bluuebunny/crossref_metadata_2025_split huggingface dataset:
CsTCP14‐CsIAA4 module‐mediated repression of auxin signaling regulates citrus somatic embryogenesis
Authors: Wang Peng‐Bo , Duan Yao‐Yuan , Quan Ru‐Meng , Feng Meng‐Qi , Ren Jie , Tang Yong‐Yu , Qing Mei , Xie Kai‐Dong , Guo Wen‐Wu , Wu Xiao‐Meng 
Published: February 2025

Summary
Somatic embryogenesis (SE) is an important in vitro regeneration approach for plants, especially in biotechnological manipulations. However, SE capability is difficult to modulate and deteriorates over time. Glycerol medium is effective in SE induction of citrus, while the mechanisms remain unclear.
We found that auxin signaling reduced soon after the citrus embryogenic callus (EC) was transferred to glycerol medium, and the expression of CsTCP14 and AUX/IAA gene CsIAA4 was induced by glycerol. Overexpression of CsIAAm that encodes a stable indole‐3‐acetic acid (IAA) protein suppressed auxin signaling in EC and enhanced SE. CsTCP14 bound to the promoter of CsIAA4 and activate CsIAA4 expression in EC with strong SE competence. Overexpression of CsTCP14 activated CsIAA4 expression and reduced auxin signaling in citrus EC, and thus enhanced SE.
Application of exogenous IAA inhibits SE, while the auxin signaling inhibitor p‐chlorophenoxyisobutyric acid (PCIB) enhances SE in citrus. The SE enhancement effect of CsIAA4 and CsTCP14 overexpression on EC was alleviated by exogenous IAA, but reinforced by PCIB.
We uncover the regulatory pathway of CsTCP14‐CsIAA4 module‐mediated repression of auxin signaling in glycerol‐induced citrus SE, which deepens our understanding of SE mechanisms in plants and supports modulation of SE in citrus breeding via biotechnological approaches.
Impact of ERP Reliability Cutoffs on Sample Characteristics and Effect Sizes: Performance‐Monitoring ERPs in Psychosis and Healthy Controls
Authors: Heindorf Gavin , Holbrook Amanda , Park Bohyun , Light Gregory A. , Rast Philippe , Foti Dan , Kotov Roman , Clayson Peter E. 
Published: February 2025

ABSTRACTIn studies of event‐related brain potentials (ERPs), it is common practice to exclude participants for having too few trials for analysis to ensure adequate score reliability (i.e., internal consistency). However, in research involving clinical samples, the impact of increasingly rigorous reliability standards on factors such as sample generalizability, patient versus control effect sizes, and effect sizes for within‐group correlations with external variables is unclear. This study systematically evaluated whether different ERP reliability cutoffs impacted these factors in psychosis. Error‐related negativity (ERN) and error positivity (Pe) were assessed during a modified flanker task in 97 patients with psychosis and 104 healthy comparison participants, who also completed measures of cognition and psychiatric symptoms. ERP reliability cutoffs had notably different effects on the factors considered. A recommended reliability cutoff of 0.80 resulted in sample bias due to systematic exclusion of patients with relatively few task errors, lower reported psychiatric symptoms, and higher levels of cognitive functioning. ERP score reliability lower than 0.80 resulted in generally smaller between‐ and within‐group effect sizes, likely misrepresenting effect sizes. Imposing rigorous ERP reliability standards in studies of psychotic disorders might exclude high‐functioning patients, which raises important considerations for the generalizability of clinical ERP research. Moving forward, we recommend examining characteristics of excluded participants, optimizing paradigms and processing pipelines for use in clinical samples, justifying reliability thresholds, and routinely reporting score reliability of all measurements, ERP or otherwise, used to examine individual differences, especially in clinical research.
Multicenter retrospective evaluation of norepinephrine extravasation in dogs and cats (2015–2021): 14 cases
Authors: Vasquez Maria P. , Daly Meredith , Boyd Corrin J. , Crandell Dawn E. , Hall Kelly E. , Mays Erin Long , Ngwenyama Tandi , Ortolani Jennifer , Smith M. Ryan , Hoehne Sabrina N. , Martin Linda , Davidow Elizabeth B. 
Published: February 2025

AbstractObjectiveTo document clinical complications and intervention options associated with norepinephrine (NE) extravasation in dogs and cats.DesignCases were identified between 2015 and 2021. Because this is an uncommon complication, the findings are compiled as a descriptive retrospective study.SettingCases were provided from 4 universities and 2 private practice groups in the United States, Canada, and Australia.AnimalsFourteen patients (13 dogs, 1 cat) that experienced extravasation events (16 total).InterventionsSmall animal patients were included where extravasation of a NE constant rate infusion (CRI) was documented. Records were reviewed for information, including suspected underlying condition, description of the interventions pursued after identification of extravasation, clinical signs after extravasation, and survival to discharge or reason for patient death or euthanasia. When available, information was collected pertaining to the NE dose, dilution, total duration of CRI, and duration of CRI before extravasation was recognized.Measurements and Main ResultsThe most commonly reported clinical signs after extravasation of NE were skin necrosis (n = 9 [64.3%]) and swelling (n = 6 [42.9%]). In 10 of 16 events (62.5%), discontinuation of the NE CRI and/or application of a warm compress to the extravasation site were performed; these were the most common nonpharmacological rescue measures. Two patients received subcutaneous phentolamine, and 1 patient underwent hyperbaric oxygen therapy. While surgical intervention was recommended for 4 dogs, 2 improved without surgical debridement. The overall survival rate from underlying disease processes was 57% (n = 8), with only 1 patient (7%) euthanized due to an injury from the extravasation.ConclusionsSevere lesions can result from NE extravasation in dogs and cats, leading to euthanasia. Although phentolamine remains the treatment of choice, lesions may heal with alternative supportive measures.
Cerebral blood flow during simulated central hypovolaemia in people with hypertension: does vertebral artery hypoplasia matter?
Authors: Neumann Sandra , Rodrigues Jonathan C. L. , Simpson Lydia L. , Lawton Chris B. , Burden Daniel , Kobetic Matthew D. , Adams Zoe H. , Hope Katrina , Paton Julian F. R. , Blythe Hazel , Manghat Nathan , Barnes Jill N. , Nightingale Angus K. , Hamilton Mark C. H. , Hart Emma C. 
Published: February 2025

AbstractAdults with hypertension have higher prevalence of vertebral artery hypoplasia (VAH), which is associated with lower resting cerebral blood flow (CBF). We examined whether VAH impacts the ability to regulate CBF during haemodynamic stress when cardiac output and blood pressure are lowered via body negative pressure (LBNP). Participants underwent magnetic resonance angiography (MRA) at 1.5T during LBNP at 0, −20 and −40 mmHg, and were assigned to VAH (n = 13) or without‐VAH (n = 11) groups post‐acquisition. Phase‐contrast MRA measured flow in the basilar artery (BA), internal carotid arteries (ICA), and the ascending aorta to measure cardiac output (CO). The CO decreased during all levels of LBNP in both groups (LBNP main effect P < 0.0001), whereas MAP was reduced in the group without VAH only (P = 0.0003). BA flow was reduced during LBNP in the group without VAH (P = 0.0267 at −20 mmHg and P < 0.0001 at −40 mmHg) but was surprisingly unchanged in the group with VAH (P > 0.05 all levels LBNP). ICA flow decreased during LBNP (P < 0.0001) and was not different between groups. Total CBF decreased during LBNP in hypertensives without VAH (P = 0.0192 at −20 mmHg and P < 0.0001 at −40 mmHg) but was unchanged in patients with VAH (P > 0.05 at all levels of LBNP). Total peripheral resistance (TPR) increased during LBNP in both groups, but the rise was greater in the group with VAH (−20 mmHg; P = 0.0129, –40 mmHg; P = 0.0016). In summary, hypertensive patients without VAH may tolerate decreases in CBF, whereas patients with VAH evoke a greater systemic TPR response to preserve CBF.
imageKey points
Vertebral artery hypoplasia (VAH) is more common in hypertensive adults and is associated with lower resting cerebral blood flow (CBF), suggesting that VAH might impair the brain's ability to maintain cerebral blood flow during haemodynamic stress using lower body negative pressure.
This study shows that hypertensive patients with VAH maintain CBF during body negative pressure, unlike those without VAH, who experience reductions in CBF. Patients with VAH show a greater rise in total peripheral resistance (TPR), suggesting a compensatory mechanism to maintain cerebral perfusion.
The findings highlight that patients with VAH have an altered physiological response to hypovolaemia, where they may rely on systemic pressor responses to maintain perfusion of posterior brain territories in already hypoperfused circulation.
This is important for understanding how VAH impacts cerebrovascular function in hypertensive patients and may influence clinical approaches to managing CBF in disease conditions.
Feasibility and acceptability of a personalised primary prevention strategy for women and men at high risk of breast and prostate cancer: the 3PC study protocol for a pilot randomised controlled trial
Authors: Souli Intissar , Lapointe Julie , Kinsley-Marlie Jura , Chiquette Jocelyne , Dorval Michel , Diorio Caroline , Lauzier Sophie , Audet-Walsh Étienne , Bilodeau Steve , Côté Madeleine , Brisson Carmen , Charette Nelson , Fortier Philippe , Paquette Jean-Sébastien , Fradet Yves , Savard Josée , Fradet Vincent , Nabi Hermann 
Published: February 2025

IntroductionSeveral primary prevention strategies, including chemoprevention, prophylactic surgery and lifestyle modifications, have been shown to reduce the risk of breast cancer (BC) and prostate cancer (Pca). However, the uptake of these preventive measures is considered suboptimal, limiting their impact on cancer prevention. A personalised primary prevention strategy has yet to be tested for cancer prevention. Therefore, we aim to determine the feasibility, acceptability and potential benefits and harms of this strategy in women and men at high risk of BC and Pca.Methods and analysisThis is a two-arm, parallel-group mixed-methods pilot randomised controlled trial with a 1:1 allocation. The study aims to recruit 60 women and 60 men at high risk of BC and PCa in two specialised sites: the Breast Diseases Center and the Department of Urologic Oncology of the CHU de Québec-Université Laval, Canada. Assessments include intentions to uptake, actual uptake rates of primary preventive measures and decision regret. Feasibility and acceptability of the intervention and the study will be measured by quantifying the recruitment rate, appropriateness of randomisation process and satisfaction metrics. Data will be collected using mixed methods. Quantitative measures will be assessed at baseline and 6 months post randomisation. Quantitative analysis will include descriptive statistics for all variables of interest. Generalised linear mixed models with random intercepts will be used to assess the overall intervention effect. Semistructured interviews will be conducted at the end of follow-up, and a thematic analysis will be performed usingNVivoto understand participants’ perspectives.Ethics and disseminationThe protocol was approved by the Institutional Review Board of CHU de Québec-Université Laval (4 October 2022; 2023-6315). The findings of the study will be published in a peer-reviewed journal and disseminated at national and international conferences and through social media.Trial registration numberThe protocol for this study was registered with the International Clinical Trials Registry (ISRCTN15749766)https://doi.org/10.1186/ISRCTN15749766).
Impact of implementing a nurse-led intraoperative cell saver service in reducing allogeneic red blood cell transfusions in Singapore General Hospital
Authors: He Yingke , Tan Yan Ru , Fu Jing , Gan Yu , Ang Ai Leen , Elisabeth Angelina , Abdullah Hairil Rizal 
Published: February 2025

IntroductionMajor perioperative blood loss often necessitates allogeneic blood transfusions, leading to adverse outcomes and straining healthcare resources. Intraoperative cell salvage (ICS) offers benefits like reduced adverse reactions, optimised blood resource allocation, and cost-effectiveness. Yet, ICS adoption remains limited. Our aim is to formalise and expand ICS as a routine service to promote wider adoption and improve patient outcomes.MethodsThe model for improvement was adopted for an ICS quality improvement initiative across two Plan-Do-Study-Act cycles. Interventions followed the ‘4E’ framework: education, empowerment, enforcement and embedding reminders. The primary outcome was the number of allogeneic red blood cell (RBC) units transfused per surgery with predicted blood loss >500 mL; the secondary outcome was the percentage of indicated surgeries using ICS. Process measure was percentage of anaesthetic unit nurses trained in ICS. Balancing measures included the number of ICS activations with no blood return and complications during and after ICS.ResultsA total of 152 surgeries used ICS postintervention (January 2023 to April 2024), marking an increase from preintervention levels. The median number of monthly mean allogeneic RBC units transfused per patient demonstrated a significant reduction from 3.10 (preintervention) to 2.44 (postintervention). The percentage of indicated surgeries utilising ICS increased from 1.4% to 12.3%. Cost savings were observed, with potential annual savings close to SGD 500 000. No complications related to the use of ICS were recorded.ConclusionThe formalisation and expansion of the ICS service within our institution resulted in notable improvements, including increased ICS adoption rates, reduced reliance on allogeneic blood transfusions and potential cost savings. Future quality improvement efforts should concentrate on further promoting ICS adoption, particularly for surgeries with clinical indications.
Mechanical insufflation-exsufflation use in neuromuscular disease: a single centre cohort study
Authors: Shah Neeraj Mukesh , Kaltsakas Georgios , Madden-Scott Sophie , Apps Chloe , Sheridan Shauna , Ramsay Michelle , Srivastava Shelley , Suh Eui-Sik , D'Cruz Rebecca , Mackie Mike , Weston Nick , Hart Nicholas , Murphy Patrick 
Published: February 2025

IntroductionMechanical insufflation-exsufflation (MIE) is a commonly used therapy to augment secretion clearance in individuals with neuromuscular disease. There are no clear evidence-based guidelines on the settings that should be used in different diagnostic groups and how they should be titrated. We report on the settings used in the largest cohort of individuals using domiciliary MIE in the literature.MethodsA retrospective observational study reporting on all individuals initiated on MIE for long-term domiciliary use at our centre, 2013–2019.ResultsThis study reports on 359 adults established on domiciliary MIE. The most common diagnostic groups were congenital neuromuscular disease (26%), spinal cord injury (23%) and amyotrophic lateral sclerosis (23%). Median age at initiation was 55 years. Median (IQR) insufflation pressure was 35 (30–40) cm H2O and exsufflation pressure was 45 (40–50) cm H2O. Inspiratory time was 2.5 (2.3–2.8) s, expiratory time was 2.7 (2.3–2.8) s, and pause between expiration and inspiration was 2.0 (1.2–2.0) s. Median (IQR) survival following the initiation of MIE was 66 (54–78) months. Increasing age and amyotrophic lateral sclerosis were significantly associated with shorter life expectancy, while the delivery of MIE via oronasal interface compared with tracheostomy was associated with longer life expectancy.ConclusionThis is the largest reported cohort of adults using domiciliary MIE. The most common groups using MIE were congenital neuromuscular disease, spinal cord injury patients and amyotrophic lateral sclerosis. The range of prescribed settings is narrow, reflecting the limited evidence base in this field and the need to better understand optimal targets for titration of different MIE settings.
Characterising alexithymia in individuals with functional motor disorders: a cross-sectional analysis of the Italian Registry of Functional Motor Disorders
Authors: Ostuzzi Giovanni , Geroin Christian , Gastaldon Chiara , Tedeschi Federico , Clesi Francesca Maria , Trevisan Giacomo , Bidello Giovanni , Vita Giovanni , Marcuzzo Enrico , Sandri Angela , Romito Luigi M , Eleopra Roberto , Tesolin Lucia , Franch Ilaria , Zappia Mario , Nicoletti Alessandra , Demartini Benedetta , Nisticò Veronica , Modugno Nicola , Olivola Enrica , Pilotto Andrea , Padovani Alessandro , Defazio Giovanni , Ercoli Tommaso , Petracca Martina , De Micco Rosa , Dallocchio Carlo , Esposito Marcello , Erro Roberto , Del Prete Eleonora , Amaddeo Francesco , Barbui Corrado , Tinazzi Michele 
Published: February 2025

BackgroundAlexithymia, a personality trait characterised by difficulty in identifying and expressing emotions, may contribute to the onset and clinical presentation of functional motor disorders (FMDs), although this association remains underexplored.MethodsFrom the Italian Registry of FMDs, we selected individuals recruited between November 2011 and January 2023, diagnosed with FMD according to Gupta and Lang criteria and assessed for various neurological and psychological features with validated rating scales. The main statistical analysis included regression models using the Toronto Alexithymia Scale 20 items as an explanatory variable for a set of clinical measures, adjusting for sociodemographic factors and correcting for multiple testing.ResultsIn a cohort of 483 individuals, 20.7% had possible alexithymia and 31.5% had definite alexithymia. Higher levels of alexithymia were strongly associated with increased severity of depression (β=0.31, p<0.001), anxiety (β=0.32, p<0.001), general psychological distress (β=−0.27, p<0.001), fatigue (β=0.05, p<0.001) and pain (β=0.32, p<0.001) and moderately associated with a slower onset of FMD (β=0.02, p=0.003). Subscale analyses revealed that difficulties identifying feelings contributed most to these associations. No significant association was observed with motor symptom severity.ConclusionsEmotional processing difficulties of individuals with FMD and alexithymia might increase their vulnerability to mental health problems, pain and fatigue, possibly aggravating the overall prognosis. Further research is needed to elucidate the underlying mechanisms linking alexithymia to FMD and to explore the efficacy of interventions targeting emotional awareness and regulation in this population and to prevent long-term mental health burdens.
Mortality predictors for ICU end-of-life decisions: delta-SOFA and SAPS 3 – retrospective evaluation
Authors: Sala-Trull Maria Carmen , Monedero Pablo , Guillen-Grima Francisco , Leon-Sanz Pilar 
Published: February 2025

ObjectivesEnd-of-life decisions in intensive care units (ICUs) are complex, influenced by patient severity, treatment efficacy and resource constraints. This study assessed the predictive value of delta-Sequential Organ Failure Assessment (SOFA) scores on days 2, 3 and 5, both independently and combined with Simplified Acute Physiology Score (SAPS) 3, for in-hospital mortality.MethodsA retrospective cohort study analysed ICU patients with stays of≥5 days from 2018 to 2020. Clinical data included SAPS 3 and SOFA scores at admission, 48 hours and on days 3 and 5, alongside mortality outcomes. Logistic regression and discriminant analysis identified mortality predictors and evaluated model performance.ResultsAmong 200 patients, 26% died in hospital. Non-survivors had significantly higher SAPS 3 scores (mean 51.9±11.9 vs 45.6±11.9 in survivors, p=0.001) and worsening SOFA scores, particularly on days 3 and 5. Combining SAPS 3 with delta-SOFA on day 5 produced an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.63 to 0.79), indicating moderate predictive ability.ConclusionsIntegrating the delta-SOFA score on day 5 with SAPS 3 improves in-hospital mortality predictions during prolonged ICU stays. Findings suggest early treatment limitations within 48 hours may be premature, as patient responses evolve and shared decision-making becomes more feasible over time.
Diagnosis of Benign and Malignant Newly Developed Nodules on the Surgical Side After Breast Cancer Surgery Based on Machine Learning
Authors: Wang Zhixiang , Li Qingqing , Wang Yiran , Qian Linxue , Hu Xiangdong , Liu Dong 
Published: February 2025

Objective: To enhance the diagnostic accuracy of new nodules on the surgical side after breast cancer surgery using machine learning techniques and to explore the role of multifeature fusion.Methods: Data from 137 breast cancer postoperative patients with new nodules from January 2016 to April 2024 were analyzed. Clinical, ultrasound, immunohistochemistry, and surgical features were combined. Multiple machine learning models, including support vector machine (SVM), random forest, gradient boosting, AdaBoost, and XGBoost, were trained and tested. Model performance was evaluated using stratified ten‐fold cross‐validation. Ablation experiments assessed the impact of different feature combinations on diagnostic performance.Results: The SVM model performed best, with an AUC of 0.8664, an accuracy of 0.8099, a sensitivity of 0.565, and a specificity of 0.9267. Ablation experiments indicated that multifeature fusion significantly improved diagnostic performance, especially when combining clinical, ultrasound, immunohistochemistry, and surgical features. Gradient boosting and random forest models showed slightly inferior performance, while AdaBoost had balanced but lower effectiveness.Conclusion: Machine learning, particularly the multifeature fusion SVM model, shows significant potential in diagnosing new nodules after breast cancer surgery. It can assist doctors in developing more effective treatment plans, improving patient outcomes. Future studies should expand sample sizes, include multicenter data, and explore advanced algorithms to further enhance diagnostic performance.
Deterministic Role of FOXF2 in Organ-Specific Macrometastasis Transition
Authors: Bado Igor L. 
Published: February 2025

The mechanisms contributing to metastasis tropism in breast cancer are far from being understood. The ability of cancer cells to adapt to new microenvironments plays a crucial role in that process. In this issue of Cancer Research, Jiang and colleagues explored the tumor-intrinsic differences that affect seeding and tissue colonization by focusing on two major sites of breast cancer metastasis: the lung and bone. They used genetic approaches and metastasis modeling to assess the role of forkhead box F2 (FOXF2) in remodeling the tumor microenvironment and promoting metastasis outgrowth. Their findings suggest that FOXF2 promotes a micrometastasis-to-macrometastasis transition in bones through the direct activation of NF-κB and BMP4 signaling pathways, independently of tumor subtype. In contrast, FOXF2 was found to hinder the ability of basal models to colonize the lung microenvironment through inhibition of TGFβ signaling. Collectively, these findings underscore the subtype-specific and tissue-dependent roles of FOXF2 in organotropism.
See related article by Jiang et al., p. 644