bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological Symptom Cluster Severity Profiles Are Associated With Higher Levels of Stress and Worse Quality of Life in Postmenopausal Women With Breast Cancer
Authors: Harris Carolyn S. , Conley Yvette P. , Rosenzweig Margaret Q. , Erickson Kirk I. , Cooper Bruce A. , Bender Catherine M. 
Published: December 2024

Background
Although common, the severity of the psychological symptom cluster (PSC) (ie, co-occurrence of anxiety, depression, fatigue, sleep disturbance) varies among women with breast cancer. In addition, the impact of various types of stress and other risk factors on its severity are understudied, and the influence of the PSC on quality of life (QOL) outcomes remains poorly characterized.

Objective
To identify subgroups of postmenopausal women with breast cancer with distinct PSC severity profiles following surgery and evaluate whether these subgroups differed in terms of demographic and clinical characteristics, symptoms, social and posttraumatic stress, and QOL.

Methods
Following surgery, 159 postmenopausal women with early-stage, hormone receptor–positive breast cancer completed assessments of anxiety, depression, fatigue, sleep disturbance, cognitive function, physical symptoms, stress, and QOL. Latent profile analysis was used to identify subgroups of women based on the severity of the prespecified PSC. Parametric and nonparametric tests were used to evaluate for subgroup differences.

Results
Three distinct PSC severity subgroups were identified (ie, Lower [71.7%], Moderate [23.9%], Higher [4.4%]). Compared with the Lower subgroup, the Moderate subgroup was less likely to have received prior radiation, and the Moderate and Higher subgroups had worse perceived cognitive function, higher symptom burden, higher posttraumatic stress, and lower QOL. Clinically relevant sleep disturbance was common across PSC subgroups.

Conclusions
PSC severity is associated with higher posttraumatic stress and poorer QOL following breast surgery. Sleep disturbance is a common problem and may be undertreated.

Implications for Practice
Assessments of posttraumatic stress and sleep disturbance are needed for timely intervention.
Development and Preliminary Testing of the Withdrawal Assessment Tool-Alpha 2 Agonist: An Assessment Instrument for Monitoring Iatrogenic Withdrawal Symptoms in Children Receiving an Alpha-2 Agonist
Authors: Solodiuk Jean C. , Donado Carolina , Wickerham Lia , Goodyear Lindsay , Hayes John , Mortell Rachel E. , Greco Christine D. , Curley Martha A. Q. 
Published: December 2024

OBJECTIVES:
To develop and conduct preliminary testing of the Withdrawal Assessment Tool-Alpha 2 Agonist (WAT-A2A) to monitor dexmedetomidine and clonidine withdrawal symptoms in acutely ill children.

DESIGN:
Three-phase instrument development study. Phase 1: retrospective chart review of symptoms exhibited by children with documented dexmedetomidine withdrawal; phase 2: WAT-A2A instrument construction based on phase 1 data; and phase 3: prospective testing of the WAT-A2A in children weaning from alpha 2 agonists (A2As).

SETTING:
Academic free-standing children’s hospital.

PATIENTS:
Acutely ill children weaning from at least 5 days of dexmedetomidine. Excluded were children concurrently weaning other sedatives.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Phase 1: In 83 of 303 children weaning from at least 5 days of dexmedetomidine who had clinician documentation and were managed for A2A withdrawal, 88% (n = 72) exhibited at least a 20% increase in heart rate (HR), 83% (n = 69) exhibited agitation or change in usual state behavior, 46% (n = 38) exhibited at least a 20% increase in diastolic blood pressure (DBP), and when documented, 56% (27/48) exhibited tremors during their A2A withdrawal episode. Phase 2: The WAT-A2A was constructed, based on phase 1 data, and includes four items: HR, state behavior, DBP, and tremors. Phase 3: The WAT-A2A was tested and performed well in 82 children weaning from A2A. The total WAT-A2A score correlated with clinician subjective assessment of A2A withdrawal (Spearman correlation = 0.5; p < 0.001). Inter-rater agreement, comparing paired ratings of prospectively collected WAT-A2A data, indicated moderate inter-rater reliability.

CONCLUSIONS:
Acutely ill children receiving sedation with an A2A for more than 5 days may develop physiologic dependence, requiring gradual dosing reductions. While further psychometric testing is advised, the WAT-A2A provides an objective instrument to help clinicians quantify dexmedetomidine withdrawal symptoms in acutely ill children may facilitate A2A weaning and limit unnecessary variation in practice.
Foreign Body Perforating the Descending Colon Incidentally Detected on 18F-FDG PET/CT
Authors: Duarte Paulo Schiavom , Coura-Filho George Barberio , Sapienza Marcelo Tatit , Zhuang Hongming , Buchpiguel Carlos Alberto 
Published: December 2024

Abstract
A 78-year-old woman was diagnosed having unresectable tongue cancer 6 months ago, for which she received radiation therapy. She was on enteral nutrition for more than 2 months due to dysphagia and underwent an 18F-FDG PET/CT for restaging. The images showed uptake in a left cervical node. In addition, there was a focal uptake in the descending colon corresponding to a foreign body in its anterior wall, which was removed by colonoscopy.
18F-FDG PET/CT Imaging of Myoepithelial Carcinoma in the Left Femur
Authors: Huang Shuhui , Xie Hangyu , Huang Rui 
Published: December 2024

Abstract
Myoepithelial carcinoma of bone is uncommon. We presented the imaging features of myoepithelial carcinoma of the left femur in a 61-year-old man on 18F-FDG PET/CT. Lytic bone destruction and the formation of a slightly low-density soft tissue mass extending to adjacent muscles with intense and circular FDG uptake were found on 18F-FDG PET/CT. Postoperative pathology confirmed the diagnosis of myoepithelial carcinoma.
FDG PET/CT in Papillary Intralymphatic Angioendothelioma of the Spleen
Authors: Jiao Benzheng , Liu Hongxia , Ma Xiaobo , Dong Aisheng , Zhao Hongguang 
Published: December 2024

Abstract
Splenic papillary intralymphatic angioendothelioma is extremely rare. We describe FDG PET/CT and MRI findings of splenic papillary intralymphatic angioendothelioma in a young adult. The splenic tumor showed hypodensity and increased FDG uptake with SUVmax of 4 on PET/CT, heterogeneous signal intensity with internal hypointense stellate scars on T2-weighted image, and progressive centripetal enhancement on dynamic contrast-enhanced T1-weighted images. This case indicates that papillary intralymphatic angioendothelioma should be included in the differential diagnosis of FDG-avid splenic lesions.
Advanced Peptide Nanoparticles Enable Robust and Efficient delivery of gene editors across cell types
Authors: Gustafsson Oskar , Krishna Supriya , Borate Sophia , Ghaeidamini Marziyeh , Liang Xiuming , Saher Osama , Cuellar Raul , Birdsong Björn K. , Roudi Samantha , Estupiñán H. Yesid , Alici Evren , Smith CI Edvard , Esbjörner Elin K. , Spuler Simone , de Jong Olivier Gerrit , Escobar Helena , Nordin Joel Z. , Andaloussi Samir EL 
Published: December 2024

AbstractEfficient delivery of the CRISPR/Cas9 system and its larger derivatives, base editors, and prime editors remain a significant challenge, particularly in tissue-specific stem cells and induced pluripotent stem cells (iPSCs). This study optimized a novel family of cell-penetrating peptides, hPep, to deliver gene-editing ribonucleoproteins. The hPep-based nanoparticles enable highly efficient and biocompatible delivery of Cre recombinase, Cas9, base-, and prime editors. Using base editors, robust and nearly complete genome editing was achieved in the human cells: HEK293T (96%), iPSCs (74%), and muscle stem cells (80%). This strategy opens promising avenues for ex vivo and, potentially, in vivo applications. Incorporating silica particles enhanced the system’s versatility, facilitating cargo-agnostic delivery. Notably, the nanoparticles can be synthesized quickly on a benchtop and stored as lyophilized powder without compromising functionality. This represents a significant advancement in the feasibility and scalability of gene-editing delivery technologies.
Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
Authors: Ferreira Beatriz H. , Mazeda Carolina , Dourado Eduardo , Simões João L. , Prata Ana Rita , Argüello Rafael J. , Duarte Iola F. , Pierre Philippe , Almeida Catarina R. 
Published: December 2024

AbstractBackgroundPlasmacytoid dendritic cells (pDCs) play a key role in systemic sclerosis (SSc) pathophysiology. However, despite the recognised importance of metabolic reprogramming for pDC function, their metabolic profile in SSc remains to be elucidated. Thus, our study aimed to investigate the role of pDC metabolism in SSc.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy donors and SSc patients. SCENITH™, a single-cell flow cytometry-based method, was applied to infer the metabolic profile of circulating pDCs from patients with SSc. pDCs (CD304+Lin-) at steady-state or stimulated with CpG A were analysed. Toll-like receptor (TLR)9 activation was confirmed by ribosomal protein S6 phosphorylation.ResultsCirculating pDCs from 10 healthy donors and 14 SSc patients were analysed. pDCs from anti-centromere antibody-positive (ACA+) patients displayed higher mitochondrial dependence and lower glycolytic capacity than those from anti-topoisomerase I antibody- positive (ATA+) patients. Furthermore, cells from both ACA+patients and limited cutaneous SSc (lcSSc) patients showed a stronger response towards TLR9 activation than cells from ATA+, anti-RNA polymerase III antibody-positive (ARA+) or diffuse cutaneous SSc (dcSSc) patients.ConclusionsOur results show that pDCs from ACA+patients rely more on oxidative phosphorylation (OXPHOS) and are more responsive to external stimuli, suggesting that pDCs from ATA+patients may be more activated or exhausted. These findings point for the possible contribution of pDC metabolism to SSc clinical course, unveiling new potential targets for therapeutic approaches in SSc.
Broadscale reconnaissance of coral reefs from citizen science and deep learning
Authors: Lawson Christopher L. , Chartrand Kathryn M. , Roelfsema Chris M. , Kolluru Aruna , Mumby Peter J. 
Published: December 2024

AbstractCoral reef managers require various forms of data. While monitoring is typically the preserve of scientists, larger scale reconnaissance data that can be used to inform spatial decisions does not usually require such precise measurement. There is an increasing need to collect such broadscale, up-to-date environmental data at massive scale to prioritise limited conservation resources in the face of global disturbances. Citizen science combined with novel technology presents an opportunity to achieve data collection at the required scale, but the accuracy and feasibility of new tools must be assessed. Here we show that a citizen science program that collects seascape images and analyses them using a combination of deep learning and online citizen scientists can produce accurate benthic cover estimates of key coral groups. The deep learning and citizen scientist analysis methods had different but complementary strengths depending on coral category. When the best performing analysis method was used for each category in all images, mean estimates from 8086 images of percent benthic cover of branchingAcropora, platingAcropora, and massive-form coral were ∼99% accurate compared to expert assessment of the same images, and >95% accurate at all coral cover ranges tested. The effort to achieve 95% accuracy at a site – our ecologically relevant target based on the accuracy of other tools – was attainable based on citizen scientist involvement in pilot years of the program, with 18-80 images needed depending on coral type and reef state. Power analyses showed that sampling up to 114 images per site was needed to detect a 10% absolute difference in coral cover per category (power = 0.8), accounting for natural heterogeneity. However, the benthic cover of ‘all other coral groups’ as a single category could only be estimated with 95% accuracy at 60% of survey sites and for images with 10-30% coral cover. Disaggregating this ‘other coral’ group into more distinct coral categories may improve accuracy. Overall, citizen science can provide an accuracy that is acceptable for many end-users for select coral morphologies. Such a combination of emerging technology and citizen science presents an attainable tool for collecting inexpensive, widespread reconnaissance data of coral reefs that can complement higher resolution survey programs or be an accessible tool for resource-poor locations.
Long-term high temperatures affect seed maturation and seed coat integrity inBrassica napus
Authors: Prabhullachandran Unnikannan , Urbánková Ivana , Medaglia-Mata Alejandro , Creff Audrey , Voxeur Aline , Petřík Ivan , Pěnčík Aleš , Novák Ondřej , Landrein Benoit , Hejátko Jan , Robert Hélène S. 
Published: December 2024

SUMMARYTemperatures above the optimum growth temperature affect seed development, producing seeds with ruptured seed coats. This phenotype is associated with accelerated embryo development. However, the molecular mechanism underlying this effect remains unclear.To investigate the occurrence of temperature-induced seed coat rupture, we combined detailed phenotyping approaches of oilseed rape seeds with transcriptomics, histology, immunolabelling, hormone and cell wall profiling.Our data suggest that high temperatures accelerate embryo growth, resulting in the formation of larger embryos but not larger seeds. The formation of large embryos increased the mechanical pressure exerted by the embryo on the seed coat cells, reducing their thickness. The seed coat began to mature prematurely with the accumulation of demethylesterified pectin, possibly making the cell wall stiffer. Application of abscisic acid, a hormone involved in seed dormancy, did not rescue the seed coat rupture phenotype. Hormonal and transcriptional profiling indicated that the embryo did not enter dormancy.Prolonged high temperatures during seed development accelerated embryo growth by stimulating cell division, while the seed coat, which depends on cell elongation, could not withstand the tension exerted by the embryo, started seed maturation and eventually ruptured.
HIFα isoform specific activities drive cell-type specificity ofVHL-associated oncogenesis
Authors: Lima Joanna D.C.C. , Hooker Madeleine , Li Ran , Barros Ayslan B. , Masson Norma , Pugh Christopher W. , Mole David R. , Adam Julie , Ratcliffe Peter J. , Kurlekar Samvid 
Published: December 2024

AbstractCancers arising from dysregulation of generally operative signaling pathways are often tissue specific, but the mechanisms underlying this paradox are poorly understood. Based on striking cell-type specificity, we postulated that these mechanisms must operate early in cancer development and set out to study them in a model of von Hippel Lindau (VHL) disease. Biallelic mutation of the VHL ubiquitin ligase leads to constitutive activation of hypoxia inducible factors HIF1A and HIF2A and is generally a truncal event in clear cell renal carcinoma. We used an oncogenic tagging strategy in whichVHL-mutant cells are marked by tdTomato, enabling their observation, retrieval, and analysis early afterVHL-inactivation. Our findings reveal markedly different consequences of HIF1A and HIF2A activation, but that both contribute to renal cell-type specific consequences ofVHL-inactivation in the kidney. Early involvement of HIF2A in promoting proliferation within proximal tubular epithelium supports therapeutic targeting of HIF2A early in VHL disease.
BECLIN-1 is Essential for the Maintenance of Gastrointestinal Epithelial Integrity by Regulating Endocytic Trafficking, F-actin Organization and Lysosomal Function
Authors: Juliani Juliani , Tran Sharon , Harris Tiffany J. , De Cruz Peter , Ellis Sarah L. , Gleeson Paul A. , Mariadason John M. , Duszyc Kinga , Yap Alpha S. , Lee Erinna F. , Fairlie Walter D. 
Published: December 2024

ABSTRACTDisrupted intestinal homeostasis and barrier function are key contributors to the development of various diseases, including inflammatory bowel disease (IBD). BECLIN-1, a core component of two class III phosphatidylinositol 3-kinase (PtdIns3K) complexes, has a dual role in autophagy and endocytic trafficking. Emerging evidence suggests it is involved in maintaining intestinal integrity which involves its endocytic trafficking function. To gain insights into the fatal gastrointestinal (GI) phenotype observed in BECLIN-1 knockout adult mice, organoids derived from these animals were used to investigate the role of BECLIN-1 in GI epithelial function. BECLIN-1 deletion led to disrupted localization of CADHERIN-1/E-CADHERIN to adherens junctions (AJs) and OCCLUDIN to tight junctions (TJs), resulting in the mislocalization of these critical barrier proteins. Lysosomal dysfunction was also observed, characterized by impaired cargo degradation. In addition, the filamentous actin (F-actin) cytoskeleton became disorganized though this was not associated with changes in the interaction between F-actin and CATENIN BETA-1/BETA-CATENIN nor in alterations in BETA-CATENIN localization, though BETA-CATENIN levels were reduced. These effects were all less pronounced or absent in organoids lacking the autophagy-only regulator ATG7 (autophagy related 7), further emphasizing the involvement of BECLIN-1’s protein trafficking role in the maintenance of gut homeostasis and barrier function. These findings provide new insights into processes involved in epithelial dysfunction, deepening our understanding of mechanisms underlying intestinal disease.
IKZF2-ERBB4 gene fusion leads toERBB4overexpression in Anal Squamous Cell Carcinoma but with no benefit for ERBB4 inhibition
Authors: Sophie Richon , Anne Schnitzler , Julien Lazartigues , Adrien Briaux , Sophie Vacher , Botty Rania El , Elsy El Alam , Pascale Mariani , Cindy Neuzillet , Astrid Lièvre , Wulfran Cacheux , Ivan Bièche , Virginie Dangles-Marie 
Published: December 2024

AbstractAnal squamous cell carcinoma (ASCC) is a rare tumour, but with increasing incidence for local and metastatic tumours. Current therapy is based on chemoradiotherapy, associated with immunotherapy in advanced stages, with frequent side effects, poor results in advanced stages and recurrence. New therapeutics, including targeted therapies, are then needed. In this context, we identified here aIKZF2-ERBB4gene fusion in a patient ASCC tumour, leading to overexpressed mRNA encoding a functional ERBB4 protein. This gene fusion has been already reported in other tumour types but not yet investigated as therapeutical target. The matched patient tumour-derived xenograft displays the same gene fusion and mRNA overexpression. It provided biological material for anti-ERBB4 testing in different cell models (in vivoxenograft,in vitrocell cultures). We used afatinib and lapatinib, 2 chemical pan-ERBB inhibitors approved in clinics, with anti-ERBB4 properties. ERBB4 inhibition did not lead to tumour growth inhibition although afatinib and lapatinib dramatically decreased ERBB4 phosphorylation with impact on downstream signalling MAPK/ERK but not PI3K/AKT pathways. Likewise, specificERBB4knock-outing did not affect tumour cell proliferation. These ‘negative’ results must be put in line with reported potential crosstalk between PI3K/AKT and MAPK/ERK pathways in therapeutic resistance.
Proximity to Explosive Synchronization Determines Network Collapse and Recovery Trajectories in Neural and Economic Crises
Authors: Lee UnCheol , Kim Hyoungkyu , Kim Minkyung , Oh Gabjin , Park Ayoung , Joo Pangyu , Pal Dinesh , Tracey Irene , Warnaby Catherine E. , Sleigh Jamie , Mashour George A. 
Published: December 2024

ABSTRACTWhen complex systems move away from criticality—a balance between order and chaos—they are no longer optimized. Furthermore, when criticality is lost too quickly, or recovery is delayed, system damage can result. However, the mechanism for these abnormally fast or slow critical transitions remains unknown. Here, we show that the proximity of a complex network to explosive synchronization (ES), a first-order phase transition, determines the trajectories of criticality loss and recovery after perturbations. Our computational models revealed characteristic dynamics based on network proximity to ES, enabling us to infer network phase transition types from empirical data and predict criticality transition patterns. We validated our predictions using empirical data from the human brain under anesthesia and the stock market during an economic crisis, demonstrating that early and prolonged recoveries can be systematically predicted. This study has implications for designing resilient networks that withstand perturbations and recover quickly.
The DNA Mismatch repair protein, MSH6 is a novel regulator of PD-L1 expression
Authors: Brooksbank Kirsten , Smith Charlotte , Maniati Eleni , Gibson Amy , Tse Wai Yiu , Hall Amy Kate , Wang Jun , Sharp Tyson V , Martin Sarah A 
Published: December 2024

ABSTRACTImmune checkpoint inhibitors (ICIs) are extremely effective in a subgroup of mismatch repair-deficient (MMRd) cancers, but ∼50% remain resistant to treatment. We have shown for the first time that this may be due to the differential regulation of factors linked to response to ICIs upon loss of the different MMR genes. Here, we show that increased PD-L1 expression is observed upon loss of the MMR genes MLH1, MSH2 and PMS2. However, this is not true upon loss of MSH6. Here, we show that this is due to a novel role for MSH6 as a direct regulator of PD-L1 transcription, dependent on recruitment by the histone trimethyltransferase SETD2. Next-generation sequencing of MLH1 and MSH6 knockout (KO) cells revealed that MSH6 KO cells have significantly lower microsatellite instability in comparison to MLH1 KO cells, despite MSH6 KO cells having a higher mutational burden. These findings emphasise the need for gene-specific stratification in the MMRd cohort.
Sex-dependent latent chilling injury changes estimates of thermal tolerance in a model insect
Authors: El-Saadi Mahmoud I. , Allen Mitchell C. , MacMillan Heath A. 
Published: December 2024

AbstractThermal tolerance limits are closely associated with insect distribution. Thermal injury sets limits to mobility or survival after removal from the stress, and these limits are frequently integrated into models describing or predicting climate suitability for species of interest. Cold stress severity, sex, and prior thermal acclimation status can all influence lower thermal limits. There is a growing understanding of chilling injuries initially manifest, but we poorly understand repair or further injury that may happen after rewarming. We exposed male and femaleDrosophila melanogasterto an acute or chronic cold stress before assessing their mobility over a 24 h period. Females progressively worsened under both conditions, but male mobility neither worsened nor improved. Female mobility declined slower in flies recovering at cooler temperatures, and cold acclimation significantly mitigated latent injury in females following the same degree of initial injury, regardless of recovery temperature. We conclude that latent chilling injury can be sex-specific, occurs independently from mechanisms driving tissue damage in the cold, is temperature-dependent, and is mitigated by prior thermal acclimation. We argue that latent chilling injury and the factors that influence it should be more carefully considered in estimating tolerance limits.