bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the mouse neural precursor line, SN4741, as a suitable proxy for midbrain dopaminergic neurons
Authors: Boyd Rachel J. , McClymont Sarah A. , Barrientos Nelson B. , Hook Paul W. , Law William D. , Rose Rebecca J. , Waite Eric L. , Rathinavelu Jay , Avramopoulos Dimitrios , McCallion Andrew S. 
Published: June 2023

AbstractTo overcome the ethical and technical limitations of in vivo human disease models, the broader scientific community frequently employs model organism-derived cell lines to investigate disease mechanisms, pathways, and therapeutic strategies. Despite the widespread use of certain in vitro models, many still lack contemporary genomic analysis supporting their use as a proxy for the affected human cells and tissues. Consequently, it is imperative to determine how accurately and effectively any proposed biological surrogate may reflect the biological processes it is assumed to model. One such cellular surrogate of human disease is the established mouse neural precursor cell line, SN4741, which has been used to elucidate mechanisms of neurotoxicity in Parkinson disease for over 25 years. Here, we are using a combination of classic and contemporary genomic techniques – karyotyping, RT-qPCR, single cell RNA-seq, bulk RNA-seq, and ATAC-seq – to characterize the transcriptional landscape, chromatin landscape, and genomic architecture of this cell line, and evaluate its suitability as a proxy for midbrain dopaminergic neurons in the study of Parkinson disease. We find that SN4741 cells possess an unstable triploidy and consistently exhibits low expression of dopaminergic neuron markers across assays, even when the cell line is shifted to the non-permissive temperature that drives differentiation. The transcriptional signatures of SN4741 cells suggest that they are maintained in an undifferentiated state at the permissive temperature and differentiate into immature neurons at the non-permissive temperature; however, they may not be dopaminergic neuron precursors, as previously suggested. Additionally, the chromatin landscapes of SN4741 cells, in both the differentiated and undifferentiated states, are not concordant with the open chromatin profiles of ex vivo, mouse E15.5 forebrain- or midbrain-derived dopaminergic neurons. Overall, our data suggest that SN4741 cells may reflect early aspects of neuronal differentiation but are likely not a suitable proxy for dopaminergic neurons as previously thought. The implications of this study extend broadly, illuminating the need for robust biological and genomic rationale underpinning the use of in vitro models of molecular processes.
Cytosine base editors (CBEs) for inducing targeted DNA base editing in Nicotiana benthamiana
Authors: Luo Juan , Abid Muhammad , Tu Jing , Cai Xinxia , Zhang Yi , Gao Puxin , Huang Hongwen 
Published: June 2023

Abstract
Background
The base editors can introduce point mutations accurately without causing double-stranded DNA breaks or requiring donor DNA templates. Previously, cytosine base editors (CBEs) containing different deaminases are reported for precise and accurate base editing in plants. However, the knowledge of CBEs in polyploid plants is inadequate and needs further exploration.

Results
In the present study, we constructed three polycistronic tRNA-gRNA expression cassettes CBEs containing A3A, A3A (Y130F), and rAPOBEC1(R33A) to compare their base editing efficiency in allotetraploid N. benthamiana (n = 4x). We used 14 target sites to compare their editing efficiency using transient transformation in tobacco plants. The sanger sequencing and deep sequencing results showed that A3A-CBE was the most efficient base editor. In addition, the results showed that A3A-CBE provided most comprehensive editing window (C1 ~ C17 could be edited) and had a better editing efficiency under the base background of TC. The target sites (T2 and T6) analysis in transformed N. benthamiana showed that only A3A-CBE can have C-to-T editing events and the editing efficiency of T2 was higher than T6. Additionally, no off-target events were found in transformed N. benthamiana.

Conclusions
All in all, we conclude that A3A-CBE is the most suitable vector for specific C to T conversion in N. benthamiana. Current findings will provide valuable insights into selecting an appropriate base editor for breeding polyploid plants.
Does the feedback of blood results in observational studies influence response and consent? A randomised study of the Understanding Society Innovation Panel
Authors: Benzeval Michaela , Andrayas Alexandria , Mazza Jan , Al Baghal Tarek , Burton Jonathan , Crossley Thomas F. , Kumari Meena 
Published: June 2023

Abstract
Background
While medical studies generally provide health feedback to participants, in observational studies this is not always the case due to logistical and financial difficulties, or concerns about changing observed behaviours. However, evidence suggests that lack of feedback may deter participants from providing biological samples. This paper investigates the effect of offering feedback of blood results on participation in biomeasure sample collection.

Methods
Participants aged 16 and over from a longitudinal study – the Understanding Society Innovation Panel—were randomised to three arms – nurse interviewer, interviewer, web survey – and invited to participate in biomeasures data collection. Within each arm they were randomised to receive feedback of their blood results or not. For those interviewed by a nurse both venous and dried blood samples (DBS) were taken in the interview. For the other two arms, they were asked if they would be willing to take a sample, and if they agreed a DBS kit was left or sent to them so the participant could take their own sample and return it. Blood samples were analysed and, if in the feedback arms, participants were sent their total cholesterol and HbA1c results.
Response rates for feedback and non-feedback groups were compared: overall; in each arm of the study; by socio-demographic and health characteristics; and by previous study participation. Logistic regression models of providing a blood sample by feedback group and data collection approach controlling for confounders were calculated.

Results
Overall 2162 (80.3% of individuals in responding households) took part in the survey; of those 1053 (48.7%) consented to provide a blood sample. Being offered feedback had little effect on overall participation but did increase consent to provide a blood sample (unadjusted OR 1.38; CI: 1.16–1.64). Controlling for participant characteristics, the effect of feedback was highest among web participants (1.55; 1.11–2.17), followed by interview participants (1.35; 0.99 –1.84) and then nurse interview participants (1.30; 0.89–1.92).

Conclusions
Offering feedback of blood results increased willingness to give samples, especially for those taking part in a web survey.
Symptoms of depression and anxiety in Chinese adolescents: heterogeneity and associations with executive function
Authors: Sun Jing , Wang Shaoxia , Mu Guoxia , Liu Jingru , Su Rina , Zhang Xiang , Fang Jianqun , Wang Yanrong 
Published: June 2023

Abstract
Background
Depression and anxiety are common symptoms associated with significant morbidity in adolescents. Few studies have explored the relationship between latent profiles of adolescent depression-anxiety symptoms and executive function (EF), which is also a major pediatric public health concern.

Methods
The sample included 1,306 participants who were recruited from two schools in Ningxia. The Depression Self-Rating Scale for Children (DSRSC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were used to assess the level of depression-anxiety symptoms in adolescents, and their executive function state was assessed using the Behavior Rating Inventory of Executive Function-Self-Report version (BRIEF-SR). Latent profile analysis (LPA) was carried out using Mplus 7.0 to explore the most likely number of profiles based on the subscales of DSRSC and SCARED. The relationship between adolescents’ executive function and depression-anxiety symptoms were analyzed by multivariable logistic regression, and the odds ratio were used to test the impact of this relationship.

Results
The LPA results show that the three-profile model was the best-fitting model for adolescent depression and anxiety symptoms. The proportions of Profile-1 (“Healthy Group”), Profile-2 (“Anxiety Disorder Group”), and Profile-3 (“Depression-Anxiety Disorder Group”) were 61.4%, 23.9%, and 14.7%, respectively. Additional analyses using multivariable logistic regression suggested that poor shifting capacity and emotional control were significantly more likely to be classified into the depression and/or anxiety groups, and worse working memory, task completion, and better inhibition were significantly more likely to be classified into the anxiety group.

Conclusions
The findings contribute to our understanding of the heterogeneity of adolescents’ depression-anxiety symptoms and highlight the important role of executive function in influencing mental health outcomes. These findings will guide the improvement and delivery of interventions for the treatment of anxiety and depression in adolescents, mitigating functional impairments in patients and reducing disease risk.
Internet addiction and mental health disorders in high school students in a Peruvian region: a cross-sectional study
Authors: Perez-Oyola Jean C. , Walter-Chavez Dionela M. , Zila-Velasque J. Pierre , Pereira-Victorio César Johan , Failoc-Rojas Virgilio E. , Vera-Ponce Víctor J. , Valladares-Garrido Danai , Valladares-Garrido Mario J. 
Published: June 2023

AbstractObjectivesTo determine the association between internet addiction disorder (IAD) and anxiety and depressive symptomatology in high school students in two private schools in Chiclayo, Peru, during the COVID-19 pandemic.Materials and methodsAnalytical cross-sectional investigation of 505 adolescents from two private schools. The dependent variables were anxiety and depressive symptomatology, measured with the Beck Adapted Depression Questionnaire (BDI-IIA) and the Beck Anxiety Inventory (BAI), respectively. The main independent variable was IAD, measured with the Internet Addiction Test instrument(IATI). Prevalence ratios (PR) and 95% confidence intervals (95%CI) were estimated.ResultsThe average age was 14.16 years and 54.9% were women. 22.2% and 3.2% presented mild and moderate IAD; respectively. 9.3% presented severe anxiety and 34.3% severe depressive symptomatology. In the simple regression, adolescents with mild, moderate and severe IAD presented 19% (PR = 1.19; 95%CI: 1.05–1.35), 25% (PR = 1.25; 95%CI: 1.02–1.53) and 53% (PR = 1.47; 95% CI: 1.47–1.60) higher prevalence of depressive symptomatology; however, this association was not maintained in the multiple model. Anxiety increased 196% in adolescents with severe IAD (PR = 2.96; 95%CI: 1.86–4.71).Conclusion We found that 2, 1, and 3 out of 10 students presented IAD, depressive symptomatology, and anxiety, respectively. We did not find an association between IAD and depressive symptomatology, but we did find an association with anxiety. Among the factors associated with the development of depressive symptomatology were the male sex, the presence of eating disorders, subclinical insomnia, using devices for more than 2 h, and using the Internet for academic activities. About anxiety, the associated factors are the female sex, the presence of eating disorders, subclinical insomnia, and the use of the Internet as social interaction. We recommend implementing counseling programs in view of the imminent introduction of the Internet as a pillar in education.
Experiences of distress and gaps in government safety net supports among parents of young children during the COVID-19 pandemic: a qualitative study
Authors: Mooney Alyssa C. , Jackson Kaitlyn E. , Hamad Rita , Fernald Lia C. H. , Hoskote Mekhala , Gosliner Wendi 
Published: June 2023

Abstract
Background
The COVID-19 pandemic prompted rapid federal, state, and local government policymaking to buffer families from the health and economic harms of the pandemic. However, there has been little attention to families’ perceptions of whether the pandemic safety net policy response was adequate, and what is needed to alleviate lasting effects on family well-being. This study examines the experiences and challenges of families with low incomes caring for young children during the pandemic.

Methods
Semi-structured qualitative interviews conducted from August 2020 to January 2021 with 34 parents of young children in California were analyzed using thematic analysis.

Results
We identified three key themes related to parents’ experiences during the pandemic: (1) positive experiences with government support programs, (2) challenging experiences with government support programs, and (3) distress resulting from insufficient support for childcare disruptions. Participants reported that program expansions helped alleviate food insecurity, and those attending community colleges reported accessing a range of supports through supportive counselors. However, many reported gaps in support for childcare and distance learning, pre-existing housing instability, and parenting stressors. With insufficient supports, additional childcare and education workloads resulted in stress and exhaustion, guilt about competing demands, and stagnation of longer-term goals for economic and educational advancement.

Conclusions
Families of young children, already facing housing and economic insecurity prior to the pandemic, experienced parental burnout. To support family well-being, participants endorsed policies to remove housing barriers, and expand childcare options to mitigate job loss and competing demands on parents. Policy responses that either alleviate stressors or bolster supports have the potential to prevent distress catalyzed by future disasters or the more common destabilizing experiences of economic insecurity.
Work-related musculoskeletal symptoms among Saudi radiologists: a cross-sectional multi-centre study
Authors: Alelyani Magbool , Gameraddin Moawia , Khushayl Abdullah Mohammed A. , Altowaijri Aljoharah M. , Qashqari Maryam Ibrahim , Alzahrani Fahad Ali Ahmed , Gareeballah Awadia 
Published: June 2023

Abstract
Background
Musculoskeletal disorders are common health problems worldwide. Several factors cause these symptoms, including ergonomics and other individual considerations. Computer users are prone to repetitive strain injuries that increase the risk of developing musculoskeletal symptoms (MSS). Radiologists are susceptible to developing MSS because they work long hours analysing medical images on computers in an increasingly digitalised field. This study aimed to identify the prevalence of MSS among Saudi radiologists and the associated risk factors.

Methods
This study was a cross-sectional, non-interventional, self-administered online survey. The study was conducted on 814 Saudi radiologists from various regions in Saudi Arabia. The study's outcome was the presence of MSS in any body region that limited participation in routine activities over the previous 12 months. The results were descriptively examined using binary logistic regression analysis to estimate the odds ratio (OR) of participants who had disabling MSS in the previous 12 months. All university, public, and private radiologists received an online survey containing questions about work surroundings, workload (e.g., spent at a computer workstation), and demographic characteristics.

Results
The prevalence of MSS among the radiologists was 87.7%. Most of the participants (82%) were younger than 40 years of age. Radiography and computed tomography were the most common imaging modalities that caused MSS (53.4% and 26.8%, respectively). The most common symptoms were neck pain (59.3%) and lower back pain (57.1%). After adjustment, age, years of experience, and part-time employment were significantly associated with increased MSS (OR = .219, 95% CI = .057–.836; OR = .235, 95% CI = 087–.634; and OR = 2.673, 95% CI = 1.434–4.981, respectively). Women were more likely to report MSS than males (OR = 2.12, 95% CI = 1.327–3.377).

Conclusions
MSS are common among Saudi radiologists, with neck pain and lower back pain being the most frequently reported symptoms. Gender, age, years of experience, type of imaging modality, and employment status were the most common associated risk factors for developing MSS. These findings are vital for the development of interventional plans to reduce the prevalence of musculoskeletal complaints in clinical radiologists.
Absence of detrusor muscle in TUR-BT specimen – can we predict who is at highest risk?
Authors: Volz Yannic , Trappmann Rabea , Ebner Benedikt , Eismann Lennert , Pyrgidis Nikolaos , Pfitzinger Paulo , Bischoff Robert , Schlenker Boris , Stief Christian , Schulz Gerald Bastian 
Published: June 2023

Abstract
Introduction
As a high-quality TUR-BT is important to ensure adequate treatment for bladder cancer patients, the aim of the current study is to investigate the impact of patient-related, surgical and tumor-specific parameters on detrusor muscle (DM) absence (primary objective) and to assess the impact of DM on the prognosis after a TUR-BT (secondary objective).

Patients and methods
Transurethral resection of bladder tumors (TUR-BTs) between 2009 and 2021 were retrospectively screened (n = 3237). We included 2058 cases (1472 patients) for the primary and 472 patients for secondary objective. Clinicopathological variables including tumor size, localization, multifocality, configuration, operation time and skill-level of the urologist were assessed. We analyzed predictors for missing DM and prognostic factors for recurrence-free survival (RFS) for the complete cohort and subgroups.

Results
DM was present in 67.6% (n = 1371/2058). Surgery duration (continuous, minutes) was an independent predictor for absence of DM in the complete cohort (OR:0.98, r:0.012, 95%CI:0.98–0.99, p = 0.001). Other significant risk factors for missing DM were papillary tumors (OR:1.99, r:0.251, 95%CI:1.22–3.27, p = 0.006) in the complete cohort and bladder-roof and posterior-bladder-wall localization for re-resections. Absence of DM in high-grade BC correlated with reduced RFS (HR:1.96, 95%CI:1.0–3.79, p = 0.045).

Conclusion
Sufficient time for a TUR-BT is mandatory to assure DM in the TUR-BT specimen. Also, cases with more difficult locations of bladder tumors should be performed with utmost surgical diligence and endourological training should incorporate how to perform such operations. Of note, DM correlates with improved oncological prognosis in high-grade BC.
Effect of immersion and thermocycling in different beverages on the surface roughness of single- and multi-shade resin composites
Authors: El-Rashidy Aiah A. , Shaalan Omar , Abdelraouf Rasha M. , Habib Nour A. 
Published: June 2023

Abstract
Background
Resin composite restorations are highly esthetic restorations, which should have and maintain high surface polish. However, esthetic restorations are subjected to different beverages at variable temperatures, which may affect their surface roughness. This study aimed to evaluate the surface roughness of single-shade (Omnichroma) and multi-shade (Filtek Z350XT) composite materials, following aging by immersion and thermocycling in different beverages, simulating one year of clinical service.

Methods
Thirty specimens of each material were prepared and divided into 6 subgroups (n = 5). In each material, the grouping of the specimens was as follows: the first subgroup was the as-prepared specimens stored dry without immersion or thermocycling. The second, third, and fourth subgroups were immersed in saliva, tea, and red wine, respectively, for 12 days at 37 °C. The fifth and sixth subgroups were thermocycled for 10,000 cycles, in tea (the fifth between 37 and 57 °C) and in red wine (the sixth between 37 °C and12°C). The resultant surface roughness was measured by two different methods, stylus profilometer and atomic force microscopy (AFM). Intergroup comparison was performed using independent t test, while intragroup comparison was performed using one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test.

Results
Intergroup comparison between both composites showed no statistically significant differences in all groups using the stylus profilometer roughness measurements (P>0.05), while the AFM measurements showed significant difference (P ≤ 0.05) within all storage media except the as-prepared control (P = 0.0645), where nanofilled Filtek Z350 XT showed lower nano-roughness. Intragroup comparison data were variable, depending on the material, aging conditions, and roughness assessment tool. However, the resultant average surface roughness (Ra) values in all groups did not exceed the threshold value of Ra 0.2 μm.

Conclusions
Both resin composites attained and retained a clinically acceptable surface finish after immersion and thermocycling in different beverages.
Twine virtual patient games as an online resource for undergraduate diabetes acute care education
Authors: Quail Nathaniel Patrick Andrew , Boyle James Graham 
Published: June 2023

Abstract
Background
Virtual patients provide a safe way to simulate authentic clinical practice. Twine is an open-source software that can be used to create intricate virtual patient games, including elements like non-linear free text history taking and time-related changes to the game’s narrative. We evaluated the incorporation of Twine virtual patient games into a diabetes acute care online learning package for undergraduate medical students at the University of Glassgow, Scotland.

Methods
Three games were developed using Twine, Wacom Intuous Pro, Autodesk SketchBook, Camtasia Studio, and simulated patients. Online material included three VP games, eight microlectures, and a single best answer multiple choice question quiz. The games were evaluated at Kirkpatrick Level 1 with an acceptability and usability questionnaire. The entire online package was evaluated at Kirkpatrick Level 2 with pre- and post-course multiple choice and confidence questions, with statistical analysis performed using paired t-tests.

Results
122 of approximately 270 eligible students provided information on resource utilisation, with 96% of these students using at least one online resource. 68% of students who returned surveys used at least one VP game. 73 students provided feedback on the VP games they had played, with the majority of median responses being “agree” on positive usability and acceptability statements. The online resources were associated with a mean multiple choice score increase from 4.37 out of 10 to 7.96 out of 10 (p < 0.0001, 95% CI + 2.99 to + 4.20, n = 52) and a mean total confidence score increase from 4.86 out of 10 to 6.70 out of 10 (p < 0.0001, 95% CI + 1.37 to + 2.30, n = 48).

Conclusions
Our VP games were well-received by students and promoted engagement with online material. The package of online material led to statistically significant increases in confidence and knowledge in diabetes acute care outcomes. A blueprint with supporting instructions has now been created to facilitate rapid creation of further games using Twine software.