bluuebunny/crossref_metadata_2025 huggingface dataset:
Redundant Robot with Pneumatic Artificial Muscles for Rehabilitation Works Using Iterative Learning Control
Authors: Chu Wen-Lin , Lin Chih-Jer , Chen You-Yuan
Published: August 2022

This study aims to develop a multi-functional robotic arm with a multi-degree of freedom using a pneumatic artificial muscle cylinder as the main actuator, with a wearable function. While wearing the robotic arm, it has four degrees of freedom and can be used as an upper limb rehabilitation aid to perform rehabilitation exercise tasks. The rotating axes are driven by pneumatic artificial muscle cylinders to ensure the safety and flexibility of the robot interaction. By integrating multiple pneumatic control valves and sensors with embedded interface cards, the control of pneumatic artificial muscle cylinders is performed, and the rehabilitation trajectory commands are planned through the kinematics of the robotic arm, and a closed-loop control system is established to enable the robotic arm to achieve the task of rehabilitation trajectory tracking. In the single-axis robotic arm controller experiment, it was found that the LMS-PID is superior to the conventional PID control method. In the control experiment of the robotic arm under the multi-axis recovery trajectory, the result showed that the training of drawing a circle on the wall could be successfully planned. In the multi-axis robotic tracking experiment under the rehabilitation trajectory, the result showed that the RMSE of the tracking trajectory decreased to 0.2444 and 0.2853. In the robotic arm joining/loading experiment, it was shown that the method of this study can withstand some loading effects. Moreover, this study introduces iterative learning control to improve the non-linear compensation and phase lag problems of the PID controller so that the robot arm can have a certain tracking accuracy under the round-trip robust trajectory.
Efficient Batch Fully Homomorphic Encryption with a Shorter Key from Ring-LWE
Authors: Chen Yuyue , Huang Ruwei , Yang Bo
Published: August 2022

Fully homomorphic encryption allows users to use the computing resources of cloud servers for the computation of encrypted data without worrying about data leakage. The fully homomorphic encryption approach has problems with excessive noise and the expansion of the ciphertext dimension after the homomorphic evaluation. The key switching technology effectively solves the problem of the ciphertext dimension expansion. The generated evaluation key is a masked secret key that must be shared between the data owner and the computational entity, so the security must be guaranteed. In the RLWE-based FHE scheme, the efficiency improvement of the key switching depends on the circular security assumption, meaning the security needs to be improved. To solve the above problems, we select the secret key from the noise distribution with variable parameters so that the evaluation key and the initial noise of the encryption scheme are smaller. Specifically, the secret key is replaced after each homomorphic evaluation to ensure the security. We use the “modulus scaling” method to control the noise generated by itself, rather than the BitDecomp technology, which is complex when applied to polynomials. Finally, we combine the packing technology that relies on the polynomial CRT (Chinese remainder theorem) to design a batch-leveled fully homomorphic encryption scheme. We analyze the scheme’s noise, security proof, and specific security parameters. Compared with the FV12 scheme, our scheme is more secure. Compared with the MB18 scheme, our evaluation key size is smaller.
Interdecadal Change in the Relationship between the Winter Siberian High and Summer Tropical Cyclone Genesis Frequency over the Western North Pacific
Authors: Gong Yi-Fei , Zhou Fang , Wang Chao , Shi Jian
Published: August 2022

Interdecadal change in the relationship between the winter Siberian high (SH) and tropical cyclone genesis frequency (TCGF) is investigated using observational and reanalysis data. Focus is on the Western North Pacific (WNP) where environmental background associated with TCGF is closely related to the winter SH. It is demonstrated that the relationship presents clear interdecadal change during 1980–2020. A significant negative correlation dominates in the last two decades of the 20th century (P1), but it clearly weakens from the early 2000s onward (P2). Observational evidence shows that such interdecadal change is related dominantly to variations in the air–sea responses associated with the winter SH over the North Pacific. During P1, when the SH is anomalously strengthened, an Aleutian Low (AL) response occurs over the downstream North Pacific, which gradually develops into a meridional dipole distribution pattern consistent with the negative North Pacific Oscillation (NPO) mode during the following spring. The northeasterly wind anomaly over the subtropical North Pacific maintains and further delivers into the tropical Pacific. It favors easterly wind anomaly enhancement over the tropical Pacific around summer and grows into an anticyclonic circulation response in the WNP, which restrains the genesis of TCs. During P2, the eastward shift of the SH anomaly favors a weak AL over the Northeast Pacific followed by a northeastward-shifted anticyclone over the subtropical central-eastern Pacific, which confines the relatively weak northeasterly wind anomalies far away from the tropical Pacific. This was concurrent with a weakening relationship between the SH and WNP TCGF, indicating weaker downstream impacts of the winter SH.
Genome-Based Analysis of Verticillium Polyketide Synthase Gene Clusters
Authors: Sayari Mohammad , Dolatabadian Aria , El-Shetehy Mohamed , Rehal Pawanpuneet Kaur , Daayf Fouad
Published: August 2022

Polyketides are structurally diverse and physiologically active secondary metabolites produced by many organisms, including fungi. The biosynthesis of polyketides from acyl-CoA thioesters is catalyzed by polyketide synthases, PKSs. Polyketides play roles including in cell protection against oxidative stress, non-constitutive (toxic) roles in cell membranes, and promoting the survival of the host organisms. The genus Verticillium comprises many species that affect a wide range of organisms including plants, insects, and other fungi. Many are known as causal agents of Verticillium wilt diseases in plants. In this study, a comparative genomics approach involving several Verticillium species led us to evaluate the potential of Verticillium species for producing polyketides and to identify putative polyketide biosynthesis gene clusters. The next step was to characterize them and predict the types of polyketide compounds they might produce. We used publicly available sequences from ten species of Verticillium including V. dahliae, V. longisporum, V. nonalfalfae, V. alfalfae, V. nubilum, V. zaregamsianum, V. klebahnii, V. tricorpus, V. isaacii, and V. albo-atrum to identify and characterize PKS gene clusters by utilizing a range of bioinformatic and phylogenetic approaches. We found 32 putative PKS genes and possible clusters in the genomes of Verticillium species. All the clusters appear to be complete and functional. In addition, at least five clusters including putative DHN-melanin-, cytochalasin-, fusarielien-, fujikurin-, and lijiquinone-like compounds may belong to the active PKS repertoire of Verticillium. These results will pave the way for further functional studies to understand the role of these clusters.
Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology
Authors: Inci Nurcan , Akyildiz Erdogan Oguzhan , Bulbul Abdullah Alper , Turanli Eda Tahir , Akgun Emel , Baykal Ahmet Tarik , Colak Faruk , Bozaykut Perinur
Published: August 2022

The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK–STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK–STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK–STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.
Autologous Platelet Concentrates (APCs) for Hard Tissue Regeneration in Oral Implantology, Sinus Floor Elevation, Peri-Implantitis, Socket Preservation, and Medication-Related Osteonecrosis of the Jaw (MRONJ): A Literature Review
Authors: Mijiritsky Eitan , Assaf Haya Drora , Kolerman Roni , Mangani Luca , Ivanova Vasilena , Zlatev Stefan
Published: August 2022

Over recent years, the usage of autologous platelet concentrates (APCs) has risen in hard tissue regeneration and oral implantology. The purpose of the present review is to offer an overview of the use of three APC techniques in dentistry: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF). A narrative summary of articles published between January 2011 and April 2022 is provided. The PubMed, Cochrane Library, Scopus, and Embase databases were used to conduct the search. The following keywords were used in the preliminary: “VEGF”, “TGF-b1”, “PRP”, “PRF”, “CGF”, AND “sinus augmentation” OR “implants” OR “peri-implantitis” OR “socket preservation” OR “MRONJ”. A total of 82 articles was finally included. The review then takes into account the application of the three techniques in different areas of treatment—including oral implantology, sinus floor elevation, peri-implantitis, socket preservation, and medication-related osteonecrosis of the jaw (MRONJ)—as well as their advantages and disadvantages.
Iridium-Functionalized Cellulose Microcrystals as a Novel Luminescent Biomaterial for Biocomposites
Authors: Maturi Mirko , Spanu Chiara , Baschieri Andrea , Comes Franchini Mauro , Locatelli Erica , Sambri Letizia
Published: August 2022

Microcrystalline cellulose (MCC) is an emerging material with outstanding properties in many scientific and industrial fields, in particular as an additive in composite materials. Its surface modification allows for the fine-tuning of its properties and the exploitation of these materials in a plethora of applications. In this paper, we present the covalent linkage of a luminescent Ir-complex onto the surface of MCC, representing the first incorporation of an organometallic luminescent probe in this biomaterial. This goal has been achieved with an easy and sustainable procedure, which employs a Bronsted-acid ionic liquid as a catalyst for the esterification reaction of -OH cellulose surface groups. The obtained luminescent cellulose microcrystals display high and stable emissions with the incorporation of only a small amount of iridium (III). Incorporation of MCC-Ir in dry and wet matrices, such as films and gels, has been also demonstrated, showing the maintenance of the luminescent properties even in possible final manufacturers.
Current Screening Strategies for Pancreatic Cancer
Authors: Vanek Petr , Urban Ondrej , Zoundjiekpon Vincent , Falt Premysl
Published: August 2022

Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Radical surgery is the only potential curative procedure. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. Early detection of PDAC is thus considered to be the most effective way to improve survival. In this regard, pancreatic screening has been proposed to improve results by detecting asymptomatic stages of PDAC and its precursors. There is now evidence of benefits of systematic surveillance in high-risk individuals, and the current guidelines emphasize the potential of screening to affect overall survival in individuals with genetic susceptibility syndromes or familial occurrence of PDAC. Here we aim to summarize the current knowledge about screening strategies for PDAC, including the latest epidemiological data, risk factors, associated hereditary syndromes, available screening modalities, benefits, limitations, as well as management implications.
Microbiota Dysbiosis in Parkinson Disease—In Search of a Biomarker
Authors: Nowak Julia Maya , Kopczyński Mateusz , Friedman Andrzej , Koziorowski Dariusz , Figura Monika
Published: August 2022

Numerous studies have highlighted the role of the gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced by specific gut bacteria. This review’s aim is to identify gut bacterial biomarkers of Parkinson disease. A comprehensive search for original research papers on gut microbiota composition in Parkinson disease was conducted using the PubMed, Embase, and Scopus databases. Research papers on intestinal permeability, nasal and oral microbiomes, and interventional studies were excluded. The yielded results were categorized into four groups: Parkinson disease vs. healthy controls; disease severity; non-motor symptoms; and clinical phenotypes. This review was conducted in accordance with the PRISMA 2020 statement. A total of 51 studies met the eligibility criteria. In the Parkinson disease vs. healthy controls group, 22 bacteria were deemed potentially important. In the disease severity category, two bacteria were distinguished. In the non-motor symptoms and clinical phenotypes categories, no distinct pathogen was identified. The studies in this review report bacteria of varying taxonomic levels, which prevents the authors from reaching a clear conclusion. Future research should follow a unified methodology in order to identify potential biomarkers for Parkinson disease.
Applications of Gelatin in Biosensors: Recent Trends and Progress
Authors: Guan Yuepeng , Huang Yaqin , Li Tianyu
Published: August 2022

Gelatin is a natural protein from animal tissue with excellent biocompatibility, biodegradability, biosafety, low cost, and sol–gel property. By taking advantage of these properties, gelatin is considered to be an ideal component for the fabrication of biosensors. In recent years, biosensors with gelatin have been widely used for detecting various analytes, such as glucose, hydrogen peroxide, urea, amino acids, and pesticides, in the fields of medical diagnosis, food testing, and environmental monitoring. This perspective is an overview of the most recent trends and progress in the development of gelatin-based biosensors, which are classified by the function of gelatin as a matrix for immobilized biorecognition materials or as a biorecognition material for detecting target analytes.
Integration of Multiple Interferometers in Highly Multiplexed Diagnostic KITs to Evaluate Several Biomarkers of COVID-19 in Serum
Authors: Murillo Ana María M. , Valle Luis G. , Ramírez Yolanda , Sánchez María Jesús , Santamaría Beatriz , Molina-Roldan E. , Ortega-Madueño Isabel , Urcelay Elena , Tramarin Luca , Herreros Pedro , Díaz-Perales Araceli , Garrido-Arandia María , Tome-Amat Jaime , Hernández-Ramírez Guadalupe , Espinosa Rocío L. , Laguna María F. , Holgado Miguel
Published: August 2022

In the present work, highly multiplexed diagnostic KITs based on an Interferometric Optical Detection Method (IODM) were developed to evaluate six Coronavirus Disease 2019 (COVID-19)-related biomarkers. These biomarkers of COVID-19 were evaluated in 74 serum samples from severe, moderate, and mild patients with positive polymerase chain reaction (PCR), collected at the end of March 2020 in the Hospital Clínico San Carlos, in Madrid (Spain). The developed multiplexed diagnostic KITs were biofunctionalized to simultaneously measure different types of specific biomarkers involved in COVID-19. Thus, the serum samples were investigated by measuring the total specific Immunoglobulins (sIgT), specific Immunoglobulins G (sIgG), specific Immunoglobulins M (sIgM), specific Immunoglobulins A (sIgA), all of them against SARS-CoV-2, together with two biomarkers involved in inflammatory disorders, Ferritin (FER) and C Reactive Protein (CRP). To assess the results, a Multiple Linear Regression Model (MLRM) was carried out to study the influence of IgGs, IgMs, IgAs, FER, and CRP against the total sIgTs in these serum samples with a goodness of fit of 73.01% (Adjusted R-Squared).
Low Platinum-Content Electrocatalysts for Highly Sensitive Detection of Endogenously Released H2O2
Authors: Morais Ana , Rijo Patrícia , Batanero Belen , Nicolai Marisa
Published: August 2022

The commercial viability of electrochemical sensors requires high catalytic efficiency electrode materials. A sluggish reaction of the sensor’s primary target species will require a high overpotential and, consequently, an excessive load of catalyst material to be used. Therefore, it is essential to understand nanocatalysts’ fundamental structures and typical catalytic properties to choose the most efficient material according to the biosensor target species. Catalytic activities of Pt-based catalysts have been significantly improved over the decades. Thus, electrodes using platinum nanocatalysts have demonstrated high power densities, with Pt loading considerably reduced on the electrodes. The high surface-to-volume ratio, higher electron transfer rate, and the simple functionalisation process are the main reasons that transition metal NPs have gained much attention in constructing high-sensitivity sensors. This study has designed to describe and highlight the performances of the different Pt-based bimetallic nanoparticles and alloys as an enzyme-free catalytic material for the sensitive electrochemical detection of H2O2. The current analysis may provide a promising platform for the prospective construction of Pt-based electrodes and their affinity matrix.
Recent Advances in Digital Biosensing Technology
Authors: Curtin Kathrine , Fike Bethany J. , Binkley Brandi , Godary Toktam , Li Peng
Published: August 2022

Digital biosensing assays demonstrate remarkable advantages over conventional biosensing systems because of their ability to achieve single-molecule detection and absolute quantification. Unlike traditional low-abundance biomarking screening, digital-based biosensing systems reduce sample volumes significantly to the fL-nL level, which vastly reduces overall reagent consumption, improves reaction time and throughput, and enables high sensitivity and single target detection. This review presents the current technology for compartmentalizing reactions and their applications in detecting proteins and nucleic acids. We also analyze existing challenges and future opportunities associated with digital biosensing and research opportunities for developing integrated digital biosensing systems.
Astrocytic CD24 Protects Neuron from Recombinant High-Mobility Group Box 1 Protein(rHMGB1)-Elicited Neuronal Injury
Authors: Pang Cong , Gao Sen , Liu Xun-Zhi , Li Xiao-Jian , Peng Zheng , Zhang Hua-Sheng , Zhou Yan , Chen Xiang-Xin , Tao Tao , Lu Yue , Li Wei , Hang Chun-Hua
Published: August 2022

Endogenous host-derived molecules named damage-associated molecular patterns (DAMPs) can induce excessive non-sterile inflammatory responses on recognition of specific membrane-tethered receptors. Here in this study, we aimed to explore the role of DAMP molecule HMGB1 in astrocyte-mediated sterile neuroinflammation and the resultant influences on neurons. In vitro cultured astrocytes were challenged with rHMGB1 and then harvested at 6 h, 12 h, 24 h, 36 h, and 48 h, respectively. The astrocytic CD24 expression was determined by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence, nuclear factor kappa B (NF-κB) binding activity was detected by electrophoretic mobility shift assay (EMSA), and the proinflammatory factors, tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β), were measured by qPCR. The neuronal morphology was assessed with phase-contrast microscopy. The results showed that astrocytic mRNA and protein CD24 expression began to rise at 24 h, peaked at 36 h, and remained elevated at 48 h after rHMGB1 stimulation, accompanied with enhanced NF-κB binding activity and augmented expression of TNF-α and IL-1β. Furthermore, rHMGB1 caused cocultured neuron damage and was aggregated upon CD24 knockdown. Taken together, these novel findings suggested that rHMGB1 could promote astrocytic CD24 expression, the inhibition of which could aggregate neuronal damage.
The Over-Strength Coefficient of Masonry-Infilled RC Frame Structures under Bidirectional Ground Motions
Authors: Wang Xiaomin , Su Yuhan , Kong Jingchang , Gong Maosheng , Liu Chunhui
Published: August 2022

The over-strength coefficient is one of the key factors for the seismic safety of a structure. For RC frames, the infill wall may improve the lateral bearing capacity, while the seismic demand increases as well, which leads to the unexpected seismic performance of an infilled RC frame in past earthquakes. Therefore, it is necessary to systematically study the over-strength effect of the infilled RC frames from the point of seismic capacity and demand. In this paper, 36 RC frame structures with/without infill walls are designed, and the corresponding finite element modelings, considering the in-plane and out-of-plane performance coupling effect of infill walls, are established to conduct incremental dynamic analyses (IDA). The seismic capacity values of over-strength coefficients are calculated, utilizing the IDA results under bidirectional ground motions. The effects of seismic precautionary intensity and number of stories on the over-strength coefficient of the RC frame with/without infill walls are discussed. The over-strength coefficient capacity value of the infilled frame is apparently higher than that of the bare frame, due to the contribution of infill walls. However, the seismic demand analysis of the over-strength coefficient shows that the capacity–demand ratio of masonry-infilled RC frame structures is greatly reduced, especially for the bottom soft-story infilled frame.
A Comprehensive Study on the Effect of Regular and Staggered Openings on the Seismic Performance of Shear Walls
Authors: Saeed Ahmed , Najm Hadee Mohammed , Hassan Amer , Qaidi Shaker , Sabri Mohanad Muayad Sabri , Mashaan Nuha S.
Published: August 2022

Shear walls have high strength and stiffness, which could be used at the same time to resist large horizontal loads and weight loads, making them pretty beneficial in several structural engineering applications. The shear walls could be included with openings, such as doors and windows, for relevant functional requirements. In the current study, a building of G + 13 stories with RC shear walls with and without openings has been investigated using ETABS Software. The seismic analysis is carried out for the determination of parameters like shear forces, drift, base shear, and story displacement for numerous models. The regular and staggered openings of the shear wall have been considered variables in the models. The dynamic analysis is carried out with the help of ETABS software. It has been observed that shear walls without openings models perform better than other models, and this is in agreement with the previous studies published in this area. This investigation also shows that the seismic behaviour of the shear wall with regular openings provides a close result to the shear wall with staggered openings. At the roof, the displacement of the model with regular openings was 38.99 mm and approximately 39.163 mm for the model with staggered openings. However, the model without a shear wall experienced a displacement of about 56 mm at the roof. Generally, it can be concluded that the openings have a substantial effect on the seismic behaviour of the shear wall, and that should be taken into consideration during the construction design. However, the type of opening (regular or staggered) has a slight effect on the behaviour of shear walls.
Pegfilgrastim in Supportive Care of Hodgkin Lymphoma
Authors: Cerchione Claudio , Nappi Davide , Romano Alessandra , Martinelli Giovanni
Published: August 2022

Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment.
BRAF Mutations in Colorectal Liver Metastases: Prognostic Implications and Potential Therapeutic Strategies
Authors: Wang Pei-Pei , Lin Chen , Wang Jane , Margonis Georgios Antonios , Wu Bin
Published: August 2022

Surgery combined with chemotherapy and precision medicine is the only potential treatment for patients with colorectal cancer liver metastases (CRLM). The use of modern molecular biotechnology to identify suitable biomarkers is of great significance for predicting prognosis and formulating individualized treatment plans for these patients. BRAF mutations, particularly V600E, are widely believed to be associated with poor prognosis in patients with metastatic CRC (mCRC). However, it is unclear which specific factors affect the prognosis of CRLM patients with BRAF mutations. It is also unknown whether patients with resectable CRLM and BRAF mutations should undergo surgical treatment since there is an increased recurrence rate after surgery in these patients. In this review, we combined the molecular mechanism and clinical characteristics of BRAF mutations to explore the prognostic significance and potential targeted therapy strategies for patients with BRAF-mutated CRLM.
Characterization of the Metabolome of Breast Tissues from Non-Hispanic Black and Non-Hispanic White Women Reveals Correlations between Microbial Dysbiosis and Enhanced Lipid Metabolism Pathways in Triple-Negative Breast Tumors
Authors: Smith Alana , Cao Xueyuan , Gu Qingqing , Kubi Amos-Abanyie Ernestine , Tolley Elizabeth A. , Vidal Gregory , Lyn-Cook Beverly , Starlard-Davenport Athena
Published: August 2022

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that is non-responsive to hormonal therapies and disproportionately impact women of African ancestry. We previously showed that TN breast tumors have a distinct microbial signature that differs from less aggressive breast tumor subtypes and normal breast tissues. However, it is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The goal of this global metabolomic profiling study was to investigate alterations in microbial metabolism pathways in normal and breast tumor tissues, including TNBC, of non-Hispanic black (NHB) and non-Hispanic white (NHW) women. In this study, we profiled the microbiome (16S rRNA) from breast tumor tissues and analyzed 984 metabolites from a total of 51 NHB and NHW women. Breast tumor tissues were collected from 15 patients with TNBC, 12 patients with less aggressive luminal A-type (Luminal) breast cancer, and 24 healthy controls for comparison using UHPLC-tandem mass spectrometry. Principal component analysis and hierarchical clustering of the global metabolomic profiling data revealed separation between metabolic signatures of normal and breast tumor tissues. Random forest analysis revealed a unique biochemical signature associated with elevated lipid metabolites and lower levels of microbial-derived metabolites important in controlling inflammation and immune responses in breast tumor tissues. Significant relationships between the breast microbiome and the metabolome, particularly lipid metabolism, were observed in TNBC tissues. Further investigations to determine whether alterations in sphingolipid, phospholipid, ceramide, amino acid, and energy metabolism pathways modulate Fusobacterium and Tenericutes abundance and composition to alter host metabolism in TNBC are necessary to help us understand the risk and underlying mechanisms and to identify potential microbial-based targets.
Dysregulated Expression of Three Genes in Colorectal Cancer Stratifies Patients into Three Risk Groups
Authors: Rodriguez Alba , Corchete Luís Antonio , Alcazar José Antonio , Montero Juan Carlos , Rodriguez Marta , Chinchilla-Tábora Luis Miguel , Vidal Tocino Rosario , Moyano Carlos , Muñoz-Bravo Saray , Sayagués José María , Abad Mar
Published: August 2022

Despite advances in recent years in the study of the molecular profile of sporadic colorectal cancer (sCRC), the specific genetic events that lead to increased aggressiveness or the development of the metastatic process of tumours are not yet clear. In previous studies of the gene expression profile (GEP) using a high-density array (50,000 genes and 6000 miRNAs in a single assay) in sCRC tumours, we identified a 28-gene signature that was found to be associated with an adverse prognostic value for predicting patient survival. Here, we analyse the differential expression of these 28 genes for their possible association with tumour local aggressiveness and metastatic processes in 66 consecutive sCRC patients, followed for >5 years, using the NanoString nCounter platform. The global transcription profile (expression levels of the 28 genes studied simultaneously) allowed us to discriminate between sCRC tumours and nontumoral colonic tissues. Analysis of the biological and functional significance of the dysregulated GEPs observed in our sCRC tumours revealed 31 significantly altered canonical pathways. Among the most commonly altered pathways, we observed the increased expression of genes involved in signalling pathways and cellular processes, such as the PI3K-Akt pathway, the interaction with the extracellular matrix (ECM), and other functions related to cell signalling processes (SRPX2). From a prognostic viewpoint, the altered expression of BST2 and SRPX2 genes were the only independent variables predicting for disease-free survival (DFS). In addition to the pT stage at diagnosis, dysregulated transcripts of ADH1B, BST2, and FER1L4 genes showed a prognostic impact on OS in the multivariate analysis. Based on the altered expression of these three genes, a scoring system was built to stratify patients into low-, intermediate-, and high-risk groups with significantly different 5-year OS rates: 91%, 83%, and 52%, respectively. The prognostic impact was validated in two independent series of sCRC patients from the public GEO database (n = 562 patients). In summary, we show a strong association between the altered expression of three genes and the clinical outcome of sCRC patients, making them potential markers of suitability for adjuvant therapy after complete tumour resection. Additional prospective studies in larger series of patients are required to confirm the clinical utility of the newly identified biomarkers because the number of patients analysed remains small.
Active Observation of Biochemical Recurrence without Treatment following Radical Prostatectomy: Long-Term Analysis of Outcomes
Authors: Huang Erica , Huynh Linda My , Tran Joshua , Gordon Adam M. , Chandhoke Ryan , Morales Blanca , Skarecky Douglas , Ahlering Thomas E.
Published: August 2022

Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of prostate cancer (PC) progression. This study was a retrospective cohort analysis of prospectively collected data (407/1895) of men with BCR at a tertiary referral center. Patients were assessed for active observation (AO) compared with a treatment group (TG) utilizing doubling time (DT) kinetics. Risk assessment was based on the initial DT (>12 vs. <12 months), then based on the DT pattern (changed over time). Those with unstable, rapidly decreasing DTs received treatment. Those with increasing and slowly decreasing DTs prompted observation. The primary outcome was PC mortality, safety, and efficacy of observations based on DT kinetics. The secondary outcome was BCR patients managed with or without treatment. The median follow-up was 7.5 years (IQR 3.9–10.7). The PCSM in TG and AO was 10.7% and 0%, respectively (p < 0.001). The initial DT was >12 months in 73.6% of AO versus 22.6% of TG (p < 0.001). An increasing DT pattern was observed in 71.5% of AO versus 32.7% of TG (p < 0.001). Utilizing the Cleveland Clinic’s PCSM nomogram, at 10 years, predicted and observed PCSM was 8.6% and 9.5% (p = 0.78), respectively. In conclusion, one-third of patients with BCR post-RP were managed without treatment using DT kinetics, avoiding treatment-related complications, quality-of-life issues, and expenses.
Multiple Myeloma Therapy: Emerging Trends and Challenges
Authors: Dima Danai , Jiang Dongxu , Singh Divya Jyoti , Hasipek Metis , Shah Haikoo S. , Ullah Fauzia , Khouri Jack , Maciejewski Jaroslaw P. , Jha Babal K.
Published: August 2022

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergence of genetically heterogeneous sub-clones are the major causes of the relapsed-refractory state of MM. Cytopenias from cumulative treatment toxicity and disease refractoriness limit therapeutic options, hence creating an urgent need for innovative approaches effective against highly heterogeneous myeloma cell populations. Here, we present a comprehensive overview of the current and future treatment paradigm of MM, and highlight the gaps in therapeutic translations of recent advances in targeted therapy and immunotherapy. We also discuss the therapeutic potential of emerging preclinical research in multiple myeloma.
Sr2TiO4 Prepared Using Mechanochemical Activation: Influence of the Initial Compounds’ Nature on Formation, Structural and Catalytic Properties in Oxidative Coupling of Methane
Authors: Pavlova Svetlana , Ivanova Yulia , Tsybulya Sergey , Chesalov Yurii , Nartova Anna , Suprun Evgenii , Isupova Lyubov
Published: August 2022

Methane oxidative coupling (OCM) is considered a potential direct route to produce C2 hydrocarbons. Layered perovskite-like Sr2TiO4 is a promising OCM catalyst. Mechanochemical activation (MA) is known to be an environmentally friendly method for perovskite synthesis. Sr2TiO4 were synthesized using MA of the mixtures containing SrCO3 or SrO and TiO2 or TiO(OH)2 and annealing at 900 and 1100 °C. XRD and FT-IRS showed that MA leads to the starting component disordering and formation of SrTiO3 only for SrO being pronounced when using TiO(OH)2. After annealing at 900 °C, Sr2TiO4 was mainly produced from the mixtures of SrCO3 or SrO and TiO(OH)2. The single-phase Sr2TiO4 was only obtained from MA products containing SrCO3 after calcination at 1100 °C. The surface enrichment with Sr was observed by XPS for all samples annealed at 1100 °C depending on the MA product composition. The OCM activity of the samples correlated with the surface Sr concentration and the ratio of the surface oxygen amount in SrO and perovskite (Oo/Op). The maximal CH4 conversion and C2 yield (25.6 and 15.5% at 900 °C, respectively), and the high long-term stability were observed for the sample obtained from (SrCO3 + TiO2), showing the specific surface morphology and optimal values of the surface Sr concentration and Oo/Op ratio.
Chemical Composition of the Surface and Subsurface of Pt–Pd–Rh–Ru Catalytic Gauzes Used in the NH3 Oxidation with Air at 1133 K
Authors: Salanov Aleksei , Serkova Alexandra , Kalinkin Alexandr , Isupova Lyubov , Parmon Valentin
Published: August 2022

High-temperature oxidation of NH3 on Pt alloy gauzes to NO is widely employed in industry for the production of HNO3, which is used to obtain agricultural fertilizers. Particular attention is paid now to the investigation of the chemical composition of gauzes used in NH3 oxidation. X-ray photoelectron and energy-dispersive X-ray spectroscopies with the depth of analysis ca. 5 nm and ca. 500 nm were applied to investigate the chemical composition of surface and subsurface layers of the new and used in NH3 oxidation with air at T = 1133 K Pt–Pd–Rh–Ru catalytic gauzes (81, 15, 3.5, 0.5 wt.%, respectively). For all the gauzes, adsorption (OHad, COad), graphitic (Cgr) and oxide (Rh2O3) films were found on the surface of the metallic alloy. Under these films, Cab, Nab and Oab atoms absorbed in the subsurface layers were detected on the gauzes used in NH3 oxidation. The obtained data testify to the penetration of Oab and Nab atoms into deeper layers of the alloy during etching with elevation of the catalyst temperature. Oab atoms were accumulated predominantly on dislocations, etch pits and grain boundaries, whereas Nab atoms intercalated mostly into interstitial sites of the alloy lattice.
Hepatic, Extrahepatic and Extracellular Vesicle Cytochrome P450 2E1 in Alcohol and Acetaminophen-Mediated Adverse Interactions and Potential Treatment Options
Authors: Kumar Santosh , Singla Bhupesh , Singh Ajay K. , Thomas-Gooch Stacey M. , Zhi Kaining , Singh Udai P.
Published: August 2022

Alcohol and several therapeutic drugs, including acetaminophen, are metabolized by cytochrome P450 2E1 (CYP2E1) into toxic compounds. At low levels, these compounds are not detrimental, but higher sustained levels of these compounds can lead to life-long problems such as cytotoxicity, organ damage, and cancer. Furthermore, CYP2E1 can facilitate or enhance the effects of alcohol-drug and drug-drug interactions. In this review, we discuss the role of CYP2E1 in the metabolism of alcohol and drugs (with emphasis on acetaminophen), mediating injury/toxicities, and drug-drug/alcohol-drug interactions. Next, we discuss various compounds and various nutraceuticals that can reduce or prevent alcohol/drug-induced toxicity. Additionally, we highlight experimental outcomes of alcohol/drug-induced toxicity and potential treatment strategies. Finally, we cover the role and implications of extracellular vesicles (EVs) containing CYP2E1 in hepatic and extrahepatic cells and provide perspectives on the clinical relevance of EVs containing CYP2E1 in intracellular and intercellular communications leading to drug-drug and alcohol-drug interactions. Furthermore, we provide our perspectives on CYP2E1 as a druggable target using nutraceuticals and the use of EVs for targeted drug delivery in extrahepatic and hepatic cells, especially to treat cellular toxicity.
Molecular Mechanism and Regulation of Autophagy and Its Potential Role in Epilepsy
Authors: Zhu Hanxiao , Wang Wei , Li Yun
Published: August 2022

Autophagy is an evolutionally conserved degradation mechanism for maintaining cell homeostasis whereby cytoplasmic components are wrapped in autophagosomes and subsequently delivered to lysosomes for degradation. This process requires the concerted actions of multiple autophagy-related proteins and accessory regulators. In neurons, autophagy is dynamically regulated in different compartments including soma, axons, and dendrites. It determines the turnover of selected materials in a spatiotemporal control manner, which facilitates the formation of specialized neuronal functions. It is not surprising, therefore, that dysfunctional autophagy occurs in epilepsy, mainly caused by an imbalance between excitation and inhibition in the brain. In recent years, much attention has been focused on how autophagy may cause the development of epilepsy. In this article, we overview the historical landmarks and distinct types of autophagy, recent progress in the core machinery and regulation of autophagy, and biological roles of autophagy in homeostatic maintenance of neuronal structures and functions, with a particular focus on synaptic plasticity. We also discuss the relevance of autophagy mechanisms to the pathophysiology of epileptogenesis.
Blood Coagulation on Titanium Dioxide Films with Various Crystal Structures on Titanium Implant Surfaces
Authors: Huang Her-Hsiung , Chen Zhi-Hwa , Nguyen Diem Thuy , Tseng Chuan-Ming , Chen Chiang-Sang , Chang Jean-Heng
Published: August 2022

Background: Titanium (Ti) is one of the most popular implant materials, and its surface titanium dioxide (TiO2) provides good biocompatibility. The coagulation of blood on Ti implants plays a key role in wound healing and cell growth at the implant site; however, researchers have yet to fully elucidate the mechanism underlying this process on TiO2. Methods: This study examined the means by which blood coagulation was affected by the crystal structure of TiO2 thin films (thickness < 50 nm), including anatase, rutile, and mixed anatase/rutile. The films were characterized in terms of roughness using an atomic force microscope, thickness using an X-ray photoelectron spectrometer, and crystal structure using transmission electron microscopy. The surface energy and dielectric constant of the surface films were measured using a contact angle goniometer and the parallel plate method, respectively. Blood coagulation properties (including clotting time, factor XII contact activation, fibrinogen adsorption, fibrin attachment, and platelet adhesion) were then assessed on the various test specimens. Results: All of the TiO2 films were similar in terms of surface roughness, thickness, and surface energy (hydrophilicity); however, the presence of rutile structures was associated with a higher dielectric constant, which induced the activation of factor XII, the formation of fibrin network, and platelet adhesion. Conclusions: This study provides detailed information related to the effects of TiO2 crystal structures on blood coagulation properties on Ti implant surfaces.
The Proteome Signatures of Fibroblasts from Patients with Severe, Intermediate and Mild Spinal Muscular Atrophy Show Limited Overlap
Authors: Brown Sharon J. , Kline Rachel A. , Synowsky Silvia A. , Shirran Sally L. , Holt Ian , Sillence Kelly A. , Claus Peter , Wirth Brunhilde , Wishart Thomas M. , Fuller Heidi R.
Published: August 2022

Most research to characterise the molecular consequences of spinal muscular atrophy (SMA) has focused on SMA I. Here, proteomic profiling of skin fibroblasts from severe (SMA I), intermediate (SMA II), and mild (SMA III) patients, alongside age-matched controls, was conducted using SWATH mass spectrometry analysis. Differentially expressed proteomic profiles showed limited overlap across each SMA type, and variability was greatest within SMA II fibroblasts, which was not explained by SMN2 copy number. Despite limited proteomic overlap, enriched canonical pathways common to two of three SMA severities with at least one differentially expressed protein from the third included mTOR signalling, regulation of eIF2 and eIF4 signalling, and protein ubiquitination. Network expression clustering analysis identified protein profiles that may discriminate or correlate with SMA severity. From these clusters, the differential expression of PYGB (SMA I), RAB3B (SMA II), and IMP1 and STAT1 (SMA III) was verified by Western blot. All SMA fibroblasts were transfected with an SMN-enhanced construct, but only RAB3B expression in SMA II fibroblasts demonstrated an SMN-dependent response. The diverse proteomic profiles and pathways identified here pave the way for studies to determine their utility as biomarkers for patient stratification or monitoring treatment efficacy and for the identification of severity-specific treatments.
Ba-Modified ZnO Nanorods Loaded with Palladium for Highly Sensitive and Rapid Detection of Methane at Low Temperatures
Authors: Cai Yijing , Luo Shirui , Chen Renjie , Yu Junxia , Xiang Lan
Published: August 2022

Exploring novel sensing materials to rapidly identify CH4 at low temperatures is crucial for various practical applications. Herein, a novel ZnO-xBa/Pd with Ba of cocatalyst loading from 0 to 2.0 wt% was facilely prepared using a two-step impregnation method to improve the sensitivity of the CH4 gas sensor. The microstructure, chemical states of the elements, and surface properties of ZnO-Ba/Pd were characterized, and the gas-sensitive performance of ZnO-Ba/Pd sensors was investigated. Compared to methane sensors based on other inorganic and organic material sensors, the sensor based on ZnO-1.0Ba/Pd exhibited a faster response/recovery time (1.4 s/8.3 s) and higher response (368.2%) for 5000 ppm CH4 at a lower temperature (170 °C). Moreover, the ZnO-1.0Ba/Pd sensor exhibited full reversibility and long-term stability, as well as excellent selectivity at 170 °C. The excellent performance of the ZnO-Ba/Pd sensor was attributed to the electron donation by Ba, which increases the electron density around Pd, thus enhancing the catalytic activity of Pd and promoting oxygen adsorption on the ZnO surface. The present work provides a method for the rational design and synthesis of sensitive materials in practical CH4 detection.
Implications of Regional Droughts and Transboundary Drought Risks on Drought Monitoring and Early Warning: A Review
Authors: Krishna Prabhakar Sivapuram Venkata Rama
Published: August 2022

Regional droughts are increasing in frequency and climate change projections indicate an exacerbation in the occurrence of regional droughts in the future. Droughts are complex hydrometeorological events, and the complexity of cause-and-effect relationships across administrative and political borders can make drought management a challenge. While countries are largely focused on assessing drought impacts within their borders, thereby providing focused information for the relevant administration, the impact on communities, industries, and countries that are distantly connected with the affected location must also be taken into consideration. If not considered, drought impacts can be underestimated, and adaptation actions undertaken may not completely address the drought risks. Understanding transboundary drought risks is an important and integral part of drought risk reduction and it will grow in importance as the world experiences more integration at regional and global levels on multiple fronts. To address drought risks comprehensively, the new paradigm demands that the impacts of regional droughts are fully understood, that this understanding is incorporated into drought monitoring and early warning systems, and that drought early warning information is provided to all stakeholders, including those beyond the boundaries of the affected region, thereby eliciting appropriate action.