bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Use of Cold Atmospheric Plasma to Overcome Drug Resistance in Cancer
Authors: Murillo Dzohara , Huergo Carmen , Gallego Borja , Rodríguez René , Tornín Juan
Published: January 2023

Drug resistance is a major problem in cancer treatment, as it limits the effectiveness of pharmacological agents and can lead to disease progression. Cold atmospheric plasma (CAP) is a technology that uses ionized gas (plasma) to generate reactive oxygen and nitrogen species (RONS) that can kill cancer cells. CAP is a novel approach for overcoming drug resistance in cancer. In recent years, there has been a growing interest in using CAP to enhance the effectiveness of chemotherapy drugs. In this review, we discuss the mechanisms behind this phenomenon and explore its potential applications in cancer treatment. Going through the existing literature on CAP and drug resistance in cancer, we highlight the challenges and opportunities for further research in this field. Our review suggests that CAP could be a promising option for overcoming drug resistance in cancer and warrants further investigation.
Age-Related Decline in Gangliosides GM1 and GD1a in Non-CNS Tissues of Normal Mice: Implications for Peripheral Symptoms of Parkinson’s Disease
Authors: Chowdhury Suman , Wu Gusheng , Lu Zi-Hua , Kumar Ranjeet , Ledeen Robert
Published: January 2023

The purpose of this study was to determine whether the age-related decline in a-series gangliosides (especially GM1), shown to be a factor in the brain-related etiology of Parkinson’s disease (PD), also pertains to the peripheral nervous system (PNS) and aspects of PD unrelated to the central nervous system (CNS). Following Svennerholm’s demonstration of the age-dependent decline in a-series gangliosides (both GM1 and GD1a) in the human brain, we previously demonstrated a similar decline in the normal mouse brain. The present study seeks to determine whether a similar a-series decline occurs in the periphery of normal mice as a possible prelude to the non-CNS symptoms of PD. We used mice of increasing age to measure a-series gangliosides in three peripheral tissues closely associated with PD pathology. Employing high-performance thin-layer chromatography (HPTLC), we found a substantial decrease in both GM1 and GD1a in all three tissues from 191 days of age. Motor and cognitive dysfunction were also shown to worsen, as expected, in synchrony with the decrease in GM1. Based on the previously demonstrated parallel between mice and humans concerning age-related a-series ganglioside decline in the brain, we propose the present findings to suggest a similar a-series decline in human peripheral tissues as the primary contributor to non-CNS pathologies of PD. An onset of sporadic PD would thus be seen as occurring simultaneously throughout the brain and body, albeit at varying rates, in association with the decline in a-series gangliosides. This would obviate the need to postulate the transfer of aggregated α-synuclein between brain and body or to debate brain vs. body as the origin of PD.
Biomechanical Properties of the Aortic Wall: Changes during Vascular Calcification
Authors: Zhou Jinwen , Gummi Manasa Reddy , Greco Anna , Babic Milen , Herrmann Jaqueline , Kandil Farid I. , van der Giet Markus , Tölle Markus , Schuchardt Mirjam
Published: January 2023

Medial vascular calcification (MAC) is characterized by the deposition of hydroxyapatite (HAP) in the medial layer of the vessel wall, leading to disruption of vessel integrity and vascular stiffness. Because currently no direct therapeutic interventions for MAC are available, studying the MAC pathogenesis is of high research interest. Several methods exist to measure and describe the pathophysiological processes in the vessel wall, such as histological staining and gene expression. However, no method describing the physiological properties of the arterial wall is currently available. This study aims to close that gap and validate a method to measure the biomechanical properties of the arterial wall during vascular calcification. Therefore, a stress–stretch curve is monitored using small-vessel-myography upon ex vivo calcification of rat aortic tissue. The measurement of biomechanical properties could help to gain further insights into vessel integrity during calcification progression.
Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study
Authors: Morimoto Daisaku , Washio Yosuke , Tamai Kei , Sato Takeshi , Okamura Tomoka , Watanabe Hirokazu , Fukushima Yu , Yoshimoto Junko , Kageyama Misao , Baba Kenji , Tsukahara Hirokazu
Published: January 2023

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.
Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe–Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type
Authors: Werneburg Glenn T. , Hettel Daniel , Adler Ava , Mukherjee Sromona D. , Lundy Scott D. , Angermeier Kenneth W. , Wood Hadley M. , Gill Bradley C. , Vasavada Sandip P. , Goldman Howard B. , Rackley Raymond R. , Shoskes Daniel A. , Miller Aaron W.
Published: January 2023

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe–metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.
The Regional Burden and Disability-Adjusted Life Years of Knee Osteoarthritis in Kazakhstan 2014–2020
Authors: Zhakhina Gulnur , Gusmanov Arnur , Sakko Yesbolat , Yerdessov Sauran , Semenova Yuliya , Saginova Dina , Batpen Arman , Gaipov Abduzhappar
Published: January 2023

A Global Burden of Disease (GBD) study reported that 9.6 million years lived with disability (YLDs) were lost due to hip and knee osteoarthritis (KOA) in 2017. Although the GBD study presents the disease burden at the global level, there is no information on any Central Asian country. This study aims to investigate the epidemiology of knee osteoarthritis in Kazakhstan. The data of 56,895 people with KOA between 2014–2020 was derived from the Unified National Electronic Health System of Kazakhstan and retrospectively analyzed. The majority of the cohort (76%) were women, of Kazakh ethnicity (66%), and older than 50 years of age (87%). The risk of gonarthrosis escalated for women after 50 years and peaked at 75 years with a rate of 3062 females admitted to hospital per 100,000 women in the population. This observation is approximately three times higher than for men of the same age group. A geographical analysis showed that the Jambyl oblast, West Kazakhstan, North Kazakhstan, and the Akmola oblast have the highest burden of disease. During the observation period, 127,077 age-adjusted YLDs were lost due to knee osteoarthritis. This is the first study in Kazakhstan to investigate the burden of knee osteoarthritis. This research recognizes age and sex-based differences, and regional disparities in the incidence of knee osteoarthritis. This knowledge can lead to the development of more specific diagnostic approaches and gender-personalized therapy protocols for patients.
Green Synthesized Silver Nanoparticle-Loaded Liposome-Based Nanoarchitectonics for Cancer Management: In Vitro Drug Release Analysis
Authors: Jayachandran Priyanka , Ilango Suganya , Suseela Vivekananthan , Nirmaladevi Ramalingam , Shaik Mohammed Rafi , Khan Mujeeb , Khan Merajuddin , Shaik Baji
Published: January 2023

Silver nanoparticles act as antitumor agents because of their antiproliferative and apoptosis-inducing properties. The present study aims to develop silver nanoparticle-loaded liposomes for the effective management of cancer. Silver nanoparticle-encapsulated liposomes were prepared using the thin-film hydration method coupled with sonication. The prepared liposomes were characterized by DLS (Dynamic Light Scattering analysis), FESEM (Field Emission Scanning Electron Microscope), and FTIR (Fourier Transform Infrared spectroscopy). The in vitro drug release profile of the silver nanoparticle-loaded liposomes was carried out using the dialysis bag method and the drug release profile was validated using various mathematical models. A high encapsulation efficiency of silver nanoparticle-loaded liposome was observed (82.25%). A particle size and polydispersity index of 172.1 nm and 0.381, respectively, and the zeta potential of −21.5 mV were recorded. FESEM analysis revealed spherical-shaped nanoparticles in the size range of 80–97 nm. The in vitro drug release profile of the silver nanoparticle-loaded liposomes was carried out using the dialysis bag method in three different pHs: pH 5.5, pH 6.8, and pH 7.4. A high silver nanoparticle release was observed in pH 5.5 which corresponds to the mature endosomes of tumor cells; 73.32 ± 0.68% nanoparticle was released at 72 h in pH 5.5. Among the various mathematical models analyzed, the Higuchi model was the best-fitted model as there is the highest value of the correlation coefficient which confirms that the drug release follows the diffusion-controlled process. From the Korsmeyer–Peppas model, it was confirmed that the drug release is based on anomalous non-Fickian diffusion. The results indicate that the silver nanoparticle-loaded liposomes can be used as an efficient drug delivery carrier to target cancer cells of various types.
Mesenchymal Stromal Cell Therapy Reverses Detrusor Hypoactivity in a Chronic Kidney Patient
Authors: Coelho Henrique Rodrigues Scherer , Neves Silvia Cordeiro das , Menezes Jovino Nogueira da Silva , Antoniolli-Silva Andréia Conceição Milan Brochado , Oliveira Rodrigo Juliano
Published: January 2023

Detrusor hypoactivity (DH) is characterized by low detrusor pressure or a short contraction associated with low urinary flow. This condition can progress to chronic renal failure (CRF) and result in the need for dialysis. The present case report demonstrates that a patient diagnosed with DH and CRF who received two transplants with 2 × 106 autologous mesenchymal stromal cells at an interval of 30 days recovered the contractile strength of the bladder and normalized his renal function. The patient had a score of 19 on the ICIQ-SF before cell therapy, and that score was reduced to 1 after transplantation. These results demonstrate that there was an improvement in his voiding function, urinary stream and urine volume as evaluated by urofluxometry. In addition, a urodynamic study carried out after treatment showed an increase in the maximum flow from 2 mL/s to 23 mL/s, the detrusor pressure in the maximum flow from 21 cm H2O to 46 cm H2O and a BCI that went from 31 to 161, characterizing good detrusor contraction. Thus, in the present case, the transplantation of autologous mesenchymal stromal cells proved to be a viable therapeutic option to allow the patient to recover the contractile strength of the bladder, and reversed the CRF.
Resveratrol and Its Role in the Management of B-Cell Malignancies—A Recent Update
Authors: Gupta Dhruv Sanjay , Gadi Vaishnavi , Kaur Ginpreet , Chintamaneni Meena , Tuli Hardeep Singh , Ramniwas Seema , Sethi Gautam
Published: January 2023

The growing incidence of B cell malignancies globally has prompted research on the pharmacological properties of phytoconstituents in cancer management. Resveratrol, a polyphenolic stilbenoid widely found in nature, has been explored for its anti-inflammatory and antioxidant properties, and promising results from different pre-clinical studies have indicated its potential for management of B cell malignancies. However, these claims must be substantiated by a greater number of clinical trials in diverse populations, in order to establish its safety and efficacy profile. In addition to this, there is a need to explore nanodelivery of this agent, owing to its poor solubility, which in turn may impact its bioavailability. This review aims to offer an overview of the occurrence and pathogenesis of B cell malignancies with a special focus on the inflammatory pathways involved, the mechanism of actions of resveratrol and its pharmacokinetic profile, results from pre-clinical and clinical studies, as well as an overview of the marketed formulations. The authors have also presented their opinion on the various challenges associated with the clinical development of resveratrol and future perspectives regarding therapeutic applications of this agent.
Expression of E4 Protein and HPV Major Capsid Protein (L1) as A Novel Combination in Squamous Intraepithelial Lesions
Authors: Przybylski Marcin , Pruski Dominik , Millert-Kalińska Sonja , Krzyżaniak Monika , de Mezer Mateusz , Frydrychowicz Magdalena , Jach Robert , Żurawski Jakub
Published: January 2023

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically suspicious cervix. A novel HPV-encoded marker, SILgrade-E4 (XR-E4-1), and an HPV (clone K1H8) antibody were used to demonstrate the expression in terminally differentiated epithelial cells with a productive HPV infection in the material. A semiquantitative analysis was performed based on light microscope images. The level of E4 protein decreased with the disease severity. Patients with LSIL-CIN 1 and HSIL-CIN 2 diagnoses had significantly lower levels of HPV major capsid protein (L1) than those without confirmed cervical lesions. Our analysis confirms a higher incidence of L1 in patients with molecularly diagnosed HPV infections and excluded lesions of LSIL-CIN 1 and HSIL-CIN 2. Further studies on the novel biomarkers might help assess the chances of the remission of lesions such as LSIL-CIN 1 and HSIL-CIN 2. Higher levels of E4 protein and L1 may confirm a greater probability of the remission of lesions and incidental infections. In the cytological verification or HPV-dependent screening model, testing for E4 protein and L1 expression may indicate a group with a lower risk of progression of histopathologically diagnosed lesions.
Network-Based Assessment of Minimal Change Disease Identifies Glomerular Response to IL-7 and IL-12 Pathways Activation as Innovative Treatment Target
Authors: Eikrem Øystein , Lillefosse Bjørnar , Delaleu Nicolas , Strauss Philipp , Osman Tarig , Vikse Bjørn Egil , Debiec Hanna , Ronco Pierre , Sekulic Miroslav , Koch Even , Furriol Jessica , Leh Sabine Maria , Marti Hans-Peter
Published: January 2023

Background: Minimal change disease (MCD), a major cause of nephrotic syndrome, is usually treated by corticosteroid administration. MCD unresponsiveness to therapy and recurrences are nonetheless frequently observed, particularly in adults. To explore MCD-related pathogenetic mechanisms and to identify novel drug targets ultimately contributing to novel therapeutic avenues with a certain specificity for MCD, we compared glomerular transcriptomes from MCD with membranous nephropathy (MN) patients and healthy controls. Methods: Renal biopsies from adult patients with MCD (n = 14) or MN (n = 12), and non-diseased controls (n = 8) were selected from the Norwegian Kidney Biopsy Registry. RNA for 75 base-pair paired-end RNASeq were obtained from laser capture micro-dissected (LCM) glomeruli from FFPE sections. Transcriptional landscapes were computed by combining pathway-centered analyses and network science methodologies that integrate multiple bioinformatics resources. Results: Compared to normal glomeruli, cells from MCD displayed an inflammatory signature apparently governed by the IL1 and IL7 systems. While enrichment of IL1 production and secretion was a shared feature of MCD and MN compared to normal tissue, responses involving IL7 pathway activation were unique to MCD. Indeed, IL7R expressed by glomeruli was the most upregulated gene of the interleukin family in MCD versus normal controls. IL7 pathway activation was paralleled by significant enrichment in adaptive immune system processes and transcriptional regulation and depletion in pathways related to energy metabolism and transcription. Downregulation of these organ function-related themes again occurred predominately in MCD and was significantly less pronounced in MN. Immunofluorescence and immunohistochemistry, respectively, confirmed the expression of phosphorylated IL-7 receptor alpha (IL7RA, CD127) and IL12 receptor beta 1 (IL12RB1) proteins. Conclusions: Gene expression profiling of archival FFPE-biopsies identifies MCD-specific signatures with IL7RA and IL12RB1 as novel targets for MCD treatment.
Potential Protective Effect of Dengue NS1 Human Monoclonal Antibodies against Dengue and Zika Virus Infections
Authors: Sootichote Rochanawan , Puangmanee Wilarat , Benjathummarak Surachet , Kowaboot Siriporn , Yamanaka Atsushi , Boonnak Korbporn , Ampawong Sumate , Chatchen Supawat , Ramasoota Pongrama , Pitaksajjakul Pannamthip
Published: January 2023

Due to the lack of an effective therapeutic treatment to flavivirus, dengue virus (DENV) nonstructural protein 1 (NS1) has been considered to develop a vaccine owing to its lack of a role in antibody-dependent enhancement (ADE). However, both NS1 and its antibody have shown cross-reactivity to host molecules and have stimulated anti-DENV NS1 antibody-mediated endothelial damage and platelet dysfunction. To overcome the pathogenic events and reactogenicity, human monoclonal antibodies (HuMAbs) against DENV NS1 were generated from DENV-infected patients. Herein, the four DENV NS1-specific HuMAbs revealed the therapeutic effects in viral neutralization, reduction of viral replication, and enhancement of cell cytolysis of DENV and zika virus (ZIKV) via complement pathway. Furthermore, we demonstrate that DENV and ZIKV NS1 trigger endothelial dysfunction, leading to vascular permeability in vitro. Nevertheless, the pathogenic effects from NS1 were impeded by 2 HuMAbs (D25-4D4C3 and D25-2B11E7) and also protected the massive cytokines stimulation (interleukin [IL-]-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-13, IL-17, eotaxin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, Inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1 α, MIP-1β, tumor necrosis factor-α, platelet-derived growth factor, and RANTES). Collectively, our findings suggest that the novel protective NS1 monoclonal antibodies generated from humans has multiple therapeutic benefits against DENV and ZIKV infections.
On-Chip Electromembrane Surrounded Solid Phase Microextraction for Determination of Tricyclic Antidepressants from Biological Fluids Using Poly(3,4-ethylenedioxythiophene)—Graphene Oxide Nanocomposite as a Fiber Coating
Authors: Zamani Razieh , Yamini Yadollah
Published: January 2023

In the present study, on-chip electromembrane surrounded solid phase microextraction (EM-SPME) was employed in the determination of tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, desipramine, maprotiline, and sertraline, from various biological fluids. In this regard, poly(3,4-ethylenedioxythiophene)–graphene oxide (PEDOT-GO) was electrodeposited on an SPME fiber as a conductive coating, then the fiber played the acceptor-electrode role during the extraction. Thus, the immigration of the analytes under the influence of an electric field and their absorption onto the fiber coating were accomplished simultaneously. Under the optimized conditions, the limits of detection for the target analytes were acquired in the range of 0.005–0.025 µg L−1 using gas chromatography–mass spectrometry. The linearity of the method was 0.010–500 µg L−1 for the imipramine and sertraline, 0.025–500 µg L−1 for the amitriptyline, nortriptyline, and desipramine, and 1.000–250 µg L−1 for the maprotiline (R2 ≥ 0.9984). Moreover, this method provided suitable precision and fiber-to-fiber reproducibility, with RSDs ≤ 8.4%. The applicability of the proposed setup was eventually investigated for extraction of the drugs from human bone marrow aspirate, urine, plasma, and well water samples, in which satisfactory relative recoveries, from 93–105%, were obtained.
Recent Progress in Electrochemical Nano-Biosensors for Detection of Pesticides and Mycotoxins in Foods
Authors: Gong Zhaoyuan , Huang Yueming , Hu Xianjing , Zhang Jianye , Chen Qilei , Chen Hubiao
Published: January 2023

Pesticide and mycotoxin residues in food are concerning as they are harmful to human health. Traditional methods, such as high-performance liquid chromatography (HPLC) for such detection lack sensitivity and operation convenience. Efficient, accurate detection approaches are needed. With the recent development of nanotechnology, electrochemical biosensors based on nanomaterials have shown solid ability to detect trace pesticides and mycotoxins quickly and accurately. In this review, English articles about electrochemical biosensors in the past 11 years (2011–2022) were collected from PubMed database, and various nanomaterials are discussed, including noble metal nanomaterials, magnetic metal nanoparticles, metal–organic frameworks, carbon nanotubes, as well as graphene and its derivatives. Three main roles of such nanomaterials in the detection process are summarized, including biomolecule immobilization, signal generation, and signal amplification. The detection targets involve two types of pesticides (organophosphorus and carbamate) and six types of mycotoxins (aflatoxin, deoxynivalenol, zearalenone, fumonisin, ochratoxin A, and patulin). Although significant achievements have been made in the evolution of electrochemical nano-biosensors, many challenges remain to be overcome.
Dual-Emission Carbon-Dot Ratiometric Fluorescence Sensor for Morphine Recognition in Biological Samples
Authors: Yin Qinhong , Wang Yijie , Li Xuerong , Yang Dezhi , Yang Yaling , Yang Cheng , Zhu Yanqin
Published: January 2023

Herein, a novel nitr[ogen-doped carbon dot (N-CD) fluorescence sensor with a dual emission ratio is developed using the microwave-assisted synthesis of m-phenylenediamine and spermidine. As a result of the fluorescence inner filtration effect (IFE) effect between morphine (MOR) and N-CD, the blue fluorescence of N-CDs at 350 nm was reduced in the presence of MOR, whereas the fluorescence of N-CDs at 456 nm increased substantially. The results demonstrated that the approach has a tremendous potential and that the linear range of MOR detection is 0.25–25 µg/mL, with a 71.8 ng/mL detection limit. Under UV light, the blue fluorescent system is easily visible to the naked eye. More significantly, the sensor proved successful in providing satisfactory results for the speciation measurement of MOR in a variety of biological samples.
Zip Nucleic Acid-Based Genomagnetic Assay for Electrochemical Detection of microRNA-34a
Authors: Erdem Arzum , Eksin Ece
Published: January 2023

Zip nucleic acid (ZNA)-based genomagnetic assay was developed herein for the electrochemical detection of microRNA-34a (miR-34a), which is related to neurological disorders and cancer. The hybridization between the ZNA probe and miR-34a target was performed in the solution phase; then, the resultant hybrids were immobilized onto the surface of magnetic beads (MBs). After magnetic separation, the hybrids were separated from the surface of MBs and then immobilized on the surface of pencil graphite electrodes (PGEs). In the case of a full-match hybridization, the guanine oxidation signal was measured via the differential pulse voltammetry (DPV) technique. All the experimental parameters that influenced the hybridization efficiency (i.e., hybridization strategy, probe concentration, hybridization temperature, etc.) were optimized. The cross-selectivity of the genomagnetic assay was tested against two different miRNAs, miR-155 and miR-181b, individually as well as in mixture samples. To show the applicability of the ZNA-based genomagnetic assay for miR-34a detection in real samples, a batch of experiments was carried out in this study by using the total RNA samples isolated from the human hepatocellular carcinoma cell line (HUH-7).
Acknowledgment to the Reviewers of Biosensors in 2022
Authors:   Biosensors Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Bio-Psycho-Social Approach to Reproductive Mental Health and Reproductive Decisions
Authors: Bielawska-Batorowicz Eleonora
Published: January 2023

The reproductive period in the human life cycle covers a great part of a person’s existence and is associated with many significant life changes [...]
Influence of Piloti Forms on Wind Comfort of Different Building Group Layouts by Large Eddy Simulation
Authors: Hu Yueyun , Hu Congchuan , Liu Guangdong , Shan Xiaofang , Deng Qinli , Ren Zhigang , Tang Qianyu
Published: January 2023

This paper studies the influence of different piloti rates (0%, 20%, 40%, 60%, 80%, 100%) on outdoor wind comfort for three building groups, i.e., determinant type, point type, and enclosure type. LES (Large Eddy Simulation) is used to simulate the wind environment of three clusters at six different piloti rates. This paper mainly studies the effect of piloti rate on wind speed at pedestrian level (1.5 m). The outdoor wind environment was analyzed using the average wind speed ratio, and outdoor wind comfort was evaluated using the comfortable wind ratio. The following results were obtained: (1) The piloti setting has little influence on the overall wind speed in the target area, and even an inappropriate piloti rate setting may reduce the overall average wind speed in the target area. (2) A comprehensive comparison of the three building layouts shows that the comfortable wind ratio of the determinant layout is the highest when the piloti ratio is 80%. The results of this study can provide architects and urban planners with reference for piloti and urban layout settings.
Investigation on the Influence of Active Underpinning Process on Bridge Substructures during Shield Tunnelling: Numerical Simulation and Field Monitoring
Authors: Zheng Fengqu , Jiang Yalong , Wang Ning , Geng Daxin , Xu Changjie
Published: January 2023

The pile foundation cutting and underpinning process during shield tunnelling significantly impacts the stability of bridge substructures. In this paper, the shield tunnel area from Hongguzhong Avenue Station to Yangming Park Station of Nanchang Metro Line 2 was taken as the research subject, which crosses the pile foundation underpinning project of the south approach section of Bayi Bridge. Through numerical simulation and on-site monitoring analysis, the influence of the active underpinning process of shield tunnelling pile foundation on the deformation of bridge substructure was studied. First, through analyzing on-site conditions and comparing technical solutions, an active gantry bridge pile foundation underpinning technology was proposed, and the specific construction steps were determined. On this basis, for the C15 pile foundation with the most complex working conditions, ABAQUS software was applied to simulate the jack-up, unloading and pile-cutting process during the pile foundation underpinning construction, and the displacement development of the bridge pier, underpinning beam and new pile during the whole construction process were analyzed. Finally, through on-site monitoring data analysis, the technology’s feasibility and safety were further verified. At the same time, according to the analysis of the monitoring results of the bridge piers, underpinning beams and new piles, the results from the finite element software were nearly the same as the trend shown by the monitoring results, and the displacement of the main structures of the lower part of the bridge was small and within the control range. The above research work verified the applicability of the active gantry type bridge pile foundation underpinning technology in the pile foundation underpinning condition of the single-column single-pile bridge in the narrow space curved bridge section, and is worthy of further promotion and application.
Modernist Heritage versus Contested Legacy: The Case of “Radio City”
Authors: Tranavičiūtė Brigita
Published: January 2023

The industrial legacy of the Soviet period in Lithuania has become an object of social tension. Even though the industrial heritage of the Soviet period is not directly related to the crimes of the occupying authorities, the conversion of industrial objects in the historical parts of cities or of buildings with symbolic significance is contentious among members of the public. For this reason, the conversion of industrial areas in Lithuania has become not only an economic challenge, but also a problem of adaptating to society’s needs, changing society’s attitude toward this type of heritage, and organically integrating that heritage into the city structure. The “Radio City” conversion project is being developed in the context of this social tension but has become an example of adaptation in harmony with the architectural heritage that occupies a dominant position on the block, which is located in one of the historically formed residential districts of Kaunas city.
Citizen Perception and Ex Ante Acceptance of a Low-Emission Zone Implementation in a Medium-Sized Spanish City
Authors: Jiménez-Espada Montaña , García Francisco Manuel Martínez , González-Escobar Rafael
Published: January 2023

The public decision-making process at the municipal level becomes extremely complicated for government managers when unpopular measures must be adopted. In this sense, citizen participation processes become a tool of undoubted added value that allows municipalities to adapt their policies to the needs and feelings of their inhabitants. The aim of this research was to focus on addressing the point of view of the citizens of a medium-sized Spanish city in the face of the imminent implementation of a low-emission zone, in order to identify which aspects were of concern to citizens. The methodology used in the research was based on a declared preferences survey that allowed us to determine the daily behaviour of the user in terms of urban mobility and to anticipate the citizen’s reaction to the implementation of socially unacceptable initiatives, such as restrictions on access, circulation, and the parking of vehicles. The results obtained in relation to the consultation on alternative measures to tackle pollution, noise and traffic jams showed that citizens are receptive to improvements in universal accessibility, subsidies for public transport, increased road safety for PMV’s infrastructure, subsidies for the purchase of environmentally friendly vehicles and PMV, and the promotion of pedestrianisation. However, there are undoubted threats to the implementation of the LEZ, such as the lack of acceptance of the measure. Therefore, it is considered imperative for public administrations to work on the search for sustainable actions that contribute to improving the degree of compliance with the measure, while at the same time making an effort to disseminate the advantages of the LEZ for the quality of life and health of citizens (through information campaigns). There is a knowledge gap in scientific research on the ex ante assessment of the effects of possible transport measures to improve air quality in city centres and consultation through citizen participation. It is estimated that the resolution of this research gap could contribute to a more feasible, reasonable, and effective implementation of various urban mobility policies in medium-sized Spanish cities.
Impact of Derived Features from the Controlled Environment Agriculture Scenarios on Energy Consumption Prediction Model
Authors: Cao Yifan , Chen Yangda , Shi Mingwen , Li Chuanzhen , Wu Weijun , Li Yapeng , Guo Xuxin , Sun Xianpeng
Published: January 2023

The high energy consumption CEA building brings challenges to the management of the energy system. An accurate energy consumption prediction model is necessary. Although there are various prediction methods, the prediction method for the particularity of CEA buildings is still a gap. This study proposes some derived features based on the CEA scenarios to improve the accuracy of the model. The study mainly extracts the time series and logical features from the agricultural calendar, the botanical physiological state, building characteristics, and production management. The time series and logical features have the highest increase of 2.8% and 3.6%, respectively. In addition, four automatic feature construction methods are also used to achieve varying degrees of influence from −9% to 8%. Therefore, the multiple feature extraction and feature construction methods proposed in this paper can effectively improve the model performance.
Modeling Performance and Uncertainty of Construction Planning under Deep Uncertainty: A Prediction Interval Approach
Authors: Wang Shuo , Feng Kailun , Wang Yaowu
Published: January 2023

In construction planning, decision making has a great impact on final project performance. Hence, it is essential for project managers to assess the construction planning and make informed decisions. However, disproportionately large uncertainties occur during the construction planning stage; in the worst case, reliable probability distributions of uncertainties are sometimes unavailable due to a lack of information before construction implementation. This situation constitutes a deep uncertainty problem, making it a challenge to perform a probability-based uncertainty assessment. The current study proposes a modeling approach that applies prediction intervals for construction planning via the integration of discrete-event simulation (DES), fuzzy C-means clustering (FCM), Bayesian regularization backpropagation neural networks (BRBNNs), and particle swarm optimization (PSO). The DES is used to perform data sampling of the construction alternatives and assess their performances under uncertainty. Based on the generated samples, the FCM, BRBNN, and PSO are integrated in a machine learning algorithm to model the prediction intervals that represent relationships between construction planning schemes, performances, and the corresponding uncertainties. The proposed approach was applied to a case project, with the results indicating that it is capable of modeling construction performance and deep uncertainties with a defined 95% confidence level and fluctuation within 1~9%. The presented research contributes a new and innovative option, using prediction intervals to solve deep uncertainty problems, without relying on the probability of the uncertainty. This study demonstrates the effectiveness of the proposed approach in construction planning.
Development of a New Response Spectrum Analysis Approach for Determining Elastic Shear Demands on Shear-Dominated Steel Building Frames
Authors: Li Junlin , Wang Wei
Published: January 2023

This research is focused on improving the conventional response spectrum analysis (CRSA) method for the elastic shear demands estimation of shear-dominated steel building frames. An alternative approach named the improved response spectrum analysis (IRSA) method is proposed and validated in this paper. A simplified procedure to capture the dynamic features of a continuous shear beam (CSB) with stepped stiffness is first presented, and then validated. The CSB is employed in IRSA to replace the original eigenvalue analysis in CRSA to provide the modal parameter estimation for the considered system. A modified SRSS (MSRSS) mode superposition based on a genetic algorithm is then proposed and employed in IRSA. Based on the analyses conducted in this research, it is found that using first three modes in MSRSS to execute mode superposition could provide a great estimation of the elastic shear demands distribution. The amplification of weighting coefficients for the second and third mode contribution indicates the underestimation of the high mode effect in CSRSS. Further, response history analyses (RHA) are performed on two demonstration building frames to evaluate the improvement of the IRSA. The results indicate that IRSA provides a more precise estimation on the elastic shear force demand distribution in shear-dominated steel building frames under seismic effects compared with that which was achieved by CRSA.
Characteristics and Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Receiving Ibrutinib for ≥5 Years in the RESONATE-2 Study
Authors: Woyach Jennifer A. , Barr Paul M. , Kipps Thomas J. , Barrientos Jacqueline C. , Ahn Inhye E. , Ghia Paolo , Girardi Vincent , Hsu Emily , Jermain Mandy , Burger Jan A.
Published: January 2023

Primary results from the phase 3 RESONATE-2 study demonstrated superior efficacy and tolerability with ibrutinib versus chlorambucil in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Here, we describe characteristics and outcomes of patients who received ibrutinib treatment for ≥5 years in RESONATE-2. Patients aged ≥65 years with previously untreated CLL/SLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5–0.8 mg/kg for ≤12 cycles (n = 133). Baseline characteristics in ibrutinib-randomized patients (n = 136) were generally similar between patients on ibrutinib treatment for ≥5 years (n = 79) versus those on treatment for <5 years (n = 57). In patients on ibrutinib treatment for ≥5 years, complete response rates improved over time, reaching 42% by 5 years. Estimated 7-year progression-free survival and overall survival rates were 82% and 94%, respectively. Adverse events (AEs) led to dose reductions in 16/79 patients (20%); these AEs were resolved for 13/16 patients (81%). AEs led to dose holds (≥7 days) in 45/79 patients (57%); these AEs were resolved for 43/45 patients (96%). More than half (58%) of ibrutinib-randomized patients benefitted from ibrutinib treatment for ≥5 years regardless of baseline characteristics. Dose modification resolved AEs for most patients, thereby facilitating continued treatment.
The Role of Intratumor Microbiomes in Cervical Cancer Metastasis
Authors: Jiang Lu , Duan Baofeng , Jia Peng , Zhang Yan , Yan Xin
Published: January 2023

Background: Intratumor microbiomes can influence tumorigenesis and progression. The relationship between intratumor microbiomes and cervical cancer metastasis, however, remains unclear. Methods: We examined 294 cervical cancer samples together with information on microbial expression, identified metastasis-associated microbiomes, and used machine learning methods to validate their predictive ability on tumor metastasis. The tumors were subsequently typed based on differences in microbial expression. Differentially expressed genes in different tumor types were combined to construct a tumor-prognostic risk score model and a multiparameter nomogram model. In addition, we performed a functional enrichment analysis of differentially expressed genes to infer the mechanism of action between microbiomes and tumor cells. Results: Based on the 15 differentially expressed microbiomes, machine learning models were able to correctly predict the risk of cervical cancer metastasis. In addition, both the risk score and the nomogram model accurately predicted tumor prognosis. Differences in the expression of endogenous genes in tumors can influence the distribution of the intracellular microbiomes. Conclusions: Intratumoral microbiomes in cervical cancer are associated with tumor metastasis and influence disease prognosis. A change in gene expression within tumor cells is responsible for differences in the microbial populations within the tumor.
Heavy Ion-Responsive lncRNA EBLN3P Functions in the Radiosensitization of Non-Small Cell Lung Cancer Cells Mediated by TNPO1
Authors: Tang Haoyi , Huang Hao , Guo Zi , Huang Haitong , Niu Zihe , Ji Yi , Zhang Yuyang , Bian Huahui , Hu Wentao
Published: January 2023

In recent decades, the rapid development of radiotherapy has dramatically increased the cure rate of malignant tumors. Heavy-ion radiotherapy, which is characterized by the “Bragg Peak” because of its excellent physical properties, induces extensive unrepairable DNA damage in tumor tissues, while normal tissues in the path of ion beams suffer less damage. However, there are few prognostic molecular biomarkers that can be used to assess the efficacy of heavy ion radiotherapy. In this study, we focus on non-small cell lung cancer (NSCLC) radiotherapy and use RNA sequencing and bioinformatic analysis to investigate the gene expression profiles of A549 cells exposed to X-ray or carbon ion irradiation to screen the key genes involved in the stronger tumor-killing effect induced by carbon ions. The potential ceRNA network was predicted and verified by polymerase chain amplification, western blotting analysis, colony formation assay, and apoptosis assay. The results of the experiments indicated that lncRNA EBLN3P plays a critical role in inhibiting carbon ion-induced cell proliferation and inducing apoptosis of NSCLC cells. These functions were achieved by the EBLN3P/miR-144-3p/TNPO1 (transportin-1) ceRNA network. In summary, the lncRNA EBLN3P functions as a ceRNA to mediate lung cancer inhibition induced by carbon ion irradiation by sponging miR-144-3p to regulate TNPO1 expression, indicating that EBLN3P may be a promising target for increasing the treatment efficacy of conventional radiotherapy for NSCLC.
AtomNet-Aided OTUD7B Inhibitor Discovery and Validation
Authors: Chen Jianfeng , Bolhuis Derek L. , Laggner Christian , Kong Deyu , Yu Le , Wang Xiaodong , Emanuele Michael J. , Brown Nicholas G. , Liu Pengda
Published: January 2023

Protein deubiquitinases play critical pathophysiological roles in cancer. Among all deubiquitinases, an oncogenic function for OTUD7B has been established in genetic NSCLC murine models. However, few deubiquitinase inhibitors have been developed due to technical challenges. Here, we report a putative small molecule OTUD7B inhibitor obtained from an AI-aided screen of a 4 million compound library. We validated the effects of the OTUD7B inhibitor (7Bi) in reducing Akt-pS473 signals in multiple NSCLC and HEK293 cells by blocking OTUD7B-governed GβL deubiquitination in cells, as well as inhibiting OTUD7B-mediated cleavage of K11-linked di-ub in an in vitro enzyme assay. Furthermore, we report in leukemia cells, either genetic depletion or 7Bi-mediated pharmacological inhibition of OTUD7B reduces Akt-pS473 via inhibiting the OTUD7B/GβL signaling axis. Together, our study identifies the first putative OTUD7B inhibitor showing activities both in cells and in vitro, with promising applications as a therapeutic agent in treating cancer with OTUD7B overexpression.
Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort
Authors: Xiao Xue , Huang Yi , Sadeghi Fetemeh , Feychting Maria , Hammar Niklas , Fang Fang , Zhang Zhe , Liu Qianwei
Published: January 2023

Background: Previous studies have examined the link between blood metabolic biomarkers and risk of thyroid cancer, with inconclusive results. We performed a cohort study based on the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) Cohort, including 561,388 individuals undergoing health examinations during 1985–1996 with a follow-up of >30 years. Methods: Newly diagnosed cases of thyroid cancer were identified from the Swedish Cancer Register. We assessed the associations of nine blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolism measured at the time of health examinations with the subsequent risk of thyroid cancer and demonstrated the temporal trend of these biomarkers during the 30 years before diagnosis of thyroid cancer. Results: After multivariable adjustment, there was a lower risk of thyroid cancer, per standard deviation increase in total cholesterol (TC; HR 0.91; 95%CI 0.82–0.99) and HDL-C (HR 0.86; 95%CI 0.75–0.99). During the 20 to 30 years before diagnosis, patients with thyroid cancer, as a group, demonstrated constantly lower levels of TC and HDL-C, compared to controls. Further, patients with thyroid cancer demonstrated declining levels of these biomarkers during the ten years before diagnosis, whereas controls demonstrated stable or increasing levels. Conclusions: Taken together, we found blood levels of TC and HDL-C to be associated with the risk of thyroid cancer and that there was a declining level of metabolic biomarkers during the 10 years before diagnosis of thyroid cancer.
Host Microbiomes Influence the Effects of Diet on Inflammation and Cancer
Authors: Mahmood Ramsha , Voisin Athalia , Olof Hana , Khorasaniha Reihane , Lawal Samuel A. , Armstrong Heather K.
Published: January 2023

Cancer is the second leading cause of death globally, and there is a growing appreciation for the complex involvement of diet, microbiomes, and inflammatory processes culminating in tumorigenesis. Although research has significantly improved our understanding of the various factors involved in different cancers, the underlying mechanisms through which these factors influence tumor cells and their microenvironment remain to be completely understood. In particular, interactions between the different microbiomes, specific dietary factors, and host cells mediate both local and systemic immune responses, thereby influencing inflammation and tumorigenesis. Developing an improved understanding of how different microbiomes, beyond just the colonic microbiome, can interact with dietary factors to influence inflammatory processes and tumorigenesis will support our ability to better understand the potential for microbe-altering and dietary interventions for these patients in future.