bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial Cell Flow–Mediated Quiescence Is Temporally Regulated and Utilizes the Cell Cycle Inhibitor p27
Authors: Tanke Natalie T. , Liu Ziqing , Gore Michaelanthony T. , Bougaran Pauline , Linares Mary B. , Marvin Allison , Sharma Arya , Oatley Morgan , Yu Tianji , Quigley Kaitlyn , Vest Sarah , Cook Jeanette Gowen , Bautch Victoria L. 
Published: April 2024

BACKGROUND:
Endothelial cells regulate their cell cycle as blood vessels remodel and transition to quiescence downstream of blood flow–induced mechanotransduction. Laminar blood flow leads to quiescence, but how flow-mediated quiescence is established and maintained is poorly understood.

METHODS:
Primary human endothelial cells were exposed to laminar flow regimens and gene expression manipulations, and quiescence depth was analyzed via time-to-cell cycle reentry after flow cessation. Mouse and zebrafish endothelial expression patterns were examined via scRNA-seq (single-cell RNA sequencing) analysis, and mutant or morphant fish lacking p27 were analyzed for endothelial cell cycle regulation and in vivo cellular behaviors.

RESULTS:

Arterial flow–exposed endothelial cells had a distinct transcriptome, and they first entered a deep quiescence, then transitioned to shallow quiescence under homeostatic maintenance conditions. In contrast, venous flow–exposed endothelial cells entered deep quiescence early that did not change with homeostasis. The cell cycle inhibitor p27 (
CDKN1B
) was required to establish endothelial flow–mediated quiescence, and expression levels positively correlated with quiescence depth. p27 loss in vivo led to endothelial cell cycle upregulation and ectopic sprouting, consistent with loss of quiescence. HES1 and ID3, transcriptional repressors of p27 upregulated by arterial flow, were required for quiescence depth changes and the reduced p27 levels associated with shallow quiescence.

CONCLUSIONS:
Endothelial cell flow–mediated quiescence has unique properties and temporal regulation of quiescence depth that depends on the flow stimulus. These findings are consistent with a model whereby flow-mediated endothelial cell quiescence depth is temporally regulated downstream of p27 transcriptional regulation by HES1 and ID3. The findings are important in understanding endothelial cell quiescence misregulation that leads to vascular dysfunction and disease.
Linking the neural signature of response time variability to Alzheimer’s disease pathology and cognitive functioning
Authors: Teng James , McKenna Michael R. , Gbadeyan Oyetunde , Prakash Ruchika S. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2024

Abstract
Promising evidence has suggested potential links between mind-wandering and Alzheimer’s disease (AD). Yet, older adults with diagnosable neurocognitive disorders show reduced meta-awareness, thus questioning the validity of probe-assessed mind-wandering in older adults. In prior work, we employed response time variability as an objective, albeit indirect, marker of mind-wandering to identify patterns of functional connectivity that predicted mind-wandering. In the current study, we evaluated the association of this connectome-based, mind-wandering model with cerebral spinal fluid (CSF) p-tau/Aβ42 ratio in 289 older adults from the Alzheimer’s Disease NeuroImaging Initiative (ADNI). Moreover, we examined if this model was similarly associated with individual differences in composite measures of global cognition, episodic memory, and executive functioning. Edges from the high response time variability model were significantly associated with CSF p-tau/Aβ ratio. Furthermore, connectivity strength within edges associated with high response time variability was negatively associated with global cognition and episodic memory functioning. This study provides the first empirical support for a link between an objective neuromarker of mind-wandering and AD pathophysiology. Given the observed association between mind-wandering and cognitive functioning in older adults, interventions targeted at reducing mind-wandering, particularly before the onset of AD pathogenesis, may make a significant contribution to the prevention of AD-related cognitive decline.
Distinguishing Impacts on Winter Temperatures in Northern Mid–High-Latitude Continents during Multiyear and Single-Year La Niña Events: A Modeling Study
Authors: Zhu Tingting , Yu Jin-Yi 
Published: April 2024

Abstract
Utilizing a 2200-yr CESM1 preindustrial simulation, this study examines the influence of property distinctions between single-year (SY) and multiyear (MY) La Niñas on their respective impacts on winter surface air temperatures across mid–high-latitude continents in the model, focusing on specific teleconnection mechanisms. Distinct impacts were identified in four continent sectors: North America, Europe, Western Siberia (W-Siberia), and Eastern Siberia (E-Siberia). The typical impacts of simulated SY La Niña events are featured with anomalous warming over Europe and W&E-Siberia and anomalous cooling over North America. Simulated MY La Niña events reduce the typical anomalous cooling over North America and the typical anomalous warming over W&E-Siberia but intensify the typical anomalous warming over Europe. The distinct impacts of simulated MY La Niñas are more prominent during their first winter than during the second winter, except over W-Siberia, where the distinct impact is more pronounced during the second winter. These overall distinct impacts in the CESM1 simulation can be attributed to the varying sensitivities of these continent sectors to the differences between MY and SY La Niñas in their intensity, location, and induced sea surface temperature anomalies in the Atlantic Ocean. These property differences were linked to the distinct climate impacts through the Pacific North America, North Atlantic Oscillation, Indian Ocean–induced wave train, and tropical North Atlantic–induced wave train mechanisms. The modeling results are then validated against observations from 1900 to 2022 to identify disparities in the CESM1 simulation.
Distinct profiles of mental health need and high need overall among New Zealand adolescents – Cluster analysis of population survey data
Authors: Sutcliffe Kylie , Wilson Marc , Clark Terryann C , Crengle Sue , Fleming Terry (Theresa) 
Published: April 2024

Objective: The objective was to identify clinically meaningful groups of adolescents based on self-reported mental health and wellbeing data in a population sample of New Zealand secondary school students. Methods: We conducted a cluster analysis of six variables from the Youth19 Rangatahi Smart Survey ( n = 7721, ages 13–18 years, 2019): wellbeing (World Health Organization Well-Being Index), possible anxiety symptoms (Generalized Anxiety Disorder 2-item, adapted), depression symptoms (short form of the Reynolds Adolescent Depression Scale) and past-year self-harm, suicide ideation and suicide attempt. Demographic, contextual and behavioural predictors of cluster membership were determined through multiple discriminant function analysis. We performed cross-validation analyses using holdout samples. Results: We identified five clusters ( n = 7083). The healthy cluster ( n = 2855, 40.31%) reported positive mental health across indicators; the anxious cluster ( n = 1994, 28.15%) reported high possible anxiety symptoms and otherwise generally positive results; the stressed and hurting cluster ( n = 667, 9.42%) reported sub-clinical depression and possible anxiety symptoms and some self-harm; the distressed and ideating cluster ( n = 1116, 15.76%) reported above-cutoff depression and possible anxiety symptoms and high suicide ideation; and the severe cluster ( n = 451; 6.37%) reported the least positive mental health across indicators. Female, rainbow, Māori and Pacific students and those in higher deprivation areas were overrepresented in higher severity clusters. Factors including exposure to sexual harm and discrimination were associated with increasing cluster severity. Conclusion: We identified high prevalence of mental health challenges among adolescents, with distinct clusters of need. Youth mental health is not ‘one size fits all’. Future research should explore youth behaviour and preferences in accessing support and consider how to best support the mental health of each cluster.
A scoping review of guidelines and frameworks for advance care planning for adolescents and young adults with life-limiting or life-threatening conditions
Authors: Linane Hannah , Tanjavur Bhavana , Sullivan Lindsay 
Published: April 2024

Background: Advance care planning discussions are crucial in the management and support of individuals with life-limiting or life-threatening conditions. Few studies have examined best practices for advance care planning with adolescents and young adults. Aim: To identify core components of current guidelines, frameworks and tools for advance care planning discussions with adolescents and young adults with life-limiting or life-threatening conditions and their families. Design: A scoping review of the literature was conducted followed by a thematic analysis of the included papers. The scoping review was reported according to the Joanna Briggs Institute approach to the conduct of scoping reviews. Data sources: Five databases [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, PsycInfo, PubMed and Scopus] were searched for English-language papers published between inception until January 2023. Results: The search yielded 2976 papers, of which 9 met the inclusion criteria. Five main themes were identified: (i) utilisation of standardised documents and protocols; (ii) shared decision-making between the adolescents and young adults, their families and the healthcare team; (iii) the importance of open and honest communication with adolescents and young adults during advance care planning discussions; (iv) individualisation and flexibility in the advance care planning process and (v) timing of advance care planning initiation. Conclusions: Results highlight the importance of engaging adolescents and young adults in advance care planning and considering their unique needs when initiating and framing these discussions. Our findings can be used by healthcare professionals to inform advance care planning in this group.
A Rare Case of Sjogren’s Syndrome with Polymyositis: A Case Report
Authors: Gohil Namra , Patel Apurva , Gohil Aasvi , Solanki Dipak 
Published: April 2024

Introduction: Sjogren’s syndrome (SS) is an autoimmune chronic inflammatory disorder affecting women in their fourth to sixth decade, affecting gastrointestinal, and musculoskeletal systems. A 35-year-old female with SS with polymyositis (PM) presented with symptoms of weakness in all four limbs, difficulty in sitting, rising, swallowing solid foods, vomiting, and difficulty in climbing stairs. She was diagnosed with SS in 2018 and was treated with prednisolone, Vitamin D, calcium, pyridoxine, methylcobalamin, artificial tears, pilocarpine, and painkillers. However, a muscle biopsy was never done. Methods: The data were collected from the patient’s file along with her consent when she came for follow-up. Results: A muscle biopsy was done at our center to confirm the diagnosis of PM. The patient was prescribed IV prednisolone and other symptomatic treatment until symptoms resolved and was discharged with oral drugs when they were manageable. Conclusion: The diagnosis of primary SS along with PM is a rare occurrence. Although it does not change the treatment plan much, its diagnosis is very important for managing any complications that may arise from it. Patients’ noncompliance and loss of follow-up can create issues in the treatment. Such cases help in forming the guidelines for the future and restructuring the classification of autoimmune conditions.
Atypical phacolytic glaucoma diagnosed by biometry and anterior segment optical coherence tomography (OCT) in a patient with CMV anterior uveitis
Authors: Karmiris Efthymios , Papakonstantinou Evangelia , Tsiripidis Konstantinos , Stavrakas Panagiotis , Giannakis Ioannis , Chalkiadaki Evangelia 
Published: April 2024

Purpose To report a case of phacolytic glaucoma with atypical presentation in a patient which was diagnosed with biometry swept source optical coherence tomography (SS-OCT) and anterior segment spectral domain OCT (SD-OCT). Methods A 56-year-old male with a history of cytomegalovirus (CMV) chronic anterior uveitis in the right eye presented with a white cataract, minimal anterior chamber reaction and intraocular pressure (IOP) of 56 mmHg. Visual acuity was light perception. The anterior chamber was deep, without evidence of macroscopically visible capsular rupture. A surgical intervention was necessitated with the puzzle being whether to proceed with a trabeculectomy or a combined phaco-trabeculectomy. After a routine preoperative assessment with intraocular lens Master700, the disintegration of the natural lens was noticed. Anterior segment Spectralis OCT confirmed a lamellar separation of the anterior one third of the lens, resembling a poultaceous material. After an uneventful phacoemulsification, visual acuity was 6/6, IOP was well-controlled on maximum topical antiglaucoma treatment and no CMV recurrence was observed. Results The diagnosis of phacolytic glaucoma was established with the aid of current imaging OCT systems. Both OCT images were suggestive of a phacolytic nature of our case, despite the fact that the clinical presentation was not in concordance with such a typical case. In view of our findings the decision was to proceed with cataract extraction alone. Conclusion This is the first time that we image and document the phacolytic nature of a natural lens. Our patient did not have the typical clinical presentation and was differentially diagnosed with biometry SS-OCT and confirmed by anterior segment SD-OCT.
Mutational spectrum and deep phenotyping in Pseudoxanthoma Elasticum: Findings from a Portuguese cohort
Authors: Dias Margarida Q. , Gouveia Nuno , Félix Raquel , Estrela-Silva Sérgio , Cabral Diogo , Carvalho Ana Luísa , Murta Joaquim , Silva Rufino , Marques João Pedro 
Published: April 2024

Introduction Pseudoxanthoma Elasticum (PXE) is a rare autosomal recessive disorder originated by disease-causing variants in ABCC6 gene. The purpose of this study was to characterize the genetic landscape, phenotypic spectrum and genotype-phenotype correlations in a Portuguese cohort of PXE patients. Methods Multicentric cross-sectional study conducted in patients with a clinical and genetic diagnosis of PXE. Patients were identified using the IRD-PT registry ( www.retina.com.pt ). Genotypes were classified into 3 groups: (1) two truncating variants, (2) two non-truncating variants, or (3) mixed variants. Deep phenotyping comprised a comprehensive ophthalmologic and systemic evaluation using the updated Phenodex Score (PS). Results Twenty-seven patients (23 families) were included. Sixteen different ABCC6 variants were identified, 7 of which are novel. The most prevalent variant was the nonsense variant c.3421C > T p.(Arg1141*) with an allele frequency of 18.5%. All patients exhibited ocular manifestations. Cutaneous manifestations were present in most patients (88.9%, n = 24/27). A PS score > E2 was strongly associated with worse visual acuity (B = −29.02; p = 0.001). No association was found between genotypic groups and cutaneous, vascular or cardiac manifestations. Conclusions This study describes the genetic spectrum of patients with PXE for the first time in a Portuguese cohort. A total of 16 different variants in ABCC6 were found (7 of which are novel), thus highlighting the genotypic heterogeneity associated with this condition and expanding its mutational spectrum. Still, no major genotype-phenotype associations could be established.
A cross-sectional study of variations in schoolwork stress in academic upper secondary school classes in Mid-Norway
Authors: Johansen Vegard , Røsand Ingvild 
Published: April 2024

Aims: This paper investigates stress related to schoolwork among students in academic upper secondary schools. The research questions asked are: 1. To what degree does students’ schoolwork stress vary between academic classes?; And 2. are perceptions of classroom goal orientation, academic achievement, sex and parental education related to schoolwork stress? Methods: A cross-sectional survey was done in the final year of upper secondary school in 71 school classes from 13 schools. A total of 1955 students in academic education programs were invited to participate in the survey, and 1511 completed the survey; the response rate was 77%. The outcome measure was a composite measure of schoolwork stress (alpha = 0.81). Multilevel modeling was used to estimate school class-level effects. Results: The mean value of schoolwork stress was 4.0, on a scale of 1 (very little schoolwork stress) to 6 (very high schoolwork stress). About half of the students reported a score of 4 or higher. The analysis showed that individual characteristics explained most of the variation in schoolwork stress. Girls experienced a much higher level of schoolwork stress than boys (mean values of 4.3 and 3.6, respectively). There was also a significant class-level effect, estimated to 6% of the variance. Students’ perceptions of classroom goal orientation was also associated with schoolwork stress. Conclusions: The main contribution was the discovery of significant variations in schoolwork stress between school classes. We also found that higher mastery climate was linked to lower schoolwork stress, whereas higher performance climate was linked to higher schoolwork stress.
Predicting Language Function Post-Stroke: A Model-Based Structural Connectivity Approach
Authors: Hildesheim Franziska E. , Ophey Anja , Zumbansen Anna , Funck Thomas , Schuster Tibor , Jamison Keith W. , Kuceyeski Amy , Thiel Alexander 
Published: April 2024

Background The prediction of post-stroke language function is essential for the development of individualized treatment plans based on the personal recovery potential of aphasic stroke patients. Objective To establish a framework for integrating information on connectivity disruption of the language network based on routinely collected clinical magnetic resonance (MR) images into Random Forest modeling to predict post-stroke language function. Methods Language function was assessed in 76 stroke patients from the Non-Invasive Repeated Therapeutic Stimulation for Aphasia Recovery trial, using the Token Test (TT), Boston Naming Test (BNT), and Semantic Verbal Fluency (sVF) Test as primary outcome measures. Individual infarct masks were superimposed onto a diffusion tensor imaging tractogram reference set to calculate Change in Connectivity scores of language-relevant gray matter regions as estimates of structural connectivity disruption. Multivariable Random Forest models were derived to predict language function. Results Random Forest models explained moderate to high amount of variance at baseline and follow-up for the TT (62.7% and 76.2%), BNT (47.0% and 84.3%), and sVF (52.2% and 61.1%). Initial language function and non-verbal cognitive ability were the most important variables to predict language function. Connectivity disruption explained additional variance, resulting in a prediction error increase of up to 12.8% with variable omission. Left middle temporal gyrus (12.8%) and supramarginal gyrus (9.8%) were identified as among the most important network nodes. Conclusion Connectivity disruption of the language network adds predictive value beyond lesion volume, initial language function, and non-verbal cognitive ability. Obtaining information on connectivity disruption based on routine clinical MR images constitutes a significant advancement toward practical clinical application.
Comparison of nebulisation 0.75% ropivacaine with 2% lignocaine for attenuation of haemodynamic response due to intubation: A prospective randomised study
Authors: Geetha Singam , Prashanth Naramoni VSSK , Durga Padmaja , Jayaram Kavitha , Farooq Mohamad , Chandra Sharath , Sushma  
Published: April 2024

Introduction: Laryngoscopy and intubation are associated with the reflex response of hypertension, tachycardia and other intraoperative complications. Nebulised route drug administration and entropy-guided induction enable optimal intubating conditions. Aims: To compare pre-induction nebulisation between 0.75% ropivacaine and 2% lignocaine in blunting the nasotracheal intubation response. Materials and Methods: A total of 100 patients undergoing elective faciomaxillary surgeries were prospectively randomised to receive pre-induction nebulisation: 5mL of 2% lignocaine (100mg) (Group L) or 5mL of 0.75% ropivacaine (37.5mg) (Group R). Patients were induced and intubated (nasotracheal) with entropy monitoring. Observed parameters included systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, entropy at baseline, induction, intubation, post-intubation one, three and five minutes, propofol induction dose, electrocardiogram changes and peri-intubation cough reflex. Results: Ropivacaine aerosol proved significantly better than lignocaine aerosol on haemodynamics (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate) and cough reflex ( p < 0.05). Both groups experienced similar entropy changes and propofol induction dose requirements and no fresh electrocardiogram changes (compared with the baseline). Conclusion: Pre-induction nebulised ropivacaine offers superior intubating conditions than lignocaine regarding haemodynamic response and cough reflex for faciomaxillary surgeries.
A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product
Authors: Bernstein James S. , Dhingra Om P. 
Published: April 2024

Background: Oral testosterone undecanoate (TU) formulations may provide effective, safe, and easily titratable testosterone replacement therapy. Objective: Demonstrate efficacy and safety of a novel oral TU formulation. Design: An open-label, single-arm, multi-center trial treated 155 hypogonadal men for 180 days. Treatment began at 200 mg TU twice daily with meals; doses were titrated over two 28-day cycles to between 100 and 800 mg TU daily, measuring average testosterone (T Cavg) after 90 days. Ambulatory blood pressure monitoring (ABPM) occurred at baseline, 120, and 180 days. Methods: Titrations used a randomized blood sample taken 3-, 4-, or 5-h post-morning dose. Outcomes used sodium fluoride/ethylenediaminetetraacetate plasma testosterone (T) values; serum results were also reported. Blood pressure (ABPM and in-clinic) was evaluated for change from baseline. Results: After titration, 87.8% of KYZATREX™ treated participants (worse-case scenario) and 96.1% of 90-day completers achieved eugonadal mean plasma T values. Serum T Cavg was 452 ng/dL and maximum T concentrations (T Cmax) met all FDA criteria. Participant eugonadal percentages were comparable across subgroups for age, weight, and body mass index. Diet had no effect on participant eugonadal percentages. KYZATREX was well tolerated, with no drug-related serious adverse events (SAE) and one adverse drug reaction (hypertension) observed in 2% or more of participants. Systolic ambulatory blood pressure increased 1.7 mmHg (95% confidence interval: 0.3–3.1). At baseline, 36% of 155 participants were receiving anti-hypertensive medication and 22% were diabetic. No dose increases occurred in existing anti-hypertensive medication; five participants (3.2%) started anti-hypertensive medication. Conclusion: KYZATREX provided safe and effective testosterone levels within the normal range in hypogonadal male study participants. Clinical trial registration: URL: https://clinicaltrials.gov/ unique identifier NCT04467697, conducted under NCT03198728. Post-completion, clinicaltrials.gov requested creation of the separate NCT04467697 identifier. All subjects were recruited under NCT03198728.