bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres
Authors: Lee Jennifer J , Kim Hyungmin , Park Haemin , Lee UkJin , Kim Chaelim , Lee Min , Shin Yongdae , Jung Ji-Jung , Lee Han-Byoel , Han Wonshik , Lee Hyunsook 
Published: April 2024

Abstract
Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing RNA (TERRA)-R-loop accumulation, triggering liquid–liquid phase separation (LLPS) and the assembly of Alternative Lengthening of Telomeres (ALT)-associated promyelocytic leukemia (PML) bodies (APBs). Disruption of R-loops abolishes LLPS and impairs telomere synthesis. Artificial engineering of telomeric LLPS restores telomere synthesis, underscoring the critical role of LLPS in ALT. TERRA-R-loops also recruit Polycomb Repressive Complex 2 (PRC2), leading to tri-methylation of Lys27 on histone H3 (H3K27me3) at telomeres. Half of paraffin-embedded tissue sections from human breast cancers exhibit APBs and telomere length heterogeneity, suggesting that BRCA2 mutations can predispose individuals to ALT-type tumorigenesis. Overall, BRCA2 abrogation disrupts the dynamicity of telomeric G4, producing TERRA-R-loops, finally leading to the assembly of telomeric liquid condensates crucial for ALT. We propose that modulating the dynamicity of telomeric G4 and targeting TERRA-R-loops in telomeric LLPS maintenance may represent effective therapeutic strategies for treating ALT-like cancers with APBs, including those with BRCA2 disruptions.
The management of very mild and mild asthma in preschoolers, children, and adolescents
Authors: Yang Connie L , Zysman-Colman Zofia , Chétrit Estelle , Hicks Anne , Reisman Joseph , Glicksman Amy 
Published: April 2024

Abstract
This practice point summarizes recommendations from the Canadian Thoracic Society’s 2021 “Guideline update: Diagnosis and management of asthma in preschoolers, children, and adults.” New recommendations include: a decrease in the frequency of daytime symptoms and reliever use to ≤2 per week in the asthma control criteria; assessing for risk of asthma exacerbation; not using as-needed short-acting beta-agonists alone in patients at higher risk for exacerbation; and the option of as-needed budesonide/formoterol (bud/form) in those ≥12 years old if they are unable to take daily inhaled corticosteroids despite extensive asthma education and support. The preference for daily inhaled corticosteroids to manage mild asthma in children, and the recommendation against intermittent short courses of inhaled corticosteroids, are unchanged.
Global dynamics and cytokinin participation of salt gland development trajectory in recretohalophyte Limonium bicolor
Authors: Zhao Boqing , Gao Yaru , Ma Qiuyu , Wang Xi , Zhu Jian-Kang , Li Weiqiang , Wang Baoshan , Yuan Fang 
Published: April 2024

Abstract
Salt gland is an epidermal Na+ secretory structure that enhances salt resistance in the recretohalophyte sea lavender (Limonium bicolor). To elucidate the salt gland development trajectory and related molecular mechanisms, we performed single-cell RNA sequencing of L. bicolor protoplasts from young leaves at salt gland initiation and differentiation stages. Dimensionality reduction analyses defined 19 transcriptionally distinct cell clusters, which were assigned into 4 broad populations—promeristem, epidermis, mesophyll, and vascular tissue—verified by in situ hybridization. Cytokinin was further proposed to participate in salt gland development by the expression patterns of related genes and cytological evidence. By comparison analyses of Single-cell RNA sequencing with exogenous application of 6-benzylaminopurine, we delineated 5 salt gland development-associated subclusters and defined salt gland-specific differentiation trajectories from Subclusters 8, 4, and 6 to Subcluster 3 and 1. Additionally, we validated the participation of TRIPTYCHON and the interacting protein Lb7G34824 in salt gland development, which regulated the expression of cytokinin metabolism and signaling-related genes such as GLABROUS INFLORESCENCE STEMS 2 to maintain cytokinin homeostasis during salt gland development. Our results generated a gene expression map of young leaves at single-cell resolution for the comprehensive investigation of salt gland determinants and cytokinin participation that helps elucidate cell fate determination during epidermis formation and evolution in recretohalophytes.
Age-dependent changes in leaf size in apple are governed by a cytokinin-integrated module
Authors: Jia Xumei , Xu Shuo , Wang Yuting , Jin Lu , Gao Tengteng , Zhang Zhijun , Yang Chao , Qing Yubin , Li Chao , Ma Fengwang 
Published: April 2024

Abstract
Plants undergo various age-dependent changes in leaf morphology during juvenile to adult vegetative stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a–MdSPL14–MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a–MdSPL14–MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.
Daily associations between salivary cortisol and electroencephalographic-assessed sleep: a 15-day intensive longitudinal study
Authors: Yap Yang , Tung Natasha Yan Chi , Shen Lin , Bei Bei , Phillips Andrew , Wiley Joshua F 
Published: April 2024

Abstract

Study Objectives
Current evidence suggests that cortisol levels are bi-directionally associated with sleep. However, the daily, naturalistic cortisol-sleep associations remain unclear, as current evidence is mostly cross-sectional. This study tested whether pre-sleep cortisol predicts sleep duration and quality, and whether these sleep parameters predict the following day’s diurnal cortisol slope using a 15-day intensive longitudinal design with electroencephalographic measures and saliva sampling.

Methods
Ninety-five young adults (Mage = 20.48 ± 1.59 years) provided saliva samples at awakening and pre-sleep over 14 consecutive days, providing 2345 samples (85% viable). The Z-Machine Insight + was used to record over 900 nights of total sleep time (TST) and sleep efficiency (SE). Multilevel models tested these data at the between- and within-person levels.

Results
Higher pre-sleep cortisol predicted shorter TST (p &lt; .001) and lower SE (p &lt; .001) at the within-person level. Individuals with shorter average TST (p = .007) or lower average SE (p &lt; .001) had flatter diurnal cortisol slopes, compared to those with longer average TST or higher average SE. Follow-up analyses showed that individuals with shorter average TST (vs. longer average TST) had higher pre-sleep cortisol levels (p = .01).

Conclusions
Our findings provide evidence that pre-sleep cortisol is associated with sleep duration and quality at the within-individual level. Furthermore, individuals with short or poor sleep had flatter diurnal cortisol slopes. Although the effect sizes are small, these findings show the naturalistic associations between sleep and cortisol in a relatively healthy sample. These findings suggest that sleep maintains the regulation of the stress-response system, which is protective against mental and physical disorders.
A comparison of DNA extraction methods used in the direct molecular detection of Burkholderia pseudomallei from blood
Authors: Mataira Georgia , Francis Fleur , Frazer Jaimie , Norton Robert 
Published: April 2024

Abstract

Background
Melioidosis is caused by Burkholderia pseudomallei. Direct molecular detection from unamplified blood remains insensitive.

Methods
Three different extraction methods—QIAamp UCP Pathogen Mini Kit, High Pure PCR template and MagNA Pure Pathogen Universal—were trialled using spiked human ethylenediaminetetraacetic acid blood. A type III secretion system 1 (TTSS-1) polymerase chain reaction was used for detection.

Results
The QIAamp UCP Pathogen Mini Kit performed best, with a limit of detection of 1.5×102 cfu/ml.

Conclusions
It is planned to use the QIAamp UCP Pathogen Mini Kit to do a larger study on blood collected from patients with melioidosis.
Missing Opportunities in the Screening of Alcohol Use and Problematic Use, and the Provision of Brief Advice and Treatment Information Among Individuals With Alcohol Use Disorder
Authors: Sharma Vinita , Falise Alyssa , Bittencourt Lorna , Zafaranian Amir , Hai Audrey Hang , Lopez-Quintero Catalina 
Published: April 2024

Objectives
The aim of this study was to identify sociodemographic and substance-related factors associated with being screened, receiving advice or treatment information from healthcare providers, among individuals who met the criteria for the past 12-month alcohol use disorder (AUD).

Methods
The 2015–2019 National Survey on Drug Use and Health data were analyzed to identify factors associated with being (1) asked about alcohol used among adults with AUD, who visited a healthcare provider within the past 12 months, and were not receiving AUD treatment (sample 1, n = 13,321); (2) asked about problematic use; (3) advised to reduce consumption; and (4) offered alcohol treatment information, among those in sample 1 who were asked about their use (n = 6,905).

Results
About half (52.9%) in sample 1 were asked about their alcohol use. Among them, 21.6% were asked about problematic use, 17.7% were advised to reduce alcohol consumption, and 7.6% were offered information. The odds of being asked about alcohol use among male participants were 0.72 times the odds of female participants; however once asked, male participants showed greater odds of being asked about problematic use (adjusted odds ratio [aOR] = 1.53, 95% confidence interval [CI] = 1.29–1.82), advised to reduce consumption (aOR = 1.64, 95% CI = 1.24–2.16), and offered treatment information (aOR = 1.77, 95% CI = 1.34–2.35). As compared with non-Hispanic White participants, other racial/ethnic groups were less likely to be asked about alcohol use; however, once asked, no differences were observed for other outcomes.

Conclusions
Significant gaps in the screening and provision of advice or treatment information were identified, particularly for racial/ethnic and sex subgroups. Reducing barriers for effective screening could help address AUD-related disparities.
Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury*
Authors: Svedung Wettervik Teodor , Beqiri Erta , Hånell Anders , Bögli Stefan Yu , Placek Michal , Donnelly Joseph , Guilfoyle Mathew R. , Helmy Adel , Lavinio Andrea , Hutchinson Peter J. , Smielewski Peter 
Published: April 2024

OBJECTIVES:
The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP – optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome.

DESIGN:
Observational cohort study.

SETTING:
Neurocritical care unit, Cambridge, United Kingdom.

PATIENTS:
Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]).

INTERVENTION:
None.

MEASUREMENTS AND MAIN RESULTS:
The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below –5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2–0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2–0.4 correlated with unfavorable outcome.

CONCLUSIONS:
Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.
The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single-center study
Authors: Chang Tien-En , Huang Kuo-Hung , Luo Jiing-Chyuan , Huang Yi-Hsiang , Lin Hung-Hsin , Fang Wen-Liang , Hou Ming-Chih 
Published: April 2024

Background:
Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls.

Methods:
We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics.

Result:
Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium, Prevotella 9, and Bacteroides plebeius DSM 17135. The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella. In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group (p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness.

Conclusion:
Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.
Hospital Performance on Hospital Consumer Assessment of Healthcare Providers and System Ratings
Authors: Rosenbaum Kathleen E. Fitzpatrick , Lasater Karen B. , McHugh Mathew D. , Lake Eileen T. 
Published: April 2024

Objective:
To determine which hospital nursing resources (staffing, skill mix, nurse education, and nurse work environment) are most predictive of hospital Hospital Consumer Assessment of Healthcare Providers and System (HCAHPS) performance.

Background:
HCAHPS surveying is designed to quantify patient experience, a measure of patient-centered care. Hospitals are financially incentivized through the Centers for Medicare and Medicaid Services to achieve high HCAHPS ratings, but little is known about what modifiable hospital factors are associated with higher HCAHPS ratings.

Patients and Methods:
Secondary analysis of multiple linked data sources in 2016 providing information on hospital HCAHPS ratings, hospital nursing resources, and other hospital attributes (eg, size, teaching, and technology status). Five hundred forty non-federal adult acute care hospitals in California, Florida, New Jersey, and Pennsylvania, and 11,786 registered nurses working in those hospitals. Predictor variables included staffing (ie, patient-to-nurse ratio), skill mix (ie, the proportion of registered nurses to all nursing staff), nurse education (ie, percentage of nurses with a bachelor’s degree or higher), and nurse work environment (ie, the quality of the environment in which nurses work). HCAHPS ratings were the outcome variable.

Results:
More favorable staffing, higher proportions of bachelor-educated nurses, and better work environments were associated with higher HCAHPS ratings. The work environment had the largest association with higher HCAHPS ratings, followed by nurse education, and then staffing. Superior staffing and work environments were associated with higher odds of a hospital being a “higher HCAHPS performer” compared with peer hospitals.

Conclusion:
Improving nursing resources is a strategic organizational intervention likely to improve HCAHPS ratings.
Feasibility and Acceptability of a Multifaceted Observational Protocol to Investigate Lucidity in Advanced Dementia
Authors: Coulson Alison , Benson Clark , Fehland Jess , Dillon Kayla , Mueller Kimberly , Gilmore-Bykovskyi Andrea 
Published: April 2024

Objective:
Episodes of lucidity (ELs), characterized by spontaneous, transient recovery of abilities, are reported across neurological conditions, including advanced dementia. Despite the significance of these events, existing research is limited to retrospective reports. Approaches to prospectively capturing and characterizing ELs in dementia are lacking.

Methods:
This pilot study determined the feasibility and acceptability of a multifaceted observational protocol to capture, characterize, and validate ELs in individuals with advanced dementia in hospice. Feasibility was measured through enrollment/retention rates, workload/usability assessment of video observation, and data processing procedures to facilitate the measurement of verbal and nonverbal features for EL characterization. The acceptability of observation and informant validation procedures was qualitatively examined with clinician and family caregiver participants.

Results:
Study procedures were endorsed as highly acceptable among clinician (N = 49) and caregiver (N = 16) participants, demonstrating higher than anticipated thresholds for observation duration. Enrollment and retention rates for patient participants (N = 6) were 100% and 84%, respectively. Workload and usability measures demonstrated low disruptiveness and high ease of use after training.

Discussion:
Longitudinal video observation among individuals with advanced dementia in hospice care for the detection of lucidity was feasible and highly acceptable. Multidimensional, temporal coding of features of ELs is feasible but time-intensive.
Comparison of the ScreenFire and Xpert HPV assays for the detection of human papillomavirus and cervical precancer among women living with HIV in Malawi
Authors: Mungo Chemtai , Guliam Anagha , Chinula Lameck , Inturrisi Federica , Msowoya Lizzie , Mkochi Tawonga , Jawadu Siniya , de Sanjosé Silvia , Schiffman Mark , Tang Jennifer H. , Smith Jennifer S. 
Published: April 2024

AbstractBackgroundThe World Health Organization (WHO) recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries (LMICs) account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi.MethodsWe utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis - cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to <CIN2.Results315 matched self- and provider-collected specimens had valid results from both Xpert and ScreenFire testing and were included in analyses. Of these, 245 (78%) had normal pathology, 21 CIN1 (7%), 14 CIN2 (4%), and 35 CIN3 (11%). Among provider-collected specimens, the assays had 80% agreement on overall HPV positivity (unweighted kappa 0.59, 95% 0.50-0.69). ScreenFire was HPV-positive in 90% of self-collected specimens that were HPV-positive on Xpert. Channel agreement between the assays was high for both self- and provider-collected specimens, but slightly lower for HPV18/45. In hierarchical analysis, ScreenFire demonstrated high concordance with Xpert testing for detecting CIN2+ cases in all channels, missing no HPV 16 or HPV 18/45 positive CIN2+ case that was positive on Xpert, in both self- and provider-collected specimens.ConclusionIn this study of stored specimens, the ScreenFire HPV assay performed well in the detection of HPV and CIN2+ among WLWH compared to the Xpert HPV assay. If supported by larger validation studies, ScreenFire could be an affordable alternative point-of-care HPV assay for use in LMICs.