bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who learns more: the impact of dual-player and single-player modes in a serious game on dental students’ factual knowledge
Authors: Krause Felix , Horn Ben , Braun Andreas , Fedrowitz Sebastian , Bell Laura , Lemos Martin 
Published: August 2024

Abstract
Background
The use of serious games in medical education provides a bridge between rapidly developing technology and traditional health-care teaching. Building on a promising web-based serious game for reviewing and acquiring factual knowledge in dental education, the present study investigated the benefits of a dual-player mode and various game options for enhancing knowledge gain and study motivation.

Methods
Before the intervention, students’ dental knowledge and game experience were assessed using a pre-knowledge test and questionnaire-based self-assessment. Students in the clinical study phase (n = 57) were stratified based on prior knowledge and gender and then randomly assigned to two groups, with two player modes: single player (SP) and dual player (DP). In the SP group, each participant played alone, whereas in the DP group, the participants played against a previously determined peer. For a period of 4 weeks, the students were able to playfully acquire knowledge from the field of operative dentistry using METIS, a serious game application with three different game options (Marathon, Sprint, and Time). After the intervention phase, both groups completed a post-knowledge test. The usability of the serious game was evaluated with a self-assessment questionnaire.

Results
The competitive game mode (DP mode; M = 8.92, SD = 1.85) resulted in an increase in the factual knowledge test that was a mean of 2.49 points higher than the SP mode (M = 5.89, SD = 2.19; p < 0.001). The DP group also found the game significantly more helpful for learning (p = 0.04) and engaged more with the teaching content because of the app (p = 0.04). Overall, the usability of METIS was rated as excellent, and students successfully improved their knowledge of dentistry after game play with both game modes (SP, DP, p < 0.001), with the game option “Marathon,” which involves playing the largest number of questions, being the most preferred.

Conclusions
These results suggest that serious games such as METIS are a suitable educational medium for increasing students’ knowledge and interest in the field, and that competition with peers provides even greater motivation to engage with the learning content.
Prediction of midpalatal suture maturation stage based on transfer learning and enhanced vision transformer
Authors: Tang Haomin , Liu Shu , Tan Weijie , Fu Lingling , Yan Ming , Feng Hongchao 
Published: August 2024

Abstract
Background
Maxillary expansion is an important treatment method for maxillary transverse hypoplasia. Different methods of maxillary expansion should be carried out depending on the midpalatal suture maturation levels, and the diagnosis was validated by palatal plane cone beam computed tomography (CBCT) images by orthodontists, while such a method suffered from low efficiency and strong subjectivity. This study develops and evaluates an enhanced vision transformer (ViT) to automatically classify CBCT images of midpalatal sutures with different maturation stages.

Methods
In recent years, the use of convolutional neural network (CNN) to classify images of midpalatal suture with different maturation stages has brought positive significance to the decision of the clinical maxillary expansion method. However, CNN cannot adequately learn the long-distance dependencies between images and features, which are also required for global recognition of midpalatal suture CBCT images. The Self-Attention of ViT has the function of capturing the relationship between long-distance pixels of the image. However, it lacks the inductive bias of CNN and needs more data training. To solve this problem, a CNN-enhanced ViT model based on transfer learning is proposed to classify midpalatal suture CBCT images. In this study, 2518 CBCT images of the palate plane are collected, and the images are divided into 1259 images as the training set, 506 images as the verification set, and 753 images as the test set. After the training set image preprocessing, the CNN-enhanced ViT model is trained and adjusted, and the generalization ability of the model is tested on the test set.

Results
The classification accuracy of our proposed ViT model is 95.75%, and its Macro-averaging Area under the receiver operating characteristic Curve (AUC) and Micro-averaging AUC are 97.89% and 98.36% respectively on our data test set. The classification accuracy of the best performing CNN model EfficientnetV2_S was 93.76% on our data test set. The classification accuracy of the clinician is 89.10% on our data test set.

Conclusions
The experimental results show that this method can effectively complete CBCT images classification of midpalatal suture maturation stages, and the performance is better than a clinician. Therefore, the model can provide a valuable reference for orthodontists and assist them in making correct a diagnosis.
Analysing the intra and interregional components of spatial accessibility gravity model to capture the level of equity in the distribution of hospital services in Italy: do they influence patient mobility?
Authors: Pecoraro Fabrizio , Cellini Marco , Luzi Daniela , Clemente Fabrizio 
Published: August 2024

Abstract
Background
An equal distribution of hospital structures represents an important factor to achieve Universal Health Coverage. Generally, the most diffused approach to measure the potential availability to healthcare is the provider-to-population ratio based on the number of beds or professionals. However, this approach considers only the availability of resources provided at regional or local level ignoring the spatial accessibility of interregional facilities that are particularly accessed by patients living at the borders. Aim of this study is to outline the distribution of the intra and interregional services in Italy to capture the level of equity across the country. Moreover, it explores the impact of the accessibility to these resources on interregional patient’s mobility to receive care.

Methods
To compute spatial accessibility, we propose an alternative approach that applies the enhanced two-step floating catchment area (ESFCA) to capture the level of attraction of intra and interregional hospitals to a given population. Moreover, the adoption of process and outcome indices captured to what extent the quality of structures influenced patients in choosing services located inside or outside their region of residence.

Results
The study confirms that there is an unequal distribution of high-quality resources at regional and national level with a high level of inequality in the availability and accessibility of quality resources between the north and south part of Italy. This is particularly true considering the accessibility of intraregional resources in the southern part of the country that clearly influences patient choice and contribute to a significant cross border passive mobility to northern regions. This is confirmed by an econometric model that showed a significant effect of spatial accessibility with the propensity of patients of travel from the region of residence to receive care.

Conclusions
The analysis of intra and interregional components of spatial accessibility may contribute to identify to what extent patients are willing to travel outside their region of residence to access to care services. Moreover, it can contribute to gain a deeper understanding of the allocation of health resources providing input for policy makers on the basis of the principles of service accessibility in order to contain patient mobility.
Artificial intelligence in COPD CT images: identification, staging, and quantitation
Authors: Wu Yanan , Xia Shuyue , Liang Zhenyu , Chen Rongchang , Qi Shouliang 
Published: August 2024

AbstractChronic obstructive pulmonary disease (COPD) stands as a significant global health challenge, with its intricate pathophysiological manifestations often demanding advanced diagnostic strategies. The recent applications of artificial intelligence (AI) within the realm of medical imaging, especially in computed tomography, present a promising avenue for transformative changes in COPD diagnosis and management. This review delves deep into the capabilities and advancements of AI, particularly focusing on machine learning and deep learning, and their applications in COPD identification, staging, and imaging phenotypes. Emphasis is laid on the AI-powered insights into emphysema, airway dynamics, and vascular structures. The challenges linked with data intricacies and the integration of AI in the clinical landscape are discussed. Lastly, the review casts a forward-looking perspective, highlighting emerging innovations in AI for COPD imaging and the potential of interdisciplinary collaborations, hinting at a future where AI doesn’t just support but pioneers breakthroughs in COPD care. Through this review, we aim to provide a comprehensive understanding of the current state and future potential of AI in shaping the landscape of COPD diagnosis and management.
Impact of radiomics features, pulmonary emphysema score and muscle mass on the rate of pneumothorax and chest tube insertion in CT-guided lung biopsies
Authors: Leonhardi Jakob , Dahms Ulrike , Schnarkowski Benedikt , Struck Manuel Florian , Höhn Anne-Kathrin , Krämer Sebastian , Ebel Sebastian , Prasse Gordian , Frille Armin , Denecke Timm , Meyer Hans-Jonas 
Published: August 2024

AbstractIatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70–0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.
Dipeptide PA3264 derived from rare and endangered Squama Manis is a novel bioactive peptide for the treatment of triple-negative breast cancer
Authors: Hou Xiaorong , Bai Zhaofang , Chen Yuanyuan , Shi Wei , Yang Huijie , Li Ruisheng , Zhan Xiaoyan , Liu Youping , Zhao Xu , Xiao Xiaohe 
Published: August 2024

Abstract
Background
Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease.

Methods
Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264.

Results
PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis.

Conclusions
This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.
The value of the reflective discussion in decision-making using multi-criteria decision analysis (MCDA): an example of determining the value contribution of tabelecleucel for the treatment of the Epstein Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD)
Authors: Badia Xavier , Calleja Miguel Ángel , Escudero-Vilaplana Vicente , Pérez-Martínez Antonio , Piñana José Luis , Poveda José Luis , Vallès Joan-Antoni 
Published: August 2024

Abstract
Background
The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) compared to salvage therapy was used as an example.

Results
Tabelecleucel obtained a value contribution score of 0.63 and increased to 0.75 after the reflective discussion. EBV+ PTLD was considered a life-threatening disease (5.0 ± 0.0), with a significant unmet need for an approved treatment (5.0 ± 0.0). Tabelecleucel was perceived as bringing improvements in terms of efficacy (4.2 ± 0.8) and safety (3.8 ± 0.8) compared to the salvage therapy. Most experts considered that the high efficacy and safety results could represent an improvement in the quality of life of patients (2.3 ± 1.2) along with savings in medical costs (2.3 ± 2.0) and non-medical costs (2.7 ± 1.6) compared to the salvage therapy. However, others emphasized the need of more evidence to confirm these improvements and savings over time. Tabelecleucel was regarded as potentially modifying the clinical course of the disease (4.3 ± 0.8) and supported by high-quality evidence (3.2 ± 0.4). All contextual criteria were valued highly positively for tabelecleucel. "Safety/Tolerability" and "Other medical costs" were the criteria that experienced the highest change in the re-test conducted after the reflective discussion. The reflective discussion allowed resolving doubts or misinterpretations of the experts, so the re-test obtained more accurate and consistent results of the value contribution of tabelecleucel.

Conclusions
The study shows that the MCDA methodology is a useful tool for decision-making on innovative treatments for the management of rare diseases. It also highlights the importance of reflective multidisciplinary discussion for its ability to resolve doubts or misinterpretations of experts, subsequently allowing to obtain more consistent and reliable results on the value contribution of the drug, being potentially more positive.
Protocadherin 19 regulates axon guidance in the developing Xenopus retinotectal pathway
Authors: Jung Jane , Park Jugeon , Park Sihyeon , Kim Chul Hoon , Jung Hosung 
Published: August 2024

AbstractProtocadherin 19 (Pcdh19) is a homophilic cell adhesion molecule and is involved in a variety of neuronal functions. Here, we tested whether Pcdh19 has a regulatory role in axon guidance using the developing Xenopus retinotectal system. We performed targeted microinjections of a translation blocking antisense morpholino oligonucleotide to knock down the expression of Pcdh19 selectively in the central nervous system. Knocking down Pcdh19 expression resulted in navigational errors of retinal ganglion cell (RGC) axons specifically at the optic chiasm. Instead of projecting to the contralateral optic tectum, RGC axons in the Pcdh19-depleted embryo misprojected ipsilaterally. Although incorrectly delivered into the ipsilateral brain hemisphere, these axons correctly reached the optic tectum. These data suggest that Pcdh19 has a critical role in preventing mixing of RGC axons originating from the opposite eyes at the optic chiasm, highlighting the importance of cell adhesion in bundling of RGC axons.
Molecular understanding and clinical aspects of tumor-associated macrophages in the immunotherapy of renal cell carcinoma
Authors: Liu Han , Lv Zongwei , Zhang Gong , Yan Zhenhong , Bai Song , Dong Dan , Wang Kefeng 
Published: August 2024

AbstractRenal cell carcinoma (RCC) is one of the most common tumors that afflicts the urinary system, accounting for 90–95% of kidney cancer cases. Although its incidence has increased over the past decades, its pathogenesis is still unclear. Tumor-associated macrophages (TAMs) are the most prominent immune cells in the tumor microenvironment (TME), comprising more than 50% of the tumor volume. By interacting with cancer cells, TAMs can be polarized into two distinct phenotypes, M1-type and M2-type TAMs. In the TME, M2-type TAMs, which are known to promote tumorigenesis, are more abundant than M1-type TAMs, which are known to suppress tumor growth. This ratio of M1 to M2 TAMs can create an immunosuppressive environment that contributes to tumor cell progression and survival. This review focused on the role of TAMs in RCC, including their polarization, impacts on tumor proliferation, angiogenesis, invasion, migration, drug resistance, and immunosuppression. In addition, we discussed the potential of targeting TAMs for clinical therapy in RCC. A deeper understanding of the molecular biology of TAMs is essential for exploring innovative therapeutic strategies for the treatment of RCC.
Association between glycemic status and all-cause mortality among individuals with dementia: a nationwide cohort study
Authors: Huh Youn , Park Kye-Yeung , Han Kyungdo , Jung Jin-Hyung , Cho Yoon Jeong , Park Hye Soon , Nam Ga Eun , Lim Soo 
Published: August 2024

Abstract
Background
To examine the association between glycemic status and all-cause mortality risk among individuals with dementia.

Methods
We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality.

Results
The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32–1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40–1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30–1.40), shorter-term DM (< 5 years) (HR 1.17; 95% CI: 1.13–1.21), and prediabetes (HR 1.03; 95% CI: 1.01–1.05). These patterns persisted across Alzheimer’s disease and vascular dementia, with more pronounced effects observed in younger patients.

Conclusions
Glucose dysregulation in dementia significantly increased mortality risk, particularly in newly diagnosed or long-standing DM. These findings suggest the potential benefits of maintaining normal glycemic levels in improving the survival of patients with dementia.
Sex-specific cardiac remodeling in aged rats after adolescent chronic stress: associations with endocrine and metabolic factors
Authors: Dearing Carley , Sanford Ella , Olmstead Nicolette , Morano Rachel , Wulsin Lawson , Myers Brent 
Published: August 2024

Abstract
Background
Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early-life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner.

Methods
Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43–62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups.

Results
Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased concentric VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity.

Conclusions
These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for assessing cardiovascular risk based on biological sex and prior adverse experiences.