bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the influence of mixed reality, a 3D viewer, and MRI on the spatial understanding of brain tumours
Authors: Fick T. , Meulstee J. W. , Köllen M. H. , Van Doormaal J. A. M. , Van Doormaal T. P. C. , Hoving E. W.
Published: August 2023

Background: Multiple 3D visualization techniques are available that obviates the need for the surgeon to mentally transform the 2D planes from MRI to the 3D anatomy of the patient. We assessed the spatial understanding of a brain tumour when visualized with MRI, 3D models on a monitor or 3D models in mixed reality.

Methods: Medical students, neurosurgical residents and neurosurgeons were divided into three groups based on the imaging modality used for preparation: MRI, 3D viewer and mixed reality. After preparation, the participants needed to position, scale, and rotate a virtual tumour inside a virtual head of the patient in the same orientation as the original tumour would be. Primary outcome was the amount of overlap between the placed tumour and the original tumour to evaluate accuracy. Secondary outcomes were the position, volume and rotation deviation compared to the original tumour.

Results: A total of 12 medical students, 12 neurosurgical residents, and 12 neurosurgeons were included. For medical students, the mean amount of overlap for the MRI, 3D viewer and mixed reality group was 0.26 (0.22), 0.38 (0.20) and 0.48 (0.20) respectively. For residents 0.45 (0.23), 0.45 (0.19) and 0.68 (0.11) and for neurosurgeons 0.39 (0.20), 0.50 (0.27) and 0.67 (0.14). The amount of overlap for mixed reality was significantly higher on all expertise levels compared to MRI and on resident and neurosurgeon level also compared to the 3D viewer. Furthermore, mixed reality showed the lowest deviations in position, volume and rotation on all expertise levels.

Conclusion: Mixed reality enhances the spatial understanding of brain tumours compared to MRI and 3D models on a monitor. The preoperative use of mixed reality may therefore support the surgeon to improve spatial 3D related surgical tasks such as patient positioning and planning surgical trajectories.
COAST Development Group's international consensus guidelines for the treatment of canine osteoarthritis
Authors: Cachon Thibaut , Frykman Ole , Innes John F. , Lascelles B. Duncan X. , Okumura Masahiro , Sousa Pedro , Staffieri Francesco , Steagall Paulo V. , Van Ryssen Bernadette
Published: August 2023

This report describes consensus guidelines and recommendations for the treatment of canine osteoarthritis (OA) according to the “Canine OsteoArthritis Staging Tool excluding radiography” (COASTeR) stage of OA, by the COAST Development Group. The recommendations are based on evidence-based medicine and clinical experience and are proposed with international relevance in mind. The aim is to provide veterinarians with a practical reference to consolidated information and to support the development of patient-specific OA management protocols and informed treatment choices based on the stage of OA.
Knowledge of lateralized brain function can contribute to animal welfare
Authors: Rogers Lesley J.
Published: August 2023

The specialized functions of each hemisphere of the vertebrate brain are summarized together with the current evidence of lateralized behavior in farm and companion animals, as shown by the eye or ear used to attend and respond to stimuli. Forelimb preference is another manifestation of hemispheric lateralization, as shown by differences in behavior between left- and right-handed primates, left- and right-pawed dogs and cats, and left- and right-limb-preferring horses. Left-limb preference reflects right hemisphere use and is associated with negative cognitive bias. Positive cognitive bias is associated with right-limb and left-hemisphere preferences. The strength of lateralization is also associated with behavior. Animals with weak lateralization of the brain are unable to attend to more than one task at a time, and they are more easily stressed than animals with strong lateralization. This difference is also found in domesticated species with strong vs. weak limb preferences. Individuals with left-limb or ambilateral preference have a bias to express functions of the right hemisphere, heightened fear and aggression, and greater susceptibility to stress. Recognition of lateralized behavior can lead to improved welfare by detecting those animals most likely to suffer fear and distress and by indicating housing conditions and handling procedures that cause stress.
Design and Experimental Study of Cavity Structure of Pneumatic Soft Actuator
Authors: Yu Yang , Fu Tao
Published: August 2023

In order to study the influence of the cavity inclination angle bending performance of pneumatic soft actuators, two kinds of soft actuators were designed, one with a five-degree-angle cavity structure, and the other with a hybrid variable-degree-angle cavity structure. The bending performance of zero-degree-angle, five-degree-angle, and hybrid variable-degree-angle soft actuators was investigated by experimental methods and the ABAQUS finite element simulation method. The results show that, under seven different pressure loads, the mean absolute error between the experimental results and the numerical simulation results for the zero-degree-angle soft actuator was 0.926, for the five-degree-angle soft actuator it was 1.472, and for the hybrid variable-degree-angle soft actuator it was 1.22. When the pressure load changed from 4 kPa to 16 kPa, the five-degree-angle soft actuator had the largest range-of-angle variation, with the bending angle increasing 193.31%, from 26.92 degrees to 78.97 degrees. In the same longitudinal displacement, the five-degree-angle soft actuator had the largest lateral displacement variation, and the bending effect was the best compared with the zero-degree-angle soft actuator and the hybrid variable-degree-angle soft actuator. According to the experimental and numerical simulation results, with the same structural parameter design, the cavity tilt angle increases, which can increase the bending angle variation range and improve the bending performance of soft actuators.
Revitalizing Business Tourism in the European Union: Strategies for Growth
Authors: Carvalho Pedro
Published: August 2023

The COVID-19 pandemic had a disastrous effect on the growth in business tourism, emphasizing the role of information and communication technologies in the implementation of new meeting models. Consequently, new needs and concerns of the business tourist may have arisen, which should lead business tourism organizations to consider new attributes in their value proposition. Thus, this study aims to understand the determinants of business tourism spending and the number of business meetings, in the European Union, to aid the formulation of economic and marketing policies, in the post-pandemic period. For this purpose, a literature review is carried out for the periods before, during, and after the pandemic phase; additionally, a panel data analysis is performed using data from the 28 countries in the European Union. The results identify new typologies of determinants, describing first-order (global-scale) and second-order (European-scale) determinants and identifying important practical implications.
Effects of Dietary Bacillus subtilis BC02 Supplementation on Growth Performance, Antioxidant Capacity, and Cecal Microbes in Broilers
Authors: Ren Xiaojie , Zhang Yan , Lu Hai , Jiao Ning , Jiang Shuzhen , Li Yang , Li Junxun , Yang Weiren
Published: August 2023

This study investigated the effects of Bacillus subtilis BC02 supplementation on broiler performance, antioxidant capacity, and cecal microbes. A total of 288 one-day-old Arbor Acres broilers were randomly divided into three groups. The control group were fed a basal diet, and experimental groups were fed a basal diet supplemented with 250 and 500 mg/kg Bacillus subtilis BC02 (BS250 and BS500), respectively. The results showed that Bacillus subtilis BC02 supplementation increased the average daily feed intake but decreased the feed to gain ratio in broilers from 0 to 14, 0 to 28, and 0 to 42 days. Meanwhile, BS500 significantly decreased triglyceride and serum urea nitrogen levels compared with the control and BS250 groups (p < 0.05). Moreover, diet supplemented with 500 mg/kg Bacillus subtilis BC02 improved the antioxidant capacity by increasing the serum and jejunum levels of superoxide dismutase and glutathione, decreasing that of malondialdehyde and increasing the jejunum mRNA expression of SOD2, CAT, GPX1, and Nrf2 (p < 0.05). Dietary Bacillus subtilis BC02 supplementation increased the villus height, velvet concealed ratio, and the mRNA expressions of IL-2, IL-4, IL-10, and IL-12 (p < 0.05). In addition, the Bacteroidota, Proteobacteria, Helicobacter, and Prevotellaceae UCG-001 were significantly increased (p < 0.05) in the BS500 group. In conclusion, dietary Bacillus subtilis BC02 supplementation can improve the growth performance, antioxidant capacity, and intestinal microflora abundances in broilers.
Ensuring Plant Nutrition through Sustainable Soil Management Strategies: Assessing Research Progress and Challenges
Authors: Monokrousos Nikolaos , Mourouzidou Snezhana
Published: August 2023

The ‘Soil and Plant Nutrition’ section of Agronomy (ISSN 2073-4395) is dedicated to sharing high-quality research articles, reviews, and communications that explore the latest scientific trends and advancements in the field [...]
Morphological and Ecogeographical Diversity of the Andean Lupine (Lupinus mutabilis Sweet) in the High Andean Region of Ecuador
Authors: Chalampuente-Flores Doris , Mosquera-Losada María Rosa , Ron Antonio M. De , Tapia Bastidas César , Sørensen Marten
Published: August 2023

Promoting food security is one of the 17 Sustainable Development Goals (SDGs) proposed by the United Nations General Assembly, with a target date of 2030. Human nutrition based on legume consumption is essential to ensuring food security while reducing greenhouse gas emissions associated with nitrogen fertilizer use. Moreover, preserving legume biodiversity is critical to increasing agricultural resilience against climate change. The Andean lupine or “tarwi” (Lupinus mutabilis Sweet) is a legume native to the Andean region with high nutritional importance. Morphological characterization processes allow the determination of local agro-biodiversity and the identification of promising materials for genetic improvement programs. In the present investigation, 173 accessions of Andean lupine from the Germplasm Bank of INIAP, Ecuador, were evaluated. Thirteen quantitative and fifteen qualitative descriptors were used in the characterization. The results revealed that the genetic variability of the Andean lupine is represented by the conformation of four groups of accessions. Among those groups, two accessions stand out for having small plants and high yields, factors that could be used for genetic improvement processes or be reintroduced into farmers’ fields as they represent an option for the production, consumption, and marketing of the local germplasm of this relevant ancient crop. A phenotypic diversity map of the cultivated tarwi explained that areas with high morphological diversity are not completely identical to areas with high ecogeographic diversity. The distribution of the genetic variability of species appears to be more related to cultural aspects than environmental conditions.
The Occurrence and Characteristics of Methicillin-Resistant Staphylococcal Isolates from Foods and Containers
Authors: Kansaen Rada , Boueroy Parichart , Hatrongjit Rujirat , Kamjumphol Watcharaporn , Kerdsin Anusak , Chopjitt Peechanika
Published: August 2023

Antimicrobial resistance (AMR) has emerged as an urgent global public health issue that requires immediate attention. Methicillin-resistant staphylococci (MRS) is a major problem, as it may cause serious human and animal infections, eventually resulting in death. This study determined the proportional distribution, genetic characteristics, and antimicrobial susceptibility of mecA- or mecC-carrying staphylococci isolated from food chain products. A total of 230 samples were taken from meat, food, fermented food, and food containers. Overall, 13.9% (32/230) of the samples were identified to have Staphylococcus aureus isolates; of those, 3.9% (9/230) were MRS, with eight mecA-positive and one mecC-positive samples, and 1.3% (3/230) methicillin-resistant Staphylococcus aureus (MRSA). MRSA strains belonging to three sequence types (ST9, ST22, and a newly identified ST), three different spa types (T005, t526, and a newly identified type), and three different SCCmec types (IV, V, and an unidentified SCCmec) were detected. Additionally, eight mecA-positive staphylococcal isolates were identified as S. haemolyticus, S. sciuri, S. simulans, and S. warneri, while the mecC-harboring isolate was S. xylosus. The enterotoxin gene, SEm, was detected at 1.56% in S. aureus, whereas SEq was detected at 0.31%, and SEi was also found in MRSA. Our study emphasizes the importance of enhanced hygiene standards in reducing the risk of occupational and foodborne MRSA infections associated with the handling or consumption of meat, food, and preserved food products.
Regulation of Ras Signaling by S-Nitrosylation
Authors: Simão Sónia , Agostinho Rafaela Ribeiro , Martínez-Ruiz Antonio , Araújo Inês Maria
Published: August 2023

Ras are a family of small GTPases that function as signal transduction mediators and are involved in cell proliferation, migration, differentiation and survival. The significance of Ras is further evidenced by the fact that Ras genes are among the most mutated oncogenes in different types of cancers. After translation, Ras proteins can be targets of post-translational modifications (PTM), which can alter the intracellular dynamics of the protein. In this review, we will focus on how S-nitrosylation of Ras affects the way these proteins interact with membranes, its cellular localization, and its activity. S-Nitrosylation occurs when a nitrosyl moiety of nitric oxide (NO) is covalently attached to a thiol group of a cysteine residue in a target protein. In Ras, the conserved Cys118 is the most surface-exposed Cys and the preferable residue for NO action, leading to the initiation of transduction events. Ras transduces the mitogen-activated protein kinases (MAPK), the phosphoinositide-3 kinase (PI3K) and the RalGEF cellular pathways. S-Nitrosylation of elements of the RalGEF cascade remains to be identified. On the contrary, it is well established that several components of the MAPK and PI3K pathways, as well as different proteins associated with these cascades, can be modified by S-nitrosylation. Overall, this review presents a better understanding of Ras S-nitrosylation, increasing the knowledge on the dynamics of these proteins in the presence of NO and the underlying implications in cellular signaling.
Multiresonances of Quasi-Trapped Modes in Metasurfaces Based on Nanoparticles of Transition Metal Dichalcogenides
Authors: Gubin Mikhail Yu. , Shesterikov Alexander V. , Tselikov Gleb I. , Volkov Valentyn S. , Prokhorov Alexei V.
Published: August 2023

The features of polarization control of multiple multiresonances for quasi-trapped modes excited by synchronization of bianisotropic dipole responses in MoS2 disks with a hole are considered. Using numerical calculations with analytical multipole analysis, we showed that the presence of a strong optical anisotropy of MoS2 nanoparticles provides an additional degree of freedom and makes it possible to observe several resonances of electric and magnetic dipoles at once in a narrow spectral range. Based on the simulation results, we obtained the frequency dependences for the dipole polarizabilities of the MoS2 disk with a hole, which can be used to distinguish the contributions of the nonlocal and bianisotropic dipole responses and possessing several features in the near-infrared range. Using the polarizability spectra of single nanoparticles and applying the tuning strategy, the design of the MoS2 metasurface placed in air and supporting three resonances of quasi-trapped modes at once in a narrow spectral range was developed. One of these resonances corresponds to the telecom wavelength of about 1550 nm. The spectrum of light reflection for the MoS2 metasurface is characterized by three narrowband dips corresponding to the wavelengths of the quasi-trapped modes. It was shown that a change in the polarization of a wave normally incident on the metasurface to orthogonal one leads to a change in the type of bianisotropic response excited in each MoS2 disk and to the excitation of three other features in the reflection spectrum of the metasurface at wavelengths close to the initial values.
Medicinal Importance and Phytoconstituents of Underutilized Legumes from the Caesalpinioideae DC Subfamily
Authors: Ogunniyi Queeneth A. , Ogbole Omonike O. , Akin-Ajani Olufunke D. , Ajala Tolulope O. , Bamidele Olorunsola , Fettke Joerg , Odeku Oluwatoyin A.
Published: August 2023

Underutilized legumes are common crops in developing countries with superior dietary potentials that could be useful sources of protein as well as some phytoconstituents. They are more tolerant of abiotic environmental conditions like drought than the major legumes. This makes them more adapted to harsh soil and climatic conditions, which helps to minimize the pressure brought on by climate change. However, despite their potential, underutilized legumes have been greatly overlooked compared to the major legumes due to supply constraints. Underutilized legumes in the subfamily Caesalpinioideae are better suited for use as animal feeds with little or no value as food for humans, and the extracts and infusions of the different parts of plant species in this subfamily are traditionally used for the treatment of different diseases. In addition, underutilized legumes in this subfamily contain phytoconstituents that are of pharmacological relevance, some of which have been isolated, characterized and evaluated for use in the treatment of a variety of disorders. Therefore, this review describes the medicinal activities of some selected underutilized legumes from five genera in the subfamily Caesalpinioideae as well as their phytoconstituents, which could be exploited as lead compounds for drug discovery.
A Study of the Field Test Method for the Adhesive Performance Evaluation of Self-Adhesive Waterproofing Sheets
Authors: Park Jeong-Hwa , Oh Kyu-Hwan , Oh Sang-Keun , Seo Hyun-Jae , Kang Boo-Sung
Published: August 2023

In the field of waterproofing concrete structures, the use of self-adhesive waterproofing sheets has become a popular technique for ensuring long-term waterproofing performance. One important characteristic of such sheet materials is maintaining their stable adhesion strength over an extended period. Adhesion testing serves as a crucial method for assessing the long-term adhesion performance. However, a standardized test method, including equipment and criteria, for directly measuring the adhesion strength of waterproofing sheets applied to onsite concrete walls has not yet been established. Therefore, reliance on laboratory evaluation results has been the only option thus far. In this study, a field-applicable adhesion measurement device was developed in an effort to provide a quality control method for self-adhesive waterproofing sheets and to demonstrate the validity of a standardized evaluation method utilizing this device. The developed adhesion measurement device was designed based on the principle of the peel-out test in compliance with the requirements outlined KS F 4934, where the test specimen backing plate can slide into a 1:1 ratio at the same distance as the rise of the tension jig when the tension jig is raised at a 45° angle. By utilizing this device, the adhesion strength values of self-adhesive waterproofing materials applied in the field were compared with those obtained using a laboratory universal testing machine (Salem, MA, USA) (UTM) on the test specimens. Comparative analysis yielded that the standard deviation of the results varied for the tested waterproofing materials, and the overall standard deviation for the UTM measurements was 0.17, while it was 0.18 for the portable field measurement equipment. The results of the comparison indicated that when limited to the scope of the KS measurement method specifications, the possibility for a wider scope of usage can be made possible with more data and studies.
Research Progress and Trends in the Field of Satellite Ozone from 2005 to 2023: A Bibliometric Review
Authors: Liu Yin
Published: August 2023

Ozone, an important atmospheric constituent, affects various processes in the troposphere–stratosphere region and significantly contributes to climate and environmental change. The advancement of meteorological satellite technology has enabled the deployment of ozone detection instruments in space, providing accurate and global satellite ozone data in all weather conditions. This study employs scientometric methods, such as collaboration analysis, co-citation analysis, and keyword co-occurrence analysis to investigate the current status, trends, and future directions of satellite ozone research, with a broader search scope and more objective results compared with a manual review. Analyzing a dataset of 5320 bibliographic records from the WoS core collection database reveals the key intellectual frameworks shaping this field during the period from 2005 to 2023. The findings indicate that leading nations, like the United States, Germany, France, and China, along with their respective institutions and authors, spearhead satellite ozone research. Collaborative partnerships between the United States and European countries play a crucial role in advancing research efforts. Moreover, 20 distinct co-citation clusters identify the knowledge framework within the field, demonstrating a consistent progression over time. The focus has expanded from satellite ozone observation instruments to encompass broader areas, such as atmospheric pollution and environmental conditions, with “air quality” emerging as a prominent research area and future trend. Based on these insights, four major research directions are proposed: understanding atmospheric pollution mechanisms, improving ozone detection technologies, utilizing satellite ozone data for weather, and climate phenomena. This study aims to assist scholars by providing a comprehensive understanding of the developmental trajectory of satellite ozone research. Its results can serve as a valuable reference for researchers to identify relevant publications and journals efficiently. Policymakers can also utilize this systematic review as a structured point of reference.
Temperature-Controlled Expression of a Recombinant Human-like Collagen I Peptide in Escherichia coli
Authors: Xie Wenjie , Wu Qiqi , Kuang Zhanpeng , Cong Jianhang , Zhang Qirong , Huang Yadong , Su Zhijian , Xiang Qi
Published: August 2023

Collagen is the functional protein of the skin, tendons, ligaments, cartilage, bone, and connective tissue. Due to its extraordinary properties, collagen has a wide range of applications in biomedicine, tissue engineering, food, and cosmetics. In this study, we designed a functional fragment of human type I collagen (rhLCOL-I) and expressed it in Escherichia coli (E. coli) BL21(DE3) PlysS containing a thermal-induced plasmid, pBV-rhLCOL-I. The results indicated that the optimal expression level of the rhLCOL-I reached 36.3% of the total protein at 42 °C, and expressed in soluble form. In a 7 L fermentation, the yield of purified rhLCOL-I was 1.88 g/L. Interestingly, the plasmid, pBV220-rhLCOL-I, was excellently stable during the fermentation process, even in the absence of antibiotics. Functional analyses indicated that rhLCOL-I had the capacity to promote skin cell migration and adhesion in vitro and in vivo. Taken together, we developed a high-level and low-cost approach to produce collagen fragments suitable for medical applications in E. coli.
Sports-Related Concussion Assessment: A New Physiological, Biomechanical, and Cognitive Methodology Incorporating a Randomized Controlled Trial Study Protocol
Authors: Irwin Gareth , Rogatzki Matthew J. , Wiltshire Huw D. , Williams Genevieve K. R. , Gu Yaodong , Ash Garrett I. , Tao Dan , Baker Julien S.
Published: August 2023

Background: Taking part in moderate-to-vigorous exercise in contact sports on a regular basis may be linked to an increase in cerebrovascular injury and head trauma. Validated objective measures are lacking in the initial post-event diagnosis of head injury. The exercise style, duration, and intensity may also confound diagnostic indicators. As a result, we propose that the new Interdisciplinary Group in Movement & Performance from Acute & Chronic Head Trauma (IMPACT) analyze a variety of functional (biomechanical and motor control) tests as well as related biochemistry to see how they are affected by contact in sports and head injury. The study’s goal will be to look into the performance and physiological changes in rugby players after a game for head trauma and injury. Methods: This one-of-a-kind study will use a randomized controlled trial (RCT) utilizing a sport participation group and a non-participation control group. Forty male rugby 7 s players will be recruited for the study and allocated randomly to the experimental groups. The intervention group will participate in three straight rugby matches during a local 7 s rugby event. At the pre-match baseline, demographic and anthropometric data will be collected. This will be followed by the pre-match baseline collection of biochemical, biomechanical, and cognitive-motor task data. After three consecutive matches, the same measures will be taken. During each match, a notational analysis will be undertaken to obtain contact information. All measurements will be taken again 24, 48, and 72 h after the third match. Discussion: When the number of games increases owing to weariness and/or stressful circumstances, we expect a decline in body movement, coordination, and cognitive-motor tasks. Changes in blood biochemistry are expected to correspond to changes in biomechanics and cognitive-motor processes. This research proposal will generate considerable, ecologically valid data on the occurrence of head trauma events under game conditions, as well as the influence of these events on the biological systems of the performers. This will lead to a greater understanding of how sports participants react to exercise-induced injuries. This study’s scope will have far-reaching ramifications for doctors, coaches, managers, scientists, and sports regulatory bodies concerned with the health and well-being of athletic populations at all levels of competition, including all genders and ages.
Effect of Kinins on the Hepatic Oxidative Stress in Mice Treated with a Methionine-Choline Deficient Diet
Authors: Thomaz Mariana Silva , Sertorio Marcela Nascimento , Gazarini Marcos Leoni , Ribeiro Daniel Araki , Pisani Luciana Pellegrini , Nagaoka Marcia Regina
Published: August 2023

Non-alcoholic fatty liver is the leading cause of hepatic disease worldwide and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) due to cell injury, oxidative stress, and apoptosis. The kinins’ role in the liver has been studied in experimental fibrosis, partial hepatectomy, and ischemia-reperfusion and is related to cell death and regeneration. We investigated its role in experimental NASH induced by a methionine-choline deficient diet for 4 weeks. After that, liver perfusion was performed, and bradykinin (BK) or des-Arg9-BK was infused. Cell death was evaluated by cathepsin-B and caspase-3 activity and oxidative stress by catalase (CAT), glutathione S-transferase, and superoxide dismutase (SOD) activities, as well as malondialdehyde and carbonylated proteins. In control livers, DABK increased CAT activity, which was reversed by antagonist DALBK. In the NASH group, kinins tend to decrease antioxidant activity, with SOD activity being significantly reduced by BK and DABK. Malondialdehyde levels increased in all NASH groups, but carbonylated protein did not. DABK significantly decreased cathepsin-B in the NASH group, while caspase-3 was increased by BK in control animals. Our results suggest that B1R and/or B2R activation did not induce oxidative stress but affected the antioxidant system, reducing SOD in the NASH group.
A Polarity-Sensitive Far-Red Fluorescent Probe for Glucose Sensing through Skin
Authors: Colvin Lydia , Tu Dandan , Dunlap Darin , Rios Alberto , Coté Gerard
Published: August 2023

The field of glucose biosensors for diabetes management has been of great interest over the past 60 years. Continuous glucose monitoring (CGM) is important to continuously track the glucose level to provide better management of the disease. Concanavalin A (ConA) can reversibly bind to glucose and mannose molecules and form a glucose biosensor via competitive binding. Here, we developed a glucose biosensor using ConA and a fluorescent probe, which generated a fluorescent intensity change based on solvatochromism, the reversible change in the emission spectrum dependent on the polarity of the solvent. The direction in which the wavelength shifts as the solvent polarity increases can be defined as positive (red-shift), negative (blue-shift), or a combination of the two, referred to as reverse. To translate this biosensor to a subcutaneously implanted format, Cyanine 5.5 (Cy5.5)-labeled small mannose molecules were used, which allows for the far-red excitation wavelength range to increase the skin penetration depth of the light source and returned emission. Three Cy5.5-labeled small mannose molecules were synthesized and compared when used as the competing ligand in the competitive binding biosensor. We explored the polarity-sensitive nature of the competing ligands and examined the biosensor’s glucose response. Cy5.5-mannotetraose performed best as a biosensor, allowing for the detection of glucose from 25 to 400 mg/dL. Thus, this assay is responsive to glucose within the physiologic range when its concentration is increased to levels needed for an implantable design. The biosensor response is not statistically different when placed under different skin pigmentations when comparing the percent increase in fluorescence intensity. This shows the ability of the biosensor to produce a repeatable signal across the physiologic range for subcutaneous glucose monitoring under various skin tones.
Sex Difference in Cigarette-Smoking Status and Its Association with Brain Volumes Using Large-Scale Community-Representative Data
Authors: Chen Xiaofei , Cook Riley , Filbey Francesca M. , Nguyen Hang , McColl Roderick , Jeon-Slaughter Haekyung
Published: August 2023

Background: Cigarette smoking is believed to accelerate age-related neurodegeneration. Despite significant sex differences in both smoking behaviors and brain structures, the active literature is equivocal in parsing out a sex difference in smoking-associated brain structural changes. Objective: The current study examined subcortical and lateral ventricle gray matter (GM) volume differences among smokers, active, past, and never-smokers, stratified by sex. Methods: The current study data included 1959 Dallas Heart Study (DHS) participants with valid brain imaging data. Stratified by gender, multiple-group comparisons of three cigarette-smoking groups were conducted to test whether there is any cigarette-smoking group differences in GM volumes of the selected regions of interest (ROIs). Results: The largest subcortical GM volumetric loss and enlargement of the lateral ventricle were observed among past smokers for both females and males. However, these observed group differences in GM volumetric changes were statistically significant only among males after adjusting for age and intracranial volumes. Conclusions: The study findings suggest a sex difference in lifetime-smoking-associated GM volumetric changes, even after controlling for aging and intracranial volumes.
A Relational Workforce Capacity Approach to Trauma-Informed Care Implementation: Staff Rejection Sensitivity as a Potential Barrier to Organizational Attachment
Authors: Hardan Tareq , Bosk Emily A. , Mendez Alicia , Williams-Butler Abigail , Julien Fabrys , MacKenzie Michael J.
Published: August 2023

This study explores the relationship between staff rejection sensitivity (a psychological concept grounded in histories of loss and trauma) and organizational attachment among mental health agencies transitioning to Trauma-Informed Care (TIC), which is currently outside the focus of most research. Specifically, this study examines: (1) whether staff rejection sensitivity predicts organizational attachment; (2) whether staff turnover intentions account for the association between rejection sensitivity and organizational attachment; and (3) whether those associations hold once taking into account staff demographic factors (gender, race and ethnicity, education, and income)? Around 180 frontline workers in three Northeastern U.S. mental health agencies responded to surveys collected between 2016 and 2019 using the organizational attachment, rejection sensitivity and turnover intention measures, and their previous TIC training experience. Rejection sensitivity was significantly associated with organizational attachment (β = −0.39, p < 0.001), accounting for 6% of its variance in organizational attachment. The relationship between these variables retained significance, and staff education significantly predicted organizational attachment, with higher education predicting lower levels of organizational attachment (β = −0.15, p < 0.05), accounting for 22% of its variance. This study concludes that TIC transitioning mental health agencies’ staff with a higher rejection sensitivity are more likely to express lower organizational attachment and higher intent-to-turnover.
Crosstalk between Cancer Cells and Cancer-Associated Fibroblasts Mediated by TGF-β1–IGFBP7 Signaling Promotes the Progression of Infiltrative Gastric Cancer
Authors: Hong Zhijun , Xie Wen , Zhuo Huiqin , Wei Xujin , Wang Kang , Cheng Jia , Lin Lingyun , Hou Jingjing , Chen Xin , Cai Jianchun
Published: August 2023

Patients with infiltrative-type gastric cancer (GC) (Ming’s classification) have a poor prognosis due to more metastasis and recurrence. Cancer-associated fibroblasts (CAFs) in infiltrative-type extracellular matrix (ECM) have specific characteristics compared with those of expansive types with respect to metastasis, but the mechanism is still unclear. Based on our proteomics data, TCGA data analysis, and immunohistochemical staining results, significantly higher expression of IGFBP7 was observed in GC, especially in the infiltrative type, and was associated with a poor prognosis. Combining single-cell transcriptome data from GEO and multiple immunofluorescence staining on tissue showed that the differential expression of IGFBP7 mainly originated from myofibroblastic CAFs, the subgroup with higher expression of PDGFRB and α-SMA. After treating primary normal fibroblasts (NFs) with conditional medium or recombined protein, it was demonstrated that XGC-1-derived TGF-β1 upregulated the expression of IGFBP7 in the cells and its secretion via the P-Smad2/3 pathway and mediated its activation with higher FAP, PDGFRB, and α-SMA expression. Then, either conditional medium from CAFs with IGFBP7 overexpression or recombined IGFBP7 protein promoted the migration, invasion, colony formation, and sphere growth ability of XGC-1 and MGC-803, respectively. Moreover, IGFBP7 induced EMT in XGC-1. Therefore, our study clarified that in the tumor microenvironment, tumor-cell-derived TGF-β1 induces the appearance of the IGFBP7+ CAF subgroup, and its higher IGFBP7 extracellular secretion level accelerates the progression of tumors.
Therapeutic and Adverse Effect of Anti-PD1 Immunotherapy in Melanoma: A Retrospective, Single-Institute Study of 222 Patients
Authors: Eikenes Grethe , Liszkay Gabriella , Balatoni Tímea , Czirbesz Kata , Hunyadi Karen , Kozéki Zsófia , Kispál Mihály Tamás , Baranyai Fanni , Danyi Tímea , Bőcs Katalin , Kenessey István
Published: August 2023

Background: The introduction of immuno- and targeted therapeutic modalities meant a breakthrough step in the therapy of melanoma. As a checkpoint inhibitor, the more effective and less toxic anti-PD1 therapy followed an anti-CTLA4 approach. Methods: From our patient pool, 222 advanced melanoma cases were selected, where anti-PD1 (pembrolizumab, nivolumab) therapy was initiated between March 2015 and December 2020. During our retrospective analysis, the efficacy and safety of the therapy were assessed. Results: The median follow-up was 16 months (interval: 0–64 months), and 150 patients (67.6%) received therapy in the first line, while second and third line therapy was performed among 72 patients (32.4%) for the median of 7.0 months (0–60). In 50 cases, BRAF mutations were detected. Ninety-six patients showed objective response (11.3% CR, 32.0% PR). The median PFS was 10.0 months (0–60), and the median OS was 23.0 months (0–64). Autoimmune side effects were found in 79 patients (35.5%); grade 3 occurred in 6.3% of the cases, while 1 patient died due to fulminant pneumonitis (0.25%). Conclusion: Although the range of immunotherapeutic options is getting wider, in the management of melanoma patients, anti-PD1 monotherapy remains an important, effective, and safe method. However, significant correlation was found between the immune-related side effects and therapeutic efficacy.
Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results
Authors: Chick Robert Connor , Gunderson Andrew J. , Rahman Shafia , Cloyd Jordan M.
Published: August 2023

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials of immunotherapy in metastatic PDAC have yielded disappointing results. There is considerable interest in using immunotherapy approaches in the neoadjuvant setting in order to prime the immune system to detect and prevent micrometastatic disease and recurrence. A scoping review was conducted to identify published and ongoing trials utilizing preoperative immunotherapy. In total, 9 published trials and 27 ongoing trials were identified. The published trials included neoadjuvant immune checkpoint inhibitors, cancer vaccines, and other immune-modulating agents that target mechanisms distinct from that of immune checkpoint inhibition. Most of these are early phase trials which suggest improvements in disease-free and overall survival when combined with standard neoadjuvant therapy. Ongoing trials are exploring various combinations of these agents with each other and with chemotherapy and/or radiation. Rational combination immunotherapy in addition to standard neoadjuvant therapy has the potential to improve outcomes in PDAC, but further clinical trials are needed, particularly those which utilize an adaptive trial design.
Potential of miRNAs in Plasma Extracellular Vesicle for the Stratification of Prostate Cancer in a South African Population
Authors: Temilola Dada Oluwaseyi , Wium Martha , Paccez Juliano , Salukazana Azola Samkele , Otu Hasan H. , Carbone Giuseppina M. , Kaestner Lisa , Cacciatore Stefano , Zerbini Luiz Fernando
Published: August 2023

Prostate cancer (PCa) is the most common cause of cancer death among African men. The analysis of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) can be utilized as a non-invasive tool for the diagnosis of PCa. In this study, we used small RNA sequencing to profile miRNAs cargo in plasma EVs from South African PCa patients. We evaluated the differential expression of miRNAs between low and high Gleason scores in the plasma EVs of South African patients and in the prostatic tissue from data available in the Cancer Genome Atlas (TCGA) Data Portal. We identified 7 miRNAs differently expressed in both EVs and prostatic tissues. We evaluated their expression using qPCR in a larger cohort of 10 patients with benign prostatic hyperplasia (BPH) and 24 patients with PCa. Here, we reported that the ratio between two of these miRNAs (i.e., miR-194-5p/miR-16-5p) showed a higher concentration in PCa compared to BPH and in metastatic PCa compared to localized PCa. We explored for the first time the profiling of miRNAs cargo in plasma EVs as a tool for the identification of putative markers in the South African population. Our finding indicated the ratio miR-194-5p/miR-16-5p as a non-invasive marker for the evaluation of PCa aggressiveness in this population.
Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models
Authors: Datkhayev Ubaidilla M. , Rakhmetova Venera , Shepetov Abay M. , Kodasbayev Almat , Datkayeva Gulmira Makhanbetovna , Pazilov Sabit B. , Farooqi Ammad Ahmad
Published: August 2023

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the “ubiquitinome” is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.
Does Hospitalist Care Enhance Palliative Care and Reduce Aggressive Treatments for Terminally Ill Patients? A Propensity Score-Matched Study
Authors: Hsu Nin-Chieh , Huang Chun-Che , Hsu Chia-Hao , Wang Tzung-Dau , Sheng Wang-Huei
Published: August 2023

Background: Information on the use of palliative care and aggressive treatments for terminally ill patients who receive care from hospitalists is limited. Methods: This three-year, retrospective, case-control study was conducted at an academic medical center in Taiwan. Among 7037 patients who died in the hospital, 41.7% had a primary diagnosis of cancer. A total of 815 deceased patients who received hospitalist care before death were compared with 3260 patients who received non-hospitalist care after matching for age, gender, catastrophic illness, and Charlson comorbidity score. Regression models with generalized estimating equations were performed. Results: Patients who received hospitalist care before death, compared to those who did not, had a higher probability of palliative care consultation (odds ratio (OR) = 3.41, 95% confidence interval (CI): 2.63–4.41), and a lower probability to undergo invasive mechanical ventilation (OR = 0.13, 95% CI: 0.10–0.17), tracheostomy (OR = 0.14, 95% CI: 0.06–0.31), hemodialysis (OR = 0.70, 95% CI: 0.55–0.89), surgery (OR = 0.25, 95% CI: 0.19–0.31), and intensive care unit admission (OR = 0.11, 95% CI: 0.08–0.14). Hospitalist care was associated with reductions in length of stay (coefficient (B) = −0.54, 95% CI: −0.62–−0.46) and daily medical costs. Conclusions: Hospitalist care is associated with an improved palliative consultation rate and reduced life-sustaining treatments before death.
Functional Characterization of the A414G Loss-of-Function Mutation in HCN4 Associated with Sinus Bradycardia
Authors: Verkerk Arie , Wilders Ronald
Published: August 2023

Patients carrying the heterozygous A414G mutation in the HCN4 gene, which encodes the HCN4 protein, demonstrate moderate to severe bradycardia of the heart. Tetramers of HCN4 subunits compose the ion channels in the sinus node that carry the hyperpolarization-activated ‘funny’ current (If), also named the ‘pacemaker current’. If plays an essential modulating role in sinus node pacemaker activity. To assess the mechanism by which the A414G mutation results in sinus bradycardia, we first performed voltage clamp measurements on wild-type (WT) and heterozygous mutant HCN4 channels expressed in Chinese hamster ovary (CHO) cells. These experiments were performed at physiological temperature using the amphotericin-perforated patch-clamp technique. Next, we applied the experimentally observed mutation-induced changes in the HCN4 current of the CHO cells to If of the single human sinus node cell model developed by Fabbri and coworkers. The half-maximal activation voltage V1/2 of the heterozygous mutant HCN4 current was 19.9 mV more negative than that of the WT HCN4 current (p < 0.001). In addition, the voltage dependence of the heterozygous mutant HCN4 current (de)activation time constant showed a −11.9 mV shift (p < 0.001) compared to the WT HCN4 current. The fully-activated current density, the slope factor of the activation curve, and the reversal potential were not significantly affected by the heterozygous A414G mutation. In the human sinus node computer model, the cycle length was substantially increased, almost entirely due to the shift in the voltage dependence of steady-state activation, and this increase was more prominent under vagal tone. The introduction of a passive atrial load into the model sinus node cell further reduced the beating rate, demonstrating that the bradycardia of the sinus node was even more pronounced by interactions between the sinus node and atria. In conclusion, the experimentally identified A414G-induced changes in If can explain the clinically observed sinus bradycardia in patients carrying the A414G HCN4 gene mutation.