bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological determinants and evidence-based behavior change interventions in adherence to therapy for familial hypercholesterolemia
Authors: Hagger Martin S. , Hamilton Kyra 
Published: November 2024

Purpose of review
Patients with familial hypercholesterolemia have an elevated risk of premature atherosclerotic cardiovascular disease. Risks can be minimized through pharmacological and ‘lifestyle’ behavioral (low fat diet, physical activity) therapies, although therapeutic adherence is sub-optimal. Behavioral interventions to promote familial hypercholesterolemia therapy adherence should be informed by theory-based psychological determinants for maximal efficacy. The current review summarizes research on determinants of familial hypercholesterolemia therapy adherence and behavior change interventions, identifies limitations of the extant research, and sets future research agenda.

Recent findings
A recent meta-analysis identified attitudes, subjective norms, self-efficacy, and risk perceptions as key determinants of familial hypercholesterolemia therapy adherence intentions, with intentions identified as a key correlate of concurrent behavior. Studies have specified techniques targeting key theory-based determinants that may be efficacious in interventions. Research is limited by overuse of cross-sectional correlational study designs, use of self-report behavioral measures, few theory-based intervention tests, and limited consideration of nonconscious processes and effects of socio-structural variables.

Summary
Researchers should adopt study designs permitting better directional and causal inferences in determinant effects, provide tests of interventions targeting determinants and their mechanisms of action, consider determinants representing nonconscious processes (habits, implicit attitudes), and test determinants as mediators of socio-structural variables on familial hypercholesterolemia therapy adherence.
Local and systemic biodistribution of a small-molecule radiopharmaceutical probe after transcatheter embolization and intra-arterial delivery in a porcine orthotopic renal tumor model
Authors: Rice Samuel L. , Muñoz Fernando Gómez , Benjamin Jamaal L. , Alnablsi Mhd Wisam , Osborne Joseph R. , Beets-Tan Regina 
Published: November 2024

Background
Small-molecule biomacromolecules target tumor-specific antigens. They are employed as theranostic agents for imaging and treatment. Intravenous small-molecule radioligands exhibit rapid tumor uptake and excretion. However, systemic administration for peptide receptor radionuclide therapy still lacks the therapeutic index to completely treat solid tumors beyond palliation. We study intra-arterial delivery with tumor embolization of a small molecule as a means to deliver local intertumoral brachytherapy for curative internal ablation.

Results

18F-fluorodeoxyglucose (FDG) was used as a surrogate for a small-molecule theranostic agent in a porcine renal tumor model, this tumor model is not known to specifically express human tumor antigens, but the model demonstrates similar vascularity. Angiography and micron particle embolization of the tumor arterioles were performed in a renal tumor model. Significantly more tumor uptake (2–4×), was observed for intra-arterial administration (IA) compared to intravenous (IV) (%ID/g = 44.41 ± 2.48 vs. 23.19 ± 4.65; P = 0.0342 at 1 min and 40.8 ± 2.43 vs. 10.94 ± 0.42; P = 0.018 at 10 min). At later time points, up to 120 min after injection, washout of the tracer from the tumor was observed, but the percent injected dose per gram remained elevated, with three times higher concentration of FDG with IA administration compared with IV, but the difference was not statistically significant. A trend towards diminished systemic percent injected dose per gram measured in the blood, liver, kidney, spleen, muscle, and urine for study IA compared to IV administration is observed.

Conclusion
Combining IA administration of a small-molecule radioprobe surrogate with embolization of the tumor’s arterioles extending the time for interaction of the drug within the tumor by diminishing flow out of the tumor via the efferent capillaries significantly increases the first-pass uptake of the small-molecule drug within a tumor and decreases the radiation to normal nontumor tissues when compared with IV injection of the same drug. The minimally invasive drug delivery allows tumor-specific theranostic treatment of renal tumors with a brachytherapy-absorbed dose of radiation that is potentially curative.
Updates on therapeutic endoscopic ultrasound
Authors: Wahba George , Lee Jeffrey H. 
Published: November 2024

Purpose of review
Multiple endoscopic ultrasound (EUS) guided therapeutic interventions have been developed for the management of benign and malignant pancreaticobiliary and gastrointestinal luminal pathology. Recent high-quality evidence is increasingly validating these interventions and positioning them within evidence-based therapeutic algorithms.

Recent findings
Here we review therapeutic EUS-guided interventions including pancreatic fluid collection drainage, gastroenterostomy, biliary drainage, pancreatic duct drainage and gallbladder drainage. The most up-to-date high-quality evidence supporting these interventions is presented including comparative data with other conventional treatment options. Newer emerging interventions such as tumor ablation are also reviewed. Current controversies and future avenues for research are discussed. The key role of EUS-guided interventions in managing pancreaticobiliary pathology in patients with a surgically altered anatomy is highlighted.

Summary
Multiple EUS therapeutic interventions have evolved from experimental or rescue options to now well established first- and second-line interventions over other endoscopic, percutaneous and surgical alternatives with the support of high-quality data. Further research is needed to better optimize patient selection and guide long term postintervention follow-up.
Modern management of distant metastases from head and neck squamous cell carcinoma
Authors: Bradley Patrick , Montenegro Claudia , Piazza Cesare 
Published: November 2024

Purpose of review
The rate of distant metastases in patients with head and neck squamous cell carcinoma (HNSCC) ranges between 4 and 26%. Their appearance marks a critical stage in disease progression, significantly reducing survival rates. Treatment options require a multidisciplinary approach and differ based on the number and extension of distant metastases. The aim of this narrative review is to provide a comprehensive and updated overview of the current state of the art in management of such a clinical scenario.

Recent findings
Accurate detection and staging of distant metastases are essential to determine prognosis and guide therapeutic strategies. Oligometastatic condition refers to patients with only a few distant metastases (up to 5). Surgery or stereotactic body radiotherapy are the best curative treatment options for oligometastatic. However, the majority of HNSCC has a polymetastatic disease, not amenable to curative approach. Therefore, systemic therapies, including chemotherapy (CHT) or target molecular therapy and/or best supportive care, are usually reserved to these patients. Rarely, head and neck region, in particular supraclavicular cervical lymph nodes, may be a site of distant metastases from non-head and neck cancer, particularly from the genitourinary and gastrointestinal tracts.

Summary
The occurrence of distant metastases in HNSCC represents a pivotal point in the disease progression, lowering survival rates. Pattern of distant metastases has been related to survival outcomes. Patients with distant metastases from an HNSCC always require a multidisciplinary approach and an accurate selection is necessary to individualize the best treatment strategy.
Assessing the Reliability of the Bleeding Assessment Scale in Critically Ill Children (BASIC) Definition: A Prospective Cohort Study
Authors: Nellis Marianne E. , Chegondi Madhuradhar , Willems Ariane , Alqatani Mashael , McMichael Ali , Aran Adi A. , Lerner Reut Kassif , Karam Oliver ,   on behalf of the Bleeding Assessment Scale in critically Ill Children (BASIC)-Kappa Investigators, and in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: November 2024

OBJECTIVES:
To determine the reliability of the Bleeding Assessment Scale in critically Ill Children (BASIC) definition of bleeding severity in a diverse cohort of critically ill children.

DESIGN:
Prospective cohort study.

SETTING:
Eight mixed PICUs in the Netherlands, Israel, and the United States.

SUBJECTS:
Children ages 0–18 years admitted to participating PICUs from January 1, 2020, to December 31, 2022, with bleeding noted by bedside nurse.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
The bleeding events were classified as minimal, moderate, or severe, according to the BASIC definition, by two independent physicians at two different time points. Patient demographic data, laboratory values, and clinical outcomes were collected. Three hundred twenty-eight patients were enrolled. The overall inter-rater reliability was substantial (weighted kappa coefficient, 0.736; 95% CI, 0.683–0.789), and the intra-rater reliability was “almost-perfect” (weighted kappa coefficient, 0.816; 95% CI, 0.769–0.863). The platelet count (p = 0.008), prothrombin time (p = 0.004), activated partial thromboplastin time (p = 0.025), and fibrinogen levels (p = 0.035) were associated with the bleeding severity, but the international normalized ratio was not (p = 0.195). Patients were transfused blood components in response to any bleeding in 31% of cases and received hemostatic medications in 9% of cases. More severe bleeding was associated with increased 28-day mortality, longer hospital length of stay, and more days receiving inotropic support.

CONCLUSIONS:
The BASIC definition is a reliable tool for identifying and classifying bleeding in critically ill children. Implementing this definition into clinical and research practice may provide a consistent and reliable evaluation of bleeding.
Minor Head Trauma in Children Younger Than 3 Months and Clinical Predictors of Clinically Important Traumatic Brain Injuries
Authors: Vajna de Pava Marco , Samperi Martina , Bresesti Ilia , Bertù Lorenza , Plebani Anna Maria , Agosti Massimo 
Published: November 2024

Objectives
Major studies have defined clinical rules to regulate the use of computed tomography in children after head trauma. Infants younger than 3 months are considered at higher risk of brain injuries than older children and at the same time at higher risk of radiation-induced damage. Hence, it would be desirable to have clinical decision rules more adapted to this subset of patients. The objectives of this study are to compare the rate of brain injuries in children younger than 3 months or 3 to 24 months and to assess predictors of clinically important traumatic brain injuries (ciTBIs) (the ones causing death, neurosurgical intervention, long intubation, or hospitalization for 2 days or more) in the former group.

Methods
Records of children younger than 24 months evaluated in a single emergency department for minor head trauma during a 3 years period were retrospectively reviewed. The rates of brain injuries were compared in children younger or older than 3 months. Variables associated with severe lesions were assessed in younger children.

Results
The study included 744 patients, 86 (11.6%) aged 0 to 90 days and 658 (88.4%) aged 91 to 730 days. Within the young group, we found higher rates of traumatic brain injuries (14.0% vs 4.1%, P = 0.0008) and ciTBI (8.1% vs 1.5%, P = 0.002) compared with the old group. A significant correlation with ciTBI in the young group was observed for heart rate (odds ratio [OR], 12.3; 95% confidence interval [CI], 2.4–62.4), nonfrontal scalp hematoma (OR, 9.2; 95% CI, 1.8–46.1), severe mechanism (OR, 5.6; 95% CI, 1.1–27.6), presence of hematoma (OR, 6.1; 95% CI, 1.2–30.0), hematoma size >3 cm (OR, 23.8; 95% CI, 4.2–135.6), and hematoma location (OR, 9.2; 95% CI, 1.8–46.1).

Conclusions
Children younger than 3 months presenting after minor head trauma constitute a relevant population. Available clinical predictors well correlate with ciTBIs in this age group.
Large Branchial Cleft Cyst of Face and Neck
Authors: Wang Yuxin , Li Wen , Yang Liu , Chen Guo , Li Long 
Published: November 2024

Objective:
The authors present a case of a patient with a large branchial cleft cyst on the right side of the neck and face that rapidly increased after eating Angelica-stewed chicken.

Methods:
An older adult patient was admitted to West China Hospital on February 28, 2021, with a large branchial cleft cyst. Resection of the right cervical cystic tumor and partial resection of the parotid gland were performed.

Results:
After complete surgical resection of the cyst, the patient was followed up for 3 years without any recurrence in the surgical area.

Conclusions:
Angelica is a type of traditional Chinese medicine, which has the effect of promoting blood circulation to remove meridian obstruction. However, it is difficult to determine whether this case that occurred after eating Angelica-stewed chicken coincides with the sudden growth of cysts and related pathological changes.
Economic evaluation of Danhong injection for the treatment of chronic stable angina in China: A cost-effectiveness analysis
Authors: Su Pengli , Zhi Kai , Xiao Jing , Xu Huanhuan , Liu Jun , Wang Zhong , Yu Yanan , Dang Haixia 
Published: November 2024

Abstract

Objective
Danhong injection (DHI) is commonly used in China to treat chronic stable angina (CSA), demonstrating significant clinical efficacy and safety. The present study aimed to estimate the cost-effectiveness of DHI combined with standard treatment (ST) compared with ST alone in patients with CSA.

Methods
A Markov model with a 3-month cycle and a 1-year time horizon was used to assess the cost-effectiveness of DHI + ST for CSA. Health outcomes were measured as quality-adjusted life years (QALYs), and societal perspective costs were collected in China. Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed to test the robustness of results to parameter uncertainty.

Results
Analysis demonstrated DHI + ST provided 0.8190 QALYs at an average cost of $3644.24, while ST yielded 0.7884 QALYs costing $2739.54 over 1 year. The incremental analysis indicated DHI + ST dominance, with an ICER of $29,588.91 per QALY gained compared with ST. One-way sensitivity analysis confirmed the robustness of base case findings, and probabilistic sensitivity analysis suggested a 61.66% probability of DHI + ST being cost-effective over ST at a $37,663.26 per QALY threshold.

Conclusion
From a societal perspective in China, DHI + ST appears cost-effective for the treatment of CSA compared with ST alone. These findings support recommending DHI as a clinically valuable and cost-effective option in CSA treatment guidelines.
Cost-Effectiveness of Nonoperative Management vs Upfront Laparoscopic Appendectomy for Pediatric Uncomplicated Appendicitis for 1 Year
Authors: Gil Lindsay A , Asti Lindsey , Chen Huey-Fen , Saito Jacqueline M , Pattisapu Prasanth , Deans Katherine J , Minneci Peter C ,   for the Midwest Pediatric Surgery Consortium
Published: November 2024

BACKGROUND:
Nonoperative management (NOM) with antibiotics alone for pediatric uncomplicated appendicitis is accepted to be safe and effective. However, the relative cost-effectiveness of this approach compared with appendectomy remains unknown. We aimed to evaluate the cost-effectiveness of nonoperative vs operative management for pediatric uncomplicated acute appendicitis.

STUDY DESIGN:
A trial-based real-world economic evaluation from the healthcare sector perspective was performed using data collected from a multi-institutional nonrandomized controlled trial investigating NOM vs surgery. The time horizon was 1 year, with costs in 2023 US dollars. Ratio of costs-to-charges-based data for the initial hospitalization, readmissions, and unplanned emergency department visits were extracted from the Pediatric Health Information System. Utility data were derived from patient-reported disability days and health-related quality-of-life scores. Multiple scenarios and 1-way deterministic and probabilistic sensitivity analyses accounted for parameter uncertainty. Willingness-to-pay threshold was set at $100,000 per quality-adjusted life year (QALY) or disability-adjusted life year. Primary outcome measures included total and incremental mean costs, QALY, disability-adjusted life year, and incremental cost-effectiveness ratios.

RESULTS:
Of 1,068 participants, 370 (35%) selected NOM and 698 (65%) selected urgent laparoscopic appendectomy. Operative management cost an average of $9,791 per patient and yielded an average of 0.884 QALYs, whereas NOM cost an average of $8,044 per patient and yielded an average of 0.895 QALYs. NOM was both less costly and more effective in base case and scenario analyses using disability days and alternate methods of calculating uses.

CONCLUSIONS:
NOM is cost-effective compared with laparoscopic appendectomy for pediatric uncomplicated appendicitis for 1 year.
Newly found rat CD103-dendritic cells are the highly immunogenic conventional DC2 subpopulation, corresponding to the known DC subsets in mice and humans
Authors: Sawanobori Yasushi , Ogawa Tadayuki , Ueta Hisashi , Kitazawa Yusuke , Tokuda Nobuko 
Published: November 2024

AbstractDendritic cells (DCs), the primary antigen-presenting cells, have traditionally been identified by CD103 molecules in rats, whereas mouse and human DCs are identified by CD11c molecules. However, this history does not preclude the existence of CD103-DCs in rats. To explore this possibility, we examined MHCII+cells in rat spleen and thymus, identifying a novel population of CD103-MHCII+CD45R-CD172a+cells. These cells are negative for CD103 and B cell marker CD45R, but positive for the type-2 conventional DC (cDC2) marker CD172a. Transcriptomic analyses revealed that they represent a subpopulation of cDC2. Additionally, gene set enrichment analysis predicted enhanced immunogenic activities for this novel population compared to known rat cDC2s. Mixed leukocyte reaction assays confirmed that the rat CD103-cDC2s induce T cell proliferation more effectively than other DC subsets, suggesting enhanced immunogenic potential. In reaggregated thymic organ culture assays, both the rat CD103-and CD103+cDC2 subsets suppressed the total number of generated thymocytes and skewed the differentiation toward CD8 single-positive cells. Comparisons with previously published single-cell RNA-sequencing datasets showed that the rat CD103-cDC2 subset shares markers and GO terms of known mouse and human cDC2 subpopulations: cDC2a, cDC2b, inf-cDC2, and moDC. In contrast, the classic rat CD103+cDC2 subset expresses only cDC2a markers. These findings provide new insights into DC subpopulations, particularly in species other than mice and humans, where much remains to be uncovered.
ecPath detects ecDNA in tumors from histopathology images
Authors: Choudhury Mudra , Liu Lihe , Yadav Anamika , Chapman Owen , Ahmadi Zahra , Younis Raneen , Sharma Chinmay , Goel Navansh , Sridhar Sunita , Kenkre Rishaan , Dutta Aditi , Wang Shanqing , Shulman Eldad , Dhruba Saugato Rahman , Hoang Danh-Tai , Tharp Kevin , Paul Megan , Malicki Denise , Yip Kevin , Ruppin Eytan , Chavez Lukas , Sinha Sanju 
Published: November 2024

ABSTRACTCircular extrachromosomal DNA (ecDNA) can drive tumor initiation, progression and resistance in some of the most aggressive cancers and is emerging as a promising anti-cancer target. However, detection currently requires costly whole-genome sequencing (WGS) or labor-intensive cytogenetic or FISH imaging, limiting its application in routine clinical diagnosis. To overcome this, we developedecPath(ecDNA from histopathology), a computational method for predicting ecDNA status from routinely available hematoxylin and eosin (H&E) images. ecPath implements a deep-learning method we call transcriptomics-guided learning, which utilizes both transcriptomics and H&E images during the training phase to enable successful ecDNA prediction from H&E images alone, a task not achievable with models trained on H&E images only. It is trained on more than 6,000 tumor whole-slide images from the TCGA cohort with the best performance in predicting ecDNA status in brain and stomach tumors (average AUC=0.78). ecPath revealed that ecDNA-positive tumors are enriched with pleomorphic, larger and high-density nuclei. Testing in an independent cohort, ecPath predicted ecDNA status of 985 pediatric brain tumor patients with an AUC of 0.72. Finally, we applied ecPath to identify ecDNA-positive tumors in the TCGA cohort for which no WGS data were available. Like WGS-based ecDNA-positive labels, the predicted ecDNA-positive status also identify poor prognoses for low grade glioma patients. These results demonstrate that ecPath enables the detection of ecDNA from routinely available H&E imaging alone and help nominate aggressive tumors with ecDNA to study and target it.
Tissue clocks derived from histological signatures of biological aging enable tissue-specific aging predictions from blood
Authors: Abila Ernesto , Buljan Iva , Zheng Yimin , Veres Tamas , Weng Zhilong , Nackenhorst Maja , Hulla Wolfgang , Tolkach Yuri , Wöhrer Adelheid , Rendeiro André F. 
Published: November 2024

AbstractAging, the predominant risk factor for numerous diseases, manifests in various forms across the structure and architecture of tissues of the human body, offering the opportunity to quantify and interpret tissue-specific aging. To address this, we present a comprehensive assessment of tissue changes occurring during human aging, utilizing a vast array of whole slide histopathological images from the Genotype-Tissue Expression Project (GTEx). We analyzed 25,712 images from 40 distinct tissue types across 983 individuals, applying deep learning to quantify the nuanced morphological changes that tissues undergo with age.We developed ‘tissue clocks’—predictors of biological age based on tissue images—which achieved a mean prediction error of 4.9 years and were associated with telomere attrition, the incidence of subclinical pathologies, and comorbidities. In a systematic assessment of biological age rates across organs, we identified pervasive non-uniform rates of aging across the human lifespan, with some organs exhibiting earlier changes (20–40 years old) and others showing bimodal patterns of age-related changes. We also uncovered several associations between demographic, lifestyle, and medical history factors and tissue-specific acceleration or deceleration of biological age, highlighting potential modifiable risk factors that influenced the aging process at the tissue level. Finally, by combining paired histological images and gene expression data, we developed a strategy to predict tissue-specific age gaps from blood samples. This approach was validated in external cohorts of both healthy individuals and those with chronic diseases, revealing the organs most differentially affected by aging in disease contexts.This work offers a new perspective on the aging process by positioning tissue structure as an integrator of cellular and molecular changes that reflect the physiological state of organs. These findings underscore the value of histopathological imaging as a tool for understanding human aging and provide a foundation for the exploration of tissue-specific aging processes in age-associated diseases.