bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Conventional and Hybrid Thermal-Enzymatic Modified Wheat Flours as Clean Label Bread Improvers
Authors: Lewko Piotr , Wójtowicz Agnieszka , Gancarz Marek
Published: August 2024

A new flour blend (F) composed of selected milling and leaving passages with a high content of non-starch polysaccharides underwent thermal (T), hydrothermal (H) or hybrid processing and was used along with cellulase (C) and cellulase-xylanase complex (CX) to produce bread. This modified flour can be considered a clean label product. In this study, blends of common and treated flours were tested for dough properties and rheology. The modified flours were added at 10 and 20% to the base wheat flour. A pan bread was then prepared to test their suitability for bread baking. Dough and bread properties were subsequently assessed. Accordingly, dough with added thermally, hydrothermally, and hybrid modified flours revealed differences in rheology. Addition of hybrid enzymatic-hydrothermal treated flour increased dough tenacity by 23% and baking strength by 26%, but decreased dough extensibility by 19%, whereas hybrid enzymatic-thermal modification increased water absorption by 6% and bread yield from 146.77% to 150.02% when modified flour was added at 20%. Breads with added modified flours demonstrated a 16% increase in bread volume, 8% lower baking loss, and 14% greater density, with no negative effect on color and texture. Thus, hybrid thermal-enzymatic treatment of the developed flours can be recommended as a suitable method for enhancing the utilization of waste flour fractions and increasing their value by enabling them to be considered as clean label bread improvers.
E-Marketplace State of the Art and Trends: VR-ZOCO—An Architectural Proposal for the Future
Authors: Castro-Schez José Jesús , Grande Rubén , Herrera Vanesa , Schez-Sobrino Santiago , Vallejo David , Albusac Javier
Published: August 2024

E-commerce has become uniquely relevant to small- and medium-sized enterprises (SMEs) as an essential catalyst for their growth and sustainability. SMEs see e-commerce portals as a strategic way to engage in digital business activities without having to implement costly proprietary e-commerce solutions. In addition, partnering with these portals frees them from complex tasks such as positioning, portal maintenance, and adapting the portal to new technologies and trends. This multifaceted advantage positions e-commerce portals as invaluable partners, streamlining operations and allowing SMEs to focus more on their core business competencies. However, e-commerce portals or e-marketplaces are not without their challenges. Today, they face increasing pressure to reduce their environmental impact and to empower local commercial businesses, as well as local businesses in the entertainment and culture industry. To address these challenges, there is a pressing need to propose new types of e-marketplaces that support the concept of the 15-minute city and in which virtual and augmented reality play a key role. These marketplaces would not only boost environmental sustainability but also strengthen the connection between local businesses and the community, creating a stronger and more collaborative network that benefits both businesses and consumers.
RHYTHMI: A Deep Learning-Based Mobile ECG Device for Heart Disease Prediction
Authors: Eleyan Alaa , AlBoghbaish Ebrahim , AlShatti Abdulwahab , AlSultan Ahmad , AlDarbi Darbi
Published: August 2024

Heart disease, a global killer with many variations like arrhythmia and heart failure, remains a major health concern. Traditional risk factors include age, cholesterol, diabetes, and blood pressure. Fortunately, artificial intelligence (AI) offers a promising solution. We have harnessed the power of AI, specifically deep learning and convolutional neural networks (CNNs), to develop Rhythmi, an innovative mobile ECG diagnosis device for heart disease detection. Rhythmi leverages extensive medical data from databases like MIT-BIH and BIDMC. These data empower the training and testing of the developed deep learning model to analyze ECG signals with accuracy, precision, sensitivity, specificity, and F1-score in identifying arrhythmias and other heart conditions, with performances reaching 98.52%, 98.55%, 98.52%, 99.26%, and 98.52%, respectively. Moreover, we tested Rhythmi in real time using a mobile device with a single-lead ECG sensor. This user-friendly prototype captures the ECG signal, transmits it to Rhythmi’s dedicated website, and provides instant diagnosis and feedback on the patient’s heart health. The developed mobile ECG diagnosis device addresses the main problems of traditional ECG diagnostic devices such as accessibility, cost, mobility, complexity, and data integration. However, we believe that despite the promising results, our system will still need intensive clinical validation in the future.
Characteristics of PM2.5 and CO2 Concentrations in Typical Functional Areas of a University Campus in Beijing Based on Low-Cost Sensor Monitoring
Authors: Wang Qingqing , Ao Ruoxi , Chen Hongwei , Li Jialin , Wei Lianfang , Wang Zifa
Published: August 2024

The air quality in educational campuses affects the health and work efficiency of teachers and students. Studies into this matter are of great significance for optimizing the management of campus living environments. Low-cost online sensors to monitor PM2.5 and CO2 levels were used in typical functional areas of a university campus in Beijing, China, including offices, dormitories, leisure spaces, canteens, and laboratories. By comparing the findings with data from nearby national monitoring stations, the seasonal and spatial variations in PM2.5 and CO2 concentrations were analyzed. Findings indicate PM2.5 levels within the campus were notably lower compared to the surrounding urban environment. There was variation in PM2.5 and CO2 concentrations across different functional areas. Typically, indoor PM2.5 levels were lower than outdoor ones, while CO2 concentrations in enclosed indoor spaces with human activities progressively escalated. The main internal emission sources affecting the PM2.5 level on campus included traffic emissions, dust generated by human activities, and emissions from catering. In contrast, in areas with better green coverage or where a lake system participates in the atmospheric circulation, the PM2.5 level and CO2/PM2.5 were lower. This indicates that the cleansing impact of plants and aquatic systems is instrumental in lowering PM2.5 concentrations, offering healthier leisure spaces. Seasonal variations also impact PM2.5 levels. During the non-heating period, less pollution source emissions led to decreased outdoor PM2.5 concentrations. The campus monitoring sites experienced an approximate 5 µg/m3 and 29 µg/m3 reduction in the average PM2.5 levels as compared to the PM2.5 of the surrounding urban environment, respectively, during the non-heating and heating period. During indoor activities or sleep, CO2 levels can build up to as high as 2303 ppm due to breathing. It is advisable to stay indoors on days when pollution levels are high, whereas on days with clean air, it is healthier to be outdoors or to air out indoor areas by opening windows. Our research provides clearer scientific evidence for incorporating behavioral strategies for improving air quality into both daily work and life. Moreover, the findings are quite meaningful for the widespread adoption of low-cost sensor monitoring in various environments, with applications beyond just the campus settings.
Diffusion-Based Image Synthesis or Traditional Augmentation for Enriching Musculoskeletal Ultrasound Datasets
Authors: Balla Benedek , Hibi Atsuhiro , Tyrrell Pascal N.
Published: August 2024

Background: Machine learning models can provide quick and reliable assessments in place of medical practitioners. With over 50 million adults in the United States suffering from osteoarthritis, there is a need for models capable of interpreting musculoskeletal ultrasound images. However, machine learning requires lots of data, which poses significant challenges in medical imaging. Therefore, we explore two strategies for enriching a musculoskeletal ultrasound dataset independent of these limitations: traditional augmentation and diffusion-based image synthesis. Methods: First, we generate augmented and synthetic images to enrich our dataset. Then, we compare the images qualitatively and quantitatively, and evaluate their effectiveness in training a deep learning model for detecting thickened synovium and knee joint recess distension. Results: Our results suggest that synthetic images exhibit some anatomical fidelity, diversity, and help a model learn representations consistent with human opinion. In contrast, augmented images may impede model generalizability. Finally, a model trained on synthetically enriched data outperforms models trained on un-enriched and augmented datasets. Conclusions: We demonstrate that diffusion-based image synthesis is preferable to traditional augmentation. Our study underscores the importance of leveraging dataset enrichment strategies to address data scarcity in medical imaging and paves the way for the development of more advanced diagnostic tools.
Research on Move-to-Escape Enhanced Dung Beetle Optimization and Its Applications
Authors: Feng Shuwan , Wang Jihong , Li Ziming , Wang Sai , Cheng Ziyi , Yu Hui , Zhong Jiasheng
Published: August 2024

The dung beetle optimization (DBO) algorithm is acknowledged for its robust optimization capabilities and rapid convergence as an efficient swarm intelligence optimization technique. Nevertheless, DBO, similar to other swarm intelligence algorithms, often gets trapped in local optima during the later stages of optimization. To mitigate this challenge, we propose the Move-to-Escape dung beetle optimization (MEDBO) algorithm in this paper. MEDBO utilizes a good point set strategy for initializing the swarm’s initial population, ensuring a more uniform distribution and diminishing the risk of local optima entrapment. Moreover, it incorporates convergence factors and dynamically balances the number of offspring and foraging individuals, prioritizing global exploration initially and local exploration subsequently. This dynamic adjustment not only enhances the search speed but also prevents local optima stagnation. The algorithm’s performance was assessed using the CEC2017 benchmark suite, which confirmed MEDBO’s significant improvements. Additionally, we applied MEDBO to three engineering problems: pressure vessel design, three-bar truss design, and spring design. MEDBO exhibited an excellent performance in these applications, demonstrating its practicality and efficacy in real-world problem-solving contexts.
On Metacognition: Overconfidence in Word Recall Prediction and Its Association with Psychotic Symptoms in Patients with Schizophrenia
Authors: Flores-Medina Yvonne , Ávila Bretherton Regina , Ramírez-Bermudez Jesús , Saracco-Alvarez Ricardo , Flores-Ramos Monica
Published: August 2024

A two-factor account has been proposed as an explanatory model for the formation and maintenance of delusions. The first factor refers to a neurocognitive process leading to a significant change in subjective experience; the second factor has been regarded as a failure in hypothesis evaluation characterized by an impairment in metacognitive ability. This study was focused on the assessment of metacognition in patients with schizophrenia. The aims of the study were to measure the overconfidence in metacognitive judgments through the prediction of word list recall and to analyze the correlation between basic neurocognition (memory and executive function) and metacognition through a metamemory test and the severity of psychotic symptoms. Method: Fifty-one participants with a diagnosis of schizophrenia were evaluated. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychiatric symptoms, and the subtest of metamemory included in the Executive Functions and Frontal Lobe-2 battery (BANFE-2) was used to evaluate overconfidence and underestimation errors, intrusion and perseverative response, total volume of recall, and Brief Functioning Assessment Scale (FAST) for social functioning. Results: The strongest correlation is observed between overconfidence errors and the positive factor of the PANSS (r = 0.774, p < 0.001). For the enter model in the multiple linear regression (r = 0.78, r2 = 0.61; F = 24.57, p < 0.001), the only significant predictor was overconfidence errors. Conclusion: Our results highlight the relevance of a metacognitive bias of overconfidence, strongly correlated with psychotic symptoms, and support the hypothesis that metacognitive defects contribute to the failure to reject contradictory evidence. From our perspective, these findings align with current mechanistic models of schizophrenia that focus on the role of the prefrontal cortex.
Impact of Stimulation Duration in taVNS—Exploring Multiple Physiological and Cognitive Outcomes
Authors: Bömmer Till , Schmidt Luisa M. , Meier Katharina , Kricheldorff Julius , Stecher Heiko , Herrmann Christoph S. , Thiel Christiane M. , Janitzky Kathrin , Witt Karsten
Published: August 2024

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that modulates the noradrenergic activity of the locus coeruleus (LC). Yet, there is still uncertainty about the most effective stimulation and reliable outcome parameters. In a double blind, sham-controlled study including a sample of healthy young individuals (N = 29), we compared a shorter (3.4 s) and a longer (30 s) stimulation duration and investigated the effects of taVNS (real vs. sham) on saliva samples (alpha amylase and cortisol concentration), pupil (pupillary light reflex and pupil size at rest) and EEG data (alpha and theta activity at rest, ERPs for No-Go signals), and cognitive tasks (Go/No-Go and Stop Signal Tasks). Salivary alpha amylase concentration was significantly increased in the real as compared to sham stimulation for the 30 s stimulation condition. In the 3.4 s stimulation condition, we found prolonged reaction times and increased error rates in the Go/No-Go task and increased maximum acceleration in the pupillary light reflex. For the other outcomes, no significant differences were found. Our results show that prolonged stimulation increases salivary alpha-amylase, which was expected from the functional properties of the LC. The finding of longer response times to short taVNS stimulation was not expected and cannot be explained by an increase in LC activity. We also discuss the difficulties in assessing pupil size as an expression of taVNS-mediated LC functional changes.
Therapeutic Cerebral Fluid Puncture in Patients with Idiopathic Intracranial Hypertension: No Short-Term Effect on Neurocognitive Function
Authors: Thunstedt Cem , Aydemir Dilan , Conrad Julian , Wlasich Elisabeth , Loosli Sandra V. , Schöberl Florian , Straube Andreas , Eren Ozan E.
Published: August 2024

Background: Idiopathic intracranial hypertension (IIH) is typically characterized by headaches and vision loss. However, neurocognitive deficits are also described. Our study aimed to test the influence of therapeutic lumbar puncture on the latter. Methods: A total of 15 patients with IIH were tested with a battery of neurocognitive tests at baseline and after therapeutic lumbar drainage. Hereby, Logical Memory of the Wechsler Memory Scale—Revised Edition (WMS-R), the California Verbal Learning Test Short Version (CVLT), alertness, selective attention, and word fluency were used. Changes in cognitive functioning in the course of CSF pressure lowering were analysed and compared with age, sex, and education-matched healthy controls. Results: Before intervention, scores of Logical Memory, the RWT, and the HADS-D were significantly lower in IIH patients compared to matched controls. After short-term normalization of CSF pressure, the RWT improved significantly. Additionally, significant positive correlations were found between headache intensity and subjective impairment, as well as between BMI and CSF opening pressure. Conclusions: Our findings confirm lower performance in terms of long-term verbal memory and word fluency compared to controls, as well as depressive symptoms in IIH patients. Significant improvement after short-term normalization of intracranial pressure by means of CSF drainage was seen only for word fluency. This indicates that short-term normalization of CSF pressure is not sufficient to normalize observed neurocognitive deficits.
Research on Opening Design Guidelines for Zero-Energy House Based on the Family Life Cycle
Authors: Sun Xun , Dong Dekun , Yang Yang , Dong Yifan
Published: August 2024

Spatial resources and environmental problems caused by population growth are increasingly becoming the focus of global concern. The environmental sustainability of building products has become the research frontier of the industry. Previous research has proved that 25% of energy consumption comes from daily use, and realizing low-energy design based on the whole life cycle is of great significance to promoting the transformation of the building industry. This paper focuses on the wasteful energy consumption problem caused by the changes in residents’ behavioral requirements due to the changes in family structure. Based on the family life cycle analysis, this paper explores the mechanism of residents’ behavioral requirements and spatial function changes at each stage to clarify the relationship between residents’ behavior and building energy consumption. Then, by controlling factors, including Light Correction Coefficient, Effective Daylight Area, window-to-ground ratio, and window-to-wall ratio, and applying the passive design methodology, this paper establishes the zero-energy home opening design guidelines based on the family life cycle. This research guides designers in the design of zero-energy house openings and, at the same time, provides new perspectives for related research in the field of building energy consumption, which helps to promote the sustainable development of the field of architectural design.
Inverse Correlation between pks-Carrying Escherichia coli Abundance in Colorectal Cancer Liver Metastases and the Number of Organs Involved in Recurrence
Authors: Shigematsu Yasuyuki , Saito Rumiko , Kanda Hiroaki , Takahashi Yu , Takeuchi Kengo , Takahashi Shunji , Inamura Kentaro
Published: August 2024

Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of pks+ E. coli in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of pks+ E. coli in fresh-frozen specimens were quantified as “very low” (<50th percentile), “low” (50th to 75th percentiles), and “high” (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. pks+ E. coli was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of pks+E. coli were associated with decreased serum CRP levels and reduced densities of CD4+ cells and CD163+ cells in the tumor-immune microenvironment. The “high” pks+ E. coli group had fewer metastatic organs involved than the “very low” pks+ E. coli group (mean number of organs: 1.00 vs. 1.23). These findings suggest that pks+ E. coli play a modulating role in CRC metastasis.
Local Delivery of Irinotecan to Recurrent GBM Patients at Reoperation Offers a Safe Route of Administration
Authors: McConville Christopher , Lastakchi Sarah , Al Amri Ali , Ngoga Desire , Fayeye Oluwafikayo , Cruickshank Garth
Published: August 2024

Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood–brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma.
Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study
Authors: Abdelmalak Jonathan , Strasser Simone I. , Ngu Natalie L. , Dennis Claude , Sinclair Marie , Majumdar Avik , Collins Kate , Bateman Katherine , Dev Anouk , Abasszade Joshua H. , Valaydon Zina , Saitta Daniel , Gazelakis Kathryn , Byers Susan , Holmes Jacinta , Thompson Alexander J. , Howell Jessica , Pandiaraja Dhivya , Bollipo Steven , Sharma Suresh , Joseph Merlyn , Sawhney Rohit , Nicoll Amanda , Batt Nicholas , Tang Myo J. , Riordan Stephen , Hannah Nicholas , Haridy James , Sood Siddharth , Lam Eileen , Greenhill Elysia , Lubel John , Kemp William , Majeed Ammar , Zalcberg John , Roberts Stuart K.
Published: August 2024

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.
Resolution of Optimal Mitochondrial and Nuclear DNA Enrichment in Target-Panel Sequencing and Physiological Mitochondrial DNA Copy Number Estimation in Liver Cancer and Non-Liver Cancer Subjects
Authors: Lyu Xue-Ying , Tsui Yu-Man , Tam Ivan Ka-Kit , Li Po-Man , Cheung Gary Cheuk-Hang , Lee Joyce Man-Fong , Ng Irene Oi-Lin , Ho Daniel Wai-Hung
Published: August 2024

Mitochondria generate energy to support cells. They are important organelles that engage in key biological pathways. The dysfunction of mitochondria can be linked to hepatocarcinogenesis, which has been actively explored in recent years. To investigate the mitochondrial dysfunction caused by genetic variations, target-panel sequencing is a flexible and promising strategy. However, the copy number of mitochondria generally exceeds nuclear DNA, which raises a concern that uneven target enrichment of mitochondrial DNA (mtDNA) and nuclear DNA (ncDNA) in target-panel sequencing would lead to an undesirably biased representation of them. To resolve this issue, we evaluated the optimal pooling of mtDNA probes and ncDNA probes by a series of dilutions of mtDNA probes in both genomic DNA (gDNA) and cell-free DNA (cfDNA) samples. The evaluation was based on read count, average sequencing depth and coverage of targeted regions. We determined that an mtDNA:ncDNA probe ratio of around 1:10 would offer a good balance of sequencing performance and cost effectiveness. Moreover, we estimated the median physiological mtDNA:ncDNA copy ratio as 38.1 and 2.9 in cfDNA and gDNA samples of non-liver cancer subjects, respectively, whereas they were 20.0 and 2.1 in the liver cancer patients. Taken together, this study revealed the appropriate pooling strategy of mtDNA probes and ncDNA probes in target-panel sequencing and suggested the normal range of physiological variation of the mtDNA:ncDNA copy ratio in non-liver cancer individuals. This can serve as a useful reference for future target-panel sequencing investigations of the mitochondrial genome in liver cancer.
Pain Management in Animals with Oncological Disease: Opioids as Influencers of Immune and Tumor Cellular Balance
Authors: Pinheiro Ana Vidal , Petrucci Gonçalo N. , Dourado Amândio , Silva Filipe , Pires Isabel
Published: August 2024

Advancements in understanding pain physiopathology have historically challenged animals’ absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient’s individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient’s demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients.
A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer
Authors: Li Jui-Hsiang , Hsin Pei-Yi , Hsiao Yung-Chia , Chen Bo-Jun , Zhuang Zhi-Yun , Lee Chiang-Wen , Lee Wei-Ju , Vo Thi Thuy Tien , Tseng Chien-Fu , Tseng Shih-Fen , Lee I-Ta
Published: August 2024

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease’s prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin’s ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin’s application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin’s potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.
Palliative Thoracic Radiotherapy in the Era of Modern Cancer Care for NSCLC
Authors: Kępka Lucyna
Published: August 2024

Palliative thoracic radiotherapy provides rapid and effective symptom relief in approximately two-thirds of NSCLC patients treated. In patients with poor performance status, the degree of palliation appears unrelated to the radiation dose or fractionation schedule. Conversely, in patients with good performance status, higher radiation doses administered over longer periods have shown modest survival benefits. These findings stem from studies conducted before the advent of immunotherapy and targeted therapy in clinical practice. Currently, there are no large prospective studies specifically dedicated to palliative radiotherapy conducted in this new treatment era. Modern radiotherapy technologies are now widely available and are increasingly used for palliative purposes in selected patients, reflecting the expanded array of therapeutic options for disseminated NSCLC and improved prognosis. Some traditional tenets of palliative thoracic radiotherapy, such as the improvement of overall survival with a protracted radiation schedule and the use of simple, cost-effective radiation techniques for palliative purposes, may no longer hold true for patients receiving immunotherapy or targeted therapy. The application of IMRT or SBRT in the context of palliative radiotherapy for NSCLC is not yet sufficiently explored, and this is addressed in this review. Moreover, new risks associated with combining palliative radiotherapy with these systemic treatments are being explored and are discussed within the context of palliative care. The optimal timing, doses, fractionation schedules, and treatment volumes for radiotherapy combined with immunotherapy or targeted therapy are currently subjects of investigation. In emergencies, radiotherapy should be used as a life-saving measure without delay. However, for other indications of palliative thoracic radiotherapy, decisions regarding doses, timing relative to systemic treatments, and treatment volumes should be made in a multidisciplinary context, considering the patient’s prognosis, anticipated outcomes, and access to potentially effective treatments. We still lack robust data from prospective studies on this matter. This review examines and discusses available evidence on the use of palliative thoracic radiotherapy within the framework of modern treatment strategies for NSCLC.
Cell-Sonar, a Novel Method for Intracellular Tracking of Secretory Pathways
Authors: Brockmöller Sabrina , Seeger Thomas , Worek Franz , Rothmiller Simone
Published: August 2024

Background: Intracellular tracking is commonly used in trafficking research. Until today, the respective techniques have remained complex, and complicated, mostly transgenic target protein changes are necessary, often requiring expensive equipment and expert knowledge. Methods: We present a novel method, which we term “cell-sonar”, that enables the user to track expression changes of specific protein markers that serve as points of interaction. Our study provides comparable analyses of expression changes of these marker proteins by in-cell Western analyses in two otherwise isogenic cell lines that only differ in the overexpression of the tracked target protein. Using the overexpressed human adult muscle-type nicotinic acetylcholine receptor as an example, we demonstrate that cell-sonar can cover multiple intracellular compartments such as the endoplasmic reticulum, the pathway between it and the Golgi apparatus, and the endocytic pathway. Results: We provide evidence for receptor maturation in the Golgi and storage in recycling endosomes, rather than the fate of increased insertion into the plasma membrane. Additionally, we demonstrate with the implementation of nicotine that the receptor’s destiny is exasperated up to secondary degradation. Conclusions: Cell-sonar is an affordable, easy-to-implement, and cheap method that can be adapted to a broad variety of proteins and cellular pathways of interest to researchers.
The Potential Therapeutic Effects of Tadalafil on the Endothelium in a Subarachnoid Hemorrhage Animal Model: Insights from Immunohistochemical Staining
Authors: Park Kwang Hyon , Kwon Hyon-Jo , Jeong Eun-Oh , Koh Hyeon-Song , Lim Jeongwook
Published: August 2024

This study investigated the potential of phosphodiesterase type 5 (PDE-5) inhibitors, specifically tadalafil, in preventing the delayed cerebral ischemia (DCI) post-rupture of cerebral aneurysms. A total of 19 rabbits were used in this study, divided into different treatment groups, including nimodipine alone, tadalafil alone, and a combination of nimodipine and tadalafil. Both nimodipine and tadalafil showed some impact on reducing endothelial apoptosis in the basilar arteries, although the effects were not statistically significant. Notably, the nimodipine group exhibited significantly lower levels of Bax in the small arterioles compared to the SAH group. These findings suggest that while tadalafil may not directly prevent endothelial cell death like nimodipine, its neuroprotective properties hint at its potential utility in DCI treatment. Further research involving a broader range of apoptosis-related proteins is recommended to enhance our understanding in this area.
Understanding the Mechanistic Pathways of N2 Reduction to Ammonia on (110) Facets of Transition Metal Carbides
Authors: Iqbal Atef , Skúlason Egill , Abghoui Younes
Published: August 2024

The conversion of molecular dinitrogen into ammonia under mild conditions is a significant pursuit in chemistry due to its potential for sustainable and clean ammonia production. The electrochemical reduction of N2 offers a promising route for achieving this goal with reduced energy consumption, utilizing renewable energy sources. However, the exploration of effective electrocatalysts for this process, particularly at room temperature and atmospheric pressure, remains under exploration. This study addresses this gap by conducting a comprehensive investigation of potential catalysts for nitrogen electro-reduction to ammonia under ambient conditions. Using density functional theory calculations, we explore the (110) facets of rock salt structures across 11 transition metal carbides. Catalytic activity is evaluated through the construction of free energy diagrams for associative, dissociative, and Mars–van Krevelen reaction mechanisms. Additionally, we assess material stability against electrochemical poisoning and decomposition of parent metals during operation. Our findings suggest that a few of the candidates are promising for nitrogen reduction reactions, such as TaC and WC, with moderate onset potentials (−0.66 V and −0.82 V vs. RHE) under ambient conditions.
A Review of Additively Manufactured Iron-Based Shape Memory Alloys
Authors: Sun Qian , Tan Xiaojun , Ding Mingjun , Cao Bo , Iwamoto Takeshi
Published: August 2024

Iron-based shape memory alloys (Fe-SMAs), traditionally manufactured, are favored in engineering applications owing to their cost-effectiveness and ease of fabrication. However, the conventional manufacturing process of Fe-SMAs is time-consuming and raw-material-wasting. In contrast, additive manufacturing (AM) technology offers a streamlined approach to the integral molding of materials, significantly reducing raw material usage and fabrication time. Despite its potential, research on AMed Fe-SMAs remains in its early stages. This review provides updated information on current AM technologies utilized for Fe-SMAs and their applications. It provides an in-depth discussion on how printing parameters, defects, and post-printing microstructure control affect the mechanical properties and shape memory effect (SME) of AMed Fe-SMAs. Furthermore, this review identifies existing challenges in the AMed Fe-SMA approach and proposes future research directions, highlighting potential areas for development. The insights presented aim to guide improvements in the material properties of AMed Fe-SMAs by optimizing printing parameters and enhancing the SME through microstructure adjustment.
Outcomes of First Subsequent Taxane Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer Who Previously Received Docetaxel Intensification for Metastatic Castration-Sensitive Prostate Cancer
Authors: Robin Gabrielle , Basappa Naveen S. , North Scott , Ghosh Sunita , Kolinsky Michael
Published: August 2024

Background: The management of advanced prostate cancer continues to evolve rapidly, particularly with the earlier use of survival-prolonging therapies in metastatic castration-sensitive prostate cancer (mCSPC). Though approved prior to the use of intensification therapy in mCSPC, taxane-based chemotherapies remain a relevant option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is little evidence determining the outcomes of taxane chemotherapies as the first subsequent taxane (FST) in mCRPC pts who received docetaxel intensification (DI) in mCSPC. The purpose of this study is to compare outcomes between the survival-prolonging taxanes, docetaxel and cabazitaxel as FST after DI. Methods: New patient consults seen at the Cross Cancer Institute from 1 July 2014 to 31 December 2020 were retrospectively reviewed. Pts were considered eligible if they received DI for mCSPC and then received either docetaxel or cabazitaxel in mCRPC. Variables of interest were collected from electronic medical records. The primary endpoint was ≥50% PSA response at 12 weeks relative to baseline for FST. Secondary endpoints included OS from mCSPC diagnosis, as well as PFS and OS from the FST start date. PSA responses were compared using the chi-squared test, and time-based endpoints were compared using the Kaplan–Meier method. Results: In total, 34 pts were identified: docetaxel = 22 and cabazitaxel = 12 as FST. 91.2% of pts (docetaxel 95.5% vs. cabazitaxel 83.3%) received FST in 2nd line mCRPC. The median age at diagnosis (63.1 vs. 67.1 yrs, p = 0.236) and the median time to CRPC (18.6 vs. 14.2 mos, p = 0.079) were similar for docetaxel and cabazitaxel, respectively. The median time to FST (24.1 vs. 34.6 mos, p = 0.036) and OS from mCSPC diagnosis (30.9 vs. 52.7 mos, p = 0.002) were significantly shorter for pts receiving cabazitaxel vs. docetaxel. PSA responses occurred in 40.9% of pts treated with docetaxel compared to 25.0% treated with cabazitaxel (p = 0.645). There was no significant difference in median PFS (2.7 vs. 3.5 mos, p = 0.727) or median OS (11.4 vs. 8.1 mos, p = 0.132) from the time of FST for pts treated with docetaxel vs. cabazitaxel, respectively. Conclusions: Both docetaxel and cabazitaxel demonstrated activity as FST after DI in mCSPC. Pts who received cabazitaxel had a shorter time to FST and OS from mCSPC. The reasons for this may reflect clinician preference for cabazitaxel in pts with aggressive or rapidly progressing disease. No difference was found in PSA response, PFS, or OS from FST with docetaxel compared to cabazitaxel. While limited by its retrospective nature and small sample size, this study suggests that docetaxel is active as FST despite treatment with DI in mCSPC.
Updated Checklist, Traits and Conservation Status of the Ichthyofauna of Aratu Bay, Eastern Brazil
Authors: Medeiros Diego V. , Dias Marcelo A. , Cordeiro Camila C. , de Carvalho-Souza Gustavo F.
Published: August 2024

Coastal environments, such as bays, are essential to the development of fishery resources due to their economic and ecological importance. This paper presents an updated checklist of coastal marine fishes as part of a long-term monitoring program in Aratu Bay (2014–2024), Bahia state, eastern Brazil. A total of 109 species belonging to 58 families and 24 orders were cataloged. Five endemic species and ten species listed as at risk according to the IUCN criteria (from Vulnerable onwards) were identified. The Carangidae was the most representative family in terms of species number, followed by Gobiidae and Sciaenidae. The ichthyofauna was dominated by mobile invertebrate feeders and macrocarnivores. Two non-native species were observed in the region: the Muzzled blenny, Omobranchus sewalli and the mud sleeper Butis koilomatodon. Aratu Bay supports a diverse ichthyofauna with diverse trophic guilds and habitats, rendering it an important area for the feeding and development of economically valuable species, including those facing threats.
Minimally Invasive Forefoot Surgeries Using the Shannon Burr: A Comprehensive Review
Authors: Choi Jun Young , Park Chul Hyun
Published: August 2024

Since the early 2000s, minimally invasive forefoot surgery (MIS), particularly hallux valgus correction, has significantly advanced with the introduction of the Shannon burr. However, despite numerous relevant studies being published, no comprehensive review articles have summarized MIS for various forefoot conditions. Therefore, in this comprehensive review, we examined the relevant studies about the application of MIS (excluding arthroscopy and endoscopy) for various forefoot conditions. Additionally, we discuss the essential considerations for achieving favorable surgical outcomes and preventing complications associated with each technique. We analyzed the characteristics of each surgical procedure and identified areas for future focus. Effective surgical treatment not only requires MIS, but also the appropriate selection of patients based on suitable indications and executing procedures within the surgeon’s capabilities. We hope that this review will help readers to enhance their expertise in this field.
Deep Learning-Based Joint Effusion Classification in Adult Knee Radiographs: A Multi-Center Prospective Study
Authors: Won Hyeyeon , Lee Hye , Youn Daemyung , Park Doohyun , Eo Taejoon , Kim Wooju , Hwang Dosik
Published: August 2024

Knee effusion, a common and important indicator of joint diseases such as osteoarthritis, is typically more discernible on magnetic resonance imaging (MRI) scans compared to radiographs. However, the use of radiographs for the early detection of knee effusion remains promising due to their cost-effectiveness and accessibility. This multi-center prospective study collected a total of 1413 radiographs from four hospitals between February 2022 to March 2023, of which 1281 were analyzed after exclusions. To automatically detect knee effusion on radiographs, we utilized a state-of-the-art (SOTA) deep learning-based classification model with a novel preprocessing technique to optimize images for diagnosing knee effusion. The diagnostic performance of the proposed method was significantly higher than that of the baseline model, achieving an area under the receiver operating characteristic curve (AUC) of 0.892, accuracy of 0.803, sensitivity of 0.820, and specificity of 0.785. Moreover, the proposed method significantly outperformed two non-orthopedic physicians. Coupled with an explainable artificial intelligence method for visualization, this approach not only improved diagnostic performance but also interpretability, highlighting areas of effusion. These results demonstrate that the proposed method enables the early and accurate classification of knee effusions on radiographs, thereby reducing healthcare costs and improving patient outcomes through timely interventions.
Diagnostic Performance of Serum Erythropoietin to Discriminate Polycythemia Vera from Secondary Erythrocytosis through Established Subnormal Limits
Authors: Yoon Ji Sang , Kang Hyunhye , Jekarl Dong Wook , Lee Sung-Eun , Oh Eun-Jee
Published: August 2024

Serum erythropoietin (sEPO) is an initial screening tool for distinguishing polycythemia vera (PV) from secondary erythrocytosis (SE), but defining ‘subnormal’ sEPO levels for PV diagnosis remains contentious, complicating its clinical utility. This study compares the diagnostic performance of sEPO across established subnormal limits, including reference interval (RI), clinical decision limit (CDL), and functional reference limit. sEPO levels were analyzed in 393 healthy donors (HDs) and 90 patients (41 PV and 49 SE), who underwent bone marrow biopsy and genetic tests due to erythrocytosis. The RI (2.5–97.5 percentile from HDs) of sEPO was 5.3–26.3 IU/L. A CDL of 3.1 IU/L, determined by ROC analysis in erythrocytosis patients, had a sensitivity of 80.5% and specificity of 87.8% for diagnosing PV. A functional reference limit of 7.0 IU/L, estimated based on the relationship between sEPO and hemoglobin, hematocrit, and WBC, increased sensitivity to 97.6% but decreased specificity to 46.7%. Using 5.3 IU/L as a ‘subnormal’ limit identified all three JAK2-negative PV cases, increasing the sensitivity and negative predictive value to 97.6% and 97.0%, respectively. Combining the RI, CDL, and functional reference limit may improve PV diagnostic accuracy.
Monoclonal Gammopathy of Clinical Significance (MGCS) and Related Disorders: A Review and the Role of Imaging
Authors: El Sadaney Ahmed O. , Dutta Anika , Cook Joselle , Baffour Francis I.
Published: August 2024

The term monoclonal gammopathy of clinical significance (MGCS) refers to a group of symptomatic monoclonal gammopathies that do not meet the diagnostic criteria for malignant plasma cell disorders, such as multiple myeloma or Waldenström macroglobulinemia. These symptoms are attributable to the paraneoplastic effects of monoclonal immunoglobulins that occur through diverse mechanisms. The presence of symptoms distinguishes MGCS from monoclonal gammopathy of undetermined significance, which lacks significant symptomatic presentation. The presentations of MGCS are manifold, adding to the diagnostic challenge. Clinical suspicion is key for accurate and timely diagnosis. Radiologic imaging can provide pivotal information to guide the diagnosis. In this review, we discuss MGCS from a radiology perspective and highlight pertinent imaging features associated with the disorders.