bluuebunny/crossref_metadata_2025 huggingface dataset:
Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists
Authors: Hsin Chih-hsuan , Dingemanse Jasper , Henrich Andrea , Bernaud Corine , Gehin Martine , Krause Andreas
Published: September 2023

Background: The P2Y12 receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI) symptoms. The unique pharmacological profile of selatogrel (fast, potent, and short-acting) can bridge the time gap between the onset of AMI and first medical care. A clinical Phase 1 study showed a time-dependent pharmacodynamic interaction between selatogrel and loading doses of clopidogrel and prasugrel. As treatment switching is a common clinical practice, the assessment of subsequent switching from a clopidogrel loading dose to the first maintenance dose of oral P2Y12 receptor antagonists is highly relevant. Objectives: Model-based predictions of inhibition of platelet aggregation (IPA) for the drugs triggering pharmacodynamic interactions were to be derived to support clinical guidance on the transition from selatogrel to oral P2Y12 receptor antagonists. Methods: Scenarios with selatogrel 16 mg administration or placebo followed by a clopidogrel loading dose and, in turn, prasugrel or ticagrelor maintenance doses at different times of administration were studied. Population pharmacokinetic/pharmacodynamic modeling and simulations of different treatment scenarios were used to derive quantitative estimates for IPA over time. Results: Following selatogrel/placebo and a clopidogrel loading dose, maintenance treatment with ticagrelor or a prasugrel loading dose followed by maintenance treatment quickly achieved sustained IPA levels above 80%. Prior to maintenance treatment, a short time span from 18 to 24 h was identified where IPA levels were predicted to be lower with selatogrel than with placebo if clopidogrel was administered 12 h after selatogrel or placebo. Predicted IPA levels reached with placebo alone and a clopidogrel loading dose at 4 h were consistently lower than with selatogrel administration, followed by a clopidogrel loading dose at 12 h. If a clopidogrel loading dose is administered at 12 h, selatogrel maintains higher IPA levels up to 16 h. IPA levels are subsequently lower than on the placebo until the administration of the first maintenance dose. Conclusions: Model-based predictions informed the transition from selatogrel subcutaneous administration to oral P2Y12 therapy. The application of modeling techniques illustrates the value of employing pharmacokinetic and pharmacodynamic modeling for the simulation of various clinical scenarios of switching therapies.
UBL3 Interaction with α-Synuclein Is Downregulated by Silencing MGST3
Authors: Yan Jing , Zhang Hengsen , Tomochika Yuna , Chen Bin , Ping Yashuang , Islam Md. Shoriful , Aramaki Shuhei , Sato Tomohito , Nagashima Yu , Nakamura Tomohiko , Kahyo Tomoaki , Kaneda Daita , Ogawa Kenji , Yoshida Minoru , Setou Mitsutoshi
Published: September 2023

Ubiquitin-like 3 (UBL3) is a membrane-anchored protein that plays a crucial role in sorting proteins into small extracellular vesicles. Aggregations of alpha-synuclein (α-syn) are associated with the pathology of neurodegenerative diseases such as Parkinson’s disease. Recently, the interaction between UBL3 and α-syn was discovered, with potential implications in clearing excess α-syn from neurons and its role in disease spread. However, the regulator that can mediate the interaction between UBL3 and α-syn remains unclear. In this study, using the split gaussian luciferase complementation assay and RNA interference technology, we identified that QSOX2, HTATIP2, UBE3C, MGST3, NSF, HECTD1, SAE1, and ATG3 were involved in downregulating the interaction between UBL3 and α-syn. Notably, silencing MGST3 had the most significant impact. Immunocytochemistry staining confirmed the impact of MGST3 silencing on the co-localization of UBL3 and α-syn in cells. MGST3 is a part of the antioxidant system, and silencing MGST3 is believed to contribute to oxidative stress. We induced oxidative stress with hydrogen peroxide, observing its effect on the UBL3-α-syn interaction, and showing that 800 µM of H2O2 downregulated this interaction. In conclusion, silencing MGST3 downregulates the interaction between UBL3 and α-syn.
Development of a High-Accuracy, Low-Cost, and Portable Fluorometer with Smartphone Application for the Detection of Urinary Albumin towards the Early Screening of Chronic Kidney and Renal Diseases
Authors: Pinrod Visarute , Chawjiraphan Wireeya , Segkhoonthod Khoonsake , Hanchaisri Kriangkai , Tantiwathanapong Phornpol , Pinpradup Preedee , Putnin Thitirat , Pimalai Dechnarong , Treerattrakoon Kiatnida , Cha’on Ubon , Anutrakulchai Sirirat , Japrung Deanpen
Published: September 2023

This study presents the development of a portable fluorometer with a smartphone application designed to facilitate the early screening of chronic kidney and renal diseases by enabling the sensitive detection of urinary albumin. Utilizing a fluorescence-based aptasensor, the device achieved a linear calibration curve (0.001–1.5 mg/mL) with a linearity of up to 0.98022 and a detection limit of 0.203 µg/mL for human serum albumin (HSA). The analysis of 130 urine samples demonstrated comparable performance between this study’s fluorometer, a commercial fluorometer, and the standard automated method. These findings validate the feasibility of the portable fluorometer and aptasensor combination as a reliable instrument for the sensitive and specific measurement of HSA in urine samples. Moreover, the fluorometer’s portability offers potential applications in portable point-of-care testing, enhancing its utility in clinical settings for early disease screening.
Molecularly Imprinted Polymer-Coated CdTe Quantum Dots for Fluorometric Detection of Sulfonamide Antibiotics in Food Samples
Authors: Mortari Bianca , Khan Sabir , Wong Ademar , Del Pilar Taboada Sotomayor Maria
Published: September 2023

This work reports the development and application of a highly selective core@shell-based quantum dot–molecularly imprinted polymer (QD@MIP) sensor for the detection of sulfadiazine (SDZ)—an antibiotic which belongs to the sulfonamide family. The synthesis of the smart material or MIP (molecularly imprinted polymer) was carried out by a precipitation method directly on the quantum dot surface, which played the role of a fluorescent probe in the optical sensor. The synthesized polymer was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Fluorescence experiments were performed in order to evaluate the effects of pH, interaction time of the QD@MIP with the analyte and SDZ concentration in different matrices. Under optimized conditions, a linear concentration range of 10.0–60.0 ppm and a limit of detection of 3.33 ppm were obtained. The repeatability and reproducibility of the proposed QD@MIP were evaluated in terms of the RSD, where RSD values of less than 5% were obtained in both tests. Selectivity studies were carried out in the presence of four possible interfering substances with quenching properties, and the signals obtained for these interferents confirmed the excellent selectivity of the proposed sensor; the imprinting factor value obtained for SDZ was 1.64. Finally, the proposed sensor was applied in real animal-based food samples using a spiked concentration of SDZ, where the recovery values obtained were above 90% (experiments were performed in triplicate).
Rapid and Versatile Biosensing of Liposome Encapsulation Efficiency Using Electrical Conductivity Sensor
Authors: Pereira Tatiane Melo , Bonatto Cínthia Caetano , Silva Luciano Paulino
Published: September 2023

Liposomes are prominent nanosystems for drug delivery, with potential extending beyond isolated drugs. Ethanol-aqueous plant extracts can be encapsulated within liposomes to protect bioactive compounds (secondary metabolites) from rapid oxidation and enable sustained release. Determining which compound classes are present in each extract and the encapsulation efficiency (EE) of these extracts in liposomes is crucial for nanocarrier functionality. This involves assessing the ratio of bioactive substances within liposomes to the total content. However, quantifying EE for non-isolated compounds poses challenges due to the need for advanced analytical equipment and biosensing approaches. This study introduces an innovative method for EE quantification, using a conductivity electrode (k = 0.842/cm) to establish an EE biosensing technology. By correlating dynamic light scattering (DLS), zeta potential (ZP), and electrical conductivity (Cnd) data with the conductivity meter’s calibration curve, a robust relationship between the free extract concentration and Cnd (r2 ≥ 0.950) was established. Lavender-loaded liposomes demonstrated an EE of 56.33%, while wormwood and oregano formulations exhibited high EEs of 94.33% and 91.70%, respectively. In contrast, sage-loaded liposomes exhibited an inadequate EE, encapsulating only approximately 0.57% of the extract. The straightforward quantification of the free extract within liposome formulations, compared to more complex approaches, could facilitate EE determination and support future characterizations.
A Comparison of the Neuromodulation Effects of Frontal and Parietal Transcranial Direct Current Stimulation on Disorders of Consciousness
Authors: Wan Xiaoping , Wang Yong , Zhang Ye , Song Weiqun
Published: September 2023

Frontal transcranial direct current stimulation (tDCS) and parietal tDCS are effective for treating disorders of consciousness (DoC); however, the relative efficacies of these techniques have yet to be determined. This paper compares the neuromodulation effects of frontal and parietal tDCS on DoC. Twenty patients with DoC were recruited and randomly assigned to two groups. One group received single-session frontal tDCS and single-session sham tDCS. The other group received single-session parietal tDCS and single-session sham tDCS. Before and after every tDCS session, we recorded coma recovery scale-revised (CRS-R) values and an electroencephalogram. CRS-R was also used to evaluate the state of consciousness at 9–12-month follow-up. Both single-session frontal and parietal tDCS caused significant changes in the genuine permutation cross-mutual information (G_PCMI) of local frontal and across brain regions (p < 0.05). Furthermore, the changes in G_PCMI values were significantly correlated to the CRS-R scores at 9–12-month follow-up after frontal and parietal tDCS (p < 0.05). The changes in G_PCMI and CRS-R scores were also correlated (p < 0.05). Both frontal tDCS and parietal tDCS exert neuromodulatory effects in DoC and induce significant changes in electrophysiology. G_PCMI can be used to evaluate the neuromodulation effects of tDCS.
Adults with Cerebral Palsy: Navigating the Complexities of Aging
Authors: Kumar Devina S. , Perez Gabriel , Friel Kathleen M.
Published: September 2023

The goal of this narrative review is to highlight the healthcare challenges faced by adults with cerebral palsy, including the management of long-term motor deficits, difficulty finding clinicians with expertise in these long-term impairments, and scarcity of rehabilitation options. Additionally, this narrative review seeks to examine potential methods for maintaining functional independence, promoting social integration, and community participation. Although the brain lesion that causes the movement disorder is non-progressive, the neurodevelopmental disorder worsens from secondary complications of existing sensory, motor, and cognitive impairments. Therefore, maintaining the continuum of care across one’s lifespan is of utmost importance. Advancements in healthcare services over the past decade have resulted in lower mortality rates and increased the average life expectancy of people with cerebral palsy. However, once they transition from adolescence to adulthood, limited federal and community resources, and health care professionals’ lack of expertise present significant obstacles to achieving quality healthcare and long-term benefits. This paper highlights the common impairments seen in adults with cerebral palsy. Additionally, it underscores the critical role of long-term healthcare and management to prevent functional decline and enhance quality of life across physical, cognitive, and social domains.
Exploring Sociodemographic Characteristics, Adverse Childhood Experience, and Mental Health History as Predictors of Anxiety and Depression among Adolescents and Young Adults: Findings from the MoreGoodDays Support Program in Alberta, Canada
Authors: Agyapong Belinda , Shalaby Reham , Hay Katherine , Pattison Rachal , Eboreime Ejemai , Korthuis Mark , Wei Yifeng , Agyapong Vincent Israel Opoku
Published: September 2023

Background: The COVID-19 pandemic has increased psychological disorders among adolescents and young adults. Methods: This study used a cross-sectional design. An online survey questionnaire was used to collect sociodemographic and clinical information from subscribers of MoreGoodDays program, a daily supportive text message program co-designed with adolescents and young adults for their peers in Alberta. Validated instruments, the Generalized Anxiety Disorder GAD-7 scale and Patient Health Questionnaire-9 PHQ-9 were used to collect information on likely GAD and likely major depressive disorder (MDD). Data was analyzed with SPSS version 25 using chi-squared tests and binary logistic regression analysis. Results: 343 subscribers of MoreGoodDays participated in the survey. Overall, 117 (56.0%) respondents had a likely MDD and 97 (46.6%) had a likely GAD. Participants who would like to receive mental health counselling were 27 times more likely to experience GAD (OR = 27; 95% CI: 3.09–250.00) and 40 times more likely to experience MDD (OR = 40.03; 95% CI: 4.43–361.51) than those who did not. Respondents who had received mental health counselling in the past were 18.5 times more likely to experience MDD compared with those who had not (OR = 18.52; 95% CI: 1.55–200.00). Demographic variables, including age, education, employment, and relationship status, and clinical variables, such as history of anxiety, depression, obsessive-compulsive disorder, ADHD, and adverse childhood experience, did not independently the predict presence of likely GAD or MDD in subscribers of MoreGoodDays. Conclusion: The prevalence of anxiety and depression was relatively high among subscribers of MoreGoodDays, indicating the long-term effect of the COVID-19 pandemic. This finding has significant implications in the broader contextof mental health research and emphasizes the need for more research into innovative mental health support for this cohort. The desire to receive counselling was predictive of both anxiety and depression and is a positive sign of the openness of this cohort to receive psychological intervention. Since this group is mostly adapted to mobile text technology, government agencies and policymakers should prioritize and implement readily accessible interventions such as supportive text messages to support their psychological well-being.
BIM Product Style Classification and Retrieval Based on Long-Range Style Dependencies
Authors: Cui Jia , Zang Mengwei , Liu Zhen , Qi Meng , Luo Rong , Gu Zhenyu , Lu Hongju
Published: September 2023

The rapid increase in building components on the building information model (BIM) object database has created new demand for BIM product recommendations to improve design efficiency. Current efforts mainly focus on the shape and contents of the products, instead of stylistic consistency, which is a crucial factor during the practical design process. To tackle such a problem, this paper proposes a novel framework to capture stylistic features based on long-range design dependencies with structural preservation, of which the snapshots of BIM products have been used to extract the stylistic features; core patches with strong style, generated by the pre-trained saliency model, are the root nodes; stylistic correlations are calculated as the hyperedges by tree-based operations; deep features and design features are proposed to represent the low-level and style distribution based on the study of design theory; and an ensemble learning strategy is introduced to solve the unbalanced classifier performance. An ablation study is conducted to validate the effectiveness of the proposed framework, in which comparative experiments with state-of-the-art baselines demonstrate the advantages of the proposed method.
Indoor Temperature Control of Radiant Ceiling Cooling System Based on Deep Reinforcement Learning Method
Authors: Tang Mingwu , Wu Xiaozhou , Xu Jianyi , Liu Jiying , Li Zhengwei , Gao Jie , Tian Zhen
Published: September 2023

The radiant ceiling cooling system is widely adopted in modern office buildings as it improves cooling source efficiency and reduces fossil fuel usage and carbon dioxide emissions by utilizing low-grade natural energy. However, the nonlinear behavior and significant inertia of the radiant ceiling cooling system pose challenges for control systems. With advancements in computer technology and artificial intelligence, the deep reinforcement learning (DRL) method shows promise in the operation and control of radiant cooling systems with large inertia. This paper compares the DRL control method with traditional control methods for radiant ceiling cooling systems in two typical office rooms across three different regions. Simulation results demonstrate that with an indoor target temperature of 26 °C and an allowable fluctuation range of ±1 °C, the DRL on–off or varied water temperature control satisfies the indoor temperature fluctuation requirements for 80% or 93–99% of the operating time, respectively. In contrast, the traditional on–off or PID variable water temperature control only meets these requirements for approximately 70% or 90–93% of the operating time. Furthermore, compared to traditional on–off control, the DRL control can save energy consumption in the radiant ceiling cooling system by 3.19% to 6.30%, and up to 10.48% compared to PID variable water temperature control. Consequently, the DRL control method exhibits superior performance in terms of minimizing indoor temperature fluctuations and reducing energy consumption in radiant ceiling cooling systems.
Study of the Sustainable Functioning of Construction Companies in the Conditions of Risk Factors
Authors: Lapidus Azariy , Abramov Ivan , Kuzmina Tatyana , Abramova Anastasiia , AlZaidi Zaid Ali Kadhim
Published: September 2023

The risk factors that arise during the implementation of investment and construction projects differ in nature, degree of influence, and other characteristics. Ignoring these factors and measures to manage them often leads to critical consequences in the form of disruptions in the timing of work. The article discusses the risk factors arising at the construction stage, their classification, as well as the measures and strategies necessary to manage these factors. A methodology has been developed that includes conducting a survey in the form of a questionnaire in order to collect information about risk factors that affect the implementation of investment and construction projects. The fuzzy TOPSIS technique was used to compare the sustainable functioning of three construction companies (alternatives) on the basis of its application of measures and strategies necessary to deal with risk factors (criteria). Experts with experience in the construction sector were involved in the survey. The results showed that financial, technical, legal, economic, managerial, and natural factors have the greatest impact on investment and construction projects. It is recommended to pay special attention to the listed factors when developing measures aimed at preventing risks and their consequences. The methodology described in the study can be used by construction companies in strategic planning. The analysis of the stability of construction companies, depending on their use of various ways to counteract risk factors, allowed us to develop a number of practical recommendations to reduce the impact of the studied factors on achieving the goals of investment and construction projects.
A Method to Enable Automatic Extraction of Cost and Quantity Data from Hierarchical Construction Information Documents to Enable Rapid Digital Comparison and Analysis
Authors: Adanza Dopazo Daniel , Mahdjoubi Lamine , Gething Bill
Published: September 2023

Context: Despite the effort put into developing standards for structuring construction costs and the strong interest in the field, most construction companies still perform the process of data gathering and processing manually. This provokes inconsistencies, different criteria when classifying, misclassifications, and the process becomes very time-consuming, particularly in large projects. Additionally, the lack of standardization makes cost estimation and comparison tasks very difficult. Objective: The aim of this work was to create a method to extract and organize construction cost and quantity data into a consistent format and structure to enable rapid and reliable digital comparison of the content. Methods: The approach consisted of a two-step method: firstly, the system implemented data mining to review the input document and determine how it was structured based on the position, format, sequence, and content of descriptive and quantitative data. Secondly, the extracted data were processed and classified with a combination of data science and experts’ knowledge to fit a common format. Results: A large variety of information coming from real historical projects was successfully extracted and processed into a common format with 97.5% accuracy using a subset of 5770 assets located on 18 different files, building a solid base for analysis and comparison. Conclusions: A robust and accurate method was developed for extracting hierarchical project cost data to a common machine-readable format to enable rapid and reliable comparison and benchmarking.
Advanced Timber Construction Industry: A Quantitative Review of 646 Global Design and Construction Stakeholders
Authors: Orozco Luis , Svatoš-Ražnjević Hana , Wagner Hans Jakob , Abdelaal Moataz , Amtsberg Felix , Weiskopf Daniel , Menges Achim
Published: September 2023

There has been a multi-storey timber construction boom since the start of the millennium. While there is now a body of research on trends, benefits, and disadvantages of timber construction, there is not yet literature on the wider market or the impact of stakeholders on it. This research investigates the (i) architects, (ii) engineers, and (iii) manufacturers involved in the realization of 300 contemporary multi-storey timber buildings from an existing survey. The analysis is based on data sourced from stakeholder websites and the building survey. It evaluates the perceived level of timber expertise of stakeholders based on service categorization and stakeholder type and relates them to the buildings they worked on. The research uses quantitative methods to answer qualitative questions on the connection between architectural variety in timber construction and the stakeholders involved. Interconnectivity between stakeholders and projects is visualized in an interactive network graph. The study shows a segmented mass timber market with relatively few impactful design and construction stakeholders, mostly located in central and northern Europe. It also identifies fabricators as the largest group of innovators advancing the industry and enabling the construction of more complex projects. It reveals the importance of collaboration and knowledge sharing for the industry’s growth.
The Impact of Resettlement on Quality of Life in Ghana: The Mediating Role of Residential Satisfaction
Authors: Boadi Emmanuel Bosompem , Chen Shaojun , Shi Guoqing , Li Yi , Dodoo Regina Naa Amua , Mensah Francis , Dieme Isaie Steven Martin , Appiah Ruth , Mangudhla Tinashe
Published: September 2023

The effects of large-scale land acquisitions for development projects such as mining, urbanization and dams are widely contested in the literature. Prior research has focused on the difficulties that resettlement poses for the affected families in terms of their capacity to meet the demands of the new community. This study suggests that resettlement (built environment) quality may act as a predictor and influence the residential satisfaction and quality of life of project-affected families. This study investigates how residential satisfaction influences the relationship between the quality of the dwelling, the context of resettlement homes, and the quality of life of mining-affected families in Ghana. A sample of 256 household heads displaced by a large-scale mining project in Ellembelle was used to evaluate the suggested model. The findings indicate that resettlement quality greatly enhances the quality of life of the mining-affected families. The findings also revealed that residential satisfaction was a significant mediator of the quality of dwellings and the context of the resettlement, in addition to being a strong predictor of quality of life. Indirectly, resident characteristics, such as socioeconomic and demographic conditions, influenced how people felt about their homes and quality of life. These results indicate that residential satisfaction and resettlement quality are accurate indicators of the mining-affected families’ quality of life. Integrating these features make it possible to quantify the mining-affected families’ quality of life for future research and public policy.
Dynamic Compression-Bending Performance of Concrete-Filled Steel Tubular Columns under Lateral Impact
Authors: Xu Man , Ding Zhichao , Hao Xianjuan , Gao Shan
Published: September 2023

In this paper, a finite element model of concrete-filled steel tubular (CFST) columns under compression and lateral impact is developed and validated against previous experiments. After analyzing the influence of axial compression on the impact performance of CFST columns, the effects of eccentricity, material strength, and steel ratio on the dynamic compression-bending performances of CFST columns subjected to lateral impact are discussed. The simulated results show that at different axial compression ratios, CFST columns show overall bending failure under lateral impact. The axial force ratio below 0.2 shows a positive effect on the impact resistance of CFST columns, otherwise the axial force would degrade the impact resistance of CFST columns. Eccentricity has a negative effect on the dynamic compression-bending performance of CFST columns. The increase in the concrete strength has little effect on the dynamic compression-bending performance of the CFST columns under lateral impact and eccentric compression. The increases in steel strength and steel ratio can improve the dynamic compression-bending performances of the CFST columns under lateral impact and eccentric compression. Even though the prediction formula for the dynamic compression-bending performance of CFST columns shows good fitness with the simulated results, it is modified to have sufficient strength reserves for design applications.
Topical and Intralesional Immunotherapy for Melanoma In Situ: A Review
Authors: Martínez-Fernández Sandra , González-Sixto Beatriz , Espasandín-Arias Martina , Soto-García Diego , Flórez Ángeles
Published: September 2023

The incidence of in situ melanoma (MIS) has increased over the last decades. The mainstay of treatment for MIS, including lentigo maligna (LM), is complete surgical excision with clear margins (0.5 to 1.0 cm). Nevertheless, MIS lesions often affect elderly patients with comorbidities and involve large lesions in cosmetically sensitive areas, which means surgery is not always appropriate. Non-surgical treatments have a role in these cases, and include radiotherapy, cryosurgery, immunotherapy, laser therapy, and other topical medications. This study aims to review the applications of immunotherapy in MIS, either in monotherapy or in combination with other therapeutic alternatives. The main forms of immunotherapy used are imiquimod and, to a lesser extent, intralesional interferon-α (IL-INF-α) and ingenol mebutate (IM). IL-INF-α and IM have not been studied as extensively as imiquimod, whose results in real-life practice are encouraging. The clearance and recurrence rates reported in MIS treated with imiquimod as monotherapy, or as an adjuvant after surgery with affected or narrow margins, make imiquimod a reliable therapeutic alternative in selected cases. Also, its use as a neoadjuvant therapy before surgery was shown to reduce the final surgical defect size required to confirm negative histologic margins. In conclusion, local immunotherapy is frequently used in clinical practice and experience confirms it to be an excellent option for certain patients.
Redo Pelvic Surgery and Combined Metastectomy for Locally Recurrent Rectal Cancer with Known Oligometastatic Disease: A Multicentre Review
Authors: Keogh Cian , O’Sullivan Niall J. , Temperley Hugo C. , Flood Michael P. , Ting Pascallina , Walsh Camille , Waters Peadar , Ryan Éanna J. , Conneely John B. , Edmundson Aleksandra , Larkin John O. , McCormick Jacob J. , Mehigan Brian J. , Taylor David , Warrier Satish , McCormick Paul H. , Soucisse Mikael L. , Harris Craig A. , Heriot Alexander G. , Kelly Michael E.
Published: September 2023

Introduction: Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. ‘Selective’ patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. Methods: A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. Results: Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/− 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/− 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5–17.5 months) and 25.9 months (IQR 6.2–39.7 months), respectively. Conclusions: Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.
PD-L1 Expression in Pituitary Neuroendocrine Tumors/Pituitary Adenomas
Authors: Cossu Giulia , La Rosa Stefano , Brouland Jean Philippe , Pitteloud Nelly , Harel Ethan , Santoni Federico , Brunner Maxime , Daniel Roy Thomas , Messerer Mahmoud
Published: September 2023

Background and aim: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. Methods: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas’ classification as primary outcomes. Secondary outcomes included the TPS’ relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. Results: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas’ classification, we found that “proliferative” cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80–18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98–14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10–0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. Conclusions: PD-L1 expression was associated with proliferative grades of Trouillas’ classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.
Detection and Mitigation of Neurovascular Uncoupling in Brain Gliomas
Authors: Agarwal Shruti , Welker Kirk M. , Black David F. , Little Jason T. , DeLone David R. , Messina Steven A. , Passe Theodore J. , Bettegowda Chetan , Pillai Jay J.
Published: September 2023

Functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) technique is useful for preoperative mapping of brain functional networks in tumor patients, providing reliable in vivo detection of eloquent cortex to help reduce the risk of postsurgical morbidity. BOLD task-based fMRI (tb-fMRI) is the most often used noninvasive method that can reliably map cortical networks, including those associated with sensorimotor, language, and visual functions. BOLD resting-state fMRI (rs-fMRI) is emerging as a promising ancillary tool for visualization of diverse functional networks. Although fMRI is a powerful tool that can be used as an adjunct for brain tumor surgery planning, it has some constraints that should be taken into consideration for proper clinical interpretation. BOLD fMRI interpretation may be limited by neurovascular uncoupling (NVU) induced by brain tumors. Cerebrovascular reactivity (CVR) mapping obtained using breath-hold methods is an effective method for evaluating NVU potential.
MitoTam-01 Trial: Mitochondrial Targeting as Plausible Approach to Cancer Therapy. Comment on Yap et al. Complex I Inhibitor of Oxidative Phosphorylation in Advanced Solid Tumors and Acute Myeloid Leukemia: Phase I Trials. Nat. Med. 2023, 29, 115–126
Authors: Neuzil Jiri , Rohlena Jakub , Werner Lukas , Bielcikova Zuzana
Published: September 2023

A recent paper published in Nature Medicine reported on the Phase I clinical trial of a mitochondria-targeting anti-cancer agent IACS-01059 in patients with acute myeloid leukemia (AML) and solid tumors [...]
Differentiating Benign from Malignant Thyroid Tumors by Kinase Activity Profiling and Dabrafenib BRAF V600E Targeting
Authors: Hilhorst Riet , van den Berg Adrienne , Boender Piet , van Wezel Tom , Kievits Tim , de Wijn Rik , Ruijtenbeek Rob , Corver Willem E. , Morreau Hans
Published: September 2023

Differentiated non-medullary thyroid cancer (NMTC) can be effectively treated by surgery followed by radioactive iodide therapy. However, a small subset of patients shows recurrence due to a loss of iodide transport, a phenotype frequently associated with BRAF V600E mutations. In theory, this should enable the use of existing targeted therapies specifically designed for BRAF V600E mutations. However, in practice, generic or specific drugs aimed at molecular targets identified by next generation sequencing (NGS) are not always beneficial. Detailed kinase profiling may provide additional information to help improve therapy success rates. In this study, we therefore investigated whether serine/threonine kinase (STK) activity profiling can accurately classify benign thyroid lesions and NMTC. We also determined whether dabrafenib (BRAF V600E-specific inhibitor), as well as sorafenib and regorafenib (RAF inhibitors), can differentiate BRAF V600E from non-BRAF V600E thyroid tumors. Using 21 benign and 34 malignant frozen thyroid tumor samples, we analyzed serine/threonine kinase activity using PamChip®peptide microarrays. An STK kinase activity classifier successfully differentiated malignant (26/34; 76%) from benign tumors (16/21; 76%). Of the kinases analyzed, PKC (theta) and PKD1 in particular, showed differential activity in benign and malignant tumors, while oncocytic neoplasia or Graves’ disease contributed to erroneous classifications. Ex vivo BRAF V600E-specific dabrafenib kinase inhibition identified 6/92 analyzed peptides, capable of differentiating BRAF V600E-mutant from non-BRAF V600E papillary thyroid cancers (PTCs), an effect not seen with the generic inhibitors sorafenib and regorafenib. In conclusion, STK activity profiling differentiates benign from malignant thyroid tumors and generates unbiased hypotheses regarding differentially active kinases. This approach can serve as a model to select novel kinase inhibitors based on tissue analysis of recurrent thyroid and other cancers.
Construction of Supported MnOx/MgAl Hydrotalcite Catalysts and Their Highly Efficient Catalytic Performance for Low-Temperature Formaldehyde Removal
Authors: Yu Xiankun , Sun Qi , Tian Jingchen , Wan Jie , Liu Yanjun , Wang Xiaoli , Kan Jianfei , Yang Xiaojun , Wu Gongde
Published: September 2023

A series of supported MnOx/MgAl-layered double hydroxide (LDH) catalysts were prepared by hydrothermal co-precipitation to investigate their catalytic performances for low-temperature formaldehyde oxidation reactions. Activity tests show that the 10Mn/Mg3Al1-LDH catalyst exhibits higher efficiency for low-temperature formaldehyde oxidation with a high CO2 yield. It also shows remarkable long-term operational stability as well as good adaptability to different velocities and humidities. Various characterizations were carried out to establish the possible structure–activity correlations. The results show that there were a large number of hydroxyl groups in the 10Mn/MgAl-LDH catalysts, and the hydroxyl groups were positively correlated with Mg2+ content. The outstanding catalytic performance of 10Mn/Mg3Al1-LDH can be attributed to abundant surface hydroxyl groups, surface adsorbed oxygen and higher Mn4+/Mn3+ ratios. Through in situ Fourier-transform infrared spectroscopy (in situ FTIR), it was revealed that formaldehyde was gradually converted into CO2 and water with dioxymethylene (DOM), formate and carbonate as the major intermediates under the action of both active oxygen and active hydroxyl groups. The active oxygen and active hydroxyl groups consumed in the process are continuously replenished by the effective reaction between the oxygen molecules in the air and the active site of the catalyst. The low-temperature asynchronous conversion of formaldehyde results in the accumulation of some intermediates on the catalyst surface covering the active center, which induces catalyst deactivation.
Assessing the Efficacy of A Mo2C/Peroxydisulfate System for Tertiary Wastewater Treatment: A Study of Losartan Degradation, E. coli Inactivation, and Synergistic Effects
Authors: Ioannidi Alexandra A. , Vlachodimitropoulou Maria , Frontistis Zacharias , Petala Athanasia , Koutra Eleni , Kornaros Michael , Mantzavinos Dionissios
Published: September 2023

This work examines the use of pristine Mo2C as an intriguing sodium persulfate (SPS) activator for the degradation of the drug losartan (LOS). Using 500 mg/L Mo2C and 250 mg/L SPS, 500 μg/L LOS was degraded in less than 45 min. LOS decomposition was enhanced in acidic pH, while the apparent kinetic constant decreased with higher LOS concentrations. According to experiments conducted in the presence of scavengers of reactive species, sulfate radicals, hydroxyl radicals, and singlet oxygen participated in LOS oxidation, with the latter being the predominant reactive species. The presence of competitors such as bicarbonate and organic matter reduced the observed efficiency in actual matrices, while, interestingly, the addition of chloride accelerated the degradation rate. The catalyst showed remarkable stability, with complete LOS removal being retained after five sequential experiments. The system was examined for simultaneous LOS decomposition and elimination of Escherichia coli. The presence of E. coli retarded LOS destruction, resulting in only 30% removal after 3 h, while the system was capable of reducing E. coli concentration by 1.23 log. However, in the presence of simulated solar irradiation, E. coli was reduced by almost 4 log and LOS was completely degraded in 45 min, revealing a significant synergistic effect of the solar/Mo2C/SPS system.
Porous Aerogel Structures as Promising Materials for Photocatalysis, Thermal Insulation Textiles, and Technical Applications: A Review
Authors: Lee Kang Hoon , Arshad Zafar , Dahshan Alla , Alshareef Mubark , Alsulami Qana A. , Bibi Ayesha , Lee Eui-Jong , Nawaz Muddasir , Zubair Usman , Javid Amjed
Published: September 2023

Aerogels, due to their unique features like lightweight, ultra-low thermal conductivity, and design variations, have gotten a lot of interest in thermal insulation, photocatalysis, and protective areas. Besides their superior thermal properties, aerogel thermal insulation and photocatalyst materials also possess many inherent flaws, such as handling issues, high manufacturing costs, and low strength as well as toughness. The most persuasive and successful ways to improve photocatalytic and thermal insulating qualities while lowering costs are composition optimization and microstructure reconstruction. Their high surface area and porosity make them ideal for enhancing the efficiency and capacity of these devices. Research may lead to more efficient and longer-lasting energy storage solutions. This review describes the characteristics, microstructural reconstruction, design variation, and properties of all aerogel fabrication techniques and provides a comprehensive overview of scientific achievements linked to them. The effectiveness of raw material compositions, properties, and mechanical parameters are also discussed. The major goal of this review is to highlight the aerogel-based materials and design variations and to explore the most potential development trends for photocatalysis and thermal applications. The industrial as well as technical applications of silica aerogels are also highlighted. This review highlights futuristic applications of aerogel-based textile materials to alleviate the CO2 burden on our atmosphere, either by providing next-level thermal insulation or by employing them in CO2 mitigating technologies such as CO2 capture.
HDAC6 and ERK/ADAM17 Regulate VEGF-Induced NOTCH Signaling in Lung Endothelial Cells
Authors: Xia Sheng , Menden Heather L. , Mabry Sherry M. , Sampath Venkatesh
Published: September 2023

Angiogenesis plays a critical role in various physiological and pathological processes and is regulated by VEGF. Histone Deacetylase 6 (HDAC6) is a class IIB HDAC that regulates cytoplasmic signaling through deacetylation and is emerging as a target for modulating angiogenesis. We investigated the hypothesis that VEGF-induced endothelial cell (EC) NOTCH signaling is regulated by HDAC6 through acetylation of NOTCH intracellular cytoplasmic domain (NICD). In pulmonary endothelial cells (EC), VEGF-induced activation of the NICD transcriptional response was regulated by ERK1/2 and ADAM 17 and required DLL4. While HDAC6 inhibition induced the acetylation of NICD and stabilized NICD, it repressed NICD-SNW1 binding required for the NOTCH transcriptional responses. In vitro experiments showed that HDAC6 inhibition inhibited lung EC angiogenesis, and neonatal mice treated with a systemic HDAC6 inhibitor had significantly altered angiogenesis and alveolarization. These findings shed light on the role of HDAC6 in modulating VEGF-induced angiogenesis through acetylation and repression of the transcriptional regulators, NICD and SNW1.
Long-Term Alcohol-Activated c-Jun N-terminal Kinase Isoform 2 Preserves Cardiac Function but Drives Ca2+-Triggered Arrhythmias
Authors: Ricchiuti Nikola , Chenoweth Kurtis , Gao Xianlong , Bare Dan J. , Yan Jiajie , Ai Xun
Published: September 2023

Long-term alcohol consumption leads to cardiac arrhythmias including atrial fibrillation (AF), the most common alcohol-related arrhythmia. While AF significantly increases morbidity and mortality in patients, it takes years for an alcoholic individual undergoing an adaptive status with normal cardiac function to reach alcoholic cardiomyopathy. The underlying mechanism remains unclear to date. In this study, we assessed the functional role of JNK2 in long-term alcohol-evoked atrial arrhythmogenicity but preserved cardiac function. Wild-type (WT) mice and cardiac-specific JNK2dn mice (with an overexpression of inactive dominant negative (dn) JNK2) were treated with alcohol (2 g/kg daily for 2 months; 2 Mo). Confocal Ca2+ imaging in the intact mouse hearts showed that long-term alcohol prolonged intracellular Ca2+ transient decay, and increased pacing-induced Ca2+ waves, compared to that of sham controls, while cardiac-specific JNK2 inhibition in JNK2dn mice precluded alcohol-evoked Ca2+-triggered activities. Moreover, activated JNK2 enhances diastolic SR Ca2+ leak in 24 h and 48 h alcohol-exposed HL-1 atrial myocytes as well as HEK-RyR2 cells (inducible expression of human RyR2) with the overexpression of tGFP-tagged active JNK2-tGFP or inactive JNK2dn-tGFP. Meanwhile, the SR Ca2+ load and systolic Ca2+ transient amplitude were both increased in ventricular myocytes, along with the preserved cardiac function in 2 Mo alcohol-exposed mice. Moreover, the role of activated JNK2 in SR Ca2+ overload and enhanced transient amplitude was also confirmed in long-term alcohol-exposed HL-1 atrial myocytes. In conclusion, our findings suggest that long-term alcohol-activated JNK2 is a key driver in preserved cardiac function, but at the expense of enhanced cardiac arrhythmogenicity. Modulating JNK2 activity could be a novel anti-arrhythmia therapeutic strategy.