bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and Immunological Features of PR-10 Allergens: Focusing on the Major Alder Pollen Allergen Aln g 1
Authors: Melnikova Daria N. , Finkina Ekaterina I. , Potapov Andrey E. , Danilova Yulia D. , Toropygin Ilia Y. , Matveevskaya Natalia S. , Ovchinnikova Tatiana V. , Bogdanov Ivan V.
Published: May 2024

Today, allergies have become a serious problem. PR-10 proteins are clinically relevant allergens that have the ability to bind hydrophobic ligands, which can significantly increase their allergenicity potential. It has been recently shown that not only the birch pollen allergen Bet v 1 but also the alder pollen allergen Aln g 1, might act as a true sensitizer of the immune system. The current investigation is aimed at the further study of the allergenic and structural features of Aln g 1. By using qPCR, we showed that Aln g 1 was able to upregulate alarmins in epithelial cells, playing an important role in sensitization. With the use of CD-spectroscopy and ELISA assays with the sera of allergic patients, we demonstrated that Aln g 1 did not completely restore its structure after thermal denaturation, which led to a decrease in its IgE-binding capacity. Using site-directed mutagenesis, we revealed that the replacement of two residues (Asp27 and Leu30) in the structure of Aln g 1 led to a decrease in its ability to bind to both IgE from sera of allergic patients and lipid ligands. The obtained data open a prospect for the development of hypoallergenic variants of the major alder allergen Aln g 1 for allergen-specific immunotherapy.
Exploring the Enigma: The Role of the Epithelial Protein Lost in Neoplasm in Normal Physiology and Cancer Pathogenesis
Authors: Lindell Emma , Zhang Xiaonan
Published: May 2024

The cytoskeleton plays a pivotal role in maintaining the epithelial phenotype and is vital to several hallmark processes of cancer. Over the past decades, researchers have identified the epithelial protein lost in neoplasm (EPLIN, also known as LIMA1) as a key regulator of cytoskeletal dynamics, cytoskeletal organization, motility, as well as cell growth and metabolism. Dysregulation of EPLIN is implicated in various aspects of cancer progression, such as tumor growth, invasion, metastasis, and therapeutic resistance. Its altered expression levels or activity can disrupt cytoskeletal dynamics, leading to aberrant cell motility and invasiveness characteristic of malignant cells. Moreover, the involvement of EPLIN in cell growth and metabolism underscores its significance in orchestrating key processes essential for cancer cell survival and proliferation. This review provides a comprehensive exploration of the intricate roles of EPLIN across diverse cellular processes in both normal physiology and cancer pathogenesis. Additionally, this review discusses the possibility of EPLIN as a potential target for anticancer therapy in future studies.
Topology and Dynamics of Transcriptome (Dys)Regulation
Authors: Planat Michel , Chester David
Published: May 2024

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let us delve into the mathematical intricacies of these sequences. We have previously devised a mathematical approach for defining a “healthy” sequence. This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt−1, it must be aperiodic, and fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let us explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI Equation. In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a “wild” dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find many applications including cancer research and the investigation of neurodegenative diseases.
Physiological, Biochemical, and Molecular Analyses Reveal Dark Heartwood Formation Mechanism in Acacia melanoxylon
Authors: Zhang Ruping , Bai Xiaogang , Chen Zhaoli , Chen Mengjiao , Li Xiangyang , Zeng Bingshan , Hu Bing
Published: May 2024

Acacia melanoxylon is highly valued for its commercial applications, with the heartwood exhibiting a range of colors from dark to light among its various clones. The underlying mechanisms contributing to this color variation, however, have not been fully elucidated. In an effort to understand the factors that influence the development of dark heartwood, a comparative analysis was conducted on the microstructure, substance composition, differential gene expression, and metabolite profiles in the sapwood (SW), transition zone (TZ), and heartwood (HW) of two distinct clones, SR14 and SR25. A microscopic examination revealed that heartwood color variations are associated with an increased substance content within the ray parenchyma cells. A substance analysis indicated that the levels of starches, sugars, and lignin were more abundant in SP compared to HW, while the concentrations of phenols, flavonoids, and terpenoids were found to be higher in HW than in SP. Notably, the dark heartwood of the SR25 clone exhibited greater quantities of phenols and flavonoids compared to the SR14 clone, suggesting that these compounds are pivotal to the color distinction of the heartwood. An integrated analysis of transcriptome and metabolomics data uncovered a significant accumulation of sinapyl alcohol, sinapoyl aldehyde, hesperetin, 2′, 3, 4, 4′, 6′-peptahydroxychalcone 4′-O-glucoside, homoeriodictyol, and (2S)-liquiritigenin in the heartwood of SR25, which correlates with the up-regulated expression of CCRs (evm.TU.Chr3.1751, evm.TU.Chr4.654_667, evm.TU.Chr4.675, evm.TU.Chr4.699, and evm.TU.Chr4.704), COMTs (evm.TU.Chr13.3082, evm.TU.Chr13.3086, and evm.TU.Chr7.1411), CADs (evm.TU.Chr10.2175, evm.TU.Chr1.3453, and evm.TU.Chr8.1600), and HCTs (evm.TU.Chr4.1122, evm.TU.Chr4.1123, evm.TU.Chr8.1758, and evm.TU.Chr9.2960) in the TZ of A. melanoxylon. Furthermore, a marked differential expression of transcription factors (TFs), including MYBs, AP2/ERFs, bHLHs, bZIPs, C2H2s, and WRKYs, were observed to be closely linked to the phenols and flavonoids metabolites, highlighting the potential role of multiple TFs in regulating the biosynthesis of these metabolites and, consequently, influencing the color variation in the heartwood. This study facilitates molecular breeding for the accumulation of metabolites influencing the heartwood color in A. melanoxylon, and offers new insights into the molecular mechanisms underlying heartwood formation in woody plants.
Tunable Construction of Chiral Nematic Cellulose Nanocrystals/ZnO Films for Ultra-Sensitive, Recyclable Sensing of Humidity and Ethanol
Authors: Xiao Xiao , Dong Hanqi , Ping Xinxin , Shan Guowei , Chen Jie , Yan Mengxing , Li Weixing , Ling Zhe
Published: May 2024

The investigation of functional materials derived from sustainable and eco-friendly bioresources has generated significant attention. Herein, nanocomposite films based on chiral nematic cellulose crystals (CNCs) were developed by incorporating xylose and biocompatible ZnO nanoparticles (NPs) via evaporation-induced self-assembly (EISA). The nanocomposite films exhibited iridescent color changes that corresponded to the birefringence phenomenon under polarized light, which was attributed to the formation of cholesteric structures. ZnO nanoparticles were proved to successfully adjust the helical pitches of the chiral arrangements of the CNCs, resulting in tunable optical light with shifted wavelength bands. Furthermore, the nanocomposite films showed fast humidity and ethanol stimuli response properties, exhibiting the potential of stimuli sensors of the CNC-based sustainable materials.
Stem Cell and Regenerative Therapies for the Treatment of Osteoporotic Vertebral Compression Fractures
Authors: Zhang Songzi , Lee Yunhwan , Liu Yanting , Yu Yerin , Han Inbo
Published: May 2024

Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy’s transformative potential in OVCF treatment. It thoroughly describes the therapeutic possibilities and mechanisms of action of mesenchymal stem cells against OVCFs, relying on recent clinical trials and preclinical studies for efficacy assessment. Our findings reveal that stem cell therapy, particularly in combination with scaffolding materials, holds substantial promise for bone regeneration, spinal stability improvement, and pain mitigation. This integration of stem cell-based methods with conventional treatments may herald a new era in OVCF management, potentially improving patient outcomes. This review advocates for accelerated research and collaborative efforts to translate laboratory breakthroughs into clinical practice, emphasizing the revolutionary impact of regenerative therapies on OVCF management. In summary, this paper positions stem cell therapy at the forefront of innovation for OVCF treatment, stressing the importance of ongoing research and cross-disciplinary collaboration to unlock its full clinical potential.
The Impact of Financial Pressure on the Association between Employment and Depressive Symptoms for Community-Dwelling Older Adults
Authors: Costantini Hiroko , Ono Takazumi , Shogaki Nanami , Tanaka Tomoki , Lyu Weida , Son Bo-Kyung , Yoshizawa Yasuyo , Iijima Katsuya
Published: May 2024

Addressing how employment impacts older adults, including their psychological well-being, we contribute to the study of this topic by examining the association between paid work in community-dwelling older adults and their depressive mood, while considering the extent of their financial pressure. Methods: The data are from the Kashiwa longitudinal cohort study, with a 2014 baseline and a 2016 follow-up. Of the 1308 participants in the 2014 survey, 781 people were included. We conducted binary logistic regression analyses stratified by economic status with regard to the extent of the financial pressure experienced. The independent variable of interest was paid work in 2014, and the dependent variable was the extent of depressive mood (a score of 5 or more on the Geriatric Depression Scale 15) in 2016. Results: Paid work was associated with lower odds of depressive mood among those under financial pressure (odds ratio [OR] 0.46, 95% confidence interval [95%CI] 0.26, 0.81), whereas for those financially stable, we did not find an association between paid work and odds of depressive mood (OR 0.99, [95%CI] 0.26, 2.63). Discussion: We evidence that for older adults under financial pressure, employment supports the maintenance of their psychological well-being. We contribute to the literature by understanding when employment is beneficial for older adults, which is important in developing appropriate older adult employment social policies.
A Mobile App for Chronic Disease Self-Management for Individuals with Low Health Literacy: A Multisite Randomized Controlled Clinical Trial
Authors: Ownby Raymond L. , Simonson Michael , Caballero Joshua , Thomas-Purcell Kamilah , Davenport Rosemary , Purcell Donrie , Ayala Victoria , Gonzalez Juan , Patel Neil , Kondwani Kofi
Published: May 2024

The purpose of this study was to evaluate the effects of a mobile app designed to improve chronic disease self-management in patients aged 40 years and older with low health literacy and who had at least one chronic health condition, and to assess the impact of delivering information at different levels of reading difficulty. A randomized controlled trial was completed at two sites. Individuals aged 40 years and older screened for low health literacy who had at least one chronic health condition were randomly assigned to a tailored information multimedia app with text at one of three grade levels. Four primary outcomes were assessed: patient activation, chronic disease self-efficacy, health-related quality of life, and medication adherence. All groups showed overall increases in activation, self-efficacy, and health-related quality of life, but no change in medication adherence. No between-group differences were observed. The mobile app may have been effective in increasing participants’ levels of several psychosocial variables, but this interpretation can only be advanced tentatively in light of the lack of control-experimental group differences. Reading difficulty level was not significantly related to outcomes.
Evaluating the Influence of Tool Material on the Performance of Refill Friction Stir Spot Welds in AA2029
Authors: Belnap Ruth , Smith Taylor , Blackhurst Paul , Cobb Josef , Misak Heath , Bosker John , Hovanski Yuri
Published: May 2024

Joining high strength 2xxx series aluminum is known to be complex and difficult; these alloys are traditionally considered non-weldable for fusion welding. This paper describes details on welding AA2029-T8 for skin-stiffened structures using refill friction stir spot welding (RFSSW). RFSSW is a solid-state process invented in the early 2000s that produces spot welds that are strong, lightweight, flush, and hermetic. Cycle times between 1 and 3 s are discussed, and process forces within a range of 8 to 14 kN are demonstrated. Furthermore, lap-shear quasi-static tensile strengths are shown to be between 10 kN and 12 kN in 9 mm diameter spots. A comparison of the performance of RFSSW welds made with various tool materials—which include H13 tool steel, tungsten carbide, and MP159—is detailed. Comparisons of parameters, weld consolidation, and heat-affected zones are presented with discussion related to heat generation specific to each tool material.
An Experiment-Based Variable Compensation Method to Improve the Geometric Accuracy of Sub-mm Features Fabricated by Stereolithography (SLA)
Authors: Modica Francesco , Basile Vito , Fassi Irene
Published: May 2024

In this paper, we present an experimental procedure to enhance the dimensional accuracy of fabrication via stereolithography (SLA) of features at the sub-mm scale. Deviations in sub-mm hemispherical cavity diameters were detected and measured on customized samples by confocal microscopy. The characterization and experimental observations of samples allowed the identification of inaccuracy sources, mainly due to the laser beam scanning strategy and the incomplete removal of uncured liquid resin in post-processing (i.e., IPA washing). As a technology baseline, the measured dimensional errors on cavity diameters were up to −46%. A compensation method was defined and implemented, resulting in relevant improvements in dimensional accuracy. However, measurements on sub-mm cavities having different sizes revealed that a constant compensation parameter (i.e., C = 85, 96, 120 μm) is not fully effective at the sub-mm scale, where average errors remain at −24%, −18.8%, and −16% for compensations equal to 85, 96 and 120 μm, respectively. A further experimental campaign allowed the identification of an effective nonlinear compensation law where the compensation parameter depends on the sub-mm feature size C = f(D). Results show a sharp improvement in dimensional accuracy on sub-mm cavity fabrication, with errors consistently below +8.2%. The proposed method can be extended for the fabrication of any sub-mm features without restrictions on the specific technology implementation.
Changing Health Information on COVID-19 Vaccination in Asia
Authors: Costantini Hiroko , Costantini Rosa , Fuse Rie
Published: May 2024

The informational domain related to COVID-19 reflects the degree of uncertainty and pace of evolution of the pandemic. This places a burden on peoples’ searches for information to guide their choices, importantly including for COVID-19 vaccines. Thus, it is important for health communications that support vaccination campaigns to attenuate vaccine hesitancy to be accessible, including in terms of readability, and adapted to the evolving pandemic. This paper aims to understand internet searches on COVID-19 vaccination, specifically the mix of sources and readability of the sources over a two-year period (2021–2023) in Singapore, Hong Kong, and the Philippines, for search results in English, as English is a main language for each of these locations. The sources accessed through online searches in June 2021 and May 2023 were categorized by type of source and whether they were from one of the focal locations or elsewhere. The readability of information from web-search results was assessed using a set of readability tests (Flesch–Kincaid Reading Ease, Flesch–Kincaid Grade Level, Gunning Fog Index, Coleman–Liau Index, and Simple Measure of Gobbledygook Grade level). Over the two-year period there was an increase in government sources and reduction in mass media sources with distinct local patterns. Local government sources increased in Singapore whereas foreign government and multi-lateral organization sources increased in Hong Kong, with the Philippines being an intermediate pattern. In contrast to the changing mix of sources, the readability tests indicate a low proportion of URLs scoring within recommended readability thresholds across locations and types of sources over the two years. Information on COVID-19 vaccine development and deployment is an important part of health communications that includes internet search. The paper contributes to understanding health communications during a pandemic, including mix of local and non-local sources and contingency on local social and health context.
Botanic Garden Tourism, Social Value, Health, and Well-Being
Authors: Catahan Nicholas , Hopwood Michelle , Suraweera Piumie
Published: May 2024

Many botanic gardens are flourishing, and many others can learn from those leading the way; at the same time, all can form new allegiances informed by service research. We developed this paper to plant seeds for different stakeholders interested in putting a spotlight on botanic garden tourism opportunities. It is in response to a call to action by many stakeholders across the botanic garden sector for greater public engagement, to challenge plant awareness disparity, and to ensure the vitality and viability of the sector. Our commentary considers positive, transformative service making, marketing, management, and development. We recommend holistic, integrated services via ecosystemic thinking and collaborative partnerships across the sector and with non-traditional partnerships in the design of sustainable service ecosystems. It is envisaged that service research will spur on a more responsible, ethical, moral enterprise and sustainable botanic garden tourism with opportunities to drive positive, transformative change in meeting sustainable development goals for the good of plants, people, and planet.
The Rise of Lymphatic Intervention: A Rapid Evolution
Authors: Majdalany Bill S.
Published: May 2024

For centuries, the lymphatic system was a known unknown [...]
Formulation and Characterization of Chitosan-Based Mixed-Matrix Scaffold for Tissue Engineering
Authors: Lopes Rita , Gordo Paulo M. , Costa Benilde F. O. , Alves Patrícia
Published: May 2024

The use of scaffolds, three-dimensional porous, biodegradable and biocompatible structures, that can be produced from natural polymers, synthetics, ceramics and metals is crucial in the tissue engineering field. Chitosan is a polysaccharide of natural origin, found in the exoskeleton of marine arthropods and in the cell wall of fungi, with enormous popularity in the production of three-dimensional materials for Tissue Engineering, in particular bone repair. This polymer has several advantages in the production of these structures in bone regeneration and repair: biodegradability, biocompatibility, non-toxicity and antimicrobial properties. This study aimed to prepare porous scaffolds, for bone repair of degenerative diseases in the spine with better performance and less secondary effects, based on chitosan and another biopolymer (sodium alginate) with the incorporation of calcium phosphates (hydroxyapatite and β-tricalcium phosphate), for tissue engineering application. The obtained scaffolds were object of a detailed characterization, namely with regard to their porosity through the ethanol method, degradation, positron annihilation spectroscopy (PAS), mechanical properties, scanning electronic microscope (SEM), thermal stability through thermogravimetric analysis (TGA), chemical composition through X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The results obtained showed that the different scaffolds presented pores able to support osteoid matrix growth. The crosslinking of scaffolds was also evaluated and resulted in pores with smaller dimensions and higher regularity in the chitosan-sodium alginate polymer without calcium phosphate scaffold. It was also possible to observe the effect of inorganics on mixed-matrix scaffolds, both morphologically and chemically. These scaffolds showed promising results in terms of mechanical and chemical properties, along with promising porosity for tissue regeneration applications.
Development of a Polyethylene Breathable Packaging Film with Modified Microcrystalline Cellulose for Fresh Products
Authors: Rodrigues Pedro V. , Castro M. Cidália R. , Soares Ana M. S. , Melro Liliana , Machado Ana V.
Published: May 2024

In this study, a material based on polyethylene (PE) and microcrystalline cellulose (MC) was developed as a breathable packaging film. Surface functionalization of MC with 3-aminopropyltriethoxysilane (APTES) has been shown to be an efficient option to tailor their properties and increase opportunities for the application of MC on the reinforcement of polymers such as polyethylene (PE). The functionalization of MC with the mentioned silane derivative was achieved using a green method and later used in the development of composites with PE in three percentages (1, 3, and 5%). All the materials were prepared by melt blending and characterized in terms of structural properties (ATR-FTIR and FTIR in transmittance mode, EDX, and SEM), thermal properties (DSC and TGA), thermomechanical properties (DMA), contact angle measurements and permeability to water vapor. The materials demonstrated the potential to be used as breathable film packaging for fresh products.
Diagnostic Accuracy of Ultrasound and Fine-Needle Aspiration Cytology in Thyroid Malignancy
Authors: Boudina Maria , Katsamakas Michael , Chorti Angeliki , Panousis Panagiotis , Tzitzili Eleni , Tzikos Georgios , Chrisoulidou Alexandra , Valeri Rosalia , Ioannidis Aris , Papavramidis Theodossis
Published: May 2024

Introduction: Thyroid nodule incidence is increasing due to the widespread application of ultrasonography. Fine-needle aspiration cytology is widely applied for the detection of malignancies. The aim of this study was to evaluate the predictive value of ultrasonography in thyroid cancer. Methods: This retrospective study included patients that underwent total thyroidectomy for benign thyroid disease or well-differentiated thyroid carcinoma from January 2017 to December 2022. The study population was divided into groups: the well-differentiated thyroid cancer group and the control group with benign histopathological reports. Results: In total, 192 patients were enrolled in our study; 159 patients were included in the well-differentiated thyroid cancer group and 33 patients in the control group. Statistical analysis demonstrated that ultrasonographic findings such as microcalcifications (90.4%), hypoechogenicity (89.3%), irregular margins (92.2%) and taller-than-wide shape (90.5%) were correlated to malignancy (p < 0.001). Uni- and multivariate analysis revealed that both US score (OR: 2.177; p < 0.001) and Bethesda System (OR: 1.875; p = 0.002) could predict malignancies. In terms of diagnostic accuracy, the US score displayed higher sensitivity (64.2% vs. 33.3%) and better negative predictive value (34.5% vs. 24.4%) than the Bethesda score, while both scoring systems displayed comparable specificities (90.9% vs. 100%) and positive predictive values (97.1% vs. 100%). Discussion: The malignant potential of thyroid nodules is a crucial subject, leading the decision for surgery. Ultrasonography and fine-needle aspiration cytology are pivotal examinations in the diagnostic process, with ultrasonography demonstrating better negative predictive value.
Anatomical Possibilities of the Alveolar Bone at the Upper Second Premolar Level
Authors: Mureşan Alexandru Nicolae , Dandoczi Carol Antonio , Tudose Răzvan Costin , Hostiuc Sorin , Rusu Mugurel Constantin
Published: May 2024

Background and Objectives: The upper posterior teeth are typically regarded as being exclusively inferior to the maxillary sinus (MS). The expansion of the nasal fossa above the maxillary alveolar base (MAB) needs better investigation. The hypothesis was raised that the MAB in the upper premolar region, which is usually addressed by surgeons for the elevation of the antral floor, is not exclusively beneath the MS. Therefore, we aimed to document the possible upper relations of the MAB as antral, nasal, or both. Materials and Methods: A total of 145 CBCT scans were used to study four types of MAB: type 1—antral; type 2—antral with a palatal recess; type 3—antral and nasal; type 4—nasal. In type 2, the orthoradial width of the alveolar bone, the rectilinear width of the antral floor, and the maximum depth of the palatal recess were measured. For type 3, the MAB width and the straight widths of the antral and nasal segments of the MAB were measured. Results: Type 1 was found in 67.24%, type 2 in 13.45%, type 3 in 16.21%, and type 4 in 3.1% of the 290 MSs investigated. Palatal recesses were found in 11.72% of the MSs on the right side and 15.17% of the MSs on the left side. Types 1 and 2 exhibited strongly statistically significant bilateral symmetry (Pearson’s Chi2 = 86.42, p < 0.001). Type 3 correlated equally with contralateral types 1 and 3. The bilateral symmetry for types 1–3 was stronger in the males (Pearson’s Chi2 = 47.83, p < 0.001) than in the females (Pearson’s Chi2 = 56.96, p < 0.001). There were no statistically significant associations between sex and the unilateral anatomical type. Conclusions: The MAB in the upper second premolar area should not be considered to be exclusively antral during surgeries or in anatomical teaching.
Comparison of Inter-Method Agreement and Reliability for Automatic Brain Volumetry Using Three Different Clinically Available Software Packages
Authors: Choi Kwang Ho , Heo Young Jin , Baek Hye Jin , Kim Jun-Ho , Jang Jeong Yoon
Published: May 2024

Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer (FS), NeuroQuant® (NQ), and Heuron AD (HAD). Materials and Methods: In this study, we retrospectively included 78 patients who underwent conventional three-dimensional (3D) T1-weighed imaging (T1WI) to evaluate their memory impairment, including 21 with normal objective cognitive function, 24 with mild cognitive impairment, and 33 with Alzheimer’s disease (AD). All 3D T1WI scans were analyzed using three different volumetric software packages. Repeated-measures analysis of variance, intraclass correlation coefficient, effect size measurements, and Bland–Altman analysis were used to evaluate the inter-method agreement and reliability. Results: The measured volumes demonstrated substantial to almost perfect agreement for most brain regions bilaterally, except for the bilateral globi pallidi. However, the volumes measured using the three software packages showed significant mean differences for most brain regions, with consistent systematic biases and wide limits of agreement in the Bland–Altman analyses. The pallidum showed the largest effect size in the comparisons between NQ and FS (5.20–6.93) and between NQ and HAD (2.01–6.17), while the cortical gray matter showed the largest effect size in the comparisons between FS and HAD (0.79–1.91). These differences and variations between the software packages were also observed in the subset analyses of 45 patients without AD and 33 patients with AD. Conclusions: Despite their favorable reliability, the software-based brain volume measurements showed significant differences and systematic biases in most regions. Thus, these volumetric measurements should be interpreted based on the type of volumetric software used, particularly for smaller structures. Moreover, users should consider the replaceability-related limitations when using these packages in real-world practice.
Autoimmune Encephalitis following Checkpoint Inhibitor Therapy in a Patient with Metastatic Melanoma in Complete Remission
Authors: Civardi Giuseppe , Medioli Alessia , Braghieri Carlotta , Ambroggi Massimo , Immovilli Paolo , Orsucci Simone , Contini Paolo , Aronica Giuseppe , Cavanna Luigi
Published: May 2024

The use of immune checkpoint inhibitors (ICIs) in cancer is increasing. Their side effects are mainly due to the triggering of autoimmunity, which are mild or moderate and include skin rash, colitis, hepatitis, endocrine disorders, myositis, interstitial lung disorder, etc., in most cases during the course of therapy. Autoimmune encephalitis (AE) is rare in cancer patients treated with ICIs. Fifty patients with ICI-related encephalitis were identified in a recent review. Herein, we report a case of pembrolizumab associated with AE with a favorable short-term prognosis. A 68-year-old man with malignant metastatic melanoma achieved complete remission after pembrolizumab treatment. However, 10 months after pembrolizumab cessation due to grade 3 diarrhea, he developed confusion, an altered mental status, progressive memory loss, and gait disturbance. He was admitted to the neurologic department, and a comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, and blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, a high dose of intravenous steroids, and intravenous immunoglobulins. The patient improved, and he is now well with a performance status of 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission, and the AE showed a good response after the treatment was performed.
Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases
Authors: Dilixiati Suofeiya , Yan Jiaxi , Qingzhuoga De , Song Gengqing , Tu Lei
Published: May 2024

Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques—vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)—as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. Materials and Methods: We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. Results: Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. Conclusions: Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols.
Effects of 12 Weeks of Daily Melatonin Administration on Inflammatory Markers and Adipose Tissue Mass of Rats under Hypoestrogenism
Authors: Pejon Taciane Maria Melges , Pereira Guilherme Borges , de Castro Cynthia Aparecida , Anibal Fernanda de Freitas , Beck Wladimir Rafael
Published: May 2024

Background and Objectives: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-β-1, and leukotriene C4 (LTC4). Materials and Methods: The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg−1) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-β-1, and LTC4. Results: Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions: Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.
IL24 Expression in Synovial Myofibroblasts: Implications for Female Osteoarthritis Pain through Propensity Score Matching Analysis
Authors: Shibata Naoya , Ohashi Yoshihisa , Tsukada Ayumi , Iwase Dai , Aikawa Jun , Mukai Manabu , Metoki Yukie , Uekusa Yui , Sato Masashi , Inoue Gen , Takaso Masashi , Uchida Kentaro
Published: May 2024

(1) Introduction: Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) Methods: To assess gender-specific variations, we analyzed myofibroblast marker expression and IL24 levels in synovial tissue samples from propensity-matched male and female OA patients (each n = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between IL24 expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between IL24 and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients (n = 5), and IL24 expression was compared between these subsets. (3) Results: Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and IL24 compared to males. IL24 expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed IL24 compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) Conclusions: Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA’s multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.
The Association of Free Testosterone with Sarcopenic Obesity in Community-Dwelling Older Men: A Cross-Sectional Study
Authors: Choi Seongmin , Chon Jinmann , Yoo Myung Chul , Shim Ga Yang , Kim Miji , Soh Yunsoo , Won Chang Won
Published: May 2024

Background and Objectives: Sarcopenic obesity, a clinical condition coexisting with obesity and sarcopenia, is associated with a high risk of functional impairment, reduced quality of life, and increased mortality. A decline in age-related free testosterone (FT) levels has been reported to be associated with decreased muscle mass and muscle strength and increased fat mass. However, the association between low FT levels and risk of sarcopenic obesity has not been well studied. This study aimed to investigate the direct association between low FT levels and sarcopenic obesity. Materials and Methods: This cross-sectional study used data of 982 community-dwelling men aged 70–84 years from the Korean Frailty and Aging Cohort Study. Sarcopenia was defined according to the criteria of the Asian Group for Sarcopenia (AWGS) 2019. Obesity was defined as a body fat mass ≥28.3%. Participants who met both sarcopenia and obesity criteria were defined as having sarcopenic obesity. Low FT levels were defined as FT levels <17.35 pmol/L according to the Endocrine Society Clinical Practice Guidelines. Results: The prevalence of sarcopenia, obesity, and sarcopenic obesity was significantly higher in the low-FT group than in the normal-FT group. Low FT levels were significantly associated with a higher risk of obesity (odds ratio [OR], 2.09, 95% confidence interval [CI], 1.11–3.92), sarcopenia (2.57, 95% CI 1.08–6.10), and sarcopenic obesity (3.66, 95% CI 1.58–8.47) compared with the healthy control group. The risk of low appendicular skeletal muscle mass index (ASMI) (1.78, 95% CI 1.04–3.02) and high fat mass (1.92, 95% CI 1.12–3.31) was significantly higher in the low-FT group than in the normal-FT group. Conclusions: This study showed that low FT levels were associated with a higher risk of sarcopenic obesity. Low FT levels were mainly related to body composition parameters such as low ASMI and high fat mass.
Automated Competence Assessment Procedures in Entrepreneurship
Authors: Marschhäuser Markus , Riesel Fabienne , Bräutigam Volker
Published: May 2024

This study endeavors to automate the assessment of competencies within the domain of entrepreneurship, specifically targeting the augmentation of entrepreneurial cognition and conduct within universities in German rural regions, like Lower Franconia. Employing methods, including literature analyses and expert interviews, we formulated and validated an entrepreneurship competence profile and accompanying self-assessment tool. The ensuing evaluative framework is poised for seamless integration into learning management systems, thereby facilitating intelligent competence monitoring within educational environments. Purpose: The aim of this thesis is to develop an automated competence assessment procedure in the field of entrepreneurship. This can be used in the university environment in the long term to promote and teach entrepreneurial thinking and behavior in order to sustainably improve the quality of learning outcomes and achieve targeted promotion of entrepreneurship. Methodology: Based on a relevant literature analysis, four guideline-based expert interviews were created and conducted. The results of the interviews were compiled and validated in a structured competence profile (entrepreneurship competence profile). Based on this competence catalog for entrepreneurs, an empirically valid self-test was created using standard psychometric questionnaire construction methods. Results: The entrepreneurship competence profile and a consequential empirically validated self-test for competence assessment were created. This test provides the basis for the long-term competence development of students and can further be embedded automatically into a learning management system (LMS) as part of intelligent competence monitoring, which allows for the recording of competencies for each student and the individual incorporation of gap closure into the curriculum. Originality/value: In previous research, there were no competence profiles or competence assessment procedures in the field of entrepreneurship that derived relevant competencies directly from actors within this environment. This work illustrates the development of a competence assessment procedure for entrepreneurs and shows which methods can be used to close prevailing research gaps in the field of intelligent competence monitoring.
A Study on Prediction of Size and Morphology of Ag Nanoparticles Using Machine Learning Models for Biomedical Applications
Authors: Prasad Athira , Santra Tuhin Subhra , Jayaganthan Rengaswamy
Published: May 2024

The synthesis of silver nanoparticles (AgNPs) holds significant promise for various applications in fields ranging from medicine to electronics. Accurately predicting the particle size during synthesis is crucial for optimizing the properties and performance of these nanoparticles. In this study, we compare the efficacy of tree-based models compared with the existing models, for predicting the particle size in silver nanoparticle synthesis. The study investigates the influence of input features, such as reaction parameters, precursor concentrations, etc., on the predictive performance of each model type. Overall, this study contributes to the understanding of modeling techniques for nanoparticle synthesis and underscores the importance of selecting appropriate methodologies for accurate particle size prediction, thereby facilitating the optimization of synthesis processes and enhancing the effectiveness of silver nanoparticle-based applications.
Decoding the Atmosphere: Optimising Probabilistic Forecasts with Information Gain
Authors: Lawson John R. , Potvin Corey K. , Nelson Kenric
Published: May 2024

Probabilistic prediction models exist to reduce surprise about future events. This paper explores the evaluation of such forecasts when the event of interest is rare. We review how the family of Brier-type scores may be ill-suited to evaluate predictions of rare events, and we offer an alternative to information-theoretical scores such as Ignorance. The reduction in surprise provided by a set of forecasts is represented as information gain, a frequent loss function in machine learning training, meaning the reduction in ignorance over a baseline having received a new forecast. We evaluate predictions of a synthetic dataset of rare events and demonstrate the differences in interpretation of the same datasets depending on whether the Brier or Ignorance score is used. While the two types of scores are broadly similar, there are substantial differences in interpretation at extreme probabilities. Information gain is measured in units of bits, an irreducible unit of information, that allows forecasts of different variables to be comparatively evaluated fairly. Further insight from information-based scores is gained via a similar reliability–discrimination decomposition as found in Brier-type scores. We conclude by crystallising multiple concepts to better equip forecast-system developers and decision-makers with tools to navigate complex trade-offs and uncertainties that characterise meteorological forecasting. To this end, we also provide computer code to reproduce data and figures herein.
Water Diffusion in Additively Manufactured Polymers: Analysis of the Capillary Effect
Authors: Li Boyu , Baxevanakis Konstantinos P. , Silberschmidt Vadim V.
Published: May 2024

Additive manufacturing (AM) is an advanced manufacturing method that produces objects by sequential layering. Material extrusion AM (MEAM) with continuous-fibre reinforcement is becoming more widely used in naval structures, which are exposed to the marine environment. However, the water diffusion process and the effect of water ageing on the mechanical performance of AM materials are not yet well understood because of their complex internal structure, caused by defects generated during manufacturing. Current research on diffusion is mostly based on experimental methods for conventionally manufactured materials without considering AM-induced defects. The objective of this study is to explore how the defects inherent to MEAM affect water diffusion in a composite material by the capillary effect. Results from a numerical study of capillary flow in MEAM polymer are applied as a boundary condition in the subsequent finite-element analysis. The study illustrates that flow in the capillary reaches the steady state quicker compared to the saturation time in the matrix, predicted by Fick’s diffusion equation. It is demonstrated that the capillary effect can significantly affect the water diffusion in MEAM parts and reduce the saturation time to one-third compared to the case without accounting for this effect.