The 2023 MDPI Annual Report has
been released!
 
5 pages, 163 KiB  
Editorial
Exploring Fundamentals of Prion Biology Using Natural Yeast Prions and Mammalian PrP
by Irina L. Derkatch and Susan W. Liebman
Viruses 2024, 16(5), 790; https://doi.org/10.3390/v16050790 (registering DOI) - 16 May 2024
Abstract
The key postulate of the prion paradigm is that some proteins can take on unconventional conformations and pass these conformations to newly synthesized protein molecules with the same primary structure [...] Full article
19 pages, 2520 KiB  
Article
Sensorless Model Predictive Control of Permanent Magnet Synchronous Motors Using an Unscented Kalman Filter
by Dariusz Janiszewski
Energies 2024, 17(10), 2387; https://doi.org/10.3390/en17102387 (registering DOI) - 16 May 2024
Abstract
This paper deals with the application of the Model Predictive Control (MPC) algorithm to the sensorless control of a Permanent Magnet Synchronous Motor (PMSM). The proposed estimation strategy, based on the unscented Kalman filter (UKF), uses only the measurement [...] Read more.
This paper deals with the application of the Model Predictive Control (MPC) algorithm to the sensorless control of a Permanent Magnet Synchronous Motor (PMSM). The proposed estimation strategy, based on the unscented Kalman filter (UKF), uses only the measurement of the motor current for the online estimation of speed, rotor position and load torque. Information about the system state is fed into the MPC algorithm. The results verify the effectiveness and applicability of the proposed sensorless control technique. To demonstrate its real-world applicability, implementation in low-speed direct drive astronomy telescope mount systems is investigated. The outcomes of the implementation are thoroughly examined, leading to insightful conclusions drawn from the observed results. Through rigorous theoretical analysis and extensive simulation studies, this paper establishes a solid foundation for the proposed sensorless control technique. The results obtained from simulation studies and real-world applications underscore the efficacy and versatility of the proposed approach, offering valuable insights for the advancement of sensorless control strategies in motor applications. The main aim of this work is to demonstrate and validate the practical feasibility of combining two complex techniques, establishing that such an integration is not only possible but also effective in achieving the desired objectives. Full article
(This article belongs to the Special Issue Advanced Control in Power Electronics, Drives and Generators)
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10 pages, 290 KiB  
Article
Memory Corrections to Markovian Langevin Dynamics
by Mateusz Wiśniewski, Jerzy Łuczka and Jakub Spiechowicz
Entropy 2024, 26(5), 425; https://doi.org/10.3390/e26050425 (registering DOI) - 16 May 2024
Abstract
Analysis of non-Markovian systems and memory-induced phenomena poses an everlasting challenge in the realm of physics. As a paradigmatic example, we consider a classical Brownian particle of mass M subjected to an external force and exposed to correlated thermal fluctuations. We show that [...] Read more.
Analysis of non-Markovian systems and memory-induced phenomena poses an everlasting challenge in the realm of physics. As a paradigmatic example, we consider a classical Brownian particle of mass M subjected to an external force and exposed to correlated thermal fluctuations. We show that the recently developed approach to this system, in which its non-Markovian dynamics given by the Generalized Langevin Equation is approximated by its memoryless counterpart but with the effective particle mass M<M, can be derived within the Markovian embedding technique. Using this method, we calculate the first- and the second-order memory correction to Markovian dynamics of the Brownian particle for the memory kernel represented as the Prony series. The second one lowers the effective mass of the system further and improves the precision of the approximation. Our work opens the door for the derivation of higher-order memory corrections to Markovian Langevin dynamics. Full article
(This article belongs to the Collection Foundations of Statistical Mechanics)
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18 pages, 7901 KiB  
Article
A Tension Sensor Array for Cable-Driven Surgical Robots
by Zhangxi Zhou, Jianlin Yang, Mark Runciman, James Avery, Zhijun Sun and George Mylonas
Sensors 2024, 24(10), 3156; https://doi.org/10.3390/s24103156 (registering DOI) - 16 May 2024
Abstract
Tendon–sheath structures are commonly utilized to drive surgical robots due to their compact size, flexibility, and straightforward controllability. However, long-distance cable tension estimation poses a significant challenge due to its frictional characteristics affected by complicated factors. This paper proposes a miniature tension sensor [...] Read more.
Tendon–sheath structures are commonly utilized to drive surgical robots due to their compact size, flexibility, and straightforward controllability. However, long-distance cable tension estimation poses a significant challenge due to its frictional characteristics affected by complicated factors. This paper proposes a miniature tension sensor array for an endoscopic cable-driven parallel robot, aiming to integrate sensors into the distal end of long and flexible surgical instruments to sense cable tension and alleviate friction between the tendon and sheath. The sensor array, mounted at the distal end of the robot, boasts the advantages of a small size (16 mm outer diameter) and reduced frictional impact. A force compensation strategy was presented and verified on a platform with a single cable and subsequently implemented on the robot. The robot demonstrated good performance in a series of palpation tests, exhibiting a 0.173 N average error in force estimation and a 0.213 N root-mean-square error. In blind tests, all ten participants were able to differentiate between silicone pads with varying hardness through force feedback provided by a haptic device. Full article
(This article belongs to the Special Issue Sensing Technologies in Medical Robot)
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24 pages, 587 KiB  
Review
Assessing the Competence of Nursing Students in Clinical Practice: The Clinical Preceptors’ Perspective
by Watin Arif Alkhelaiwi, Marian Traynor, Katherine Rogers and Iseult Wilson
Healthcare 2024, 12(10), 1031; https://doi.org/10.3390/healthcare12101031 (registering DOI) - 16 May 2024
Abstract
Nursing students’ integration of theoretical knowledge and practical abilities is facilitated by their practice of nursing skills in a clinical environment. A key role of preceptors is to assess the learning goals that nursing students must meet while participating in clinical practice. Consequently, [...] Read more.
Nursing students’ integration of theoretical knowledge and practical abilities is facilitated by their practice of nursing skills in a clinical environment. A key role of preceptors is to assess the learning goals that nursing students must meet while participating in clinical practice. Consequently, the purpose of this study was to explore the current evidence in relation to competency assessment and assessment approaches, and the willingness of preceptors for assessing nursing students’ competency in a clinical setting. The scoping review used the five-stage methodological framework that was developed by Arksey and O’Malley, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Relevant studies were searched by applying a comprehensive literature search strategy up to April 2024 across the following databases: CINAHL, OVID MEDLINE, EMBASE, and PUBMED. A total of 11,297 studies published between 2000 and April 2024 were revealed, and 38 were eligible for inclusion, which the research team categorised into three main themes: definitions of competence, tools for assessing competence and preceptors’ and mentors’ viewpoints in relation to the assessment of nursing students’ competence. This review established that there are a multitude of quantitative instruments available to assess clinical competence; however, a lack of consistency among assessment instruments and approaches between countries and higher education institutions is prevalent. Existing research evidence suggests that the preceptors carried out the assessment process clinically and they found difficulties in documenting assessment. The assessing of nursing students’ competency and the complexity of assessment is a concern for educators and mentors worldwide. The main concern centers around issues such as the interpretation of competence and complex measurement tools. Full article
(This article belongs to the Collection Current Nursing Practice and Education)
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15 pages, 1101 KiB  
Article
Evaluation of Disease Spectrum in Hospitalized Cats with Hyperlipasemia: Pancreatitis Alone Is Rare, Hyperlipasemia without Suspected Pancreatitis Is Common
by Vanessa Hotz, Daniel Brugger and Peter Hendrik Kook
Animals 2024, 14(10), 1479; https://doi.org/10.3390/ani14101479 (registering DOI) - 16 May 2024
Abstract
Histological evidence of pancreatitis is commonly found in necropsy studies in cats. A clinical diagnosis of pancreatitis is challenging due to nonspecific clinical signs, a lack of diagnostic lipase cutoffs, and frequent presence of multiple diseases. It is still unknown how often pancreatitis [...] Read more.
Histological evidence of pancreatitis is commonly found in necropsy studies in cats. A clinical diagnosis of pancreatitis is challenging due to nonspecific clinical signs, a lack of diagnostic lipase cutoffs, and frequent presence of multiple diseases. It is still unknown how often pancreatitis alone is found in sick cats and how often clinicopathological evidence of pancreatitis in sick cats does not lead to a clinical diagnosis of pancreatitis. Our aims were to evaluate the extent of comorbidities in cats with suspected pancreatitis, evaluate how often sick cats with hyperlipasemia are diagnosed only with non-pancreatic diseases, and compare their clinical findings. Medical records of 563 client-owned hospitalized cats with available lipase activity measurement (LIPC Roche) > 30 U/L (RI, 6–26) were searched and medical diagnoses recorded and grouped by organ system. Clinicopathological findings were compared between cats with pancreatitis alone (PA), pancreatitis with concurrent disease (PD), and no suspected pancreatitis (NP). We found that PA was present in 33 (6%) cats, 159 cats (28%) were in the PD group, and 371 cats (66%) had no suspected pancreatitis (NP). Clinical, laboratory, and ultrasonographic findings did not differ between PA and PD cats. Lipase activities did not differ between the three groups. The most common disease categories in PD and NP cats were gastrointestinal, hepatobiliary, renal/urinary, and endocrine, and renal/urinary, gastrointestinal, cardiac, and musculoskeletal, respectively. We conclude that cats are rarely hospitalized because of suspected pancreatitis alone, and PA cats did not differ clinically from PD cats. Hyperlipasemia in sick cats without a diagnosis of pancreatitis may be due to a reactive pancreatopathy or preexisting chronic pancreatitis. Full article
(This article belongs to the Section Companion Animals)
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8 pages, 226 KiB  
Opinion
Teaching Medical Procedural Skills for Performance
by Kersi Taraporewalla, Paul Barach and André van Zundert
Clin. Pract. 2024, 14(3), 862-869; https://doi.org/10.3390/clinpract14030067 (registering DOI) - 16 May 2024
Abstract
Procedures are a core element of medical professional practice. Today’s training approach was formulated in the mid-twentieth century based on a computer analogue of the brain. Despite minor modifications, the system has remained relatively unchanged for the past 70 years. It delivers competence. [...] Read more.
Procedures are a core element of medical professional practice. Today’s training approach was formulated in the mid-twentieth century based on a computer analogue of the brain. Despite minor modifications, the system has remained relatively unchanged for the past 70 years. It delivers competence. However, competence is not reliable performance. The inability to adapt to the variety of patients and variations in the performance environments, such as the operating room, results in patient morbidity and mortality. There is a need for changes in the development and training of medical procedural skills based on current theories of skill acquisition, movement theory, and motor control. Achieving optimal performance necessitates the ability to adapt through training in diverse patient and performance environments rather than merely imitating prescribed movements. We propose a novel model of training, the Constraints-Led Approach, which allows for robust training by altering the factors affecting skill acquisition and lifelong learning. Full article
10 pages, 1855 KiB  
Article
An Overlooked Group of Citizen Scientists in Non-Indigenous Species (NIS) Information: Shell Collectors and Their Contribution to Molluscan NIS Xenodiversity
by Argyro Zenetos, Christiane Delongueville and Roland Scaillet
Diversity 2024, 16(5), 299; https://doi.org/10.3390/d16050299 (registering DOI) - 16 May 2024
Abstract
This work reports on 60 marine alien mollusks from nine countries across the Mediterranean Sea and the Sea of Marmara collected by two Belgian citizen scientists. Some of their published observations concerning collection dates are compared with the year of first publication for [...] Read more.
This work reports on 60 marine alien mollusks from nine countries across the Mediterranean Sea and the Sea of Marmara collected by two Belgian citizen scientists. Some of their published observations concerning collection dates are compared with the year of first publication for these alien mollusks reported in the literature, which enable us to backdate some of their introductions and set new first Mediterranean records for two species. This underlines the importance of collaboration between volunteers and institutional scientists in tracing variations and changes in the environment and biodiversity. Full article
(This article belongs to the Special Issue 2024 Feature Papers by Diversity’s Editorial Board Members)
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16 pages, 3054 KiB  
Article
Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype
by Shorouk Makhlouf, Nehal M. Atallah, Susanna Polotto, Andrew H. S. Lee, Andrew R. Green and Emad A. Rakha
Cancers 2024, 16(10), 1893; https://doi.org/10.3390/cancers16101893 (registering DOI) - 16 May 2024
Abstract
Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This [...] Read more.
Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes. Methods: A large (n = 7140) well-characterised and histologically reviewed BC cohort with treatment and long-term follow-up data was investigated. The cohort was classified based on the WHO classification of tumours into main histological subtypes, including ILC and IDC-NST. ILCs were further classified into variants. Clinicopathological parameters and patient outcomes in terms of BC-specific survival (BCSS) and disease-free survival (DFS) were evaluated. Results: ILC constituted 11% of the cohort. The most common non-classic ILC variants were pleomorphic (pILC) and solid (sILC), constituting 19% of ILC. Compared to classic and related variants (alveolar, trabecular, papillary, and tubulolobular; cILC), pILC and sILC variants were associated with aggressive tumour characteristics. The histologic grade of ILC was an important prognostic variable. The survival patterns identified an aggressive ILC subtype encompassing pILC and high-grade sILC. These tumours, which comprised 14% of the cases, were associated with clinicopathological characteristics of poor prognosis and had high BC-specific death and recurrence rates compared not only to cILC (p < 0.001) but also to IDC-NST (p = 0.02) patients. Contrasting this, cILC patients had significantly longer BCSS and DFS than IDC-NST patients in the first 10 to 15 years of follow-up. Adjuvant chemotherapy did not improve the outcome of patients with aggressive ILC subtypes. Conclusions: pILC and high-grade sILC variants comprise an aggressive ILC subtype associated with poor prognostic characteristics and a poor response to chemotherapy. These results warrant confirmation in randomised clinical trials. Full article
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12 pages, 752 KiB  
Article
Unlocking the Potential of Pepper Plants under Salt Stress: Mycorrhizal Effects on Physiological Parameters Related to Plant Growth and Gas Exchange across Tolerant and Sensitive Genotypes
by Ozlem Altuntas, Hayriye Yildiz Dasgan, Yelderem Akhoundnejad and Yahya Nas
Plants 2024, 13(10), 1380; https://doi.org/10.3390/plants13101380 (registering DOI) - 16 May 2024
Abstract
Agriculture is confronted with the challenge of ensuring global food security, yet the rapid expansion of salinity stress undoubtedly restricts plant productivity in cultivable areas, posing a significant threat to crop yields. Arbuscular mycorrhizal fungi (AMFs) have emerged as a biological tool for [...] Read more.
Agriculture is confronted with the challenge of ensuring global food security, yet the rapid expansion of salinity stress undoubtedly restricts plant productivity in cultivable areas, posing a significant threat to crop yields. Arbuscular mycorrhizal fungi (AMFs) have emerged as a biological tool for enhancing plant salt stress tolerance. To utilize this biological tool, this study evaluated the response in growth and physiological parameters of tolerant (Karaisali) and sensitive (Demre) pepper genotypes. The experiment involved mycorrhizal-treated (Glomus clarium) and non-mycorrhizal (control) plants of both the tolerant and sensitive pepper genotypes. The plants were subjected to two salt doses: 75 and 150 mM. The plant growth and physiological parameters were measured at 40 days after transplanting. The mycorrhizal activity was found to be significantly more effective in the sensitive genotype. We found notable differences in mycorrhizal activity between the pepper genotypes under salt stress conditions, with the sensitive genotype “Demre” showing greater responsiveness to mycorrhizal association compared with the “Karaisali” variety. Under both moderate (75 mM NaCl) and higher salt stress levels (150 mM NaCl), both the “Karaisali” and “Demre” varieties exhibited substantial increases in their shoot dry weights. However, these increases were consistently higher in the “Demre” plants. Moreover, the AMFs demonstrated significant enhancements in photosynthesis rates under both moderate and high salinity levels in both genotypes. Overall, our findings suggest that AMFs play a crucial role in improving plant growth, water status, and photosynthesis characteristics, particularly in salt-sensitive pepper genotypes, under moderate-to-high salinity levels. In conclusion, the plant growth, water status, and photosynthesis characteristics of the salt-sensitive pepper genotype were significantly improved by AMFs at medium and high salinity levels, such as 75 mM and 150 mM NaCl, respectively. Full article
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13 pages, 8984 KiB  
Article
Fly-Cutting Processing of Micro-Triangular Pyramid Arrays and Synchronous Micro-Scrap Removal
by Jiashun Gao, Zhilong Xu, Yu Lei and Su Huang
Micromachines 2024, 15(5), 655; https://doi.org/10.3390/mi15050655 (registering DOI) - 16 May 2024
Abstract
Many micro-scraps are generated when a micro-triangular pyramid array (MTPA) is machined by the fly-cutting method. Micro-scraps are generally not removed quickly enough; therefore, these residual micro-scraps participate in the cutting process again, scratching the workpiece surface and accelerating diamond tool wear. To [...] Read more.
Many micro-scraps are generated when a micro-triangular pyramid array (MTPA) is machined by the fly-cutting method. Micro-scraps are generally not removed quickly enough; therefore, these residual micro-scraps participate in the cutting process again, scratching the workpiece surface and accelerating diamond tool wear. To remove micro-scraps rapidly, a fly-cutting method to produce MTPAs on vertically oriented working surfaces was developed during this study. The results show that an MTPA produced by fly cutting on a vertical workpiece had a clearly outlined structure, high dimensional accuracy, and a low surface roughness. There was no micro-scrap residue on the workpiece surface and the diamond tool wear was small. The cutting inlet edges had no burrs, and the cutting outlet edges had only a small number of burrs. This method of fly cutting MTPAs on vertically oriented working surfaces provides a foundation for the development of high-precision micro-triangular pyramid optical elements. Full article
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13 pages, 1417 KiB  
Article
Deep Compressed Communication and Application in Multi-Robot 2D-Lidar SLAM: An Intelligent Huffman Algorithm
by Liang Zhang and Jinghui Deng
Sensors 2024, 24(10), 3154; https://doi.org/10.3390/s24103154 (registering DOI) - 16 May 2024
Abstract
Multi-robot Simultaneous Localization and Mapping (SLAM) systems employing 2D lidar scans are effective for exploration and navigation within GNSS-limited environments. However, scalability concerns arise with larger environments and increased robot numbers, as 2D mapping necessitates substantial processor memory and inter-robot communication bandwidth. Thus, [...] Read more.
Multi-robot Simultaneous Localization and Mapping (SLAM) systems employing 2D lidar scans are effective for exploration and navigation within GNSS-limited environments. However, scalability concerns arise with larger environments and increased robot numbers, as 2D mapping necessitates substantial processor memory and inter-robot communication bandwidth. Thus, data compression prior to transmission becomes imperative. This study investigates the problem of communication-efficient multi-robot SLAM based on 2D maps and introduces an architecture that enables compressed communication, facilitating the transmission of full maps with significantly reduced bandwidth. We propose a framework employing a lightweight feature extraction Convolutional Neural Network (CNN) for a full map, followed by an encoder combining Huffman and Run-Length Encoding (RLE) algorithms to further compress a full map. Subsequently, a lightweight recovery CNN was designed to restore map features. Experimental validation involves applying our compressed communication framework to a two-robot SLAM system. The results demonstrate that our approach reduces communication overhead by 99% while maintaining map quality. This compressed communication strategy effectively addresses bandwidth constraints in multi-robot SLAM scenarios, offering a practical solution for collaborative SLAM applications. Full article
(This article belongs to the Special Issue UAV and Sensors Applications for Navigation and Positioning)
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17 pages, 5291 KiB  
Article
Optimization of High-Density Fermentation Conditions for Saccharomycopsis fibuligera Y1402 through Response Surface Analysis
by Hongyang Yuan, Qi Sun, Lanshuang Wang, Zhilei Fu, Tianze Zhou, Jinghao Ma, Xiaoyan Liu, Guangsen Fan and Chao Teng
Foods 2024, 13(10), 1546; https://doi.org/10.3390/foods13101546 (registering DOI) - 16 May 2024
Abstract
Saccharomycopsis fibuligera, which produces enzymes like amylase and protease as well as flavor substances like β-phenyl ethanol and phenyl acetate, plays a crucial role in traditional fermented foods. However, this strain still lacks a high-density fermentation culture, which has had an impact [...] Read more.
Saccharomycopsis fibuligera, which produces enzymes like amylase and protease as well as flavor substances like β-phenyl ethanol and phenyl acetate, plays a crucial role in traditional fermented foods. However, this strain still lacks a high-density fermentation culture, which has had an impact on the strain’s industrial application process. Therefore, this study investigated the optimization of medium ingredients and fermentation conditions for high-density fermentation of S. fibuligera Y1402 through single-factor design, Plackett–Burman design, steepest ascent test, and response surface analysis. The study found that glucose at 360.61 g/L, peptone at 50 g/L, yeast extract at 14.65 g/L, KH2PO4 at 5.49 g/L, MgSO4 at 0.40 g/L, and CuSO4 at 0.01 g/L were the best medium ingredients for S. fibuligera Y1402. Under these conditions, after three days of fermentation, the total colony count reached 1.79 × 108 CFU/mL. The optimal fermentation conditions were determined to be an initial pH of 6.0, an inoculum size of 1.10%, a liquid volume of 12.5 mL/250 mL, a rotation speed of 120 r/min, a fermentation temperature of 21 °C and a fermentation time of 53.50 h. When fermentation was conducted using the optimized medium and conditions, the total colony count achieved a remarkable value of 5.50 × 109 CFU/mL, exhibiting a substantial increase of nearly 31 times the original value in the optimal culture medium. This significant advancement offers valuable insights and a reference for the industrial-scale production of S. fibuligera. Full article
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16 pages, 1691 KiB  
Article
Impact of CDK Inhibitors on TBXT Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma
by Sarah Bette, Luisa Haase, Juliane Nell, Thomas Grieser, Alexandra von Baer, Markus Schultheiss, Ralf Marienfeld, Peter Möller, Thomas F. E. Barth and Kevin Mellert
Diagnostics 2024, 14(10), 1028; https://doi.org/10.3390/diagnostics14101028 (registering DOI) - 16 May 2024
Abstract
Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the TBXT gene, resulting in detectable nuclear amounts of its gene product [...] Read more.
Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the TBXT gene, resulting in detectable nuclear amounts of its gene product brachyury. This T-Box transcription factor is commonly recognised as being essential in chordoma cells, and limiting TBXT expression is thought to be the key factor in controlling this tumour. Although the tumour is rare, distinct molecular differences and vulnerabilities have been described with regard to its location and the progression status of the disease, rendering it mandatory for novel cell lines to reflect all relevant chordoma subtypes. Here, we describe a novel chordoma cell line arising from the pleural effusion of a disseminated, poorly differentiated chordoma. This cell line, U-CH22, represents a highly aggressive terminal chordoma and, therefore, fills a relevant gap within the panel of available cell culture models for this orphan disease. CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum. Full article
(This article belongs to the Special Issue Bone Tumours: From Molecular Pathology to Clinical Practice)
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24 pages, 3864 KiB  
Article
Presenilin Deficiency Results in Cellular Cholesterol Accumulation by Impairment of Protein Glycosylation and NPC1 Function
by Marietta Fabiano, Naoto Oikawa, Anja Kerksiek, Jun-ichi Furukawa, Hirokazu Yagi, Koichi Kato, Ulrich Schweizer, Wim Annaert, Jongkyun Kang, Jie Shen, Dieter Lütjohann and Jochen Walter
Int. J. Mol. Sci. 2024, 25(10), 5417; https://doi.org/10.3390/ijms25105417 (registering DOI) - 16 May 2024
Abstract
Presenilin proteins (PS1 and PS2) represent the catalytic subunit of γ-secretase and play a critical role in the generation of the amyloid β (Aβ) peptide and the pathogenesis of Alzheimer disease (AD). However, PS proteins also exert multiple functions beyond Aβ generation. In [...] Read more.
Presenilin proteins (PS1 and PS2) represent the catalytic subunit of γ-secretase and play a critical role in the generation of the amyloid β (Aβ) peptide and the pathogenesis of Alzheimer disease (AD). However, PS proteins also exert multiple functions beyond Aβ generation. In this study, we examine the individual roles of PS1 and PS2 in cellular cholesterol metabolism. Deletion of PS1 or PS2 in mouse models led to cholesterol accumulation in cerebral neurons. Cholesterol accumulation was also observed in the lysosomes of embryonic fibroblasts from Psen1-knockout (PS1-KO) and Psen2-KO (PS2-KO) mice and was associated with decreased expression of the Niemann-Pick type C1 (NPC1) protein involved in intracellular cholesterol transport in late endosomal/lysosomal compartments. Mass spectrometry and complementary biochemical analyses also revealed abnormal N-glycosylation of NPC1 and several other membrane proteins in PS1-KO and PS2-KO cells. Interestingly, pharmacological inhibition of N-glycosylation resulted in intracellular cholesterol accumulation prominently in lysosomes and decreased NPC1, thereby resembling the changes in PS1-KO and PS2-KO cells. In turn, treatment of PS1-KO and PS2-KO mouse embryonic fibroblasts (MEFs) with the chaperone inducer arimoclomol partially normalized NPC1 expression and rescued lysosomal cholesterol accumulation. Additionally, the intracellular cholesterol accumulation in PS1-KO and PS2-KO MEFs was prevented by overexpression of NPC1. Collectively, these data indicate that a loss of PS function results in impaired protein N-glycosylation, which eventually causes decreased expression of NPC1 and intracellular cholesterol accumulation. This mechanism could contribute to the neurodegeneration observed in PS KO mice and potentially to the pathogenesis of AD. Full article
(This article belongs to the Section Molecular Neurobiology)
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30 pages, 10047 KiB  
Article
The Influence of Soy Isoflavones and Soy Isoflavones with Inulin on Kidney Morphology, Fatty Acids, and Associated Parameters in Rats with and without Induced Diabetes Type 2
by Kamila Misiakiewicz-Has, Dominika Maciejewska-Markiewicz, Dagmara Szypulska-Koziarska, Agnieszka Kolasa and Barbara Wiszniewska
Int. J. Mol. Sci. 2024, 25(10), 5418; https://doi.org/10.3390/ijms25105418 (registering DOI) - 16 May 2024
Abstract
Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague–Dawley (SD) rats segregated into [...] Read more.
Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague–Dawley (SD) rats segregated into two cohorts: non-diabetic and diabetic, induced with type 2 diabetes (high-fat diet + two intraperitoneal streptozotocin injections). Each cohort was further divided into three subgroups (n = 6): control, isoflavone-treated, and isoflavone plus inulin-treated rats. Tail blood glucose and ketone levels were gauged. Upon termination, blood samples were drawn directly from the heart for urea, creatinine, and HbA1c/HbF analyses. One kidney per rat underwent histological (H-E) and immunohistochemical assessments (anti-AQP1, anti-AQP2, anti-AVPR2, anti-SLC22A2, anti-ACC-alpha, anti-SREBP-1). The remaining kidney underwent fatty acid methyl ester analysis. Results unveiled notable alterations in water intake, body and kidney mass, kidney morphology, fatty acids, AQP2, AVPR2, AcetylCoA, SREBP-1, blood urea, creatinine, and glucose levels in control rats with induced type 2 diabetes. Isoflavone supplementation exhibited favorable effects on plasma urea, plasma urea/creatinine ratio, glycemia, water intake, and kidney mass, morphology, and function in type 2 diabetic rats. Additional inulin supplementation frequently modulated the action of soy isoflavones. Full article
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11 pages, 570 KiB  
Article
B–NHL Cases in a Tertiary Pediatric Hematology—Oncology Department: A 20-Year Retrospective Cohort Study
by Ioannis Kyriakidis, Iordanis Pelagiadis, Maria Stratigaki, Nikolaos Katzilakis and Eftichia Stiakaki
Life 2024, 14(5), 633; https://doi.org/10.3390/life14050633 (registering DOI) - 16 May 2024
Abstract
Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies –with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased [...] Read more.
Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies –with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer). Full article
(This article belongs to the Special Issue B-cell Lymphoma)
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14 pages, 973 KiB  
Article
A Comparative Study and Prediction of the Ex Vivo Permeation of Six Vaginally Administered Drugs across Five Artificial Membranes and Vaginal Tissue
by Eleni Tsanaktsidou, Aikaterini-Theodora Chatzitaki, Anatoli Chatzichristou, Dimitrios G. Fatouros and Catherine K. Markopoulou
Molecules 2024, 29(10), 2334; https://doi.org/10.3390/molecules29102334 (registering DOI) - 16 May 2024
Abstract
The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were [...] Read more.
The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally administered drugs (econazole, miconazole, metronidazole, clindamycin, lidocaine, and nonoxynol-9). This study was performed (in vitro) on different membranes of polyvinylidene fluoride (PVDF), plain cellulose or cellulose impregnated with isopropyl myristate (IPM), and cellulose combined with PVDF or IPM. The results were compared with those obtained from cow vaginal tissue (ex vivo), where cellulose was proven to be the best simulant. According to the permeability profiles (Papp), the water solubility of the drugs was considered a necessary criterion for their transport in the membranes or in the tissue, while the size was important for their penetration. Furthermore, it was found that polar compounds show clear superiority when penetrating cellulose or tissue, while non-polar ones show superiority when penetrating the lipophilic PVDF membrane. Finally, a successful attempt was made to predict the Papp values (|Papp-predPapp| < 0.005) of the six drugs under study based on a PLS (Partial Least Squares) in silico simulation model. Full article
(This article belongs to the Section Analytical Chemistry)
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13 pages, 2251 KiB  
Article
An Interface to Monitor Process Variability Using the Binomial ATTRIVAR SS Control Chart
by João Pedro Costa Violante, Marcela A. G. Machado, Amanda dos Santos Mendes and Túlio S. Almeida
Algorithms 2024, 17(5), 216; https://doi.org/10.3390/a17050216 (registering DOI) - 16 May 2024
Abstract
Control charts are tools of paramount importance in statistical process control. They are broadly applied in monitoring processes and improving quality, as they allow the detection of special causes of variation with a significant level of accuracy. Furthermore, there are several strategies able [...] Read more.
Control charts are tools of paramount importance in statistical process control. They are broadly applied in monitoring processes and improving quality, as they allow the detection of special causes of variation with a significant level of accuracy. Furthermore, there are several strategies able to be employed in different contexts, all of which offer their own advantages. Therefore, this study focuses on monitoring the variability in univariate processes through variance using the Binomial version of the ATTRIVAR Same Sample S2 (B-ATTRIVAR SS S2) control chart, given that it allows coupling attribute and variable inspections (ATTRIVAR means attribute + variable), i.e., taking advantage of the cost-effectiveness of the former and the wealth of information and greater performance of the latter. Its Binomial version was used for such a purpose, since inspections are made using two attributes, and the Same Sample was used due to being submitted to both the attribute and variable stages of inspection. A computational application was developed in the R language using the Shiny package so as to create an interface to facilitate its application and use in the quality control of the production processes. Its application enables users to input process parameters and generate the B-ATTRIVAR SS control chart for monitoring the process variability with variance. By comparing the data obtained from its application with a simpler code, its performance was validated, given that its results exhibited striking similarity. Full article
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15 pages, 1361 KiB  
Article
Elucidating Cancer Subtypes by Using the Relationship between DNA Methylation and Gene Expression
by Muneeba Jilani, David Degras and Nurit Haspel
Genes 2024, 15(5), 631; https://doi.org/10.3390/genes15050631 (registering DOI) - 16 May 2024
Abstract
Advancements in the field of next generation sequencing (NGS) have generated vast amounts of data for the same set of subjects. The challenge that arises is how to combine and reconcile results from different omics studies, such as epigenome and transcriptome, to improve [...] Read more.
Advancements in the field of next generation sequencing (NGS) have generated vast amounts of data for the same set of subjects. The challenge that arises is how to combine and reconcile results from different omics studies, such as epigenome and transcriptome, to improve the classification of disease subtypes. In this study, we introduce sCClust (sparse canonical correlation analysis with clustering), a technique to combine high-dimensional omics data using sparse canonical correlation analysis (sCCA), such that the correlation between datasets is maximized. This stage is followed by clustering the integrated data in a lower-dimensional space. We apply sCClust to gene expression and DNA methylation data for three cancer genomics datasets from the Cancer Genome Atlas (TCGA) to distinguish between underlying subtypes. We evaluate the identified subtypes using Kaplan–Meier plots and hazard ratio analysis on the three types of cancer—GBM (glioblastoma multiform), lung cancer and colon cancer. Comparison with subtypes identified by both single- and multi-omics studies implies improved clinical association. We also perform pathway over-representation analysis in order to identify up-regulated and down-regulated genes as tentative drug targets. The main goal of the paper is twofold: the integration of epigenomic and transcriptomic datasets followed by elucidating subtypes in the latent space. The significance of this study lies in the enhanced categorization of cancer data, which is crucial to precision medicine. Full article
(This article belongs to the Special Issue Bioinformatics of Disease Research)
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18 pages, 3768 KiB  
Article
Quantifying Downstream Climate Impacts of Sea Surface Temperature Patterns in the Eastern Tropical Pacific Using Clustering
by Jason Finley, Boniface Fosu, Chris Fuhrmann, Andrew Mercer and Johna Rudzin
Climate 2024, 12(5), 71; https://doi.org/10.3390/cli12050071 (registering DOI) - 16 May 2024
Abstract
El Niño–Southern Oscillation (ENSO) phases and flavors, as well as off-equatorial climate modes, strongly influence sea surface temperature (SST) patterns in the eastern tropical Pacific and downstream climate. Prior studies rely on EOFs (which characterize fractional SST variance) to diagnose climate-scale SST structures, [...] Read more.
El Niño–Southern Oscillation (ENSO) phases and flavors, as well as off-equatorial climate modes, strongly influence sea surface temperature (SST) patterns in the eastern tropical Pacific and downstream climate. Prior studies rely on EOFs (which characterize fractional SST variance) to diagnose climate-scale SST structures, limiting the ability to link individual ENSO flavors with downstream phenomena. Hierarchical and k-means clustering methods are used to construct Eastern Pacific patterns from the ERSST dataset spanning 1950 to 2021. Cluster analysis allows for the direct linkage of individual SST years/seasons to ENSO phase, providing insight into ENSO flavors and associated downstream impacts. In this study, four clusters are revealed, each depicting unique SST patterns influenced by ENSO and Pacific Meridional Mode (PMM) phases. A case study demonstrating the utility of the clusters was also carried out using accumulated cyclone energy (ACE) in the Atlantic and Eastern Pacific basins. Results showed that Eastern Pacific (EP) El Niño suppresses Atlantic tropical cyclone (TC) activity, while Central Pacific (CP) La Niña enhances it. Further, EP El Niño, coupled with positive PMM, amplifies ACE. Ultimately, the methods used herein offer a cleaner analysis tool for identifying dominant SSTA patterns and employing those patterns to diagnose downstream climatic effects. Full article
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23 pages, 29792 KiB  
Article
Raw Material Stage Assessment of Seating Elements as Urban Furniture and Eco-Model Proposals
by Serkan Sipahi and Merve Sipahi
Sustainability 2024, 16(10), 4163; https://doi.org/10.3390/su16104163 (registering DOI) - 16 May 2024
Abstract
As cities strive to become sustainable, it is imperative to consider even the smallest components of the urban environment and prioritize sustainability. Ensuring the sustainability of urban furniture, especially the numerous benches found in cities, is crucial. This study proposes an alternative solution [...] Read more.
As cities strive to become sustainable, it is imperative to consider even the smallest components of the urban environment and prioritize sustainability. Ensuring the sustainability of urban furniture, especially the numerous benches found in cities, is crucial. This study proposes an alternative solution to the sustainability issue in cities regarding urban furniture. This is because a review of the literature indicates that while efforts have been made to evaluate the sustainability of urban amenities and furniture, studies conducting life cycle analysis specifically for urban furniture are lacking. This study will contribute to the identified gap in the literature by analyzing 14 different seating elements in recreational areas located in the city of Rize, Turkey, using the Ccalc program to calculate their carbon footprints. In the subsequent phase of this study, an eco-design process will be conducted based on the findings, aiming to create an eco-seating unit design. Based on the data obtained, materials with high environmental impact were identified, material replacement recommendations were made, and consequently, a model proposal was presented. The potential reduction in carbon footprints with the use of transformed materials was discussed. The findings revealed that carbon footprint values were particularly high in the seating units where concrete and polypropylene materials were used. Additionally, it was determined that solvent paint, especially varnish, affects the carbon footprint, and it was recommended that would be used in its natural form, which is eco-friendly. In conclusion, the recommendations developed for the sustainability of urban furniture in coastal areas will contribute to the future of cities and humanity. Full article
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9 pages, 257 KiB  
Article
Decabromodifenyl Ether (BDE-209) in Surface Soils from Warsaw and Surrounding Areas: Characterization of Non-Carcinogenic Risk Associated with Oral and Dermal Exposure
by Wojciech Korcz, Katarzyna Czaja, Monika Liszewska, Radosław Lewiński, Anna Słomczyńska and Paweł Struciński
Molecules 2024, 29(10), 2335; https://doi.org/10.3390/molecules29102335 (registering DOI) - 16 May 2024
Abstract
Polybrominated diphenyl ethers (PBDEs) have been used for many years as flame retardants. Due to their physicochemical and toxicological properties, they are considered to be persistent organic pollutants (POPs). BDE-209 is the main component of deca-BDE, the one PBDE commercial mixture currently approved [...] Read more.
Polybrominated diphenyl ethers (PBDEs) have been used for many years as flame retardants. Due to their physicochemical and toxicological properties, they are considered to be persistent organic pollutants (POPs). BDE-209 is the main component of deca-BDE, the one PBDE commercial mixture currently approved for use in the European Union. The aim of this study was to analyse BDE-209 in surface soil samples from Warsaw and surrounding areas (Poland) as an indicator of environmental pollution with PBDEs, and to characterise the associated health risk. A total of 40 samples were analysed using gas chromatography with electron capture detection (GC-µECD). Concentrations of BDE-209 in soil ranged from 0.4 ng g−1 d.w. (limit of quantification) to 158 ng g−1 d.w. Overall, 52.5% of results were above the method’s limit of quantification. The highest levels were found at several locations with heavy traffic and in the vicinity of a CHP plant in the city. The lowest concentrations were observed in most of the samples collected from low industrialized or green areas (<0.4 to 1.68 ng g−1 d.w.). Exposure to BDE-209 was estimated for one of the most sensitive populations, i.e., young children. The following exposure routes were selected: oral and dermal. No risk was found to young children’s health. Full article
(This article belongs to the Special Issue Environmental Analysis of Organic Pollutants, 2nd Edition)

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