bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis
Authors: White Justin S , Atherwood Serge , Apollonio Dorie E
Published: December 2024

Background

In May 2020, Oakland became the most populous city in California to implement a minimum floor price law (MFPL), requiring tobacco retailers to sell cigarettes and cigars at $8 or more per pack/package. Policy enforcement began in August 2020.

Methods

We estimated changes in cigarette and cigar prices and unit sales for Oakland versus a matched comparator during the first 20 months following MFPL implementation using a synthetic difference-in-differences approach. We estimated outcome changes overall and by lower-priced (<$8) versus higher-priced (≥$8) segments based on pre-MFPL prices. We also assessed retailer compliance with the MFPL. We further estimated cross-border shopping as a means of price increase avoidance and substitution to electronic nicotine delivery systems (ENDS) and nicotine replacement therapy (NRT) products as alternative consumer responses to the MFPL.

Results

Retailer compliance was high for cigarettes (97.5%) but extremely low for cigars (7.4%). Lower-priced cigarettes in Oakland exhibited: increased median price per pack of 9.0%, a decline in mean monthly sales of 25.2%, and no evidence of significant cross-border shopping (−1.2%) following MFPL enforcement. Lower-priced cigars in Oakland experienced no price change, yet a large sales decline post-enforcement (−58.8%), with a partially-offsetting increase in cross-border shopping (11.0%) post-enforcement. We observed no significant product substitution to higher-priced cigarettes or cigars nor to ENDS or NRT products.

Conclusions

Oakland’s MFPL produced an aggregate decline in cigarette sales of 15%. MFPLs hold promise as a complement to tobacco taxation for reducing tobacco use, especially in localities that pre-empt local tobacco taxation.
Canonical quantum quantization for interior of black hole and white hole
Authors: Martins L. G. , Luz-Burgoa K. , Nogales José A. C.
Published: December 2024

In this paper, we investigate the Schwarzschild metric and extend it to the Kruskal-type metric to explore the interior structure of black holes and white holes within the framework of canonical quantum gravity. We applied a canonical quantization procedure to examine the key features of these objects, focusing on the quantization of the event horizon and continuous extension of the Schwarzschild metric to study white holes using the De Broglie–Bohm interpretation approach. Our findings demonstrate that the horizon of the black hole becomes quantized, leading to the disappearance of central singularity. Furthermore, by extending the Schwarzschild metric into a Kruskal–Schwarschild form, we were able to analyze both black and white holes within a unified approach. Through this quantization process, we derive a regular and effective spacetime model for a white hole, which eliminates singularities and provides new insights into the quantum characteristics of black and white holes.
MKGFA: Multimodal Knowledge Graph Construction and Fact-Assisted Reasoning for VQA
Authors: Wang Longbao , Zhang Jinhao , Zhang Libing , Zhang Shuai , Xu Shufang , Yu Lin , Gao Hongmin
Published: December 2024

Knowledge-based visual question answering relies on open-ended external knowledge and a fine-grained comprehension of both the visual content of images and semantic information. Existing methods for utilizing knowledge have the following limitations: (1) Language pre-training methods output answers in the form of plain text, which only understand shallow visual content; (2) The knowledge retrieved by image objects as labels is represented as first-order logic, making it difficult to infer complex questions. To address the above problems, this paper integrates visual-textual multimodal information, accumulates domain-specific and external multi-modal knowledge, introduces and supplements external objective facts, and proposes a multimodal knowledge graph construction and fact-assisted reasoning network (MKGFA). The network consists of three parts: the multimodal knowledge graph construction module (MKGC), the objective fact-assisted reasoning module (FAR), and the answer inference module. The MKGC engages in the coarse-to-fine-grained learning of triplet representations for multimodal knowledge units. The FAR establishes deep cross-modal relations between visual objects and factual words for correlating real answers. The answer inference module makes the final decision based on the results of both. Among them, the former two modules employ a pre-training and fine-tuning strategy, systematically accumulating foundational and domain-specific knowledge. Compared with the state-of-the-arts, MKGFA achieves 1.09% and 0.7% higher accuracy on the two challenging OKVQA and KRVQA datasets, respectively. The experimental results demonstrate the complementary advantages of the integration of the two modules.
Software Fairness Debt: Building a Research Agenda for Addressing Bias in AI Systems
Authors: de Souza Santos Ronnie , Fronchetti Felipe , Freire Sávio , Spinola Rodrigo
Published: December 2024

Ensuring fairness in software systems has become a critical concern in software engineering. Motivated by this challenge, this paper explores the multifaceted nature of bias in software systems, providing a comprehensive understanding of its origins, manifestations, and impacts. Through a scoping study, we identified the primary causes of fairness deficiencies in software development and highlighted their adverse effects on individuals and communities, including instances of discrimination and the perpetuation of inequalities. Our investigation culminated in the introduction of the concept of software fairness debt. In addition to defining fairness debt, we propose a socio-technical roadmap that addresses broader aspects of fairness in AI-driven systems. This roadmap is structured around six goals: bridging the gap between research and real-world applications, developing a framework for fairness debt, equipping practitioners with tools and knowledge, improving bias mitigation, integrating fairness tools into industry practice, and enhancing explainability and transparency in AI systems. This roadmap provides a holistic approach to managing biases in software systems through software fairness debt, offering actionable steps for both research and practice. By guiding researchers and practitioners, our roadmap aims to foster the development of more equitable and socially responsible software systems, ensuring fairness is embedded throughout the software lifecycle.
Predicting Cardiovascular Diseases Using Neural Networks: Validation With the SCORE2 Risk Assessment Tool
Authors: Saim Mohammed Marouane , Ammor Hassan , Alami Mohamed
Published: December 2024

This study introduces an approach to predicting cardiovascular diseases (CVDs) by leveraging neural networks and evaluates its performance against the widely recognized SCORE2 risk assessment tool. Given the significant global health impact of CVDs, our research aims to assess the effectiveness of deep learning‐based models compared with traditional methods. Our methodology involves developing and deploying a neural network model capable of learning intricate patterns and relationships from a comprehensive dataset. Leveraging a large population cohort with extended follow‐up enables precise and long‐term risk estimation. We utilize the T‐paired test to compare risk predictions between our neural network model and the SCORE2 tool. Our results indicate a notable accuracy of 0.77 for our neural network‐based model in predicting CVDs, with the T‐paired test revealing no significant variations in risk levels between the two methods. These findings underscore the effectiveness of neural networks as a robust tool for CVD risk prediction and advocate for further exploration and integration of these technologies to enhance cardiovascular risk assessment, thereby advancing predictive modeling in healthcare.
Bacterial Muscle Necrosis in Cultured Penaeus vannamei in Latin America
Authors: Intriago Pablo , Montiel Bolivar , Valarezo Mauricio , Arteaga Kelly , Romero Xavier , Montenegro Alejandra
Published: December 2024

A pathology characterized by multifocal reddish patches on the cuticle of shrimp has been reported by shrimp farmers in Latin America. These red patches are commonly associated with small black necrotic spots and white muscle necrosis. One significant impact of this pathology is the reduction in shrimp prices due to the appearance of the animals before and after cooking. The disease is more prevalent in areas with salinities above 5 ppt, with one farm reporting a 45% incidence in one pond. Histopathological examination revealed infiltration of hemocytes in the muscle tissue, melanosis, muscle necrosis, and the presence of Gram‐negative rods in the muscle tissue. Given the presence of bacteria and negative polymerase chain reaction (PCR) results for muscle‐infecting viruses such as infectious myonecrosis virus (IMNV) and Penaeus vannamei nodavirus (PvNV), this pathology is likely due to bacterial infection, though environmental stressors cannot be ruled out as contributing factors in this complex condition. Several Vibrio strains were isolated from the affected tissue and identified using API 20E and PCR. Two strains were selected for in vivo experimentation: Vibrio parahaemolyticus (C8Cg, PirAB toxin‐positive) and V. alginolyticus (C3Ver, PirAB toxin‐negative). Shrimp injected with both live and autoclaved bacteria showed similar histopathological changes, suggesting that the pathology is due to virulence factors within the bacterial cells that can still provoke a strong immune or toxic response even in the absence of live, actively replicating bacteria.
Stochastic Optimal Control for Dynamic Pricing and Production in Fashion Retailing: An Economic Sustainability Approach
Authors: Wang Xin , Chen Qi
Published: December 2024

This study develops a stochastic optimal control model to optimize dynamic pricing and production strategies for fashion retailers facing uncertain demand and rapid product devaluation. Applying the Hamilton–Jacobi–Bellman equation approach, we derive profit‐maximizing joint pricing and production policies. Key findings include the following: (1) Dynamic pricing and responsive production strategies outperform static pricing in terms of expected discounted profit under various market conditions. (2) Optimal dynamic prices exhibit a declining trend over the product lifecycle, aligning with observed practices in fast fashion. (3) The optimal production rate adapts to current inventory levels and market conditions, balancing the trade‐off between stockouts and holding costs. (4) The model demonstrates robustness to variations in price elasticity, providing a flexible decision framework for diverse fashion market segments. (5) Extreme demand volatility reduces the economic benefits of dynamic policies, highlighting the need for additional risk management strategies. This research contributes to sustainable operations’ literature by integrating pricing and production decisions under uncertainty, offering theoretically grounded and practical insights for fashion retailers to enhance profitability and reduce waste.
Damage and Failure of Aeroengine Blades Under Small UAV Impacts
Authors: Wu Zhibin , Chen Chi , Chen Feiying , Liu Jun
Published: December 2024

Unmanned aerial vehicles (UAVs) may collide with vulnerable parts of other aircrafts, such as engine blades, causing accidents. The research on small UAV impact is limited. Besides, UAV impact with propeller and rotor blades is poorly understood. In this paper, a finite element (FE) model of a UAV with a weight of 4.78 kg, turbofan blades, propeller blades, and helicopter tail rotor blades was developed. The FE modelling was carried out by commercial software named LS‐DYNA R13.1.0, which is one of the most advanced simulation tools for nonlinear dynamic structural analysis, mainly solving numerical simulations of collision and penetration problems. First, the UAV FE model was validated by comparing the simulation results against the experiments. Next, simulations were conducted to investigate the damage of the three blades under UAV impact with different heading angles. The damage type and effect of UAV’s heading angle were analyzed and identified. The simulation results indicated that the turbofan blades experienced the more severe damage, compared with the propeller blades and tail rotor blades. The head orientation of the UAV has a significant effect on the impact force of the three aircraft engine blades. In addition, certain parts of the UAV (e.g., battery) can produce significant damage to the blades. The research findings are helpful for the safety assessment of the UAV impact damages to different aircraft engines.
An ECA–ResNet‐Based Intelligent Communication Scenario Identification Algorithm for 6G Wireless Communications
Authors: Zhou Wenqi , Wang Cheng-Xiang , Huang Chen , Feng Rui , Lv Zhen , Qian Zhongyu , Ding Shuyi
Published: December 2024

The sixth generation (6G) wireless communication envisions global coverage, all spectra, and full applications, which correspondingly creates many new communication scenarios. As the foundation of 6G communication system design, network planning, and optimization, more intelligent scenario identification algorithms are necessitated in wireless channel modeling to automatically match suitable parameters for various scenarios. With channel statistics and the efficient channel attention (ECA) mechanism, we propose an improved residual network (ResNet) to identify scenarios in the 6G space–air–ground–sea framework. Datasets from both channel measurements and 6G pervasive channel model (6GPCM) simulations are collected to establish a scenario channel characteristic database, including the numbered scenarios and channel statistical properties such as root mean square (RMS) delay spread (DS), RMS angle spread (AS), and stationary distance/time/bandwidth, etc. During the training and verification process, the proposed algorithm is optimized for 29 scenarios, and the identification accuracy of the proposed ECA–ResNet is higher than the convolutional neural network (CNN) and recurrent neural network (RNN). Finally, the cumulative distribution functions (CDFs) of RMS AS and RMS DS for interoffice main road, office outdoor, office, and industrial Internet of Things (IIoT) scenarios are verified according to the measurement data.
ST6GAL1-Mediated Sialylation of PECAM-1 Promotes a Transcellular Diapedesis-Like Process that Directs Lung Tropism of Metastatic Breast Cancer
Authors: Chen Shih-Yin , He Pei-Lin , Lu Li-Yu , Lin Meng-Chieh , Chan Shih-Hsuan , Tsai Jia-Shiuan , Luo Wen-Ting , Wang Lu-Hai , Li Hua-Jung
Published: December 2024

Metastasis is the leading cause of mortality in breast cancer, with lung metastasis being particularly detrimental. Identification of the processes determining metastatic organotropism could enable the development of approaches to prevent and treat breast cancer metastasis. Here, we found that lung-tropic and non-lung-tropic breast cancer cells differ in their response to sialic acids, affecting the sialylation of surface proteins. Lung-tropic cells showed higher levels of ST6GAL1, while non-lung-tropic cells had more ST3GAL1. ST6GAL1-mediated α-2,6-sialylation, unlike ST3GAL1-mediated α-2,3-sialylation, increased lung metastasis by promoting cancer cell migration through pulmonary endothelial layers and reducing junction protein levels. α-2,6-sialylated PECAM-1 on breast cancer cells facilitated extravasation through the pulmonary endothelium, a critical step in lung metastasis. Knockdown of ST6GAL1 or PECAM-1 significantly reduced lung metastasis. Human pulmonary endothelium displayed high PECAM-1 levels. Through transhomophilic interaction with pulmonary PECAM-1, α-2,6-sialylated PECAM-1 on ST6GAL1-positive cancer cells increased pulmonary extravasation in a diapedesis-like, cell-autonomous manner. Additionally, lung-tropic cells and their exosomes increased the permeability of pulmonary endothelial cells, promoting metastasis in a non-cell-autonomous manner. Analysis of human breast cancer samples showed a correlation between elevated ST6GAL1/PECAM-1 expression and lung metastasis. These results suggest that targeting ST6GAL1-mediated α-2,6-sialylation could be a potential therapeutic strategy to prevent lung metastasis in breast cancer patients.
Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1–Pretreated Metastatic Non–Small Cell Lung Cancer and Metastatic Cutaneous Melanoma
Authors: Lee Sylvia M. , Hamid Omid , Jotte Robert , Zakharia Yousef , Medina Theresa , Gillespie-Twardy Amanda , Mehmi Inderjit , Chandra Sunandana , Watson Graham , Ward Patrick , Chaney Marya , Lu Hailing , Berndt Jason , O’Connor Brian P. , Rathi Kapil , Shaikh Eeman , Cowey Charles Lance
Published: December 2024

Purpose:

Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells that express CD30 and resensitize tumors to anti–PD-1 therapy. This study evaluated responses to BV + pembrolizumab after PD-1 therapy and explored corresponding biomarkers.

Patients and Methods:

A total of 55 patients with metastatic non–small cell lung cancer and 58 patients with metastatic cutaneous melanoma received ≥1 dose of BV + pembrolizumab. Patients had received a median of 2.0 prior lines of systemic therapies (range, 1–7). The primary endpoint was confirmed objective response rate (ORR). Exploratory endpoints included overall survival (OS) and biomarker analysis in blood and tumor.

Results:

For the secondary refractory metastatic non–small cell lung cancer cohort (RECIST v1.1), the ORR was 14%, median progression-free survival (PFS) was 5.85 months, and median OS was 14.4 months. For the secondary refractory metastatic cutaneous melanoma cohort (immune RECIST), the ORR was 24%, median PFS was 4.44 months, and median OS was 21.9 months. Overall, the median duration of OS follow-up was 17.2 months (95% confidence interval, 14.62–22.87). No new safety signals were identified. No treatment-related grade 5 toxicity was seen. Longitudinal immune phenotyping in peripheral blood demonstrated a transient decrease in T regulatory cells. Paired tumor biopsies from baseline and cycle 3 day 1 showed a trend of increased CD8 T-cell infiltration, especially in responding patients.

Conclusions:

BV + pembrolizumab in solid tumor malignancies resulted in clinically meaningful, durable responses with encouraging OS and PFS rates supportive of the immunomodulatory activity of this combination. Stronger antitumor activity was observed in secondary refractory cohorts. The safety profile of this combination was consistent with the individual drug risk profiles.
Activity and Safety of Avelumab in High-Grade Neuroendocrine Tumors and Poorly Differentiated Neuroendocrine Carcinomas Progressive after Chemotherapy (AveNEC Trial)
Authors: Fottner Christian , Apostolidis Leonidas , Krug Sebastian , Rinke Anja , Grün Barbara , Michl Patrick , Gress Thomas M. , Wagner Daniel-Christoph , Roth Wilfried , Mettler Esther , Topsch Jana , Ruckes Christian , Galle Peter R. , Weber Matthias M.
Published: December 2024

Purpose:

Neuroendocrine neoplasms grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear.

Patients and Methods:

The phase II AveNEC study evaluated the effect of avelumab (AVE, 10 mg/kg i.v. every 2 weeks) in 60 patients with well-differentiated high-grade neuroendocrine tumors (N = 22) or poorly differentiated neuroendocrine carcinomas (N = 38) progressing after ≥1 prior chemotherapy (excluding Merkel cell carcinoma and small cell lung cancer).

Results:

The best overall response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) was partial response (PR) in three (5%) and stable disease (SD) in nine (15%) patients, with a disease control rate at 16 weeks of 15% (3 PRs; 6 SDs) and a median duration of response of 4.3 months. Six (10%) patients achieved SD or PR for >6 months and two for >1 year. Response rates were similar regardless of differentiation, Ki-67 expression, or primary localization. The median progression-free survival was 1.9 months, and the overall survival was 6.6 months. After a median follow-up of 3.6 years, only four (7%) patients were still alive; 1- and 2-year survival rates were 33% and 17%, respectively. Responders had a significantly longer overall survival of 30.2 months compared with 4.8 months in nonresponders. AVE was well tolerated, with few treatment-related grade 3/4 adverse events, and the quality of life remained stable during treatment.

Conclusions:

In patients with progressive high-grade NEN G3, AVE was well tolerated and provided disease control with significant clinical benefit in 15% of heavily pretreated patients.
RAD51 Testing in Patients with Early HER2-Negative Breast Cancer and Homologous Recombination Deficiency: A Post Hoc Analysis of the GeparOLA Trial
Authors: Villacampa Guillermo , Llop-Guevara Alba , Filmann Natalie , Herencia-Ropero Andrea , Fasching Peter A. , Karn Thomas , Marmé Frederik , Klare Peter , Müller Volkmar , Stefek Andrea , Schem Christian , Uleer Christoph , Fehm Tanja , Doering Gabriele , Stickeler Elmar , van Mackelenbergh Marion , Felder Bärbel , Nekljudova Valentina , Balmaña Judith , Denkert Carsten , Loibl Sibylle , Serra Violeta
Published: December 2024

Purpose:

The randomized GeparOLA trial reported comparable pathologic complete response (pCR) rates with neoadjuvant treatment containing olaparib versus carboplatin. In this study, we evaluate the association between functional homologous recombination deficiency (HRD) by RAD51 foci and pCR and the potential of improving patient selection by combining RAD51 and stromal tumor-infiltrating lymphocytes.

Patients and Methods:

This is a post hoc blinded biomarker analysis from the randomized GeparOLA trial. Patients with early-stage HER2-negative breast cancer and HRD assessed by Myriad MyChoice or BRCA1/BRCA2 mutations were randomized 1:1 to receive (i) paclitaxel plus olaparib or (ii) paclitaxel plus carboplatin, both followed by epirubicin/cyclophosphamide. Functional HRD was predefined as a RAD51 score ≤10% (RAD51-low).

Results:

Overall, 90 of 97 (92.8%) samples were evaluable for RAD51 testing, and 72 of 90 (80.0%) were RAD51-low. The pCR rate in patients with RAD51-low tumors was 66.7% (48/72), whereas it decreased to 22.2% (4/18) in those with RAD51-high. In the multivariable model including clinicopathologic factors and treatment, the RAD51 score remained significantly associated with pCR (OR = 12.03; 95% confidence interval, 2.60–55.73; P = 0.002). Patients with RAD51-low and high stromal tumor-infiltrating lymphocytes in their tumors achieved a pCR rate of 75.0% (27/36). Similar results were observed for olaparib or carboplatin. In the exploratory disease-free survival analysis, no differences were observed between RAD51 groups (high vs. low: HR = 0.85; 95% confidence interval, 0.25–2.97).

Conclusions:

In a preselected population with HRD, according to a genetic test, RAD51 testing identifies patients with different pCR rates under PARP inhibitor-based or platinum-based therapies. Future biomarker-driven studies should consider this information to refine stratification factors and to improve patient selection.
OBI-992, a Novel TROP2-Targeted Antibody–Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models
Authors: Li Wan-Fen , Chiang Ming-Feng , Weng Hao-Cheng , Yang Jhih-Jie , Wu Hsin-Shan , Wu Szu-Yu , Chen Yu-Jung , Lu Chi-Huan , Tu Jyy-Shiuan , Hsu Ren-Yu , Shia Chi-Sheng , Huang Teng-Yi , Lai Ming-Tain
Published: December 2024

Trophoblast cell surface antigen 2 (TROP2) is highly expressed in multiple cancers relative to normal tissues, supporting its role as a target for cancer therapy. OBI-992 is an antibody–drug conjugate (ADC) derived from a novel TROP2-targeted antibody linked to the topoisomerase 1 (TOP1) inhibitor exatecan via an enzyme-cleavable hydrophilic linker, with a drug–antibody ratio of 4. This study evaluated and compared the antitumor activity of OBI-992 with that of benchmark TROP2-targeted ADCs datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan (SG) in cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) models. OBI-992 treatment exhibited statistically significant antitumor activity versus controls at doses of 3 and 10 mg/kg in various CDX and PDX models, demonstrating comparable or better antitumor activity with benchmark ADCs. In a large-tumor model, longer survival times were observed in OBI-992-treated mice compared with Dato-DXd-treated mice. OBI-992 treatment induced marked bystander killing of TROP2-negative cells in the presence of nearby TROP2-positive cells in both in vitro and in vivo studies. In lung adenocarcinoma CDX models with overexpression of either P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) to mimic ATP-binding cassette transporter–mediated multidrug resistance, OBI-992 treatment maintained antitumor activity when Dato-DXd treatment became less effective. The combination of OBI-992 at suboptimal doses with either poly (ADP-ribose) polymerase (PARP) inhibitors or an immune check point inhibitor produced synergistic antitumor effects in mouse models. Taken together, these translational results support further development of OBI-992 as a cancer therapy.
Supplementary Table 1 from Tumor Expression of CD83 Reduces Glioma Progression and Is Associated with Reduced Immunosuppression
Authors: McDonald Malcolm F. , Curry Rachel Naomi , O’Reilly Isabella , Lozzi Brittney , Cervantes Alexis , Lee Zhung-Fu , Rosenbaum Anna , He Peihao , Mohila Carrie , Harmanci Arif O. , Serin Harmanci Akdes , Deneen Benjamin , Rao Ganesh
Published: December 2024

Clinical characteristics
Figure 6 from Tumor Expression of CD83 Reduces Glioma Progression and Is Associated with Reduced Immunosuppression
Authors: McDonald Malcolm F. , Curry Rachel Naomi , O’Reilly Isabella , Lozzi Brittney , Cervantes Alexis , Lee Zhung-Fu , Rosenbaum Anna , He Peihao , Mohila Carrie , Harmanci Arif O. , Serin Harmanci Akdes , Deneen Benjamin , Rao Ganesh
Published: December 2024

ALTs alter the myeloid compartment of the tumor immune microenvironment. Immunofluorescence for Cd11b in pB-IUE control, CD83OE, and Cd83KO tumors (A and B; one-way ANOVA P value < 0.0001, Tukey MCT: Cd83KO vs. CD83OEP value < 0.0001, Cd83KO vs. control P value = 0.588, CD83OE vs. control P value < 0.0001). Cd11b score in macrophages vs. CD83 gene scoring showing a positive relationship between CD83 signature and Cd11b score (C). Immunofluorescence for Iba1 in control, CD83OE, and Cd83KO tumors (D and E; one-way ANOVA P value = 0.0961). CellChat comparison between CD83OE and control tumor displaying number of signaling interactions (F), strength of the interactions (G), and overrepresented signaling pathways (H). The relative difference in number and strength of interactions within Cd45+ immune cells, tumor cells, and T cells between CD83OE and control mouse tumor (I). CellChat comparison between high and low CD83 gene scoring displaying the number of signaling interactions (J), the strength of the interactions (K), and overrepresented signaling pathways (L). The relative difference in number and strength of interactions within Cd45+ immune cells, tumor cells, and T cells between high and low CD83 gene scoring human tumors (M). (Created with Biorender.com.)
Figure 5 from Tumor Expression of CD83 Reduces Glioma Progression and Is Associated with Reduced Immunosuppression
Authors: McDonald Malcolm F. , Curry Rachel Naomi , O’Reilly Isabella , Lozzi Brittney , Cervantes Alexis , Lee Zhung-Fu , Rosenbaum Anna , He Peihao , Mohila Carrie , Harmanci Arif O. , Serin Harmanci Akdes , Deneen Benjamin , Rao Ganesh
Published: December 2024

ALTs are sufficient to activate CD8+ T cells and act via cytokine release. In vitro tumor cells cocultured with isolated naïve CD8+ T cells (A). Multispectral imaging and flow cytometry for cocultured naïve CD8+ T cells demonstrating higher expression of mature CD3+CD8+ markers (B–E). ELISA for IFNγ showing increased in CD83OE cocultured T cells compared with control (two-way ANOVA: tumor type P value = 0.7105, treatment P value = 0.0021, interaction P value = 0.6425, Šidák MCT: tumor vs. treated tumor control P value = 0.1160, tumor vs. treated tumor control P value = 0.00236; F). ELISA for IL-2 in control and CD83OE tumors and cocultured T cells (two-way ANOVA: tumor type P value = 0.1314, treatment P value = 0.0232, interaction P value = 0.8087, Šidák MCT: tumor vs. treated tumor control P value = 0.2739, tumor vs. treated tumor control P value = 0.1437; G). ELISA for TNFα in control and CD83OE tumors and cocultured T cells (two-way ANOVA: tumor type P value = 0.8411, treatment P value = 0.9121, interaction P value = 0.3234; H). Increased expression of TNFα and IL-2 by CD83OE tumors compared with CD83KO and control tumors in scRNA-seq from pB-IUE tumors (I). *, P value < 0.05. (Created with Biorender.com.)
Figure 2 from Tumor Expression of CD83 Reduces Glioma Progression and Is Associated with Reduced Immunosuppression
Authors: McDonald Malcolm F. , Curry Rachel Naomi , O’Reilly Isabella , Lozzi Brittney , Cervantes Alexis , Lee Zhung-Fu , Rosenbaum Anna , He Peihao , Mohila Carrie , Harmanci Arif O. , Serin Harmanci Akdes , Deneen Benjamin , Rao Ganesh
Published: December 2024

CD83 influences tumor growth in the pB-IUE system. Kaplan–Meier survival curve of pB-IUE tumors control (n = 17, Med OS = 102 days), CD83KO (n = 20, Med OS = 94 days), and CD83OE (n = 16, Med OS = 116 days; log-rank, all three curves, P value = 0.018; A). Age-matched P60 brains demonstrating decreased growth of CD83OE tumors compared with control and CD83KO tumors (B). Hematoxylin and eosin stain of pB-IUE control, CD83OE, and CD83KO tumors (C and D). IHC for Ki67 of pB-IUE control, CD83OE, and CD83KO tumors (one-way ANOVA P value = 0.0133. Tukey MCT: CD83KO vs. CD83OEP value = 0.0158, CD83KO vs. control P value = 0.8075, and CD83OE vs. control P value = 0.0454; E and F). EdU staining of in vitro cultured control, CD83OE, and CD83KO tumors (one-way ANOVA P value < 0.0001. Tukey MCT: CD83KO vs. CD83OEP value = 0.0193, CD83KO vs. control P value < 0.0001, and CD83OE vs. control P value < 0.0001; G and H). *, P value < 0.05; ****, P value < 0.0001. (Created with Biorender.com.)
Acute Liver Failure and Human Herpesvirus 6 Infection: Reactivation in Immunoparesis?
Authors: Marques Correia Isabel , Rodrigues Ana Isabel , Henriques Adriana , Ferreira Diana M. , Cipriano M. Augusta , Lima Jandira
Published: December 2024

Introduction: HHV-6 infection is usually asymptomatic or self-limited, although in certain populations, particularly in immunocompromised patients, it can cause serious infections. Hepatic involvement, previously described in immunocompromised and occasionally in immunocompetent adults, can lead to acute liver failure (ALF).
Case Presentation: We report a case of a 20-year-old female with no known liver disease, who presented with a 4-day history of diffuse abdominal pain, vomiting and fever on the first day. She reported an influenza-like syndrome the previous week and undetermined weight loss over the last 2 months, associated with a behavior compatible with a purging eating disorder. She had a binge drinking pattern of alcohol consumption, followed by paracetamol intake for veisalgia, and occasional cannabinoid use. The patient denied other exposures. She developed grade 1 hepatic encephalopathy and was diagnosed with ALF. Further work-up for underlying etiology detected HHV-6B, both in peripheral blood and liver tissue.
Discussion: This ALF has a viral cause due to a possible reactivation of HHV-6 in the context of immunoparesis secondary to malnutrition and binge drinking, though we cannot exclude a contribution from a toxic cause due to paracetamol overuse, facilitated by these same susceptibility factors. HHV-6 should be included in the differential diagnosis of ALF of undetermined cause, particularly in immunocompromised and seriously ill patients.
The Effect of Earnings Management, Liquidity, and Leverage on Tax Aggressiveness
Authors: Mustapa Eka Sri Murni , Junus Onong , Saprudin  , Abdullah Julie , Hasan Wahyudin
Published: December 2024

This research aims to examine the influence of Profit Management, Liquidity, Leverage on Tax Aggressiveness. This research is a type of quantitative research using secondary data. The population in this study are mining companies listed on the Indonesia Stock Exchange for the 2018-2022 period. The sample used a purposive sampling method with a total sample of 65 consisting of 13 companies. This research uses SPSS 22. Based on the results of this research, it shows that Profit Management partially has no effect on Tax Aggressiveness because managers do not use earnings management to carry out tax aggressiveness. The Liquidity Ratio partially has a negative and significant effect on Tax Aggressiveness, because a liquidity percentage of 73% means that the company has a 73% ability to pay its short-term obligations including the tax burden. The leverage ratio partially has a negative and significant effect on Tax Aggressiveness. This research found a leverage effect of 53% where a company has high debt, so the company will tend to choose to pay its debt. Simultaneously (together) the variables Profit Management, Liquidity Ratio and Leverage Ratio have a negative and significant effect on Tax Aggressiveness.
Diabetes Management among Type 2 DM Patient: Descriptive Study
Authors: Ni Wayan Trisnadewi  , Oktaviani Ni Putu Wiwik , Ni Komang Ayu Resiyanthi
Published: December 2024

Introduction: The primary issue facing diabetes patients today is the lack of adherence to their treatment plans. The high prevalence of diabetes poses a significant challenge for both patients and their fami-lies. This study aims to describe medication adherence, dietary habits, and physical exercise among patients with type 2 diabetes.Methods: This study is a descriptive analysis involving 82 partici-pants selected through a purposive sampling technique. The study in-cluded patients with type 2 diabetes mellitus who had been diagnosed for at least one year, lived with their families, and did not have any men-tal health issues. Data collection was conducted by visiting respondents at their homes. The questionnaire was administered with the assis-tance of a researcher and an enumerator, taking approximately 20 to 25 minutes to complete.Results: The study found that nonadherence to diet, medication, and exercise among type 2 diabetes patients remains high, with rates of 73.2%, 72.0%, and 61.0%, respectively.Conclusion: Patients with type 2 diabetes mellitus who have been diagnosed for more than one year exhibit poor diabetes management. These patients struggle to maintain a consistent medication and die-tary schedule and fail to engage in regular physical exercise.
Student Satisfaction in Student Affairs and Services: Ordinary Least Squares Model Insights
Authors: Albarracin Melanie R. , Caynila Rhea Jane L. , Manzanades Glazalle Marie , Segovia Christel Kate
Published: December 2024

This research examines the factors influencing student satisfaction with the services offered by the Office of Student Affairs and Services (OSAS) at Cebu Technological University - Argao Campus. The study gathered data from 242 students using a survey questionnaire and used Ordinary Least Squares (OLS) model analysis to measure the impact of personnel competency and professionalism, service experience and interaction, and service commitment and environmental factors on overall satisfaction. The findings emphasize the significance of having knowledgeable, competent, and compassionate staff, as they suggest that personnel competency and professionalism greatly influences student satisfaction. The result also stresses the importance of service experience and interaction, indicating that higher education institutions should prioritize being responsive to student inquiries, providing a safe campus environment, and promoting open communication with students. Additionally, the study highlights the importance of environmental factors and service commitment, arguing that improving student satisfaction requires operational enhancements such as quicker service, easy navigation, and facility maintenance. Addressing these issues could lead to higher satisfaction levels, aligning with the university's goal of creating a welcoming and engaging learning environment
РОЛЬ ПРОБІОТИЧНИХ КУЛЬТУР У ФОРМУВАННІ МІКРОБІОТИ КИШКИ. ВІСЬ МІКРОБІОТА-КИШЕЧНИК-МОЗОК
Authors: Куновський В. В. , Лаба О. В. , Куновська Л. М.
Published: December 2024

Мета роботи – проаналізувати взаємозв’язок між кишковою мікробіотою та центральною нервовою системою – ЦНС (вісь мікробіота-кишечник-мозок).
Пробіотики та пребіотики модулюють вісь кишечник-мозок, що має підтримуючий вплив на центральну нервову систему, а також зменшує або контролює захворюваність на деякі психічні розлади (депресія, тривога, аутизм, шизофренія та хвороба Альцгеймера). Коменсальна мікробіота відіграє центральну роль у взаємозв’язку між кишковою мікробіотою та центральною нервовою системою (вісь мікробіота-кишечник-мозок). Кишково-мозкова вісь (gut-brain axis; GBA) складається з двоспрямованого зв’язку між центральною та ентеральною нервовою системою, зв’язуючи емоційні та когнітивні центри мозку з периферичними кишковими функціями. Як наслідок, модуляція мікробіоти кишечнику вважається ключовим аспектом у лікуванні нервових розладів. Дослідження показують, що мікробіота кишки може впливати на кишково-мозкову вісь і відігравати важливу роль у профілактиці та контролі деяких захворювань мозку, таких як стрес, хвороба Альцгеймера, депресія та безсоння.
Висновки. Представлені дані літератури можуть скласти мотиваційну основу для здійснення додаткових і поглиблених досліджень патогенетичних аспектів тривожного синдрому та стресу.
ЕТІОЛОГІЧНІ, ЕПІДЕМІОЛОГІЧНІ ТА КЛІНІЧНІ АСПЕКТИ ГАРЯЧКИ ЗАХІДНОГО НІЛУ
Authors: Копча В. С.
Published: December 2024

Вірус Західного Нілу (ВЗН) переважно інфікує комарів, птахів, коней і людей. Цей збудник може спричиняти безсимптомне інфікування або захворювання з різноманітними клінічними проявами – від легкої гарячки до смертельно небезпечних нейроінвазивних форм хвороби. Останнім часом в Європейському Союзі та сусідніх країнах зросла частота і тяжкість захворювань, зумовлених ВЗН, особливо в середземноморському регіоні. Ймовірно ця тенденція пов’язана з підвищенням як середньої температури повітря, так і кількості опадів, що є сприятливими для поширення ВЗН. Завдяки помітному та зростаючому географічному розповсюдженню переносника та високому ендемічному потенціалу ВЗН, він викликає дедалі більше побоювань для громадської охорони здоров’я.
Клінічний спектр симптоматичної гарячки Західного Нілу (ГЗН) у людей широкий. У близько 80 % людей інфекція перебігає безсимптомно, у 20 % виявляють неспецифічне гарячкове захворювання, ступінь тяжкості якого може варіювати від легкого до тяжкого, тоді як у невеликої групи пацієнтів (<1 %) розвивається потенційно летальне нейроінвазивне захворювання. Одужання від ГЗН може бути повільним, а рівень смертності досягає 10 %, хоча й залежить від віку та імунного стану пацієнтів.
Особливо непокоїть той факт, що наразі немає вакцини або специфічних противірусних засобів для лікування таких хворих.
СИНТЕЗ, АНТИРАДИКАЛЬНА ТА АНТИМІКРОБНА АКТИВНІСТЬ 6-[(АЗАГЕТЕРОЦИКЛІЛ(АРИЛАМІНО)ЕТИЛ]-3-R-2H-[1,2,4]ТРИАЗИНО[2,3-C] ХІНАЗОЛІН-2-OНІВ
Authors: Грицак O. A.
Published: December 2024

РЕЗЮМЕ. Представлена робота присвячена пошуку біологічно активних речовин серед 6-заміщених 3-R1-2H-[1,2,4]триазино[2,3-c]хіназолін-2-oнів, що поєднують у своїй структурі конденсовану гетеросистему та «фармакофорні» насичені азагетероцикли (піперидин, піперазин, азепін) або заміщені аніліни, які поєднані через етильну «лінкерну» групу.
Матеріал і методи. Загальноприйняті методи препаративної органічної хімії були використані для одержання цільових сполук. Їх чистота та структура підтверджена методами елементного аналізу, ВЕРХ-МС та 1Н ЯМР-спектрометрії. Для оцінки протимікробного потенціалу та антирадикальної активності 6-[(азагетероцикліл-(ариламіно-)етил]-3-R1-2H-[1,2,4]триазино[2,3-c]хіназолін-2-oнів використані тест-культури бактерій Escherichia colі, Staphylococcus aureus, Mycobacterium luteum та грибів Candida tenuis, Aspergillus niger. Мінімальну інгібуючу (МІК), бактерицидну (МБК) і фунгіцидну (МФК) концентрацію визначали методом серійних розведень. Антирадикальну активність вивчали на моделі зв’язування ДФПГ-радикалу.
Результати. Реакція 6-(1-хлороетил)-3-R1-2H-[1,2,4]триазино[2,3-c]хіназолін-2-онів з насиченими азагетероциклами або анілінами дозволила одержати ряд 6-[(азагетероцикліл-(ариламіно)етил]-3-R-2H-[1,2,4]триазино[2,3-c]хіназолін-2-oнів, для яких встановлено задовільні показники прогнозованої токсичності, фармакокінетичних параметрів та відповідності основним критеріям лікоподібності. Проведений скринінг протимікробної дії показав, що одержані речовини є практично неактивними по відношенню до штамів Escherichia colі, Staphylococcus aureus, Candida tenuis, Aspergillus niger. В той самий час сполуки 2.3 та 3.1 проявлять помірну антибактеріальну дію по відношенню до Mycobacterium luteum. Серед одержаних речовин лише 6-(1-((4-фторфеніл)аміно)етил)-3-метил-2H-[1,2,4]триазино[2,3-c]хіназолін-2-он проявив здатність ефективно зв’язувати ДФПГ-радикал.
Висновки. Продукти алкілування насичених азагетероциклів та анілінів 6-(1-хлороетил)-3-R1-2H-[1,2,4]триазино[2,3-c]хіназолін-2-онами мають задовільні значення прогнозованої токсичності та фармакокінетичних параметрів. Окремі з синтезованих речовин проявляють помірну антибактеріальну дію по відношенню до штаму Mycobacterium luteum та антирадикальну активність.
КІЛЬКІСНА ХАРАКТЕРИСТИКА РЕАКЦІЙ РІЗНИХ ЛАНОК НИРКОВИХ АРТЕРІЙ БІЛИХ ЩУРІВ ЗАЛЕЖНО ВІД ТРИВАЛОСТІ ЗАГАЛЬНОГО ЗНЕВОДНЕННЯ
Authors: Вахновська Х. І.
Published: December 2024

РЕЗЮМЕ. При дефіциті води в організмі виникає порушення водно-електролітного балансу, що може суттєво впливати на загальний гомеостаз. В нирках при цьому на перший план виступають зміни зі сторони кровоносного русла.
Мета – дати кількісну характеристику структурних змін у компонентах ниркової паренхіми та у кровоносному руслі нирок білих щурів за різних ступенів загального зневоднення.
Матеріал і методи. Експерименти проведені на 30 білих щурах. Загальну дегідратацію моделювали шляхом годування сухим вівсом без доступу до води протягом 3, 6 і 10 діб (загальне зневоднення легкого, середнього та тяжкого ступенів відповідно). Морфометричні дослідження включали визначення площі клубочка з капсулою Шумлянського-Боумена, площі капілярних петель клубочка, площі сечового простору в нирковому тільці, а також визначення показника функціональної активності стінок артерій – індексу Вогенворта.
Результати й обговорення. При легкому ступені загальної дегідратації артеріальне судинне русло реагує деяким зниженням пропускної спроможності дугових і дещо більшим – міжчасткових артерій. Міжчасточкові артерії при цьому залишаються індиферентними.
При середньому ступені загального зневоднення міжчасткові артерії продовжують знижувати свою пропускну спроможність, а дугові артерії змінюють констрикторні реакції на дилатаційні, які ще у більшій мірі стають притаманними для міжчасточкових артерій. Усі ці зміни продовжують прогресувати і свого найбільшого вираження набувають у 10-денний термін безводного періоду, тобто при дегідратації тяжкого ступеня.
Виявлені судинні реакції безпосередньо впливають на стан ниркових тілець з відповідною перебудовою їх структурних компонентів та зміною кількісних характеристик. Набуває вираженої тенденції до зменшення площа клубочків з капсулою Шумлянського-Боумена з одночасним паралельним прогресивним достовірним при середньому і тяжкому ступенях зневоднення зменшенням площі капілярних петель клубочків. Останнє призводить до достовірного наростання площі сечових просторів при всіх ступенях модельованої дегідратації.
Висновки. Загальне зневоднення призводить до перебудови кровоносного русла нирок, характер і інтенсивність якої залежить від ступеня зневоднення і визначає ступінь перебудови ниркових тілець, яка полягає у прогресивному зменшенні площі тілець і їх капілярних клубочків з одночасним збільшенням площі сечових просторів.
ВІДНОВЛЕННЯ РУХОМОСТІ Й МОБІЛЬНОСТІ В НИЖНІХ КІНЦІВКАХ ПРИ МІННО-ВИБУХОВИХ ТРАВМАХ
Authors: Давибіда Н. О. , Баврук П. О. , Людвік В. Є.
Published: December 2024

Вступ. Мінно-вибухові травми є одним з найсерйозніших видів ушкоджень, які часто трапляються за умов військових конфліктів і терористичних атак. Вони можуть призвести до значних руйнувань кістково-м’язової системи, ампутацій і втрати функціональності нижніх кінцівок. Відновлення рухомості й мобільності в таких випадках є надзвичайно складним процесом, який потребує комплексного підходу, що включає хірургічні втручання, реабілітацію та психологічну підтримку. Мінно-вибухові травми виникають унаслідок впливу вибухової хвилі, осколків та уламків, які призводять до тяжких поранень тканин, м’язів, кісток, судин і нервів. Часто це супроводжується множинними переломами, ампутаціями і великими дефектами шкіри та м’язів. Ураження нижніх кінцівок унаслідок вибухів викликає критичне порушення функцій ходьби і стабільності.
Мета роботи – дослідити ефективність комплексів реабілітаційних заходів для відновлення мобільності в нижніх кінцівках при роботі з пацієнтами з мінно-вибуховими ураженнями нижніх кінцівок.
Основна частина. Проведено аналіз ефективності реабілітаційних втручань для покращення якості життя пацієнтів з мінно-вибуховими ураженнями нижніх кінцівок. Розроблено реабілітаційну програму, спрямовану на оптимізацію відновлювального процесу в таких пацієнтів. При цьому враховано індивідуальні особливості та комплексний підхід, що забезпечує високу ефективність її застосування в широкого кола пацієнтів. Мінно-вибухові ураження є складними через специфічні особливості патогенезу, діагностики і терапії, а для реабілітологів – через поєднання порушень функціонування одразу декількох систем організму. Тому для ефективного відновлення функцій опорно-рухового апарату і максимального повернення працездатності пацієнтів застосовують комплексні програми фізичної реа­білітації. Ми розробили загальні комплекси вправ для двох рухових режимів. Кожен комплекс підбирають індивідуально під пацієнта, змінюючи склад та кількість повторень вправ. Також варіативність вправ залежить від інвентарю і стану пацієнта. Для ускладнення та збільшення навантаження рекомендують виконувати їх у декілька підходів. При виникненні труднощів з виконанням тих чи інших вправ радять використовувати пасивну допомогу для розробки суглобів, м’язів та збільшення амплітуди руху.
Висновки. Відновлення рухомості й мобільності в нижніх кінцівках при мінно-вибухових травмах є складним і тривалим процесом, що потребує мультидисциплінарного підходу. Хірургічні втручання, інтенсивна фізична реабілітація, протезування та психологічна підтримка допомагають пацієнтам повернутися до максимально активного і незалежного життя. Інновації в протезуванні та методах реабілітації дозволяють досягти значних результатів, покращуючи якість життя постраждалих.