bluuebunny/crossref_metadata_2025 huggingface dataset:
AZD-7648, a DNA-PK Inhibitor, Induces DNA Damage, Apoptosis, and Cell Cycle Arrest in Chronic and Acute Myeloid Leukemia Cells
Authors: Lapa Beatriz Santos , Costa Maria Inês , Figueiredo Diana , Jorge Joana , Alves Raquel , Monteiro Ana Raquel , Serambeque Beatriz , Laranjo Mafalda , Botelho Maria Filomena , Carreira Isabel Marques , Sarmento-Ribeiro Ana Bela , Gonçalves Ana Cristina
Published: October 2023

The non-homologous end joining pathway is vital for repairing DNA double-strand breaks (DSB), with DNA-dependent protein kinase (DNA-PK) playing a critical role. Altered DNA damage response (DDR) in chronic (CML) and acute myeloid leukemia (AML) offers potential therapeutic opportunities. We studied the therapeutic potential of AZD-7648 (DNA-PK inhibitor) in CML and AML cell lines. This study used two CML (K-562 and LAMA-84) and five AML (HEL, HL-60, KG-1, NB-4, and THP-1) cell lines. DDR gene mutations were obtained from the COSMIC database. The copy number and methylation profile were evaluated using MS-MLPA and DDR genes, and telomere length using qPCR. p53 protein expression was assessed using Western Blot, chromosomal damage through cytokinesis-block micronucleus assay, and γH2AX levels and DSB repair kinetics using flow cytometry. Cell density and viability were analyzed using trypan blue assay after treatment with AZD-7648 in concentrations ranging from 10 to 200 µM. Cell death, cell cycle distribution, and cell proliferation rate were assessed using flow cytometry. The cells displayed different DNA baseline damage, DDR gene expressions, mutations, genetic/epigenetic changes, and p53 expression. Only HEL cells displayed inefficient DSB repair. The LAMA-84, HEL, and KG-1 cells were the most sensitive to AZD-7648, whereas HL-60 and K-562 showed a lower effect on density and viability. Besides the reduction in cell proliferation, AZD-7648 induced apoptosis, cell cycle arrest, and DNA damage. In conclusion, these results suggest that AZD-7648 holds promise as a potential therapy for myeloid leukemias, however, with variations in drug sensitivity among tested cell lines, thus supporting further investigation to identify the specific factors influencing sensitivity to this DNA-PK inhibitor.
Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation
Authors: Kim Chaekyun
Published: October 2023

Bone homeostasis is regulated by the balanced actions of osteoblasts that form the bone and osteoclasts (OCs) that resorb the bone. Bone-resorbing OCs are differentiated from hematopoietic monocyte/macrophage lineage cells, whereas osteoblasts are derived from mesenchymal progenitors. OC differentiation is induced by two key cytokines, macrophage colony-stimulating factor (M-CSF), a factor essential for the proliferation and survival of the OCs, and receptor activator of nuclear factor kappa-B ligand (RANKL), a factor for responsible for the differentiation of the OCs. Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), p38, and c-Jun N-terminal kinases, play an essential role in regulating the proliferation, differentiation, and function of OCs. ERKs have been known to play a critical role in the differentiation and activation of OCs. In most cases, ERKs positively regulate OC differentiation and function. However, several reports present conflicting conclusions. Interestingly, the inhibition of OC differentiation by ERK1/2 is observed only in OCs differentiated from RAW 264.7 cells. Therefore, in this review, we summarize the current understanding of the conflicting actions of ERK1/2 in OC differentiation.
Plasma Expression of Carotid Plaque Presence-Related MicroRNAs Is Associated with Inflammation in Patients with Rheumatoid Arthritis
Authors: Llop Dídac , Paredes Silvia , Ibarretxe Daiana , Taverner Delia , Plana Núria , Rosales Roser , Masana Lluís , Vallvé Joan Carles
Published: October 2023

Rheumatoid arthritis (RA) is associated with problems beyond the joints such as cardiovascular (CV) disease. MicroRNA-24, -146 and -Let7a are associated with carotid plaque presence in RA patients. We evaluated whether these microRNAs were involved in the inflammatory state of RA, and we studied their gene targets to understand their role in inflammation and atherosclerosis. A total of 199 patients with RA were included. Inflammatory variables such as disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR) were quantified. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were used for analysis. The multivariate models showed that diminished expression of microRNA-146 was associated with inferior levels of DAS28-ESR, and the decreased expression of microRNA-24, -146 and -Let7a were associated with lowered ESR in the overall cohort. When microRNAs were evaluated globally, a global increase was associated with increased DAS28-ESR and ESR in the overall cohort. Sex-stratified analyses showed different associations of these microRNAs with the inflammatory variables. Finally, random forest models showed that microRNAs have a pivotal role in classifying patients with high and low inflammation. Plasmatic expressions of microRNA-24, -146 and -Let7a were associated with inflammatory markers of RA. These microRNAs are associated with both inflammation and atherosclerosis and are potential therapeutic targets for RA.
Effect of Mowing on Wheat Growth at Seeding Stage
Authors: Li Song , Wang Shaoyu , Ye Wenjie , Yao Yaxin , Sun Fengli , Zhang Chao , Liu Shudong , Xi Yajun
Published: October 2023

Winter wheat is used as forage at the tillering stage in many countries; however, the regrowth pattern of wheat after mowing remains unclear. In this study, the growth patterns of wheat were revealed through cytological and physiological assessments as well as transcriptome sequencing. The results of agronomic traits and paraffin sections showed that the shoot growth rate increased, but root growth was inhibited after mowing. The submicroscopic structure revealed a decrease in heterochromatin in the tillering node cell and a change in mitochondrial shape in the tillering node and secondary root. Analysis of the transcriptome showed the number of differentially expressed genes (DEGs) involved in biological processes, cellular components, and molecular functions; 2492 upregulated DEGs and 1534 downregulated DEGs were identified. The results of the experimental study showed that mowing induced expression of DEGs in the phenylpropanoid biosynthesis pathway and increased the activity of PAL and 4CL. The upregulated DEGs in the starch and sucrose metabolism pathways and related enzyme activity alterations indicated that the sugar degradation rate increased. The DEGs in the nitrogen metabolism pathway biosynthesis of the amino acids, phenylpropanoid biosynthesis metabolism, and in the TCA pathway also changed after mowing. Hormone content and related gene expression was also altered in the tillering and secondary roots after mowing. When jasmonic acid and ethylene were used to treat the wheat after mowing, the regeneration rate increased, whereas abscisic acid inhibited regrowth. This study revealed the wheat growth patterns after mowing, which could lead to a better understanding of the development of dual-purpose wheat.
Hepatoprotective and Antioxidant Effects of Nanopiperine against Cypermethrin via Mitigation of Oxidative Stress, Inflammations and Gene Expression Using qRT-PCR
Authors: Hussain Sohail , Jali Abdulmajeed M. , Alshahrani Saeed , Khairat Khairat H. M. , Siddiqui Rahimullah , Alam Mohammad Intakhab , Ali Raisuddin , Mohammed Manal , Khan Andleeb , Al Shahi Hamad , Hanbashi Ali , Qadri Marwa , Ashafaq Mohammad
Published: October 2023

Cypermethrin (Cyp) is a pyrethroid that has been associated with the toxicity of various organs. The aim of our study was to evaluate the hepatoprotective and antioxidant activities of nano-piperine (NP) against Cyp toxicity. Cyp (50 mg/kg) was administered orally in all animals of groups III–VI for 15 days. Groups IV–VI each received three doses of NP (125, 250, and 500 µg/kg/day) for 10 days after receiving the Cyp dosage, which was given after 1 h. A rise in serum biomarkers (ALT, AST, ALP, total protein, and albumin), which are indicators of toxicity alongside anomalous oxidative stress indices (lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase), was detected. After Cyp treatment, we observed upregulated cytokines, caspase expression, and histological analysis that the showed distortion of cell shape. However, the administration of NP dramatically reversed all of the Cyp-induced alterations, inducing reductions in serum marker levels, stress level, the production of cytokines, and caspase expression. Additionally, all of the histopathological alterations were minimized to values that were comparable to normal levels. The present findings suggested that NP exhibits potent antioxidant and anti-inflammatory activities that can protect rats’ livers against Cyp-induced liver damage through hepatoprotective activities.
Elevated Fecal Calprotectin Accompanied by Intestinal Neutrophil Infiltration and Goblet Cell Hyperplasia in a Murine Model of Multiple Sclerosis
Authors: Nouri Mehrnaz , Weström Björn , Lavasani Shahram
Published: October 2023

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system caused by myelin-specific autoreactive T cells. We previously demonstrated intestinal barrier disruption and signs of inflammation in experimental autoimmune encephalomyelitis (EAE), a model of MS. Fecal calprotectin is a disease activity biomarker in inflammatory bowel diseases, released by neutrophils in response to inflammation. We aimed to further investigate EAE manifestations in the gastrointestinal tract and to determine whether calprotectin is a useful biomarker of intestinal inflammation in EAE. Calprotectin was analyzed in feces, cecal contents, and plasma of EAE mice. Infiltrating neutrophils and goblet cells were investigated in different parts of the gastrointestinal tract before the onset of neurological symptoms and during established disease. We found increased calprotectin levels in feces, cecal content, and plasma preceding EAE onset that further escalated during disease progression. Increased neutrophil infiltration in the intestinal tissue concomitant with IL-17 expression and myeloperoxidase activity was found to correlate well with clinical activity. Increased goblet cells in the intestine, similar to irritable bowel syndrome (IBS), were also observed. The results suggest calprotectin as a good biomarker of gastrointestinal inflammation in EAE and the potential of this model as a useful animal model for IBS.
The Significance of Microenvironmental and Circulating Lactate in Breast Cancer
Authors: Frisardi Vincenza , Canovi Simone , Vaccaro Salvatore , Frazzi Raffaele
Published: October 2023

Lactate represents the main product of pyruvate reduction catalyzed by the lactic dehydrogenase family of enzymes. Cancer cells utilize great quantities of glucose, shifting toward a glycolytic metabolism. With the contribution of tumor stromal cells and under hypoxic conditions, this leads toward the acidification of the extracellular matrix. The ability to shift between different metabolic pathways is a characteristic of breast cancer cells and is associated with an aggressive phenotype. Furthermore, the preliminary scientific evidence concerning the levels of circulating lactate in breast cancer points toward a correlation between hyperlactacidemia and poor prognosis, even though no clear linkage has been demonstrated. Overall, lactate may represent a promising metabolic target that needs to be investigated in breast cancer.
Generative Adversarial Networks (GANs) for Audio-Visual Speech Recognition in Artificial Intelligence IoT
Authors: He Yibo , Seng Kah Phooi , Ang Li Minn
Published: October 2023

This paper proposes a novel multimodal generative adversarial network AVSR (multimodal AVSR GAN) architecture, to improve both the energy efficiency and the AVSR classification accuracy of artificial intelligence Internet of things (IoT) applications. The audio-visual speech recognition (AVSR) modality is a classical multimodal modality, which is commonly used in IoT and embedded systems. Examples of suitable IoT applications include in-cabin speech recognition systems for driving systems, AVSR in augmented reality environments, and interactive applications such as virtual aquariums. The application of multimodal sensor data for IoT applications requires efficient information processing, to meet the hardware constraints of IoT devices. The proposed multimodal AVSR GAN architecture is composed of a discriminator and a generator, each of which is a two-stream network, corresponding to the audio stream information and the visual stream information, respectively. To validate this approach, we used augmented data from well-known datasets (LRS2-Lip Reading Sentences 2 and LRS3) in the training process, and testing was performed using the original data. The research and experimental results showed that the proposed multimodal AVSR GAN architecture improved the AVSR classification accuracy. Furthermore, in this study, we discuss the domain of GANs and provide a concise summary of the proposed GANs.
Clinical Evidence Regarding the Dynamic of Baker Cyst Dimensions after Intermittent Vacuum Therapy as Rehabilitation Treatment in Patients with Knee Osteoarthritis
Authors: Ionescu Elena-Valentina , Stanciu Liliana-Elena , Bujduveanu Andreea , Minea Mihaela , Oprea Doinita , Petcu Adina , Iliescu Madalina-Gabriela , Ciortea Viorela-Mihaela , Popa Florina-Ligia , Gheorghe Emma , Obada Bogdan , Oprea Carmen
Published: October 2023

The Baker cyst (BC), also known as the popliteal cyst or parameniscal cyst, is a fluid-filled sac that normally develops in the back of the knee, between the semimembranosus and medial head of the gastrocnemius. We aimed to evaluate the effectiveness of physiotherapy (10 days of treatment) that associates intermittent vacuum therapy (IVT) on the lower limbs in the treatment of the BC, respectively, in its size reduction. Sixty-five patients with knee osteoarthritis using Kellgren–Lawrence criteria and the presence of BC (ultrasonography evaluation), were divided into the Control and Vacuum groups. We collected the following features: sex, age, level of education, occupation, environment, body mass index, Knee Injury and Osteoarthritis Outcome Score, Western Ontario, and McMaster Universities Osteoarthritis Index, the Functional Independence Measurement, the Fall Risk Score, and the Visual Analog Scale were recorded at baseline and after 10 days. Both groups are similar in terms of demographic features. Regarding the clinical functional parameters, the results elicit a statistically significant change in all parameters between admission and discharge, including the echo volume at BC. Physical medicine and rehabilitation increase the autonomy of patients with BC. Clinical-functional improvement begins in the first 10 days of complex rehabilitation treatment; it is statistically significant and is not different between the two groups, which brings an additional argument for the effectiveness of conservative therapy in the treatment of BC. Although IVT has not demonstrated its superiority over classical balneo-physical therapy, additional research, and long-term monitoring are needed to provide additional arguments regarding this aspect.
Long-Term Oncologic Outcomes in Robot-Assisted and Video-Assisted Lobectomies for Non-Small Cell Lung Cancer
Authors: Fabbri Giulia , Femia Federico , Lampridis Savvas , Farinelli Eleonora , Maraschi Alessandro , Routledge Tom , Bille Andrea
Published: October 2023

This study compares long-term outcomes in patients undergoing video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS) lobectomy for non-small cell lung cancer (NSCLC); all consecutive patients who underwent RATS or VATS lobectomy for NSCLC between July 2015 and December 2021 in our center were enrolled in a single-center prospective study. The primary outcomes were overall survival (OS), disease-free survival (DFS), and recurrence rate. The secondary outcomes were complication rate, length of hospitalization (LOS), duration of chest tubes (LOD), and number of lymph node stations harvested. A total of 619 patients treated with RATS (n = 403) or VATS (n = 216) were included in the study. There was no significant difference in OS between the RATS and VATS groups (3-year OS: 75.9% vs. 82.3%; 5-year OS: 70.5% vs. 68.5%; p = 0.637). There was a statistically significant difference in DFS between the RATS and VATS groups (3-year DFS: 92.4% vs. 81.2%; 5-year DFS: 90.3% vs. 77.6%; p < 0.001). Subgroup analysis according to the pathological stage also demonstrated a significant difference between RATS and VATS groups in DFS in stage I (3-year DFS: 94.4% vs. 88.9%; 5-year DFS: 91.8% vs. 85.2%; p = 0.037) and stage III disease (3-year DFS: 82.4% vs. 51.1%; 5-year DFS: 82.4% vs. 37.7%; p = 0.024). Moreover, in multivariable Cox regression analysis, the surgical approach was significantly associated with DFS, with an HR of 0.46 (95% CI 0.27–0.78, p = 0.004) for RATS compared to VATS. VATS lobectomy was associated with a significantly higher recurrence rate compared to RATS (21.8% vs. 6.2%; p < 0.001). LOS and LOD, as well as complication rate and in-hospital and 30-day mortality, were similar among the groups. RATS lobectomy was associated with a higher number of lymph node stations harvested compared to VATS (7 [IQR:2] vs. 5 [IQR:2]; p < 0.001). In conclusion, in our series, RATS lobectomy for lung cancer led to a significantly higher DFS and significantly lower recurrence rate compared to the VATS approach. RATS may allow more extensive nodal dissection, and this could translate into reduced recurrence.
Anesthesia Management via an Automated Control System for Propofol, Remifentanil, and Rocuronium Compared to Management by Anesthesiologists: An Investigator-Initiated Study
Authors: Nagata Osamu , Matsuki Yuka , Matsuda Shuko , Hazama Keita , Fukunaga Saiko , Nakatsuka Hideki , Yasuma Fumiyo , Maehara Yasuhiro , Fujioka Shoko , Tajima Karin , Kondo Ichiro , Ginoza Itaru , Hayashi Misuzu , Kakinohana Manabu , Shigemi Kenji
Published: October 2023

Background: We previously developed an automated total intravenous anesthesia control system that uses new closed-loop system algorithms to administer propofol, remifentanil, and rocuronium based on the bispectral index and train-of-four data. We recently improved this automated control system by adding a safety mechanism and using a modified monitoring device. Methods: Patients scheduled for elective surgery were randomly assigned to closed-loop feedback control (automatic group) or the manual administration of propofol, remifentanil, and rocuronium (manual group). The proportion of time during which the proper management of three-agent anesthesia was maintained during surgery was determined as the primary endpoint. Results: The proportion of time during which the three components of sedation, analgesia, and muscle relaxation were adequately controlled was 87.21 ± 12.79% in the automatic group, which was non-inferior to the proportion of 65.19 ± 20.16% in the manual group (p < 0.001). Adverse events during the operative or postoperative observation periods were significantly less frequent in the automatic group (54 patients, 90.0%) than in the manual group (60 patients, 100.0%; p = 0.027). Conclusion: Our three-agent automated control system, which features an improved muscle relaxation monitor and safety mechanism added to the basic control algorithms, maintained sedation, analgesia, and muscle relaxation appropriately in a manner non-inferior to anesthesiologists without compromising safety.
Wear, Osteolysis, and Aseptic Loosening Following Total Hip Arthroplasty in Young Patients with Highly Cross-Linked Polyethylene: A Review of Studies with a Follow-Up of over 15 Years
Authors: Deans Christopher F. , Buckner Brandt C. , Garvin Kevin L.
Published: October 2023

Total hip arthroplasty (THA) has in recent years trended toward a younger, more physically demanding patient population. Mid- to long-term studies of all ages of THA patients using highly cross-linked polyethylene (HXLPE) have been favorable, but concerns about its long-term failure and wear-related complications remain for young THA patients. In this narrative review, a search of the PubMed/MEDLINE and Cochrane databases was performed, and we identified six studies with a minimum 15-year follow-up of HXLPE with various femoral head materials. Wear-related revisions were exceedingly low for patients under the age of 55, with variable reports of non-clinically significant osteolysis. Higher activity levels, a larger femoral head size, and femoral head material were not associated with greater long-term wear rates. Young THA with metal or ceramic on HXLPE is exceedingly durable with favorable outcomes at follow-ups of over 15 years.
The Impact of Transfer-Related Ischemia on Free Flap Metabolism and Electrolyte Homeostasis—A New In Vivo Experimental Approach in Pigs
Authors: Stephan Daniel , Blatt Sebastian , Riedel Julian , Mohnke Katja , Ruemmler Robert , Ziebart Alexander , Al-Nawas Bilal , Kämmerer Peer W. , Thiem Daniel G. E.
Published: October 2023

Free flap tissue transfer represents the gold standard for extensive defect reconstruction, although malperfusion due to thrombosis remains the leading risk factor for flap failure. Recent studies indicate an increased immune response and platelet activation in connection with pathologic coagulation. The underlying cellular and molecular mechanisms remain poorly understood, however. The presented study, therefore, aims to investigate if transfer-related ischemia alters intra-flap metabolism and electrolyte concentrations compared to central venous blood after free flap transfer in pigs to establish a novel experimental model. Free transfer of a myocutaneous gracilis flap to the axillary region was conducted in five juvenile male pigs. The flap artery was anastomosed to the axillary artery, and intra-flap venous blood was drained and transfused using a rubber-elastic fixed intravenous catheter. Blood gas analysis was performed to assess the effect of transfer time-induced ischemia on intra-flap electrolyte levels, acid–base balance, and hemoglobin concentrations compared to central venous blood. Time to flap reperfusion was 52 ± 10 min on average, resulting in a continuous pH drop (acidosis) in the flaps’ venous blood compared to the central venous system (p = 0.037). Potassium (p = 0.016), sodium (p = 0.003), and chloride (p = 0.007) concentrations were significantly increased, whereas bicarbonate (p = 0.016) and calcium (p = 0.008) significantly decreased within the flap. These observations demonstrate the induction of anaerobic glycolysis and electrolyte displacement resulting in acidosis and hence significant tissue damage already after a short ischemic period, thereby validating the novel animal model for investigating intra-flap metabolism and offering opportunities for exploring various (immuno-) thrombo-hemostatic issues in transplantation surgery.
Effects of Angiotensin Receptor Blockers on Streptozotocin-Induced Diabetic Cataracts
Authors: Ishigooka Gaku , Mizuno Hiroshi , Oosuka Shou , Jin Denan , Takai Shinji , Kida Teruyo
Published: October 2023

This study aimed to determine the role of oxidative stress produced by the renin–angiotensin system (RAS) in cataract formation in streptozotocin-induced diabetic rats (STZ) using angiotensin II receptor blockers (ARBs). Rats were treated with streptozotocin and orally administered candesartan (2.5 mg/kg/day) or a normal diet for 10 weeks until sacrifice. Cataract progression was assessed through a slit-lamp examination. Animals were euthanized at 18 weeks, and the degree of cataract progression was evaluated. Oxidative stress was also assessed. In STZ-treated rats, lens opacity occurred at 12 weeks. Cataract progression was inhibited in the ARB-treated group compared with the placebo group (p < 0.05). STZ-treated rats exhibited upregulated angiotensin-converting enzyme (ACE) gene expression than control rats. Oxidative stress-related factors were upregulated in the placebo-treated group but suppressed in the ARB-treated group. A correlation coefficient test revealed a positive correlation between ACE gene expression and oxidative stress-related factors and a negative correlation between ACE and superoxide dismutase. Immunostaining revealed oxidative stress-related factors and advanced glycation end products in the lens cortex of the placebo-treated group. The mechanism of diabetic cataracts may be related to RAS, and the increase in focal ACE and angiotensin II in the lens promotes oxidative stress-related factor production.
Impact of Non-Pharmaceutical Interventions on the Incidence and Treatment of Chronic Rhinosinusitis during the COVID-19 Pandemic: A Nationwide Retrospective Cohort Study
Authors: Jung Chan Min , Han Minkyung , Cho Hyung-Ju , Kim Chang-Hoon , Jung Inkyung , Rha Min-Seok
Published: October 2023

Many countries have implemented non-pharmaceutical interventions (NPIs) to prevent the spread of COVID-19. However, the impacts of NPIs on the epidemiology and treatment of chronic rhinosinusitis (CRS) remain unclear. We analyzed 671,216 patients to investigate changes in the incidence rate and treatment frequency of CRS using Korean nationwide health insurance data between 2017 and 2021. The incidence rate (p < 0.001) and the number of outpatients (p < 0.001), patients hospitalized (p < 0.001), and patients prescribed antibiotics (p < 0.001) or steroids (p = 0.024) were significantly lower in the pandemic period than in the pre-pandemic period; however, the number of patients who underwent surgery was not different (p = 0.205). Additionally, the frequency of surgeries per patient was significantly lower in patients during the pandemic period (p < 0.001). In the interrupted time series analysis, the trends in the number of outpatients (p < 0.001), patients hospitalized (p < 0.001), patients who underwent surgery (p < 0.001), and patients prescribed antibiotics (p < 0.001) or steroids (p < 0.001) significantly changed after the onset of the COVID-19 pandemic. In summary, NPI implementation during the COVID-19 pandemic was associated with a reduction in the incidence and treatment of CRS.
Biotechnology of Edible Fungi
Authors: Zou Gen , Zhu Jing , Zhao Mingwen
Published: October 2023

Edible fungi are generally defined as macrofungi with large fruiting bodies that may be consumed by humans and are commonly referred to as mushrooms [...]
Effect of Ligand Binding on Polymer Diffusiophoresis
Authors: Annunziata Onofrio
Published: October 2023

Diffusiophoresis is the migration of a macromolecule in response to a concentration gradient of a cosolute in liquids. Diffusiophoresis of polyethylene glycol (PEG) in water occurs from high to low concentration of trimethylamine-N-oxide (TMAO). This is consistent with the preferential hydration of PEG observed in the presence of TMAO. In other words, PEG migrates in the direction in which it lowers its chemical potential. On the other hand, although PEG is found to preferentially bind urea in water, PEG diffusiophoresis still occurs from high to low urea concentration. Thus, PEG migrates in the direction that increases its chemical potential in the urea case. Here, a ligand-binding model for polymer diffusiophoresis in the presence of a cosolute that preferentially binds to polymer is developed. It includes both actual polymer–ligand binding and the effect of the polymer on cosolute thermodynamic activity. This model shows that polymer–cosolute binding has a marginal effect on polymer diffusiophoresis and indicates that weak repulsive interactions, such as hard-core exclusion forces, are the main factor responsible for the observed PEG diffusiophoresis from high to low urea concentration. This work contributes to a better understanding of diffusiophoresis of macromolecules in response to gradients of nonelectrolytes.
A Sliding Mode Approach-Based Adaptive Steering Control Algorithm for Path Tracking of Autonomous Mobility with Weighted Injection
Authors: Kim Sehwan , Oh Kwangseok
Published: October 2023

The increasing complexity of mathematical models developed as part of the recent advancements in autonomous mobility platforms has led to an escalation in uncertainty. Despite the intricate nature of such models, the detection, decision, and control methods for autonomous mobility path tracking remain critical. This study aims to achieve path tracking based on pixel-based control errors without parameters in the mathematical model. The proposed approach entails deriving control errors from a multi-particle filter based on a camera, estimating the error dynamics coefficients through a recursive least squares (RLS) approach, and using the sliding mode approach and weighted injection to formulate a cost function that leverages the estimated coefficients and control errors. The resultant adaptive steering control expedites the convergence of control errors towards zero by determining the magnitude of the injection variable based on the control errors and the finite-time convergence condition. The efficacy of the proposed approach is evaluated through an S-curved and elliptical path using autonomous mobility equipped with a single steering and driving module. The results demonstrate the capability of the approach to reasonably track target paths through driving and steering control facilitated by a multi-particle filter and a lidar-based obstacle detection system.
Swirling of Horizontal Skyrmions into Hopfions in Bulk Cubic Helimagnets
Authors: Leonov Andrey O.
Published: October 2023

Magnetic hopfions are three-dimensional topological solitons embedded into a homogeneously magnetized background. The internal structure of hopfions is distinguished by the linked preimages—closed loops with a single orientation of the magnetization on the target space S2—and is thus characterized by the integer Hopf index QH. Alternatively, hopfions can be visualized as a result of the swirling of two-dimensional bimerons around the direction of an applied magnetic field. Since the bimeron consists of a circular core and an anti-skyrmion crescent, two hopfion varieties can be achieved with either bimeron constituent facing the hopfion interior. In bulk cubic helimagnets, however, the applied magnetic field leads to a spontaneous collapse of hopfions, i.e., the eigen-energy of hopfions has the minimum for zero hopfion radius R. Anti-hopfions with QH=−1, in this case, pass through the intermediate toron state with two-point defects. Here, we demonstrate that the competing cubic and exchange anisotropies inherent in cubic non-centrosymmetric magnets (e.g., in the Mott insulator Cu2OSeO3) as a third level of the hierarchy of energy scales following the exchange and Dzyaloshinskii–Moriya interactions, may shift the energy minimum into the region of finite hopfion radii.
A Hybrid Large Eddy Simulation Algorithm Based on the Implicit Domain Decomposition
Authors: E. Fard Amir , Utyuzhnikov Sergey
Published: October 2023

The resolution of small near-wall eddies encountered in high-Reynolds number flows using large eddy simulation (LES) requires very fine meshes that may be computationally prohibitive. As a result, the use of wall-modeled LES as an alternative is becoming more popular. In this paper, the near-wall domain decomposition (NDD) approach that was originally developed for Reynolds-averaged Navier–Stokes simulations (RANSs) is extended to the hybrid RANS/LES zonal decomposition. The algorithm is implemented in two stages. First, the solution is computed everywhere with LES on a coarse grid using a new non-local slip boundary condition for the instantaneous velocity at the wall. The solution is then recomputed in the near-wall region with RANS. The slip boundary conditions used in the first stage guarantee that the composite solution is smooth at the inner/outer region interface. Another advantage of the model is that the turbulent viscosity in the inner region is computed based on the corresponding RANS velocity. This shows improvement over those hybrid models that have only one velocity field in the whole domain obtained from LES. The model is realized in the open source code OpenFOAM with different approximations of turbulent viscosity and is applied to the planar channel flow at frictional Reynolds numbers of Reτ=950, 2000, and 4200. Mean streamwise velocity and Reynolds stress intensities are predicted reasonably well in comparison to the solutions obtained with unresolved LES and available DNS benchmarks. No additional forcing at the interface is required, while the log–layer mismatch is essentially reduced in all cases.
Safe Optimal Control of Dynamic Systems: Learning from Experts and Safely Exploring New Policies
Authors: Candelieri Antonio , Ponti Andrea , Fersini Elisabetta , Messina Enza , Archetti Francesco
Published: October 2023

Many real-life systems are usually controlled through policies replicating experts’ knowledge, typically favouring “safety” at the expense of optimality. Indeed, these control policies are usually aimed at avoiding a system’s disruptions or deviations from a target behaviour, leading to suboptimal performances. This paper proposes a statistical learning approach to exploit the historical safe experience—collected through the application of a safe control policy based on experts’ knowledge— to “safely explore” new and more efficient policies. The basic idea is that performances can be improved by facing a reasonable and quantifiable risk in terms of safety. The proposed approach relies on Gaussian Process regression to obtain a probabilistic model of both a system’s dynamics and performances, depending on the historical safe experience. The new policy consists of solving a constrained optimization problem, with two Gaussian Processes modelling, respectively, the safety constraints and the performance metric (i.e., objective function). As a probabilistic model, Gaussian Process regression provides an estimate of the target variable and the associated uncertainty; this property is crucial for dealing with uncertainty while new policies are safely explored. Another important benefit is that the proposed approach does not require any implementation of an expensive digital twin of the original system. Results on two real-life systems are presented, empirically proving the ability of the approach to improve performances with respect to the initial safe policy without significantly affecting safety.
Influence of Internal Erosion on Rainfall-Induced Instability of Layered Deposited-Soil Slopes
Authors: Lei Xiaoqin , Zhang Weiyu , Chen Xiaoqing , Ming Liu
Published: October 2023

Layered deposited-soil slopes are widely distributed in mountainous terrain. The rainfall-induced instability of layered deposited-soil slopes is not only controlled by the unsaturated infiltration process but also by the seepage-induced internal-erosion process within the deposited soils. In this paper, the main physical processes within two-layer deposited-soil slopes under rainfall infiltration are summarized, and a coupled seepage–erosion finite element model is established to analyze the interactions between the rainfall infiltration process and the internal-erosion process within layered deposited-soil slopes. This finite element model was validated by simulating the coupled seepage–erosion process in a one-dimensional layered soil column. Then, serials of two-dimensional coupled seepage–erosion simulations were conducted to investigate the rainfall-induced seepage–erosion patterns, as well as their impact on the stability evolution of the layered deposited slopes. It was shown that the rainfall-induced seepage–erosion accelerate the water infiltration into the slope and facilitate the generation of subsurface stormflow near the layer interface, which will weaken the soils around the layer interface and accelerate the slope failure process inevitably. Special attention should be paid to the rainfall-induced seepage–erosion effect when evaluating the stability of layered deposited-soil slopes.
The Molecular Characterization of blaNDM-1-Positive Acinetobacter baumannii Isolated in Central Greece
Authors: Tsilipounidaki Katerina , Gkountinoudis Christos-George , Florou Zoi , Fthenakis George C. , Miriagou Vivi , Petinaki Efthymia
Published: October 2023

The objective of the present study is to report the detection and the molecular characterization of nine blaNDM-1-positive Acinetobacter baumannii isolates, which were isolated from patients in a tertiary care hospital in Central Greece from December 2022 to August 2023. The isolates were characterized by whole genome sequencing to obtain Pasteur multilocus sequencing typing (MLST) and to identify the blaNDM-1-environment, resistome, and virulence genes content. In silico MLST analysis showed that the isolates belonged to four different clones (STs 160, 2, 85, and 2493). All strains, apart from the blaNDM-1-gene, possessed at least eight different genes, encoding resistance to various antimicrobial agents. Whole genome sequencing revealed two different structures of the blaNDM-1 environment. The first, detected in ST160 strain, was identical with the Tn125, whereas the second, found in STs 2, 85, and 2493 was associated with Tn7382. To our knowledge, after a sole strain reported in 2016 and imported by a patient hospitalized in a Libyan hospital, this is the first report of the emergence of polyclonal blaNDM-1-positive Acinetobacter baumannii in Greece. Our findings re-emphasize the need to apply diligent surveillance protocols in order to limit the horizontal transfer of the blaNDM-1 gene to other A. baumannii clones or to other recipient strains.
Genome-Wide Analysis of the Cytochrome P450 Monooxygenases in the Lichenized Fungi of the Class Lecanoromycetes
Authors: Mlambo Gugulethu , Padayachee Tiara , Nelson David R. , Syed Khajamohiddin
Published: October 2023

Lichens are unique organisms that exhibit a permanent symbiosis between fungi and algae or fungi and photosynthetic bacteria. Lichens have been found to produce biotechnologically valuable secondary metabolites. A handful of studies showed that tailoring enzymes such as cytochrome P450 monooxygenases (CYPs/P450s) play a key role in synthesizing these metabolites. Despite the critical role of P450s in the biosynthesis of secondary metabolites, the systematic analysis of P450s in lichens has yet to be reported. This study is aimed to address this research gap. A genome-wide analysis of P450s in five lichens from the fungal class Lecanoromycetes revealed the presence of 434 P450s that are grouped into 178 P450 families and 345 P450 subfamilies. The study indicated that none of the P450 families bloomed, and 15 P450 families were conserved in all five Lecanoromycetes. Lecanoromycetes have more P450s and higher P450 family diversity compared to Pezizomycetes. A total of 73 P450s were found to be part of secondary metabolite gene clusters, indicating their potential involvement in the biosynthesis of secondary metabolites. Annotation of P450s revealed that CYP682BG1 and CYP682BG2 from Cladonia grayi and Pseudevernia furfuracea (physodic acid chemotype) are involved in the synthesis of grayanic acid and physodic acid, CYP65FQ2 from Stereocaulon alpinum is involved in the synthesis of atranorin, and CYP6309A2 from Cladonia uncialis is involved in the synthesis of usnic acid. This study serves as a reference for future annotation of P450s in lichens.
Exploring Correlations of Food-Specific Disgust with Eating Disorder Psychopathology and Food Interaction: A Preliminary Study Using Virtual Reality
Authors: Bektas Sevgi , Natali Ludovica , Rowlands Katie , Valmaggia Lucia , Di Pietro Jerome , Mutwalli Hiba , Himmerich Hubertus , Treasure Janet , Cardi Valentina
Published: October 2023

The emotion of disgust is thought to play a critical role in maintaining restrictive eating among individuals with anorexia nervosa. This exploratory cross-sectional study examined correlations between food-specific trait and state disgust, eating disorder psychopathology, illness severity (body mass index: BMI), and interactions with virtual foods in people with anorexia nervosa. Food-specific trait disgust and eating disorder symptoms were measured before exposure to virtual foods in one of three virtual reality (VR) kitchens to which participants were randomly allocated. Food interactions (eye gaze and reaching towards virtual foods) were measured during the VR exposure. Food-specific state disgust ratings were collected after the VR exposure. In the entire sample, eating disorder symptoms correlated positively with food-specific trait disgust (rs (68) = 0.45, p < 0.001). We also found a significant association between food-specific state disgust and eating disorder symptoms in each virtual kitchen scenario: virtual kitchen only (rs (22) = 0.40, p = 0.05), virtual kitchen plus pet (rs (22) = 0.80, p < 0.001), and virtual kitchen plus avatar (rs (20) = 0.78, p < 0.001). No significant correlation was observed for the link between food-specific disgust measures and food-related touch. Correlations between food-specific trait disgust and food-related eye gaze differed across scenarios. The current experimental paradigm needs to be improved to draw firm conclusions. Both food-specific trait and state disgust are associated with eating disorder psychopathology, and therefore, effective strategies are warranted to attenuate food-specific disgust.
Factors Influencing HPV Vaccine Intentions in Malaysian Men Who Have Sex with Men: A Cross-Sectional Study in Malaysia
Authors: Wong Li Ping , Alias Haridah , Lim Sin How
Published: October 2023

In the landscape of healthcare disparities and the marginalized status of men who have sex with men (MSM) in Malaysia, understanding the dynamics surrounding HPV vaccination is of paramount importance. The purpose of this study is to examine the knowledge and attitudes of MSM regarding HPV vaccination and to identify factors that may hinder or facilitate its uptake. The findings will contribute to the development of targeted interventions to promote HPV vaccination and reduce the burden of HPV-related health issues among Malaysian MSM. Between May 2019 and September 2022, an online cross-sectional survey was conducted to collect data through popular social media platforms targeting MSM in Malaysia. A multivariable logistic regression model was employed to investigate the associations between HPV vaccination intention and various influencing factors. Out of the total 411 respondents in the study, 266 (60.3%) indicated an intent to receive the HPV vaccination, falling under the categories of “certain to happen”, “very likely”, and “likely”. The average knowledge score for participants was 6.82 (SD = 3.93, range 0–13) out of a total possible score of 13. In the multivariate logistic model, participants who identified themselves as bisexual (OR 6.93, 95% CI 2.35–20.41) and gay/homosexual (OR 4.36, 95% CI 1.66–11.42) showed a greater inclination to receive the HPV vaccine compared to heterosexual participants. High intent to be vaccinated for HPV infection was positively and significantly associated with a high level of knowledge (OR 1.79, 95% CI 1.09–2.95). In the multivariable model, there was no significant association between all variables of attitudes towards HPV infection and HPV vaccinations and the intention to receive HPV vaccination. Study participants reported a low level of susceptibility to HPV infection despite their perception that HPV infection is severe. Two-thirds of participants expected to encounter stigma in healthcare settings during future implementation of HPV vaccination programs. This study underscores the importance of improving HPV vaccine acceptance among Malaysian MSM due to the moderate acceptance level observed. In Malaysia, promoting HPV awareness, enhancing risk perception, and addressing stigma and sensitivity surrounding HPV vaccination may be beneficial in increasing the vaccination willingness among MSM.
NO Addition during Gas Oxygenation Reduces Liver and Kidney Injury during Prolonged Cardiopulmonary Bypass
Authors: Radovskiy Aleksey Maksimovich , Bautin Andrey Evgenevich , Marichev Alexander Olegovich , Osovskikh Victor Vasilyevich , Semenova Natalia Yuryevna , Artyukhina Zoya Evgenyevna , Murashova Lada Aleksandrovna , Zinserling Vsevolod Alexandrovich
Published: October 2023

Objective. To evaluate the effect of NO added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) on the liver and kidneys in pigs. Methods. An experiment was carried out on 10 pigs undergoing cardiac surgery using CPB. NO was added to the sweep gas of the oxygenator at a concentration of 100 ppm for the animals in the experimental group (CPB-NO, n = 5). Animals in the control group (CPB-contr, n = 5) did not receive NO in the sweep gas of the oxygenator. The CPB lasted 4 h, followed by postoperative monitoring for 12 h. To assess the injury to the liver and kidneys, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were determined initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. The glomerular filtration rate (GFR) was evaluated initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. A pathomorphological study of the liver and kidneys was performed using semiquantitative morphometry. Results. The long four-hour period of CPB deliberately used in our experiment caused liver and kidney injury. In the CPB-contr group, an increase in the ALT concentration was found: 43 (34; 44) U/L at baseline to 82 (53; 99) U/L 12 h after CPB, p < 0.05. The AST concentration in the CPB-contr group increased from 25 (17; 26) U/L at baseline to 269 (164; 376) U/L 12 h after CPB, p < 0.05. We found no significant increase in the ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between the CPB-NO and CPB-contr groups at all the study time-points. In the CPB-contr group, an increase in the creatinine level was found from 131 (129; 133) µmol/L at baseline to 273 (241; 306) µmol/L 12 h after CPB, p < 0.05. We found no significant increase in creatinine level in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-contr group 12 h after weaning from CPB: 183 (168; 196) vs. 273 (241; 306) µmol/L; p = 0.008. The GFR in the CPB-NO group was significantly higher than in the CPB-contr group 6 h after weaning from CPB: 78.9 (77.8; 82.3) vs. 67.9 (62.3; 69.2) mL/min; p = 0.016. GFR was significantly higher in the CPB-NO group than in the CPB-contr group 12 h after weaning from CPB: 67.7 (65.5; 68.0) vs. 50.3 (48.7; 54.9) mL/min; p = 0.032. We found no significant differences between the study groups in the level of NGAL. We found several differences between the groups in the pathomorphological study. Conclusions. NO added to the sweep gas of the oxygenator reduces creatinine levels and increases GFR during prolonged CPB injury. Further research is required.