bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral Vestibulopathy: What Can the Video Head Impulse Test Tell Us?
Authors: Waissbluth Sofia , Viñuela Macarena , Escobedo Emilia , Pastore Antonia , Novoa Ivan
Published: February 2025

Bilateral vestibulopathy (BV) is a known cause of chronic vestibular syndrome. With the video head impulse test (VHIT), we can now evaluate all six semicircular canals independently and establish BV subgroups based on canal gain patterns. Background/objectives: To assess canal gain patterns for BV with VHIT, and evaluate subgroups with regard to sex, age, and hearing loss. Methods: A retrospective chart review was performed of all patients who underwent a VHIT between January 2021 and July 2024. Patients with decreased lateral canal gains, bilaterally, were included. Results of canal gains, VHIT patterns, audiometry, and videonystagmography (VNG) results were reviewed. Results: 101 cases were included. Patients were 75.5 ± 13.1 years old and 64.4% were women. Various VHIT patterns were observed; the most frequent being decreased canal gains across all six canals (44.6%), followed by a mix of canals with decreased gains with no clear pattern (34.7%). Decreased gains limited to the lateral canals were rare. We did not observe any significant difference between subgroups with regard to gender or age. Concomitant hearing loss was common (89.6%). A trend was noted, suggesting that severity of hearing loss increased with the number of affected canals. An abnormal VNG test was common (73.3%). Conclusions: Various patterns of canal gains were observed for patients with BV. Audiometry and VNG should be considered as part of BV studies since abnormalities are commonly found. Further research is needed to understand VHIT patterns in BV.
Light Exposure, Physical Activity, and Indigeneity Modulate Seasonal Variation in NR1D1 (REV-ERBα) Expression
Authors: Gubin Denis , Kolomeichuk Sergey , Danilenko Konstantin , Stefani Oliver , Markov Alexander , Petrov Ivan , Voronin Kirill , Mezhakova Marina , Borisenkov Mikhail , Shigabaeva Aislu , Boldyreva Julia , Petrova Julianna , Weinert Dietmar , Cornelissen Germaine
Published: February 2025

Nuclear receptor subfamily 1 group D member 1 (NR1D1 or REV-ERBα) is a crucial element of the circadian clock’s transcriptional and translational feedback loop. Understanding its expression in humans is critical for elucidating its role in circadian rhythms and metabolic processes, and in finding potential links to various pathologies. In a longitudinal survey, we examined REV-ERBα expression at 08:00 using a real-time polymerase chain reaction (qRT-PCR) in blood mononuclear cells from Arctic native and non-native residents during equinoxes and solstices. REV-ERBα expression exhibited a pronounced seasonality, peaking at the summer solstice, and reaching a nadir at the winter solstice in both natives and non-natives, with a relatively higher summer peak in natives. After adjusting for age, sex, and body mass index, the amount and timing of light exposure, the amount of physical activity, and indigeneity emerged as significant predictors of REV-ERBα expression.
Exploring Climate-Driven Mismatches Between Pollinator-Dependent Crops and Honeybees in Asia
Authors: Rahimi Ehsan , Jung Chuleui
Published: February 2025

In Asia, Apis cerana (native) and Apis mellifera (introduced) are the primary managed honeybee species, vital for pollination and honey production. However, climate change and other threats are driving pollinator declines, while research on their ecology in Asia remains limited. Bridging these knowledge gaps is crucial for developing conservation strategies to sustain pollination services and agricultural systems in the region. In this study, we evaluated the potential impacts of climate change on the spatial interactions between two honeybee species (A. cerana and A. mellifera) and 20 pollinator-dependent crops across 23 countries in Asia. We used species distribution models (SDMs) to generate habitat suitability maps for both honeybees and crops under current and future climate scenarios (SSP585 for 2070). Schoener’s D statistic was employed to quantify the spatial overlap, and a novel spatial approach was applied to create mismatch maps that identified areas of increased or decreased interactions. We found that, on average, A. cerana demonstrated higher overlap with 12 crops compared to 8 for A. mellifera in future projections. Key crops like sesame, eggplant, and mango retained strong overlaps with both pollinators, while mismatches were more pronounced for A. cerana, particularly with watermelon, strawberry, and buckwheat. In contrast, A. mellifera showed greater stability and resilience in spatial overlaps with crops such as soybean and sunflower. Overall, A. cerana is expected to face more significant spatial mismatches, highlighting its vulnerability to climate-induced changes and the critical need for targeted conservation efforts. This study highlights the urgent need for region-specific conservation strategies by identifying areas at risk of losing critical pollination services. Our results provide a crucial framework for informed management and policy interventions to safeguard pollination-dependent agricultural systems and biodiversity in Asia amidst accelerating environmental challenges.
Research Progress on the Influence of Novel Targeted Drugs for Osteoporosis on Glucose Metabolism
Authors: Meng Lingyang , Sun Lei , Li Mei
Published: February 2025

Both diabetes and osteoporosis are serious chronic conditions. Evidence is mounting that several bone-derived hormones play a role in glucose metabolism in patients with diabetes. Notably, novel biotargeted anti-osteoporotic agents have been recently found to reduce the risk of diabetes. This review explores the correlation of osteokines, including the receptor activator of nuclear factor-κB ligand (RANKL), sclerostin, and Dickkopf-1 (DKK1) with glycemic indicators in patients with diabetes, as well as the effects of their respective monoclonal antibodies on glucose metabolism and their possible mechanisms. Denosumab, the monoclonal antibody against RANKL, has been shown to reduce glycated hemoglobin (HbA1c) and the risk of diabetes, possibly by enhancing pancreatic β-cell survival and glucagon-like peptide-1 secretion. Sclerostin was positively correlated with HbA1c and may induce insulin resistance via endoplasmic reticulum stress. The association of DKK1 with fasting plasma glucose and HbA1c is still unclear, though decreasing DKK1 levels may correlate with β-cell survival. However, few studies have investigated the effects of antibodies against sclerostin or DKK1 on glucose metabolism. Further research is required to elucidate the influence of novel anti-osteoporotic biotargeted agents on glucose homeostasis in patients with diabetes and their underlying mechanisms.
Applying Wearable Sensors and Machine Learning to the Diagnostic Challenge of Distinguishing Parkinson’s Disease from Other Forms of Parkinsonism
Authors: Khalil Rana M. , Shulman Lisa M. , Gruber-Baldini Ann L. , Reich Stephen G. , Savitt Joseph M. , Hausdorff Jeffrey M. , Coelln Rainer von , Cummings Michael P.
Published: February 2025

Background/Objectives: Parkinson’s Disease (PD) and other forms of parkinsonism share motor symptoms, including tremor, bradykinesia, and rigidity. The overlap in their clinical presentation creates a diagnostic challenge, as conventional methods rely heavily on clinical expertise, which can be subjective and inconsistent. This highlights the need for objective, data-driven approaches such as machine learning (ML) in this area. However, applying ML to clinical datasets faces challenges such as imbalanced class distributions, small sample sizes for non-PD parkinsonism, and heterogeneity within the non-PD group. Methods: This study analyzed wearable sensor data from 260 PD participants and 18 individuals with etiologically diverse forms of non-PD parkinsonism, which were collected during clinical mobility tasks using a single sensor placed on the lower back. We evaluated the performance of ML models in distinguishing these two groups and identified the most informative mobility tasks for classification. Additionally, we examined the clinical characteristics of misclassified participants and presented case studies of common challenges in clinical practice, including diagnostic uncertainty at the patient’s initial visit and changes in diagnosis over time. We also suggested potential steps to address the dataset challenges which limited the models’ performance. Results: Feature importance analysis revealed the Timed Up and Go (TUG) task as the most informative for classification. When using the TUG test alone, the models’ performance exceeded that of combining all tasks, achieving a balanced accuracy of 78.2%, which is within 0.2% of the balanced diagnostic accuracy of movement disorder experts. We also identified differences in some clinical scores between the participants correctly and falsely classified by our models. Conclusions: These findings demonstrate the feasibility of using ML and wearable sensors for differentiating PD from other parkinsonian disorders, addressing key challenges in its diagnosis and streamlining diagnostic workflows.
Reversing Pathology in an Aggravated Fabry Mouse Model Using Low-Dose Engineered Human Alpha-Galactosidase A AAV Gene Therapy
Authors: Ruangsiriluk Wanida , Deshpande Mugdha , Boukharov Natalia , Rajarshi Girija , Mukherji Shreya , Yuan Shipeng , Wiseman Jennifer , Chen Nancy , Park Eric , Cho Hyelim , Islam Rizwana
Published: February 2025

Background/Objectives: Fabry disease is an X-linked disorder caused by lysosomal accumulation of glycosphingolipids due to the deficiency of α-Galactosidase (α-GAL), which leads to pathology in multiple organ systems. The standard of care is enzyme replacement therapy (ERT) with recombinant native α-GAL protein. Shortcomings of the native α-GAL include low stability, a short circulating half-life, and inadequate uptake by affected tissues that limits the efficacy of ERT and could potentially reduce AAV gene therapy (GT) benefits. Cross-correction by secreted α-GAL is essential for liver-targeted as well as ubiquitous AAV GT due to poor transduction and/or short half-life of some of the significantly affected cell types. Methods: To overcome potential limitations of AAV GT delivering native α-GAL, we used an engineered GLA transgene product to improve enzyme stability and reduce predicted immunogenicity. Results: The stabilized α-GAL variant, Eng-C, had an extended circulatory half-life, allowing for enhanced distribution and efficient uptake by target organs. AAV gene therapy with Eng-C demonstrated significantly greater substrate reduction in the severe Fabry G3Stg/GlaKO mouse model across all affected tissues. Efficacy of the Eng-C AVV GT was equal to or greater than the efficacy of the higher doses of the AAV GT with native α-GAL. Furthermore, this study is the first to demonstrate that the pre-existing pathology in some tissues in G3Stg/GlaKO mice can be reversed with efficient treatment. Conclusions: Our findings demonstrate that an AAV-based gene therapy expressing an engineered α-GAL with improved stability and lower immunogenicity could be effective at lower doses than other AAV GTs, potentially offering lower safety risks typically associated with high AAV vector doses.
Nanoparticle-Enhanced Acoustic Wave Biosensor Detection of Pseudomonas aeruginosa in Food
Authors: Spagnolo Sandro , Davoudian Katharina , Franier Brian De La , Kocsis Robert , Hianik Tibor , Thompson Michael
Published: February 2025

A biosensor was designed for detecting Pseudomonas aeruginosa (P. aeruginosa) bacteria in whole milk samples. The sensing layer involved the antifouling linking molecule 3-(2-mercaptoethanoxy)propanoic acid (HS-MEG-COOH), which was covalently linked to an aptamer for binding P. aeruginosa. The aptasensor uses the thickness shear mode (TSM) system for mass-sensitive acoustic sensing of the bacterium. High concentrations (105 CFU mL−1) of nonspecific bacteria, E. coli, S. aureus, and L. acidophilus, were tested with the aptasensor and caused negligible frequency shifts compared to P. aeruginosa. The aptasensor has high selectivity for P. aeruginosa, with an extrapolated limit of detection (LOD) of 86 CFU mL−1 in phosphate-buffered saline (PBS) and 157 CFU mL−1 in milk. To improve the sensitivity of the sensor, gold nanoparticles (AuNPs) were functionalized with the same aptamer for P. aeruginosa and flowed through the sensor following bacteria, reducing the extrapolated LOD to 68 CFU mL−1 in PBS and 46 CFU mL−1 in milk. The frequency variations in the aptasensor are proportional to various concentrations of P. aeruginosa (102–105 CFU mL−1) with and without AuNPs, respectively. The low and rapid mass-sensitive detection demonstrates the ability of the aptasensor to quantitatively identify bacterial contamination in buffer and milk.
Structure-Based Modeling of the Gut Bacteria–Host Interactome Through Statistical Analysis of Domain–Domain Associations Using Machine Learning
Authors: Kiouri Despoina P. , Batsis Georgios C. , Mavromoustakos Thomas , Giuliani Alessandro , Chasapis Christos T.
Published: February 2025

The gut microbiome, a complex ecosystem of microorganisms, plays a pivotal role in human health and disease. The gut microbiome’s influence extends beyond the digestive system to various organs, and its imbalance is linked to a wide range of diseases, including cancer and neurodevelopmental, inflammatory, metabolic, cardiovascular, autoimmune, and psychiatric diseases. Despite its significance, the interactions between gut bacteria and human proteins remain understudied, with less than 20,000 experimentally validated protein interactions between the host and any bacteria species. This study addresses this knowledge gap by predicting a protein–protein interaction network between gut bacterial and human proteins. Using statistical associations between Pfam domains, a comprehensive dataset of over one million experimentally validated pan-bacterial–human protein interactions, as well as inter- and intra-species protein interactions from various organisms, were used for the development of a machine learning-based prediction method to uncover key regulatory molecules in this dynamic system. This study’s findings contribute to the understanding of the intricate gut microbiome–host relationship and pave the way for future experimental validation and therapeutic strategies targeting the gut microbiome interplay.
A Novel Simplified Physical Model Testing Method for Ground Settlement Induced by Shield Tunnel Excavation
Authors: Guo Hanzhang , Zhang Guangcheng , Mao Xiongyao , Zan Jianhang
Published: February 2025

In order to investigate the mechanism of ground settlement induced by shield tunnels better, this study proposes a novel simplified physical model testing method. In this physical model, double layer tubes with different materials are used to model the tunnel boring machine (TBM) and tunnel, respectively. When the outer tube in the experimental box is removed, the gap between the two different tubes can be utilized to reflect the ground settlement caused by TMB construction. Meanwhile, 3D image monitoring technology is introduced to collect ground settlement data for research on the mechanism of ground settlement induced by TBM construction. In order to validate the proposed testing method, firstly, the pilot experiment is performed; then, the obtained settlement curve obeys the Gaussian distribution, and the obtained settlement process is similar to that of the practical situation. Furthermore, based on the proposed testing method, an orthogonal experiment is designed to investigate the influences of the ground loss ratio, burial depth, and stratum condition on the ground settlement during the construction process. The results indicate that the ground loss ratio caused by the gap during construction excavation has a more significant impact than the tunnel burial depth and ground conditions. The findings in this study provide a quantitative guide for settlement monitoring during TBM construction, demonstrating that the ground loss ratio has the most significant impact on settlement (up to 28.7% deviation), while the effects of burial depth and stratum conditions are relatively minor (4.4% and 4.2% deviation, respectively). This method offers a practical and efficient approach for predicting and controlling ground settlement in TBM construction, which is of great importance in its practical application.
Development of BIM Platform for Semantic Data Based on Standard WBS Codes
Authors: Kim Dongwook , Matos Jose , Dang Son N.
Published: February 2025

Building Information Modeling (BIM) has become an indispensable tool for risk management and construction oversight, especially in the case of complex and irregularly shaped buildings. BIM’s ability to reduce construction errors has been proven through advanced features like clash detection, schedule forecasting, and cost estimation. As the adoption of BIM grows, software providers such as Autodesk, Bentley, Trimble, and Nemetschek have developed advanced tools that incorporate Project Lifecycle Management (PLM). However, these tools are not easily transferable to Asian countries, where construction management often uses unit pricing rather than the more intricate systems common in Europe and the US. Legacy data also play a crucial role in Asian construction management, impacting risk profiling and cost predictions for similar projects. This study explores the integration of 4D BIM data within a Work Breakdown Structure (WBS) framework in a real-world setting. The first step was the creation of an in-house BIM platform, CEV (Civil Easy View), built on the Autodesk Forge viewer. CEV is designed as a BIM viewer tailored for field staff and supervisors. This 4D BIM application showed strong connectivity through standardized WBS codes, allowing for automatic synchronization between object and schedule data.
Path Planning for Construction Robot Based on the Improved A* Algorithm and Building Information Modeling
Authors: Wang Dejiang , Liu Bolong , Jiang Haili , Liu Panpan
Published: February 2025

Path planning is a key technology in the automation of construction robots, and its implementation mainly relies on navigation algorithms and the generation of environment maps. However, the original A* algorithm has issues such as not considering dimensional constraints, a high number of turning nodes, and unsmooth paths. Moreover, traditional environment map generation is time-consuming and energy-consuming. Therefore, this paper proposes a path-planning method for construction robots based on an improved A* algorithm and BIM. First, the A* algorithm is improved by incorporating dimensional constraints for both the building and the robot and by reasonably setting virtual obstacles to enhance the feasibility of robot movement. Additionally, B-spline curves are used to optimize the path, reduce turning points, and achieve a smoother trajectory. Second, Dynamo visual programming is used to process the building’s BIM model, enabling efficient generation of the environment map while preserving the rich semantic and geometric information of the building. Finally, the improved A* algorithm is employed to perform path planning within the environment map generated from the BIM model, resulting in the generation of the optimal path. Through experimental verification on the civil engineering building of a university, the results show that the improved A* algorithm can successfully navigate within the BIM-generated map. It not only ensures the safety and smoothness of path planning but also enables the fast and efficient generation of environment maps. This effectively advances the research and application of BIM technology in the field of robot navigation.
Assessing Construction Safety Performance in Urban Underground Space Development Projects from a Resilience Enhancement Perspective
Authors: Yang Xiaohua , Xiahou Xiaer , Li Kang , Li Qiming
Published: February 2025

Urban underground space construction frequently encounters issues of inadequate prevention and ineffective resistance to various disturbances, resulting in safety accidents that are difficult to recover from. Resilience pertains to a system’s capacity to absorb, resist, recover, and adapt when faced with disruptions. Enhancing the construction safety resilience of underground spaces can effectively tackle the issue of frequent accidents and the challenge of pre-controlling risks at construction sites. Utilizing systems engineering theory, this paper investigates the factors that affect the construction safety resilience of underground spaces and establishes a general framework for evaluating the safety performance of the construction process. Utilizing a large-scale underground construction project as a case study, the Bayesian network inference technique is applied to ascertain the project’s safety resilience value. Through reverse reasoning, the method identifies the most likely sequence of causes leading to construction safety incidents, and subsequently, the resilience assessment framework’s efficacy is tested. The research findings suggest that the core of construction safety management is the prevention of unsafe human behaviors and that the key to enhancing resilience lies in the optimization of response capabilities. The proposed “PFR-EFR-LFR” whole-process resilience analysis method can be applied to safety assessments for various types of underground space construction projects.
Research on BIM-Based Visualization, Simulation, and Early Warning System for Shield Tunnel Construction
Authors: Cheng Qian , Wang Xiangyu , Sun Junbo , Zhao Hongyu , Liu Xianda
Published: February 2025

This study aims to facilitate a comparison between construction monitoring data and simulation results, focusing on the dynamic adjustment of safety monitoring parameters in shield construction. First, a finite element simulation was performed to define a reasonable range for shield parameters based on settlement control values, thereby determining the theoretical settlement value. An early warning system was then developed integrating two key factors: theoretical and control settlement values. Finally, Dynamo was used to merge the digital and analog data, enhancing the visual representation of the monitoring information. The findings show that combining simulations with an early warning system effectively addresses the dynamic control challenges of shield construction parameters. Furthermore, integrating digital and analog monitoring significantly improves the efficiency of real-time visualization in monitoring data. This research provides a novel and effective methodology for enhancing shield tunnel construction safety, precision, and efficiency, offering critical insights for large-scale infrastructure projects and contributing to more reliable monitoring systems in complex construction environments.
Restorative Environment Design Drives Well-Being in Sustainable Elderly Day Care Centres
Authors: Li Yuting , Lin Xiayan , Li Shimin , Huang Min , Ren Zhipeng , Song Qi
Published: February 2025

At present, China is facing a serious aging problem. Although community daycare centers have been built, they generally have problems such as inadequate facilities, single-service provision, and insufficient environmental design. These problems make it impossible to meet the multifaceted needs of the elderly in their old age, enhance their sense of wellbeing, and achieve sustainable development. Therefore, relevant policies indicate that the elderly service model of community day care centers should be actively constructed and upgraded. However, most of the existing research focuses on service models or single-design practice studies, and there are relatively few studies that address the integration of restorative environmental design and sustainability. Therefore, this paper systematically explores the current research status of restorative environmental design in daycare centers for the elderly through macro quantitative bibliometric analysis and micro qualitative content analysis based on Web of Science (WOS) data, then proposes design practice strategies, implementation paths, and evaluation methods to enhance wellbeing. Through keyword network visualization analysis, this paper identifies eight main clusters: physical literacy, public preschool services, social support, elderly day care centers, hospice use, designing leisure products, risk factors, and communicative skills. The high-frequency keywords “health”, “elderly”, “cultural diversity”, “children”, and “quality of life” are further categorized into “caregiving”, “Alzheimer’s disease”, “adult day care”, and “daycare centers”, with the latter split into three further categories: design strategy, implementation approach, and evaluation. In addition, this paper combines SDG3 goals such as reducing premature mortality from non-communicable diseases, achieving universal health coverage, etc., in order to explore the potential of resilience-based environmental design to promote the sustainable development of elderly daycare centers. This study not only complements the research related to restorative environmental design in daycare centers for the elderly but also provides specific guidelines and references for future environmental design, policy planning, and elderly service practices.
Primary Intrathoracic Synovial Sarcoma: An Analysis of Outcomes of This Rare Disease
Authors: Patel Riddhi R. , Bishop Andrew J. , Lazar Alexander J. , Lin Patrick P. , Benjamin Robert S. , Patel Shreyaskumar R. , Ludwig Joseph , Ravi Vinod , Vaporciyan Ara A. , Araujo Dejka M.
Published: February 2025

Background: Primary intrathoracic synovial sarcoma (SS) is a rare entity. The objective of this study was to evaluate survival outcomes for patients with intrathoracic SS presenting with localized disease at diagnosis. Methods: We conducted a retrospective review of 63 patients diagnosed with intrathoracic SS between 1997 and 2020. The Kaplan–Meier method and log-rank test were used to estimate the progression-free survival (PFS), overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS). The hazard ratios were estimated by using Cox proportional hazards regression. Median follow-up time, age-at-diagnosis, and primary tumor size were 31 months (range: 4–218 months), 43 years (range: 18–77), and 7 cm (range: 1–23), respectively. Results: Sixty-two of sixty-three (98%) patients had their primary tumor resected, from whom eighteen (29%) and forty-three (69%) had received neo/adjuvant radiotherapy and chemotherapy, respectively. Median PFS, OS, and MFS were 1.2, 3.0, and 1.1 years, respectively. Based on multivariable analyses, patients with ≥5 cm tumor size had poorer OS (versus < 5 cm; HR: 2.66; 95% CI: 1.16, 6.11; LR-p = 0.014). Importantly, the receipt of neo/adjuvant chemotherapy was the only factor associated with both a more favorable PFS (HR: 0.33; 95% CI: 0.17, 0.65; LR-p = 0.0002) and a more favorable MFS (median 1.33 years versus no chemo 0.5 years; HR: 0.35; 95% CI: 0.17, 0.73; LR-p = 0.005). Conclusions: Outcomes associated with intrathoracic SS remain poor. Factors associated with poorer outcomes include larger tumors and omission of chemotherapy in the management of localized disease. We recommend providing perioperative chemotherapy to all patients with ≥5 cm tumor size to improve progression and metastasis-free survival.
The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches
Authors: Catalano Teresa , Selvaggi Federico , Cotellese Roberto , Aceto Gitana Maria
Published: February 2025

Altered levels of reactive oxygen species (ROS) are recognized as one of the key factors in mediating tumor cell survival in the tissue microenvironment, where they play a role in the initiation, progression and recurrence/relapse of colorectal cancer (CRC). Tumor cells can adapt to oxidative stress (OS) using genetic or metabolic reprogramming in the long or short term. In addition, tumor cells defend themselves through positive regulation of antioxidant molecules, enhancing ROS-driven proliferation. Balanced oxidative eustress levels can influence chemotherapy resistance, allowing tumor cells to survive treatment. Secondary effects of chemotherapy include increased ROS production and redox stress, which can kill cancer cells and eliminate drug resistance. Anticancer treatments based on manipulating ROS levels could represent the gold standard in CRC therapy. Therefore, exploring the modulation of the response to OS in deregulated signaling pathways may lead to the development of new personalized CRC treatments to overcome therapy resistance. In this review, we explore the role of ROS in the initiation and progression of CRC and their diagnostic implications as biomarkers of disease. Furthermore, we focused on the involvement of ROS in different CRC therapeutic options, such as surgery, radiotherapy, theranostic imaging, chemotherapy and immunotherapy and other precision medicine approaches.
Targeting STAT3 for Cancer Therapy: Focusing on Y705, S727, or Dual Inhibition?
Authors: Berkley Kyli , Zalejski Julian , Sharma Ashutosh
Published: February 2025

Background/Objectives: Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor that is strongly implicated in various cancers. In its canonical signaling pathway, Janus kinases (JAKs) phosphorylate STAT3 at the Y705 residue in response to cytokines or growth factors, with pY705 serving as a key marker of STAT3 oncogenic activity. Elevated pY705 levels correlate with poor prognosis, and numerous small-molecule inhibitors have been developed to block this phosphorylation site. More recently, phosphorylation at the S727 residue (pS727) has emerged as a critical contributor to STAT3-mediated oncogenesis, particularly due to its role in mitochondrial translocation. Evidence suggests that pS727 may even surpass pY705 in driving oncogenic activity. These findings prompt an important question: Which residue should be prioritized for effective STAT3 inhibition in cancer therapy? Methods: This review compiles and critically analyzes the current literature on STAT3 inhibitors targeting pY705 and/or pS727, evaluating their therapeutic efficacy in vitro, in vivo, and in clinical trials. We assess the unique effects of targeting each residue on downstream signaling, toxicity, and clinical outcomes. Results: Our analysis indicates that inhibitors targeting both pY705 and pS727 achieve the greatest therapeutic effectiveness. However, pS727 targeting is associated with higher toxicity risks. Conclusions: Comprehensive evaluation of STAT3 inhibitors underscores the importance of targeting pY705 for maximum therapeutic benefit. The analysis also shows that co-targeting pS727 may increase overall efficacy. However, pS727 inhibition should be approached with lower affinity to minimize toxicity and enhance the clinical feasibility of dual-targeting strategies.
Advances in Surgery and Sustainability: The Use of AI Systems and Reusable Devices in Laparoscopic Colorectal Surgery
Authors: Iwai Takuma , Shinji Seiichi , Yamada Takeshi , Uehara Kay , Matsuda Akihisa , Yokoyama Yasuyuki , Takahashi Goro , Miyasaka Toshimitsu , Matsui Takanori , Yoshida Hiroshi
Published: February 2025

The sustainability of the surgical workforce, environmental pollution caused by disposable instruments, and the rising costs of medical care are pressing issues worldwide. This review explores sustainable surgical practices for laparoscopic surgery through the application of surgical AI systems and reusable energy devices. Surgical AI systems enable the precise real-time visualization of organ anatomy, enhance surgical accuracy, and support educational initiatives. The Reusable Energy Device Laparoscopic-Assisted Colectomy (RE-LAC) technique, which employs reusable energy devices, has the potential to reduce medical waste and costs while maintaining safety and quality standards. A comparative analysis of RE-LAC and conventional disposable devices showed no significant differences in operative time or blood loss, suggesting that RE-LAC may be a viable alternative for sustainable surgical practice. These approaches align with the Sustainable Development Goals, contributing to sustainable healthcare by improving workforce efficiency, reducing environmental impacts, and promoting economic feasibility. Further large-scale, multi-institutional studies are necessary to optimize their implementation and maximize their global impact.
Melanoma Arising in Tattoos: A Case Series and Scoping Review of the Literature
Authors: Brusasco Marco , Spagnolini Sofia , Mazzoni Laura , Magi Serena , Scarcella Giuseppe , Stanganelli Ignazio
Published: February 2025

Background/Objectives: The prevalence of tattoos has risen globally in recent decades, ranging from 10% to 29%. Although rare, melanomas arising within tattoos are challenging for dermatologists due to the complexities in clinical and dermoscopic evaluation. In this article, we report two cases of melanoma on tattoos, review the reported cases in the literature, and examine the role of reflectance confocal microscopy (RCM) in improving the diagnosis of melanoma on tattooed skin. Methods: We conducted a systematic literature search on Medline/Pubmed for the period from the inception of the databases to 31 October 2024, using the Mesh major topics ‘melanoma’ AND ‘tattoo’ OR ‘tattoo skin tumor’. Out of the 268 citations identified by our search, 37 studies met the eligibility criteria. Results: In total, 43 cases of melanoma arising on tattooed skin were identified, to which we add our 2 cases, bringing the total to 45. The most common locations were the upper limbs (53%) and trunk (38%), predominantly arisen on black and blue tattoos. Of 40 cases with known depth of invasion, 4 were in situ and 36 invasive, with a mean Breslow thickness of 2.7 mm. Seven patients had a positive sentinel lymph node. Of 16 cases with an available horizontal diameter, 12 melanomas had a diameter of ≥1 cm. Conclusions: The limited cases of ‘’melanoma on tattoos” reported in the literature suggest a coincidental association rather than a direct causal link. Nevertheless, increased awareness among patients and tattoo artists about potential risks and preventive measures may enhance the management of melanocytic lesions in tattooed individuals. Lastly, integrating reflectance confocal microscopy with dermoscopy increases the overall diagnostic accuracy for melanoma, enhancing the identification of pigmented and non-pigmented skin lesions.
Expanding Indications in Transplant Oncology
Authors: Allkushi Erlind , Wehrle Chase J. , Kim JaeKeun , Khalil Mazhar , Kwon David C. H. , Fujiki Masato , Pinna Antonio D. , Miller Charles , Schlegel Andrea , Aucejo Federico , Hashimoto Koji , Pita Alejandro
Published: February 2025

Liver transplantation is aptly described as the only curative treatment for cirrhosis and cirrhosis with co-morbid hepatocellular carcinoma (HCC). Its utility in the management of various other primary and secondary liver cancers is gaining traction rapidly, with more thorough assessments on broader populations continuing to emerge. Most prominently, this includes colorectal cancer liver metastasis (CRLM), cholangiocarcinoma (CCA), neuroendocrine tumors (NETs), and more. Furthermore, despite being a well described treatment for HCC for many years, growing evidence supports a change in oncological strategy for HCC, with broadened selection criteria and more advanced systemic and locoregional therapies available. Our review aims to describe the evidence supporting the expansion of indications and selection criteria for liver transplantation in various oncologic indications of primary and secondary liver tumors.
Characterizing the Natural History of Pediatric Brain Tumors Presenting with Metastasis
Authors: Lu Victor M. , Niazi Toba N.
Published: February 2025

Background: The natural history of pediatric patients with metastasis of primary brain tumors within and outside the central nervous system is poorly understood, as too are possible clinical correlates with outcome. Correspondingly, the aim of this study was to interrogate a national database to characterize this diagnosis and its clinical course in pediatric patients. Methods: The U.S. National Cancer Database (NCDB) was interrogated between the years 2005–2016 for all patients aged 18 years and younger with a primary brain tumor diagnosis, as well as evidence of disease metastasis at initial diagnosis. Data were summarized and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. Results: Out of a total of 8615 pediatric brain tumor patients, 356 (4%) had evidence of metastasis at initial diagnosis. Compared to patients without metastasis, patients with metastasis were statistically younger, more often male, and less likely to have private health insurance (all p < 0.050). With respect to clinical characteristics, the primary tumors of patients with metastasis were statistically more likely to be located in the cerebellum; be of higher histologic grading, with a higher proportion of medulloblastoma diagnoses and lower proportion of malignant glioma and pilocytic astrocytoma diagnoses; and were more likely to be treated by subtotal surgical resection, chemotherapy and radiation therapy (all p < 0.050) when compared to patients without metastasis. Five-year OS for those with metastasis was significantly lower than those without (48% vs. 75%, p < 0.001), with the median overall survival for patients with metastasis being 53 months (95% CI 29–86). Multivariate analysis indicated that a shorter OS was independently associated with the primary diagnoses of malignant glioma (HR 27.7, p = 0.020) and Atypical Teratoid/Rhabdoid Tumor (ATRT, HR 41.1, p = 0.041) and with WHO grades 3 (HR 20.1, p = 0.012) and 4 (HR 11.5, p < 0.001). Longer OS was significantly and independently associated with surgery (HR 0.49, p < 0.001), chemotherapy (HR 0.53, p = 0.041), and radiation therapy (HR 0.57, p = 0.026). Conclusions: Although uncommon, pediatric brain tumors with evidence of metastasis at initial diagnosis will present with a distinct socioeconomic and clinical profile compared to patients without metastasis. Multiple predictors are independently associated with overall prognosis, and understanding these features should be validated in prospective efforts to identify vulnerable patients earlier in order to maximize the impact of treatment.
Detection of Genomic Copy Number Variations in Ovarian Cancer in the Peripheral Blood System
Authors: Wahl Lena , Hliabtsova Ulyana , Qian Xueqian , Klopf Anastasia , Hedemann Nina , Flörkemeier Inken , Rogmans Christoph , Kalab Michael , Dempfle Astrid , Maass Nicolai , Bauerschlag Dirk Olaf , van Mackelenbergh Marion Tina , Weimer Jörg Paul , Le Huy Duc
Published: February 2025

Ovarian cancer has an incidence of 11 [...]
ctDNA as an Objective Marker for Postoperative Residual Disease in Primary Advanced High-Grade Serous Ovarian Cancer
Authors: Glueck Valentina , Grimm Christoph , Postl Magdalena , Brueffer Christian , Segui Nuria , Alcaide Miguel , Oton Lucia , Chen Yilun , Saal Lao H. , Hofstetter Gerda , Polterauer Stephan , Muellauer Leonhard
Published: February 2025

Background/Objectives: The surgeon’s subjective intraoperative evaluation is the standard of care to assess postoperative residual disease (RD) in advanced epithelial ovarian cancer (EOC). We investigated the feasibility of ctDNA as an objective marker for postoperative RD. Methods: This prospective study included 27 patients with advanced ovarian cancer (FIGO IIIA1–IVB) who underwent primary surgery between July 2021 and July 2022. Blood samples were analyzed preoperatively and on days 2 (d2) and 10 (d10) postoperatively. Low-coverage whole genome sequencing (WGS) was used to identify structural variants (SVs) at single-base pair resolution, single nucleotide variants (SNVs), and indels in tumor tissue to develop personalized, tumor-informed digital polymerase chain reaction (dPCR) fingerprint assays for each patient. Results: dPCR fingerprint assays were successfully developed for all patients by identifying one to eight SVs/SNVs per patient. ctDNA was detected in 96% (n = 26/27) of patients preoperatively and in 81% (n = 22/27) of patients at d10. Median ctDNA levels at d10 were significantly higher in patients with postoperative RD (median 367.38 copies (cps)/mL, 2.84% variant allele frequency; VAF) than in patients without postoperative RD (median 0.92 cps/mL, 0.017% VAF, p < 0.001). In patients with postoperative RD, ctDNA levels increased from the preoperative stage to d10 in seven out of eight patients (p = 0.016). In patients with complete tumor resection, ctDNA levels decreased from the preoperative stage to d10 in 17/19 patients (p < 0.001). Conclusions: A tumor-informed personalized ctDNA approach demonstrated feasibility, providing extremely high detection rates pre- and postoperatively. These results indicate that this approach could potentially be used for postoperative RD assessment in patients with primary advanced EOC.
Systematic Comparison of FBS and Medium Variation Effect on Key Cellular Processes Using Morphological Profiling
Authors: Lebedev Timofey , Mikheeva Alesya , Gasca Valentina , Spirin Pavel , Prassolov Vladimir
Published: February 2025

Although every cell biologist knows the importance of selecting the right growth conditions and it is well known that the composition of growth medium may vary depending on a product brand or lot affecting many cellular processes, still those effects are poorly systematized. We addressed this issue by comparing the effect of 12 fetal bovine sera (FBS) and eight growth media from different brands on the morphological and functional parameters of five cell types: lung adenocarcinoma, neuroblastoma, glioblastoma, embryonic kidney, and colorectal cancer cells. Using high-throughput imaging, we compared cell proliferation; performed morphological profiling based on the imaging of 561,519 cells; measured extracellular regulated kinases (ERK1/2) activity, mitochondria potential, and lysosome accumulation; and compared cell sensitivity to drugs, response to EGF stimulation, and ability to differentiate. We found that changes in cell proliferation and morphology were independent, and morphological changes were associated with differences in mitochondria potential or the cell’s ability to differentiate. Surprisingly, the most drastic differences were detected in serum-free conditions, where medium choice affected cell survival and response to EGF. Overall, our data may be used to improve the reproducibility of experiments involving cell cultures, and the effects of 28 growth conditions on proliferation and 44 morphological parameters can be explored through a Shinyapp.
Identification and Validation of Key Biomarkers in the Proximal Aqueous Humor Outflow Pathway
Authors: Du Rong , Yang Enzhi , Clark Madison , Wang Ningli , Du Yiqin
Published: February 2025

Glaucoma is a leading cause of irreversible blindness, with elevated intraocular pressure (IOP) as the most important risk factor. The trabecular meshwork (TM) and Schlemm’s canal are the main components of the proximal aqueous humor outflow pathway. Their dysfunction is a major contributor to IOP elevation. This study aims to identify and validate key biomarkers for TM and Schlemm’s canal endothelial (SCE) cells. A Microarray was performed on characterized human TM and SCE cells to analyze their transcriptome profiling. Differentially expressed genes (DEGs) were identified and cross-referenced with published single-cell RNA sequencing (scRNA-Seq) datasets to ensure cell-specific relevance. Further validation was performed using qPCR and re-confirmed on the scRNA-seq datasets. One-way ANOVA was used for statistical analysis, and p < 0.05 was considered significant. The Microarray revealed 341 DEGs, with TM cells enriched in metabolic and signaling pathways and SCE cells enriched in adhesion, immune, and morphogenesis-related processes. Cross-referencing with scRNA-Seq data refined the list of candidate biomarkers, and qPCR confirmed the significant gene expression differences between TM and SCE cells. CTTNBP2 and MGARP were identified as TM cell markers. JAM2, PODXL, and IFI27 are new SCE cell biomarkers. The validated biomarkers offer insights into glaucoma pathophysiology and lay the groundwork for targeted therapies.
Extracranial Effects of Traumatic Brain Injury: A Narrative Review
Authors: Evanson Nathan K. , Veldhi Pratyusha , Scherpenberg Caitlyn , Riccobono John M. , Eid Haitham , McGuire Jennifer L.
Published: February 2025

Background: Traumatic brain injury (TBI) is often associated with other injuries and comorbidities. However, even isolated TBI directly leads to dysfunction in multiple body systems outside the central nervous system. These extracranial effects of TBI target systems including the autonomic nervous, cardiovascular, renal, pulmonary, immune, gastrointestinal, and hemostasis systems, as well as causing significant alteration to systemic metabolism. Aim: This review is intended to outline the effects of TBI on other body systems, and place these in context with treatment considerations for these patients. Significance: Systemic effects of TBI have implications for acute and critical care management of patients with TBI, including pharmacologic treatment. They also affect treatment decisions in chronic TBI care, as well as TBI-unrelated routine medical care for patients with chronic TBI. In addition, extracranial effects of TBI should be considered in research settings. Conclusions: It is important for clinicians and researchers to be aware of these extracranial effects, and consider their effects on pathology, treatment decisions, and interpretation of research findings.
COVID-19 and Pandemic Preparedness in the Built Environment from a Scientometric Perspective
Authors: Oguntona Olusegun , Emere Chijioke , Ohiomah Ifije , Ayorinde Emmanuel
Published: February 2025

The novel coronavirus (COVID-19) pandemic has become one of the most devastating epidemics recorded in world history. The adverse impact of the pandemic is significant within the architecture, engineering, and construction (AEC) industry and other sectors of the economy. A considerable number of COVID-19 research studies have been undertaken in response to this global challenge across disciplines, with minimal output in the built environment. Thus, this study aims to identify, analyse, and visualise COVID-19 research trends in the AEC industry to unfold the sector’s response and readiness for possible future global pandemics. The study employed the scientometric approach to explore COVID-19 research outputs in the AEC industry, an aspect of health and safety in construction that has not been considered in past studies owing to the novel nature of the coronavirus pandemic. The findings revealed that the USA, China, and the United Kingdom were the top published countries and most affected as well. Co-occurring keywords analysis further showed that the predominant focus of scholarly outputs on the subject is around four clusters focusing on sustainable resilience, pandemic pathways and insights, land use and energy strategies, and indoor air excellence. Notwithstanding its limitations, the findings establish the need for the AEC industry to adopt innovative and holistically sustainable construction practices in the event of future disasters and pandemics. The findings of the study provide a robust theoretical foundation for researchers and stakeholders in the built environment, improving the sector’s mitigative and adaptive capacity in the potential occurrence of future pandemics.