bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antileukemia efficacy of the dual BCL2/BCL-XL inhibitor AZD0466 in acute lymphoblastic leukemia preclinical models
Authors: Kannan Sankaranarayanan , Li Yizhen , Baran Natalia , Yang Xu , Ghotbaldini Sanaz , Zhang Tatarata Qi , Yoshimura Satoshi , Li Zhenhua , Hsiao YuChih , Balachander Srividya , Andersen Courtney L. , Cidado Justin , Yu Jiyang , Jain Nitin , Yang Jun J. , Konopleva Marina 
Published: November 2024

Abstract
The upregulation of B-cell lymphoma 2 (BCL2) and B-cell lymphoma–extra large (BCL-XL), 2 proteins in the BCL2 family of proteins, leads to a disproportional expression of prodeath and prosurvival proteins in favor of leukemia survival, tumorigenesis, and chemoresistance. In different subsets of acute lymphoblastic leukemia (ALL), the proportion of these 2 proteins varies, and their potential as therapeutic targets needs detailed characterization. Here, we investigated BCL2 and BCL-XL, the genes that encode BCL2 and BCL-XL, and their expression differences between B-cell acute lymphoblastic leukemia (B-ALL) and T-cell ALL (T-ALL). We also evaluated the therapeutic potential of targeting these proteins with AZD0466, a novel drug-dendrimer conjugate of the BCL2/BCL-XL inhibitor AZD4320, and with BCL2 inhibitor venetoclax (ABT-199). Gene expression and activity analyses supported by the protein expression patterns in ALL cell lines and primary samples demonstrated increased levels of BCL2 expression in B-ALL, with high sensitivity to venetoclax or AZD4320. In contrast, strong BCL-XL expression and sensitivity to dual BCL2/BCL-XL inhibition was observed specifically in T-ALL samples. This observation was confirmed by BH3 profiling, demonstrating BCL2/BCL-XL codependence in T-ALL and BCL2 dependence in B-ALL. In a mouse model of T-ALL, AZD0466 but not venetoclax reduced leukemic burden and prolonged survival without significant toxicities. Our findings therefore suggest that the novel dual BCL2/BCL-XL inhibitor AZD0466 outperforms single BCL2 inhibition by venetoclax in T-ALL. These findings facilitate the translation of dual BCL2/BCL-XL inhibitors into ALL clinical trials, either alone or in combination with standard-of-care chemotherapy and immune therapies.
CHIP away at the marrow-clot connection: inflammation, clonal hematopoiesis, and thromboembolic disease
Authors: Todorovski Angela , Wang Tzu-Fei , Carrier Marc , Xu Yan 
Published: November 2024

Abstract
Both the incidence and prognosis of arterial atherothrombosis and venous thromboembolism are strongly correlated with increasing age. Over the past decade, clonal hematopoiesis of indeterminate potential (CHIP) has been identified as a novel biomarker for cardiovascular disease. Driven by somatic mutations in the hematopoietic system, the epidemiology of CHIP is highly age dependent: among individuals aged ≥70 years in the general population, estimated prevalence of CHIP exceeds 10%. Several additional risk factors for CHIP have emerged in recent years, including smoking, receipt of anticancer therapy, and germ line predispositions. CHIP carriers consistently have higher risk of incident arterial atherothrombosis, even after accounting for traditional cardiovascular risk factors. However, the magnitude of this association varies across studies. In addition, individuals with established cardiovascular disease and CHIP have higher risks of recurrence and all-cause mortality than their non-CHIP counterparts. An association between CHIP carriership and incident venous thromboembolism has recently been made, although additional studies are needed to confirm this finding. No approved therapy exists to modify the cardiovascular risk among CHIP carriers. However, canakinumab showed promise in a post-hoc analyses of patients with TET2-mutated CHIP, and other anti-inflammasome agents are actively under development or evaluation. In this review, we provide an overview of CHIP as a mediator of thromboembolic diseases and discuss emerging therapeutics aimed at intervening on this thrombo-inflammatory nexus.
Pre-market health systems barriers and enablers to infectious diseases point-of-care diagnostics in Australia: qualitative interviews with key informants
Authors: Lafferty Lise , Applegate Tanya L. , Lewis Sophie , Drysdale Kerryn , Monaghan Robert , Kelly-Hanku Angela , Guy Rebecca , Treloar Carla 
Published: November 2024

Abstract
Background
There exist multiple regulatory layers for point-of-care (POC) testing to be implemented within Australia. This qualitative analysis sought to understand the pre-market barriers and facilitators to scale-up infectious diseases POC testing in primary care settings at the national level.

Methods
Key informant interviews were undertaken with people (n = 30) working in high- level positions relevant to infectious diseases POC testing in Australia. Participants were recruited from federal and state health departments, industry, and nongovernment national peak bodies. The Unitaid scalability framework informed this analysis to understand barriers and enablers to creating access conditions and establishing country readiness for market access of POC tests.

Results
Participants identified regulatory frameworks as significant barriers to market access. National strategies and advocacy were viewed as potential enablers to establishing country readiness. It was recommended that the national system for universal health care should fund infectious disease POC tests to ensure financial sustainability, though the existing pathology infrastructure was regarded as a likely inhibitor.

Conclusions
Current regulatory frameworks inhibit market access for infectious disease POC testing devices for use in the primary care setting. National advocacy is urgently needed to gain government support and align national policies with regulatory frameworks.
Associations of multiple lifestyle behaviors with allergic disease symptoms and sensitization in 9–11-year-old Finnish children
Authors: Peltonen Henna , Kukkonen Anna Kaarina , Korkalo Liisa , Fogelholm Mikael , Mäkelä Mika J. , Erkkola Maijaliisa , Vepsäläinen Henna 
Published: November 2024

Abstract
Background
The increase in allergic diseases in children has coincided with the westernization of lifestyles. Although clustering of modifiable lifestyles has been frequently reported in children, there is limited research on how lifestyle factors collectively contribute to allergic conditions. Our aim was to identify lifestyle clusters among Finnish school-aged children and explore their associations with the prevalence of allergic disease symptoms and sensitization.

Methods
We used cross-sectional data from the international ISCOLE survey and its Finnish ancillary allergy study conducted in 2012–2013. We studied 148–461 children aged 9–11 years living in the metropolitan area of Finland. Parents completed a questionnaire on their child’s allergic disease symptoms, and specific IgE responses from blood samples were analyzed to determine allergic sensitization. Lifestyle factors considered in clustering were moderate-to-vigorous-physical activity (MVPA) and nighttime sleep recorded by accelerometers, screen time inquired via a questionnaire, and healthy and unhealthy dietary patterns from food frequency questionnaire data. Lifestyle clusters were identified using K-means cluster analysis, and their associations with allergic disease symptoms and sensitization were explored using logistic regression models.

Results
Two distinct and stable clusters were identified: ‘healthier lifestyle & lower MVPA’ and ‘unhealthier lifestyle & higher MVPA’. After adjustments, children in the ‘unhealthier lifestyle & higher MVPA’ cluster did not show significantly different odds for symptoms of asthma (OR: 0.80, 95% CI: 0.46–1.37), allergic rhinitis (OR: 1.32, 95% CI: 0.77–2.24), or eczema (OR: 0.89, 95% CI: 0.43–1.77) as compared to those in the ‘healthier lifestyle & lower MVPA’ cluster. Similar results were observed for sensitization to ≥ 1 inhaled allergen (OR: 1.27, 95% CI: 0.53–3.10) and sensitization to ≥ 1 food allergen (OR: 0.91, 95% CI: 0.30–2.60).

Conclusions
The results suggest that modifiable lifestyle factors may not play a significant role in allergic conditions within the examined age group. Lifestyle behaviors established in earlier childhood may serve as more credible predictors of allergic outcomes.
Periodontitis and dental quality of life predict long-term survival in head and neck cancer
Authors: Farran Mirna , Neppelberg Evelyn , Løes Sigbjørn , Aarstad Anne K. H. , Moe Svein Erik , Aarstad Hans Jørgen 
Published: November 2024

Abstract
Background
Our aim was to investigate oral health in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients in relation to long-term survival. We assessed whether the level of alveolar bone loss due to periodontitis at diagnosis, measured from orthopantomogram (OPG), and reported dental health-related quality of life (HRQoL) scores obtained at diagnosis contain prognostic information for HNSCC patients.

Methods
A total of 79 patients from a consecutive cohort of 106 diagnosed with HNSCC between November 2002 and June 2005 were included. All patients reported dental HRQoL, OPG-determined alveolar bone loss were measured in 79 patients at diagnosis. Reduced alveolar bone loss (≥ 4 mm) from cement-enamel junction on at least two molars or premolars registered both horizontally and vertically served as indicator of periodontal disease.

Results
With alveolar bone loss, we determined increased mortality by univariate analysis (RR = 2.28, CI: 1.22–4.28, p = 0.01) and a strong trend by multivariate analyses adjusted for standard clinical information (RR = 1.95, CI: 0.98–3.87, p = 0.056). Reported lowered dental HRQoL scores predicted long-term survival in both univariate (RR = 3.58, CI: 1.99–6.45, p < 0.001) and multivariate adjusted for standard clinical information (RR = 2.17, CI: 1.17–4.01, p = 0.014). When analyzed with Cox regression, including alveolar bone loss and dental HRQoL, both factors, adjusted by clinical variables, were significant predictors of long-term survival: dental HRQoL (p = 0.007) and present alveolar bone loss (p = 0.034). Non-HNSCC disease-specific long-term survival predicted was also predicted when alveolar bone loss and dental HRQoL were analyzed simultaneously and adjusted for standard clinical information.

Conclusions
The degree of alveolar bone loss, as determined by OPG, and dental HRQoL both obtained at the time of HNSCC diagnosis, predicted long-term survival. When analyzed simultaneously, both factors remained significant in both univariate and multivariate analyses, adjusted by pertinent clinical variables, highlighting their unique prognostic value.
Considerations in the search for epistasis
Authors: Balvert Marleen , Cooper-Knock Johnathan , Stamp Julian , Byrne Ross P. , Mourragui Soufiane , van Gils Juami , Benonisdottir Stefania , Schlüter Johannes , Kenna Kevin , Abeln Sanne , Iacoangeli Alfredo , Daub Joséphine T. , Browning Brian L. , Taş Gizem , Hu Jiajing , Wang Yan , Alhathli Elham , Harvey Calum , Pianesi Luna , Schulte Sara C. , González-Domínguez Jorge , Garrisson Erik ,   Lorentz workshop on epistasis, Al-Chalabi Ammar , Cartes Jorge Avila , Baaijens Jasmijn , von Berg Joanna , Bolognini Davide , Bonizzoni Paola , Guarracino Andrea , Koyuturk Mehmet , Markowska Magda , Dandinasivara Raghuram , van Bemmelen Jasper , Vorbrugg Sebastian , Zhang Sai , Pasanuic Bogdan , Snyder Michael P. , Schönhuth Alexander , Sng Letitia M. F. , Twine Natalie A. 
Published: November 2024

Abstract
Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability. We identify key challenges and propose that future works need to leverage idealized systems, known biology and even previously identified epistatic interactions, in order to guide the search for new interactions.
Decoding VExUS: a practical guide for excelling in point-of-care ultrasound assessment of venous congestion
Authors: Assavapokee Taweevat , Rola Philippe , Assavapokee Nicha , Koratala Abhilash 
Published: November 2024

Abstract
Venous congestion, often associated with elevated right atrial pressure presents a clinical challenge due to its varied manifestations and potential organ damage. Recognizing the manifestations of venous congestion through bedside physical examination or laboratory tests can be challenging. Point-of-care ultrasound (POCUS) is emerging as a valuable bedside tool for assessing venous congestion, with the Venous Excess Ultrasound (VExUS) technique gaining prominence. VExUS facilitates non-invasive quantification of venous congestion, relying on measurements of the inferior vena cava (IVC) size and Doppler assessments of the hepatic vein (HV), portal vein (PV), and intrarenal vein, thereby providing real-time insights into hemodynamic status and guiding therapeutic interventions. The grading system outlined in VExUS aids in stratifying the severity of congestion. However, achieving proficiency in VExUS requires a comprehensive understanding of Doppler techniques and their clinical applications. This review article provides practical guidance on performing VExUS, encompassing equipment requirements, preparation, machine settings, and examination techniques for assessing the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV), and intrarenal vein. Potential pitfalls and troubleshooting strategies are discussed to ensure accurate interpretation of Doppler waveforms.
Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy
Authors: Cao Dan-Feng , Zhou Xin-Yu , Guo Qian , Xiang Ming-Yao , Bao Mei-Hua , He Bin-Sheng , Mao Xiao-Yuan 
Published: November 2024

AbstractEpilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators responsible for gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There are also substantial evidences supporting that aberrant expressions and/activities of HDAC isoforms are reported in epilepsy and HDAC inhibitors (HDACi) have been successfully utilized for therapeutic purposes in this condition. However, the specific mechanisms underlying the role of HDACs in epileptic progression have not been fully understood. Herein, we reviewed the basic information of HDACs, summarized the recent findings associated with the roles of diverse HDAC subunits in epilepsy and discussed the potential regulatory mechanisms by which HDACs affected the development of epilepsy. Additionally, we also provided a brief discussion on the potential of HDACs as promising therapeutic targets for epilepsy treatment, serving as a valuable reference for basic study and clinical translation in epilepsy field.
Thangka image captioning model with Salient Attention and Local Interaction Aggregator
Authors: Hu Wenjin , Zhang Fujun , Zhao Yinqiu 
Published: November 2024

Abstract
Thangka image captioning aims to automatically generate accurate and complete sentences that describe the main content of Thangka images. However, existing methods fall short in capturing the features of the core deity regions and the surrounding background details of Thangka images, and they significantly lack an understanding of local actions and interactions within the images. To address these issues, this paper proposes a Thangka image captioning model based on Salient Attention and Local Interaction Aggregator (SALIA). The model is designed with a Dual-Branch Salient Attention Module (DBSA) to accurately capture the expressions, decorations of the deity, and descriptive background elements, and it introduces a Local Interaction Aggregator (LIA) to achieve detailed analysis of the characters’ actions, facial expressions, and the complex interactions with surrounding elements in Thangka images. Experimental results show that SALIA outperforms other state-of-the-art methods in both qualitative and quantitative evaluations of Thangka image captioning, achieving BLEU4: 94.0%, ROUGE_L: 95.0%, and CIDEr: 909.8% on the D-Thangka dataset, and BLEU4: 22.2% and ROUGE_L: 47.2% on the Flickr8k dataset.
Small bowel intussusception due to adenocarcinoma of ectopic pancreas in the jejunum: a case report
Authors: Yamamoto Kota , Ishimori Takahiro , Okada Taiki , Sasaki Takeshi , Mikajiri Yumi , Terashima Takahiro , Kawamoto Shunji 
Published: November 2024

Abstract
Introduction
We encountered a case of adenocarcinoma of the ectopic pancreas, causing intussusception.

Case presentation
A 76-year-old man presented with complaints of abdominal distention and vomiting to the emergency department in March 2022. Computed tomography showed that the small bowel piled up approximately 20 cm from the ligament of the traits. Endoscopic repair was challenging; therefore, laparoscopic repair and partial resection of the small bowel were performed. The specimen showed a mass in the small bowel arising from an ectopic pancreas that had caused accumulation. Pathological examination revealed ectopic pancreatic cancer. Two years postoperatively, no apparent recurrence has been observed. We report a relatively rare case of a cancerous ectopic jejunal pancreas causing a mass, with a discussion in the literature.

Conclusions
Detection typically requires surgery due to advanced-stage intestinal obstruction or accumulation, as observed in the present case. However, preoperative diagnosis and early detection of ectopic pancreatic cancer are challenging. The disease progresses similarly to pancreatic cancer, highlighting the need for early detection methods. Additionally, accumulating more case reports is essential for establishing an effective treatment strategy.
Image biomarkers and explainable AI: handcrafted features versus deep learned features
Authors: Rundo Leonardo , Militello Carmelo 
Published: November 2024

Abstract
Feature extraction and selection from medical data are the basis of radiomics and image biomarker discovery for various architectures, including convolutional neural networks (CNNs). We herein describe the typical radiomics steps and the components of a CNN for both deep feature extraction and end-to-end approaches. We discuss the curse of dimensionality, along with dimensionality reduction techniques. Despite the outstanding performance of deep learning (DL) approaches, the use of handcrafted features instead of deep learned features needs to be considered for each specific study. Dataset size is a key factor: large-scale datasets with low sample diversity could lead to overfitting; limited sample sizes can provide unstable models. The dataset must be representative of all the “facets” of the clinical phenomenon/disease investigated. The access to high-performance computational resources from graphics processing units is another key factor, especially for the training phase of deep architectures. The advantages of multi-institutional federated/collaborative learning are described. When large language models are used, high stability is needed to avoid catastrophic forgetting in complex domain-specific tasks. We highlight that non-DL approaches provide model explainability superior to that provided by DL approaches. To implement explainability, the need for explainable AI arises, also through post hoc mechanisms.

Relevance statement
This work aims to provide the key concepts for processing the imaging features to extract reliable and robust image biomarkers.

Key Points

The key concepts for processing the imaging features to extract reliable and robust image biomarkers are provided.

The main differences between radiomics and representation learning approaches are highlighted.

The advantages and disadvantages of handcrafted versus learned features are given without losing sight of the clinical purpose of artificial intelligence models.

Graphical Abstract
Thermographic and ultrasound assessment in patients with rheumatoid arthritis: can thermography detect subclinical synovitis at the wrist?
Authors: Tan York Kiat , Lim Gek Hsiang , Ooi Chin Chin , Ma Voon Chee , Vora Bimal Mayur Kumar 
Published: November 2024

Abstract
Background
Thermography is an emerging imaging modality which allows for a quick and objective measure of joint surface temperature in patients with rheumatoid arthritis (RA). To date, there are no published studies comparing thermography with ultrasonography in the subclinical assessment of joint inflammation at the wrist of patients with RA, and no published data on inter-rater reliability for multiple raters for thermographic assessment at the RA wrist. In our study comparing thermography and ultrasonography at the RA wrist, we aim to determine if thermography can detect subclinical synovitis. Additionally, we performed inter-reliability testing (multiple raters) for both thermography and ultrasonography.

Methods
Thermographic (average (Tavg), maximum (Tmax) and minimum (Tmin) temperatures) and ultrasound (total grey-scale (TGS) score and total power Doppler (TPD) scores) parameters were compared between two patient groups: Asymptomatic Group (with non-swollen and non-tender wrists) and Symptomatic Group (with swollen and/or tender wrists). Among Asymptomatic Group patients, thermographic parameters were compared between those with and without wrist joint recess(es) having ultrasound synovitis (PD ≥ 1 or GS ≥ 2); Spearman’s correlation and simple linear regression were used to study the relationship between thermographic and ultrasound parameters. Intra-class correlation coefficient (ICC) was used for inter-rater reliability calculation.

Results
Eighty-seven RA patients’ right wrists were imaged in this cross-sectional study. Thermographic temperatures, TPD and TGS scores were all significantly (p < 0.05) greater among Symptomatic Group versus Asymptomatic Group patients. Among Asymptomatic Group patients, thermographic temperatures were all significantly higher (P < 0.01) in wrists having joint recess(es) with ultrasound PD ≥ 1 or GS ≥ 2, while all thermographic parameters correlated significantly with TPD (correlation coefficient ranging from 0.43 to 0.48, p < 0.001) and TGS (correlation coefficient ranging from 0.33 to 0.37, p < 0.01). The ICC values based on a subset of images obtained for inter-reliability testing were high for thermography (0.994 to 0.998) and ultrasonography (0.933 to 0.952).

Conclusions
Swollen and/or tender RA wrists displayed greater thermographic and ultrasound-detected joint inflammation. At clinically quiescent (non-swollen; non-tender) wrists, thermographic temperatures significantly correlated with ultrasound-detected joint inflammation.

Clinical trial number
Not applicable.