bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronization of an Exciter and Three Cylindrical Rollers with Different Dry Friction via Dynamic Coupling
Authors: Gu Dawei , Zhang Juqian , Wu Quanhui , Shen Pengfei , Pan Baisong , Wen Bangchun
Published: May 2022

In this paper, the dynamics of a mechanical exciter and three cylindrical rollers (CRs) with the non-identical friction coefficients interacting through a rigid platform is considered. Sufficient conditions for the existence and stability of synchronous solutions in the coupled system are derived by using the average method of modified small parameters and Routh-Hurwitz principle. The obtained theoretical results are illustrated and analysed based on numerical calculations. In the analysis, the numerical results are presented for simple one-parameter variation, as well as for a group of varied parameters, when the influence of the coupling structure’s parameters on synchronization and stability is studied. An appropriate selection of the key parameters will eventually lead to desired synchronization performance. Finally, the theoretical and numerical results are supported by computer simulations. The stable synchronized states can be observed in the simulations even when there are unavoidably small differences in the three friction coefficients. If we mismatch the friction coefficients of the CRs, they are seen to synchronize with a constant phase difference. The key feature of the proposed coupled system is the dynamic coupling torque, which serves as the vehicle for transferring energy from an induction motor to three CRs without the direct driving sources and the synchronization controller for maintaining the originally synchronous and stable states against the disturbance in the simulations.
BearingCog: A Bearing Fault Diagnosis Method under Variable Operational Conditions
Authors: Fu Lei , Ma Zepeng , Wu Debin , Liu Jia , Xu Fang , Zhong Qi , Zhu Tiantian
Published: May 2022

Rolling bearing is a pivotal component for rotating equipment, which has high failure rates. Bearing failure can cause the equipment to lose control or even casualties, resulting in significant economic losses. This article diagnoses the bearings in variable operational conditions. A novel fault diagnosis framework is proposed to improve the efficiency of fault classification. The variational modal decomposition (VMD) is first utilized to expand the features of the fault signal. Then, principal component analysis (PCA) selects the most representative fault features from the VMD results. After that, the multi-information fusion data is applied to improve the classification accuracy of the support vector machine (SVM). The comparison with respect to some traditional classification methods is illustrated in detail. The diagnostic results show that the proposed framework is a validated tool for diagnosing the bearings.
Ubiquitous Tourist System Based on Multicriteria Decision Making and Augmented Reality
Authors: Rokhsaritalemi Somaiieh , Sadeghi-Niaraki Abolghasem , Kang Ho-San , Lee Jong-Won , Choi Soo-Mi
Published: May 2022

Increasing global demand for travel has drawn public attention to the tourism industry. This industry needs the design of intelligent systems based on new concepts to facilitate better service delivery. To this end, this study proposes a ubiquitous tourist system based on context-awareness, multicriteria decision making (MCDM), and augmented reality (AR) using a geospatial information system (GIS). This system provides two services to the user. First, it recommends a hotel in the vicinity of the user based on their preferences. Subsequently, it modifies the information property to augment the information concerning the visited object using AR technology. This system offers the advantage of adapting its models based on the user and their environment using context-awareness, thereby facilitating increased system automation during service delivery. Furthermore, this system enables personalization based on user needs. Our system was evaluated via a usability test using a Likert scale based on two system aspects, namely, system design, and user acceptance of the result. The output of this test yielded an average score of 4.112. The proximity of this score to the highest level of the Likert scale indicates the acceptance of the system by users.
Natural and Anthropogenic Radioactivity Content and Radiation Hazard Assessment of Baby Food Consumption in Italy
Authors: Caridi Francesco , Paladini Giuseppe , Venuti Valentina , Spoto Sebastiano Ettore , Crupi Vincenza , Belmusto Giovanna , Majolino Domenico
Published: May 2022

The natural (40K) and anthropogenic (137Cs) radioactivity concentration in four different typologies of early childhood (up to two years old) foods, i.e., homogenized fruit, homogenized meat, childhood biscuits and baby pasta, produced in Italy and sold in Italian large retailers, was investigated through High Purity Germanium (HPGe) gamma spectrometry. The present study is carried out with the aim to: (i) evaluate the background levels of the investigated radionuclides in the analyzed early childhood foods, (ii) identify whether the twenty analyzed samples were appropriate for infant consumption and (iii) contribute to construct a database on the radioactivity of early childhood foods sold in Italy.
Theoretical Study on Design of Composite Lining Structure with Rigid–Flexible Combination for Trenchless Pipeline Rehabilitation
Authors: Ti Zhongsen , Wang Fuzhi , Zhao Yahong , Ma Baosong , Zeng Cong , Liao Baoyong
Published: May 2022

Trenchless rehabilitation lining can be divided into flexible solid wall lining structures, rigid lining structures and rigid–flexible composite lining structures. This paper reviews the research status of the design theory of trenchless rehabilitation lining pipes, analyzes the theory of rigid–flexible composite lining structures, and points out that the value of the factor determined from non-grouting angle K1 is not clear in the design formula of the rigid–flexible composite lining structure mentioned in the ASTM ‘Standard Practice for Installation of Machine Spiral Wound Poly (Vinyl Chloride) (PVC) Liner Pipe for Rehabilitation of Existing Sewers and Conduits (ASTM F 1741)’. The value of K1 was obtained by the numerical analysis method with MATLAB software. Through the analysis of the variation trend of the K1 value, it is concluded that the design formula in the ASTM standard is only applicable to the case of incomplete grouting filling between the original pipe and the lining pipe, and is not applicable to the composite lining pipe with complete grouting filling. Finally, the explicit formula of the non-grouting angle is obtained by fitting, which is more convenient to use.
Prediction of Cell-Penetrating Peptides Using a Novel HSIC-Based Multiview TSK Fuzzy System
Authors: Liu Peng , Zhao Shulin , Zou Quan , Ding Yijie
Published: May 2022

Cell-penetrating peptides (CPPs) are short peptides that can carry cargo into cells. CPPs are widely utilized due to their powerful loading capacity and transduction efficiency. Identifying CPPs is the basis for studying their functions and mechanisms; however, experimental methods to identify CPPs are expensive and time-consuming. Recently, CPP predictors based on machine learning methods have become a research hotspot. Although considerable progress has been made, some challenges remain unresolved. First, most predictors employ a variety of feature descriptors to transform an original sequence into multiview data; however, extant methods ignore the relationships between different views, limiting further performance improvement. Second, most machine learning models are actually black boxes and cannot offer insightful advice. In this paper, a novel Hilbert–Schmidt independence criterion (HSIC)-based multiview TSK fuzzy system is proposed. Compared with other machine learning methods, TSK fuzzy systems have better interpretability, and the introduction of multiview mechanisms provides comprehensive insight into the intrinsic laws of the data. HSIC is utilized here to measure the independence and enhance the complementarity between different views. Notably, the proposed method attained prediction accuracy results of 92.2% and 96.2% for the training and independent test sets, respectively. The empirical results show that our promising approach features greater recognition performance than the state-of-the-art method.
Interval Type-3 Fuzzy Aggregation of Neural Networks for Multiple Time Series Prediction: The Case of Financial Forecasting
Authors: Castillo Oscar , Castro Juan R. , Melin Patricia
Published: May 2022

In this work, we present an approach for fuzzy aggregation of neural networks for forecasting. The interval type-3 aggregator is used to combine the outputs of the networks to improve the quality of the prediction. This is carried out in such a way that the final output is better than the outputs of the individual modules. In our approach, a fuzzy system is used to estimate the prediction increments that will be assigned to the output in the process of combining them with a set of fuzzy rules. The uncertainty in the process of aggregation is modeled with an interval type-3 fuzzy system, which, in theory, can outperform type-2 and type-1 fuzzy systems. Publicly available data sets of COVID-19 cases and the Dow Jones index were utilized to test the proposed approach, as it has been stated that a pandemic wave can have an effect on the economies of countries. The simulation results show that the COVID-19 data does have, in fact, an influence on the Dow Jones time series and its use in the proposed model improves the forecast of the Dow Jones future values.
Development of Patent Technology Prediction Model Based on Machine Learning
Authors: Lee Chih-Wei , Tao Feng , Ma Yu-Yu , Lin Hung-Lung
Published: May 2022

Intellectual property rights have a great impact on the development of the automobile industry. Issues related to the timeliness of patent applications often arise, such as the inability of firms to predict new technologies and patents developed by peers. To find the proper direction of product development, the R&D departments of enterprises need to accurately predict the technology trends. Machine learning adopts calculation through a large amount of data through mathematical models and methods and finds the best solution at the fastest speed through repeated simulation and experiments, to provide decision makers with a reference basis. Therefore, this paper provides accurate forecasts through established models. In terms of the significance of management, the planning of future enterprise strategy can be divided into three stages as a short-term plan of 1–3 years, a medium-term plan of 3–5 years, and a long-term plan of 5–10 years. This study will give appropriate suggestions for the development of automobile industry technology.
Modelling 5-km Running Performance on Level and Hilly Terrains in Recreational Runners
Authors: Melo Onécimo Ubiratã Medina , Tartaruga Marcus Peikriszwili , de Borba Edilson Fernando , Boullosa Daniel , da Silva Edson Soares , Bernardo Rodrigo Torma , Coimbra Renan , Oliveira Henrique Bianchi , da Rosa Rodrigo Gomes , Peyré-Tartaruga Leonardo Alexandre
Published: May 2022

Incline and level running on treadmills have been extensively studied due to their different cardiorespiratory and biomechanical acute responses. However, there are no studies examining the performance determinants of outdoor running on hilly terrains. We aimed to investigate the influence of anthropometrics, muscle strength, and cardiorespiratory and gait spatiotemporal parameters during level (0%) and inclined (+7%) running on performance in level and hilly 5-km races. Twenty male recreational runners completed two 5-km outdoor running tests (0% vs. +7% and −7%), and two submaximal (10 km·h−1) and incremental treadmill tests at 0 and 7% slopes, after complete laboratory evaluations. The velocity at maximal oxygen consumption (VO2max) evaluated at 7% incline and level treadmill running were the best performance predictors under both hilly (R2 = 0.72; p < 0.05) and level (R2 = 0.85; p < 0.01) conditions, respectively. Inclusion of ventilatory and submaximal heart rate data improved the predictive models up to 100%. Conversely, none of the parameters evaluated in one condition contributed to the other condition. The spatiotemporal parameters and the runners’ strength levels were not associated to outdoor performances. These results indicate that the vVO2max evaluated at similar slopes in the lab can be used to predict 5-km running performances on both level and hilly terrains.
Restoring Genetic Resource through In Vitro Culturing Testicular Cells from the Cryo-Preserved Tissue of the American Shad (Alosa sapidissima)
Authors: Xu Hong-Yan , Hong Xiao-You , Zhong Chao-Yue , Wu Xu-Ling , Zhu Xin-Ping
Published: May 2022

Germ cells, as opposed to somatic cells, can transmit heredity information between generations. Cryopreservation and in vitro culture of germ cells are key techniques for genetic resource preservation and cellular engineering breeding. In this study, two types of cryopreserved samples, namely testis pieces and testicular cells of American shad, were comparatively analyzed for cell viability. The results showed that the cell viability of the cryopreserved testis pieces was much higher than that of the cryopreserved testicular cells. The viability of cells from the cryopreserved testis pieces ranged from 65.2 ± 2.2 (%) to 93.8 ± 0.6 (%), whereas the viability of the dissociated cells after cryopreservation was 38.5 ± 0.8 (%) to 87.1 ± 2.6 (%). Intriguingly, the testicular cells from the post-thaw testicular tissue could be cultured in vitro. Likewise, most of the cultured cells exhibited germ cell properties and highly expressed Vasa and PCNA protein. This study is the first attempt to effectively preserve and culture the male germ cells through freezing tissues in the American shad. The findings of this study would benefit further investigations on genetic resource preservation and other manipulations of germ cells in a commercially and ecologically important fish species.
Glutamine Metabolism Is Required for Alveolar Regeneration during Lung Injury
Authors: Wang Sisi , Li Xue , Ma Qingwen , Wang Qi , Wu Junping , Yu Hongzhi , Li Kuan , Li Yu , Wang Jianhai , Zhang Qiuyang , Wang Youwei , Wu Qi , Chen Huaiyong
Published: May 2022

(1) Background: Abnormal repair after alveolar epithelial injury drives the progression of idiopathic pulmonary fibrosis (IPF). The maintenance of epithelial integrity is based on the self-renewal and differentiation of alveolar type 2 (AT2) cells, which require sufficient energy. However, the role of glutamine metabolism in the maintenance of the alveolar epithelium remains unclear. In this study, we investigated the role of glutamine metabolism in AT2 cells of patients with IPF and in mice with bleomycin-induced fibrosis. (2) Methods: Single-cell RNA sequencing (scRNA-seq), transcriptome, and metabolomics analyses were conducted to investigate the changes in the glutamine metabolic pathway during pulmonary fibrosis. Metabolic inhibitors were used to stimulate AT2 cells to block glutamine metabolism. Regeneration of AT2 cells was detected using bleomycin-induced mouse lung fibrosis and organoid models. (3) Results: Single-cell analysis showed that the expression levels of catalytic enzymes responsible for glutamine catabolism were downregulated (p < 0.001) in AT2 cells of patients with IPF, suggesting the accumulation of unusable glutamine. Combined analysis of the transcriptome (p < 0.05) and metabolome (p < 0.001) revealed similar changes in glutamine metabolism in bleomycin-induced pulmonary fibrosis in mice. Mechanistically, inhibition of the key enzymes involved in glucose metabolism, glutaminase-1 (GLS1) and glutamic-pyruvate transaminase-2 (GPT2) leads to reduced proliferation (p < 0.01) and differentiation (p < 0.01) of AT2 cells. (4) Conclusions: Glutamine metabolism is required for alveolar epithelial regeneration during lung injury.
Targeting Nrf2 with Probiotics and Postbiotics in the Treatment of Periodontitis
Authors: Karaca Basar , Yilmaz Mustafa , Gursoy Ulvi Kahraman
Published: May 2022

Periodontitis is a destructive disease of the tooth-surrounding tissues. Infection is the etiological cause of the disease, but its extent and severity depend on the immune–inflammatory response of the host. Immune cells use reactive oxygen species to suppress infections, and there is homeostasis between oxidative and antioxidant mechanisms during periodontal health. During periodontitis, however, increased oxidative stress triggers tissue damage, either directly by activating apoptosis and DNA damage or indirectly by activating proteolytic cascades. Periodontal treatment aims to maintain an infection and inflammation-free zone and, in some cases, regenerate lost tissues. Although mechanical disruption of the oral biofilm is an indispensable part of periodontal treatment, adjunctive measures, such as antibiotics or anti-inflammatory medications, are also frequently used, especially in patients with suppressed immune responses. Recent studies have shown that probiotics activate antioxidant mechanisms and can suppress extensive oxidative stress via their ability to activate nuclear factor erythroid 2-related factor 2 (Nrf2). The aim of this narrative review is to describe the essential role of Nrf2 in the maintenance of periodontal health and to propose possible mechanisms to restore the impaired Nrf2 response in periodontitis, with the aid of probiotic and postbiotics.
A Comparative Study of Milk Fat Extracted from the Milk of Different Goat Breeds in China: Fatty Acids, Triacylglycerols and Thermal and Spectroscopic Characterization
Authors: Korma Sameh A. , Li Li , Wei Wei , Liu Pengzhan , Zhang Xinghe , Bakry Ibrahim A. , An Peipei , Abdrabo Khaled A. E. , Manzoor Muhammad Faisal , Umair Muhammad , Cacciotti Ilaria , Lorenzo José M. , Conte-Junior Carlos Adam
Published: May 2022

Goat milk (GM) is an excellent alternative to cow milk and has recently been used in commercial infant formula preparation due to its superior fat composition. Here, the fatty acid (FA) composition, triacylglycerol (TAG) molecular species, thermal behavior and infrared spectra of extracted milk fat from the milk of the two main breeds of dairy goat bred in China (Guanzhong GM (GZG) and Xinong Saanen GM (XSG)) are investigated. Gas chromatography, Fourier-transform infrared spectroscopy, differential scanning calorimetry and ultra-performance convergence chromatography with quadrupole time-of-flight mass spectrometry are applied. The obtained results evidence significant fat compositional differences based on the breed that produced the considered GM. The major FAs in both GM fats were capric (C10:0), myristic (C14:0), palmitic (C16:0), stearic (C18:0) and oleic (C18:1 n-9c). GZG presented a higher content of medium-chain saturated FAs, while XSG had higher unsaturated FAs with higher ratios of L/Ln and n-6/n-3. A total of 339 and 359 TAGs were detected and quantified in GZG and XSG, and the major TAGs were those of m/z 740.6712 (14.10 ± 0.27%) and m/z 684.6094 (10.94 ± 0.02%), respectively. Milk TAGs of GZG and XSG showed 24–54 and 26–54 total acyl carbon numbers with a 0–4 and 0–5 double bond number at 68 and 72 various retention times, respectively. Thermal analysis showed that all GM fat samples melted below normal body temperature. Infrared spectra revealed higher absorption values of GZG milk fat. This study provides valuable information to the dairy industry sector about GM fat produced in China, assessing the appropriateness of Chinese GM fat to be applied in Chinese infant formula.
Modeling Joint Stiffness Change by Pelvic Tightening Based on Pelvic Alignment
Authors: Yoshida Michihiro , Tanaka Takayuki , Tsuchiya Yoshio
Published: May 2022

This paper aims to develop a regression model that explains the relationship between changes in lumbar joint stiffness and pelvic alignment (posture or shape of the bones of the pelvis and lumbar spine) due to pelvic tightening. The proposed model is based on the hypothesis that lumbar joint stiffness increases with changes in pelvic alignment. The proposed model is based on experimentally measured stiffness values and pelvic alignment data sets. The stiffness of the lumbar joint was estimated by motion analysis using a motion-capture system. Ninety-six volunteers participated in the experiment to estimate stiffness values, and the validity of using lumbar joint stiffness as the output of the model was examined. The pelvic alignment was measured through X-ray images. Pelvic alignment was measured using radiographic images, and 25 volunteers participated. The Results section states that the amount of change in the posture of the sacrum relative to the pelvis and the curvature of the lumbar spine contributes to the change in lumbar joint stiffness. Future work will include FEM analysis to validate the overall hypothesis and the validity of applying the model to a group other than those who participated in the development of the model.
Combined Treatment of Nitrated [6,6,6]Tricycles Derivative (SK2)/Ultraviolet C Highly Inhibits Proliferation in Oral Cancer Cells In Vitro
Authors: Wang Sheng-Chieh , Yen Ching-Yu , Shiau Jun-Ping , Chang Meng-Yang , Hou Ming-Feng , Tang Jen-Yang , Chang Hsueh-Wei
Published: May 2022

Combined treatment is an effective strategy to improve anticancer therapy, but severe side effects frequently limit this application. Drugs inhibiting the proliferation of cancer cells, but not normal cells, display preferential antiproliferation to cancer cells. It shows the benefits of avoiding side effects and enhancing antiproliferation for combined treatment. Nitrated [6,6,6]tricycles derivative (SK2), a novel chemical exhibiting benzo-fused dioxabicyclo[3.3.1]nonane core with an n-butyloxy substituent, exhibiting preferential antiproliferation, was chosen to evaluate its potential antioral cancer effect in vitro by combining it with ultraviolet C (UVC) irradiation. Combination treatment (UVC/SK2) caused lower viability in oral cancer cells (Ca9-22 and OC-2) than single treatment (20 J/m2 UVC or 10 μg/mL SK2), i.e., 42.3%/41.1% vs. 81.6%/69.2%, and 89.5%/79.6%, respectively. In contrast, it showed a minor effect on cell viability of normal oral cells (HGF-1), ranging from 82.2 to 90.6%. Moreover, UVC/SK2 caused higher oxidative stress in oral cancer cells than normal cells through the examination of reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane potential. UVC/SK2 also caused subG1 increment associated with apoptosis detections by assessing annexin V; panaspase; and caspases 3, 8, and 9. The antiproliferation and oxidative stress were reverted by N-acetylcysteine, validating the involvement of oxidative stress in antioral cancer cells. UVC/SK2 also caused DNA damage by detecting γH2AX and 8-hydroxy-2′-deoxyguanosine in oral cancer cells. In conclusion, SK2 is an effective enhancer for improving the UVC-caused antiproliferation against oral cancer cells in vitro. UVC/SK2 demonstrated a preferential and synergistic antiproliferation ability towards oral cancer cells with little adverse effects on normal cells.
A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
Authors: Störmer Johanna , Gwinner Wilfried , Derlin Katja , Immenschuh Stephan , Rong Song , Jang Mi-Sun , Shushakova Nelli , Haller Hermann , Gueler Faikah , Greite Robert
Published: May 2022

Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical AKI on the further course of AKI and on long-term renal consequences. Unilateral renal ischemia–reperfusion injury (IRI) for 15 min was performed in male CD1 mice to induce subclinical AKI. Immediately after surgery, single oral doses (100 mg or 200 mg) of diclofenac were administered. In a separate experimental series, repetitive treatment with 100 mg diclofenac over three days was performed after IRI and sham surgery. Renal morphology and pro-fibrotic markers were investigated 24 h and two weeks after the single dose and three days after the repetitive dose of diclofenac treatment using histology, immunofluorescence, and qPCR. Renal function was studied in a bilateral renal IRI model. A single oral dose of 200 mg, but not 100 mg, of diclofenac after IRI aggravated acute tubular injury after 24 h and caused interstitial fibrosis and tubular atrophy two weeks later. Repetitive treatment with 100 mg diclofenac over three days aggravated renal injury and caused upregulation of the pro-fibrotic marker fibronectin in the setting of subclinical AKI, but not in sham control kidneys. In conclusion, diclofenac aggravated renal injury in pre-existing subclinical AKI in a dose and time-dependent manner and already a single dose can cause progression to chronic kidney disease (CKD) in this model.
Resting-State Neural-Activity Alterations in Subacute Aphasia after Stroke
Authors: Xie Xiaohui , Zhang Ting , Bai Tongjian , Chen Chen , Ji Gong-Jun , Tian Yanghua , Yang Jinying , Wang Kai
Published: May 2022

Linguistic deficits are frequent symptoms among stroke survivors. The neural mechanism of post-stroke aphasia (PSA) was incompletely understood. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) was widely used among several neuropsychological disorders. However, previous rs-fMRI studies of PSA were limited to very small sample size and the absence of reproducibility with different neuroimaging indexes. The present study performed comparisons with static and dynamic amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) based on modest sample size (40 PSA and 37 healthy controls). Compared with controls, PSA showed significantly increased static ALFF predominantly in the bilateral supplementary motor area (SMA) and right hippocampus-parahippocampus (R HIP-ParaHip) and decreased static ALFF in right cerebellum. The increased dynamic ALFF in SMA and decreased dynamic ALFF in right cerebellum were also found in PSA. The static and dynamic ALFF in right cerebellum was positively correlated with spontaneous speech. The FC between the SMA and R HIP-ParaHip was significantly stronger in patients than controls and positively correlated with ALFF in bilateral SMA. In addition, the FC between the R HIP-ParaHip and the right temporal was also enhanced in patients and negatively correlated with repetition, naming, and comprehension score. These findings revealed consistently abnormal intrinsic neural activity in SMA and cerebellum, which may underlie linguistic deficits in PSA.
Immune Checkpoint Inhibitors as a Neoadjuvant/Adjuvant Treatment of Muscle-Invasive Bladder Cancer: A Systematic Review
Authors: Barone Biagio , Calogero Armando , Scafuri Luca , Ferro Matteo , Lucarelli Giuseppe , Di Zazzo Erika , Sicignano Enrico , Falcone Alfonso , Romano Lorenzo , De Luca Luigi , Oliva Francesco , Mirto Benito Fabio , Capone Federico , Imbimbo Ciro , Crocetto Felice
Published: May 2022

Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer.
Prognostic Value of Preclinical Markers after Radiotherapy of Metastatic Spinal Cord Compression—An Additional Analysis of Patients from Two Prospective Trials
Authors: Rades Dirk , Cacicedo Jon , Lomidze Darejan , Al-Salool Ahmed , Segedin Barbara , Groselj Blaz , Schild Steven E.
Published: May 2022

For optimal personalization of treatment for metastatic spinal cord compression (MSCC), the patient’s survival prognosis should be considered. Estimation of survival can be facilitated by prognostic factors. This study investigated the prognostic value of pre-treatment preclinical markers, namely hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), and c-reactive protein (CRP), in 190 patients from two prospective trials who had poor or intermediate survival prognoses and were irradiated for MSCC with motor deficits. In addition, clinical factors including radiation regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, visceral metastases, other bone metastases, time developing motor deficits, ambulatory status, sensory function, and sphincter function were evaluated. On univariate analyses, NLR (p = 0.033), LDH (p < 0.001), CRP (p < 0.001), tumor type (p < 0.001), pre-radiotherapy ambulatory status (p < 0.001), and sphincter function (p = 0.011) were significant. In the subsequent Cox regression analysis, LDH (p = 0.007), CRP (p = 0.047), tumor type (p = 0.003), and ambulatory status (p = 0.010) maintained significance. In addition to clinical factors, preclinical markers may help in estimating the survival of patients irradiated for MSCC. Additional prospective trials are warranted.
The Molecular Biology of Soft Tissue Sarcomas: Current Knowledge and Future Perspectives
Authors: Vibert Julien , Watson Sarah
Published: May 2022

Soft tissue sarcomas are malignant tumors of mesenchymal origin, encompassing a large spectrum of entities that were historically classified according to their histological characteristics. Over the last decades, molecular biology has allowed a better characterization of these tumors, leading to the incorporation of multiple molecular features in the latest classification of sarcomas as well as to molecularly-guided therapeutic strategies. This review discusses the main uses of molecular biology in current practice for the diagnosis and treatment of soft tissue sarcomas, in addition to perspectives for this rapidly evolving field of research.
Suppressors of Cytokine Signaling and Hepatocellular Carcinoma
Authors: Masuzaki Ryota , Kanda Tatsuo , Sasaki Reina , Matsumoto Naoki , Nirei Kazushige , Ogawa Masahiro , Karp Seth J. , Moriyama Mitsuhiko , Kogure Hirofumi
Published: May 2022

Cytokines are secreted soluble glycoproteins that regulate cellular growth, proliferation, and differentiation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling and form a classical negative feedback loop in the signaling pathways. There are eight members of the SOCS family. The SOCS proteins are all comprised of a loosely conserved N-terminal domain, a central Src homology 2 (SH2) domain, and a highly conserved SOCS box at the C-terminus. The role of SOCS proteins has been implicated in the regulation of cytokines and growth factors in liver diseases. The SOCS1 and SOCS3 proteins are involved in immune response and inhibit protective interferon signaling in viral hepatitis. A decreased expression of SOCS3 is associated with advanced stage and poor prognosis of patients with hepatocellular carcinoma (HCC). DNA methylations of SOCS1 and SOCS3 are found in HCC. Precise regulation of liver regeneration is influenced by stimulatory and inhibitory factors after partial hepatectomy (PH), in particular, SOCS2 and SOCS3 are induced at an early time point after PH. Evidence supporting the important role of SOCS signaling during liver regeneration also supports a role of SOCS signaling in HCC. Immuno-oncology drugs are now the first-line therapy for advanced HCC. The SOCS can be potential targets for HCC in terms of cell proliferation, cell differentiation, and immune response. In this literature review, we summarize recent findings of the SOCS family proteins related to HCC and liver diseases.
Blockade LAT1 Mediates Methionine Metabolism to Overcome Oxaliplatin Resistance under Hypoxia in Renal Cell Carcinoma
Authors: Xu Qingwen , Liu Yuxi , Sun Wen , Song Tiantian , Jiang Xintong , Zeng Kui , Zeng Su , Chen Lu , Yu Lushan
Published: May 2022

Hypoxic microenvironment and metabolic dysregulation of tumor impairs the therapeutic efficacy of chemotherapeutic drugs, resulting in drug resistance and tumor metastasis, which has always been a challenge for the treatment of solid tumors, including renal cell carcinoma (RCC). Herein, starting from the evaluation of methionine metabolism in RCC cells, we demonstrated that the increased methionine accumulation in RCC cells was mediated by L-type amino acid transporter 1 (LAT1) under hypoxia. Glutathione (GSH), as a methionine metabolite, would attenuate the therapeutic efficacy of oxaliplatin through chemical chelation. Reducing methionine uptake by LAT1 inhibitor JPH203 significantly enhanced the sensitivity of RCC cells to oxaliplatin by reducing GSH production in vitro and in vivo. Therefore, we proposed an effective and stable therapeutic strategy based on the combination of oxaliplatin and LAT1 inhibitor, which is expected to solve the resistance of RCC to platinum-based drugs under hypoxia to a certain extent, providing a meaningful insight into the development of new therapeutic strategies and RCC treatment
Monocarboxylate Transporters 1 and 4 and Prognosis in Small Bowel Neuroendocrine Tumors
Authors: Hiltunen Niko , Rintala Jukka , Väyrynen Juha P. , Böhm Jan , Karttunen Tuomo J. , Huhta Heikki , Helminen Olli
Published: May 2022

Monocarboxylate transporters (MCTs) are cell membrane proteins transporting lactate, pyruvate, and ketone bodies across the plasma membrane. The prognostic role of MCTs in neuroendocrine tumors is unknown. We aimed to analyze MCT1 and MCT4 expression in small bowel neuroendocrine tumors (SB-NETs). The cohort included 109 SB-NETs and 61 SB-NET lymph node metastases from two Finnish hospitals. Tumor samples were immunohistochemically stained with MCT1 and MCT4 monoclonal antibodies. The staining intensity, percentage of positive cells, and stromal staining were assessed. MCT1 and MCT4 scores (0, 1 or 2) were composed based on the staining intensity and the percentage of positive cells. Survival analyses were performed with the Kaplan–Meier method and Cox regression, adjusted for confounders. The primary outcome was disease-specific survival (DSS). A high MCT4 intensity in SB-NETs was associated with better DSS when compared to low intensity (85.7 vs. 56.6%, p = 0.020). A high MCT4 percentage of positive cells resulted in better DSS when compared to a low percentage (77.4 vs. 49.1%, p = 0.059). MCT4 scores 0, 1, and 2 showed DSS of 52.8 vs. 58.8 vs. 100% (p = 0.025), respectively. After adjusting for confounders, the mortality hazard was lowest in the patients with a high MCT4 score. MCT1 showed no association with survival. According to our study, a high MCT4 expression is associated with an improved prognosis in SB-NETs.
Infertility in Men: Advances towards a Comprehensive and Integrative Strategy for Precision Theranostics
Authors: Assidi Mourad
Published: May 2022

Male infertility is an increasing and serious medical concern, though the mechanism remains poorly understood. Impaired male reproductive function affects approximately half of infertile couples worldwide. Multiple factors related to the environment, genetics, age, and comorbidities have been associated with impaired sperm function. Present-day clinicians rely primarily on standard semen analysis to diagnose male reproductive potential and develop treatment strategies. To address sperm quality assessment bias and enhance analysis accuracy, the World Health Organization (WHO) has recommended standardized sperm testing; however, conventional diagnostic and therapeutic options for male infertility, including physical examination and semen standard analysis, remain ineffective in relieving the associated social burden. Instead, assisted reproductive techniques are becoming the primary therapeutic approach. In the post-genomic era, multiomics technologies that deeply interrogate the genome, transcriptome, proteome, and/or the epigenome, even at single-cell level, besides the breakthroughs in robotic surgery, stem cell therapy, and big data, offer promises towards solving semen quality deterioration and male factor infertility. This review highlights the complex etiology of male infertility, especially the roles of lifestyle and environmental factors, and discusses advanced technologies/methodologies used in characterizing its pathophysiology. A comprehensive combination of these innovative approaches in a global and multi-centric setting and fulfilling the suitable ethical consent could ensure optimal reproductive and developmental outcomes. These combinatorial approaches should allow for the development of diagnostic markers, molecular stratification classes, and personalized treatment strategies. Since lifestyle choices and environmental factors influence male fertility, their integration in any comprehensive approach is required for safe, proactive, cost-effective, and noninvasive precision male infertility theranostics that are affordable, accessible, and facilitate couples realizing their procreation dream.
Colonic Fluid and Electrolyte Transport 2022: An Update
Authors: Negussie Abel B. , Dell Annika C. , Davis Bruce A. , Geibel John P.
Published: May 2022

Colonic epithelial cells are responsible for maintaining a delicate balance between luminal secretion and the absorption of fluids and ions. This review aims to discuss and update the model of colonic electrolyte secretion and absorption via the cystic fibrosis transmembrane regulator (CFTR), epithelial sodium channel (ENaC), Na-K-Cl cotransporters (NKCC1 and 2), Na-H exchangers (NHE1–4), colonic H,KATPase, and several other key components involved in multi-level transepithelial ion transport. Developments in our understanding of the activity, regulation, localization, and relationships of these ion transporters and their interactions have helped forge a more robust understanding of colonic ion movement that accounts for the colonic epithelium’s role in mucosal pH modulation, the setting of osmotic gradients pivotal for fluid retention and secretion, and cell death regulation. Deviations from homeostatic ion transport cause diarrhea, constipation, and epithelial cell death and contribute to cystic fibrosis, irritable bowel syndrome (IBS), ulcerative colitis, and cancer pathologies. Signal transduction pathways that regulate electrolyte movement and the regulatory relationships between various sensors and transporters (CFTR as a target of CaSR regulation and as a regulator of ENaC and DRA, for example) are imperative aspects of a dynamic and comprehensive model of colonic ion homeostasis.
Mitochondrial Membrane Potential Identifies a Subpopulation of Mesenchymal Progenitor Cells to Promote Angiogenesis and Myocardial Repair
Authors: Li Xiuchun , Wang Xiaoliang , He Pan , Bennett Edward , Haggard Erin , Ma Jianjie , Cai Chuanxi
Published: May 2022

Identifying effective donor cells is one of obstacles that limits cell therapy for heart disease. In this study, we sorted a subpopulation of human mesenchymal progenitor cells (hMPCs) from the right atrial appendage using the low mitochondrial membrane potential. Compared to the non-sorted cells, hMPCs hold the capacity for stemness and enrich mesenchymal stem cell markers. The hMPCs display better ability for survival, faster proliferation, less production of reactive oxygen species (ROS), and greater release of cytoprotective cytokines. The hMPCs exhibit decreased expression of senescence genes and increased expression of anti-apoptotic and antioxidant genes. Intramyocardial injection of hMPCs into the infarcted heart resulted in increased left ventricular ejection fraction and reduced cardiac remodeling and infarct size in the group of animals receiving hMPCs. Both in vitro and in vivo studies indicated hMPCs have the potential to differentiate into endothelial cells and smooth muscle cells. Immunohistochemistry staining showed that cell therapy with hMPCs enhances cardiac vascular regeneration and cardiac proliferation, and decreases cardiac cell apoptosis, which is associated with the increased secretion of cytoprotective and pro-angiogenic cytokines. Overall, we discovered a subpopulation of human mesenchymal progenitor cells via their low mitochondrial membrane potential, which might provide an alternative donor cell source for cellular therapy for ischemic heart disease.
Self-Assembly of a Rare High Spin FeII/PdII Tetradecanuclear Cubic Cage Constructed via the Metalloligand Approach
Authors: Min Hyunsung , Craze Alexander R. , Taira Takahiro , Wallis Matthew J. , Bhadbhade Mohan M. , Tian Ruoming , Fanna Daniel J. , Wuhrer Richard , Hayami Shinya , Clegg Jack K. , Marjo Christopher E. , Lindoy Leonard F. , Li Feng
Published: May 2022

Polynuclear heterobimetallic coordination cages in which different metal cations are connected within a ligand scaffold are known to adopt a variety of polyhedral architectures, many of which display interesting functions. Within the extensive array of coordination cages incorporating Fe(II) centres reported so far, the majority contain low-spin (LS) Fe(II), with high-spin (HS) Fe(II) being less common. Herein, we present the synthesis and characterisation of a new tetradecanuclear heterobimetallic [Fe8Pd6L8](BF4]28 (1) cubic cage utilising the metalloligand approach. Use of the tripodal tris-imidazolimine derivative (2) permitted the formation of the tripodal HS Fe(II) metalloligand [FeL](BF4)2·CH3OH (3) that was subsequently used to form the coordination cage 1. Magnetic and structural analyses gave insight into the manner in which the HS environment of the metalloligand was transferred into the cage architecture along with the structural changes that accompanied its occupancy of the eight corners of the discrete cubic structure.
Multiphase Interpolating Digital Power Amplifiers for TX Beamforming
Authors: Bai Zhidong , Yuan Wen , Azam Ali , Walling Jeffrey S.
Published: May 2022

This paper presents a four-channel beamforming TX implemented in 65 nm CMOS. Each beamforming TX is comprised of a C-2C split-array multiphase switched-capacitor power amplifier (SAMP-SCPA). This is the first use of multiphase interpolation (MPI) for beam steering. This technique is ideal for low-frequency beamforming and MIMO, as it does not require passive or LO-based phase shifters. The SCPA is ideal for use as the core element since it can perform frequency translation and data conversion, and drive an output at high power and efficiency in a compact die area. A prototype four-element beamforming TX, occupying 2mm×2.5mm, can achieve a peak output power of 24.4 dBm with a peak system efficiency (SE) of 24%, while achieving <1∘ phase resolution and <1 dB gain error. When transmitting a 15 MHz, 64-QAM long-term evolution (LTE) signal it outputs 18.4 dBm at 14% SE with a measured adjacent channel leakage ratio (ACLR) of <−30 dBc and an error vector magnitude (EVM) of 3.27% RMS at 1.75 GHz. A synthesized beam pattern based on measured results from a single die achieves <0.32∘ RMS beam angle error and <0.1 dB RMS beam amplitude error.
Controlled Synthesis and Photoresponsive Properties of Spiropyran End-Functionalized Poly(vinyl ether)s
Authors: Motoyanagi Jin , Fujishima Ayane , Minoda Masahiko
Published: May 2022

Due to the need to develop smart materials for a variety of applications such as catalysts and drug delivery, the development of photoresponsive polymers is receiving increasing attention. In particular, the photoisomerization of spiropyran (SP), unlike many other photoresponsive compounds, has attracted attention because it dramatically changes not only the molecular structure but also the polarity of the molecule. However, in most cases where SP is used as a photoresponsive functional group, SP is introduced in the side chain of the polymer, and few cases have been reported in which SP is introduced at the end of the polymer chain. Therefore, we designed a new amphipathic poly(vinyl ether) with an SP moiety at the end of the polymer chain. First, an initiator having an SP moiety was synthesized and used for living cationic polymerization to synthesize a poly(vinyl ether) bearing an SP moiety at the end of the polymer chain. Furthermore, we investigated the photoresponsive properties of the obtained polymers, we found that self-assembly of the amphiphilic polymers could be controlled by photoirradiation.
High Temperature Superconducting Flux Pumps for Contactless Energization
Authors: Wen Zezhao , Zhang Hongye , Mueller Markus
Published: May 2022

The development of superconducting technology has seen continuously increasing interest, especially in the area of clean power systems and electrification of transport with low CO2 emission. Electric machines, as the major producer and consumer of the global electrical energy, have played a critical role in achieving zero carbon emission. The superior current carrying capacity of superconductors with zero DC loss opens the way to the next-generation electric machines characterized by much higher efficiency and power density compared to conventional machines. The persistent current mode is the optimal working condition for a superconducting magnet, and thus the energization of superconducting field windings has become a crucial challenge to be tackled, to which high temperature superconducting (HTS) flux pumps have been proposed as a promising solution. An HTS flux pump enables current injection into a closed superconducting coil wirelessly and provides continuous compensation to offset current decay, avoiding excessive cryogenic losses and sophisticated power electronics facilities. Despite many publications regarding the design and analyses of various types of HTS flux pumps, the practical application of HTS flux pumps in a high-performance superconducting machine has been rarely reported. Therefore, it is of significance to specify the main challenges for building and implementing a reliable HTS flux pump. In addition, the physical mechanisms of distinct HTS flux pumps have caused some confusion, which should be clarified. Above all, a systematic review of the recent development and progress of HTS flux pumps remains lacking. Given the above-mentioned issues, this paper summarized the most up-to-date advances of this emerging technology, clarified the working mechanisms and commonly adopted modeling approaches, presented objective analyses of the applicability of various HTS flux pumps, specified the primary challenges for implementing HTS flux pumps, and proposed useful suggestions to improve this wireless excitation technology. The overall aim of this work is to bring a deep insight into the understanding of HTS flux pumps and provide comprehensive guidance for their future research and applications.