsic timer to control progenitor addition to the presomitic mesoderm.
A BubR1-independent pathway for CENP-E targeting to the outer corona of kinetochores
Authors: Legal Thibault , Paterson Calum , Gluszek Agata , Davies Owen R. , Welburn Julie P.I. 
Published: May 2023

AbstractFor chromosome segregation to take place, unattached kinetochores expand in early mitosis, forming a fibrous structure called the fibrous corona that is captured by microtubules. The corona is assembled from the RZZ complex, Spindly, CENP-E and the Mad1/Mad2 spindle assembly checkpoint proteins. CENP-E aligns chromosomes along the mitotic spindle by moving them to the plus ends of microtubules. Here, we show that CENP-E is recruited to the outer corona independently of BubR1 in a dynein-dependent fashion. We determine the structure of this domain and show that a conserved loop is essential for CENP-E targeting to the outer corona. We show that both domains are essential for CENP-E recruitment to unattached kinetochores. We also report that the kinetochore-targeting domain of CENP-E contributes to the recruitment of the RZZ complex, Mad1 and Spindly, providing a feedback loop to assemble the outer corona. In this study, we propose that CENP-E uses 2 pathways to target to the kinetochore, which allows it to optimize kinetochore capture by microtubules for chromosome alignment and mitotic progression.
The action of physiological and synthetic steroids on the calcium channel CatSper in human sperm
Authors: Wehrli Lydia , Galdadas Ioannis , Voirol Lionel , Smieško Martin , Cambet Yves , Jaquet Vincent , Guerrier Stéphane , Gervasio Francesco Luigi , Nef Serge , Rahban Rita 
Published: May 2023

AbstractThe sperm-specific channel CatSper (cation channel ofsperm) controls the intracellular Ca2+concentration ([Ca2+]i) and plays an essential role in sperm function. It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial. To investigate the effect of these compounds on CatSper and sperm function, we developed a high-throughput-screening (HTS) assay to measure changes in [Ca2+]iin human sperm and screened 1,280 approved and off-patent drugs including 90 steroids from the Prestwick chemical library. More than half of the steroids tested (53%) induced an increase in [Ca2+]iand reduced the P4-induced Ca2+influx in human sperm in a dose-dependent manner. Ten of the most potent steroids (activating and inhibiting) were selected for a detailed analysis of their action on CatSper and their ability to act on sperm motility, acrosomal exocytosis (AR), and penetration in viscous media. We found that these steroids show an inhibitory effect on P4 but not on prostaglandin E1-induced CatSper activation, suggesting that they compete for the same binding site as P4. Pregnenolone, dydrogesterone, epiandrosterone, nandrolone, and dehydroepiandrosterone acetate (DHEA) were found to activate CatSper at physiological concentrations. Stanozolol, epiandrosterone, and pregnenolone induced AR similarly to P4, whereas stanozolol and estropipate induced an increase in sperm penetration into viscous medium. Furthermore, using a hybrid approach integrating pharmacophore analysis and statistical modelling, we were able to screenin silicofor steroids that can activate the channel and define the physicochemical and structural properties required for a steroid to exhibit agonist activity against CatSper. Overall, our results indicate that not only physiological but also synthetic steroids can modulate the activity of CatSper with varying potency and affect human sperm functionsin vitro.
From a short-term study abroad student to a future expatriate – contrasting the effects of social support from the host-country nationals, sociocultural adaptation, and acculturation attitude
Authors: Kingminghae Worapinya , Lin Yi 
Published: May 2023

PurposeThe purpose of this study is to explore how three experiential factors – perceived social support from host-country nationals (HCNs), adaptation difficulties, and attitude towards assimilating into the host culture and society – influence the generation of worthwhile feelings and the intention to pursue expatriate career opportunities in the host country among short-term studying abroad (STSA) students.Design/methodology/approachThis study used data from a survey of 297 Thai students who studied in Chinese universities between 2015 and 2019. A bivariate probit model was applied due to its ability to account for the potential correlation of errors between the two binary outcome variables: worthwhileness and aspiration for expatriate careers.FindingsAdaptation difficulties reported by students negatively impacted their willingness to work in the host country, but did not diminish their perception of the sojourn as worthwhile. Satisfaction with social support from HCNs was found to not only enhance the worthwhileness of the sojourn but also inspire students' expatriate career intentions in the host country. The study also found that while willingness to assimilate into the host culture and society primarily enhanced the worthwhileness of the trip, its effect on students' willingness to consider working in the host country was relatively weak, compared with the effect of social support from HCNs.Research limitations/implicationsThe generalizability of the findings from this study may be limited to country pairs that are geographically and culturally similar.Originality/valueAlthough it is commonly believed that STSA programs help inspire students to develop aspirations for international careers or lifestyles, the specific roles of various factors in their experiences abroad have not been sufficiently studied. This study aims to clarify the different effects between social support received, adaptation difficulties experienced, and inner acculturation attitudes on both the evaluation of the trip itself and the long-term life goals of students participating in STSA programs.
Closed-form and technology independent phase noise relation for LC oscillators
Authors: Moradnezhad Mehrdad , Miar-Naimi Hossein 
Published: May 2023

Purpose
The purpose of this paper is to find a closed relation for the phase noise of LC oscillators.

Design/methodology/approach
The governing equation of oscillators is generally a stochastic nonlinear differential equation. In this paper, a closed relation for the phase noise of LC oscillators was obtained by approximating the I–V characteristic of the oscillator with third-degree polynomials and analyzing its differential equation.

Findings
This relation expresses phase noise directly in terms of circuit parameters, including the sizes of the transistors and the bias. Next, for evaluation, the phase noise of the cross-coupled oscillator without tail current was calculated with the proposed model. In this approach, the obtained equations are expressed independently of technology by combining the obtained phase noise relation and gm/ID method.

Originality/value
A technology-independent method using the gm/ID method and the closed relationship is provided to calculate phase noise.
Multiphase, three-dimensional PEM fuel cell numerical model with a variable cross-sectional area flow channel
Authors: Tian Jinbei , Ismail Mohammed S. , Ingham Derek , Hughes Kevin J. , Ma Lin , Pourkashanian Mohamed 
Published: May 2023

Purpose
This paper aims to investigate the impact of three different flow channel cross sections on the performance of the fuel cell.

Design/methodology/approach
A comprehensive three-dimensional polymer electrolyte membrane fuel cell model has been developed, and a set of conservation equations has been solved. The flow is assumed to be steady, fully developed, laminar and isothermal. The investigated cross sections are the commonly used square cross section, the increasingly used trapezoidal cross section and a novel hybrid configuration where the cross section is square at the inlet and trapezoidal at the outlet.

Findings
The results show that a slight gain is obtained when using the hybrid configuration and this is because of increased velocity, which improves the supply of the reactant gases to the catalyst layers (CLs) and removes heat and excess water more effectively compared to other configurations. Further, the reduction of the outlet height of the hybrid configuration leads to even better fuel cell performance and this is again because of increased velocity in the flow channel.

Research limitations/implications
The data generated in this study will be highly valuable to engineers interested in studying the effect of fluid cross -sectional shape on fuel cell performance.

Originality/value
This study proposes a novel flow field with a variable cross section. This design can supply a higher amount of reactant gases to the CLs, dissipates heat and remove excess water more effectively.
Daily online review sentiment and hotel performance
Authors: Nicolau Juan Luis , Xiang Zheng , Wang Dan 
Published: May 2023

Purpose
This paper aims to investigate the links between daily review sentiment and the hotel performance measures of occupancy rate (OR), average daily rate (ADR) and revenue per available room (RevPAR).

Design/methodology/approach
The authors conducted review sentiment analyses in three moments (−1, −7 and −14 days) before arrival time using a data set of budget hotel performance and online reviews. The aim was to identify the effect of review sentiment in the budget hotel market on the three performance metrics.

Findings
Daily sentiment positively affects ADR and negatively affects OR and RevPAR, but only up to a certain threshold, after which the trend reverses. Prices increase with the level of sentiment, and high prices lead to low OR and RevPAR only when the sentiment scores are low. When they are high, they are associated with low rates, which lead to high OR and RevPAR.

Research limitations/implications
Daily review sentiment can be viewed as a valuable “barometer” indicating a hotel’s daily operational effectiveness. Daily sentiment can thus allow hotel managers to adjust their dynamic pricing strategies more accurately.

Originality/value
This study identifies daily sentiment as an alternative predictor of hotel performance. In addition to the roles of valence and volume in the decision-making process, the authors found that daily review sentiment can be an “in-the-moment” factor with a high impact, encouraging consumers to complete their transactions. This study suggests that aggregated measures such as the total number of reviews and overall ratings of the hotel should not be the sole consideration in reputation management.